[Characteristics of metastatic prostate cancer occurring in patients under 50 years of age]. / Patrón de presentación del cáncer de próstata avanzado en pacientes menores de cincuenta años.

OBJECTIVE: To identify the clinical features, diagnostic approach, and treatment of metastatic prostate cancer in young adult patients. METHODS: A retrospective review was made of the clinical histories of patients under 50 years of age diagnosed with prostate cancer at the urology department of the National Institute for Neoplastic Diseases from 1952 to 2005. Demographic characteristics and data on history, symptoms, diagnostic procedures, treatment, and disease course were collected. Data were statistically analyzed and compared to information obtained from a literature search. RESULTS: There were 69 patients aged less than 50 years who had been diagnosed with prostate cancer, 60% of whom had metastatic tumors. Mean patient age was 45.5 years, with a lower range of 29. All patients reported bone pain, associated to other signs and symptoms such as spinal cord compression (19.5%), lower limb edema (17%), peripheral adenopathies (36.5%), and abdominal tumor (2.4%). All patients had bone metastases, of which 14.6% were in solid organs (lung and liver), 48.7% in retroperitoneum, and 7.3% in mediastinum. Initially, three patients were diagnosed a lymphoproliferative syndrome, one patient a retroperitoneal tumor of unknown etiology, and four patients a metastasis from an unknown primary tumor. Mean prostate-specific antigen (PSA) level was 795 ng/mL (3-6500). All pathologies were reported as poorly differentiated or undifferentiated. Mean survival was 16.1 months (1-84), and all patients died due to disease progression. CONCLUSIONS: Advanced prostate cancer is an uncommon condition in young adults. Its clinical presentation is atypical, as metastases may mimic other diseases. The course of disease is indolent, and prognosis is poor. In patients with risk factors, PSA testing should be started before 50 years of age.

Oncogenes E6-E7 de los papilomavirus humanos de alto riesgo detectados por PCR en biopsias de pene incluidas en parafina / Oncogenes E6-E7 of the human papillomavirus of high risk detected by PCR in penile biopsia included in paraffin

La alta prevalencia del papilomavirus humano (PVH), referida a nivel mundial, en lesiones genitales de ambos sexos, el rol del varón como reservorio pasivo del virus, y el incremento de la mortalidad por cáncer genital en la mujer en nuestro país, motiva la determinación y correlación de los oncogenes de los PVH de alto riesgo con la neoplasia de pene. Informamos de diez casos de biopsias de carcinoma escamoso de pene, incluidos en parafina, los cuales fueron investigados para la presencia de los oncogenes E6-E7 de PVH de alto riesgo, utilizando cebadores tipo específico para los PVH-16 y 18, mediante la reacción en cadena de polimerasa (PCR). El 40 de los casos mostró un producto de amplificación ADN E6-E7 de los PVH estudiados, correspondiendo el 75 de ellos a detección simple por PVH-18 y el 25 presentó mixta ADN E6-E7 del PVH-16 y 18 simultáneamente. El producto de amplificación fue sometido a comprobación por análisis de restricción específico. La prevalencia obtenida de los oncogenes E6-E7 de los PVH de alto riesgo, usando un método tan sensible como la PCR, apoya el rol de estos virus en el proceso de carcinogénesis de la neoplasia de pene

Increased incidence of non-transitional cell carcinoma of the bladder in women of the Texas Gulf Coast region.

The objective of our study was to verify a suspected increased incidence of non-transitional cell carcinoma (TCC) of the bladder in female patients treated at our institution. The study included 169 patients, 83% of whom resided in the Texas Gulf Coast region. Tumors were considered TCC or non-TCC on the basis of their predominant histologic pattern. The incidence of non-TCC among men (8.1%) was comparable with data from American tumor registries and European studies. In contrast, our female patients exhibited a marked increased incidence of non-TCC (42.3%), which is approximately five times higher than that in other series. All male and female patients with non-TCC had invasive disease. History of urinary tract infections was strongly associated with non-TCC. Our results suggest that our sample of the female population in the Texas Gulf Coast region has a significantly high incidence of non-TCC. This unusual trend merits further investigation.

Mechanism of healing of the human prostatic urethra following thermal injury.

