Sensitivity of computed tomography in detecting local recurrence of prostatic carcinoma following radical prostatectomy

The aim of this study was to evaluate CT imaging in the post-operative follow-up and in the detection of recurrence after radical prostatectomy in cases of prostatic carcinoma. In over 500 patients undergoing radical prostatectomy for prostatic carcinoma, 22 cases with local recurrence were found. CT examinations of the pelvis were retrospectively evaluated in these patients. Local recurrence was detected by PSA uptake and confirmed by transrectal ultrasound (TRUS) in combination with guided biopsy. In 22 cases of confirmed local recurrence, positive results on CT were found in eight patients (36%) and negative results in nine patients (41%). In the remaining five cases (23%), no distinction could be made between scar and local recurrence. All cases definitively classified as recurrent tumour disease showed a soft tissue mass of 2 cm or more. CT sensitivity in local recurrence of prostatic carcinoma after surgery is low. Even in a very careful follow-up, the understaging would be up to 41%. In comparison, PSA, TRUS and needle biopsy are the methods of choice and are superior to CT imaging. Based on these results, there would be no reason for including pelvic CT examinations in the follow-up of prostatic carcinoma after radical prostatectomy.     

Predictors of pathological stage before neoadjuvant androgen withdrawal therapy and radical prostatectomy. The Canadian Urologic Oncology Group

PURPOSE: This prospective randomized trial was used to compare predictive factors for organ confined margin negative status after radical prostatectomy with and without a 3-month course of neoadjuvant androgen withdrawal therapy. MATERIALS AND METHODS: A total of 213 patients with localized adenocarcinoma of the prostate were randomized to radical prostatectomy with or without a 3-month course of 300 mg. neoadjuvant cyproterone acetate daily. Multivariate logistic regression analysis was used to determine significant predictors of organ confined margin negative status after radical prostatectomy in both groups. Parameters evaluated included baseline prostate specific antigen (PSA 4 or less, 4.1 to 10, greater than 10 ng./ml.), clinical stage (T2c versus T2b or less), biopsy Gleason score and percentage of surface area of biopsies involved with cancer. The multivariate analysis was repeated with PSA density and the natural logarithm of PSA to optimize the model. RESULTS: In the radical prostatectomy alone arm a model incorporating only PSA density was the best predictor of organ confined margin negative status. In the neoadjuvant androgen withdrawal therapy arm a model incorporating biopsy Gleason score, PSA density and clinical stage was the best predictor. CONCLUSIONS: The conventional predictors of pathology at radical prostatectomy, biopsy Gleason score, PSA density and clinical stage retain significance as predictors in patients treated with a 3-month course of neoadjuvant androgen withdrawal therapy before radical prostatectomy.     

Transrectal ultrasonography to assess local extent of prostatic cancer before radical prostatectomy

BACKGROUND: The safety and efficacy of operations for gastrointestinal diseases in very elderly patients has been a matter of debate in recent years. STUDY DESIGN: One hundred seventy-seven instances of carcinoma of the colon and rectum in patients more than 80 years of age who wee surgically treated between 1961 and 1987 were reviewed. They were compared with 623 similar instances in patients younger than 80 years of age who were treated during the same time period. RESULTS: Octogenarians and nonagenarians significantly more often displayed obstruction or perforation, elevated preoperative carcinoembryonic antigen, right-sided lesions, and solitary hepatic metastases, when present. Patients more than 80 years of age received adjuvant chemotherapy or radiotherapy less often. Carcinoma recurrence in very elderly patients implied a very poor prognosis, with only a 4 percent salvage rate. The actuarial five year survival rate was 32 percent for the older patients and 48 percent in the younger group (p < 0.05). There was no significant difference in operative mortality between the two groups. CONCLUSIONS: In general, age alone should not alter treatment strategy in patients with carcinoma of the colon and rectum.     

The value of prostatic acid phosphatase and prostate specific antigen as serum markers in carcinoma of the prostate

The value of prostatic acid phosphatase (PAP) and prostate specific antigen (PSA) as serum markers in carcinoma of the prostate (CaP) was investigated in this study. A group of 75 patients entered this trial, 25 with CaP, 25 with benign prostatic hyperplasia (BPH) and 25 with urologic disorders other than prostatic diseases. In the CaP group, PAP was above normal levels in 48% of the patients and PSA in 92%. In the BPH group these rates were 20% and 72%, respectively. No elevation was detected in the third group. In CaP patients with capsular invasion, PAP and PSA levels were above normal in 25 and 87.5%. In metastatic carcinoma, PAP was high in 75% and PSA in 100%. Our study reveals that neither of these markers is useful in the initial diagnosis of CaP. Though PSA seems to be more sensitive, it is not more specific than PAP.     

