Variability of assay methods for total and free PSA after WHO standardization.

The variability of total PSA (tPSA) and free PSA (fPSA) results among commercial assays has been suggested to be decreased by calibration to World Health Organization (WHO) reference materials. To characterize the current situation, it is necessary to know its impact in the critical cutoffs used in clinical practice. In the present study, we tested 167 samples with tPSA concentrations of 0 to 20 µg/L using seven PSA and six fPSA commercial assays, including Access, ARCHITECT i2000, ADVIA Centaur XP, IMMULITE 2000, Elecsys, and Lumipulse G1200, in which we only measured tPSA. tPSA and fPSA were measured in Access using the Hybritech and WHO calibrators. Passing-Bablok analysis was performed for PSA, and percentage of fPSA with the Hybritech-calibrated access comparison assay. For tPSA, relative differences were more than 10 % at 0.2 µg/L for ARCHITECT i2000, and at a critical concentration of 3, 4, and 10 µg/L, the relative difference was exceeded by ADVIA Centaur XP and WHO-calibrated Access. For percent fPSA, at a critical concentration of 10 %, the 10 % relative difference limit was exceeded by IMMULITE 2000 assay. At a critical concentration of 20 and 25 %, ADVIA Centaur XP, ARCHITECT i2000, and IMMULITE 2000 assays exceeded the 10 % relative difference limit. We have shown significant discordances between assays included in this study despite advances in standardization conducted in the last years. Further harmonization efforts are required in order to obtain a complete clinical concordance.

Pain on injection from propofol may be avoided by changing its formulation.

BACKGROUND: After using propofol for a decade, pain on injection had been considered routine by patients and medical personnel. When given propofol from a different manufacturer, patients did not complain. Two preparations of propofol were compared. METHODS: A comparative, double-blind, randomized study was conducted in 22 adult patients undergoing pain relief procedures; they received sedation by an intravenous injection of 1.7 mg/kg of propofol and then were treated with paravertebral injections. Pain on injection was assessed by verbal complaint, movement of the extremity, of the whole body and recollection of pain at induction, when discharged. Propofol from Baxter Laboratories, mixed with either 5 ml of 2% lidocaine or 5 ml of NaCl 0.9%, was compared with propofol Laboratorios Gray, which was similarly mixed. Injections were randomly administered four times, blindly, to each of 22 patients. Statistical analysis was conducted using the analysis of variance method. RESULTS: A total of 352 propofol injections were given. Each of the four propofol solutions was administered 88 times; of patients receiving Baxter propofol+saline, 74 (84%) had pain; when mixed with 2% lidocaine 45 (50.2%) complained. After propofol Gray with NaCl 0.9% was given, two patients (2.2%) experienced pain. Propofol Gray with 2% lidocaine produced no pain. None of the latter group remembered having pain, whereas, those given propofol Baxter 54 (61.3%) and 26 (29.5%) remembered experiencing pain at injection. Pain on injection was prevented and statistically reduced (<0.01) with the propofol from Laboratorios Gray. CONCLUSIONS: By changing the formulation (size of molecules and their dispersion) of propofol, pain on injection was avoided.

Bone metaplasia of urothelial mucosa: an unusual biological phenomenon causing kidney stones.

A kidney stone was analyzed by infrared spectrometry, by petrography using ground slices, and by undecalcified histology. Infrared spectrometry showed that the stone was composed of calcium oxalate monohydrate (whewellite), calcium oxalate dihydrate (weddellite), and calcium phosphocarbonate (apatite). Optical microscopy of the ground sections revealed tissue fragments within the stone containing small spaces resembling empty osteocyte lacunae. Histological analysis of methacrylate-embedded sections confirmed the presence of an area of heterotopic ossification. Urothelial mucosa is potentially capable of inducing bone formation and in this case the bony tissue had apparently functioned as a nucleation site for the calculus.

Clinical evaluation of free PSA/total PSA (prostate-specific antigen) ratio in the diagnosis of prostate cancer.

