Cystoprostatectomy Specimens Research Articles

Incidentally Detected Prostate Cancer in Cystoprostatectomy Specimens

Objectives: Bladder and prostate cancers occur with increasing prevalence in the ageing population. Our study aims to quantify the incidence of prostate cancer in patients undergoing cystoprostatectomy for bladder cancer and assess the impact of that incidental prostate cancer on oncological outcome. Methods and Materials: We retrospectively reviewed the pathology reports of 128 men who underwent cystoprostatectomy for bladder cancer. Results: Twenty-three men (18%) were found to have incidental prostate cancer. All incidental prostate cancers were organ confined and 91% were well or moderately differentiated. At a mean follow-up of 55 months the prostate cancer-free survival was 96%. Conclusion: The incidence of prostate cancer in cystoprostatectomy specimens is high. When the prostate is removed completely the presence of incidental prostate cancer does not influence the overall oncological outcome.

Outcome of Patients with Fortuitous Prostate Cancer after Radical Cystoprostatectomy for Bladder Cancer

ObjectivesTo analyze the outcome of patients after fortuitous diagnosis of prostate cancer (PCa) on cystoprostatectomy (CPT) specimen. MethodsThe medical charts of 141 male patients who underwent radical CPT for urothelial cell carcinoma of the bladder between january 1995 and april 2000 were retrospectively reviewed. None of the patients had preoperative clinical or biological suspicion of PCa. ResultsPathological examination of the CPT specimens showed PCa in 20 patients (14.2%). Of these, 6 had a microfocal PCa, 10 had a pT2a tumour, 2 had a pT2b tumour, and 2 had a pT3a tumour. The Gleason score was ≤5 in 5 cases, 6 in 13 cases, and 7 in 2 cases. Two patients were lost to follow-up. Ten patients died of bladder cancer after a median follow-up of 13 months. Eight patients remained free of disease after a median follow-up of 64.5 months. None of the 20 patients experienced PCa recurrence during follow-up. ConclusionsIn our experience, the rate of unsuspected PCa on cystoprostatectomy specimens was 14.2%. The majority of these PCas were organ-confined, and there was no PCa recurrence during follow-up.

Incidentally detected prostate cancer in cystoprostatectomies: pathological and morphometric comparison with clinically detected cancer in totally embedded specimens

There are limited data regarding the pathological features of incidentally detected prostate cancer. Examination of cystoprostatectomy specimens obtained during bladder cancer treatment affords a unique opportunity to examine incidentally detected prostate cancer and determine its relationship with clinically detected prostate cancer obtained during radical prostatectomy. We compared the pathological findings of incidentally detected prostate cancer in 132 consecutive cystoprostatectomy specimens from patients treated for bladder cancer with a consecutive series of 228 radical prostatectomy specimens from patients treated for prostate cancer. All specimens were totally embedded and whole-mounted. Karyometry was evaluated in select subsets of patients from the study groups. Incidentally detected cancer was found in 42% of cystoprostatectomy specimens, and the cancers were of lower Gleason score and lower pathological stage with fewer positive surgical margins than in clinically detected cancers in age-matched radical prostatectomies. High-grade prostatic intraepithelial neoplasia (PIN) was present in 82% of radical prostatectomy specimens, in 70% of cystoprostatectomies with incidentally detected prostate cancer, and in 54% of cystoprostatectomies without prostate cancer. Mean nuclear and nucleolar area was lower in incidentally detected cancer and PIN when compared with clinically detected cancer and PIN, respectively, similar to the results with proliferative indices. We conclude that incidentally detected cancer is less aggressive than clinically detected cancer.

