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D J Grignon

Publications and source records attributed to D J Grignon.

At least 37 records · Page 2Linked to original sources
PubMed2000

Patients with abnormal ultrasound of the prostate but normal digital rectal examination should be classified as having clinical stage T2 tumors.

PURPOSE: The current TNM staging system classifies prostate tumors with abnormal transrectal ultrasound but normal digital rectal examination as clinical stage T2. However, most urologists consider these tumors as clinical stage T1c due to the perceived inaccuracy of transrectal ultrasound in clinical staging. To determine the role of transrectal ultrasound in the clinical staging of prostate cancer we evaluated the pathological stage and disease-free survival of patients undergoing radical prostatectomy who had tumor detected by needle biopsy because of elevated serum prostate specific antigen with or without transrectal ultrasound abnormalities. MATERIALS AND METHODS: Between 1991 and 1996, 738 patients underwent radical retropubic prostatectomy as monotherapy for clinically localized prostate cancer. Patients were classified into group 1-normal digital rectal examination and transrectal ultrasound (138), group 2-normal digital rectal examination but abnormal transrectal ultrasound (366) and group 3 -abnormal digital rectal examination (234). We compared pathological parameters and disease-free-survival among the 3 groups. RESULTS: Tumors were organ confined in 61%, 42% and 41% of patients in groups 1, 2 and 3, respectively (p = 0.0001). Overall disease-free survival was 80% with a mean followup of 68 months. Disease recurred in 8%, 22% and 25% of patients in groups 1, 2 and 3, respectively (p = 0.007). Group 1 had better disease-free survival compared to groups 2 and 3 (p = 0.003 and p = 0.002, respectively), and there was no difference in disease-free survival between groups 2 and 3 (p = 0.39). CONCLUSIONS: We provide evidence to support the use of transrectal ultrasound findings in the clinical staging system for prostate cancer. Patients with normal digital rectal examination, elevated serum prostate specific antigen and abnormal transrectal ultrasound should be considered as having clinical stage T2 disease.

Adult↗
PubMed2000

Epidemiology and molecular biology of early prostatic neoplasia.

This paper provides our institutional data with respect to the prevalence of early neoplastic changes within the prostate gland and the age and race distribution of the patients. The changes examined were prostatic intraepithelial neoplasia (PIN) and preclinical (latent) cancers. The literature on the prevalence of these early lesions among different geographic and ethnic groups is summarized, and an abbreviated review of the more common molecular alterations reported at this early phase of prostatic neoplasia is offered.

Adenocarcinoma↗
PubMed2000

Significance of the Gleason scoring system after neoadjuvant hormonal therapy.

Neoadjuvant hormonal therapy (NHT) induces morphologic changes in prostate adenocarcinoma that result in the assignment of higher Gleason scores on average than in pretreatment biopsy specimens. This outcome has led to the recommendation that the Gleason scoring system not be applied to prostate adenocarcinoma specimens after NHT. We reviewed the radical prostatectomy specimens of 116 patients who had received NHT. Gleason scores were assigned on the post-treatment specimens by applying the usual criteria; in addition, an estimated pretreatment Gleason score was assigned on the basis of knowledge of the morphologic alterations associated with NHT. Finally, an estimate of the degree of therapy effect was assigned: little or no evidence of hormonal effect (grade 1) to marked therapy-related changes (grade 3). Both the post-treatment and the estimated pretreatment Gleason score correlated significantly with biochemical progression (P = 0.03 and P = 0.03, respectively; log-rank test). The degree of therapy effect did not correlate with progression (P = 0.46; log-rank test). This limited analysis suggests that despite the morphologic alterations induced by NHT, post-treatment Gleason score remains a significant prognostic measure. Further studies in more uniformly treated populations are required to confirm this observation.

Adenocarcinoma↗
PubMed1999

Relationship of p21(WAF1) expression with disease-free survival and biochemical recurrence in prostate adenocarcinomas (PCa).

