Metabolic syndrome is not associated with greater evidences of proliferative inflammatory atrophy and inflammation in patients with suspected prostate cancer.

INTRODUCTION AND OBJECTIVES: To evaluate the association between metabolic syndrome (MetS) and proliferative inflammatory atrophy (PIA) in patients with suspected prostate cancer (PCa). PATIENTS AND METHODS: From June 2015 to July 2016, we conducted the FIERY (Flogosis Increased Events of pRostatic biopsY) study at the Urology section, Department of Surgery of the University of Catania (Local registration number: #131/2015). A total of 205 patients with elevated prostate-specific antigen (≥ 4 ng/ml) or clinical suspicion of PCa who underwent primary transperineal prostate biopsy were included in this cross-sectional study. The assessment of PIA, HGPIN, and PCa were performed by 2 experienced pathologists and samples were investigated for the presence of an inflammatory infiltrate, according to the Irani score. Primary and secondary Gleason grade of tumor in positive biopsies were evaluated according to the 2016 ISUP Modified Gleason System. RESULTS: In the entire cohort, median age was 68.0 (interquartile range: 62.0-74.5), median prostate-specific antigen was 6.5 (interquartile range: 5.51-9.57). The prevalence of MetS was 34.1%, the detection rate of PCa was 32.7%, the rate of PIA was 28.3%, the rate of HGPIN was 32.2%, whereas the rate of severe intraprostatic inflammation (Irani-score ≥4) was 28.8%. When comparing clinical and histological variables in patients without and with PIA, metabolic aberrations where not significantly different in both groups. We did not find statistical association in detection rate of PCa (29.3% vs. 34.0%; P = 0.07) and HGPIN (27.6% vs. 34.0%; P = 0.37) in patients with and without PIA, respectively. When considering metabolic aberrations, MetS was not associated with Irani-score ≥4 (28.6% vs. 28.4%; P = 0.96) and none of each component was statistically predictive of severe inflammation. At the multivariable logistic regression analysis, PIA, HGPIN, and MetS were not associated with greater risk of PCa. CONCLUSION: In this study, we did not show an association between MetS and PIA and PCa. Although the small sample size and the cross-sectional nature of the study, we do not suppose that MetS could be associated with greater evidence of PIA. Further studies should be conducted to evaluate the exact nature of this pathological lesion.

"Finding the needle in a haystack": oncologic evaluation of patients treated for LUTS with holmium laser enucleation of the prostate (HoLEP) versus transurethral resection of the prostate (TURP).

PURPOSE: To evaluate oncologic parameters of men with bothersome LUTS undergoing surgical treatment with HoLEP or TURP. METHODS: Five hundred and eighteen patients undergoing HoLEP (n = 289) or TURP (n = 229) were retrospectively analyzed for total PSA, prostate volume, PSA density, history of prostate biopsy, resected prostate weight, and histopathological features. Univariate and multivariate logistic regression models were used to identify independent predictors of incidental PCa (iPCa). RESULTS: Men undergoing HoLEP had a significantly higher total PSA (median 5.5 vs. 2.3 ng/mL) and prostate volume (median 80 vs. 41 cc), and displayed a greater reduction of prostate volume after surgery compared to TURP patients (median 71 vs. 50%; all p < 0.001). With a prevalence of incidental PCa (iPCa) of 15 and 17% for HoLEP and TURP, respectively, the choice of procedure had no influence on the detection of iPCa (p = 0.593). However, a higher rate of false-negative preoperative prostate biopsies was noted among iPCa patients in the HoLEP arm (40 vs. 8%, p = 0.007). In multivariate logistic regression, we identified patient age (OR 1.04; 95% CI 1.01-1.07, p = 0.013) and PSA density (OR 2.13; 95% CI 1.09-4.18, p = 0.028) as independent predictors for the detection of iPCa. CONCLUSIONS: Despite differences in oncologic parameters, the choice of technique had no influence on the detection of iPCa. Increased patient age and higher PSA density were associated with iPCa. A higher rate of false-negative preoperative prostate biopsies was noted in HoLEP patients. Therefore, diagnostic assessment of LUTS patients requires a more adapted approach to exclude malignancy, especially in those with larger prostates.

