Molecular markers and their prognostic impact in patients with advanced prostate cancer undergoing intermittent androgen suppression.

OBJECTIVE: Tumour features were evaluated during intermittent androgen suppression (IAS), and their prognostic impact on the first off-treatment time was analysed. PATIENTS AND METHODS: Twenty patients with advanced prostate cancer underwent three consecutive prostate biopsies during the first cycle, namely at the beginning of androgen deprivation, 8 months after continuous therapy and at the time of prostate-specific antigen (PSA) progression above 20 ng/ml. Biopsy specimens were immunohistochemically processed and analysed for the apoptotic index (AI), Ki-67, p53 and Bcl-2 to investigate eventual changes over time. Correlations and regression analysis were performed to assess the prognostic significance of clinical and pathological parameters in predicting the first off-treatment time. RESULTS: In contrast to the AI, p53 and Bcl-2, Ki-67 was the only marker that significantly changed over time (P=0.008). The first off-treatment time correlated significantly with pretreatment PSA (r=-0.594; P<0.01), testosterone recovery time (r=0.590; P=0.013) and biopsy grade (r=-0.738; P<0.01); only the latter gaining an independent factor in the multivariate analysis (P=0.022). CONCLUSIONS: During IAS, Ki-67 was the only molecular marker that consistently changed over time. However, it did not correlate with off-treatment time that was predicted independently by the initial biopsy grade only. First off-treatment time was best predicted by clinical parameters and molecular markers from needle biopsies did not further contribute to a better patient selection.

Does extended lymphadenectomy increase the morbidity of radical cystectomy?

OBJECTIVE: To report the events during and after radical cystectomy and urinary diversion for bladder cancer, in terms of major and minor complications, comparing a minimal with an extended lymphadenectomy, as more lymph nodes obtained during radical cystectomy may improve staging and thus the outcome. PATIENTS AND METHODS: We reviewed 92 consecutive patients who underwent radical cystectomy from March 1998 to February 2002; 46 had a minimal (group A) and 46 an extended lymphadenectomy (group B). Cases were selected according to the American Society of Anesthesiologists classification, only including those graded 2 or 3. We specifically evaluated the incidence and type of complications within 30 days after surgery. RESULTS: Because of extending the lymphadenectomy the operative duration was a median of 63 min longer in group B (P < 0.01). Complications requiring surgical interventions occurred in four (9%) patients in group A and five (11%) in group B (P = 0.28). Complications requiring no surgical intervention were also similar in both groups. Three patients died, two in group A and one in group B (P = 0.57). CONCLUSION: Extended lymphadenectomy in radical cystectomy does not increase the morbidity within 30 days of surgery.

Sacral distribution of prostatic lymph nodes visualized on spiral computed tomography with three-dimensional reconstruction.

OBJECTIVE: To evaluate the involvement of sacral lymph nodes in prostatic lymphatic drainage, using contemporary radiological imaging techniques. PATIENTS AND METHODS: The study included six patients (mean age 61.8 years, range 51-75) with suspected prostate cancer. First, an oil-based contrast medium was injected into the prostate under transrectal ultrasonographic and fluoroscopic guidance, after which a standard ultrasound-guided sextant biopsy was taken. Before injecting the contrast medium, and 20 min and 24 h thereafter, the patients underwent spiral computed tomography of the pelvic region with three-dimensional reconstruction. RESULTS: In all patients the prostate drained via the sacral lymphatic region. Compared with the iliac lymphatic drainage system, there were fewer and narrower sacral lymph nodes. Prostatic sacral lymph nodes were located at S2 to S5, with an emphasis on S3-4. Lymph nodes were detected as presacral and in the sacral foramen, suggesting a direct lymphatic connection to the bony pelvis. CONCLUSION: These results suggest that sacral prostatic lymphatics are a potential route of spread of prostate cancer cells.

Lymphatic drainage of prostatic transition and peripheral zones visualized on a three-dimensional workstation.