BACKGROUND: The p21(WAF1) gene is considered to be one of the major regulators of the cell cycle. Its level of expression has been shown to correlate with pathologic stage and Gleason score in prostatic cancer. However, its relationship to clinical outcome is not yet well-characterized. METHODS: Immunohistochemical staining for p21(WAF1) protein expression was performed in 62 consecutive radical prostatectomy specimens from our institution. The results were correlated with the disease-free survival and biochemical recurrence of the patients. RESULTS: Thirty-four of the 62 patients were Caucasian and 28 were African American. There was a significant correlation between p21(WAF1) expression and biochemical recurrence after radical prostatectomy (P < 0.0095). However, while p21(WAF1) staining in prostate cancer was a prognostic indicator of disease-free survival in Caucasians (P < 0.0001), it appeared not to be a factor in African-American men (P = 0.908). CONCLUSIONS: This study suggests that p21(WAF1) may have a role in the pathogenesis and progression of prostate carcinoma, and may serve as a predictor of biochemical recurrence of this tumor. The differences in the values of p21(WAF1) as a prognostic marker of disease-free survival in Caucasians vs. African Americans suggest that progression of prostate cancer may have different mechanisms in different ethnic groups.

Adenocarcinoma↗
PubMed1999

Severe combined immunodeficient-hu model of human prostate cancer metastasis to human bone.

Commonly used in vivo models of prostate cancer metastasis include syngeneic rodent cancers and xenografts of human cancer in immunodeficient mice. However, the occurrence of osseous metastases in these models is rare, and in xenograft models, species-specific factors may limit the ability of human cells to metastasize to rodent bones. We have modified the severe combined immunodeficient (SCID)-human model to test the ability of circulating human prostate cancer cells to home to macroscopic fragments of human bone and other organs previously implanted into SCID mice. We have also compared the growth of human prostate cancer cells in various human and mouse tissue microenvironments in vivo. Macroscopic fragments of human fetal bone, lung, or intestine (16-22 weeks gestation) or mouse bone were implanted s.c. into male CB.17 SCID mice. Four weeks later, human prostate cancer cells were injected either i.v. via the tail vein (circulating cell colonization assay) or directly into the implanted tissue fragments transdermally (end organ growth assay). Tumor growth was followed for 6 weeks by palpation and magnetic resonance imaging. After 6 weeks, tumors were enumerated in implanted human and mouse organ fragments and native mouse tissue. Tumors were characterized by histology, immunohistochemistry, and chromosomal analysis. After i.v. injection, circulating PC3 cells successfully colonized implanted human bone fragments in 5 of 19 mice. Tumors were easily followed by palpation and imaging and had an average volume of 258 mm3 at autopsy. Histological examination revealed osteolysis and a strong desmoplastic stromal response, which indicated intense stromal-epithelial interaction. Bone tumors were subcultured, and chromosomal analysis demonstrated that the tumors were derived from the parental prostate cancer cell line. Microscopic tumor colonies were also found in a few mouse lungs after i.v. injection of PC3, DU145, and LNCaP cells, however the volume of the lung nodules was less than 1 mm3 in all of the cases. No colonization of human lung or intestine implants, the mouse skeleton, or other mouse organs was detected, demonstrating a species- and tissue-specific colonization of human bone by PC3 cells. Direct injection of 10(4) prostate cancer cells into human bone implants resulted in large tumors in 75-100% of mice. PC3 and DU145 bone tumors were primarily osteolytic, whereas LNCaP bone tumors were both osteoblastic and osteolytic. PC3 and LNCaP bone tumors showed a desmoplastic stromal response, which indicated intense stromal-epithelial interaction. All three of the cell lines formed tumors in implanted human lung tissue; however, the tumors were all < or = 10 mm3 in volume and showed minimal stromal involvement. No tumors formed after either s.c. injection or injection of cells into implanted mouse bone demonstrating both species- and tissue-specific enhancement of growth of human prostate cancer cells by human bone. The severe combined immunodeficient-human model provides a useful system to study species-specific mechanisms involved in the homing of human prostate cancer cells to human bone and the growth of human prostate cancer cells in human bone.

Animals↗
PubMed1999

Chromosomal analysis of renal angiomyolipoma by comparative genomic hybridization: evidence for clonal origin.