OBJECTIVES: To characterize histopathologically the healing response of the prostatic urethra after laser thermal coagulation and standard transurethral resection of the prostate (TURP). METHODS: The study included 31 patients who underwent radical prostatectomy because of malignancy. Twenty-two (first group) had laser radiation either at the time of surgery (18 patients) or from 1 to 12 weeks prior to prostatectomy (4 patients). Nine patients (second group) had TURP from 6 to 96 weeks prior to prostatectomy. RESULTS: Coagulation necrosis followed by sloughing was observed during the first 10 weeks after laser radiation. After the first 10 weeks, the healing response was otherwise stereotypical and comparable for both groups of patients. Re-epithelialization was prominent and resulted from migration of proliferating epithelial cells from the remaining acinar and ductal epithelium. Squamous metaplasia was conspicuous and present indefinitely. Development of inflammatory reaction followed by granulation tissue and well-organized fibroblastic stroma were sequentially recognized, but less prominent. Complete re-epithelialization and wound sealing was not observed before the first 12 weeks of healing. CONCLUSIONS: Our study suggests that laser thermal coagulation and TURP are partial-thickness injuries. Because of the abundant germinal epithelium in the remaining prostatic glands and ducts, the healing response of the prostatic urethra is relatively unimpeded and free of contractures, analogous to second-degree skin burns.

Accumulation of porphyrins in plasma and tissues of dogs after delta-aminolevulinic acid administration: implications for photodynamic therapy.

Protoporphyrin accumulates in tissues after administration of delta-aminolevulinic acid, and can be used as a photosensitizer for photodynamic therapy. To determine the distribution of porphyrins in a large animal model after administration of this porphyrin precursor, delta-aminolevulinic acid was administered to anesthetized dogs (100 mg/kg body weight intravenously) and porphyrin concentrations were measured in tissues (liver, pancreas, prostate, bladder, muscle and skin), plasma and urine for 6-10 h. Porphyrins increased markedly (up to 50-fold) in plasma within 1 h, were still markedly increased at 8 h, and consisted mostly of coproporphyrin III and protoporphyrin. Tissue porphyrin concentrations increased more slowly, were highest in liver, pancreas and prostate 7-10 h after delta-aminolevulinic acid administration, and were predominantly protoporphyrin. Maximum porphyrin concentrations in liver were 3- and 4-fold higher than in pancreas and prostate, respectively. Urinary delta-aminolevulinic acid excretion increased and was greatest 2-4 h after dosing; urinary porphobilinogen and porphyrins increased more gradually and remained increased up to at least 8 h. Coproporphyrin III was the predominant porphyrin in urine at all times, but hepta-, hexa- and pentacarboxyl porphyrins increased proportionally after administration of delta-aminolevulinic acid. These results indicate that porphyrins accumulate in plasma as well as tissues and urine after administration of delta-aminolevulinic acid, and may contribute to tumor necrosis during photodynamic therapy.

Healing response of the canine prostate to Nd:YAG laser radiation.

The objective of the study was to characterize the healing response of the canine prostate to laser thermal injury. The study included 20 canine prostates that underwent transurethral laser radiation. The prostates were retrieved 1 hr after laser radiation in 7 dogs (acute group), and from 3 days to 9 weeks in 13 dogs (chronic group). Two distinct features were observed. First, reepithelialization of the prostate urethra resulted from mobilization of proliferating epithelial cells from acinar and ductal prostatic epithelium into the cavity surface, and not from the edges of the wound at the bladder neck. Squamous cell metaplasia was a prominent feature of reepithelialization. Second, the healing process in the canine prostate was relatively unimpeded. The large glandular component provided abundant germinal epithelial growth, and the absence of stromal elements allowed for complete sloughing of necrotic tissue without residual eschars. Further, the lesions in the chronic group had a tendency to be larger than those in the acute group, suggesting that extended delayed necrosis may occur at deep prostatic tissue layers.

Histopathologic effects of laser radiation on the human prostate.

High levels of applied laser irradiation to the prostate will carbonize or vaporize tissue, and may cause explosive expansion of superheated tissue water. Lower levels, used most often to relieve obstruction caused by benign prostatic hypertrophy, will cause coagulation necrosis. This effect is apparent within 1 h of application. In contrast to the canine, in which laser-coagulated prostate sloughs in 2 to 3 weeks leaving a smooth cavity, in the human necrotic tissue is sloughed irregularly over a period ranging up to 12 weeks. This difference is attributed to the dominantly glandular nature of the canine prostate, and the dense fibromuscular composition of the human prostate stroma. Sloughing is accomplished by surface liquefaction, cavitation of the necrotic coagulum, and to a lesser degree, formation of granulation tissue at the margins. As often occurs at the margin of spontaneous infarcts in the prostate, squamous metaplasia may be prominent at the margins of laser-induced coagulation necrosis.