MT1G Hypermethylation Is Associated with Higher Tumor Stage in Prostate Cancer

Zinc is involved in several physiologic processes, including cell growth and proliferation. Although in normal prostate tissue zinc levels are high, there is a marked decrease in prostate cancer. Metallothioneins control the bioavailability of zinc and one isoform, MT1G, was reported down-regulated in prostate cancer. Here, we investigated whether promoter methylation might cause MT1G silencing in prostate cancer. The MT1G promoter was assessed by quantitative methylation-specific PCR on prospectively collected tissue samples from 121 patients with prostate cancer, 39 paired high-grade prostatic intraepithelial neoplasias (HGPIN), 29 patients with benign prostatic hyperplasia, 13 normal prostate tissue samples from cystoprostatectomy specimens, and prostate cancer cell lines. The methylation levels were calculated and were correlated with clinical and pathologic variables. Reverse transcription-PCR was done in cell lines to assess MT1G mRNA expression before and after demethylating treatment. MT1G promoter hypermethylation was found in 29 of 121 prostate cancer, 5 of 39 HGPIN, 3 of 29 benign prostatic hyperplasia, and 0 of 13 normal prostate tissue samples. No significant differences in methylation frequencies or levels were found (P = 0.057, for both). Methylation levels were found to correlate with tumor stage but not with Gleason grade. MT1G hypermethylation was more frequent in prostate cancer that spread beyond the prostate capsule. All prostate cancer cell lines tested showed MT1G promoter methylation, but no differences in expression were apparent after demethylation. Our findings suggest that MT1G promoter methylation is associated with tumor aggressiveness in prostate cancer and it might be a marker of locally advanced disease.

Ethnic differences in neuroendocrine cell expression in normal human prostatic tissue

Objectives To determine whether any differences exist in neuroendocrine (NE) cell differentiation in normal prostates among various ethnic groups because the incidence and mortality from prostate cancer vary across racial groups. Methods Archived paraffin-embedded prostate samples not containing any malignancy were obtained from cystoprostatectomy specimens. Prostatic tissue was obtained from 15 African Americans, 13 Hispanics, 15 Asians, and 16 whites. NE cells were identified based on immunoreactivity for chromogranin A. The mean number of NE cells per high power field (HPF) for each patient was determined using a visual quantitative method by two observers who were unaware of the race of the patients. Results The geometric mean number of NE cells was 6.1/HPF for Asians, 5.6/HPF for whites, 4.0/HPF for Hispanics, and 0.7/HPF for African Americans. A highly significant difference was observed in the distribution of NE cells between African Americans and each of the other races ( P ≤0.003). A trend toward greater NE expression was noted in Asians and whites compared with Hispanics; however, this difference did not reach statistical significance. Conclusions We found a fivefold to eightfold difference in the distribution of NE cells in the normal prostates of African-American men compared with that of other races. The comparatively low NE cell expression in African-American men may play a role in the greater rate of prostate carcinogenesis seen in this ethnic group.

Carcinosarcoma of the prostate: two cases with distinctive morphologic and immunohistochemical findings

Carcinosarcomas (CS) of the prostate are very uncommon neoplasms defined by the admixture of malignant epithelial and mesenchymal components. We describe here two new examples of CS in two patients aged 66 and 77 years, the first without previous history of prostate adenocarcinoma and the second with a 5-year history of acinar type prostate adenocarcinoma. The diagnosis of CS was made on the cystoprostatectomy specimen in the first case and transurethral resection in the second case. Both biphasic tumours exhibited papillary areas of ductal differentiation and conventional adenocarcinoma in the epithelial component, as well as malignant fibrous histiocytoma and angiosarcomatous areas in the first case and solid, poorly differentiated epithelial areas with neuroendocrine features in the second case. Immunohistochemistry revealed over-expression of c-erb B2 in the papillary epithelial component of both cases, whereas the solid undifferentiated epithelial areas in the second patient expressed c-kit, CD10 and synaptophysin, thus conforming a very undifferentiated cell population. The angiosarcomatous component of the first case expressed CD31 and CD10. The clinical course of the cases was divergent; the first patient is free of disease after radical surgery and adjuvant therapy and the other died 5 months after the diagnosis of CS, having already developed liver metastases.

Preservation of prostate during radical cystectomy: Evaluation of prevalence of prostate cancer associated with bladder cancer