The cytochemical demonstration of prostatic acid phosphatase using a new substrate, phosphorylcholine

Prostatic acid phosphatase (PAP), an acid phosphatase specific to the prostate gland, is demonstrated cytochemically for both light and electron microscopy with a new substrate phosphorylcholine. Lead ion is used as capture agent for liberated phosphate ion in a modified Gomori medium. PAP is demonstrated in the tubuloaveolar epithelial secretory cells of the rat ventral prostate gland. In the apical portion of the cell it is found in secretory granules and in the matrix of multivescular bodies. In the Golgi area it is localized in Golgi cisternae, Golgi related vacuoles and multivescular bodies. Evidence is presented that PAP is not a lysosomal enzyme, as are other acid phosphatases, and that phosphorylcholine is a highly specific substrate for PAP. As based on the role of pentavalent nitrogen on substrate structure, it is apparent that PAP is to other acid phosphatases what the cholinesterases are to other esterases.     

Total protein and acid phosphatase concentrations in prostatic fluid from patients with BPH compared to carcinoma

Efficacy of reperfusion therapy in acute myocardial infarction is strictly time dependent. As is evidenced by several studies, most benefit in terms of myocardial salvage and short- and long-term mortality is achieved with initiation of therapy within the first 60-90 minutes after onset of symptoms. Nearly exclusively, prehospital initiation of thrombolysis makes it possible to take advantage of this early time window. Moreover a time gain of more than 30 minutes, up to 130 minutes, is possible by prehospital initiation of thrombolysis, depending on local circumstances. Randomized studies yielded a better outcome when a time gain of > or = 90 minutes was achieved. Since it has been shown that prehospital diagnosis of an acute myocardial infarction is reliable and out-of-hospital initiation of therapy has no additional specific risk, patients seen within the first 60-90 minutes after onset of symptoms or for whom a relevant time gain of > or = 90 minutes can be expected are ideal candidates for, and therefore should receive, prehospital thrombolysis.     

External beam radiotherapy versus radical prostatectomy for clinical stage T1-2 prostate cancer: therapeutic implications of stratification by pretreatment PSA levels and biopsy Gleason scores

There is a diversity of opinions concerning the function of the blood-brain barrier and the blood-cerebrospinal fluid barrier (BCB) in Alzheimer disease and other neuropsychiatric disorders. In this paper we investigate and review the evidence for BCB dysfunction in Alzheimer disease and major depression. The hypothetical roles of immunologically mediated mechanisms in the central nervous system (CNS) are discussed. Special consideration is given to methodological factors influencing BCB function and analysis. Serum and cerebrospinal fluid (CSF) of 29 patients with major depression (MD) and 51 patients with "probable Alzheimer disease" (AD) were investigated. The AD patients were subdivided in two groups of 21 early-onset (EO) and 30 late-onset (LO) cases and assayed for concentrations of albumin and IgG. The results were compared with those for 11 age-matched healthy controls. The severity of dementia was assessed with the Mini-Mental State Examination (MMSE). AD and MD patients showed significantly lower serum albumin [AD: p < 0.05 (LO: p < 0.038); MD p < 0.01] and IgG (AD: p < 0.01; MD: p < 0.013) concentrations compared with controls. MD (p < 0.001) and LO-AD (p < 0.07) patients displayed significantly lower absolute serum albumin levels than did EO-AD patients. The CSF/serum ratio for albumin and IgG was used to evaluate BCB function. There were no significant group differences; however, subsets of MD (29%) and AD (16%) patients showed a higher frequency of a pathological albumin ratio than did control subjects. Furthermore, a subset of 24% of MD and18% of AD patients and none of the controls showed an elevated IgG ratio. Different mechanisms of alteration of IgG distribution are presented. The degree of cognitive impairment in AD did not correlate positively with protein and ratio parameters. The BCB is critical to the maintenance of homeostasis within nervous system tissue. We suggest that the altered function can result from immune-mediated events such as altered levels of circulating inflammatory mediators. Furthermore, we assume that in the AD and MD subgroups, the BCB dysfunction for high molecular weight proteins permits access of components of the immune system to the CNS, which may contribute to disease pathology.     

