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Incidental carcinoma of the prostate. How much sampling is adequate?

A prospective study of 386 consecutive transurethral prostatic resections from 383 patients with clinically benign glands was undertaken to determine the optimal sampling of chips required for the histologic detection of all clinically significant prostatic carcinomas. Cancers were graded according to two systems and staged by counting involved chips as well as estimating volume density. All Stage A2 prostatic carcinomas were detected by histologic examination of 6 g of randomly selected chips. Although additional tumors were detected in direct proportion to the amount of tissue examined, they were small, well-differentiated, Stage A1 lesions. Histologic sampling of 12 g of randomly selected prostatic chips detected almost 90% of incidental carcinomas, including all clinically significant neoplasms.

Adult↗

The utility of basal cell-specific anti-cytokeratin antibody (34 beta E12) in the diagnosis of prostate cancer. A review of 228 cases.

Basal cell-specific anti-cytokeratin antibody (34 beta E12) decorates the basal cells of benign prostatic epithelium by standard immunohistochemical techniques, whereas adenocarcinoma of the prostate lacks immunoreactivity with this antibody. We reviewed our experience with this antibody to determine its utility in the diagnosis of adenocarcinoma of the prostate as well as its pattern of usage at a tertiary medical center. In all, 7,242 prostate specimens from 5,262 men were seen at Johns Hopkins Hospital between 1/89 and 4/93. Immunostaining for basal cell-specific cytokeratin (34 beta E12) was originally used for diagnostic purposes in 289 questionable area from 228 cases; 45% of these cases were seen in consultation. The distribution of cases using 34 beta E12 was 52% needle biopsies, 32% transurethral prostatic resections (TURPs). 13% radical prostatectomies, and 3% open enucleations. These procedures constituted 2.8% of all needle biopsies, 7.2% of all TURPs, 1.7% of all radical prostatectomies, and 3.5% of all enucleations seen during this time period. For this study the hematoxylin and eosin stain was reviewed without knowledge of the original diagnosis, a diagnosis was favored, the 34 beta E12 stain was examined, and a final diagnosis was determined. The 34 beta E12 stain established (14%), confirmed (58%), or changed (2%) our favored diagnoses, while 18% remained or became equivocal. The 34 beta E12 stain was of no use in 8% of the cases, yet we felt we were still able to render a final diagnosis even without the help of the stain. The differential diagnoses in the questionable foci using 34 beta E12 were cancer versus focus of atypical glands (44%), adenosis (39%), prostatic intraepithelial neoplasia (PIN) (8%), basal cell hyperplasia (5%), and atrophy (4%). However, 34 beta E12 was used in only 15-20% of all cases of adenosis and basal cell hyperplasia and in < 2% of PIN and atrophy cases seen during this time. Reasons for equivocal results were loss of suspicious glands on cut downs used for staining (49%), too few glands to rely on negative staining (23%), technical problems (15%), limited number of positive staining glands in a small focus (7%), and cautery artifact (6%). Although equivocal cases tended to have fewer negative stained glands than cases diagnosed with cancer, there was no minimum number of negative stained glands required to establish a diagnosis of cancer. From these data we conclude that 34 beta E12 staining is a useful tool in confirming, establishing, or changing the diagnosis in questionable foci seen in the everyday practice of surgical pathology.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗

P504S: a new molecular marker for the detection of prostate carcinoma.

The ability to diagnose prostate carcinoma would be improved by the detection of a tumor-associated antigen. P504S, a cytoplasmic protein, was recently identified by cDNA library subtraction in conjunction with high throughput microarray screening from prostate carcinoma. The aim of this study was to establish the pattern of expression of P504S in prostate carcinoma and benign prostatic tissue. A total of 207 cases, including 137 cases of prostate carcinoma and 70 cases of benign prostate, from prostatectomies (n = 77), prostate needle biopsies (n = 112), and transurethral prostate resections (n = 18) were examined by immunocytochemistry for P504S. P504S showed strong cytoplasmic granular staining in 100% of prostate carcinomas regardless of Gleason scores and diffuse (>75% of tumor) staining in 92% of cases. In contrast, 171 of 194 (88%) of benign prostates, including 56 of 67 (84%) benign prostate cases and 115 of 127 (91%) cases of benign glands adjacent to cancers were negative for P504S. The remainders of benign prostates were focally and weakly positive for P504S. The staining pattern of these normal glands was different and easily distinguishable from that observed in prostate carcinoma. Expression of P504S was not found in basal cell hyperplasia, urothelial cells/metaplasia and small atrophic glands that may mimic prostate carcinoma. Our findings indicate that P504S is a highly sensitive and specific positive marker for prostate carcinoma.