Objectives To estimate the frequency and characteristics of prostatic lesions discovered incidentally in radical cystoprostatectomy specimens and to determine whether any factors would allow for the detection of prostate cancer preoperatively. Methods A total of 100 radical cystoprostatectomy specimens with orthotopic bladder reconstruction were performed for malignant bladder disease between 1990 and 2000. The mean patient age at surgery was 62 ± 8 years (range 32 to 75). Digital rectal examination and prostate-specific antigen (PSA) assay were done routinely before surgery. During the 10-year study period, the same pathologist examined the prostatic tissues from radical cystoprostatectomy specimens using McNeal’s technique on fine slices every 2.5 mm. Results The overall incidence of prostate cancer discovered incidentally in radical cystoprostatectomy specimens was 51%, of which 29% were microcancers (volume less than 0.5 cm 3) and 22% were significantly larger (volume 0.5 cm 3 or more). The mean Gleason score was 6. Of the tumors, 24% could be considered “clinically nonsignificant” (less than 0.5 cm 3 and Gleason score less than 7). The mean preoperative PSA level was 4.13 ± 1.36 ng/mL. Of 66 patients with a PSA level of less than 4 ng/mL (mean PSA 1.5 ± 0.8) and a normal digital rectal examination before surgery, 50% had prostate cancer, of which 69% were microcancers. Conclusions The prevalence of prostate cancer (51%) in our series is among the highest in published reports. Furthermore, our results stress that currently no factors are available to enable the detection of “clinically significant” prostate cancer preoperatively.

Alpha-methylacyl-CoA racemase (AMACR) expression in normal prostatic glands and high-grade prostatic intraepithelial neoplasia (HGPIN): Association with diagnosis of prostate cancer

Alpha-methylacyl-CoA racemase (AMACR) is strongly expressed in prostate cancer with variable expression in high-grade prostatic intraepithelial neoplasia (HGPIN) and low expression in normal prostate. We examined whether AMACR expression in HGPIN and normal tissue was associated with subsequent diagnosis of cancer or proximity to a cancer focus. Needle core biopsies from 45 patients with isolated HGPIN, 12 radical prostatectomy (RP) specimens with prostatic carcinoma and 6 cystoprostatectomies without prostatic carcinoma were immunostained for AMACR. Among patients with HGPIN, 23 (cases) showed cancer on a later biopsy and 22 (controls) had no cancer with at least 3 consecutive negative biopsies. In the biopsy set, the mean AMACR expression per gland in the normal compartment of the cases (0.29) was significantly higher than the controls (0.21) (P = 0.0006). In the RP set, normal glands near a cancer focus had higher mean AMACR expression than those that were distant (P = 0.0006). There was no difference within the HGPIN compartment between cases and controls in the biopsies, or between near and distant glands in the RP set. Mean AMACR staining of normal glands in the cystoprostatectomy specimens was significantly lower than in normal glands in close proximity to a cancer focus. Higher expression of AMACR in normal glands near a focus of cancer, as well as in the subjects eventually showing cancer, suggests a possible field effect in prostatic carcinogenesis. AMACR expression in normal glands therefore might be a useful predictor for repeat biopsy outcomes or as an intermediate endpoint in chemoprevention studies.

What is the ratio of urethral recurrence risk after radical cystoprostatectomy for bladder cancer?

There is always a risk of urethral recurrence after radical cystoprostatectomy in patients with bladder transitional cell cancer. Taking these risk factors of urethral recurrence into account, orthotopic neobladders or urinary diversions without using the urethra are performed. But urethral tumour recurrence occurs much less than the expected. We assessed the etiological factors that affect the urethral recurrence in orthotopic and nonorthotopic urinary diversion cases. Sixty-four patients with bladder cancer who underwent radical cystoprostatectomy and urinary diversion between 1994 and 2002 were included this study. Conventional risk factors effecting the selection of operation type and urethral recurrence were evaluated in these patients. Cystoscopy and biopsy were done and pathologic specimen was obtained preoperatively, and cystoscopy and urethral washout cytology were done postoperatively. Routine bladder biopsies were done in uncertain cases at follow-up. Risk factors increasing the urethral recurrence are as follows: papillary and multiple tumours, tumour invading bladder neck and trigone, extensive CIS, prostatic stromal and urethral invasion, positive surgical margin and history of upper urinary tract tumour. In 31 patients having one or more of these criteria, continent nonorthotopic urinary diversion was performed, but 33 patients without these risk factors underwent orthotopic urinary diversion. Simultaneous urethrectomy was not done in any of these patients. Among the patients who underwent radical cystoprostatectomy, none was with positive surgical margin in the distal end of the prostatic urethra. In preoperative cystoscopy, tumoural mass was seen near to collum in eight patients and in the prostatic urethra in three patients. Histopathological examination of cystoprostatectomy specimen displayed transient epithelial cell carcinoma of prostatic urethra in three patients, transient epithelial cell metaplasia inside the prostate in five patients and invasion to the urothelium of bladder neck in three patients. There were not any transient epithelial cell cancer metastases in prostatic stroma in any of these patients. One patient underwent urethrectomy, since atypical cells were observed in postradical prostatectomy urethral washout cytology but there was no tumour found in pathological examination of the specimen. Therefore, urethral tumour recurrence did not occur after 25 months follow up. These findings suggest that some of the conventional risk factors of urethral recurrence were exaggerated. We may also conclude that there is no need for prophylactic urethrectomy unless there is urethral cancer or cancer in the surgical margin. But if utilization of urethra is planned, evaluation of prostatic stroma by TUR biopsies and urethral anastomose margin by frozen section during the operation is necessary.

