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The partial purification and characterization of GnRH-like activity from prostatic biopsy specimens and prostatic cancer cell lines.

We have investigated the possibility of the secretion of gonadotrophin-releasing-hormone (GnRH)-like peptides by prostatic cancer cells in culture and their presence in cytosolic preparations from human prostatic biopsy specimens. A GnRH-specific radioimmunoassay showed GnRH-like activity in concentrated cytosolic preparations and conditioned media from DU 145, an androgen-insensitive human prostatic cell line and from LNCaP, an androgen-responsive prostatic cancer cell line. GnRH immunoreactivity in culture media correlated directly with cell numbers. HPLC demonstrated that this GnRH-like material co-migrated with synthetic GnRH. This homology between synthetic GnRH and partially purified prostatic GnRH was confirmed following V8 protease and trypsin digestion which resulted in similar alterations in HPLC characteristics. The mean content of GnRH-like activity/g specimen tissue was significantly more in malignant tissue (88.5 +/- 80.5 fmol) than in benign (29.6 +/- 22 fmol), though more specimens of benign tissue were positive (37/54) than malignant tissue (6/22). This observation, taken with an earlier finding of GnRH-specific receptors in a hormone-sensitive cell line and human cancer specimens provides supportive evidence for the autocrine hypothesis of cell regulation.

Gonadotropin-Releasing Hormone↗

The necessity of a second prostate biopsy cannot be predicted by PSA or PSA derivatives (density or free:total ratio) in men with prior negative prostatic biopsies.

Serum prostate specific antigen, prostate specific antigen density and free:total prostate specific antigen are known to be useful for determining the risk of prostate cancer in patients undergoing prostate cancer screening. The patient with a positive biopsy presents no future prostate specific antigen dilemma. Those with negative biopsies often go on to numerous repeat biopsies. Our goal was to establish criteria that could be used to identify patients who will require repeat prostate biopsies (possibly false negative initial biopsy), while not exposing the low risk population (probable true negative initial biopsy) to additional invasive procedures. Between March 1991 and March 1998, 148 patients who had a biopsy for an elevated prostate specific antigen value (4.1-10.0) or an altered digital rectal examination, had no cancer found in the specimen. From these, 51 (34.4%) had repeated biopsies, while the others persisted on close follow-up. We examined their serum prostate specific antigen, prostate specific antigen density and free:total prostate specific antigen value, as well as their age and histology results of the initial and repeat biopsy, to determine if any predictor of the need for a repeat biopsy could be identified. Eight (15.7%) from 51 men who had repeat biopsy had prostate cancer detected. Forty three (84.3%) patients persisted with a negative biopsy, despite filling the criteria for re-biopsy. Multivariate analysis failed to identify any significant predictors of prostate cancer in the repeat biopsy group. Despite initial success, the prostate specific antigen derivatives and free:total prostate specific antigen have not safely limited the number of biopsies performed for an abnormal prostate specific antigen (4.1-10.0). Neither prostate specific antigen density nor free:total prostate specific antigen predicted the need for repeat biopsy in this specific group. The results of this ongoing study demonstrate that to date, prostate specific antigen and prostate specific antigen derivatives can not be utilized to determine which patients will be at high risk for requiring repeat prostate biopsy. All patients must be closely monitored for evidence of a change in status from benign to malignant disease, and new markers for this purpose are urgently needed.

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[Determining factors in the presence of carcinoma in prostate biopsies].