Antibodies, Monoclonal↗

Ratio of free-to-total prostate specific antigen in serum cannot distinguish patients with prostate cancer from those with chronic inflammation of the prostate.

PURPOSE: We demonstrate the effect of chronic inflammation of the prostate on the ratio of free-to-total prostate specific antigen (PSA) in serum calculated as a percentage of free PSA and, therefore, that percentage of free PSA is an unspecific means to distinguish among prostate cancer, chronic prostatitis and benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Total, free and percentage of free PSA was measured in 66 men with prostate cancer, 119 with BPH and 17 with asymptomatic chronic prostatitis. In all patients the diagnosis was histopathologically confirmed by microscopic examination of prostatic specimens after sextant biopsy, transurethral prostatic resection or prostatectomy. RESULTS: The median values of total, free and percentage of free PSA were 4.11 microg./l., 0.75 microg./l. and 20.4% in patients with BPH, 10.0 microg./l., 0.84 microg./l. and 8.5% in those with prostate cancer, and 7.60 microg./l., 1.23 microg./l. and 10.6% in those with chronic prostatitis. Patients with prostate cancer and chronic prostatitis had a significantly lower percentage of free PSA than those with BPH. Receiver operating characteristics curve analysis showed that percentage of free PSA as a discriminator between prostate cancer and BPH was not suitable for differentiating between prostate cancer and chronic prostatitis. CONCLUSIONS: Chronic prostatitis is not characterized by elevated total PSA concentrations alone but also by a decreased percentage of free PSA, a tendency similar to that in prostate cancer. This unspecific change in percentage of free PSA must be considered to interpret the percentage of free PSA correctly.

Aged↗

Bilateral pelvic lymphadenectomy, iridium 192 template, and external beam therapy for localized prostatic carcinoma: complications and results.

Thirty-five patients with prostatic adenocarcinoma were treated by bilateral pelvic lymphadenectomy and temporary implantation of iridium 192 strands with adjuvant external beam radiotherapy. With the implant the prostate received between 3,200 and 3,500 gray (Gy) followed in two weeks by small-field external beam irradiation for an additional dose of approximately 3,400 Gy. Morbidity included an ileofemoral thrombosis in one patient, and transient radiation proctitis in four patients; one patient required transurethral prostatic resection for obstruction at one year. Local response of the primary tumor was dramatic in every case at three-month follow-up. In 11 of 15 patients (73%), biopsy at one year showed no evidence of disease.

Adenocarcinoma↗

The impact of polymorphism on prostate specific antigen gene on the risk, tumor volume and pathological stage of prostate cancer.

PURPOSE: A single nucleotide polymorphism with adenine (A) to guanine (G) substitution is identified at position -158 in the androgen response elements region of the prostate specific antigen (PSA) gene. We evaluated the relationship between the PSA -158A/G polymorphism and the risk, tumor volume and pathological stage of prostate cancer. MATERIALS AND METHODS: Peripheral venous blood samples were obtained from 122 patients with prostate cancer and 84 controls with benign prostatic hyperplasia. The diagnosis, tumor volume and pathological stage of prostate cancer were all determined according to the pathological reports of transrectal ultrasound guided prostate biopsy, transurethral prostate resection and radical prostatectomy. The PSA -158A/G polymorphism was determined by polymerase chain reaction based restriction fragment length polymorphism methods. RESULTS: Patients with prostate cancer had significantly greater frequencies of the G allele (87.3% vs 77.4%) and GG genotype (78.7% vs 61.9%) than the control group (p = 0.008 and 0.028, respectively). The OR of GG to AG and AA was 2.27 (p = 0.008). In the prostate cancer group the GG genotype was also associated with larger tumor volume (2.34 vs 0.82 ml) and higher pathological stage (organ confined cancer 68.2% vs 31.8% and extracapsular extension 100% vs 0%) than the GA and AA genotypes (p = 0.013 and 0.036, respectively). CONCLUSIONS: The PSA -158A/G polymorphism is associated with prostate cancer. The G allele increases the risk of prostate cancer and the GG genotype is associated with larger tumor volume and higher pathological stage.

Aged↗

Ferromagnetic thermal ablation of locally recurrent prostate cancer: prostate specific antigen results and immediate/intermediate morbidities.