OBJECTIVES: To determine whether the prostate has lymphatic/lymph node drainage that is not sampled by conventional lymphadenectomy and whether the transition and peripheral zones of the prostate have a different lymphatic drainage, because up to one quarter of lymph-node-negative patients who undergo radical prostatectomy will develop distant metastases. METHODS: Ten patients (mean age 62.3 years, range 50 to 76) scheduled for transrectal ultrasound-guided sextant biopsy because of an elevated serum prostate-specific antigen level of 4 to 10 ng/mL and a normal digital rectal examination were included in this study. All patients underwent ultrasound-guided sextant biopsies. Subsequently, an oily contrast medium was injected into the transition zone (group A, n = 5) or peripheral zone (group B, n = 5) of the prostate under transrectal ultrasound guidance and fluoroscopy. Immediately, 1 hour, and 24 hours after the procedure, anteroposterior and lateral radiographs were obtained. In addition, spiral computed tomography of the abdomen was performed 10 minutes after the procedure and analyzed on a three-dimensional workstation. RESULTS: No difference in the lymphatic drainage system between the transition and peripheral zones of the prostate was found. In all patients (n = 10), the lymphatic drainage comprised three major routes: (1) the prostate to the lymph nodes along the lateral bony wall of the pelvis to the angle of internal/external iliac lymph nodes to the common iliac lymph nodes, (2) the prostate to the perineal floor to the pudenda internal lymph nodes to the angle of the internal/external iliac lymph nodes to the common iliac lymph nodes, and (3) the prostate to the sacral lymph nodes. In all 10 patients, main contrast medium enhancement was seen immediately after procedure indicating drainage from the prostate to the lymph nodes along the lateral bony wall of the pelvis. Presacral lymph node enhancement was seen in all patients only in the late (24 hours after contrast injection) radiograph. CONCLUSIONS: Our data suggest that the main lymphatic drainage, irrespective of the prostatic region (transition or peripheral zone), runs to the pelvic regions that are mostly removed by standard lymphadenectomy techniques. However, one has to bear in mind that the prostate has some lymphatic drainage that is not covered by standard lymphadenectomy and therefore carries the risk of metastatic tumor spread.

Twelve prostate biopsies detect significant cancer volumes (> 0.5 mL).

OBJECTIVES: To compare, in a retrospective study, pathological specimens of prostate cancer detected in additional areas of a 12-core biopsy with tumours detected using traditional sextant biopsy. PATIENTS AND METHODS: The study included 27 patients who had undergone radical prostatectomy (RP) for prostate cancer. Prostatectomy specimens of cancers detected using standard sextant biopsies were compared with those detected using six additional core biopsies. The RP specimens were analysed for cancer volume, Gleason score, tumour grade (Mostofi) and pathological stage. RESULTS: Of the 27 patients, six (29%) had cancer detected in the extra six biopsy cores which would have otherwise have been undetected using sextant biopsy. Only two insignificant cancers were detected. The mean Gleason score was 6.1 for cancer detected by the sextant or 12-core method (P = 0.907); the mean grade (Mostofi) was 2.1 and 2. 33, respectively (P = 0.29). The final tumour stage in the 21 patients undergoing sextant biopsy was pT2 in 13 and pT3 in eight, compared with six pT2 tumours in the six patients diagnosed using extra biopsies. The mean (median, range) tumour volume was 5.7 (3.5, 0.312-23.75) mL for cancers detected on sextant biopsy and 1.99 (1. 85, 0.4-3.6) mL in the six cancers detected using extra cores (P = 0. 0138). CONCLUSION: The detection of prostate cancer was increased using extra biopsy cores. There was a significant difference in tumour volume but not in Gleason score, Mostofi grade or final pathological tumour stage between tumours diagnosed using 12 cores and those detected on sextant biopsy.

A comparative study of a double-line versus a fan-shaped technique for obtaining transrectal ultrasound-guided biopsies of the prostate.

INTRODUCTION AND OBJECTIVES: Transrectal ultrasound-guided biopsy of the prostate is an established method to obtain prostate specimens for histological analysis. The aim of this prospective study was to compare the prostate cancer detection rate of the conventional double-line biopsy to a more fan-shaped biopsy technique. METHODS: A total of 107 men were included in this study. The indication for performing a prostate biopsy was a serum prostate-specific antigen level exceeding 4 ng/ml and/or suspicious findings on digital rectal examination. 53 patients were biopsied by the conventional double-line technique (method A): 3 biopsies in the midparasagittal plane from each lobe at the apex, middle and basis, at an angle of approximately 45 degrees C. 54 patients were biopsied with the so-called fan-shaped technique (method B): 6 biopsies were taken from the left to the right lateral margin in one plane at the same angle. RESULTS: 642 prostate biopsy cores were obtained, a subset of 133 biopsies were identified to yield prostate cancer. The percentage of positive biopsies was higher in group B (n = 81; 61%) as compared to group A (n = 52; 39%). The overall prostate cancer detection rate by the fan-shaped technique was 37% (20/54) as compared 30.1% (16/53) to the conventional double-line technique, but this difference did not reach statistical significance (p < 0.05) presumably because of the small number of patients. CONCLUSION: These data suggest that the fan-shaped biopsy technique seems to have a higher cancer detection rate and a higher number of positive core biopsies than the conventional double-line technique, because of more presence in the apex and the peripheral zone of the prostate where most prostate cancers originate from.