PURPOSE: Prostate biopsy is the diagnostic method to detect prostate carcinoma. We try to identify the optimal PSA cut-off, biopsy indication and the clinico-pathological characteristics in order to differentiate those patients with negative biopsy in which we should repeat the proceeding. METHOD: We study 344 biopsies in 292 patients for 16 months. An univariate and multivariate study to identify the influent factors in the existence of prostate cancer in the first biopsy and in the patients with a second one was taken place. RESULTS: Patients in the first biopsy Univariate study: Out of these variables (PSA, PSA ratio, digital rectal examination and prostate volume) just the PSA has statistical significance. Multivariate study: Only the the PSA is an indepent influence factor. Receiving Operated Curve: The optimal cut-off is 10.5 ng/ml. Patients with a second biopsy Univariate study: None of the variables is related with the existence of prostate cancer. Groups comparison: A comparison between the patients in the first biopsy and the patients with a second biopsy is performance with no statistical differences in the variables already mentioned. CONCLUSION: The patient with a PSA greater than 4 ng/ml should be perform a prostate biopsy, mostly if his PSA is over 10 ng/ml. In our experience we do not related the need of a second biopsy with any factor in particular, therefore in our opinion and because of the high rate of negative false, all of the patients should be controlled and undergo a second biopsy if any change in PSA or clinics modification takes place.

Adenocarcinoma↗

Effect of cystoscopy, prostate biopsy, and transurethral resection of prostate on serum prostate-specific antigen concentration.

To assess the effect of cystoscopy, prostate biopsy, and transurethral resection of the prostate (TURP) on the serum prostate-specific antigen (PSA) concentration, 101 patients were evaluated. For cystoscopic examination, 69 men were randomized in a prospective manner to one of three groups: flexible cystoscopy, rigid cystoscopy, and a control cohort. The median change in serum PSA was 0.1 ng/mL following flexible cystoscopy, 0.05 ng/mL after rigid cystoscopy, and 0.05 ng/mL for the control group, in which two serum PSA determinations were obtained without an intervening cystoscopy. The differences between the three groups were not statistically significant. The effect of prostate biopsy and TURP was examined in 32 men. Prostate biopsy caused an immediate elevation in the serum PSA level, with a median increase of 7.9 ng/mL (p < 0.0001). Similarly, TURP produced an elevation in the serum PSA concentration, with a median change of 5.9 ng/mL (p < 0.001). The median time required for the serum PSA value to return to a stable level after prostate biopsy was fifteen days (range: 5-21 days) for men with prostate cancer and seventeen days (range: 3-30+ days) for men without cancer, and eighteen days (range: 12-30+ days) for men who underwent TURP. These findings indicate that a serum PSA determination after either a flexible or a rigid cystoscopy is accurate and reliable. Both biopsy and TURP cause an immediate increase in the serum PSA level, which usually returns to a stable, baseline level within three weeks. However, because in some patients the serum PSA still remained elevated after four weeks, it is recommended that a serum PSA determination not be obtained for at least six weeks after either a prostate biopsy or TURP.

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[Four regions 12-core systemic prostate biopsy for diagnosis of prostate cancer].

OBJECTIVE: To evaluate the clinical value of the four regions 12-core systemic prostate biopsy. METHODS: Ninety-one patients suspected of prostate cancer received four regions 12-core systemic prostate biopsy, and the detection rate and complications were compared with those of the sextant method. RESULTS: More positive results were obtained in detecting prostate cancer with the four regions 12-core method, and the complications were similar to those of the sextant biopsy. CONCLUSION: The four regions 12-core biopsy was suggested for patients suspected of prostate cancer with enlarged prostate gland above 40 ml.

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Larger prostate causes higher frequency of infectious complications in prostate biopsy.