The objective of this study was to evaluate the utility of the free/total prostate-specific antigen (PSA) ratio (per cent free PSA) in the diagnosis of prostate cancer. Serum total PSA and free PSA concentrations were measured in 156 patients with benign prostate hyperplasia (BPH) and 74 patients with prostate cancer using Hybritech Tandem immunoradiometric assays. Patients with prostate cancer had a significantly lower free/total PSA ratio than patients with BPH, although the distributions across study groups overlapped. In patients with a total PSA level between 4 micrograms/l and 25 micrograms/l, free/total PSA demonstrated better diagnostic utility than total PSA alone.

Free to complexed PSA ratio in differentiating benign prostate hyperplasia from prostate cancer.

BACKGROUND: The description of the different forms of circulating PSA has opened a new strategy in the diagnosis of prostate cancer. The aim of our study was to assess the diagnostic potential of PSA and the PSA fractions in the diagnosis of benign prostate hyperplasia (BPH) and prostate cancer. PATIENTS AND METHODS: We measured the serum levels of PSA (Elecsys 2010, Roche Diagnostics, Mannheim, Germany), complexed PSA (Immuno 1 system, Bayer, Tarrytown, NY USA) and free PSA (Elecsys 2010, Roche Diagnostics, Mannheim, Germany) in 178 patients with BPH and 44 patients with prostate cancer. RESULTS: ROC curves were used for comparison of the diagnostic utility of the tests assessed. The biggest areas under the curve were obtained for the ratios between free/complexed PSA and free/total PSA (0.887 and 0.872, respectively). When choosing the cut-off values to obtain a 90% sensibility, we found that the specificity for the free/total PSA ratio was 59% and for the free/complexed PSA ratio 72%. CONCLUSION: Our results suggest that replacement of the measurement of total PSA by complexed PSA in prostate cancer diagnosis may be interesting. Nevertheless, as this is a retrospective study limited to a small number of patients, it is obvious that we need more data to make a final decision with regard to this subject.

TPA prognostic value in superficial bladder cancer.

We determined the levels of TPA in 133 patients with superficial bladder cancer. 79 cases were Ta stages, and 54 cases T1 stages. 53 of the tumors were well differentiated (I), 65 moderately differentiated (II) and 15 undifferentiated (III). The average follow-up time of these patients was 8.3 months; the standard deviation being 5.2 months (median value 7 months). In 43 cases a relapse of the tumor was observed. We detected high TPA levels in 25% of the patients, without observing meaningful differences in tumor invasion or in its differentiation degree. The usefulness of the TPA, the degree of tumor invasion, and the degree of cell differentiation were evaluated by means of single-variate and multivariate analysis in order to forecast tumor relapse. Only the TPA had a prognostic value, the relative risk of developing relapse being 2.03 times higher in patients with high TPA than patients with normal TPA.

BTA TRAK urine test increases the efficacy of cytology in the diagnosis of low-grade transitional cell carcinoma of the bladder.

BACKGROUND: Among urinary tumor markers we studied the utility of the BTA TRAK assay to diagnose transitional cell carcinoma of the bladder in highly suspiscious patients, in comparison to urine cytology. MATERIALS AND METHODS: A preliminary study of 65 patients was made (21 transitional cell carcinoma (TCC), 36 without TCC and 8 excluded patients who received BCG therapy, endocavitary mytomicin or radiotherapy), using the BTA TRAK, cytology and cystoscopy. RESULTS: 12 out of the 21 selected patients were pTa (9 G1and 3 G2), 2 carcinoma in situ (CIS), 2pT1 (1 G2 and 1 G3) and 5 muscle invasive tumors (all of them G3). Setting our cut-off at 18 U/ml, a sensitivity of 52.3% and a specificity of 88.9% was reached. BTA TRAK detected 11 out of 21 of the tumors as well as urine cytology. However, BTA TRAK was more sensitive in the detection of low grade tumors (p<0.05). When considering both tests as complementary, a combined sensitivity of 80.9% and specificity of 88.5% were obtained. CONCLUSION: BTA TRAK is a valid test for the diagnosis of TCC of the bladder, which is not superior to urine cytology but complementary. More extensive prospective studies are required to validate this application and others of the BTA TRAK assay used either alone or in combination with urinary cytology in the management of bladder cancerpatients.

Usefulness of urinary nuclear matrix protein 22 (NMP22) as a marker for transitional cell carcinoma of the bladder.