Angiomyolipoma has long been considered a hamartomatous polyclonal proliferation. However, recent molecular analyses have indicated that these tumors may be clonal neoplasms rather than polyclonal proliferations. We investigated chromosomal imbalances in angiomyolipoma by comparative genomic hybridization. DNA was extracted from archival paraffin-embedded and frozen tissues of 12 angiomyolipomas (10 usual variant, two epithelioid variant). The 10 angiomyolipomas of the usual variant included bilateral tumors from one tuberous sclerosis patient. Fluorescence ratio distributions from tumor hybridizations were compared with those from control hybridizations to detect changes in DNA copy number with high sensitivity and specificity. We identified 20 chromosomal imbalances in seven sporadic angiomyolipomas, including both tumors of the epithelioid variant. The remaining five tumors, including the two angiomyolipomas from a tuberous sclerosis patient, were devoid of chromosomal imbalances. Seventy-five percent of the imbalances were partial or whole chromosomal deletions involving disparate genomic regions, some of which have previously been associated with tumors of adipose tissue and smooth muscle tumors. Four angiomyolipomas of the usual variant showed 5q deletions with a common region of deletion spanning 5q33 to q34. In two tumors, deletion on 5q was the sole abnormality. One epithelioid angiomyolipoma showed 5q gain encompassing the same region in addition to other alterations. We concluded that (1) Chromosomal imbalances are common in renal angiomyolipomas; (2) Presence of clonal genomic alterations lends further support to the neoplastic pathogenesis of these tumors; (3) The 5q33-q34 region may contain a tumor suppressor gene significant in the histogenesis of some renal angiomyolipomas.

Adult↗
PubMed1999

Should Gleason score 7 prostate cancer be considered a unique grade category?

OBJECTIVES: To evaluate pathologic characteristics and biochemical survival rate differences between patients with Gleason score 6 or less, 7, and 8 or more prostate cancer. METHODS: A total of 652 patients who underwent a radical prostatectomy for clinically localized prostate cancer between March 1991 and December 1995 were selected for this study. Patients who underwent neoadjuvant or adjuvant hormonal therapy or radiotherapy were excluded. Clinical and pathologic data were obtained from our prostate cancer data base. Serum prostate-specific antigen (PSA) level, pathologic stage, and disease-free survival (DFS) were analyzed between the three Gleason score groups. RESULTS: The overall mean pretreatment serum PSA level was 12.9 ng/mL, being 8.4, 13.4, and 23 ng/mL for Gleason score 6 or less, 7, and 8 or more prostate cancers, respectively (P = 0.0001). Of patients with specimen Gleason score 6 or less, 7, and 8 or more, pathologic organ-confined disease was present in 69.4%, 43.1 %, and 9.2%, respectively (P = 0.001). Extraprostatic extension was present in 30.6%, 56.9%, and 90.8% (P = 0.0001); positive surgical margins, considered independently from the other pathologic findings, were present in 31 %, 47.6%, and 67.8% of patients with Gleason score 6 or less, 7, and 8 or more, respectively (P = 0.0001). DFS was 34.5% for patients with Gleason score 8 or more, 75% for Gleason score 7, and 91.2% for Gleason score 6 or less prostate cancers, at a median follow-up of 34.2 months (P = 0.0001). On multivariable analysis, after adjusting for serum PSA level (10 or less or more than 10 ng/mL) and pathologic stage, Gleason score (6 or less, 7, 8 or more) remained a statistically significant predictor of DFS (P = 0.0001). CONCLUSIONS: Patients with Gleason score 7 prostate cancer should be considered a specific prognostic category. We believe that this distinction is critical to obtain more reliable results from prostate cancer analyses about prognosis of patients treated with curative intent.

Disease-Free Survival↗
PubMed1999

Lymph node size does not correlate with the presence of prostate cancer metastasis.

OBJECTIVES: To determine whether lymph node size is a surrogate marker for lymph node metastasis. METHODS: We reviewed 980 patients who underwent radical retropubic prostatectomy with bilateral pelvic lymph node dissection for clinically localized prostate cancer, of whom 63 had lymph node metastases. A comparable group of patients with prostate cancer undergoing radical prostatectomy who did not have lymph node involvement was identified using the following parameters: serum prostate-specific antigen level, clinical and pathologic stage, and pre- and postoperative Gleason score. The axial and longitudinal dimensions of the nodes from patients with and without metastases were analyzed to assess the significance of lymph node size in predicting the presence of metastases. All patients had negative preoperative computed tomography (CT) and bone scans. Of the 63 patients with lymph node metastases, 48 had tissue available for measuring the dimensions of the lymph nodes. RESULTS: A total of 76 metastatic and 92 negative lymph nodes were identified from the patients with and without metastatic nodes, respectively. The mean nodal longitudinal size was 1.65 cm (range 0.2 to 6.5) and 3.50 cm (range 0.5 to 9) for positive and negative nodes, respectively (P = 0.0001). The mean axial nodal size was 0.8 cm (range 0.2 to 3.2) and 1.0 cm (range 0.2 to 2.2) for positive and negative lymph nodes, respectively. In 56 metastatic nodes (74%), the axial size was less than 1 cm and in 20 (26%) less than 5 mm. CONCLUSIONS: Lymph node size should not be used as a surrogate for the presence of lymph node metastases. Although no patient had enlarged lymph nodes by CT scan criteria (greater than 1.5 cm), 6 (8%) of 48 and 19 (12%) of 48 patients with and without lymph node metastases, respectively, had nodes with an axial dimension greater than 1.5 cm.