PURPOSE: Curative options for locally recurrent prostate cancer following external beam radiotherapy are limited due to the significant morbidity associated with surgical therapy. ThermoRods (Ablation Technologies, San Diego, California) are permanently implantable, 14 mm cobalt-palladium alloy rods that produce heat through oscillation of a magnetic field. The rod is designed to self-regulate the temperature to 70C by a temperature dependent magnetic transition (Curie effect). We determined whether patients with prostate cancer and local failure could be treated with thermal ablation of the prostate using this novel technology. MATERIALS AND METHODS: A total of 14 men with an average age of 72 years (range 62 to 81) were enrolled in the study. All had biopsy proven prostate cancer with increasing prostate specific antigen (PSA) (1.0 to 10.3 ng/ml). The seminal vesicles were not routinely biopsied. Metastatic disease was assayed in all men with bone scan and in later patients with abdominopelvic computerized tomography. Patients had ThermoRods placed under transrectal ultrasound guidance, similar to brachytherapy. The pre-plan was rigorously followed to produce a 3-dimensional array with rods separated by 1 cm across the short axis. Patients were treated in a magnetic field for 1 hour. Urethral and rectal temperatures were also monitored and cooled appropriately. Serial PSA measurements and 6 month posttreatment biopsies were obtained after the procedure. RESULTS: Average time since radiation was 4.5 years. PSA nadir values after radiation were between 0.3 and 2.2 ng/ml. Prostatic temperatures were homogeneously increased greater than 50C, while rectal and urethral temperatures did not exceed 44C at any point. The urethral catheter was removed 2 weeks postoperatively in all cases. Six months after the procedure 8 of the 14 men (57%) had a PSA decrease to less than 0.1 ng/ml. Complications included urinary retention as well as incontinence. Incontinence was generally temporary and only 1 patient (7%) had long-term incontinence. Most patients were impotent after treatment. Of the patients 21% experienced urinary retention. Five patients (36%) needed to undergo secondary procedures after therapy, including transurethral prostate resection in 2, balloon dilation in 1, cystoscopic removal of necrotic tissue in 1 and bladder irrigation in 1. CONCLUSIONS: This novel means of thermal ablation produces significant PSA decreases in patients. Morbidity is predominantly in the form of incontinence and impotence. Incontinence is generally temporary. The use of ferromagnetic rods enables the precise control of tissue destruction with the sparing of immediately adjacent structures. The technology uses skills familiar to the urologist and avoids radiation. The durability of the PSA response and incidence of late morbidity remain to be defined.

Aged↗

Serenoa repens treatment modifies bax/bcl-2 index expression and caspase-3 activity in prostatic tissue from patients with benign prostatic hyperplasia.

PURPOSE: Permixon is a lipidosterolic extract of Serenoa repens (SR) widely used to treat men with benign prostatic hyperplasia (BPH). We tested the effect of this drug on molecular mechanisms associated with apoptosis, such as the Bax-to-Bcl-2 expression ratio and caspase-3 activity, in prostatic tissue from men with symptomatic BPH treated for 3 months before surgery. MATERIALS AND METHODS: An open, multicenter pilot study of 2 parallel groups of patients with BPH was done. They were randomized to be followed for 3 weeks without any treatment before surgery (control group) or to receive 160 mg SR orally twice daily for a 3-month period preceding the same surgery. Surgery was ultimately performed in 17 controls and 12 patients by transurethral prostate resection or retropubic adenomectomy. Bax and Bcl-2 expression, and caspase-3 activity were determined by Western blot in 15 controls and 10 patients, and reported in blinded fashion. RESULTS: The Bax-to-Bcl-2 ratio, which is used as an apoptotic index, was significantly increased in the prostatic tissue of treated patients. The level of the intact 116 kDa poly (adenosine diphosphate-ribose) polymerase form, an enzyme involved in the cell death apoptotic pathway, was also found to be decreased in prostatic tissue from SR treated patients, suggesting increased caspase 3 activity in the prostate. CONCLUSIONS: Permixon increased molecular markers involved in the apoptotic process, ie the Bax-to-Bcl-2 expression ratio and caspase-3 activity. This could have clinical relevance due to the improvement in symptoms produced by treatment with this drug.

Aged↗

Urinary fistulas following external radiation or permanent brachytherapy for the treatment of prostate cancer.