OBJECTIVES: The purpose of this study was to evaluate an immunoassay for urinary nuclear matrix protein, NMP22, as a novel marker for urothelial cancer. PATIENTS AND METHODS: NMP22 values were determined for 71 patients and 21 healthy volunteers. Each subject provided a single (3 voids) urine sample for analysis at the time of entry into the study. Each sample was assayed for levels of NMP22. RESULTS: When the cut-off value was set at 10 U/ml, the positive rate for urinary NMP22 in bladder cancer was 37.8% (17 out of 45), whereas that in post-treatment cases and benign diseases was 30.8% (8 out of 26) compared to 14.3% (3 out of 21) for healthy volunteers. This cut-off value provided a sensitivity of 37.8% and a specificity of 80.9%. In the bladder cancer group, NMP22 levels were related to tumor size, shape, grade and stage. CONCLUSIONS: Despite the many reports that suggest NMP22 as a promising urinary marker for monitoring transitional cell carcinoma, this study does not support its usefulness as a substitute tool for urinary cytology in the control of bladder tumors.

Skeletal response to clodronate in prostate cancer with bone metastases.

Bone metastases, together with generalized bone resorption, represent the main complication in patients with advanced prostate cancer, and palliative treatments are required to delay the progression of the metastases and improve the quality of life of these patients. For this reason, the bisphosphonate clodronate was administered to 18 patients (clodronate group) from a total of 30, all of whom were receiving complete androgenic blockade; the remaining 12 formed the control group. Transiliac bone biopsies were taken at the beginning of the study and 6 months later to determine the effect of the bisphosphonate on the skeleton. The results were assessed by bone histomorphometry and showed, although without statistical significance between the groups, an antiresorptive effect of the clodronate expressed as the eroded surface/bone surface and as the osteoclast number/bone surface. However, the bone volume also decreased after 6 months of treatment. Similarly, osteoid formation decreased as indicated by the osteoid surface and by the osteoid volume, probably due to the effect of the drug on the osteoblasts. The mineralization rate was apparently slightly retarded in the clodronate group, although to a lesser degree than in the control group. The results confirm the antiresorptive effect of clodronate and its detrimental effect on osteoblast activity.

[Interaction between sildenafil and calcineurin inhibitors in renal transplant recipients with erectile dysfunction]. / Interacción entre sildenafilo y los inhibidores de la calcineurina en trasplantados renales con disfunción eréctil.

AIM: Hepatic metabolism of sildenafil uses the same metabolic pathway as the calcineurin inhibitors (cyclosporine/tacrolimus), through the CYP3A4 isoenzyme. The aim of this pilot study was to evaluate the potential interaction between sildenafil therapy and circulating levels of cyclosporine and tacrolimus in a group of steady-state renal transplant recipients with erectile dysfunction. MATERIAL AND METHODS: A prospective pilot study of sildenafil interactions was carried out in 9 stable male renal transplant recipients with severe erectile dysfunction (mean age 50 +/- 8 years, range 38-64). All patients were receiving therapy with calcineurin inhibitors (5 with cyclosporine and 4 with tacrolimus). Erectile dysfunction was evaluated by clinical history, physical examination, International Index of Erectile Function (IIEF) questionnaire and the nocturnal penile tumescence test (RigiScan). Each patient received a first dose of 50 mg of sildenafil, one hour before sexual activity and a second dose at 72 hours of 50 or 100 mg according to the clinical response to the first dose. We evaluated the efficacy and safety of sildenafil and the evolution of cyclosporine-tacrolimus levels. Cyclosporine and tacrolimus trough whole blood concentrations were determined in basal conditions (before starting sildenafil) and on days 1, 4 and 7 after sildenafil therapy. RESULTS: Eighty-nine percent of patients (n = 8) required a complete 100 mg dose of sildenafil. There was a positive clinical response in two-thirds of cases (6 patients). In 5 patients (55%) sildenafil administration produced a complete response, in one patient the response was incomplete, and in the remaining 3 cases (33%) no clinical response was observed. Associated side effects included self-limited tachycardia in one patient and mild visual disturbances in another. Cyclosporine and tacrolimus levels remained stable in all patients. There were no significant differences in circulating levels of cyclosporine (basal 120 +/- 47; day 1: 116 +/- 55; day 4: 123 +/- 56 and day 7: 121 +/- 56 ng/ml p = NS) or tacrolimus (basal 11.6 +/- 1.3; day 1: 11.9 +/- 1.3; day 4: 11.1 +/- 1.0 and day 7: 11.8 +/- 0.9 ng/ml p = NS) over the study period. CONCLUSIONS: Sildenafil therapy is safe and effective for the treatment of erectile dysfunction in renal transplant recipients. Recommended therapeutic doses of sildenafil did not modify cyclosporine and tacrolimus trough blood levels.