Aged↗
PubMed1999

Prostate cancer histologic trends in the metropolitan Detroit area, 1982 to 1996.

OBJECTIVES: One of the concerns regarding the widespread use of serum prostate-specific antigen (PSA) as a screening tool for prostate cancer is the possibility that it may detect latent or clinically insignificant cancers. One indicator of clinical importance is thought to be histologic grade, with clinically unimportant cancers more likely to be well differentiated and clinically important tumors more likely to be moderately or poorly differentiated. METHODS: Data from the metropolitan Detroit population-based Surveillance, Epidemiology, and End Results Program were examined to determine trends in prostate cancer histologic grading before and after the introduction of PSA screening. RESULTS: From 1989 through 1996, the most recent year for which data are available, a dramatic increase in the incidence of prostate cancer occurred in the Detroit area, corresponding to the routine use of PSA as a screening test for prostate cancer. Local stage cancer demonstrated the largest increase in incidence. The incidence of moderately differentiated cancers also rose substantially during the same period; the incidence of poorly differentiated tumors remained about the same, and the incidence of well differentiated tumors decreased. Coincident with the increasing proportion of moderately differentiated cancers was a significant increase in the proportion of prostate biopsies performed (P = 0.001). CONCLUSIONS: These population-based data add important evidence that prostate cancers identified with PSA are more likely to be moderately than well differentiated. Additionally, if the definition of clinical significance depends on histopathologic grade, this finding could further be interpreted as evidence that PSA is more likely to detect clinically significant prostate cancer.

Adult↗
PubMed1999

Urinary diversion-related outcome in patients with pelvic recurrence after radical cystectomy for bladder cancer.

OBJECTIVES: To evaluate the impact of urinary diversion on disease status, complications, and subsequent treatment in patients with pelvic tumor recurrence after radical cystectomy for bladder cancer. METHODS: A retrospective review of 201 consecutive cases of radical cystectomy for bladder cancer, performed at our institution between March 1991 and March 1996, identified 33 patients (16.4%) with disease recurrence in the pelvis with or without systemic metastasis. Urinary diversion in patients with tumor recurrence was an ileal conduit, continent cutaneous diversion, or orthotopic neobladder in 19, 3, and 11 patients, respectively. The mean follow-up for all patients undergoing cystectomy was 25.9 months (range 8 to 75). The mean time to diagnosis of local disease recurrence after cystectomy was 13.9 months (range 5 to 50). RESULTS: In 21 (63.6%) of 33 patients, pelvic recurrence and systemic metastasis were present simultaneously. Disease recurrence was associated with poor outcome: only 8 patients (24.2%) were alive and disease free, 7 of whom had isolated local recurrence without evidence of systemic metastasis. There was no difference in overall survival or type of therapy delivered once disease recurrence was diagnosed between patients with an orthotopic neobladder and those with a cutaneous (continent or incontinent) urinary diversion. The only diversion-related complication resulting from pelvic recurrence was 1 case of tumor invasion into an orthotopic neobladder, requiring conversion to an ileal conduit. CONCLUSIONS: The type of urinary diversion did not impact a patient's risk of complications, the ability to receive salvage treatment, or overall survival once pelvic recurrence was diagnosed. Patients at high risk of pelvic recurrence should not be excluded from receiving an orthotopic urinary diversion.

Adult↗
PubMed1999

Prostate. Practice parameters, pathologic staging, and handling radical prostatectomy specimens.

