Monoclonal antibody FC-5.01, directed against CD63 antigen, is internalized into cytoplasmic vesicles in the IIB-BR-G human breast cancer cell line

PURPOSE: Benign prostatic hyperplasia is common among men who may be candidates for prostate cancer screening using prostate-specific antigen (PSA) testing. Patterns of PSA testing among men with evidence of benign prostatic hyperplasia have not been studied. METHODS: We examined the prevalence and correlates of a self-reported history of PSA testing. In 1994, 33,028 US health professionals without prostate cancer aged 47 to 85 years provided information on prior PSA testing, lower urinary tract symptoms characteristic of benign prostatic hyperplasia, history of prostatectomy, and prostate cancer risk factors. In 1995, a subset of 7,070 men provided additional information on diagnosis and treatment of benign prostatic hyperplasia. RESULTS: From 39% of men in their 50s to 53% of men in their 80s reported PSA testing in the prior year (P <0.0001 for trend with age). Men were more likely to report PSA testing if they had lower urinary tract symptoms characteristic of benign prostatic hyperplasia (age-adjusted odds ratio for severe symptoms 2.2, 95% confidence interval 1.8 to 2.6), a prior history of prostatectomy (age-adjusted odds ratio 1.1, 95% confidence interval 1.02 to 1.2), or a physician diagnosis of benign prostatic hyperplasia (odds ratio 1.9, 95% confidence interval 1.7 to 2.2; adjusted for age, signs or symptoms of benign prostatic hyperplasia, and prostate cancer risk factors). CONCLUSIONS: These US health professionals reported preferential use of PSA testing among men least likely to benefit from early cancer detection (older men) and among men most likely to have a false-positive PSA result (men with benign prostatic hyperplasia). Physician and patient education are needed to promote more rational and selective use of this screening test.     

Pharmacologic therapy for prostatism

Although the general approach to management of a sufficient degree of benign prostatic hyperplasia in the past was surgical intervention (transurethral resection of the prostate), the current availability of effective pharmacologic therapy has changed the initial management strategy. At present, two types of drugs are available for treatment of prostatism: (1) selective alpha-adrenergic blocking agents (terazosin, doxazosin, and tamsulosin) and (2) an inhibitor of the 5 alpha-reductase enzyme (finasteride). Pharmacologic blockade of the alpha(1)-adrenoceptors is thought to result in relaxation of the smooth muscle in the prostate and bladder neck, which reduces urethral resistance, improves voiding function, and minimizes the symptoms of prostatism. These effects may be noted by the patient within several weeks after initiation of treatment. The mechanism of action of finasteride is a blocking of the conversion of testosterone to dihydrotestosterone and an associated volume shrinkage of the prostate. On the average, a 25% reduction in prostate volume can be achieved, but a period of 12 months or longer of finasteride therapy is needed for maximal shrinkage and maximal decrease in symptoms of prostatism. The expanding population of middle-aged and elderly men with prostatism of moderate severity will undoubtedly prompt the development of additional pharmacologic options for treatment of prostatism and benign prostatic hyperplasia.     

Holmium:yttrium-aluminum-garnet laser prostatectomy

As alternatives to transurethral resection of the prostate for treatment of benign prostatic hyperplasia, various types of laser prostatectomy-most notably, neodymium:yttrium-aluminum-garnet (YAG) and potassium titanyl phosphate laser procedures-have proved to be associated with considerably less morbidity (for example, bleeding, need for transfusion, intraoperative fluid absorption, and postoperative incontinence). Despite these advantages, certain disadvantages (need for prolonged postoperative catheterization and delayed symptomatic improvement) prompted investigation of the holmium:YAG laser for performance of prostatectomy. The holmium:YAG laser is highly absorbed by tissue water and causes rapid vaporization of exposed soft tissue. After initial studies in canine prostates and human prostatectomy specimens, clinical studies with the holmium:YAG laser showed no fluid absorption, appreciable blood loss, or complications, and voiding outcomes were improved immediately, similar to the result with transurethral resection of the prostate. In addition, the holmium:YAG laser has been used to perform transurethral incision of the prostate rapidly and hemostatically. Holmium laser resection of the prostate is a safe and efficacious procedure for relief of symptomatic bladder outlet obstruction due to benign prostatic hyperplasia.     