Metabolic syndrome diagnosis and widespread high grade prostatic intraepithelial neoplasia significantly increase prostate cancer risk: results from a multicenter biopsy study.

BACKGROUND: To test in multicenter setting if patients affected of metabolic syndrome (MetS) and initial widespread high grade prostatic intraepithelial neoplasia (wHGPIN) diagnosis are at higher risk of prostate cancer (PCa) on repeat biopsy. METHODS: Patients clinical charts from three European Academic Hospital were reviewed in order to identify patients with initial diagnosis of HGPIN undergone to repeat biopsy. Inclusion and exclusion criteria were adopted to minimize patient heterogeneity. MetS was defined according to Word Heart Organization criteria while initial wHGPIN when ≥ 4 cores biopsy were involved. A multivariate logistic model was computed to assess the association between PCa and clinical-pathological variables. RESULTS: Overall 283 patients were scheduled. Median age was 67 years (IQR 62-72). MetS was diagnosed in 116/283 (41%) patients and PCa was detected in 84/283 (29.7%) patients. In particular, PCa was more frequently diagnosed in patients affected of wHGPIN and MetS (45/86, 52.3%) than in patients with wHGPIN and normal metabolic profile (28/95, 29.5%), p = 0.002. The multivariate logistic model confirmed that wHGPIN and MetS are independent risk factors for following PCa diagnosis, respectively OR 2.4 (95% CI 1.01-5.71, p = 0.04), OR 2.79 (95% CI 1.49-5.22, p = 0.01) while total PSA and DRE findings are not able to predict PCa at repeat biopsy, OR 1.05 (95% CI 0.98-1.03 p = 0.69) and OR 1.01 (95% CI 0.55-1.84, p = 0.96) respectively. CONCLUSIONS: wHGPIN is positively associated to PCa; assessing metabolic profile and repeat prostate biopsy is advisable in patients with initial diagnosis of wHGPIN.

Patients with metabolic syndrome and widespread high grade prostatic intraepithelial neoplasia are at a higher risk factor of prostate cancer on re-biopsy: a prospective single cohort study.

OBJECTIVES: To test the hypothesis that patients with widespread high grade prostatic intra epithelial neoplasia (wHGPIN) and metabolic syndrome (MetS) are at a higher risk of prostate cancer (PCa) at a repeat biopsy. METHODS AND MATERIALS: We prospectively evaluated 161 patients submitted from December 2004 to December 2011 to prostate rebiopsy after a initial diagnosis of HGPIN in a tertiary academic center. A 12 core biopsy template was used for all the biopsies. Rebiopsy was performed six months after the initial biopsy independently from PSA level and the DRE finding. wHGPIN was defined as≥4 biopsy cores involved. MetS was defined according to the National Cholesterol Education Program's Adult Treatment Panel III criteria. RESULTS: Overall, 64 patients (39.7%) presented wHGPIN and 97 isolated HGPIN (60.3%). MetS was found in 63 patients, 39.1% of the whole population. Out of them 16 (25.3%) and 47 (74.7%) patients had a diagnosis of isolated and wHGPIN (P = 0.001). PCa detection rate at repeat biopsy was significantly higher in patients with MetS and wHGPIN than in those with wHGPIN and no MetS (57.4% Vs 23.5%; P = 0.016). A logistic regression model confirmed that wHGPIN and MetS are independent risk factors of prostate cancer diagnosis (respectively: Odds ratio (OR) = 4.187, 95%CI: 1.65-10.57 p = 0.002 and OR=3.603, 95%CI: 1.41-9.19, p = 0.007). CONCLUSION: Patients with MetS and wHGPIN are at a higher risk of PCa, therefore performing a new prostate biopsy in those patients should be recommended.