A 3,500-gram leiomyoma of the bladder: case report on a 3-year follow-up after surgical enucleation.

We report on a unique-sized large leiomyoma of the bladder wall in a male patient. After open surgical intervention all symptoms resolved spontaneously and no relapse occurred within a 3-year follow-up period. In conclusion, for symptomatic leiomyoma of the bladder surgical intervention should be considered as an early treatment option since it is associated with low morbidity, a high cure rate for this type of tumor and an immediate relief of urological symptoms.

Value of routine sonography in the diagnosis and conservative management of renal angiomyolipoma.

A prospective study was undertaken to assess the value of ultrasonography in the clinical monitoring of angiomyolipomas. 26 patients with angiomyolipomas as diagnosed by sonography and verified by computerized tomography (CT) were followed up by sonographic monitoring over a mean period of 45 months. One case was associated with tuberous sclerosis. Inclusion criteria for conservative management had been clinically asymptomatic angiomyolipomas smaller than 5 cm. Significant tumor growth and a change of the sonographic pattern during follow-up was seen in 2 patients. After renewed follow-up CT scanning failed to reveal negative density values, both patients were nephrectomized. Histologic examination showed hemorrhage in the tumor. The remaining 24 patients (92%) showed no changes in the sonographic patterns. Minor tumor growth of 0.5 cm on average was seen in 6 patients over a mean follow-up period of 52 months. Surgical intervention was refrained from in these 24 patients due to the consistent sonographic pattern and the absence of clinical symptoms. Once the angiomyolipoma is verified by CT, sonographic monitoring suffices if the sonostructure remains unchanged. Minor asymptomatic angiomyolipomas today no longer require surgical intervention as this benign tumor has a pathognomonic sonographic appearance.

Risk factors for bilateral testicular germ cell tumors. Does heredity play a role?

Twenty-three bilateral testicular germ cell tumors (four synchronous and 19 sequential tumors) were investigated for potential risk factors. The incidence of maldescensus testis was not found to be higher than in patients with unilateral disease. The histologic findings of the first tumor did not have any effect on the incidence of the second tumor. In 21 patients (four synchronous and 17 sequential tumors), histocompatibility antigens (HLA) were determined; HLA-B14 was increased significantly in the sequential tumor group. Tendencies toward an increase of HLA-DR5 and HLA-DR7 also were found. The HLA-DR1, HLA-DR3, and HLA-DR4 showed a tendency toward a decreased frequency. Therefore genetic factors might be important in the development of sequential bilateral testicular cancers.

Effects of the duration of therapy with the LHRH agonist D-ser (BUT)6 Azgly10-LHRH (ICI 118-630) on the steroid hormone content and the morphology of human testicular tissue in the treatment of patients with advanced prostate cancer.

In 20 patients with locally advanced or metastatic prostate cancer, testicular tissue obtained by bilateral subcapsular orchidectomy was examined for steroid hormone content and morphological changes. Eight patients (group I) had not received previous treatment. Twelve patients had been treated with monthly subcutaneous doses of the depot luteinizing hormone-releasing hormone (LHRH) agonist D-ser (BUT)6 Azgly10-LHRH (ICI 118-630). Six patients (group II) had been treated for less than 6 months and 6 patients (group III) for more than 6 months. The longest duration of treatment with depot LHRH was 36 months. After 2 months of treatment (group II), maximum hormone suppression was achieved and remained unchanged even if treatment was continued for 3 years. The mean serum testosterone levels were decreased in group II (means = 0.586 mg/ml) and in group III (means = 0.575 mg/ml) and were found to be in the range of castration; a statistically significant reduction in luteinizing hormone (P less than 0.000001) and follicle-stimulating hormone (P less than 0.05) was observed in the treated patient groups. The content of the steroid hormones dihydroepiandrosterone sulfate (DHEA)-S, testosterone, androstenedione, oestradiol, progesterone and 17-alpha-hydroxyprogesterone/g testicular tissue was significantly lower in patients on LHRH agonists. The differences in concentration were particularly pronounced for DHEA-S, T and A. As in the case of serum concentrations, the testicular tissues showed no differences between groups II and III. In the treated groups a significant reduction in weight was seen, depending on the duration of therapy. Similarly, the structural changes visible by the aid of light and electron microscopes increased with the duration of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

