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Purpose: Radioligand therapy is an increasingly important option for the treatment of metastatic castrate-resistant prostate cancer (mCRPC). Radiohybrid ligands targeting prostate-specific membrane antigen (PSMA) are a novel group of theranostic radioligand therapy agents for which higher tumour absorbed radiation doses have been demonstrated compared to established PSMA ligands. Here, we report data from ten patients who were treated within a compassionate use program with the radiohybrid PSMA-ligand [ 177 Lu]Lu-rhPSMA-10.1 after experiencing disease progression under treatment with [ 177 Lu]Lu-PSMA-I&T., Methods: Ten patients with advanced PSMA-positive prostate cancer who showed progression under treatment with [ 177 Lu]Lu-PSMA-I&T received up to three cycles of rescue therapy with [ 177 Lu]Lu-rhPSMA-10.1 (7.4-8.1 GBq per cycle). Efficacy (PSA response according to PCWG3 and RECIP) and overall survival were evaluated. Adverse events were recorded from first application., Results: Despite progression with [ 177 Lu]Lu-PSMA-I&T, after the first cycle of [ 177 Lu]Lu-rhPSMA-10.1 rescue therapy, five patients (50%) showed a decrease in serum PSA level. In imaging, three of the ten patients (30%) showed a partial radiologic response. Four of the five patients with a decrease of serum PSA under [ 177 Lu]Lu-rhPSMA-10.1 had initially responded to treatment with [ 177 Lu]Lu-PSMA-I&T but had become resistant. However, the remaining patient had shown continuous disease progression during [ 177 Lu]Lu-PSMA-I&T therapy but showed an immediate response to [ 177 Lu]Lu-rhPSMA-10.1. The additional treatment with [ 177 Lu]Lu-rhPSMA-10.1 was generally well tolerated by all patients., Conclusions: Patients showing tumour progression while receiving [ 177 Lu]Lu-PSMA-I&T radioligand therapy may benefit from rescue therapy with the novel radiohybrid PSMA ligand, [ 177 Lu]Lu-rhPSMA-10.1. Higher tumour absorbed radiation doses with [ 177 Lu]Lu-rhPSMA-10.1 may overcome primary and acquired radiation resistance., Competing Interests: Declarations. Ethical approval: This study was conducted in accordance with the Helsinki Declaration and with national regulations. The local institutional review board (review board of the Ludwig-Maximilians-Universität München, Munich, Germany) approved this analysis (permit number 22-1011). Consent to participate: All patients gave written informed consent to the imaging and therapeutic procedures. Competing interests: CL reports prior consulting activities for Blue Earth Diagnostics Ltd. (BED, Oxford, UK) and Novartis. RAB is Consultant for and has received speaker´s honoraria from Bayer Healthcare (Leverkusen, Germany), Novartis (Nürnberg, Germany) and Eisai GmbH (Frankfurt, Germany) and has received travel expenses from BED. No other potential conflicts of interest relevant to this article exist., (© 2024. The Author(s).)

We recently published the first dosimetry data, to our knowledge, for the radioligand therapy agent 177 Lu-rhPSMA-10.1, providing an intrapatient comparison with 177 Lu-PSMA-I&T in patients with metastatic prostate cancer. Here, we report efficacy and safety findings from these patients. Methods: Four consecutive patients with prostate-specific membrane antigen (PSMA)-positive metastatic prostate cancer received up to 6 cycles of 177 Lu-rhPSMA-10.1 (7.4-7.7 GBq per cycle). Efficacy (prostate-specific antigen response according to Prostate Cancer Working Group 3 criteria and the Response Evaluation Criteria in PSMA PET/CT), progression-free survival, and overall survival were evaluated. Adverse events were recorded from the first dose until 16-24 mo after treatment. Results: The patients received a total activity of 29.6-59.4 GBq (4-6 cycles). Prostate-specific antigen was reduced by 100%, 99%, 88%, and 35%. Progression-free survival was not reached for 2 patients at 24 and 18 mo of follow-up and was 15 and 12 mo for the other 2 patients. One patient had a sustained complete response with 2 y of follow up. All patients were alive at the last time point of data collection. No serious adverse events were reported. Conclusion: 177 Lu-rhPSMA-10.1 demonstrated encouraging preliminary efficacy and was well tolerated. Formal clinical trials are now under way to evaluate its potential prospectively (NCT05413850)., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

As the use of radioligand therapy moves earlier in the prostate cancer timeline, minimizing the absorbed dose to normal organs while maintaining high tumor radiation doses becomes more clinically important because of the longer life expectancy of patients. We performed an intrapatient comparison of pretherapeutic dosimetry with the novel radiohybrid prostate-specific membrane antigen-targeting radiopharmaceutical 177 Lu-rhPSMA-10.1, along with 177 Lu-PSMA-I&T, in patients with metastatic castration-resistant prostate cancer. Methods: Four consecutive patients with advanced histologically proven metastatic castration-resistant prostate cancer who were scheduled for radioligand therapy were evaluated. Before undergoing therapy, each patient received 1.06 ± 0.05 GBq of 177 Lu-rhPSMA-10.1 and 1.09 ± 0.02 GBq of 177 Lu-PSMA-I&T at least 7 d apart. For dosimetric assessment, whole-body planar scintigraphy was performed after 5 min, 4 h, 1 d, 2 d, and 7 d. In addition, SPECT/CT images were acquired over the thorax and the abdomen, 4 h, 1 d, 2 d, and 7 d after injection. Dosimetry of the whole body and salivary glands was based on the evaluation of the counts in whole-body planar imaging. Dosimetry of the kidneys, liver, spleen, bone marrow, and tumor lesions (≤4 per patient) was based on the activity in volumes drawn on SPECT/CT images. Doses were calculated using OLINDA/EXM version 1.0. The therapeutic index (TI), or ratio between mean dose of the metastases and mean dose of the kidneys, was calculated for each patient. Results: We found the dose to the kidneys to be higher with 177 Lu-rhPSMA-10.1 than with 177 Lu-PSMA-I&T (0.68 ± 0.30 vs. 0.46 ± 0.10 mGy/MBq); however, 177 Lu-rhPSMA-10.1 delivered an average of a 3.3 times (range, 1.2-8.3 times) higher absorbed radiation dose to individual tumor lesions. Consequently, intraindividual comparison revealed a 1.1-3.1 times higher TI for 177 Lu-rhPSMA-10.1 than for 177 Lu-PSMA-I&T in all evaluated patients. The effective whole-body dose was 0.038 ± 0.008 mSv/MBq for 177 Lu-rhPSMA-10.1 and 0.022 ± 0.005 mSv/MBq for 177 Lu-PSMA-I&T. Conclusion: Using 177 Lu-rhPSMA-10.1 can significantly increase the tumor-absorbed dose and improve the TI compared with 177 Lu-PSMA-I&T. An improved TI gives the flexibility to maximize tumor-absorbed doses up to a predefined renal dose limit or, in earlier disease, to reduce the radiation exposure to the kidney while still achieving an effective tumor dose. The function of at-risk organs such as the kidneys is being assessed in a prospective clinical trial., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Background and Objectives: Although the incidence of bladder cancer among women is lower, they tend to more often have advanced disease at presentation with a more aggressive course. It is still unclear which factors are responsible for the poorer prognosis of bladder cancer in women., Materials and Methods: Original papers and reviews from 2004 until 2022 were identified in a PubMed search and evaluated., Results: Multiple factors are likely responsible for the different courses of bladder cancer in women versus men. In the literature, epidemiologic and clinical aspects are discussed. Furthermore, genetic and hormonal causes and the role of the urobiome have been the focus of discussion more recently., Conclusions: Earlier diagnosis and better surgical treatment could lead to a more favorable course of bladder cancer in women. Further analyses of genetic, hormonal, und microbiological factors could open new perspectives in the prevention, diagnosis, and treatment of bladder cancer., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