INTRODUCTION: Prostate biopsy (PBX) is being performed more often than ever before for the early detection of prostate cancer, but some patients may have febrile infectious complications after biopsy. The risk factors of infectious complications need to be considered. METHODS: We investigated the pre-biopsy risk factors and febrile infectious complications in 120 patients who underwent PBX in our institution. The pre-biopsy risk factors set were prostate volume (> or = 40 ml), transitional zone (TZ) volume (> or = 20 ml), core number of biopsy (> or = 10 cores), and additional performance of TZ biopsy. We analyzed statistically the correlations between these risk factors and C-reactive protein and peripheral white blood cell (WBC) count elevation on day 1 and day 7 after biopsy. RESULTS: Our results showed that a prostate volume > or = 40 ml and a TZ volume > or = 20 ml caused a significantly higher elevation of the C-reactive protein level compared with a prostate volume < 40 ml (p = 0.0055 on day 1 and p = 0.0225 on day 7, respectively) on day 1 and day 7, and a TZ volume < 20 ml (p = 0.0008) on day 1. Regarding WBC count, those patients with a prostate volume > or = 40 ml and a TZ volume > or = 20 ml had a tendency to have an elevated WBC count on day 1 compared with those patients with a prostate volume < 40 ml and a TZ volume < 20 ml, and however these changes were not significant. CONCLUSIONS: This study showed that a larger prostate volume and a larger TZ volume may possibly be risk factors in infectious complications after PBX, although we can perform additional TZ biopsy and increase biopsy core number safely if necessary.

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[Indication of repeat prostate biopsy for the diagnosis of prostate cancer].

There is no standard criterion for repeat prostate biopsy in cases with a negative initial biopsy. We retrospectively analyzed our experience of repeat prostate biopsy to establish its indication for the diagnosis of prostate cancer. From April 1997 to March 2005, 35 consecutive patients underwent repeat prostate biopsy at the department of Urology, Asahikawa Medical College Hospital because of clinically suspicious prostate cancer despite a negative initial biopsy. We compared patients' age, number of cores obtained during repeat biopsy, digital rectal examination findings, total prostate volume, the time from the first to the last biopsy, total prostate specific antigen (PSA) value, free PSA/total PSA ratio, PSA density and PSA velocity between cancer-positive and cancer-negative groups. Prostate cancer was detected in 17 of 35 patients (49%). Fifteen patients with prostate cancer were diagnosed by the first repeat biopsy and other 2 patients were diagnosed by the second repeat biopsy. A statistically significant difference was only noted in age and PSA density. Persistently elevated total PSA and a higher PSA density in cases with a negative initial biopsy might be a good indication of repeat prostate biopsy for the diagnosis of prostate cancer.

Age Factors↗

Prostate Biopsy in the staging of prostate cancer.

The use of prostate biopsies was developed in parallel with progress in our knowledge of prostate cancer and the use of prostate-specific antigen (PSA). Prostate biopsies were initially indicated for the diagnosis of cancer, by the perineal approach under general anesthesia. Nowadays prostate biopsies are not only for diagnostic purposes but also to determine the prognosis, particularly before radical prostatectomy. They are performed in patients with elevated PSA levels, by the endorectal approach, sometimes under local anesthesia. The gold standard is the sextant biopsy technique described by Hodge, which is best to diagnose prostate cancer, particularly in case of T1c disease (patients with serum PSA elevation). Patients with a strong suspicion of prostate cancer from a negative series of biopsies can undergo a second series with transition zone biopsy or lateral biopsy. Karakiewicz et al and Uzzo et al proposed that the number of prostate biopsies should depend on prostate volume to improve the positivity rate. After the diagnosis of prostate cancer, initial therapy will depend on several prognostic factors. In the case of radical prostatectomy, the results of sextant biopsy provide a wealth of information. The aim of this report is to present the information given by prostate biopsy in the staging of prostate cancer.

Journal Article↗

Transrectal prostatic biopsy.

Transrectal prostatic biopsy specimens were taken from 218 patients with prostatic symptoms-138 by the Franzen aspiration technique without anaesthesia as outpatients and 80 by the Silverman technique under general anaesthesia. A reliable diagnosis was obtained in 82% of the former and 95% of the latter.

Anesthesia, General↗

[Multiresistant Escherichia coli meningitis after transrectal prostate biopsy].

Transrectal prostate biopsy represents the most accurate technique to diagnose prostate cancer. More vigilance is necessary when fluoroquinolones are given as prophylactic agents because of the increase in Escherichia coli resistant strains. We report a case of multiresistant E. coli meningitis after transrectal biopsy resulting in the death of the patient.