Development of human papillomavirus type 16 associated squamous cell carcinoma of the scrotum in a patient with Darier's disease treated with systemic isotretinoin.

In contrast to squamous cell carcinoma of the penis, scrotal carcinoma has historically been associated with exposure to environmental or industrial carcinogens and has only rarely been correlated with human papillomavirus. We report on a patient with squamous cell carcinoma of the scrotum in which human papillomavirus type 16 was integrated into the tumor cell genome, suggesting a causal role of human papillomavirus in the development of squamous cell carcinoma of the scrotum. Other unique features of our case include the presence of Darier's disease, an uncommon genodermatosis, and treatment with oral retinoids, which have prophylactic value in the prevention of cutaneous malignancies.

Thermocoagulation effect of diode laser radiation in the human prostate: acute and chronic study.

OBJECTIVES: To evaluate the safety and efficacy of low-power slow-heating diode laser-induced photocoagulation of prostatic tissue for treatment of benign prostatic hyperplasia, we conducted a series of acute and chronic studies using a diode laser (810 nm) to irradiate human prostate. METHODS: The study included 6 patients undergoing radical prostatectomy because of malignancy. Laser radiation to the prostate was given transurethrally, in a noncontact mode, at the time of the procedure in 2 patients (acute group): 10 W for 300 seconds on the right side of the prostate and 15 W for 180 seconds on the left. In the remaining 4 patients (chronic group), laser radiation was given at 1, 7, 10, and 12 weeks prior to the prostatectomy. RESULTS: In the acute group the average depth of coagulation was 8.5 and 9.0 mm for the laser regimens of 15 W for 180 seconds and the 10 W for 300 seconds, respectively. In the chronic group, the average depth of coagulation was 8.9 mm for both laser regimens studied. In the acute group, there was an ill-defined hemorrhagic ring at the periphery of the lesion. At 1 week, an intact necrotic coagulum was present. At 7 weeks, some of the coagulated tissue had already sloughed off. Longer follow-up at 10 and 12 weeks demonstrated formation of a well-defined cavity with mostly re-epithelialized surface. CONCLUSIONS: Our findings suggest that noncontact diode laser (810 nm) irradiation can induce in the human prostate significant coagulation necrosis followed by sloughing of tissue and cavitation of the prostatic urethra.

Histopathological evaluation of laser thermocoagulation in the human prostate: optimization of laser irradiation for benign prostatic hyperplasia.

We have previously shown in a canine prostate model that a noncontact low power neodymium:YAG laser regimen of 15 watts for 180 seconds yields a larger volume of coagulation necrosis than the currently recommended high power regimen of 50 watts for 60 seconds. These 2 regimens have not yet been compared in humans. The objective of this study was to evaluate histopathologically the thermocoagulation effect of these 2 laser regimens in the human prostate and the effect of the spatial distribution of the laser lesions on the extent of coagulation necrosis. The study was conducted in 10 patients undergoing radical prostatectomy or cystoprostatectomy. The laser treatment was given transurethrally 1 hour before removal of the specimen. There were no fractures of the prostate. The coagulation necrosis did not reach the peripheral zone and it was minimal in areas rich in fibromuscular tissue, such as the bladder neck. At times, nodular benign prostatic hyperplasia was unaffected. A 4-quadrant treatment in the same plane often yielded small nonconfluent lesions. Confluent lesions in the same plane yielded approximately 30% greater depth of coagulation necrosis, which was achieved when 3 or 4 lesions were created on each side of the prostate (per single transverse plane). Likewise, coagulation necrosis observed with 15 watts for 180 seconds was approximately 40% greater than that noted with the 50 watts for 60 seconds regimen. Our findings suggest that noncontact laser prostatectomy is a safe procedure that can be improved by modifying the laser regimen and the spatial distribution of lesions.

Randomized clinical trial comparing low power-slow heating versus high power-rapid heating noncontact neodymium:yttrium-aluminum-garnet laser regimens for the treatment of benign prostatic hyperplasia.