IgG4-related pseudotumours (IgG4-RPT) represent a distinctive manifestation in the broad spectrum of IgG4-related diseases (IgG4-RD). Due to their wide morphology and rarity, IgG4-RPTs represent a diagnostic challenge in the differential between reactive lesions and a fibrous soft tissue tumours. Thus, our aim was to characterise our cases and review the literature, focusing on the macroscopic and microscopic features of the lesions. In this paper, we summarise the possible presentations and histomorphological features of IgG4-RPT based on data collected from the literature and from cases at our institute and provide an overview of the pathogenesis and histological characteristics based on the knowledge accumulated in recent years. We collected surgical cases with a diagnosis of IgG4-RPT over the period 2013-2020 at two centres and analysed their macroscopic, histological, and immunohistochemical profiles. Furthermore, we performed a literature research in the MEDLINE and EBSCO databases regarding case reports and studies with the explicit diagnosis of IgG4-RPT. Our cases consist of nine men and three women, with an average age of 60±14 years, representing about 0.05% of the lesions evaluated at the two departments. The involved sites include the kidney, lung, gallbladder, pterygopalatine fossa, spleen, tongue, mediastinum, and submandibular gland. Grossly, nine lesions showed sharp margins. On histological examination, all the lesions showed an abundant inflammatory infiltrate with lymphocytes and IgG4-positive plasma cells as well as characteristic fibroblastic storiform proliferation. The literature search revealed 266 cases and similar histomorphological features in 23 locations. In 30 of these cases (11%), IgG4-RPTs were multifocal. IgG4-RPT are exceedingly rare lesions, which makes them challenging to diagnose. They can affect different sites, and the histomorphological presentation may differ., (Copyright © 2022 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Introduction: Penile cancer (PeCa) is an orphan disease in European countries. The current guidelines are predominantly based on retrospective studies with a low level of evidence. In our study, we aimed to identify predictors for guideline-conform treatment and hypothesize that reference centers for PeCa and physicians' experience promote guideline compliance and therefore correct local tumor therapy., Methods: This study is part of the European PROspective Penile Cancer Study (E-PROPS), an international collaboration group evaluating therapeutic management for PeCa in Central Europe. For this module, a 14-item-survey was developed and sent to 681 urologists in 45 European centers. Three questions focused on therapeutic decisions for PeCa in clinical stage Tis, Ta-T1a, and T1b. Four questions addressed potential personal confounders. Survey results were analyzed by bootstrap-adjusted stepwise multivariate linear regression analysis to identify predictors for EAU guideline-conform local treatment of PeCa., Results: For local therapy of cTis 80.4% recommended guideline-conform treatment, for cTa-cT1a 87.3% and for cT1b 59.1%. In total, 42.4% chose a correct approach in all tumor stages. The number of PeCa patients treated at the hospital, a higher level of training of the physicians, resource-based answering and the option of penile-sparing surgery offered at the hospital matched with giving guideline-conform recommendations and thus accurate local tumor treatment., Conclusion: Patients with PeCa are best treated by experienced physicians, in centers with a high number of cases, which also offer a wide range of local tumor therapy. This could be offered in reference centers.

Background: The changing conditions in German hospitals is causing a shortage of young people. In order to identify starting point for improvements, the Bavarian association of urologists in collaboration with the German Society of Residents in Urology (GeSRU) conducted an online survey among residents in urology in summer of 2017., Materials and Methods: A standardised survey composed of 38 questions was distributed to participants through a mailing list of the GeSRU. Most questions were closed-ended; however, some did allow participants to respond by means of an open-ended answer., Results: A total of 218 participants provided a total of 11,764 responses: 58% were female and 42% were male. Over 70% were aged between 31 and 35 years. In all, 29% of participants responded negatively to the question asking whether they feel like their medical studies at university prepared them well for the daily routine in their workplace. Participants particularly demanded a higher degree of practical experience during their studies, as well as more teaching of soft skills. In relation to choosing their specialisation, participants considered the intern year and their clinical traineeships as crucial factors. Participants did express appreciation of their field of specialization in relation to the broad range of available treatments, the opportunity of further specialising, the clientele of patients, the opportunity of working in a small team, innovations, and the high possibilities of opening their own medical practice. On a personal level, participants specifically wished for a more structured plan relating to their further internship, involving regular meetings. They also expressed the wish for more personalised career plans, more flexible work hours, and improved advanced training, both internally and externally., Conclusions: With the aim of making urology even more attractive, participants' wishes and suggestions should be taken into consideration. These, in general, involve a more structured training plan, better working conditions with part-time programmes, and improved surrounding conditions at the workplace, in particular for families.

Background and Objectives: The adjuvant treatment of non-muscle-invasive bladder cancer (NMIBC) is based on the individual risk profile (RP) and its sufficient transfer from the clinic to the doctor's office. The objectives of our study were to verify the importance and degree of transfer of RP and recommendation for risk-adapted adjuvant treatment (RAAT) in patients with NMIBC as well as to develop appropriate tools for this purpose, if necessary., Materials and Methods: An email-based survey distributed to urologists in Brandenburg, Berlin, Bavaria and Lower Saxony explored the questions mentioned above. In addition, a tool for risk stratification and information transfer for patients with NMIBC was developed and validated., Results: From a total of 134 questionnaires analyzed, 55 were from clinic urologists (CUs) and 79 were from ambulant urologists (AUs). Although 9 out of 10 urologists considered the RP of importance, only 29 % of CUs and 24 % of AUs (p = 0.553) confirmed that the RP was always mentioned in medical reports. The recommendation for RAAT was confirmed from 62 % of CUs and 20 % of AUs (p < 0.001). A recommendation for RAAT in the medical report was requested by 86 % of AUs. The risk calculator presented here - to our knowledge the first with integration of the 2004 WHO grading - is delivered in all mathematically possible constellations a RP, according to guideline recommendations., Conclusion: Urologists in the clinic and doctor's office both attach considerable importance to the determination and transfer of RP and the recommendation for RAAT. There was evidence to suggest an overestimation of the quality of medical reports by the CU. The risk calculator provides an easy and cost-neutral option to improve risk stratification and information transfer from the clinic to the doctor's office.