This article addresses the handling, processing, and reporting of radical prostatectomy specimens with the goal of providing general guidelines and practical suggestions for the surgical pathologist. During the last decade, pathologists in academic and community institutions have witnessed a surge in the number of radical prostatectomy specimens evaluated in their departments. Unlike the relative familiarity most pathologists have with other major oncologic resections, radical prostatectomy specimens present an interesting and occasionally frustrating challenge with respect to gross evaluation, sampling, and reporting.

Humans↗
PubMed1999

p53 gene alterations in prostate cancer after radiation failure and their association with clinical outcome: a molecular and immunohistochemical analysis.

This study evaluates the prevalence of p53 gene mutations in prostate cancer in salvage prostatectomies after radiation failure using single strand conformational polymorphism (SSCP) and direct sequencing of the polymerase chain reaction (PCR) product. Findings were correlated with immunohistochemically (IHC) detectable p53 expression in residual prostate cancer. The usefulness of p53 as a marker of clinical outcome was evaluated. Thirty-three cases were available for molecular and immunohistochemical analysis. Immunohistochemical stains for p53 were performed with clone DO7. PCR-SSCP for mutations in the coding region of p53 DNA (exons 4-9) was performed on all immunopositive cases and 12 of 23 immunonegative cases. All samples with an SSCP shift were sequenced for the respective exon. Patients were evaluated for biochemical failure for 1-82 months (median 38 months) following surgery. Immunohistochemical p53 reactivity was noted in 10 of 33 (30%) patients. Among p53 immunopositive cases SSCP shifts were seen in 7 of 10 (70%) samples with 5 of the 7 (71%) showing p53 mutations. Univariate analysis revealed abnormal expression of p53 protein by immunohistochemistry to be a significant predictor of poorer outcome (p = 0.025, log rank), however this was not independent of pathologic stage, surgical margin status and Gleason score. The presence of p53 gene mutations by PCR-SSCP and direct sequencing did not predict for outcome. In our study 30% of prostate cancers at the time of salvage prostatectomy after radiation failure expressed immunohistochemically detectable p53. PCR-SSCP and sequencing shows that not all of these cases have detectable mutations in the most frequent mutation sites (exons 4-9). Clinical failure is more common in the group of prostate cancer patients with abnormal p53 immunoreactivity.

Aged↗
PubMed1999

Responsiveness of human prostate carcinoma bone tumors to interleukin-2 therapy in a mouse xenograft tumor model.

We have tested an immunotherapy approach for the treatment of metastatic prostate carcinoma using a bone tumor model. Human PC-3 prostate carcinoma tumor cells were heterotransplanted into the femur cavity of athymic Balb/c nude mice. Tumor cells replaced marrow cells in the bone cavity, invaded adjacent bone and muscle tissues, and formed a palpable tumor at the hip joint. PC-3/IF cell lines, generated from bone tumors by serial in vivo passages, grew with faster kinetics in the femur and metastasized to inguinal lymph nodes. Established tumors were treated with systemic interleukin-2 (IL-2) injections. IL-2 significantly inhibited the formation of palpable tumors and prolonged mouse survival at nontoxic low doses. Histologically IL-2 caused vascular damage and infiltration of polymorphonuclear cells and lymphocytes in the tumor as well as necrotic areas with apoptotic cells. These findings suggest destruction of tumor cells by systemic IL-2 therapy and IL-2 responsiveness of prostate carcinoma bone tumors.

Animals↗
PubMed1999

[Primary small cell carcinoma of the bladder].

OBJECTIVES: Primary small cell carcinomas of the bladder differ from transitional cell carcinomas by their rarity, histological characteristics, malignant potential and treatment. This study analysed the diagnostic criteria and therapeutic results obtained in a consecutive patient series over a 6-year period. MATERIALS AND METHODS: 7 patients (6 men and one woman) suffering from primary small cell carcinoma of the bladder were evaluated. Histological slides, treatment modalities and duration of survival were reviewed. RESULTS: The commonest clinical presentation was macroscopic haematuria. All tumours were invasive at the time of diagnosis. Two patients were treated by partial cystectomy, one of whom also received adjuvant chemotherapy. One patient was treated by radical cystectomy and 4 also received adjuvant chemotherapy, including 2 with neoadjuvant radiotherapy at a dosage of 65 Gy. The three patients treated by a single treatment modality (surgery alone or chemotherapy alone) had a shorter survival, in contrast with patients treated by a combination of chemotherapy and/or surgery. CONCLUSION: Primary small cell carcinomas of the bladder are rare and have a poor prognosis. Treatment must consist of a combination of neoadjuvant or adjuvant chemotherapy and surgery or radiotherapy to achieve the best results.