[Chemical castration using a depot LHRH-agonist as a palliative therapy concept in prostatic carcinoma--clinical, endocrinological and experimental studies]. / Chemische Kastration mit einem Depot LHRH-Agonisten als palliatives Therapiekonzept beim Prostatakarzinom--klinische, endokrinologische und experimentelle Untersuchungen.

79 patients with locally advanced and/or metastatic prostate cancer were treated by means of a biodegradeable depot formulation of the luteinizing hormone releasing hormone analogue Goserelin (Zoladex). All patients received 3.6 mg depot Goserelin (Zoladex 3.6 mg implantate) subcutaneously into the anterior abdominal wall at 4 weekly intervals. The average time of observation was 24.2 months. The best objective response rate was found in 62%. Serum testosterone levels initially increased after the first depot injection and then decreased ultimately to castrate range (less than 0.6 ng/ml) between day 15 and day 27 (median 21) in the majority of patients. Castrate testosterone levels were still found 48 months after the start of treatment with depot Goserelin. 6 months after institution of treatment in 66.7% of cases evident signs of histological regression were found in the primary tumour tissue. Adenocarcinoma presented with a highly significantly better response pattern than anaplastic carcinoma. In animal experiments a single dose of 1 mg depot Goserelin was administered to adult male rats and the effect on serum testosterone levels and target organs (testes and ventral prostate) were investigated. Mean testosterone levels (mean = 0.31 ng/ml) decreased to castrate range (less than 0.3 ng/ml). 4 weeks after depot injection weight of the testes and prostate weight were significantly reduced. However 8 weeks after administration of 1 mg depot Goserelin there was no significant between the control group and the treated group. We conclude that the depot formulation of Goserelin (Zoladex) is effective, simple, practicable and safe in the treatment of advanced prostatic cancer. Current clinical studies are confirming the importance of reversible medical castration by LHRH agonists before radical prostatectomy.

Surveillance strategy for intratesticular cysts: preliminary report.

We treated 15 patients with all sonographic criteria of a simple testicular cyst. Of the patients 6 were operated on and the diagnosis was confirmed histologically, while 9 did not undergo an operation but are under close observation (mean surveillance 11 months). All patients are without any detectable malignancy. The possibility of a surveillance strategy in simple intratesticular cysts is discussed.

Has ultrasound influenced the therapy concept of blunt scrotal trauma?

We present the ultrasonic diagnoses and treatment of 44 patients with blunt scrotal trauma (rupture of the testis, hematocele, intratesticular hematoma and hematoma of the scrotal layers). Purely intratesticular hematoma without any other accompanying injury also can be detected sonographically. When massive scrotal swelling is present ultrasound is valuable to determine the status of the underlying testis even if discrete fracture planes of the tunica cannot always be detected. To achieve best long-term results early surgical intervention should be performed in cases of rupture of the testicle and hematocele, while hematoma of the scrotal layers and purely intratesticular hematoma can be treated conservatively.

[Hydatid torsion as a cause of acute scrotum--clinical, sonographic and anatomic aspects]. / Hydatidentorsion als Ursache des akuten Skrotums--klinische, sonographische und anatomische Aspekte.