Purpose: To assess the efficacy of individual sentinel node (SN)-guided pelvic intensity modulated radiation therapy (IMRT) by determining nodal clearance rate [(n expected nodal involvement - n observed regional recurrences)/n expected nodal involvement] in comparison with surgically staged patients., Methods and Materials: Data on 475 high-risk prostate cancer patients were examined. Sixty-one consecutive patients received pelvic SN-based IMRT (5 × 1.8 Gy/wk to 50.4 Gy [pelvic nodes + individual SN] and an integrated boost with 5 × 2.0 Gy/wk to 70.0 Gy to prostate + [base of] seminal vesicles) and neo-/adjuvant long-term androgen deprivation therapy; 414 patients after SN-pelvic lymph node dissection were used to calculate the expected nodal involvement rate for the radiation therapy sample. Biochemical control and overall survival were estimated for the SN-IMRT patients using the Kaplan-Meier method. The expected frequency of nodal involvement in the radiation therapy group was estimated by imputing frequencies of node-positive patients in the surgical sample to the pattern of Gleason, prostate-specific antigen, and T category in the radiation therapy sample., Results: After a median follow-up of 61 months, 5-year OS after SN-guided IMRT reached 84.4%. Biochemical control according to the Phoenix definition was 73.8%. The nodal clearance rate of SN-IMRT reached 94%. Retrospective follow-up evaluation is the main limitation., Conclusions: Radiation treatment of pelvic nodes individualized by inclusion of SNs is an effective regional treatment modality in high-risk prostate cancer patients. The pattern of relapse indicates that the SN-based target volume concept correctly covers individual pelvic nodes. Thus, this SN-based approach justifies further evaluation, including current dose-escalation strategies to the prostate in a larger prospective series., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Extended pelvic lymph node dissection allows exact lymph node staging and has the potential to improve prognosis. In addition to these advantages, there are some perioperative and postoperative complications. In case of transection of the obturator nerve, a microsurgical end-to-end anastomosis should be performed. The most frequent postoperative complication is (symptomatic) lymphocele which is predominantly diagnosed after extraperitoneal surgery. Meticulous lymph node dissection with clipping of lymphatic vessels, sparing the lateral wall of the external iliac artery from dissection, sufficient postoperative drainage, and application of low molecular weight heparin in the upper arm may reduce their incidence. Instillation of sclerosing agents and sufficient drainage are normally successful. If not, laparoscopic fenestration of lymphocele should be performed. Regular ultrasound examinations are necessary to diagnose and treat postoperative lymphocele in a timely manner.

The prognosis of prostate and bladder cancer patients is predominantly determined by the detection of distant sites of metastasis. In clinical routine, virtually only lymph node staging is of relevance to determine metastasis. Detection and characterization of disseminated tumor cells in peripheral blood or bone marrow is an additional parameter of prognostic significance. In this article, we will summarize recent progress on the prognostic value of disseminated tumor cells in bone marrow and its translation into routine clinical analysis.

Purpose: The EAU guidelines recommend extended pelvic lymphadenectomy (ePLND) or sentinel-guided PLND (SLNE) for lymph node (LN) stag-ing in prostate cancer. However, the additional expenditure and increased morbidity of ePLND has led to a limitation of the PLND area and so to a reduced detection of metastases in many clinics. The SLNE offers the advantage of selective removal of sentinel LN. Therefore, we have compared the complications of SLNE and other different PLND techniques., Materials and Methods: Patients with prostate cancer who had received an open PLND (PLND: n = 90, PLND + radical retropubic prostatectomy: n = 409) were assessed. The complications of three PLND techniques were compared: group 1 (n = 216): SLNE, group 2 (n = 117): SLNE + modified (m) PLND (fossa obturatoria- und Iliaca-externa-region), group 3 (n = 163): SLNE + ePLND (fossa obturatoria- + Iliaca-externa- + Iliaca-interna-region). The complications were evaluated with special reference to the PLND-induced morbidity (e. g., lymphoceles)., Results: In SLNE the total complications were low-er than in the two more extended PLND variants. The lymphatic complications (11.2 %) were significant (χ (2) = 8.616, p = 0.013) lower than in SLNE + mPLND (21.2 %) and SLNE + ePLND (22.0 %). With an increasing number of dissected LN the complication rate increased significantly. If ≥ 15 LN have been removed total and lymphatic complications increased significantly (χ (2) = 11.578, p = 0.021; χ (2) = 12.271, p = 0.015)., Conclusions: In PLND the lymphatic complications increase significantly with the number of dissected LN. The SLNE has, in spite of the dissection of LN in difficultly accessible regions (presacral, iliaca-interna-region), a low complication rate. As a method with a small number of LN to be removed, the SLNE offers a good compromise between high sensitivity and low morbidity and is therefore preferable to the more extended PLND variants., (Georg Thieme Verlag KG Stuttgart New York.)

Purpose: Sentinel lymph node dissection (SLND) has replaced extended lymphadenectomy for nodal staging in several solid tumours. We present our results of SLND in prostate cancer in regard to detection and false-negative rate., Methods: In a 2-day protocol about 300 MBq (99m)Tc-nanocolloid are injected into the prostate. Two hours later static scans of the pelvis are performed to get information about the number and location of radioactive lymph nodes. During surgery the radioactive nodes are excised with the help of a gamma probe and sent separately to the pathologist. The histological procedure includes haematoxylin and eosin staining, serial sections and immunohistochemistry., Results: Since 1999, a total of 2,020 men underwent SLND alone or in combination with either standard or extended lymphadenectomy after radical retropubic prostatectomy. Lymph nodes positive for metastases were found in 16.7% of patients. The scintigraphic detection rate was 97.6% and the intraoperative detection rate 98%. For 187 lymph node-positive men who had either standard or extended lymphadenectomy in addition to SLND the false-negative rate could be calculated, resulting in false-negative findings in 11 of 187 patients (6%)., Conclusion: Our results demonstrate that SLND in prostate cancer is a reliable procedure for nodal staging.

Purpose: The outcome of prostate cancer is highly unpredictable. To assess the dynamics of systemic disease and to identify patients at high risk for early relapse we followed the fate of disseminated tumor cells in bone marrow for up to 10 years and genetically analyzed such cells isolated at various stages of disease., Patients and Methods: Nine hundred bone marrow aspirates from 384 patients were stained using the monoclonal antibody A45-B/B3 directed against cytokeratins 8, 18, and 19. Log-rank statistics and Cox regression analysis were applied to determine the prognostic impact of positive cells detected before surgery (244 patients) and postoperatively (214 patients). Samples from primary tumors (n = 55) and single disseminated tumor cells (n = 100) were analyzed by comparative genomic hybridization., Results: Detection of cytokeratin-positive cells before surgery was the strongest independent risk factor for metastasis within 48 months (P < .001; relative risk [RR], 5.5; 95% CI, 2.4 to 12.9). In contrast, cytokeratin-positive cells detected 6 months to 10 years after radical prostatectomy were consistently present in bone marrow with a prevalence of approximately 20% but had no influence on disease outcome. Characteristic genotypes of cytokeratin-positive cells were selected at manifestation of metastasis., Conclusion: Cytokeratin-positive cells in the bone marrow of prostate cancer patients are only prognostically relevant when detected before surgery. Because we could not identify significant genetic differences between pre- and postoperatively isolated tumor cells before manifestation of metastasis, we postulate the existence of perioperative stimuli that activate disseminated tumor cells. Patients with cytokeratin-positive cells in bone marrow before surgery may therefore benefit from adjuvant therapies.