A comparison of transurethral resection of the prostate and medical treatment for the patient with moderate symptoms of benign prostatic hyperplasia

Transurethral resection of the prostate is the most common surgical treatment for benign prostatic hyperplasia. We conducted a prospective randomized clinical trial to compare this surgery with medical treatment in men with moderate symptoms of benign prostatic hyperplasia. Of 98 men over the age of 54 years who were screened between June 1993 and June 1995, 53 were studied (25 in the surgery group and 28 in the medication group). Patients' symptoms and the degree to which they were bothered by urinary difficulties were measured with standardized questionnaires and medical evaluations. The men randomly assigned to the surgery group underwent surgery within 2 weeks after the assignment. Surgery was not associated with an impotence or urinary incontinence. The follow-up period was 1 year. Surgery was significantly associated with improvement in residual urinary volume and peak flow rate; and also in the scores for urinary difficulties, sexual performance and interference with activities of daily living (P < 0.001 for all comparisons). We concluded that for patients with moderate symptoms of benign prostatic hyperplasia, surgery is more effective than medication in improving genitourinary symptoms and enhancing the quality of life. Thus, medication as treatment should be reserved for patients who are less bothered by urinary difficulty or who wish to delay surgery.     

The precursor form of the human kallikrein 2, a kallikrein homologous to prostate-specific antigen, is present in human sera and is increased in prostate cancer and benign prostatic hyperplasia

Prostate-specific antigen (PSA, hK3) is a diagnostic marker for prostatic cancer but lacks the specificity to sufficiently distinguish between prostatic cancer and benign prostatic hyperplasia (BPH). Human glandular kallikrein 2 (hK2) has been proposed as a potential diagnostic marker for prostate cancer that could complement the current PSA test. Recently we demonstrated that proPSA is present in prostate cancer sera. This study examines the expression of prohK2 in prostate cells and its presence in human sera. Western blot analysis was used to assess prohK2 expression in the human carcinoma cell line, LNCaP. A highly specific and sensitive dual monoclonal immunoassay for prohK2 was developed and used to assess the presence of prohK2 in human sera. prohK2 was detected in the spent media of LNCaP cells. Furthermore, prohK2 was present at immunodetectable concentrations in human sera, and its concentration was increased in prostatic cancer and BPH. These results indicate for the first time that prohK2 is secreted by human prostate cells and is a major component of uncomplexed (free) hK2 in human sera. In addition, prohK2 in human sera is associated with prostate disease and thus may be a useful marker for prostatic cancer and BPH.     

Antidiarrhoeic activity of Euphorbia hirta extract and isolation of an active flavonoid constituent

Recently great interest has been generated in alternatives to transurethral resection for benign prostatic hyperplasia. Lasers are currently being assessed, but marketing has for the moment outstripped basic science. A cystoscopic approach was used delivering Nd:YAG or KTP laser energy via forward and sidefiring fibers and contact tip devices in 51 patients. The sidefiring device is intended to coagulate a volume of prostate that subsequently sloughs, leaving a cavity. Treatment of the apical and middle lobe tissue using this technique was unsatisfactory. A further disadvantage was the interval between treatment and improvement in urine flow, which was approximately 6 weeks. The use of temporary prostatic stents has helped to overcome this delay in treatment effect. Encouraging early results have been achieved using forward-firing fibers to treat apical and middle lobe tissue. The use of contact tip devices to perform bloodless prostatotomies in combination with sidefire or bare fiber has also proved useful. Laser prostatectomy is an exciting field with considerable potential but remains in the developmental stage.     

