[[¹¹C]choline as a pharmacodynamic marker for docetaxel therapy. Response assessment in a LNCaP prostate cancer xenograft mouse model]. / Ansprechen auf eine Docetaxeltherapie im LNCaP-Prostatakarzinom-Xenograft-Mausmodell. Untersuchung mit der [¹¹C]Cholin-Kleintier-PET/CT.

UNLABELLED: The AIM of this study was to determine whether [¹¹C]choline can be used for docetaxel therapy response assessment in a LNCaP-prostate cancer xenograft mouse model using [¹¹C]choline small-animal PET/CT. ANIMALS, METHODS: The androgen-dependent human prostate cancer cell line LNCaP was implanted subcutaneously into the left flanks of 17 SCID-mice, 12.5 mg testosterone platelets were implanted in the neck wrinkle. All mice were injected 4-6 weeks after xenograft implantation with 37 MBq [¹¹C]choline via the tail vein. Dynamic imaging was performed for 60 minutes with a small-animal PET/CT scanner. After the first [¹¹C]choline PET/CT imaging 8 mice were subsequently injected intravenously with docetaxel twice (days 1 and 5) at a dose of 3 mg/kg body weight. 8 mice were treated with PBS as a control. [¹¹C]choline PET/CT imaging was performed on day 7, 14 and 21 after treatment. Image analysis was performed using tumor/muscle (T/M) ratios (ROI(T)/ROI(M) = T/M ratio). RESULTS: All LNCaP tumours could be visualized by [¹¹C]choline PET/CT. Before treatment the mean T/M ratio was 2.0 ± 0.2 in the docetaxel-treated group and 1.9 ± 0.2 in the control group (p = 0.837). There was a reduction in the mean [¹¹C]choline uptake after docetaxel treatment of the tumours of the LNCaP cell line as early as 1 week after initiation of therapy (T/M(mean) ratio 1.5 ± 0.2 after one week, 1.3 ± 0.2 after 2 weeks and 1.4 ± 0.2 after 3 weeks). There was no decrease in [¹¹C]choline uptake in the control group. CONCLUSION: Our results show that [¹¹C]choline has the potential for use in the early monitoring of the therapeutic effect of docetaxel in a LNCaP prostate cancer xenograft animal model.

[Lichen sclerosus in the genitourinary region]. / Lichen sclerosus im Urogenitalbereich.

Lichen sclerosus (LS) is a chronic inflammatory disorder of the skin and mucosa, presenting to genitourinary physicians, pediatricians, and dermatologists. It affects both sexes with a lower incidence in men than in women. Autoimmune factors, infections, and genetic disposition are implicated in its pathogenesis. The classic clinical picture is of atrophic white plaques in the anogenital region. Pruritus, soreness, difficulty retracting the foreskin, and obstructive urinary symptoms are frequent complaints. Early histological confirmation by biopsy is recommended. The disorder is usually highly responsive to ultrapotent topical steroids. This may help arrest or delay the progressive nature of this disorder. Surgical treatment may be needed in cases of disease progression despite medical therapy. Circumcision is a successful treatment, if LS is limited to the glans and foreskin. In cases of meatal stenosis meatoplasty and in cases of urethral involvement one- or two-stage oral graft urethroplasty is necessary.

The detection rate of [11C]choline-PET/CT depends on the serum PSA-value in patients with biochemical recurrence of prostate cancer.