Incidence and Location of Prostate and Urothelial Carcinoma in Prostates From Cystoprostatectomies: Implications for Possible Apical Sparing Surgery

Prostatic carcinoma (Pca) at cystoprostatectomy is usually an incidental finding with the majority thought to be clinically insignificant. Most studies have not specifically addressed the location of Pca or the incidence and location of in situ or invasive urothelial carcinoma (Uca) in prostates of cystoprostatectomy specimens. The frequency of involvement of the apex with these processes has clinical implications. Specifically urinary continence following orthotopic diversion may be enhanced by prostate apical sparing. In this study the pathological features of Pca and Uca, and the frequency of apical involvement were investigated in prostates from cystoprostatectomy specimens. Whole mounted prostates from 121 consecutive cystoprostatectomy specimens were analyzed. Pca location, tumor volume, grade, stage, surgical margin and pelvic lymph node status of Pcas were assessed. Clinically insignificant Pcas had a volume of less than 0.5 cc without Gleason pattern 4, extracapsular extension, seminal vesicle invasion, lymph node involvement or positive surgical margins. Prostate involvement by Uca or urothelial carcinoma in situ (CIS)/severe dysplasia and its location were assessed. Of 121 prostates 50 (41%) had unsuspected Pca, of which 24 (48%) were clinically significant. Of Pcas 30 of 50 (60%) involved the apex, including 19 of 24 (79%) that were significant and 11 of 26 (42%) that were insignificant. Of 121 prostates 58 (48%) had Uca involving the prostatic stroma, noninvasive Uca or urothelial CIS/severe dysplasia in the prostatic urethra or periurethral ducts, of which 19 (33%) had apical involvement. Overall only 32 of 121 patients (26%) had no Pca or prostate Uca/CIS and only 45 (37%) had no clinically significant Pca or Uca/CIS in the prostate. However, 74 of the 121 patients (61%) had no prostatic apical involvement by Pca or Uca/CIS and 85 (70%) had no apical involvement by clinically significant Pca or Uca/CIS. Patients with prostatic apical involvement by invasive or in situ Uca uniformly had involvement of more proximal (toward the base) portions of the prostate. The majority of prostates from cystoprostatectomies had no involvement of the prostatic apex by Uca or clinically significant Pca. Hence, most patients may be candidates for prostate apical sparing. However, involvement of the apex by Uca in any patient raises concern about procedures that leave portions of the prostate urethra after cystectomy in an effort to improve continence. In candidates for orthotopic neobladder reconstruction removing all of the prostatic urethra and sparing the remainder of the prostatic apex may allow improved preservation of urinary continence with an acceptable low risk of clinical Pca progression. Whether future strategies for preoperative exclusion of apical Pca and intraoperative assessment of more proximal prostate to help exclude apical urothelial disease may identify patients suitable for prostatic apical sparing remains to be determined. The impact on functional outcomes and cancer control also require additional study.

Pathologic characterization of prostate cancers with a very low serum prostate specific antigen (0–2 ng/mL) incidental to cystoprostatectomy: is PSA a useful indicator of clinical significance?