OBJECTIVES: To evaluate and compare the safety and effectiveness of two noncontact laser regimens for the treatment of human benign prostatic hyperplasia (BPH), and to assess the impact of the spatial distribution of the laser-induced lesions on treatment outcome. METHODS: This was a prospective, double-blind, randomized study that included 29 patients with BPH (both the patients and the study physician assistant in charge of the follow-up evaluation were blinded to the treatment rendered). The patients were randomized to receive either a 15 W for 180 s (15 patients) or 50 W for 60 s (14 patients) laser regimen (powers measured at the fiber tip). There were two study phases for each treatment group: the irradiated sites were not overlapping during the first phase (lesions 1.5 cm apart), and were overlapping during the second phase (lesion less than 1.0 cm apart). RESULTS: Morbidity was minimal in both groups. At 1 year of follow-up, there was significant improvement of the American Urological Association-7 symptom score, the peak urinary flow rate, and the postvoid residual in both treatment groups. These improvements were not statistically significantly different regardless of time or the phase of the study for the two treatment groups. There were 3 treatment failures, 2 of whom were later successfully re-treated with larger amounts of laser energy. Furthermore, the peak flows in the second phase of the study were statistically significantly higher than those in the first phase of the study, regardless of the treatment group. CONCLUSIONS: Our results suggest that both the 15 W for 180 s and the 50 W for 60 s are equally safe and effective treatments for BPH. Perhaps more importantly, they also suggest that the spatial distribution of lesions and overlapping of treated (irradiated) sites has significant impact on treatment outcome.

Effect of temperature and flow rate of irrigant on coagulation necrosis in canine prostate treated with neodymium:YAG laser.

We studied the effect of the irrigant temperature (5 degrees-38 degrees C) and flow rate (100-500 mL/min) on the extent of coagulation necrosis induced during Nd:YAG laser irradiation in the canine prostate model. The tissue response was quantified based on histopathologic evaluation of the lesions. Changing the irrigant temperature or the flow rate within the ranges studied did not significantly affect the size of the thermal lesions. The intraprostatic temperature distribution during laser irradiation is mainly governed by blood perfusion rather than by irrigant variables.

Nd: YAG laser thermocoagulation of the prostate: the barbecue effect.

OBJECTIVE: To determine systematically the depth of coagulation necrosis induced during Nd: YAG laser irradiation in the canine prostate model, and to define the correlation of laser dose with depth of the lesions. METHODS: We investigated the effect of various dosimetries on prostatic tissue of 17 mongrel canines using laser power in the range of 8 to 60 watts (W) at varying exposure times, from 20 to 300 seconds (S). Applied energy ranged from 1,000 to 5,500 Joules (J). RESULTS: Three distinct features were observed. First, deep coagulation necrosis was induced only with laser regimens of > or = 2,100J, suggesting that there is a threshold of energy that must be overcome in order to achieve significant coagulation depth. Second, the deepest coagulation necrosis was achieved with a low power slow-heating regimen (15W X 180S). Tissue surface changes appeared to be responsible for the reduced depth of coagulation necrosis seen with higher power regimens (> 20 W). Third, increasing the energy above 3,600J did not augment the depth of coagulation, suggesting that a steady state for temperature distribution is reached at that rate of heating. CONCLUSIONS: Our study suggests that in the canine prostate, a low power slow-heating regimen of 15W X 180S may yield larger volumes of coagulation necrosis than other regimens.

Comparison of thermocoagulation effects of low power, slow heating versus high power, rapid heating Nd: YAG laser regimens in a canine prostate model.

We compared the thermocoagulation effects of low power, slow heating (15 W x 180 seconds) versus high power, rapid heating (50 W x 60 seconds) laser regimens in the canine prostate. The study was performed in 20 mongrel canines. On each prostate, the low power regimen was delivered at the 2 and 4 o'clock positions, and the high power at the 8 and 10 o'clock positions. The laser power was measured at the fiber tip. Seven dogs (acute group) were sacrificed 1 hour after the procedure. The other 13 dogs (chronic group) were sacrificed at different time intervals from 3 days to 9 weeks after the procedure. The average depth of coagulation was significantly greater in lesions treated at low power (acute: 10.7 mm., chronic: 13.3 mm.) than in those treated at high power (acute: 8.5 mm., chronic: 11.6 mm.). Another potential benefit of the low power regimen observed in the study was preservation of the integrity and efficiency of the laser probe.

Laser photocoagulation of prostate: influence of dosimetry.