Association between biomarkers of obesity and risk of high-grade prostatic intraepithelial neoplasia and prostate cancer--evidence of effect modification by prostate size.

Prostate enlargement is common with aging and obesity. We investigated the association between obesity and prostate cancer controlling for differential detection related to prostate enlargement. In an analysis of 500 men, we found body mass index, waist-hip ratio, and blood leptin levels were significantly associated with high-grade PC, but only among men without prostate enlargement. Leptin was also significantly associated with high-grade prostatic intraepithelial neoplasia (HGPIN) in the absence of prostate enlargement. Our results suggest obesity advances prostate carcinogenesis, and that detection biases at prostate biopsy may explain past inconsistencies in the association between obesity and PC.

Inflammation, focal atrophic lesions, and prostatic intraepithelial neoplasia with respect to risk of lethal prostate cancer.

BACKGROUND: A challenge in prostate cancer (PCa) management is identifying potentially lethal disease at diagnosis. Inflammation, focal prostatic atrophy, and prostatic intraepithelial neoplasia (PIN) are common in prostate tumor specimens, but it is not clear whether these lesions have prognostic significance. METHODS: We conducted a case-control study nested in a cohort of men diagnosed with stage T1a-b PCa through transurethral resection of the prostate in Sweden. Cases are men who died of PCa (n = 228). Controls are men who survived more than 10 years after PCa diagnosis without metastases (n = 387). Slides were assessed for Gleason grade, inflammation, PIN, and four subtypes of focal prostatic atrophy: simple atrophy (SA), postatrophic hyperplasia (PAH), simple atrophy with cyst formation, and partial atrophy. We estimated OR and 95% CI for odds of lethal PCa with multivariable logistic regression. RESULTS: Chronic inflammation and PIN were more frequently observed in tumors with PAH, but not SA. No specific type of atrophy or inflammation was significantly associated with lethal PCa overall, but there was a suggestion of a positive association for chronic inflammation. Independent of age, Gleason score, year of diagnosis, inflammation, and atrophy type, men with PIN were 89% more likely to die of PCa (95% CI: 1.04-3.42). CONCLUSION: Our data show that PIN, and perhaps presence of moderate or severe chronic inflammation, may have prognostic significance for PCa. IMPACT: Lesions in tumor adjacent tissue, and not just the tumor itself, may aid in identification of clinically relevant disease.

Significance of perineural invasion, lymphovascular invasion, and high-grade prostatic intraepithelial neoplasia in robot-assisted laparoscopic radical prostatectomy.

BACKGROUND: Recently, more detailed histopathological variables such as perineural invasion (PNI), lymphovascular invasion (LVI), and high-grade prostatic intraepithelial neoplasia (HGPIN) have been investigated as prognostic factors for adverse pathologic findings on the radical prostatectomy specimen. We aim to determine whether these pathological factors are associated with adverse pathologic features after robot-assisted laparoscopic radical prostatectomy (RALP). METHODS: All 407 patients who underwent RALP with pelvic lymphadenectomy between July 2005 and December 2009 were analyzed, retrospectively. We investigated the association of these three pathological parameters with adverse pathological findings in RALP specimen and biochemical recurrence using Kaplan-Meier analysis with log-rank test and a multivariate Cox proportional hazard model. RESULTS: The PNI and LVI were significantly associated with a higher pathological stage, a higher pathological Gleason score, a higher tumor volume in RALP specimen, a higher frequency of positive surgical margins, and a higher frequency of seminal vesicle invasion. In addition, PNI correlated with preoperative PSA, clinical stage, and Gleason score on needle biopsy. However, the HGPIN was not significantly associated with the clinicopathological characteristics studied. Using log-rank test, presence of PNI (P < 0.001) increases the probability of biochemical recurrence. On multivariate analysis, all three pathological parameters were not significantly correlated with biochemical recurrence. CONCLUSION: Although presence of PNI and LVI in RALP specimen correlated with multiple adverse clinicopathological factors, it did not predict biochemical recurrence, thus limiting its clinical usefulness. HGPIN was not significantly associated with the clinicopathological characteristics studied.