Out of 82 patients with acute swelling of the scrotum, 25 (30.5%) had hydatid torsion. Hydatid torsion was the second most common cause of acute scrotal swelling in the entire patient group. In the group of patients up to 14 years of age (n = 36), hydatid torsion was found in 47.2% and was the most common cause of acute scrotal swelling, followed by torsion of the spermatic cord. Only 3 patients had torsion of an appendage of the epididymis. All other patients (n = 22) had torsion of the hydatid of Morgagni (appendage of the testicle). A difference in anatomical structure and vascularization during childhood seems to be the most important aspect regarding hydatid torsion and hemorrhagic infarction. Ultrasonographic examination of the scrotum and checking to see if the typical physical signs are present can help in making the exact diagnosis. In 13 patients with hydatid torsion, the scrotum was examined with ultrasound high-frequency transducers (7.5, 10 and 12 MHz). In 4 patients, the diagnosis was hydatid torsion, as determined by ultrasonography. Two patients were treated conservatively with a daily follow-up including a clinical examination and investigation of the scrotum with ultrasound. The patients recovered very quickly and the acute symptoms resolved within a few days in virtually all instances. Thus, in cases where the diagnosis is proven and the course of the disease is reasonably mild and painless, conservative management of intrascrotal hydatid torsion is possible and can be an effective means of treatment in lien of surgical intervention.

Sonographic appearance of benign intratesticular lesions.

58 patients with a purely intratesticular lesion were investigated with scrotal ultrasound. A pathognomonic echo pattern could be found for simple parenchymal cysts and hemangiomas only. The nature of all other lesions (chronic orchitis, hematoma, epidemoid cyst, testicular necrosis, abscess and tuberculosis) could not be defined solely on sonographic grounds.

Impact of sonography on diagnosis of scrotal diseases: a multicenter study.

Scrotal ultrasound was carried out since 1980 in five centers. 1,971 cases presenting with pathological conditions of scrotal content were reviewed to asses limitations and possibilities of the method. Scrotal sonography was found to be a highly reliable method to distinguish between intra- and extratesticular lesions. The data presented reveal that sonography is not capable of differentiating reliably between benign and malignant lesions. In the decision-making process ultrasound is sometimes of great help to the urologist but surely no substitution for careful examination and history taking.

Texture analysis--a new method of differentiating prostatic carcinoma from prostatic hypertrophy.

This study compares the results of a new computer assisted evaluation program of sonographic images of the prostate with the histological examination of the operative specimen. This computer program is based on the fact that the human eye is not capable of distinguishing picture distribution points which differ in higher than second order statistics. The sensitivity of the method was 89%, the specificity 86% and the diagnostic accuracy 88%. The results are discussed by comparing them to results of transrectal sonography and digital palpation as reported in the literature.

[Late result following successful penis replantation with spontaneous closure of a urethral fistula]. / Spätergebnis nach erfolgreicher Penisreplantation mit spontanem Urethrafistelverschluss.

We report about the postoperative course and late result in a case of successful reimplantation of a totally amputated penis. A small urethral fistula closed spontaneously during the postoperative. Follow-up at five years shows a satisfactory cosmetical and functional result.

[Clinical, endocrinological and pathohistologic aspects of beta-HCG positive seminoma]. / Klinische, endokrinologische und pathohistologische Aspekte zum Beta-HCG-positiven Seminom.

The most important aspects of the clinical findings, endocrinology and course of the disease in 14 patients with the histological diagnosis of pure seminoma of the testis and positive serum beta-HCG levels are presented. In addition to routine investigations, immunohistochemical examination of the formalin-fixed specimen by the immunoperoxidase technique was also carried out. Serum alpha-feto-protein levels remained normal in all 14 patients. There was no correlation between serum beta-HCG level and tumour stage. The longest period of observation was 76 months and the shortest 8 months. Patients with no evidence of metastatic disease (5 patients, N0M0) or patients with low-stage disease (5 patients, N1 or N2M0) respond very well to radiotherapy. 4 patients (N3-N4M0) with large retroperitoneal metastases or distant lymph node metastases underwent different combinations of treatment.

Experience with beta-HCG-positive seminoma.

The clinical findings, diagnosis and course of disease of eight patients with histological pure seminoma of the testis and positive serum beta-HCG levels are presented. In addition to routine investigations, immunohistochemical examination of the formalin-fixed specimen by the immunoperoxidase technique was also carried out. Serum alpha-feto-protein levels of all eight patients remained normal. There was no correlation between serum beta-HCG level and tumour stage. The longest period of observation was 48 months, the shortest 11 months. All patients were treated primarily by radiotherapy. One patient also received chemotherapy and one patient underwent bilateral lymphadenectomy 13 months after radiotherapy.