Aged↗
PubMed1999

Membrane type 1-matrix metalloproteinase (MT1-MMP) and MMP-2 immunolocalization in human prostate: change in cellular localization associated with high-grade prostatic intraepithelial neoplasia.

Membrane type 1-matrix metalloproteinase (MT1-MMP) is a known activator of latent MMP-2 (pro-MMP-2), and increased MMP-2 expression has been associated with tumor aggressiveness in prostate cancer. However, expression of MT1-MMP in human prostate tissue has not been described. We investigated the expression and immunolocalization of MT1-MMP and MMP-2 in the epithelial components of benign prostate epithelium, high-grade prostatic intraepithelial neoplasia (HGPIN), and prostate cancer. Tissue sections from the peripheral zone of 50 prostates (radical prostatectomy specimens) were chosen based on their containing benign glands, HGPIN, and prostate cancer glands. All 50 sections were immunostained for MT1-MMP and MMP-2 and were evaluated for staining pattern, uniformity, and intensity. Western blotting and gelatin zymography were done to confirm expression of MT1-MMP and activity of MMP-2, respectively. Comparisons were made between benign epithelium, HGPIN, and cancer. In benign glands, basal cells (BCs) uniformly stained intensely for MT1-MMP, whereas secretory cells (SCs) were rarely positive (P < 0.0001). Conversely in HGPIN, SCs showed consistent cytoplasmic staining (P < 0.0001). In cancer cells, staining was heterogeneous and varied from no staining to very intense staining in select glands. MMP-2 in normal tissue stained both BCs and the apical region of SCs, whereas in HGPIN, staining was observed in the SC in a predominantly cytoplasmic pattern. Similar to MT1-MMP, staining in cancer tissue for MMP-2 was heterogeneous; however, there was a significant association between the pattern of MMP-2 and MT1-MMP staining within the epithelial components of the cancer glands in individual specimens (P < 0.001). Finally, MMP-2 and MT1-MMP were confirmed to be expressed in the prostate tissues by gelatin zymography and Western blotting. In conclusion, we found that consistent changes in localization and intracellular distribution of MMP-2 and MT1-MMP were associated with the transition from benign prostate epithelium to HGPIN, suggesting that regulation of these enzymes is altered during the earliest stages of prostate cancer.

Adult↗
PubMed1998

Racial differences and prognostic significance of tumor location in radical prostatectomy specimens.

BACKGROUND: Our objective was to evaluate radical prostatectomy specimens for possible racial differences in tumor location, as well as to correlate tumor location with pathologic stage and disease-free survival. METHODS: Between January 1991-December 1997, 1,245 patients underwent radical prostatectomy with bilateral pelvic lymphadenectomy for clinically localized prostate cancer. Seven hundred and eighty-five patients who were treated with surgery as monotherapy were evaluated. Tumor location, defined as mainly anterior, mainly posterior, or both (anterior and posterior), was obtained from review of tumor maps prepared from pathological evaluation of completely embedded, resected specimens. RESULTS: Overall tumor location was anterior in 107 (14%), posterior in 459 (58%), and both in 219 (28%) cases. The incidence of anterior tumors was higher in African American men compared to Caucasians (16% vs. 11%, P = 0.045). The rate of positive surgical margins in anteriorly and posteriorly located tumors was 60% vs. 38% in African American men (P = 0.001) and 48% vs. 27% in Caucasians (P = 0.001), respectively. African American men were found to have a higher incidence of positive surgical margins (50%; 174/348) compared to Caucasian men (34%; 150/437; P = 0.001). CONCLUSIONS: Anterior tumors were present in 14% of our patients. African American men have a greater percentage of anterior tumors than do Caucasians. In addition, a higher rate of positive surgical margins was encountered in patients with anterior tumors, especially if they were African American men. In patients with an abnormal serum prostate-specific antigen level and negative sextant prostate biopsies, we recommend biopsy of the anterior zone of the prostate.

Adult↗