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Race is not independently associated with a positive prostate biopsy in men suspected of having prostate cancer.

OBJECTIVES: To examine whether race is associated with the prostate biopsy result after controlling for other clinical factors in men undergoing ultrasound-guided prostate biopsy to evaluate an elevated serum prostate-specific antigen (PSA) or an abnormal digital rectal examination (DRE), or both. METHODS: We reviewed the records of all men undergoing transrectal ultrasound-guided prostate biopsy at our facilities from January 1990 through March 1998. This included 1056 white men and 874 black men. Patient age, serum PSA, indication for prostate biopsy, and race were examined for association with the biopsy result. RESULTS: Of the 1 930 black and white men who underwent prostate biopsy, 639 (33%) had cancer, including 355 (41%) of 874 black men and 284 (27%) of 1056 white men. Serum PSA, abnormal DRE, and age were independent predictors of a prostate biopsy being positive for cancer. Race was not an independent predictor of cancer being identified in the prostate biopsy. CONCLUSIONS: After controlling for PSA, DRE, and age, black men were not at an increased risk of a positive prostate biopsy relative to white men. Our data do not support the need to consider race when estimating the probability that a man has prostate cancer.

Adult↗

Complications of invasive, urodynamic examinations and prostate biopsies in patients with benign prostatic hyperplasia.

We studied 85 men with moderate to severe symptoms of benign prostatic hyperplasia (BPH) who completed two placebo-controlled studies of drug therapy. During the 48 week period of treatment and follow-up the patients underwent 164 procedures which included urethral instrumentation, predominantly without antibiotic prophylaxis, and 187 procedures of urethral instrumentation in combination with transperineal prostate biopsy with antibiotic prophylaxis. The risk for a patient to acquire clinically significant urinary tract infection was 2.4% after urethral instrumentation alone and 7.5% when urethral instrumentation was combined with prostate biopsy. Invasive urodynamic examinations of prostate biopsies in studies of new treatment modalities for BPH should only be performed when necessary to obtain important information, and after full informed patient consent. The combination of prostate biopsy and urethral instrumentation increases the infection rate considerably and should be avoided.

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Absence of lower urinary tract symptoms is an independent predictor for cancer at prostate biopsy, but prostate-specific antigen is not: results from a prospective series of 569 patients.

PURPOSE: Prostate needle biopsy (PNB) is the definitive method for the diagnosis of prostate cancer. Our objective was to evaluate prebiopsy parameters, including lower urinary tract symptoms, that may be predictive of positive biopsy. PATIENTS AND METHODS: We performed a prospective review of 569 consecutive men who underwent transrectal ultrasound (TRUS)-guided PNB. The prebiopsy variables recorded included age, prostate-specific antigen (PSA) levels, prostate volume (PV), percent free PSA levels, suspicious digital rectal examination (DRE) findings, TRUS-detected lesions, race, and American Urologic Association Symptom Score (AUASS). RESULTS: Low AUASS, PV, patient age, and abnormal TRUS findings were independent predictors of positive PNB results (P < 0.05). In patients with PSA levels between 4 and 10 ng/mL, the positive predictive value of a low AUASS (< 8) in predicting a positive PNB result is 68.7%. When race was considered (black vs. white), univariate analysis (UVA) indicated that race was a significant predictor (P = 0.034) of positive PNB. A subgroup analysis was performed for black men undergoing PNB (n = 256). Multivariate analysis (MVA) indicates that abnormal TRUS findings; low AUASS, PV, and PSA levels; and absence of prior biopsy are all independent predictors of PNB in the black patient group. A final subgroup analysis (UVA and MVA) was performed for white men (n = 310). Only patient age and PV demonstrated significance as independent predictors of PNBs in this group. CONCLUSION: This prospective analysis of 569 men demonstrates that traditional indicators for PNB (abnormal DRE findings and PSA levels) are not significant predictors of prostate cancer. Independent predictors for prostate included age, low AUASS, low PV, and abnormal TRUS findings. A low AUASS (indicative of the absence of benign disease) is an important predictor of prostate cancer.