PURPOSE: An increase of the serum PSA-level is a sensitive in vitro marker for recurrent prostate cancer. However, it remains difficult to differentiate between local, regional or distant recurrent disease. The aim of this study was to assess the relationship between the detection rate of [(11)C]Choline-PET/CT and the serum PSA-level in patients with a biochemical recurrence of prostate cancer with the view towards localisation of recurrent disease. METHODS: Sixty-three patients (mean age, 68.8 +/- 6.9; range, 45-83 years) with biochemical recurrence after primary therapy for prostate cancer were included in the analysis. Mean PSA-levels were 5.9 +/- 9.7 ng/ml (range, 0.2-39 ng/ml; median, 2.15). Of the 63 patients, 17 were under anti-androgen therapy at the time of [(11)C]Choline PET/CT. Patients underwent a [(11)C]Choline-PET/CT study after injection of 656 +/- 119 MBq [(11)C]Choline on a Sensation 16 Biograph PET/CT scanner. RESULTS: Of the 63 patients, 35 (56%) showed a pathological [(11)C]Choline uptake. The detection rate of [(11)C]Choline-PET/CT showed a relationship with the serum PSA-level: The detection rate was 36% for a PSA-value <1 ng/ml, 43% for a PSA-value 1-<2 ng/ml, 62% for a PSA-value 2-<3 ng/ml and 73% for a PSA-value >or=3 ng/ml. Anti-androgen therapy did not show a significant effect on the detection rate of [(11)C]Choline-PET/CT (p = 0.374). CONCLUSION: As an important result our study shows that even for PSA-values <1.0 ng/ml the detection efficiency of [(11)C]Choline-PET/CT is 36%. Furthermore, the detection rate of [(11)C]Choline-PET/CT shows a positive relationship with serum PSA-levels in patients with biochemical recurrence of prostate cancer after primary therapy. Therefore, in these patients, [(11)C]Choline PET/CT allows not only to diagnose but also to localise recurrent disease with implications on disease management (localised vs systemic therapy).

[Transurethral resection for benign prostatic hyperplasia. current developments]. / Transurethrale Resektion bei benigner Prostatahyperplasie. Aktuelle Entwicklungen.

Transurethral resection of the prostate still represents the "gold standard" in surgical treatment of symptomatic benign prostatic enlargement (BPE). New demands were made on transurethral electrosurgery with the appearance of alternative, minimal invasive procedures. Bleeding complications had to be reduced. Different attempts were made to improve the conventional TURP. Band loops and roller bars were developed in order to gain a more effective coagulation during the cutting process by a larger tissue contact. Major advances could be achieved by modifications of the high-frequency generator. Improved procedures like the "Coagulating-Intermittent-Cutting" (CIC), the "Instant-Response-", as well as the "Dry-Cut-Technology" combine cutting and coagulating effects to realize lowered bleeding and an efficient resection process. The introduction of bipolar currency flow opens the possibility of conventional TUR-P with saline solutions and thus to the theoretical avoidance of the TUR-syndrome. By the neoadjuvant use of 5alpha-reductase-inhibitors before planned TUR-P, bleeding- and irrigation fluid absorption should be reduced by lowering perfusion and the size of the prostate. Regarding these innovative approaches which improve the surgical standard and minimize the risk of perioperative complications, transurethral electrosurgery remains the method of choice in instrumental therapy of symptomatic BPE. In the future efficacy and costs will be comparable to those of the transurethral laser-resection or laser-vaporisation.

[Pseudoaneurysm of a subsegmental renal artery after percutaneous nephrolitholapaxy]. / Pseudoaneurysma eines Nierenarterienastes nach perkutaner Nephrolitholapaxie.

At postoperative day 10 of a percutaneous nephrolitholapaxy for a large stone in the right renal pelvis of a 78-year-old female patient, persistent gross hematuria, requiring blood transfusions, occurred. Selective renovasography showed a pseudoaneurysm of the branch of a segmental artery close to the lower renal calices. Subsequent selective placement of two "steel-coils" in the feeding artery through a coaxial catheter system resulted in complete and stable occlusion without loss of renal parenchyma. Thereafter, bleeding immediately stopped and the patient suffered no further complications. This tool of interventional radiology should be kept in mind before open surgery is considered.

Significance of random bladder biopsies in superficial bladder cancer.