Progression from high-grade prostatic intraepithelial neoplasia to cancer: a randomized trial of combination vitamin-E, soy, and selenium.

PURPOSE: High-grade prostatic intraepithelial neoplasia (HGPIN) is a putative precursor of invasive prostate cancer (PCa). Preclinical evidence suggests vitamin E, selenium, and soy protein may prevent progression of HGPIN to PCa. This hypothesis was tested in a randomized phase III double-blind study of daily soy (40 g), vitamin E (800 U), and selenium (200 µg) versus placebo. PATIENTS AND METHODS: Three hundred three men in 12 Canadian centers were analyzed. The main eligibility criterion was confirmed HGPIN in at least one of two biopsies within 18 months of random assignment. Treatment was administered daily for 3 years. Follow-up prostate biopsies occurred at 6, 12, 24, and 36 months postrandomization. The primary end point was time to development of invasive PCa. Kaplan-Meier plots and log-rank tests were used to compare two treatment groups for this end point. RESULTS: For all patients, the median age was 62.8 years. The median baseline prostate-specific antigen (PSA; n = 302) was 5.41 ug/L; total testosterone (n = 291) was 13.4 nmol/L. Invasive PCa developed among 26.4% of patients. The hazard ratio for the nutritional supplement to prevent PCa was 1.03 (95% CI, 0.67 to 1.60; P = .88). Gleason score distribution was similar in both groups with 83.5% of cancers graded Gleason sum of 6. Baseline age, weight, PSA, and testosterone did not predict for development of PCa. The supplement was well tolerated with flatulence reported more frequently (27% v 17%) among men receiving micronutrients. CONCLUSION: This trial does not support the hypothesis that combination vitamin E, selenium, and soy prevents progression from HGPIN to PCa.

Increased serum level of early prostate cancer antigen is associated with subsequent cancer risk in men with high-grade prostatic intraepithelial neoplasia.

Early prostate cancer antigen (EPCA) has been recently suggested as a novel biomarker in malignant and premalignant lesions of the prostate. This study was to examine serum expression of EPCA and to further clarify the relationship between initial serum EPCA levels and the presence of subsequent cancer in the individuals with isolated high-grade prostatic intraepithelial neoplasia (HGPIN). An indirect ELISA was used for initial serum EPCA measurement in 112 men with isolated HGPIN, who were enrolled and completed a follow-up of >or=5 years. All patients had a detectable concentration of EPCA in the initial serum, with a mean of 0.64+/-0.13 absorbance at 450 nm. Thirty-three patients had an initial serum EPCA level of >or=1.10, in which 31 cases were subsequently identified as having prostate cancer on follow-up. However, in the remaining 79 cases, serum EPCA levels were all <1.10, and none was diagnosed with cancer later. Statistical analysis showed a significantly higher serum ECPA level in isolated HGPIN patients with subsequent cancer than those without cancer (P<0.001). The area under the receiver operating characteristic curves showed that serum EPCA level had better predictive accuracy of cancer onset on follow-up than prostate specific antigen velocity and abnormal digital rectal examination findings. Furthermore, univariate and multivariate Cox regression analyses demonstrated the predictive performance independently by initial serum EPCA>or=1.10 absorbance (relative risk, 3.32; 95% confidence intervals, 2.62-5.03, P<0.001). These preliminary findings first show the potential of serum EPCA to serve as a significant predictor for subsequent cancer in isolated HGPIN.