Age Factors↗

[Prostate cancer detection by prostate biopsy among Japanese with prostate-specific antigen below 4.0 ng/ml].

The cases of prostate cancer diagnosed at our hospital after the introduction of transrectal ultrasound-guided prostate biopsy were analyzed to ascertain the cancer detection rate among individuals with a prostate-specific antigen (PSA) below 4.0 ng/ml and to assess the pathological characteristics of the prostatectomy specimens. During the period from January 1997 to December 2003, 1,167 individuals received prostate biopsies at our hospital. Before March 2003, the PSA cut-off level for biopsy was set at 4.0 ng/ml, but a biopsy was sometimes performed if a rectal examination revealed abnormalities or the patient desired a biopsy with a PSA below 4.0 ng/ml. After April 2003, all individuals with a PSA over 3.1 ng/ml were biopsied. The results of the prostate biopsy and the pathology data on radical prostatectomy specimens were compared between individuals with a PSA below 4.0 ng/ml and those with a PSA of 4.1-10 ng/ml. The prostate cancer detection rate among individuals with a PSA between 3.1 and 4.0 ng/ml was 19.4% (12/62) before March 2003 and 15.6% (7/45) after April 2003. The number of cancer-positive core was significantly lower among individuals with a PSA below 4.0 ng/ml. On prostatectomy specimens the percentage of surgical margin positive cases was significantly higher among individuals with a PSA below 4.0ng/ml (17 cases) than those with a PSA of 4.1-10 ng/ml (67 cases), although there was no significant difference between these two groups in terms of the pathological stage and Gleason score. Our results indicate that the prostate cancer detection rate is also high among Japanese men with a PSA below 4.0 ng/ml. The biopsy results and pathological features for prostate cancer with a PSA below 4.0 ng/ml did not differ markedly from prostate cancer with a PSA in the gray zone (4.1-10.0 ng/ml).

Aged↗

[Systematic prostate biopsy before transurethral resection of the prostate].

PURPOSE: With the aim of evaluating the clinical significance of systematic prostate biopsy before transurethral resection of the prostate (TUR-P), clinical data were reviewed retrospectively in patients who had underwent prostate biopsy prior to scheduled TUR-P. PATIENTS AND METHODS: Between July, 1994 and June, 2000, TUR-P was scheduled in a total number of 456 patients with clinically diagnosed benign prostatic hyperplasia (BPH). RESULTS: In 218 (47.8%) out of 456 cases, prostatic biopsy was conducted prior to TUR-P due to abnormally elevated serum prostate specific antigen (PSA) levels of 4.0 ng/ml or more, revealing only 22 (10.1%) cases of prostatic cancer. Between these 22 cases with biopsy proven prostatic cancer and 189 cases with BPH confirmed both by biopsy and following TUR-P, statistically significant differences were noted in age (p < 0.05), prostate volume (p < 0.0001) and PSA density (p < 0.01). CONCLUSION: Considering the low positive rate of preoperative prostatic biopsy, it might be suggested that a considerable number of biopsy could be avoided in patients with clinically diagnosed BPH. Based on the results obtained from this study, prostatic biopsy might be unnecessary before TUR-P for those with prostate volume greater than 60 ml or PSA density less than 0.15.

Age Factors↗

Polymerase chain reaction amplification of bacterial 16s rRNA genes in prostate biopsies from men without chronic prostatitis.