The current literature was reviewed for articles focusing on radioguided surgery in urological malignancies.In penile cancer sentinel lymph node dissection is part of international guidelines. By detailed histopathological analysis (serial sections, immunohistochemical staining) more micrometastases are detectable improving the histopathological staging.In prostate cancer this technique also improves staging since a high percentage of patients have lymph node metastases located outside the region of standard lymphadenectomy. Compared to extended lymph node dissection radioguided surgery has a lower morbidity, especially a lower rate of lymphoceles.In bladder cancer the sentinel lymph node (SLN) technique has some limitations. Combined with extended lymph node dissection more positive lymph nodes are removed which possibly improves survival.In renal cell and testicular cancer there are only preliminary results. Further investigations will show whether this technique will play an important role in the diagnostics and therapy of these tumors.In all urological malignancies the SLN concept is only a staging procedure. When the sentinel node(s) is (are) negative, the other lymph nodes are negative, too. Since there are no randomized prospective trials comparing the results of sentinel lymphadenectomy with other techniques of lymph node dissection, it is not clear whether sentinel lymph node dissection also has a prognostic impact.

Sentinel lymph node (SLN) dissection is an excellent staging procedure with high sensitivity (>95%) for detecting positive nodes. When the sentinel node is negative, there is high certainty that other lymph nodes are also negative. Limitations of this technique include the use of hormone therapy over several months and a preceding transurethral resection or suprapubic adenomectomy. When sentinel node dissection is performed in patients with intermediate and high-risk prostate cancer, it should be kept in mind that when the SLN is positive, other lymph nodes can be positive, too. The positive non-SLN can be located outside the SLN region. Therefore, both sentinel and extended lymph node dissection should be used in men with a higher risk of lymph node metastases.

Background: The impact of infections with the human cytomegalovirus (HCMV) for the development of atherosclerosis and restenosis is still unclear. Both a clear correlation and no correlation at all have been reported in clinical, mostly serological studies. In our study we employed a human non-injury ex vivo organ culture model to investigate the effect of an in vitro permissive HCMV-infection on cell proliferation and neointimal hyperplasia for a period of 56 days., Results: During routine-nephrectomies parts of renal arteries from 71 patients were obtained and prepared as human organ cultures. Cell free HCMV infection was performed with the fibroblast adapted HCMV strain AD169, the endotheliotropic strain TB40E, and a clinical isolate (AN 365). After 3, 7, 14, 21, 28, 35, and 56 days in culture staining of HCMV-antigens was carried out and reactive cell proliferation and neointimal thickening were analysed. Successful HCMV-infection was accomplished with all three virus strains studied. During the first 21 days in organ culture no cell proliferation or neointimal hyperplasia was detected. At day 35 and day 56 moderate cell proliferation and neointimal hyperplasia was found both in HCMV-infected segments and mock infected controls. Neointimal hyperplasia in productively HCMV-infected segments was lower than in non infected at day 35 and day 56, but relatively higher after infection with the endotheliotropic TB40E in comparison with the two other strains., Conclusion: The data do not support the hypothesis that HCMV-infection triggers restenosis via a stimulatory effect on cell proliferation and neointimal hyperplasia in comparison to non infected controls. Interestingly however, even after lytic infection, a virus strain specific difference was observed.

Introduction: Distant metastases of solid tumors are usually associated with fatal outcome. Disseminated cancer cells are considered early indicators of metastasis. Their sensitive detection and quantification would be a valuable tool for staging of disease and as guidance for therapeutic decisions., Experimental Design: We established a highly sensitive and quantitative multimarker real-time RT-PCR assay for amplification of cancer-related genes MAGE-A1, -A2, -A3/6, -A4, -A10 and -A12 using SYBR green I to detect one single tumor cell in 2 mL of blood or bone marrow. The feasibility of the assay was tested in a large cohort of 177 patients with locally confined prostate carcinoma., Results: Analysis revealed frequent MAGE expression in venous blood and bilateral bone marrow samples (25.5% of all cases) and yielded the first quantitative profile of MAGE expression with a broad range of transcript concentrations for individual markers in the minimal systemic tumor load of patients with localized cancer., Conclusions: Rare transcripts of different MAGE-A genes can be quantified in clinical samples of cancer patients by a sensitive multimarker real-time RT-PCR. Because of frequent expression of MAGE genes in various types of cancer the multimarker MAGE real-time RT-PCR may be generally useful for detection, quantification and characterization of the individual disseminated tumor load in cancer patients.

Objectives: To determine how many men with high-risk prostate cancer (prostate-specific antigen [PSA]>20 ng/ml or biopsy Gleason score 8-10) have positive lymph nodes (sentinel lymph nodes [SLNs] and nonsentinel lymph nodes [NSLNs]) and whether these positive nodes are localised in the region of SLN dissection or in other regions, too., Methods: In 228 men with high-risk prostate cancer radical retropubic prostatectomy combined with radioguided pelvic lymph node dissection and extended lymphadenectomy were performed. Serial sections of the SLNs were analysed immunohistochemically., Results: A median of 7 SLNs (mean, 7) and 11 NSLNs (mean, 11) were dissected per patient. Ninety-six of 228 men (42.1%) had lymph node metastases. Most men had positive lymph nodes along the internal iliac artery alone or in combination with other regions. Twenty-two men had only micrometastatic disease. In 94 of 96 men the SLNs were positive. Twenty-six of 96 men had also positive NSLNs. When SLNs and NSLNs were positive, in more than half the patients the NSLNs were localised outside the region of sentinel lymphadenectomy., Conclusions: The dissection of SLNs in prostate cancer has a high sensitivity in detecting positive nodes. When SLNs are negative, the other pelvic lymph nodes are also negative in a high percentage of men (sensitivity 97.1%). When the SLNs are positive, patients with high-risk disease also have a high incidence of positive NSLNs. Therefore, when it is aspired to remove all pelvic lymph node metastases sentinel and extended lymphadenectomy should be performed.

Objective: To investigate the reliability of preoperative diagnostics in predicting the true histopathological stage and grade of prostate cancer, and to examine whether lymph node (LN) metastases in unilateral prostate cancer are located unilaterally and therefore whether it is justified to dissect only the ipsilateral LNs in presumed unilateral disease., Patients and Methods: LN metastases in clinically localized prostate cancer are often located near the internal iliac vessels. They will be detected by extended or sentinel pelvic LN dissection (PLND). Both techniques might be time-consuming and require extensive surgical experience. In all, 564 men with impalpable or unilateral palpable prostate cancer and positive biopsy cores only in one prostate lobe had a radical prostatectomy (RP) combined with radio-guided PLND and in some cases an extended PLND., Results: A median of six sentinel LNs (mean, seven) and six non-sentinel LNs (mean, seven) were dissected per patient; 52 of 564 men (9.2%) had positive LNs. Most men with unilateral disease had LN metastases on the same side of the pelvis. Comparing the clinical stage and grade with the tumour stage and grade of the RP specimen, there was a high percentage of upstaging and upgrading even in men with only one positive biopsy core., Conclusion: Unilateral prostate cancer preferentially metastasizes to the ipsilateral pelvic LNs. Because there are a few cases of bilateral LN metastases even in unilateral disease, and as it is not possible to reliably predict unilateral disease on the basis of biopsy features, PLND only on the tumour-bearing side has a high risk of understaging, and would possibly leave LN metastases behind.