PURPOSE: Prostate cancer (PCa) radiotherapy (RT), including brachytherapy, may lead to significant morbidity, including urinary fistulas. If conservative measures fail, urinary and/or fecal diversion is often required. In this study we examined a series of patients with fistulas that developed after pelvic radiation therapy and explored potential predisposing factors and treatment recommendations for refractory fistulas. MATERIALS AND METHODS: Patients were identified who received radiation therapy for PCa between 1977 and 2002, and subsequently had a fistula to the urinary tract. Patients were excluded who had diverticulitis, inflammatory bowel disease, a history of recent radical retropubic prostatectomy (possible iatrogenic etiology) or cancer in the excised fistula. Data were extracted from patient charts, mailed questionnaires and outside records. RESULTS: A total of 51 patients were identified with a history of radiation for PCa who subsequently had a urinary fistula. Of 20 patients meeting inclusion criteria 30% received external beam RT alone, 30% received brachytherapy and 40% received combined external beam RT/brachytherapy. Most fistulas (80%) were from the rectum to the urinary tract with an average diameter of 3.2 cm. Of patients with rectal fistulas 81% had a history of rectal stricture, urethral stricture, rectal biopsy, rectal argon beam therapy or transurethral prostate resection after radiation. All patients with rectourethral fistulas who achieved symptomatic resolution required urinary and fecal diversion. CONCLUSIONS: Conservative treatment is generally ineffective in the management of large urinary fistulas. Surgical intervention offers symptomatic relief and improved quality of life in most patients.

Aged↗

The endocrine-paracrine cells of von Brunn's nests and glandular metaplasia in the supramontanal prostatic urethra.

Endocrine-paracrine (EP) cells are normal cellular constituents of the human genitourinary tract. We examined the distribution and immunostaining profile of EP cells in von Brunn's nests and glandular metaplasia in the supramontanal (proximal) prostatic urethra of adult males and in prostatic ducts of the male fetal urethra. In 15/17 transurethral prostatic resection specimens there were argyrophilic cells and/or serotonin and neuronspecific enolase containing cells in von Brunn's nests/glandular metaplasia and in the supramontanal prostatic urethra. All seven fetal specimens examined contained EP cells and five had focal calcitonin immunoreactivity in prostatic ducts and ductal buds. One adult resection specimen had focal staining for human chorionic gonadotrophin and no case showed staining for somatostatin. These results further support the contention that von Brunn's nests and glandular metaplasia are probably normal urothelial variants in the adult supramontanal prostatic urethra.

Calcitonin↗

Serum concentrations and urinary excretion of lidocaine and its two desethylated metabolites after spinal anaesthesia using lidocaine or lidocaine with phenylephrine.

In 13 patients undergoing transurethral prostatic resection under spinal anaesthesia with heavy lidocaine or with heavy lidocaine plus phenylephrine hydrochloride, the serum concentrations of lidocaine, monoethylglycinexylidide and glycinexylidide and their renal excretion were measured with a HPLC method. Seven patients were given lidocaine alone 1.25 mg/kg and six lidocaine 1.25 mg/kg mixed with phenylephrine hydrochloride 3 mg. There was no significant difference between the two groups either in the serum levels of lidocaine or in the renal excretion rate of lidocaine and its metabolites. This finding gives support to the opinion that phenylephrine in low doses has no prolonging effect on spinal anaesthesia performed with heavy lidocaine.

Aged↗

Estimating allowable blood loss with correction for variations in blood volume.

All the theoretical relationships between blood loss and change in haematocrit used for calculating the allowable pre-transfusion blood loss assume a strictly normovolaemic situation. In this study a formula was derived in which account was taken of the variation in blood volume. The formula was based on clinical data. Measurements of the blood loss, the blood haemoglobin concentration and the haematocrit (HCT) were performed on 230 occasions in the course of 35 transurethral prostatic resections. The change in blood volume was estimated by the haemoglobin dilution method and the value so obtained was compared to both the measured haematocrit and the theoretical value that would presumably have been recorded if there had been no change in blood volume. The relationship established from these comparisons was: blood loss = preoperative blood volume x [In preop HCT - In postop HCT (1 + 0.15 x blood volume change)].

Aged↗

Influence of the fluid balance on the cortisol and glucose responses to transurethral prostatic surgery.

The serum cortisol and blood glucose concentrations were followed for up to 2 h after 35 transurethral prostatic resections performed under epidural anaesthesia. No significant variation in either of these levels was recorded in connection with the seven operations during which there was no disturbance of the fluid balance, or the seven where there was elevation in the central venous pressure indicative of intravenous fluid overload. In contrast, both the serum cortisol and the blood glucose level showed a significant increase in the nine patients with a blood loss of more than 800 ml, and in the nine recording absorption of irrigant in excess of 300 ml and immediate development of hyponatraemia. On the other hand, this response did not occur in the three patients with irrigant absorption where hyponatraemia developed with a delay of at least 20 min. These results suggest that the effect of surgery on the serum cortisol and blood glucose levels may be modified by disturbances of the fluid balance developing in the course of the operation.