OBJECTIVES: A previously reported study using nested polymerase chain reaction (PCR) analysis indicated the presence of DNA from a variety of prokaryotic microorganisms in 77% of transperineal prostate biopsies from patients with chronic nonbacterial prostatitis. Because that study did not include a control group, we investigated whether microbial DNA could also be found in transperineal prostate biopsies obtained from men who did not have a history of prostatitis. METHODS: Transperineal biopsies of both lobes of the prostate were obtained under ultrasound guidance from 9 patients with localized adenocarcinoma of the prostate. DNA was extracted from the prostatic tissue and two-round amplification performed using nested primers from a highly conserved region of the bacterial 16s rRNA gene. Amplified DNA was purified and sequenced, and sequences obtained were compared to bacterial rRNA genes recorded in GenBank. Results. Eleven of 18 biopsy specimens from 8 of 9 patients were positive for bacterial DNA by PCR. Sequence data indicated a predominant organism in 8 of 11 specimens, with greater than 95% homology to DNA from several different genera of bacteria, including Escherichia and Bacteroides. All 9 control samples from the instruments before biopsy were negative. CONCLUSIONS: The presence of bacterial 16s rRNA genes in prostatic tissue is not specific for chronic prostatitis and occurred in most of our patients with localized prostate cancer. Whether the presence of such bacteria is related to the development of prostatic diseases such as prostatitis or prostatic cancer will require carefully controlled trials, including appropriate control groups examined identically.

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Do all patients with high-grade prostatic intraepithelial neoplasia on initial prostatic biopsy eventually progress to clinical prostate cancer?

OBJECTIVE: To assess the clinical outcome of patients with a diagnosis of high-grade prostatic intraepithelial neoplasia (PIN) on initial prostatic biopsy, with a minimum of 5 years of follow-up, as such patients are at greater risk of having prostate cancer on subsequent biopsy. PATIENTS AND METHODS: Between November 1992 and October 1998, 21 patients were identified as having PIN on their initial transrectal ultrasonography-guided prostate biopsy. None of these patients had a focus of cancer on the initial biopsy. Their medical data were reviewed retrospectively to determine the natural history of PIN in these patients. Patients who were not identified as having cancer were followed every 6-12 months with prostate-specific antigen (PSA) testing and digital rectal examinations (DRE). RESULTS: A mean (range) of 7 (2-8) cores were taken at initial biopsy; the mean age of the patients was 63 (53-77) years and mean PSA level 9.1 (4.9-17.6) ng/mL. Six patients had an abnormal DRE at presentation. A mean of 8 (7-10) cores were obtained on the second biopsy; six patients were diagnosed with cancer, with a mean Gleason score of 6 (5-7), while three were diagnosed with persistent PIN. These three patients had a third prostate biopsy which showed cancer of Gleason score 6 in one and benign prostatic hyperplasia in two. After a mean follow-up of 72.2 (60-84) months, none of the remaining 12 patients was diagnosed with clinically significant cancer. Five of these patients went on to a third prostate biopsy, with no evidence of cancer. One patient died from unrelated causes during this period. CONCLUSION: This study affirms our current practice of following patients with PIN conservatively if a second or third subsequent prostate biopsy is negative. Whether PIN is a premalignant lesion or merely a lesion associated with cancer needs to be addressed in multicentre studies with a follow-up of > 10 years.

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[Evaluation of transition zone biopsy in systematic prostate biopsy].

We evaluated the systematic biopsies performed on 83 patients suspected of having prostate cancer. In the systematic biopsy, 6 cores were from the peripheral zone and 2 cores from the transition zone. Cancer was detected in 25 patients (30.1%). The percentage of patients who had abnormal digital rectal examination and transrectal echo findings, average PSA and PSA density, and the number of examinations which suggested cancer were higher in the cancer group than in the non-cancer group, although the mean prostate volume was smaller. Cancer was more frequently detected in the peripheral zone than in the transition zone. Cancer was detected only in the transition zone in only 1 of the 25 cancer patients. We conclude that biopsy of the transition zone to all the patients is not always needed in systematic biopsy.

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