The classification of benign and malignant human prostate tissue by multivariate analysis of 1H magnetic resonance spectra

1H magnetic resonance spectroscopy studies (360 MHz) were performed on specimens of benign (n = 66) and malignant (n = 21) human prostate tissue from 50 patients, and the spectral data were subjected to multivariate analysis, specifically linear-discriminant analysis. On the basis of histopathological assessments, an overall classification accuracy of 96.6% was achieved, with a sensitivity of 100% and a specificity of 95.5% in classifying benign prostatic hyperplasia from prostatic cancer. Resonances due to citrate, glutamate, and taurine were among the six spectral subregions identified by our algorithm as having diagnostic potential. Significantly higher levels of citrate were observed in glandular than in stromal benign prostatic hyperplasia (P < 0.05). This method shows excellent promise for the possibility of in vivo assessment of prostate tissue by magnetic resonance.     

The current approach to the management of benign hypertrophy of the prostate

Epidemiology. The incidence of benign prostatic hyperplasia (BPH) has increased in proportion to the life expectancy and has become the third leading cause of health expenditure in industrialized countries. Eighty per cent of men are treated for benign prostatic hyperplasia during their lifetime. In Europe, the mean age of diagnosis is 65 years. The clinical symptoms are assessed by the IPSS score (International Prostate Symptom Score) and by the maximum flow rate, where frank dysuria is defined as a flow rate of less than 10 ml/sec. Physiology. The prostate contains equal proportions of glandular epithelial structures and fibromuscular connective tissue stroma. The glandular prostate is innervated by cholinergic nerves, while the smooth muscle of the stroma and the urethra are innervated by adrenergic nerves. BPH arises in the transitional zone (fairly glandular). Androgen deprivation (castration, antiandrogens, progestogens, 5-alpha-reductase inhibitors) induces a 30% reduction of the prostatic volume (especially epithelial). BPH could be due to reactivation of the embryonic potential of the stroma. Certain growth factors appear to be involved in BPH. Inflammatory and immunological phenomena may also be involved. Evaluation. Plan of clinical interview, clinical examination and laboratory and radiological data. A 40-year-old man has one chance in 30 of being operated for benign prostatic hyperplasia if he lives to the age of 80. Medical treatments have been developed since 1980 which inhibit the course of BPH and minimize some of the clinical symptoms: plant extracts, alpha-blockers, 5-alpha-reductase inhibitors. Conventional surgical treatments, open prostatectomy and endoscopic resection, have been completed by laser therapy, thermotherapy and cryotherapy.     

Bilateral internal mammary angiography through a right radial approach: a case report

OBJECTIVE: To describe a case of prostatic xanthoma, a benign condition of inflammatory origin related with granulomatous prostatitis. METHODS: A 70-year-old patient with voiding syndrome and a DRE suggestive of grade II hyperplasia of the prostate is described. A bilateral biopsy of the prostate was negative. The patient was submitted to transurethral resection with normal analytical data. Histological examination of the specimen showed benign prostatic hyperplasia associated with sclerosing adenosis and a clear, foamy cytoplasmic cell and an unremarkable nucleus. Immunocytochemical analysis with the KP-1 lysosomal marker (CD-68) disclosed macrophages. Cytokeratin labelling (AE1-AE3) was negative, thereby discarding any type of epithelial cell proliferation. CONCLUSION: Due to its rarity, making the differential histological diagnosis of prostatic xanthoma can be difficulty in certain cases and it can occasionally present as a palpable mass. However, it must be emphasized that it is a benign condition and clinically irrelevant in most of the cases.     

Immunolocalization and messenger RNA expression of bone morphogenetic protein-6 in human benign and malignant prostatic tissue

Skeletal metastases are common in advanced prostate cancer, causing considerable morbidity, and they are usually osteoblastic in nature with no clear explanation for this phenomenon. Bone morphogenetic proteins (BMPs) induce bone formation in vivo, and preliminary work showed a possible association between BMPs and prostatic skeletal metastases; differential expression favors BMP-6 as a potential new marker and mediator of osteosclerotic deposit formation. We investigated BMP-6 mRNA and protein expression by in situ hybridization and immunohistochemistry in malignant and benign prostates from 40 men. BMP-6 mRNA expression was detected exclusively in malignant epithelial cells in 20 of 21 patients (95%) with metastases and in 2 of 11 patients (18%) with localized cancer, and it was absent in 8 benign samples. Immunostaining for BMP-6 was predominantly cytoplasmic and was present in all primary tumors with established metastases and in 4 of 11 (36%) organ-confined cancers. In benign prostatic hyperplasia, basal cells and areas of basal cell hyperplasia were positive for BMP-6 by immunohistochemistry. The results suggest a close association between BMP-6 expression in primary malignant prostatic tissue and skeletal metastases. BMP-6 may be responsible, in part, for the osteoblastic changes in metastatic lesions secondary to prostate cancer.     