OBJECTIVES: We investigated to what extent biopsies of normal-appearing urothelium taken from patients with superficial bladder cancer (Ta, T1, Tis) showed malignant disease and whether those findings had impact on therapeutical decisions. PATIENTS AND METHODS: 1033 consecutive patients presenting with Ta, T1 or Tis (carcinoma in situ) superficial bladder tumors at increased risk for recurrence underwent multiple random biopsies from normal-appearing urothelium during transurethral resection (TUR). Patients with small, primary, singular tumors (smaller or equal to 1cm) were excluded from random biopsies. RESULTS: No tumor was found in the random biopsies of 905 patients (87.6%). 128 patients (12.4%) showed urothelial bladder cancer in their random biopsies (Tis: 74, Ta: 41, T1: 12, T2: 1). In 14 patients, where transurethral resection of the primary tumor revealed no signs of malignancy, urothelial bladder cancer was detected in the random biopsy material: Ta 8 patients, Tis 5 patients and T1 one patient. 21 patients with Ta tumors and 29 patients with T1 disease showed concomitant Tis. Upstaging of the primary, resected tumor by histological examination of the random biopsy material occurred in 75 patients (7%). Altogether, due to the random biopsy results therapy was altered in 70 patients (6.8%) of our series: It changed intravesical chemotherapy to BCG in 45, provoked a second TUR in 48 and cystectomy in 15 patients. CONCLUSIONS: While the clinical significance of random biopsies is still controversial, random biopsy results had strong impact on therapeutical decisions in our series. Regarding random bladder biopsies a simple tool for the urologist to identify high risk groups of patients, we recommend them as part of the routine management of superficial bladder cancer.

Use of diagnostic categories in urinary cytology in comparison with the bladder tumour antigen (BTA) test in bladder cancer patients.

In recent years the use of diagnostic categories for extragenital cytology has increasingly been discussed as an approach to improve the quality of reports. Diagnostic categories reflect the adequacy of the materials for interpretation and the presence or absence of cancer cells. There is a tendency to add intermediate groups as qualifying probably malignant cases or findings associated with a serious cancer risk. Since 1971 we have added one of the following to the final diagnosis in all cases: unsatisfactory for cytological diagnosis, negative for cancer, repeat test suggested, suspicious of cancer, and positive for cancer. To evaluate whether diagnostic categories are useful for comparison of cytological results with those of an alternative test, cytological data were compared with the results of the Bard bladder tumour antigen (BTA) test in voided urine from 119 patients (76 with and 43 without bladder cancer). The diagnostic categories enabled us to calculate sensitivities and specificities of cytology based on different thresholds or decision levels. The BTA test had significantly higher sensitivity (79%) and lower specificity (60%) than urinary cytology with three different thresholds in cytology results (sensitivities: 16-43%, specificities: 81-100%). The present findings suggest that diagnostic categories improve comparison of cytologic results with those of alternative screening and diagnostic aids such as the BTA test.

Comparison of the BTA stat test with voided urine cytology and bladder wash cytology in the diagnosis and monitoring of bladder cancer.

OBJECTIVE: To compare the BTA stat test (BTA stat), a new one-step immunochromatographic assay that can be performed in the urologist's office or in the laboratory, to voided urine cytology and bladder wash cytology (cytology) in the diagnosis and monitoring of cancer of the bladder (BC). METHODS: BTA stat and cytology were performed in a double-blinded, prospective, clinical study on specimens from 240 subjects (68 females; mean age of subjects: 64 years) suspected of having BC. RESULTS: In 107 subjects with final diagnoses of BC confirmed by cystoscopy or cystoscopy and biopsy, the overall sensitivities of BTA stat and cytology were 65 and 33%, respectively. For tumor grades I, II, and III, the sensitivities of BTA stat were 39, 67 and 83%, respectively. Those of cytology were 4, 20 and 69%. Nine subjects had a diagnosis of 'suspicious for bladder cancer'. The specificities of BTA stat and cytology in the 124 subjects without BC were 64 and 99%, respectively. In the subjects with a history of BC (n = 74), the specificities of BTA stat and cytology were 72 and 99%, respectively. The specificity of BTA stat was lower in subjects with benign or malignant genitourinary disease other than BC (46%) than in subjects without genitourinary disease (71%). CONCLUSIONS: The BTA stat test is considerably more sensitive than cytology in the detection of BC and can replace cytology as an adjunct to cystoscopy in the diagnosis and follow-up of patients with BC. However, due to low specificity, BTA stat should not be used without first ruling out potential interferences such as infections, renal disease and cancer, or genitourinary trauma.

[Modified retroperitoneal lymphadenectomy in non-seminomatous stage I, IIa and IIb testicular tumors]. / Die modifizierte retroperitoneale Lymphadenektomie beim nichtseminomatösen Hodentumor im Stadium I, IIa und IIb.