Adjuvant treatment after radical prostatectomy in prostatic carcinoma (pT3 or pTxN+): prognostic factors and results

Adjuvant therapy after radical prostatectomy should ideally be limited to those patients at greatest risk for cancer recurrence, but identification of these patients remains a challenge. The local control rate in a group of 7494 patients undergoing radical prostatectomy for patients with pT2a disease of 76% is not different to pN+ disease of 80%. 95% of the pT3 patients were pN+ .90% of them received adjuvant treatment but only few patients with organ-confined cancer. A prognostic scoring system was created using the regression coefficients from the Cox multivariate model to classify patients with pathologically organ-confined prostate cancer according to risk of progression. Although tumor volume has traditionally been regarded as the most important prognostic factor in patients with localized prostate cancer, a recent multivariate analysis has shown that tumor volume is not an independent predictor. Moreover, accurate measurement of tumor volume is extremely difficult. Preoperative serum PSA levels, clinical stage, pathological grade and stage, and deoxyribonucleic acid (DNA) ploidy were evaluated by multivariate analysis to determine relative value in predicting treatment failure. Patients with the lowest score had a 92% progression free survival rate at 5 years, compared to only 39% of those with the highest scores. Patients believed to be at higher risk for cancer progression despite having organ confined disease might be targeted for adjuvant therapy and closer surveillance, while those at low risk may be followed less often.     

Covalent modification and site-directed mutagenesis of an active site tryptophan of human prostatic acid phosphatase

Because tryptophans are found as part of the phosphate binding sites in a number of proteins, human prostatic acid phosphatase (hPAP) was examined for the presence and the role of essential tryptophan residues. The pH dependence of the intrinsic fluorescence of hPAP resembled the kinetic pH dependence. Chemical modification by N-bromosuccinimide (NBS) resulted in an inactivation of the enzyme and produced a characteristic reduction of the protein absorbance at 280 nm. Two tryptophans per subunit were modified, and this was accompanied by an apparently complete loss of enzymatic activity. In the presence of the competitive inhibitor L-(+)-tartrate, the loss of enzyme activity was significantly reduced as compared to the rate of tryptophan modification. After labeling the protein with 2,4-dinitrophenylsulfenyl chloride (DNPS-Cl), two tryptic peptides containing DNPS-labeled tryptophans were isolated and the sequences were identified by amino acid sequence analysis and mass spectroscopy. One peptide corresponded to residues 172-176, and included Trp174. The other corresponded to the C-terminal sequence, including Trp336. It was concluded that Trp174 was at the active site of the human enzyme because it was protected by the competitive inhibitor tartrate in the DNPS-Cl modification studies. This is also consistent with the location of a homologous residue in the structure of the rat enzyme. Using site-directed mutagenesis, Trp174 was replaced by Phe or Leu. Both mutants showed altered kinetic properties, including lower Km values with several aromatic substrates, and also exhibited reduced stability towards urea denaturation.     

The use of polydimethylsiloxane in the treatment of incontinence after radical prostatectomy

OBJECTIVE: To report the results of transurethral submucosal injection therapy of polydimethylsiloxane (PDS) to treat incontinence after radical prostatectomy (RP). PATIENTS AND METHODS: Since 1993, about 80 retropubic RPs have been carried out at our institution each year. Severe post-operative incontinence occurred in six patients, with a mean duration of incontinence after RP of 28 months. The pre-operative evaluation consisted of cysto-urethroscopy and urodynamics. Because we have no experience with artificial sphincter implantation, transurethral injection therapy was used to treat the post-operative incontinence, using PDS (vulcanized silicone rubber particles). This material has a mean particle size of 188 microns, providing stability of the material at the injection site. The six patients with severe post-operative incontinence were treated using injection therapy with PDS. RESULTS: After a mean follow up of 15.5 months, five patients, who suffered from day and night incontinence and required at least five pads per day, were dry after injection therapy. One patient improved significantly but still required two pads during the day, but was continent during the night; three patients required a second injection. A mean of 7.5 mL of PDS was used per patient and the side-effects of therapy (dysuria and urinary retention) were minimal. CONCLUSION: Because PDS has excellent biocompatibility, few side-effects or complications, transurethral injection therapy using silicone particles is a justifiable procedure for treating incontinence after RP.     