Purpose: We determined the incidence of positive pelvic lymph nodes in men undergoing radical retropubic prostatectomy and describe the correlation with prostate specific antigen, histological grade and stage. We examined whether tumor cells are localized in the sentinel nodes only or also in other nonsentinel lymph nodes., Materials and Methods: A total of 1,055 men with prostate cancer underwent radio guided pelvic lymph node dissection and radical retropubic prostatectomy. In men with prostate specific antigen 20 ng/ml or less and biopsy Gleason score 7 or less only sentinel nodes were removed. In men with prostate specific antigen more than 20 ng/ml or Gleason score greater than 7 extended pelvic lymph node dissection was also performed., Results: Positive lymph nodes were found in 207 men (19.6%). In 63.3% of the men these lymph nodes were detected outside of the region of standard lymphadenectomy. The percent of patients with positive nodes was greater than predicted by currently used nomograms. The higher the preoperative prostate specific antigen, pathological stage and grade, the greater the percent of men with positive sentinel and nonsentinel lymph nodes (p<0.001)., Conclusions: When deciding on pelvic lymph node dissection, sentinel or extended lymphadenectomy should be performed since more than half of patients have positive nodes outside of the region of standard lymphadenectomy. In cases of positive sentinel nodes extended lymph node dissection should be performed since tumor cells are also detectable in nonsentinel lymph nodes.

Aim of the Study: Adecatumumab (also known as MT201) is a human recombinant IgG1 monoclonal antibody binding with low affinity to epithelial cell adhesion molecule (EpCAM). To explore safety, pharmacokinetics and pharmacodynamics of adecatumumab, a phase I trial in patients with hormone refractory prostate cancer (HRPC) was performed., Methods: Twenty patients were treated with two adecatumumab infusions on days 0 and 14 in cohorts with doses of ten up to 262 mg/m2., Results: Adecatumumab was well tolerated at all doses tested, and no maximum tolerated dose reached. Most adverse events were mild or moderate with pyrexia and nausea being most frequent. The highest dose of adecatumumab induced shortly after infusion robust and transient increases of TNF-alpha serum levels. At all doses, significant transient declines of peripheral natural killer cells were observed shortly after antibody infusions. Adecatumumab had a serum half-life of 15 days, and immune responses to the antibody were not detected., Conclusions: A benign safety profile, long serum half-life and low immunogenicity do warrant further exploration of adecatumumab for treatment of EpCAM-expressing neoplasia.

The role of the obligate intracellular pathogen Chlamydia pneumoniae in the development of atherosclerosis could not be completely clarified. Reasons are the highly discrepant results obtained in the hitherto existing studies and the lack of an experimental system allowing the direct examination of chlamydial effects in the human vasculature. We established a human ex vivo organ culture model for the characterization of vascular chlamydial infection. Ninety sections of renal arteries, obtained from nephrectomies, were inoculated with Chlamydia pneumoniae. Using a monoclonal FITC-conjugated antibody, chlamydial LPS was broadly detected in inoculated arteries during the entire observation period of 35 days. However, recultivation of viable organisms from the artery vessel wall was impossible, indicating that productive infection in human arteries did not occur even under optimized conditions. This was substantiated by low recovery rates of Chlamydia pneumoniae, low amounts of detectable chlamydial 16S rRNA and ultramorphological presence of polymorph multilamellar bodies in experimentally infected smooth muscle cells originating from aortas, coronary and renal arteries. We could demonstrate that the complex environment of a human artery did not support the growth of Chlamydia pneumoniae although the presence of chlamydial LPS in the artery vessel wall following experimental infection was a common event. The presence of chlamydial LPS in the absence of viable organisms within the artery vessel wall may explain the failure of antibiotic treatment strategies for atherosclerosis.

There is no consensus on which prostate cancer patients should undergo lymph node removal and which lymph nodes should be included. Therefore, most clinicians rely on nomograms and dispense with lymph node dissection in patients with low-risk disease. Meanwhile, there are some studies which prove that there are also lymph node metastases in patients with low-risk prostate cancer and that lymph node metastases are predominantly localized outside the region of standard lymphadenectomy. In more than 800 men we could show that lymph node metastases were found more often than shown in the Partin tables. These lymph node metastases were detected by sentinel lymph node dissection outside the region of standard and extended lymphadenectomy. Because of insufficient preoperative diagnostics it is unclear which patients have positive lymph nodes. Therefore, it is useful to perform lymph node dissection in every patient. Men with positive nodes could have a better prognosis, when sentinel and extended lymph node dissection are performed.

Objective: To investigate how many men with low-risk prostate cancer had positive lymph nodes detected by radio-guided surgery and whether they had a higher biochemical relapse rate after radical prostatectomy, because in such patients most urologists dispense with operative lymph node staging, as nomograms indicate only a low percentage of lymph node metastases., Patients and Methods: The study included 474 men with a prostate-specific antigen (PSA) level of < or = 10 ng/mL, biopsy Gleason score of < or = 6 and positive biopsies in one (group 1, 315 men) or both lobes (group 2, 159 men); follow-up data were available in 357 men. Men with adjuvant radiation or hormone therapy before the occurrence of biochemical relapse were excluded., Results: Positive lymph nodes were detected in 17 men in group 1, and in 18 in group 2. In more than half of the patients (19/35) these nodes were found outside the region of standard lymphadenectomy. Men with node-positive disease had a higher biochemical relapse rate (P < 0.001). When the tumour was organ-confined and well differentiated in node-positive disease (Gleason score < or = 6) the biochemical relapse rate was lower than in men with higher tumour stage and grade., Conclusions: When dissecting pelvic lymph nodes, extended or sentinel lymphadenectomy should be preferred. Removing the diseased nodes could improve the PSA progression-free survival, especially in well differentiated organ-confined disease.

Neurilemomas originate from the Schwann cells of nerve sheaths. They can occur ubiquitously as benign or malign variants. Renal neurilemomas are extremely rare. Imaging does not allow a certain diagnosis. Complete tumor resectioning is the only curative therapy. Effective conservative treatment is not known. Histological criteria of renal neurilemoma are: mesenchymal, spindle cell, capsulated tumor intensely positive to S-100 antiserum. Epithelial markers do not react.

Prostate cancer is the most common malignant disease and second in causes of cancer death among men in Western Europe and North America. Despite improved surgical and irradiation techniques tumor relapse after curatively intended therapy is not uncommon. Due to the difficulty in discriminating local and systemic progression, it is often difficult to decide what this means for the patient and what kind of second-line treatment has to be given. Modern imaging techniques (MRI with endorectal coil, Choline-PET-CT, ProstaScint-Scan) are used for diagnosis of prostate cancer relapse. Nevertheless, early detection of local tumor relapse and likewise the detection of disseminated tumor cells often fails. To differentiate between local and systemic progression, prognostic factors of the primary tumor (grading, surgical margins, infiltration of the seminal vesicles, lymph node metastases) and PSA kinetics are used. The time from initial treatment to biochemical relapse and PSA doubling time are of highest prognostic relevance. Local progression allows second-line local treatment with potentially curative results (local irradiation after radical prostatectomy, salvage-surgery / cryotherapy / HIFU after irradiation), while in the case of systemic progress a palliative systemic therapy (hormonal treatment, chemotherapy, bisphosphonates) is indicated. Before deciding on the most appropriate therapy, prognostic factors and the patient's individual situation (co-morbidity, life expectancy, individual wishes) should be taken into account.