Significado clínico de la neoplasia intraepitelial prostática y de la proliferación acinar focal atípica: relación con el cáncer de próstata / Clinical significance of prostatic intraepithelial neoplasm and atypical small acinar proliferation: relationship with prostate cancer

Introducción: El papel de la neoplasia intraepitelial prostática (PIN) y de la proliferación acinar focal atípica (ASAP) en el marco de una biopsia transrrectal todavía no se encuentra por completo definido; aunque ambas lesiones han sido consideradas clásicamente premalignas, hoy en día la necesidad de la rebiopsia sistemática sigue siendo controvertido. Objetivos: En este trabajo hemos estudiado el papel de estas lesiones y su relación con el cáncer de próstata. Material y métodos: Se incluyeron 138 sujetos (108 PIN, 30 ASAP) a los que se le practicó rebiopsia al 67%; la tasa de cáncer en la rebiopsia inmediata fue del 19 y 27% respectivamente sin identificar ningún factor clínico para predecir cáncer en la rebiopsia (PSA, edad, tacto rectal, volumen prostático).Resultados: Durante el seguimiento, la mayor tasa de cáncer se observó en el ASAP, seguido del PIN y finalmente de las lesiones benignas; el único predictor clínico-patológico independiente de cáncer en este caso fue la existencia de ASAP en la primera biopsia transrrectal. Conclusiones: La necesidad de rebiopsiar sistemáticamente a los sujetos con PIN en la biopsia de próstata ha sido puesta en duda en la literatura reciente, mientras que la necesidad de rebiopsiar los ASAP sigue estando claramente indicado (AU)

Introduction: Prostatic intraepithelial neoplasia (PIN) and atypical small acinar proliferation (ASAP) in the setting of prostatic needle biopsies are considered premalignant although questions still remain. Objetives: In this paper, we have studied the clinical relevance of these histologic findings. Material and methods: We collected 138 subjects (108 PIN, 30 ASAP); in 67% we performed a second biopsy and the rate of cancer in this late biopsy were 19% and 27% respectively. We cannot identify any clinical factor to predict the finding of cancer in the re-biopsy (PSA, age, digital rectal examination, prostatic volume).Results: In the follow-up, we observed higher rates of cancer for the ASAP; the finding of ASAP was the single clinical or histopathological factor that was an independent predictor of cancer. Conclusions: We observed that the finding of ASAP was an indication for re-biopsy because of the higher rates of cancer; on the contrary, the paper of PIN in the prostatic needle biopsy still requires further investigation (AU)

Prostatic intraepithelial neoplasia in TURP specimens and subsequent prostate cancer.

PURPOSE: Prostatic intraepithelial neoplasia (PIN) is considered as a precursor lesion for adenocarcinoma of the prostate. Most data supporting this relationship comes from the short-term follow-up of patients with repeated biopsies. We report a study in which patients were followed-up for 11 years to assess the relationships between the presence of high grade PIN, low grade PIN, and atypical adenomatous hyperplasia (AAH) and the subsequent occurrence of prostate cancer. MATERIALS AND METHODS: For 601 men treated by TURP in 1990-1993, prostate specimens were reviewed to assess the presence of high grade PIN, low grade PIN, and AAH. Incidental carcinoma was observed in 67 men. Follow-up of the 534 men without incidental prostate cancer was conducted until December 2003 and 24 new prostate cancers were diagnosed. Multivariate regression models were used to assess the relationships between PIN and AAH and prostate cancer on both cross-sectional and prospective data. RESULTS: High grade PIN (odds ratio (OR) = 6.16, 95% confidence interval (CI): 3.28-11.58), low grade PIN (OR = 3.06, 95% CI: 1.45-6.46), and AAH (OR = 2.06, 95% CI: 1.00-4.29) were significantly associated with incidental prostate cancer. In the prospective study, only high grade PIN was associated with a statistically significant increased risk of prostate cancer: hazard ratio = 3.12, 95% CI: 1.15-8.49. CONCLUSION: Although high grade PIN, low grade PIN, and AAH were all associated with incidental prostate cancer, the long-term prospective study showed that only high grade PIN was a significant determinant of the subsequent occurrence of prostate cancer.