In 60 patients with non-seminomatous testicular germ cell tumours in clinical stages I, IIa and IIb inguinal orchiectomy was performed as primary treatment, followed by modified retroperitoneal lymphadenectomy (RLA). In stage II disease chemotherapy was given in addition. After a follow-up period of at least 24 months only 5% of the patients showed progression of disease. Normal ejaculatory function was preserved in 88% of our patients. Modified RLA seems to be a safe procedure with an acceptably low rate of complications not only in stage I disease, but also in metastatic stages IIa and IIb.

Significance of the evaluation of asymptomatic microscopic haematuria in young men.

OBJECTIVE: To evaluate the extent of diagnostic evaluation that is necessary in young men with asymptomatic microscopic haematuria. PATIENTS AND METHODS: A group of 157 men (mean age 24.8 years [range 18-53]) who presented with asymptomatic haematuria were investigated with repeated urine analysis. Addis count, urinary cultures, blood tests, ultrasonography, pyelography, cystourethroscopy and finally renal biopsy. RESULTS: The results showed pathological findings in 31.2% of patients. Of the 157 individuals, 33.1% did not complete the study. In 14.6% urological disease was found, including two patients with urothelial cancer. Renal biopsy detected glomerulopathy in 16.5% of all patients. IgA nephritis being the most common diagnosis (42% of all biopsies). CONCLUSION: Even in young patients, microscopic haematuria should be investigated and followed thoroughly. Renal biopsy seems to be optional: once a diagnosis is established repeated and unnecessary examinations can be avoided.

Inhibitory effects on in vitro cell growth of human urothelial tumor cell lines under the combined administration of hematopoietic growth factors and clinically relevant antineoplastic agents.

In five of eight human transitional carcinoma cell (TCC) lines a proliferative response has been reported during exposure to interleukin-3 (IL-3), granulocyte-macrophage colony stimulating factor (GM-CSF) and granulocyte colony stimulating factor (G-CSF). To elucidate possible growth-modulating effects of these factors combined with clinically relevant antineoplastic agents, cells of the human TCC lines EJ28 and T24 were exposed to methotrexate (MTX), vinblastine (VBL), doxorubicin (DXR) and cisplating (CDDP) with and without single or continuous exposure to IL-3, GM-CSF and G-CSF at concentrations of 1-100 ng/ml. Compared with cells exposed only to chemotherapy, significant inhibitory effects occurred as a result of continuous exposure to IL-3 or GM-CSF at the highest activities with CDDP and MTX in the T24 and EJ28 lines; continuous G-CSF administration (100 ng/ml) in combination with MTX led to significant growth inhibition in the EJ28 line. In contrast, no significant growth modulation was found on combined administration of DXR or VBL with any one of the three colony stimulating factors tested.

Venous surgery in erectile dysfunction. The role of dorsal-penile-vein ligation and spongiosolysis for impotence.

We report here on our surgical experience with venous leakage of the cavernous bodies. Out of 159 patients operated on, 134 were available for long-term follow-up. Depending on the cavernosographic findings, one of three different surgical procedures was carried out: ligation of the deep dorsal vein of the penis, spongiosolysis, or ligation of the crura. 18% of the patients undergoing ligation of the deep dorsal vein, postoperatively attained spontaneous erections, while 35% needed adjuvant corpus cavernosum autoinjection therapy. Spongiosolysis gave a more favourable result: spontaneous erections in 30% and vasoactive drug-dependent erections in 35%. Crural ligation did not prove successful. No serious complications were encountered postoperatively. Our data suggest that venous surgery should only be offered to a selected group of patients comprising young impotent men with venous leakage, maybe in combination with arterial disease, and patients suffering from distal venous leakage. Old age, neurogenic disorders causing erectile dysfunction, and diabetes mellitus should represent exclusion criteria for venous surgery.

Modulation of in vitro cell growth of human and murine urothelial tumor cell lines under the influence of interleukin-3, granulocyte-, macrophage- and granulocyte-colony-stimulating factor.