Gamma probe-guided lymphadenectomy of prostate cancer that is presumed to be localized furnishes evidence that lymphogenous spread of the disease is present considerably more often and earlier than previously assumed, even when the clinical stage is considered localized. Multiinstitutional trials have confirmed that in principle sentinel lymphadenectomy on its own is able to detect lymph node positive patients with minimal complications and a sufficient degree of certainty. Sentinel lymphadenectomy for penile cancer is an undemanding surgical procedure and in contrast to inguinal lymphadenectomy can be considered minimally invasive. Decisions on indication and necessity for an additional inguinal lymphadenectomy depending on tumor stage and local findings in the inguinal lymph nodes are handled quite differently in various centers and should be further standardized. The most recent studies on sentinel lymphadenectomy for urinary bladder and testicular cancer demonstrate that on principle the procedure is likely feasible also for these tumor entities. Whether it is possible to replace standard treatment methods with these procedures or at least have them serve an ancillary function remains to be determined in further investigations. Basically, the premise holds true that for all urological tumor entities before standard diagnostic techniques are abandoned, the value of exclusively performing sentinel lymphadenectomy must be adequately validated. It does not suffice to rely on the results from other working groups. It is in fact essential that the accuracy of the method - the feasibility of which can be influenced by numerous factors - be assessed by comparison with a standard lymphadenectomy performed in one's own center.

Pain is a cardinal symptom in 70 % of cancer patients. Even in developed countries, 30 to 80 % of these patients are inadequately treated. The main cause for this lack of care is not pain refractory to treatment but inadequate or incorrect use of analgesic drugs. A sufficient treatment of pain requires knowledge of the pathomechanism of pain and of the basics of pain management in cancer patients. The choice of analgesic drugs follows the WHO-recommended increase based on need. As long as possible, analgesic drugs should be given orally following a strict schedule and pre-emptively prior to renewed pain. The non-opioids are a heterogeneous group of drugs with different actions and side effects. Maximum doses exist for this group and weak opioids. A change to strong opioids is indicated when weak opioids fail to achieve sufficient pain control despite titration to the maximum dose. No upper limit exists for strong opioids and their use is limited by the side effects. The most frequent side effects are initial emesis and vomiting as well as long-lasting constipation. For this reason, most patients should be prescribed a temporary antiemetic and a laxative on a permanent basis.

Objectives: In men with low risk prostate cancer the need for pelvic lymph node dissection is controversial. Therefore, we examined how many men with favorable preoperative risk factors had positive lymph nodes., Methods: 235 men with preoperative PSA < or =10 ng/ml, Gleason score < or =6 and positive biopsies in only one lobe, had radio-guided pelvic sentinel lymph node (SLN) dissection and radical retropubic prostatectomy (RRP) or-in case of no positive lymph nodes detected-a transperineal I(125) seed implantation. Eighty-four men with positive biopsies in both lobes and identical PSA and Gleason score had SLN dissection and RRP., Results: In 187 men with positive biopsies in one lobe RRP was performed. Sixteen patients had positive lymph nodes. Median 6 SLN (mean 6.8) and 6 non-sentinel lymph nodes (NSLN) (mean 7.3) were dissected. All men with positive lymph nodes also had positive SLN. Eighty-four men with positive biopsies in both lobes had RRP. Nine men had positive lymph nodes (10.7%). A median of 6 SLN (mean 6.6) and 5 NSLN (mean 7.5) were dissected. All men with positive nodes had a single positive SLN., Conclusions: In patients with PSA < or =10 ng/ml and biopsy Gleason score < or =6, positive lymph nodes were identified by radio-guided surgery in 6.8% (positive biopsies in one lobe) and 10.7% (positive biopsies in both lobes). Up to 4 positive SLN were found. Therefore, we suggest not to dispense with an operative lymph node staging, even in low risk disease.

GnRH agonists have a proven and well-established role in the management of prostate cancer. Further adaptations of the amino-acid sequence led to the development of antagonists with potential therapeutic uses, including a possible role in prostate cancer patients. Treatment of prostate cancer with GnRH agonists results in an initial flare of symptoms that may be prevented by co-administration of a steroidal or non-steroidal antiandrogen. However, this can be associated with additional adverse effects. Clinical studies have shown that GnRH antagonists produce a rapid decline in testosterone but without the disease flare. However these short-term effects have yet to be proven to lead to long-term survival benefits. There have been some reports that antagonists may be associated with adverse effects due to histamine release leading to severe allergic reactions. GnRH agonists are currently available in a range of depot formulations, allowing treatment to be tailored to the patient's needs. At present, the antagonists are only available as on-month depot formulations, which may limit their clinical use. Abarelix should be given intramuscularly. It is the first GnRH antagonist which is approved by the FDA for patients with advanced prostate cancer who should be treated under a risk management program. In Europe, abarelix has not been registered yet.

Objectives: Pelvic lymph node metastases indicate a poor prognosis for patients with clinically localized prostate cancer. The aim of the study was to investigate the value of extended histopathological techniques considering the extent of pelvic lymphadenectomy and preoperative risk factors., Methods: Total of 194 patients with prostate cancer were examined. At first all patients had a sampling of the sentinel lymph nodes (SLN) followed in most cases by a modified or extended pelvic lymphadenectomy. Step sections, serial sections and immunohistochemistry (IHC, pancytokeratin antibody) were analyzed in all SLN and so-called non-SLN of the first 100 patients. Later serial sections and IHC of non-SLN were left out., Results: In 26.8% lymphatic metastases were found. The detection rate of lymph node-positive patients depend significantly on the chosen extension of pelvic lymphadenectomy. Limiting the histopathological investigation to the lymph node specimen of the obturator fossa only 44.2% of lymph node-positive cases would have been identified. An additional inclusion of all lymph nodes surrounding the external iliac vessels improves the sensitivity to 65.4% (46.7% and 73.3% for the first 100 patients). Compared to the extension of pelvic lymphadenectomy the diagnostic gain of serial section and IHC (13.8% versus 53.3%) was comparably low., Conclusions: The extension of pelvic lymph node dissection is of outstanding value for the identification of node-positive patients. Limiting the number of lymph nodes to the ones with the highest probability of bearing lymphatic spread (SLN) makes the use of extensive histopathological techniques more feasible.