La neoplasia prostática intraepitelial de alto grado. La perspectiva del patólogo / High degree prostatic intraepithelial cancer. The point of view of the pathologist

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Should high-grade prostatic intraepithelial neoplasia change our approach to infravesical obstruction?

OBJECTIVES: To investigate whether coexistence of high-grade prostatic intraepithelial neoplasia (HPIN) should change our therapeutic approach to infravesical obstruction. MATERIAL AND METHODS: Of 505 patients who underwent sextant transrectal ultrasonography (TRUS)-guided prostate biopsy, 65 (12.8%) had HPIN and 29 of them underwent prostatectomy (23 transurethral resection of prostate (TURP), 6 open) due to obstructive urinary symptoms. Patients without carcinoma were followed up with semiannual prostate-specific antigen (PSA) and digital rectal examination. After a follow-up of 24.8 +/- 11.0 months, 19 of 29 patients who accepted our call had another sextant biopsy. RESULTS: Mean age and initial mean PSA values of 29 patients were 67.6 +/- 6.7 years and 9.26 +/- 5.91 ng/ml, respectively. The final pathological evaluation of the surgical specimens revealed 2 prostatic adenocarcinomas both in the TURP group. The remaining 27 (93.2%) patients were found to have benign prostatic hyperplasia (BPH) and their serum PSA levels declined from 9.26 +/- 5.91 to 4.59 +/- 2.0 ng/ml 3 months after prostatectomy. Of the 19 patients who had another biopsy with a mean PSA value of 4.06 +/- 4.61 ng/ml, 15 and 4 of them had BPH and HPIN respectively. CONCLUSIONS: Our preliminary data indicate that the presence of HPIN on TRUS-guided biopsies is not a factor to delay an indicated surgical intervention for infravesical obstruction.

Coexistence of prostate neoplasia in patients undergoing radical cystoprostatectomy due to vesical neoplasia

OBJECTIVE: To assess the incidence of bladder carcinoma infiltrating the prostate and prostate adenocarcinoma in patients undergoing radical cystoprostatectomy due to bladder cancer, as well as to assess if the characteristics of the bladder neoplasia influence the prostatic involvement by this neoplasia. MATERIALS AND METHODS: We retrospectively assessed 60 male patients, who underwent radical cystoprostatectomy between July 1997 and December 2003. Mean age was 66.7 years (40 and 93 years). The product of radical cystoprostatectomies was checked for involvement of urethra and prostate parenchyma by the primary neoplasia, and for the presence of associated prostate adenocarcinoma. Bladder neoplasia characteristics, such as localization, size, multifocality, association with in situ carcinoma and histological grade, were studied in order to assess the possibility of using such characteristics as predictive factors of prostate infiltration by bladder urothelial carcinoma. RESULTS: We observed the presence of 20 percent of patients with bladder carcinoma infiltrating the prostatic urethra, 23.3 percent of patients with infiltration of the prostate parenchyma and 28.3 percent of patients with associate prostate adenocarcinoma, resulting in a total of 55 percent of patients with prostatic involvement (infiltrative bladder carcinoma and/or adenocarcinoma). We also observed a statistically significant correlation between tumor location in the trigone, the presence of in situ carcinoma and the histological grade of the bladder tumor with prostatic infiltration by the vesical neoplasia. CONCLUSION: The coexistence of prostatic neoplasia in patients operated for bladder neoplasia was frequent in our sample (55 percent). We observed that the prostatic infiltration by bladder tumors occurs more frequently with tumors located in the trigone, with associated in situ carcinoma and with high histological grade. There was no correlation between neoplastic infiltration of prostate and multifocality or size of the bladder tumor in the studied sample.

Coexistence of prostate neoplasia in patients undergoing radical cystoprostatectomy due to vesical neoplasia.