Absorption↗

Expired-breath ethanol measurement in chronic obstructive pulmonary disease: implications for transurethral surgery.

If ethanol is added to the irrigant used during transurethral prostatic resection, the absorption of fluid can immediately be detected by measuring the ethanol concentration in the expired breath. To evaluate this method further, we studied the influence of chronic obstructive pulmonary disease (COPD) on the agreement between expired-breath and blood-ethanol concentrations. In 14 men with a mean age of 62 years (range 55-68), the concentrations of ethanol in whole blood and end-expired breath were measured at 12 exactly timed intervals before, during, and after an intravenous infusion of 0.6 g.kg-1 ethanol for 60 min. The pulmonary function was normal in seven of the subjects (control group) whereas the other seven suffered from severe COPD (study group). The results show that the accuracy and precision of breath-alcohol analysis to predict the blood-ethanol level were poorer during the infusion of ethanol than afterwards. However, at all times of sampling the estimation of blood-ethanol concentration indirectly by analysis of breath was not significantly different for COPD patients and the control group. We conclude that ethanol monitoring of irrigant absorption can be used successfully in patients with COPD.

Absorption↗

Effects of 1.5% glycine solution with and without 1% ethanol on the fluid balance in elderly men.

Ten male patients scheduled for transurethral prostatic resection (aged 57-79) were given irrigating fluid by intravenous infusion at 50 ml.min-1 over 20 min. Each patient was subjected to two infusions: 1.5% glycine in water on one occasion, and the same solution but with 1% ethanol added on the other. Urine and blood samples were collected at regular intervals for up to 2 h after infusion, and the changes in the distribution of water and electrolytes between fluid compartments were calculated. Transient prickling skin sensations were frequently reported effects of the infusions. Two patients experienced visual disturbances. There were no changes in the blood ammonia and plasma vasopressin levels. During the infusions, the estimated blood volume and the total plasma sodium and potassium content increased. The solutions produced osmotic diuresis with increased urinary excretion of water and electrolytes. After ending the fluid administration, blood volume was rapidly restored. Over the following 120 min the irrigant water was redistributed intracellularly or removed by urinary excretion. The addition of ethanol did not alter the overall effects of glycine solution on the fluid balance.

Absorption↗

Acid phosphatase levels in serum during transurethral prostatectomy.

Serum prostatic acid phosphatase (S-PAP), serum electrolytes, blood loss and volume of irrigating fluid absorbed were measured during 10-min periods in the course of 35 transurethral prostatic resections. Elevation of the S-PAP concentration occurred in association with a large blood loss, with absorption of irrigant followed immediately by hyponatraemia, and with a sudden drop in systolic blood pressure. The volume of blood lost during irrigant absorption was the most important index of the S-PAP level. A model for the transfer of PAP to the circulation during TURP is presented.

Acid Phosphatase↗

Stop-flow measurement of detrusor contractility in bladder outflow obstruction.

Detrusor contractility was evaluated by measuring the increase in isometric pressure during a stop test in 25 men with benign prostatic hyperplasia. Before transurethral prostatic resection (TUR), a low pressure increase (delta P det iso) was associated with a large volume of residual urine. After TUR both the speed and the amplitude of isometric detrusor contractions during the stop test increased. A pre-operative low detrusor pressure increase was correlated with a great improvement in flow rate after TUR. The value of the stop-flow test was limited, however, since improvement in other urodynamic parameters could not be predicted.

Aged↗

Ethanol monitoring of extravascular absorption of irrigating fluid.

Ethanol monitoring is a method for the early detection of fluid absorption by the intravascular route during transurethral prostatic resection. An analysis was made to determine whether ethanol detection could also be used to quantify extravascular absorption. The concentration-time profile of ethanol in the breath was analysed in 13 men aged between 57 and 80 years with extravasation of 860 to 3600 ml of an irrigant containing glycine 1.5% and ethanol 1%. The results showed that the volume of irrigant absorbed could be predicted from the persistently elevated breath ethanol level at the end of surgery. This prediction had a median deviation of 22% from the value obtained by careful volumetric measurement.

Absorption↗