Introduction: Having in mind the promising results of lymphoscintigraphy and intraoperative gamma probe application for the detection of sentinel lymph nodes (SLN) in malignant melanoma, breast and penis cancer, we tried to identify the SLN in prostate cancer by applying a comparable technique., Materials and Method: 350 patients with prostate cancer were examined after providing informed consent. The day before pelvic lymphadenectomy technetium-99m nanocolloid was transrectally injected into the prostate under ultrasound guidance. A single central application was done per prostate lobe in most cases. Activity attained 90- 400 MBq, and the total injected volume was about 2-3 ml. Hereafter, lymphoscintigraphy was carried out. Those lymph nodes having been identified as SLN by means of gamma probe detection and lymphoscintigraphy were removed intraoperatively. Later, most of the cases had different types of pelvic lymphadenectomy. SLN received serial sections and immunohistochemistry, non-SLN step sections., Results: 335 patients showed at least 1 SLN in lymphoscintigraphy. 24.7% had lymph node metastases. In 2 patients, metastases in non-SLN were found without at least one SLN being affected (false-negative patient)., Conclusion: Our experience suggests that the SLN identification is not only feasible in breast cancer and malignant melanoma, but also in prostate cancer with a comparable technique., (Copyright 2003 S. Karger AG, Basel)

Purpose: Unenhanced helical computerized tomography (CT) has proved to be an excellent diagnostic tool for evaluating acute flank pain with reported 95% to 100% sensitivity, 92% to 100% specificity, 96% to 100% positive and 91% to 100% negative predictive values. The diagnostic value of a new low dose protocol was prospectively studied and compared with the results of conventional unenhanced helical CT in a previous series with an effective dose equivalent (HE) of 3.1 to 4.3 mSv. and in current literature with an estimated HE of 4.3 to 4.7 mSv., Materials and Methods: In 109 patients 18 to 86 years old with acute flank pain we performed low dose unenhanced helical CT in addition to abdominal ultrasound and urinalysis with new CT parameters (120 kV. 70 mA., 5 mm. collimation, pitch 2 and incremental reconstruction each 5 mm.) that led to a more than 50% decrease in radiation exposure to 1.50 mSv. in females and 0.98 mSv. in males. Ureteral calculi were confirmed or excluded by retrograde ureteropyelography in 51 cases. In the other cases the diagnosis was verified by the clinical and ultrasound course, and/or stone asservation., Results: In 80 of the 109 patients the flank pain was caused by a ureteral calculus. Low dose unenhanced helical CT precisely identified 77 ureteral calculi with 1 false-positive finding. Thus, the sensitivity and specificity of low dose unenhanced helical CT were 96% and 97% with a 99% positive and 90% negative predictive value. In 15 of 29 patients with CT findings negative for stone disease different causes of pain were established by low dose unenhanced helical CT., Conclusions: Even with the significantly decreased radiation exposure of the low dose protocol unenhanced helical CT is still an excellent and rapid diagnostic tool for evaluating acute flank pain with lower radiation exposure than excretory urography (HE 1.3 to 2.3 mSv.) at our departments. Only in obese patients with a body mass index of greater than 31 kg./m.2 is conventional unenhanced helical CT with higher radiation exposure recommended to achieve adequate image quality.

Systemically disseminated tumor cells have become the subject of intensive research as the presumed seminal precursors of later distant metastasis. We describe here a novel sensitive multimarker nested reverse transcription (RT)-PCR capable of detecting the individual expression of human MAGE-A genes MAGE-1, -2, -3/6, -4, and -12 by rare, disseminated tumor cells in bone marrow and blood of patients with many different types of cancer. We analyzed bone marrow aspirates from 106 patients with breast, lung, colorectal, and prostate cancer and with different sarcomas. Heterogeneous expression of the different MAGE genes was found frequently in all those kinds of malignancies, in sharp contrast to 30 bone marrow and 20 blood samples from healthy donors, which were completely MAGE negative. Expression of at least one MAGE gene in bone marrow was more frequent than cytokeratin-positive tumor cells detected by immunocytochemistry, although the results of both tests overlapped considerably. In 30 patients with clinically localized prostate cancer, analysis by the multimarker MAGE RT-PCR of bilateral bone marrow aspirates from the right and left iliac crest revealed a positivity rate of 60%, which was twice as high as that obtained with either an established prostate-specific antigen RT-PCR or by cytokeratin-based immunocytochemistry. Analysis of primary prostate cancer revealed MAGE expression patterns considerably concordant with those found in the corresponding bone marrow aspirates. Prostate cancer patients carrying an exceptionally high risk of metastatic relapse, as defined by clinical prognostic factors, were significantly more often MAGE positive than patients with a distinctly lower risk (P = 0.02, Fisher's exact test). More frequent MAGE expression in the peripheral blood of patients with metastatic prostate cancer compared with those with clinically localized disease added further evidence for the prognostic impact of the multimarker MAGE RT-PCR. Moreover, MAGE-positive bone marrow samples from a small group of seven sarcoma patients demonstrated the relevance of our multimarker RT-PCR in nonepithelial tumors. Because MAGE antigens can induce autologous cytolytic T lymphocytes in vivo, the determination of individual MAGE expression patterns in cancer patients may furthermore identify candidate vaccine targets for adjuvant immunotherapy.

Purpose: The localization of lymph node metastases in prostate cancer varies enormously. Due to high morbidity complete pelvic lymphadenectomy is often decreased to modified staging lymphadenectomy, resulting in loss of sensitivity for detecting micrometastases. Based on the promising results of intraoperative gamma probe application for identifying sentinel lymph nodes in malignant melanoma, breast and penis cancer, we identified sentinel lymph nodes in prostate cancer using a comparable technique., Materials and Methods: In 117 patients 99mtechnetium nanocolloid was transrectally injected directly into the prostate under ultrasound guidance 1 day before pelvic lymphadenectomy. Thereafter dynamic lymphoscintigraphy was done. Initially lymph nodes identified as sentinel lymph nodes by the gamma probe were removed and subsequently modified pelvic lymphadenectomy was performed., Results: Lymphatic metastasis was detected in 28 cases. An average of 4 sentinel lymph nodes were identified per patient in 25 of 27 patients with micrometastasis, of which those in 24 contained micrometastasis for 96% sensitivity. In contrast, sensitivity of modified pelvic lymphadenectomy was 81.5%. In 16 patients only sentinel lymph nodes were positive. An average of 21.8 lymph nodes (range 10 to 51) was dissected per patient at pelvic lymphadenectomy. Lymph node metastasis was noted in 6 of the 46 patients with a prostate specific antigen between 4 and 10 ng./ml. and in 8 of the 64 with a stage pT2 tumor., Conclusions: Our study shows individual variability of lymphatic drainage of the prostate and limited sensitivity for detecting positive lymph nodes when the pelvic dissection area is limited. Furthermore, our experience implies that the identification of sentinel lymph nodes is feasible, not only in breast cancer and malignant melanoma, but also in prostate cancer using a comparable technique.

The diagnostic value of unenhanced helical computed tomography was investigated in a prospective study. In 53 patients (aged 35 to 82 years) with acute flank pain tomography was performed in addition to abdominal plain film and ultrasound examination. All 53 patients had a contraindication for intravenous administration of contrast medium. Ureteral calculi were either confirmed or excluded by retrograde ureteropyelography in 44 cases, in 9 patients by asservation of calculi and clinical follow-up. Helical computed tomography was able to precisely identify all of the 34 ureteral calculi, whereas abdominal plain films led to 6 false positive and 17 false negative findings. In 1 patient with retroperitoneal lymphoma (diagnosed by CT) false positive findings occurred. Unenhanced helical computed tomography reaches a distinctively increased diagnostic value (sensitivity 100%, specificity 95%, accuracy 97%) in the evaluation of acute flank pain as compared to conventional radiologic imaging and ultrasound. This non-invasive procedure is to be considered method of choice for patients with contraindications for the application of radiopaque material.