OBJECTIVE: To assess the incidence of bladder carcinoma infiltrating the prostate and prostate adenocarcinoma in patients undergoing radical cystoprostatectomy due to bladder cancer, as well as to assess if the characteristics of the bladder neoplasia influence the prostatic involvement by this neoplasia. MATERIALS AND METHODS: We retrospectively assessed 60 male patients, who underwent radical cystoprostatectomy between July 1997 and December 2003. Mean age was 66.7 years (40 and 93 years). The product of radical cystoprostatectomies was checked for involvement of urethra and prostate parenchyma by the primary neoplasia, and for the presence of associated prostate adenocarcinoma. Bladder neoplasia characteristics, such as localization, size, multifocality, association with in situ carcinoma and histological grade, were studied in order to assess the possibility of using such characteristics as predictive factors of prostate infiltration by bladder urothelial carcinoma. RESULTS: We observed the presence of 20% of patients with bladder carcinoma infiltrating the prostatic urethra, 23.3% of patients with infiltration of the prostate parenchyma and 28.3% of patients with associate prostate adenocarcinoma, resulting in a total of 55% of patients with prostatic involvement (infiltrative bladder carcinoma and/or adenocarcinoma). We also observed a statistically significant correlation between tumor location in the trigone, the presence of in situ carcinoma and the histological grade of the bladder tumor with prostatic infiltration by the vesical neoplasia. CONCLUSION: The coexistence of prostatic neoplasia in patients operated for bladder neoplasia was frequent in our sample (55%). We observed that the prostatic infiltration by bladder tumors occurs more frequently with tumors located in the trigone, with associated in situ carcinoma and with high histological grade. There was no correlation between neoplastic infiltration of prostate and multifocality or size of the bladder tumor in the studied sample.

Is low-grade prostatic intraepithelial neoplasia a risk factor for cancer?

INTRODUCTION: High-grade prostatic intraepithelial neoplasia (HGPIN) is generally accepted to be a precursor lesion of prostate cancer. The likely outcome of isolated low-grade PIN (LGPIN) lesions in prostate biopsies remains unclear. A follow-up study of 106 patients with LGPIN- and HGPIN lesions was performed. MATERIALS AND METHODS: In a 2-y period, 207 men were diagnosed with isolated PIN on standard systematic sextant biopsy of the prostate. In total, 104 patients had LGPIN and 103 had HGPIN. No patients had ever received androgen deprivation therapy, chemotherapy or radiation therapy. In all, 106 patients who underwent repeat second or third sextant biopsies were analysed in the study; 30% of these patients received a selenium-vitamin E supplement for at least 6 months. RESULTS: In total, 43 had LGPIN and 63 HGPIN on the first biopsy. The mean age was 63.5 y (range 46-77) in the LGPIN group and 64.9 y in the HGPIN group. The mean total PSA was 6.96 ng/ml (range 0.59-34.13) in the LGPIN group and 8.44 ng/ml (range 0.59-35.3) in the HGPIN group. In the LGPIN group, 30% of the patients had cancer in at least one of the repeat biopsy cores. In the HGPIN group, 27% had cancer in at least one of the repeat biopsy cores. The mean total PSA of patients who had cancer in repeat biopsies with LGPIN was 7.84 ng/ml (range 2.92-34.13). The mean total PSA of the patients who had cancer in repeat biopsy in the HGPIN was 6.73 ng/ml (range 0.56-25). There was no significant difference in PSA and pathological stage between those patients who did and those who did not receive selenium-vitamin E supplements. CONCLUSIONS: These data are intriguing since the risk of finding prostate carcinoma on repeat sextant biopsy in the LGPIN group is 30%. This is higher than commonly reported. The importance of recognising and re-biopsying HGPIN was confirmed. If chemoprevention could be shown to be effective, it might be beneficial not only in HGPIN but also in LGPIN. The possible activity of chemopreventive agents and their combination with iso-flavonoids needs further investigation.

Testosterone replacement therapy in hypogonadal men at high risk for prostate cancer: results of 1 year of treatment in men with prostatic intraepithelial neoplasia.