Transurethral thermotherapy of the prostate--a very promising treatment method for benign prostatic hyperplasia

Transurethral resection of the prostate remains the most common method for the treatment of benign prostatic hyperplasia (BPH). Due to unsatisfactory results in about 18% of the patients new methods to treat BPH have been developed. We evaluated 45 patients 6 and 12 months after transurethral microwave thermotherapy using the Prostatron device with Prostasoft 2.5 software. There was a significant improvement of the urinary symptoms and of the quality of life index from 18 to 9.5 and from 3.2 to 1.6 points, respectively. Urinary flow rate improved from 8.8 to 12.1 ml/sec and residual urine was reduced from 101 to 52 ml. The treatment was well tolerated and side effects were minimal. High-energy transurethral microwave thermotherapy is an effective and safe minimal invasive alternative to treat BPH in selected patients. As no anesthesia is required transurethral microwave thermotherapy can also be offered to high risk and elderly patients.     

Comparative study of the treatment of prostatic adenoma: laser photocoagulation versus endoscopic resection

OBJECTIVE: Resection of the prostate using a Nd YAG laser is designed to destroy benign prostatic hyperplasia responsible for bladder neck obstruction. This technique is currently under investigation. PATIENTS AND TECHNIQUE: A total of 56 patients, with a minimal follow-up of 6 months and presenting indications for endoscopic resection of the prostate were treated by TULIP [22] or VLAP [34] laser coagulation. The objective and subjective results were compared to a group of patients [30] treated by endoscopic resection during the same period. Results are expressed as the percentage of patient responding to treatment in terms of objective (peak flow rate > 15 ml/s with improvement > 30% or between 12 and 15 ml, but improvement > 50%) and subjective parameters (IPSS < 7 and improvement > 30% or between 7 and 10, but improvement < 50%). RESULTS: With a minimal follow-up of 6 months, the objective response rates were 55.5% (TULIP), 84.6% (VLAP) and 83.2% (TURP), while the subjective response rates were 55.5% (TULIP), 92.3% (VLAP) and 83.3% (TURP). The hospital stay was significantly shorter in the laser group (2.1 VLAP and 3.3 TULIP; 4.93 TURP). In the TULIP group, 3 patients were incontinent and 4 developed chronic prostatitis. At 6 months, 4 patients in the VLAP group and 6 patients in the TULIP group had to undergo a complementary TURP. CONCLUSION: These results indicate that laser photocoagulation is effective in the treatment of benign prostatic hyperplasia. The VLAP technique appears to be better adapted to this indication. The benefit of VLAP will be more clearly demonstrated by the randomized study currently underway, provided the length of hospital stay, postoperative complications and cost-effectiveness ratio are taken into account. In contrast, the TULIP system is associated with numerous complications which appear to be unacceptable.     

Public laboratories for vaccine production: a new paradigm

The development of increasingly specific diagnostic assays has allowed the detection of various forms of prostate-specific antigen (PSA). It has been found that the proportion of free to total PSA (percent free PSA) is significantly lower in men with prostate cancer than in those with other benign diseases. In order to distinguish early, curable prostate cancer from benign prostatic hyperplasia (BPH), percent free PSA measurement is most useful when the total PSA value is 3-10 ng/ml. The measurement of the proportions of these different forms of PSA, i.e., percent free PSA, may constitute an important diagnostic tool, able to differentiate between benign and malignant prostatic disease with increased specificity, reducing false-positive results and, therefore, improve patient prognosis.     