BACKGROUND AND OBJECTIVE: Recently, increasing enthusiasm has been shown for application of lasers for the treatment of benign prostate hyperplasia (BPH). However, little is known about the thermodynamics of prostatic tissue response during laser irradiation and how the treatment outcome can be optimized. Our objective was to conduct a systematic study of the influence of exposure parameters on the extent of tissue coagulation and to determine the effects of rate of tissue heating on lesion size by comparing the tissue response to high laser power rapid heating vs. low laser power slow heating. STUDY DESIGN/MATERIALS AND METHODS: Nd:YAG laser irradiation of prostate was performed in 15 mongrel canines, using an incident power of 15, 30, or 50 Watts (at the fiber tip) and an exposure time varying from 30 to 300 seconds. The laser beam was delivered via a Urolase side-emitting catheter. The tissue response was compared based on gross as well as histological evaluations of thermal lesions. RESULTS: The depth of coagulation necrosis increased as the laser power was reduced from 50 W to 30 W and further to 15 W while the total delivered energy was kept constant at 2,700 J by adjusting the exposure time. The difference between the three heating rates was more dramatic when the estimated volume of coagulated tissue was considered. Increasing the irradiation time for the low power (15 W) from 180 to 300 seconds resulted in enlarging the coagulated volume by a factor of 1.6. However, for high power (50 W), increasing the exposure time from 54 to 90 seconds resulted in increasing the coagulated volume by a factor of 1.2. CONCLUSION: This study suggests that a slow heating regimen yields larger volumes of coagulation necrosis than the currently used rapid heating approach.

Are we overlooking stage a prostate cancer in patients treated for benign prostatic hyperplasia with medical or minimally invasive modalities?

Our objective was to assess the likelihood of overlooking the diagnosis of prostate cancer (PCA), using current screening methods, in patients treated for benign prostatic hyperplasia (BPH) with medical or minimally invasive treatment modalities, which do not produce tissue specimens for histologic review. To appraise this, we examined the impact of the preoperative use of prostatic specific antigen (PSA) in combination with transrectal ultrasound (TRUS) and systematic sextant prostate needle biopsy (PNbx) on the subsequent incidence of stage A PCA in patients undergoing transurethral resection of the prostate (TURP). After excluding all patients found to have PCA during pretreatment screening, 485 patients who underwent TURP for presumed BPH from 1976 to 1994 were reviewed. From 1976 to 1989, PSA was not used for pretreatment screening, and stage A PCA was diagnosed in 11.4% of 317 patients. In 1990 and 1991, pretreatment screening included PNbx obtained under ultrasound guidance for PSA of 15.0 ng/ml or greater. Stage A PCA was diagnosed in 14.2% of 63 patients. From 1992 to 1994, pretreatment screening included systematic sextant PNbx performed for PSA greater than 4.0 ng/ml, and stage A PCA was diagnosed in 2.8% of 105 patients. The difference in incidence of stage A PCA between the first two groups and group three was significant (p = 0.021), as it was the difference in incidence of stage A(2) (P = 0.037). For stage A(1), the difference did not reach statistical significance (p = 0.089). Our findings suggest that systematic sextant PNbx for PSA greater than 4.0 ng/ml significantly reduces the risk of overlooking prostate cancer in patients undergoing treatment of BPH with modalities that do not provide tissue specimens.

Low-power laser radiation for the treatment of benign prostatic hyperplasia: initial clinical experience.

Fifteen patients with significant bladder outlet obstruction secondary to benign prostatic hyperplasia (BPH) were entered in a Phase II open pilot study designed to evaluate the effectiveness of a low-power-slow-heating (15 W x 180 seconds) laser regimen. Laser prostatectomies were performed with a right-angle firing neodymium:YAG laser fiber. Perioperative morbidity was minimal. Nine patients (60%) were able to void on their own within 72 hours after the procedure. The mean postoperative need for catheter drainage was 3.8 days (range 1 to 12). With a mean follow-up of 5 months (range 3-15 months), the improvement of the mean peak urinary flow rate was from 12.8 to 29 mL/sec, the mean postvoiding residual volume was reduced from 100 to 35 mL, and the AUA Symptom Score improved from 28.5 to 6. None of the patients required retreatment, and all the patients were pleased with the outcome. These results suggest that the laser regimen used in our study is safe and effective for the treatment of BPH.