False positive values of PAP and PSA in complicated and non-complicated benign prostatic hypertrophy.

Cancer of the prostate has become the most frequent form of cancer in men. Different tests have been used in cancer of the prostate, including prostate acid phosphatase (PAP) and the prostate specific antigen (PSA). Their value as diagnostic screening is disputed, as it is known that there are false positives for both markers in benign prostate conditions. In order to explain their possible diagnostic value, we studied 112 patients with well-documented benign prostate hyperplasia. The data included in this study were: estimated weight, urinary infection, bladder catheter and histopathological study. By using as cut-off 4 ng/ml for PAP and 10 ng/ml for PSA we found a percentage of false positives of 13% and 14% respectively. These percentages were in relation to the weight of the gland in each cases and in the case of PSA to the patient's clinical situation (infection, catheter).

[The nucleus of ossification in kidney calculus]. / Noyaux d'ossification dans les calculs du rein.

The presence of bone tissue in renal stones has been described for a long time. Two cases of heterotopic ossification are reported in this study. Stone analysis was performed by stereoscopic microscopy, infrared spectrophotometry and fine slice petrographic section and polarized light microscopy. This last technique revealed the existence of osteocytic filling defects inside the stones, an unquestionable sign of mineralized bone tissue.

[Calculi of papillary origin. An undisputed reality]. / Les calculs d'origine papillaire. Une réalité indiscutable.

In 1936, Randall formulated a hypothesis concerning stone formation related to the renal papillae. Randall's hypothesis, discussed for many years, was confirmed by Cifuentes in 1983. The authors studied 830 cases of papillary stones, eliminated spontaneously, 16 of which had a typical Randall plaque with mineralized collecting tubules (1.9%). This study was conducted by scanning electronic microscopy (SEM) using an EDX system. The papillary origin of several renal stones can be confirmed in this way. The origin of these stones would remain unknown without the use of these modern techniques.

[Treatment of tumor osteopathy in cancer of the prostate]. / Tratamiento de la osteopatía tumoral en el cáncer de próstata.

Some 40% of patients with prostate cancer present with disseminated disease at the time of diagnosis and up to 80% of the total will develop bone dissemination during the disease. The aging of the population and the elevated incidence of prostate cancer (13% of malignancies in males) bring the figure of prostate cancer diagnosed in Europe to 85,000 new cases every year. To begin with, a comment on the overall aspects of bone metastasis from prostate cancer such as incidence, development mechanisms, distribution, prognosis and clinical outcome is made placing special emphasis on the grading and the evaluation of major therapeutical regimes for this kind of patients. Bone metastasis are the most frequent cause of pain due to cancer and are also the cause of immobilization, pathological fractures, bone marrow affectation, medullary compression and sometimes hypercalcemia. It is obvious that any comprehensible therapeutical approach must be multidisciplinary.

[Prostatic adenocarcinoma presenting as retrovesical cystic formation. Report of a case]. / Presentación de un adenocarcinoma prostático como formación quística retrovesical. A propósito de un caso.

Presentation of one case of prostate adenocarcinoma with a peculiar evolution towards a large cystic formation at the expense of the left prostate lobe, clinically revealed as a picture of poor performance status and impaired consciousness secondary to obstructive renal failure. The benign evolution of the case, even though the patient received no specific therapy, is emphasized.

[Role of tissue polypeptide antigen as a marker in bladder cancer]. / Papel del TPA como marcador tumoral en el cáncer de vejiga.