An open study on the efficacy and safety of transurethral needle ablation of the prostate in treating symptomatic benign prostatic hyperplasia: the University of Florida experience

PURPOSE: We determine the safety and efficacy of transurethral needle ablation of the prostate in patients with moderate to severe symptoms of benign prostatic hyperplasia. MATERIALS AND METHODS: Transurethral needle ablation of the prostate was performed on 45 consecutive patients. For an average prostate of 2.5 to 3 cm. long treatments were performed in 2 separate planes at 4 quadrants (2, 4, 8 and 10 o'clock positions) each. The 2 planes were 1 cm. below the bladder neck and 1 cm. proximal to the verumontanum. For prostatic urethral lengths longer than 3 cm. a treatment plane was added for each additional centimeter of prostatic urethra. The procedure was performed in 26 patients under local anesthesia using 20 cc 2% intraurethral lidocaine gel (11) or supplemented with intravenous 1.25 to 5 mg. midozolam (15). Of these patients 2 had a supplemental perineal block using a mixture of equal amounts of 15 cc 2% lidocaine without epinephrine and 0.25% bripivacaine, 10 underwent the procedure under general anesthesia, 2 had epidural and 4 had spinal anesthesia, and 3 had managed anesthesia care. Mean length of each procedure was 79 minutes (range 50 to 240). All procedures were done on an outpatient basis and patients were released on the same operative day. RESULTS: Mean prostatic volume on transrectal ultrasound was estimated at 48.1 cc (range 20 to 185). Following treatment the International Prostate Symptom Score decreased from a mean of 20.9 at baseline to 15.4 at 1 month, 16.1 at 3 months, 10.7 at 6 months and 9.9 at 1 year. The peak flow rate improved from a baseline mean of 8.3 to 13.4 at 3 months, 13.1 at 6 months and 14.9 at 1 year. The quality of life score improved from a baseline of 4.8 to 3.5, 2.2, 2.5 and 1.03 at 1, 3, 6 and 12 months, respectively. Of the 2 patients in whom the procedure failed; 1 required a bladder neck incision at 3 months and the other transurethral resection of the prostate. Foley catheters were left in place in all patients for an average of 4.85 days. CONCLUSIONS: After a followup of up to 12 months we conclude that transurethral needle ablation of the prostate is an effective treatment for symptomatic benign prostatic hyperplasia. This procedure has minimal morbidity, is less costly than conventional transurethral resection of the prostate and can be performed as an outpatient office procedure under local anesthesia in a significant number of patients.     

1997 American Urological Association Gallup survey: Changes in diagnosis and management of prostate cancer and benign prostatic hyperplasia, and other practice trends from 1994 to 1997

PURPOSE: The American Urological Association first commissioned the Gallup Organization to conduct a study to assess urologist practice patterns in 1992. We present the results of the 1997 survey, the sixth consecutive Gallup survey performed for the Association. MATERIALS AND METHODS: A random sample of 502 American urologists who had completed urological residency and practiced at least 20 hours weekly in 1996 was interviewed by telephone in February and March 1997. RESULTS: Emerging trends showed significant changes since 1994 in how urologists diagnosed and treated prostate cancer. The survey revealed a significant change in the tests routinely ordered to stage newly diagnosed prostate cancer and for diagnostic evaluation of patients with benign prostatic hyperplasia. CONCLUSIONS: Urologists are becoming more cost conscious and effective in ordering pretreatment testing. Urologists are becoming more oriented toward medical treatment for the management of benign prostatic hyperplasia, and less laser surgery is being performed.     

Transurethral needle ablation of the prostate: a minimally invasive treatment for symptomatic benign prostatic hyperplasia