Cystoprostatectomy specimens removed for bladder malignancy (1988–2000) at two referral centers (Mayo Clinic, Rochester, MN, The University Hospital of Innsbruck, Innsbruck, Austria) were examined for the coincidental finding of prostate cancer (PCA). Centralized examination of the prostate by a single uropathologist was performed if at the time of surgery the patient’s serum PSA was ≤2.0 ng/mL and there were no suspicious lesions by digital prostate examination. Pathologic grade, stage, morphometric volume, number of tumor foci and association with areas of high grade prostatic intraepithelial neoplasia (HGPIN) were assessed by light microscopy. DNA ploidy and cellular proliferative index were assessed through digital image analysis. Clinically significant cancers were defined as tumors with ≥0.5 cc volume, Gleason 4 or 5 architecture, pT3, positive surgical margin, multifocality >3, nondiploid DNA content or proliferation index >5%. From nearly 1600 cystoprostatectomy specimens, 129 met the enrollment criteria. Thirty-patients (23%) within this group had PCA identified. Sixty percent of these tumors met the criteria for a clinically significant cancer. Nondiploid nuclear content was present in 17%. HGPIN was present in 70% and directly abutting carcinoma in 86% of prostates. The biologic activity of PCA appears to be independent of serum PSA. Any future definition of a clinically significant PCA should not be solely based upon histologic criteria, but needs to encompass clinical parameters (age, co-morbidities) and a noninvasive assessment of tumor volume and biologic doubling time.

Transitional cell carcinoma involving the prostate: a clinicopathological retrospective study of 76 cases.

We reviewed the degree to which extension from transitional cell carcinoma into the prostate affects survival. We also compared whether prostatic stromal invasion occurring via direct extension through the bladder wall differs from stromal invasion arising intraurethrally. A total of 76 men who underwent radical cystectomy for transitional cell carcinoma also had prostate involvement. Patients were separated into group 1-18 with primary bladder tumor extending transmurally through the bladder wall to invade the prostate and group 2-58 with prostate involvement arising from within the prostatic urethra. In the latter group the degree of prostate invasion was classified as urethral mucosal involvement, ductal/acinar involvement and stromal invasion. The 5-year overall survival and recurrence-free rate were 22% and 28% in group 1 versus 43% and 45% in group 2, respectively. In group 2 survival rates were similar in those with prostatic urethral and ductal tumors (without stromal invasion). Five-year overall survival rates without and with stromal invasion were 49% and 25%, respectively (p = 0.024). Prostate involvement decreased survival, which varied according to primary bladder stages (Pis, P1, P2a/b and P3a/b, p = 0.004) or superficial (Pis, Pa and P1) and muscle invasive (P2a/b and P3/b, p = 0.045), disease in 2 groups. Those with positive lymph nodes experienced poorer outcomes in each group. The 5-year overall survival rate in the 19 men with positive lymph nodes was 13% and it was 44% with negative lymph nodes (p = 0.034). The major prognostic factors were age, degree of prostate invasion and lymph node involvement. The invasion pathways of prostate invasion in patients with transitional cell bladder carcinoma have a statistically significant prognostic role in survival. Transitional cell carcinoma of the bladder extending into the prostate through the bladder wall and bladder carcinoma that did not directly infiltrate the prostate through the bladder wall are 2 distinct clinicopathological entities that should not be included in the same staging grade.

Clinical study of transitional cell carcinoma of the prostate associated with bladder transitional cell carcinoma.

Transitional cell carcinoma of the prostate in patients with bladder cancer appears to influence the prognosis and affects the decision about therapeutic modality. Therefore, it is important to characterize transitional cell carcinoma associated with bladder cancer. From April 1980 to December 1998, 81 male patients underwent total cystoprostatectomies for transitional cell carcinoma of the bladder. The 81 cystoprostatectomy specimens were examined to clarify the characteristics of prostatic involvement by transitional cell carcinoma. The extent, origin, mode of spread and risk factor of prostatic involvement as well as the prognosis were investigated. In 13 of 15 patients with prostatic involvement the prostate was examined by sequential step sections. Prostatic involvement was observed in 15 of 81 patients (18.5%). Prostatic urethral involvement, invasion to prostatic duct/acinus, prostatic stromal invasion and extraprostatic extension and/or seminal vesicle involvement were recognized in 12 (80%), 14 (93.3%), six (40%), and five (33.3%) of the 15 patients, respectively. Twelve of the 15 patients (80%) with prostatic involvement had papillary or non-papillary tumors (i.e. carcinoma in situ) both in the prostatic urethra and prostatic duct. In 10 of these 12 patients (88.3%), there was contiguity between prostatic urethral and ductal tumors. Seven of the 23 patients (30.4%) with carcinoma in situ of the bladder showed prostatic involvement, which increased to 50% in the presence of carcinoma in situ of the trigone or bladder neck. Eighty per cent of the patients with prostatic involvement showed papillary or non-papillary tumors both in the prostatic urethra and prostatic duct. There was a high level of contiguity between both tumors. Patients with carcinoma in situ of the trigone or bladder neck revealed significantly higher incidence of prostatic involvement.