PURPOSE: One of the greatest concerns among clinicians regarding testosterone replacement therapy (TRT) is the fear of causing or promoting prostate cancer. We evaluated prostatic changes in hypogonadal men with and without high grade prostatic intraepithelial neoplasia (PIN), which is considered a prostatic precancerous lesion, after 1 year of TRT. MATERIALS AND METHODS: A total of 75 hypogonadal who completed 12 months of TRT were studied. All underwent prostate biopsy prior to initiating treatment. Of the men 55 had benign prostate biopsies (PIN-) and 20 had PIN without frank cancer (PIN+). All men with PIN underwent repeat biopsy to exclude cancer prior to the initiation of testosterone treatment. Prostate specific antigen (PSA), and total and free testosterone were determined prior to treatment and at 1 year. Repeat biopsy was performed for a change noted on digital rectal examination or for a PSA increase of 1 ng/l or greater. RESULTS: PSA was similar at baseline in men with and without PIN (1.49 +/- 1.1 and 1.53 +/- 1.6 ng/dl, p >0.05) and after 12 months of TRT (1.82 +/- 1.1 and 1.78 +/- 1.6 ng/dl, respectively, p >0.05). A slight, similar increase in mean PSA was noted in the PIN- and PIN+ groups (0.25 +/- 0.6 and 0.33 +/- 0.6 ng/dl, p >0.05). One man in the PIN+ group had cancer after biopsy was performed due to abnormal digital rectal examination. Four additional men in the PIN- group and 2 in the PIN+ group underwent re-biopsy for elevated PSA and none had cancer. No differences were noted between the PIN- and PIN+ groups with regard to total and free testosterone at baseline and at 1 year (p = 0.267). CONCLUSIONS: After 1 year of TRT men with PIN do not have a greater increase in PSA or a significantly increased risk of cancer than men without PIN. These results indicate that TRT is not contraindicated in men with a history of PIN.

Inverted (Hobnail) high-grade prostatic intraepithelial neoplasia (PIN): report of 15 cases of a previously undescribed pattern of high-grade PIN.

We report 15 cases of a distinctive and previously unrecognized variant of high-grade prostatic intraepithelial neoplasia (HGPIN) that is characterized by polarization of enlarged secretory cell nuclei toward the glandular lumen. We designate this lesion inverted or hobnail HGPIN. In all cases inverted HGPIN was identified on needle biopsy where it merged with typical micropapillary-tufted HGPIN. Inverted secretory cell nuclei frequently demonstrated less prominent nucleoli than adjacent noninverted secretory cell nuclei, yielding a sense of maturation that falsely suggested a non-neoplastic process. Inverted HGPIN was associated with concurrent prostatic adenocarcinoma in seven cases and with atypical glands suspicious for carcinoma in two other cases, whereas in six other cases inverted HGPIN was the only lesion identified. In both radical prostatectomies that followed these biopsies that were available for review, inverted HGPIN was localized to the peripheral zone of the prostate where it merged with usual forms of HGPIN and carcinoma. Inverted HGPIN is a morphologically distinctive form of HGPIN that shares the association with carcinoma and peripheral zone localization with other recognized forms of HGPIN.

Stromal microcalcification in prostate.

Prostatic calcification is most commonly encountered as calculus or intraluminal calcifications within atypical small glandular proliferations. This study was undertaken to detect stromal microcalcifications in prostate tissue. All slides from 194 needle biopsies were retrospectively reviewed. Six cases (3.1%) had stromal microcalcifications constantly associated with mononuclear inflammatory infiltrate around the each focus. Association with prostatic glands was not seen in any of the microcalcification foci. Three cases had simultaneous adenocarcinoma and one had high-grade prostatic intraepithelial neoplasia, all of which were apart from the microcalcification foci. In conclusion, stromal microcalcification is a dystrophic, inflammation-mediated, benign process.