Transurethral needle ablation of the prostate, a relatively new minimally invasive treatment modality for patients with bladder outlet obstruction attributable to an enlarged prostate gland, has undergone extensive evaluation by numerous investigators worldwide. The results to date indicate that needle ablation is safe and effective for relieving symptoms in patients with benign prostatic hyperplasia, and the effect has been demonstrated to be durable for at least 2 years. Nevertheless, additional investigations with longer follow-up data are needed to address the important issues of extended durability (5 to 10 years) and biophysiologic mechanism of action. Comparisons between transurethral needle ablation of the prostate and transurethral resection of the prostate (TURP) have revealed that the subjective and objective measures of response are comparable, although TURP has consistently displayed a slight advantage over needle ablation for most variables analyzed, except quality of life score. The advantages of needle ablation over TURP are (1) performance in the office as an outpatient procedure, (2) no need for general or spinal anesthesia, (3) rapid recovery, (4) minimal side effects, and (5) one-time intervention. The following disadvantages exist with needle ablation: (1) it may not be indicated or effective in patients with large prostate glands (75 g or more); (2) no prostate tissue is available for histologic evaluation; and (3) no long-term efficacy or re-treatment rate data have been published. Overall, the available information indicates that transurethral needle ablation is a viable minimally invasive treatment that may be applicable in men with moderate to severe bladder outlet obstruction as a result of an enlarged prostate gland.     

Female pseudohermaphroditism due to congenital adrenal hyperplasia complicated by adenocarcinoma of the prostate and clear cell carcinoma of the endometrium

The presence of prostatic glandular tissue in female pseudohermaphrodites has previously been documented. However, prostatic neoplasia in this clinical setting has not been reported. A karyotypic female with congenital adrenal hyperplasia due to 21-hydroxylase deficiency developed a prostatic adenocarcinoma associated with elevated serum prostatic specific antigen levels and osteoblastic skeletal metastases. This demonstrates that this tissue in pseudohermaphrodites can become malignant. In addition, the patient subsequently developed clear cell carcinoma of the endometrium, possibly related to radiation therapy for the prostatic adenocarcinoma. This demonstrates that female pseudohermaphrodites may be at risk not only for malignancies seen in genotypic females but also prostate cancer.     

Prostatic needle biopsy: comparison of needles

To clarify the advantages of the 2 most commonly used biopsy needles results of 100 routine needle biopsies of the prostate are evaluated. The series includes patients selected for study concerning the medical treatment of benign prostatic hyperplasia.     

Structure of the human paralemmin gene (PALM), mapping to human chromosome 19p13.3 and mouse chromosome 10, and exclusion of coding mutations in grizzled, mocha, jittery, and hesitant mice

OBJECTIVES: To assess the correlation of total prostatic size and prostate transition zone dimensions with various measurements of the severity of bladder outlet obstruction secondary to benign prostatic hyperplasia. METHODS: Prostate-specific antigen, creatinine, American Urological Association symptom score, bother score, urinary history, uroflowmetry, and post-void residual urine volume determination was followed by measurement of the prostate gland and transition zone on transrectal ultrasound images in 136 men undergoing systematic prostate biopsies. Patients were divided into five groups based on past urinary tract treatment history and the presence of prostate cancer on the biopsies. The total prostate and transition zone dimensions, as well as calculated prostate and transition zone volumes, were compared by Pearson correlation with both the subjective and objective voiding parameters in each patient group. RESULTS: The transition zone dimensions correlated positively with American Urological Association symptom score, bother score, and post-void residual urine volume and correlated negatively with maximum and mean flow rates, particularly in patients with no history of prostate surgery, alpha-blocker administration, urinary infections, irritative voiding symptoms, or prostate cancer. CONCLUSIONS: Transrectal ultrasound measurements of transition zone dimensions correlate better than total prostatic dimensions or calculated prostatic or transition zone volumes with the severity of benign prostatic hyperplasia. Of these, the transverse transition zone dimension demonstrated the best correlation; however, this correlation is probably not adequate for clinical utility.     

Role of CT in patients with prostatic disease: usefulness of depiction of prostatic zonal anatomy

The purpose of this study was to evaluate the role of CT in patients with and without prostatic disease. CT and MR findings were reviewed in 25 patients without known prostatic disease, 11 patients with benign prostatic hyperplasia and 11 patients with prostatic cancer. Differential attenuation allowed for distinction of the peripheral zone and inner gland of the prostate by CT in 72% of normal patients. The distinction rate of prostatic zonal anatomy by CT decreased to 30% in the diseased group. When zonal anatomy of the prostate is not visualized on pelvic enhanced CT, the presence of prostatic disease might be considered.