Expression of human prostatic acid phosphatase correlates with androgen-stimulated cell proliferation in prostate cancer cell lines

Androgen plays a critical role in regulating the growth and differentiation of normal prostate epithelia, as well as the initial growth of prostate cancer cells. Nevertheless, prostate carcinomas eventually become androgen-unresponsive, and the cancer is refractory to hormonal therapy. To gain insight into the mechanism involved in this hormone-refractory phenomenon, we have examined the potential role of the androgen receptor (AR) in that process. We have investigated the expression of AR and two prostate-specific androgen-responsive antigens, prostatic acid phosphatase (PAcP) and prostate-specific antigen (PSA), for the functional activity of AR in LNCaP and PC-3 human prostate carcinoma cells. Our results are as follows. (i) Clone 33 LNCaP cells express AR, PAcP, and PSA, and cell growth is stimulated by 5alpha-dihydrotestosterone (DHT). Stimulation of cell growth correlates with decreased cellular PAcP activity. (ii) In clone 81 LNCaP cells, the expression of PAcP decreases with a concurrent decrease in the degree of androgen stimulation of cell growth, whereas the expression of PSA mRNA level is up-regulated by DHT, as in clone 33 cells. Conversely, in PAcP cDNA-transfected clone 81 cells, an additional expression of cellular PAcP correlates with an increased stimulation by androgen, higher than the corresponding control cells. (iii) PC-3 cells express a low level of functional AR with no detectable PAcP or PSA, and the growth of PC-3 cells is not affected by DHT treatment. Nevertheless, in two PAcP cDNA-transfected PC-3 sublines, the expression of exogenous cellular PAcP correlates with androgen stimulation. This androgen stimulation of cell growth concurs with an increased tyrosine phosphorylation of a phosphoprotein of 185 kDa. In summary, the data indicate that the expression of AR alone is not sufficient for androgen stimulation of cell growth. Furthermore, in AR-expressing prostate cancer cells, the expression of cellular PAcP correlates with androgen stimulation of cell proliferation.     

The effect of intermittent pneumatic compression devices on intraoperative blood loss during radical prostatectomy and radical cystectomy

Intermittent pneumatic compression devices are a widely used, effective and presumed risk-free method of deep venous thrombosis prophylaxis, presumably by increasing peak venous blood velocity, and stimulating local and systemic fibrinolysis. We investigated whether intermittent pneumatic compression devices had any effect on intraoperative blood loss or transfusion during radical pelvic urological surgery. To our knowledge no previous study has addressed these issues. Records were reviewed for patients undergoing radical retropubic prostatectomy or radical cystectomy with diversion from 1985 to 1990. A total of 91 cases was reviewed: 38 radical retropubic prostatectomies and 53 radical cystectomies with diversion (34 male and 19 female patients). There were 59 patients with intermittent pneumatic compression devices (29 radical retropubic prostatectomies and 30 radical cystectomies with diversion) and 32 without intermittent pneumatic compression devices (9 radical retropubic prostatectomies and 23 radical cystectomies with diversion). Intraoperative blood loss and transfusions were calculated for each group with and without intermittent pneumatic compression devices. No clinically apparent lower extremity deep venous thrombosis or pulmonary embolus was diagnosed in any patient. For the group with intermittent pneumatic compression devices mean intraoperative blood loss was 2,541 ml. (range 700 to 8,850) versus 1,807 ml. (range 450 to 5,100) without a device, for a statistically significant difference of 734 ml. (p = 0.005). When 5 patients with excessive intraoperative blood loss (more than 5,000 ml.) were excluded the statistically significant difference was maintained. When comparing radical retropubic prostatectomy and radical cystectomy with diversion, with and without intermittent pneumatic compression devices, blood loss was greater for the group with a device for each procedure. Differences in intraoperative blood loss were independent of sex or tumor stage. Intraoperative transfusions were increased by approximately 0.6 units per patient with the device. Our study suggests that intermittent pneumatic compression devices may increase blood loss during a radical pelvic operation.     

An enzyme linked immunosorbent assay (ELISA) for detection of seminal fluid using a monoclonal antibody to prostatic acid phosphatase

A microtitre plate format enzyme linked immunosorbent assay (ELISA), employing commercially available PASE/4LJ mouse monoclonal hybridoma antibody is described. The technique is a solid phase indirect ELISA for prostatic acid phosphatase, applicable to specific detection of semen. Maximal detectability was found to be one hundred thousand fold dilution of pooled seminal plasma. No cross reactivities with human vaginal fluid, blood, saliva, female urine, nasal discharge, earwax, sweat or faeces have been found.     

Combination of pneumatic lithotripsy and transurethral prostatectomy in bladder stones with benign prostatic hyperplasia

There are numerous reported cases of lingual thyroid with an obvious prevalence in pediatric age. Such ectopic thyroid glands are probably quantitatively deficient and thyroid function may be low or at a low normal level. Apparently, most cases of ectopic thyroid tissue develop congenital hypothyroidism, the so-called cretinism. In this report, we describe a very rare adult male case of lingual thyroid who developed hypothyroidism in adulthood; the anomaly remained undiscovered, being without local common symptoms, and permitted a normal life.     