Practice protocol for examination of cystectomy and cystoprostatectomy specimens: proposal of a standardized reporting form

Practice protocol for examination of cystectomy and cystoprostatectomy specimens: proposal of a standardized reporting form

PROSTATIC SARCOMA WITH RAPID TUMOR PROGRESSION AFTER NERVE SPARING RADICAL CYSTOPROSTATECTOMY

Prostate sarcomas are rare but aggressive neoplasms presenting unique therapeutic challenges. We report a case of prostate sarcoma, and discuss disease control and preservation of quality of life. CASE REPORT A 51-year-old healthy male with normal prostate specific antigen was referred to our institution for evaluation of an asymmetrically enlarged nodular prostate and progressive obstructive voiding symptoms. Transrectal ultrasound revealed a multilocular cystic mass replacing the left side of the prostate (fig. 1, A). Pathological examination of the biopsy cores and subsequent chips from transurethral resection of the prostate for acute urinary retention revealed an indeterminate subtype of prostatic sarcoma. Further diagnostic evaluation included pelvic magnetic resonance imaging which demonstrated a complex multilocular solid mass of the left peripheral prostatic lobe displacing the seminal vesicles but without evidence of local invasion (fig. 1, B). Computerized tomography of the chest, abdomen, pelvis and brain, bone scan and fluorodeoxyglucose whole body tumor scan revealed no evidence of metastatic disease. The patient subsequently elected to undergo radical cystoprostatectomy with unilateral sparing of the neurovascular bundle and continent urinary diversion. Pathological examination of the cystoprostatectomy specimen revealed 5 5.5 cm. high grade prostatic sarcoma with focal chondroid differentiation arising from the left prostatic lobe. All surgical margins were negative. The patient presented with bloody urethral discharge 2 months postoperatively. Urethroscopy and biopsy revealed recurrent sarcoma at the level of the external urethral sphincter. Repeat computerized tomography further demonstrated interval development of multiple bilateral pulmonary nodules. The patient was subsequently started on systemic chemotherapy with dacarbazine, ifosfamide, doxorubicin and mesna. DISCUSSION

Human rhabdosphincter cell culture: a model for videomicroscopy of cell contractions.

Physiology of the human rhabdosphincter and its innervation are still a subject to controversy. A better understanding of rhabdosphincter function and anatomy might help to solve important urological problems like urinary incontinence. It was the aim of the present study to develop a human sphincter cell culture model for investigation of contraction mechanisms in vitro. METHODS AND RESULTS Cells were isolated from human rhabdosphincter tissue obtained from prostatectomy and cystoprostatectomy specimens. Cultured cells expressed typical features of striated muscle cells. By means of videomicroscopy with a time lapse videosystem cell contractions could be documented. Under control conditions without any contractile stimulant 8% of the cells were seen to contract. Cholinergic stimulation with 10 mM of acetylcholine induced a significant increase in contraction rate to 49%. These results demonstrate that cholinergic stimulation triggers contraction of cultured human rhabdosphincter cells. This model might help to understand external urethral sphincter physiology and to establish new therapies for the treatment of sphincter dysfunctions. Prostate 47:189-193, 2001.

High-Grade Prostatic Intraepithelial Neoplasia in Cystoprostatectomy Specimens

High-Grade Prostatic Intraepithelial Neoplasia in Cystoprostatectomy Specimens

Significance of high-grade prostatic intraepithelial neoplasia in needle biopsy specimens