Purpose: Previous investigations have shown that cytokeratin 18 positive bone marrow cells in localized and lymphatically spread prostate cancer correlates with neither established prognostic factors nor with the biochemical and clinical course after radical prostatectomy. Since the well-known down-regulation of cytokeratin 18 in tumor cells may lead to false-negative results, we asked whether staining with a pan-cytokeratin antibody recognizing a common epitope of cytokeratins 8, 18 and 19 would result in different data., Materials and Methods: Preoperative bone marrow aspirates of 82 patients with localized (N0) and lymphatically spread (N1) prostate cancer were examined using the monoclonal antibody cytokeratin 2 and the pan-cytokeratin antibody A 45-B/B3, called A 45., Results: In contrast to findings with the cytokeratin 18 antibody, those with the pan-cytokeratin antibody correlated with the biochemical course. At a median followup of 1,477 days (4 years) patients with pan-cytokeratin positive cells in the preoperative bone marrow aspirate had biochemical progression significantly earlier than those with pan-cytokeratin negative results (mean time to prostate specific antigen relapse 886 versus 1,409 days, p < or =0.004). Compared with other parameters, such as prostate specific antigen, pathological stage and Gleason score, preoperative pan-cytokeratin findings proved to be an independent prognostic factor., Conclusions: Cytokeratin positive cells in the bone marrow also have prognostic relevance in prostate cancer. The comprehensive analysis of these cells, studies of the individual course of these findings and sufficiently long followup allow us to discuss whether and under what conditions metastasis may develop from 1 or several cytokeratin positive cells.

Objective: The diagnostic value of unenhanced helical computed tomography (CT) for the evaluation of acute flank pain is investigated in a prospective study., Patients and Methods: In 125 patients aged 18-86 years, we performed unenhanced helical CT in addition to abdominal plain film, abdominal ultrasound and urinalysis as a diagnostic measure for acute flank pain. Ureteral calculi were confirmed or, respectively, excluded by retrograde ureteropyelography in 80 cases. In the other cases, diagnosis was verified by clinical course and/or stone asservation., Results: In 91 of 125 patients the flank pain was caused by a ureteral calculus. In 67 of 91 patients with urolithiasis, stones could be collected for analysis. Helical CT was able to precisely identify 90 ureteral calculi. Abdominal plain films led to 8 false-positive and 48 false-negative findings. Thus, sensitivity of plain radiography, ultrasound and urinalysis was 47, 11 and 84% with a specificity 76, 97 and 32%, respectively., Conclusions: Unenhanced helical CT reaches a distinctively increased diagnostic value (sensitivity 99%, specificity 97%) in the evaluation of acute flank pain as compared to plain radiography, ultrasound and urinalysis.

Objective: To investigate prognostic factors in localized and lymphatically spread prostate cancer., Methods: The biochemical course after radical retropubic prostatectomy in 306 patients was subject to a retrospective analysis., Results: Prostate-specific antigen (PSA), Gleason score (prostatectomy specimen) and pathological stage proved to be prognostically relevant (p < 0.0001). PSA, Gleason score and tumor stage also were to be considered as (independent) prognostic factors by means of a multivariate analysis (p < 0.001), whereas perineural invasion (prostatectomy specimen) and preoperative bone marrow findings (CK 2) had no impact on the course of the disease. After a median follow-up of 1,307 days (3.6 years), a biochemical relapse occurred in 41.8%., Conclusion: High preoperative PSA values and the resulting high portion of advanced tumor stages are a possible basis for the high biochemical relapse rate in our collective. The learning curves of several surgeons and the previously more restrictive pelvic lymphadenectomy (surgical understaging) may also be considered causes.

Because of the curative approach, the detection of lymph node metastases in squamous cell carcinoma (SCC) of the penis is of significant clinical relevance. Sentinel lymph node (SLN) identification by means of lymphangiography has been proven to be insufficiently safe. However, the high morbidity of inguinal lymphadenectomy and the considerable individual variability regarding the location of lymph node metastases justify the necessity of a technique that enables the identification of SLNs. Since 1998, SLNs have been intraoperatively identified and selectively dissected, after peritumoral injection of technetium-99m nanocolloid and using lymphoscintigraphy, in three patients (one with malignant melanoma and two with SCC). At least one SLN could be detected in each patient. The maximum surgical time was 30 min. There were no severe complications. Lymph node metastases did not occur in any patient. Upon a mean follow-up of 10 months, all patients are currently free of tumor. Owing to the long-term results of sentinel lymphadenectomy in malignant melanoma of other locations and our preliminary results with respect to penile carcinoma. we consider the current method appropriate as the only primary operation for lymph node staging in early stages and, in combination with modified inguinal lymphadenectomy, in locally advanced stages.

Objective: The goal of this study was to show lymphatic drainage and to verify the validity of lymphoscintigraphy for the identification of the sentinel lymph node (SLN) in prostate cancer. Furthermore, the question is to be raised whether the standardized pelvic lymphadenectomy is a sufficient means for also detecting solitary micrometastases., Patients and Methods: Eleven patients with prostate cancer received a sonographically controlled, transrectal administration of a technetium-99m colloid injected directly into the prostate 1 day prior to pelvic lymphadenectomy. 20 min later the dynamic lymphoscintigraphy was carried out. During surgery, the SLNs were identified by using a gamma probe. The standard pelvic lymphadenectomy was performed after removal of the SLN., Results: In 3 of 4 patients with micrometastasis the spread of the tumor could exclusively be found in those nodes which had been identified as SLNs by means of scintigraphy by combining preoperative lymphoscintigraphy and intraoperative gamma probe detection. In 2 cases, the pathologically proved SLNs were situated at the anteromedial region of the internal iliac artery, thus being located outside of the standard pelvic lymphadenectomy area. In 1 patient, however, the micrometastasis was found beyond those nodes which had been identified as SLN intraoperatively., Conclusions: In the future, we expect the restriction of pelvic staging lymphadenectomy to scintigraphically proved SLN. The perioperative morbidity may be reduced by increasing the sensitivity of the detection of micrometastases. Our data confirm earlier perceptions, according to which even modified standardized pelvic lymphadenectomy is considered insufficient in terms of the detection of micrometastases., (Copyright 1999 S. Karger AG, Basel.)

Purpose: The presence of cytokeratin 18-positive cells in bone marrow correlates with conventional risk factors in many tumors. We examined whether this was also valid for localized or lymphatically spread prostate cancer., Patients and Methods: Immediately before radical prostatectomy, bone marrow aspirates from both sides of the iliac crest were taken from 287 patients. The presence of cells containing cytokeratin 18 was interpreted as micrometastasis., Results: In patients with negative lymph nodes (n = 219), conventional risk factors (Gleason score, pathologic stage, ploidy, and preoperative prostate-specific antigen) did not correlate with the preoperative detection of cells containing cytokeratin 18. There was also no correlation with lymph node metastases. Furthermore, there was no interdependency between the preoperatively detected number of cells and the established risk factors., Conclusion: We assume the presence of epithelial cells in bone marrow to be an independent parameter, the clinical importance of which must be substantiated by further studies.