The relationship between serum PSA value and the weight of the inner gland of the prostate in the cases of benign prostatic hyperplasia

(BACKGROUND): To study reasons why serum PSA value (Markit-F) elevates in benign prostatic hyperplasia (BPH). (METHODS): The relationship between total prostatic weight and the outer gland weight in 48 cases of BPH undergoing subcapsular prostatectomy was studied by ultrasound measurement. PSA was compared with prostatic weight, inner gland weight, outer gland weight, growth speed of the inner gland and age in the 48 cases. (RESULTS): 1) The weight of the outer gland increased slightly in proportion to the development of BPH. However, the increase was not significant statistically. 2) PSA correlated with the inner gland weight and growing speed of the inner gland well. 3) PSA did not correlate with the outer gland weight and age. (CONCLUSIONS): It is well known that PSA elevates not only in the cases of prostatic cancer but also in the cases of BPH and that PSA correlates with the whole prostatic weight. This study revealed that the elevation of PSA in the cases of BPH was caused by enlargement of the inner gland.     

Tyrosine phosphorylation of c-ErbB-2 is regulated by the cellular form of prostatic acid phosphatase in human prostate cancer cells

Human prostatic acid phosphatase (PAcP) is a prostate epithelium-specific differentiation antigen. In prostate carcinomas, the cellular PAcP is decreased. We investigated its functional role in these cells. Several lines of evidence support the hypothesis that cellular PAcP functions as a neutral protein-tyrosine phosphatase and is involved in regulating prostate cell growth. In this study, we identify its in vivo substrate. Our results demonstrated that, in different human prostate cancer cell lines, the phosphotyrosine (Tyr(P)) level of a 185-kDa phosphoprotein (pp185) inversely correlates with the cellular activity of PAcP. On SDS-PAGE, this pp185 co-migrates with the c-ErbB-2 oncoprotein. Immunodepletion experiments revealed that c-ErbB-2 protein is the major pp185 in cells. Results from subclones of LNCaP cells indicated the lower the cellular PAcP activity, the higher the Tyr(P) levels of c-ErbB-2. This inverse correlation was further observed in PAcP cDNA-transfected cells. In clone 33 LNCaP cells, L-(+)-tartrate suppresses the cellular PAcP activity and causes an elevated Tyr(P) level of c-ErbB-2 protein. Epidermal growth factor stimulates the proliferation of LNCaP cells, which concurs with a decreased cellular PAcP activity as well as an increased Tyr(P) level of c-ErbB-2. Biochemically, PAcP dephosphorylates c-ErbB-2 at pH 7.0. The results thus suggest that cellular PAcP down-regulates prostate cell growth by dephosphorylating Tyr(P) on c-ErbB-2 oncoprotein in those cells.     

Clinical and cost impact of second-opinion pathology. Review of prostate biopsies prior to radical prostatectomy

Despite numerous studies evaluating second-opinion surgical programs, we are unaware of work evaluating the cost effectiveness of a second opinion for pathology prior to surgery. One of six pathologists reviewed the pathology of the outside needle biopsies of 535 consecutive men referred to Johns Hopkins Hospital for radical prostatectomy over a 12-month period (from October 1993 until October 1994) before the men underwent surgery. Of the 535 needle biopsies initially diagnosed on the outside as adenocarcinoma of the prostate, seven (1.3%) were reclassified as benign upon pathology review at Johns Hopkins Hospital. The most common lesion misinterpreted as adenocarcinoma was adenosis or less pronounced examples of adenosis consisting of foci of crowded glands (five cases). Foci of atrophy in the remaining two cases were misdiagnosed as adenocarcinoma of the prostate. Upon subsequent clinical work up, six of seven men were considered not to have adenocarcinoma, and their surgery was cancelled. The cost for reviewing all 535 preoperative needle biopsies was $44,883, which included the cost of immunohistochemical studies for high-molecular-weight cytokeratin and repeat biopsies and ultrasounds in men whose diagnoses were reversed. The total cost of the radical prostatectomies had the six men undergone surgery was estimated at $85,686, including hospitalization, anesthesia, radical prostatectomy pathology, and surgery. This cost savings did not include other costs resulting from lost wages, morbidity, or potential litigation. Second-opinion pathological evaluation of prostate biopsy before radical prostatectomy is cost effective and has a major impact on clinical treatment for a subset of patients.