Objectives. To examine the significance of high-grade prostatic intraepithelial neoplasia (HGPIN) in biopsy specimens. Methods. We performed sextant biopsies on a series of 83 cystoprostatectomy specimens removed for bladder cancer. For each case the number of foci and volume of both HGPIN and prostate cancer were assessed in the prostatectomy specimens and compared with the number of biopsy specimens involved by HGPIN. Results. We identified HGPIN in 82 (99%) of 83 prostatic glands, whereas prostate cancer was found in 41 cases (49%). Corresponding sextant biopsies harbored both HGPIN and prostate cancer in 6 cases (7%), whereas only HGPIN was diagnosed in 29 sextant biopsies (35%). There was a positive correlation between the number of biopsy specimens containing HGPIN and the volume and multifocality of HGPIN in the corresponding prostatic glands. Prostates with HGPIN on sextant biopsy contained prostate cancer significantly more often when compared to cases with no HGPIN on sextant biopsy. Frequency of concurrent prostate cancer was higher in cases with two or more biopsy specimens containing HGPIN than in cases with only one such biopsy specimen, but case numbers of these categories were too small to render this difference statistically significant. Conclusions. The presence of HGPIN in sextant biopsies is a significant predictor of concurrent prostate cancer. Multifocality of HGPIN is a useful parameter in assessing the extent of HGPIN in the corresponding prostates. Its value in predicting a significantly increased risk of concurrent prostate cancer needs to be further investigated in larger case studies.

INCREASED PROSTATIC LYSOPHOSPHATIDYLCHOLINE ACYLTRANSFERASE ACTIVITY IN HUMAN PROSTATE CANCER:: A MARKER FOR MALIGNANCY

Phospholipase A2 and lysophosphatidylcholine acyltransferase (LAT) constitute a deacylation-reacylation cycle that incorporates arachidonic acid into the lipid membrane. In a preliminary report we found increased LAT activity in malignant prostate tissue. We measured LAT activity in prostate tissue from a large number of patients undergoing prostatectomy. Prostate tissue from 93 patients undergoing radical prostatectomy for prostate carcinoma, 14 undergoing cystoprostatectomy for bladder cancer, 55 undergoing transurethral resection for benign prostatic hyperplasia and 11 with prostate cancer undergoing transurethral resection for relief of obstructive symptoms was analyzed for LAT activity. In radical prostatectomy specimens using oleoyl coenzyme A as substrate mean increase in LAT activity between malignant and benign portions of the same specimen was 0.68 +/- 0.12 nmol./mg. protein per minute (p <0.00001). In all radical prostatectomy specimens analyzed LAT activity was 43% higher in the malignant than benign portions (2.25 +/- 0.15 versus 1.57 +/- 0.11 nmol./mg. protein per minute, p <0.001). In the 10 benign prostate specimens obtained from cystoprostatectomy mean LAT activity was 1.12 +/- 0.18 nmol./mg. protein per minute, which was significantly lower than that of benign portions of radical prostatectomy (p <0.05). LAT activity in benign cystoprostatectomy specimens was significantly higher than that in the 50 benign transurethral resection specimens (0.54 +/- 0.05, p <0.01), possibly due to heat damage in transurethral resection specimens during collection. However, LAT activity in transurethral resection specimens from patients with known prostate cancer was similarly increased. Similar results were obtained using arachidonoyl coenzyme A. We demonstrated increased LAT activity in malignant tissue from patients with prostate cancer. Thus, the deacylation-acylation remodeling cycle may be enhanced to provide more arachidonic acid to meet the demand for prostaglandin E2 synthesis in malignant tissue.

An in vitro model for videoimaging of human bladder smooth muscle cell contractions.

Knowledge regarding human bladder smooth muscle cell (SMC) physiology is very limited. Only a few specific medical therapies for bladder disorders have therefore been established. The objective of this study was to develop a model for videomicroscopy of bladder SMC contractions. Cells were isolated from human cystoprostatectomy specimens and cultured in a modified EMEM medium. These cells were identified as SMCs by means of immunohistochemistry. For videomicroscopy, the culture flasks were coated with a viscous agent to allow cell contraction. Contractions were visualized by means of a cell culture microscope with a time-lapse videosystem. For cholinergic stimulation of the cells, acetylcholine, in concentrations ranging from 100 microM to 10 mM, was applied. The percentage of contracting cells within the observation field was evaluated for quantitative analysis. In control experiments without contractile stimulant 6% of the cells were observed to contract. Stimulation with acetylcholine induced a significant dose-dependent increase to 47% in contracting cells. These results demonstrated that videomicroscopy is an appropriate tool to investigate the contraction mechanisms of bladder SMCs. This model offers the possibility of studying drug effects on the human detrusor in vitro.