Presentation of a review of TPA serum levels in 207 patients, 160 of which had vesical carcinoma. This population comprises 37 patients who had suffered vesical carcinoma but whom, at entry in the study, did not display clinic evidence of that: 11 patients with benign vesical pathology; 84 patients with primary vesical tumour, and 76 patients with relapsing vesical tumour. Tumoral staging resulted in 72 Ta, 49 T1, 10 T2, 14 T3, and 15 Ta. Distribution with regard to degree of differentiation was as follows: 52 GI, 61 GII and 40 GIII. Sensitivity of serum TPA in our series was 39% and specificity 94%. When tumours were subdivided into surface and infiltrant tumours, sensitivity was 28% and 72% respectively (p < 0.01). Patients presenting normal levels of serum TPA took longer to relapse than those who had high levels. Mean time to relapse was 17 months for the first group, and 12 months for the second group. Serum TPA increased its performance with carcinomas of higher grade and stage, but it does not have enough sensitivity to be considered a useful marker in low stages. However, serum TPA relationship to the tumour's invasive degree and the disease-free interval are an indication for their likely use as a prognostic factor to delimit the groups with higher risk of relapse.

[The diagnostic utility of PSA density]. / Utilidad diagnóstica de la densidad de PSA.

Recently, the concept of PSA density has been introduced in order to increase the diagnosis sensitivity obtained with serum PSA dosing. The usefulness of this parameter has been assessed in 47 patients with benign prostate hyperplasia (BHP) and 26 patient with non-disseminated prostate adenocarcinoma. Using 0.15 as cut-off value, below which were 97% of patients with uncomplicated BHP, we obtained a 73% overall sensitivity. This sensitivity was stage related, reaching 100% in stage C patients. On the contrary, the test specificity was relatively low, since it considered patients with complicated HPB with urinary infection or with in-dwelling vesical catheter, obtaining 41% false positives. These results suggest a special usefulness of this test for the correct diagnosis of those prostate cases with mild suspicion of cancer.

[Correlation between bone gammagraphy and biochemical parameters in bone turnover in patients with prostate cancer]. / Correlación entre gammagrafía ósea y parámetros bioquímicos del recambio óseo en pacientes con cáncer de próstata.

Evaluation of osteocalcin (BGP), hydroxyproline/creatinine (HxP/Cr) and PSA values in 43 patients with prostate cancer, 25 with spread disease (bone metastasis) and 18 with no bone dissemination. Correlation of values obtained with the patient's clinical status: complete response, partial response, steady state and progression. Mann-Whitney's U test shows statistical significance (P < 0.001) when patient's PSA values are compared to non-disseminated disease with regard to those with bone metastasis, the same result being obtained with the HxP/Cr ratio. Comparison of BGP figures within the same groups did not reach statistical significance, although the number of patients with abnormally high BGP values was considered to be much higher in patients with disseminated (52%) versus non-disseminated (11%) condition. We conclude that both a deeper knowledge of bone dynamics in these patients and, therefore, evolutive follow-up of bone turnout and resorption is required in order to establish clinically useful criteria.

[Unilateral spontaneous adrenal hematoma: an unusual cause of retroperitoneal hemorrhage]. / Hematoma suprarrenal espontáneo unilateral una causa excepcional de hemorragia retroperitoneal.

Presentation of one case of spontaneous retroperitoneal haemorrhage in a 72 year-old male, his first symptom being a left retrothoracic pain of sudden onset. The supplementary studies performed (ultrasound, CAT and MNR) pointed to the adrenal gland as the origin of the haemorrhage. Faced eith the uncertainty of the etiological diagnosis, a left supra-renalectomy was conducted which confirmed the pathological anatomy of the piece and the presence of massive haematoma of the suprarenal gland with no other pathological data. The clinical, diagnostic and therapeutical aspects are discussed.

[Acute peritonitis as a clinical manifestation of xanthogranulomatous pyelonephritis]. / Peritonitis aguda como manifestación clínica de pielonefritis xantogranulomatosa.

Xanthogranulomatous pyelonephritis can become clinically apparent in a variety of manners. The paper contributes a very infrequent presentation; a picture of acute peritonitis following non-focal generalized toxic syndrome and haematuria episodes.