To elucidate possible growth-modulating effects of interleukin 3 (IL-3), granulocyte-macrophage-colony-stimulating factor (GM-CSF) and granulocyte-colony-stimulating factor (G-CSF), human transitional cell carcinoma (TCC) cell lines T24, RT112, EJ and 647 V were solitarily and continuously exposed to these hematopoietic growth factors at concentrations of 1-100 ng/ml. The murine line MBT-2 was used as a negative and the colon carcinoma cell line HTB38 as a positive control, because of species specificity and known proliferation in response to growth factors, respectively. In the T24 TCC-line solitary and continuous exposure to IL-3, GM-CSF and G-CSF at the highest concentration of 100 ng/ml led to a significant proliferation of cell growth in vitro. Significant proliferation in the RT112 line was only achieved with continuous exposure to IL-3 and GM-CSF (100 ng/ml); G-CSF failed to induce growth modulation in the RT112 line. No significant proliferative effect of any of cytokines administered was observed in the 647V line. Exposure of the EJ line to cytokines at the highest activity levels had a proliferative effect only in suboptimal growth conditions.

Surgical treatment of Peyronie's disease.

Surgical measures usually represent the last step in the treatment of Peyronie's disease. Straightening of the penile shaft and relief of pains during erection are the main goals of the operation. From December 1987 to April 1990, 11 patients with a mean age of 58.3 years underwent surgical treatment. Three of them complained of erectile dysfunction prior to surgery. The plaques were located distally in 8 patients, proximally in 1 patient and in the middle of the shaft in 2 patients. Complete resection was performed and defects of the tunica albuginea were closed by means of running sutures (3 patients) or grafts of autologous skin (5 patients) and lyophilized dura mater (3 patients), respectively. After a mean follow-up of 21 months, 6 patients reported spontaneous erections, whereas 3 patients needed corpus cavernosum autoinjection therapy. In 2 cases implantation of a penile prosthesis was necessary. Surgical treatment of Peyronie's disease yields satisfactory results if conservative therapy proves unsuccessful. However, diagnostic evaluation of erectile dysfunction should precede operative treatment and if present, be treated accordingly.

Nd:YAG coagulation of the verumontanum: an endoscopic attempt at sterilization.

In order to develop a new and less invasive method of sterilization in men we performed photocoagulation of the verumontanum in 10 rams, using a Nd:YAG laser, wavelength 1,060 nm. Under general anesthesia a perineal urethro-cutaneous fistula was achieved, and, by means of a 16F laser-endoscope, transurethral coagulation of the ejaculatory ducts, located in the verumontanum, was carried out, using pulses of 1.5 sec in duration and 20-30 W in power. The animals were killed at different postoperative time intervals, ranging from 1 day to 8 weeks. Injection of methylene-blue into the testicular ducts of the resected prostate-bladder specimen and histologic studies of the coagulated tissue revealed that complete bilateral occlusion of the ejaculatory ducts had been achieved in 4 rams. Failures were due to over-extended irradiation of the verumontanum. Except for urinary tract infections occurring in 4 animals, no serious complications were encountered. Further investigations are still necessary to determine the role of lasers in male sterilization.

Venous surgery in erectile dysfunction: a critical report on 116 patients.

From June, 1985, to December, 1987, we operated on 116 impotent patients suffering from venous incompetence of the cavernous bodies. A total of 115 patients underwent ligation of the deep dorsal vein of the penis. After a mean follow-up of 12.9 months, 67 patients (58.3%) were still able to obtain satisfactory erections. In 39 cases (33.9%), however, adjuvant corpus cavernosum autoinjection therapy was necessary. Eleven patients were submitted to spongiosolysis after ligation of the deep dorsal penile vein because of a distal venous leakage, consisting of venous shunts between the corpora cavernosa and the corpus spongiosum. After a mean follow-up of 14.2 months, 9 patients (81.8%) reported excellent penile rigidity; 5 of these patients, however, needed corpus cavernosum autoinjection therapy to maintain erectile function. One patient with ectopic veins emerging from the right crus of the penis was operated on successfully from a perineal approach. Serious complications did not occur in any of the patients. Despite the recurrence rate of 13 percent, venous surgery is an effective treatment for most patients concerned and offers a more physiologic erectile function than can be achieved by implantation of a penile prosthesis.