Radical cystectomy under continuous antiplatelet therapy with acetylsalicylic acid.

INTRODUCTION: Aim of this study was to analyse the perioperative outcome of patients undergoing radical cystectomy under continuous antiplatelet therapy with acetylsalicylic acid. MATERIALS AND METHODS: Using prospectively maintained databases of two departments of urology, we identified 461 consecutive patients who underwent radical cystectomy for bladder cancer (2011-2017). Patients were divided into three groups: 1) on-going antiplatelet therapy with acetylsalicylic acid (n = 50), 2) discontinuing antiplatelet therapy (n = 65) and 3) no antiplatelet therapy (n = 346). Perioperative outcome was compared between the three groups using ANOVA, likelihood ratio or Kruskal Wallis test with post-hoc testing. Uni- and multivariate analyses were performed to identify predictor for perioperative complications and transfusion. RESULTS: Group 1 showed an average estimated blood loss of 732 ±â€¯424, group 2 752 ±â€¯488 and group 3 810 ±â€¯544 ml (p = 0.51). There was no significant difference in transfusion rate (44% in group 1, 45% and 39% in groups 2 and 3, p = 0.63). Severe complications occurred in 26%, 15% and 15% in groups 1-3 (p = 0.19). Ischemic complications were more often observed in group 1 (n = 4, 8%) and 2 (n = 5, 8%) than group 3 (n = 7, 2%), p = 0.02. 90-day readmission (n = 99, 22%) and mortality rate (n = 10, 2.2%) were low and did not show any significant differences between the groups. In uni- and multivariate analysis ongoing therapy with acetylsalicylic acid was no independent risk factor for transfusion or severe complications. CONCLUSION: Perioperative continuation of therapy with acetylsalicylic acid in radical cystectomy is safe with no difference in intraoperative blood loss, transfusion rate, complications or mortality.

Biomodulatory Treatment of Patients with Castration-Resistant Prostate Cancer: A Phase II Study of Imatinib with Pioglitazone, Etoricoxib, Dexamethasone and Low-Dose Treosulfan.

Therapeutic options for patients with castration-resistant prostate cancer (CRPC) remain limited. In a multicenter, Phase II study, 65 patients with histologically confirmed CRPC received a biomodulatory regimen during the six-month core study. Treatment comprised daily doses of imatinib mesylate, pioglitazone, etoricoxib, treosulfan and dexamethasone. The primary endpoint was prostate-specific antigen (PSA) response. Responders could enter an extension phase until disease progression or intolerable toxicity occurred. Mean PSA was 45.3 ng/mL at baseline, and 77 % of patients had a PSA doubling time <3 months. Of the 61 evaluable patients, 37 patients (60.6 %) responded or had stable disease and 23 of them (37.7 % of 61 patients) were PSA responders. Among the 23 responders mean PSA decreased from 278.9 ± 784.1 ng/mL at baseline to 8.8 ± 11.6 ng/mL at the final visit (week 24). The progression-free survival (PFS) was 467 days in the ITT population. Of the 947 adverse events, 57.6 % were suspected to be drug-related, 13.8 % led to dose adjustment or permanent discontinuation and 40.2 % required concomitant medication. This novel combination approach led to an impressive PSA response rate of 37.7 % in CRPC patients. The good PSA response and PFS rate combined with the manageable toxicity profile suggest an alternative treatment option.

[Metastatic renal cell cancer in Germany in 2010. Impact of different target therapies]. / Sequenztherapie beim metastasierten Nierenzellkarzinom in Deutschland 2010. Bedeutung der verschiedenen Target-Substanzen.

BACKGROUND: Since 2006 in Germany six different target drugs for therapy in metastatic renal cell cancer (mRCC) have been used. Comparative studies for the application with the same indication are absent, and the order of potential sequential therapy is up to now unclear. The aim of the study was to collect data on therapy decisions in Germany regarding mRCC in the age of "targeted therapy". At the same time the study addressed the central question of sequencing of the different therapy options. In addition, the data of this study were to be compared to a study already published in 2008. PATIENTS AND METHODS: In 2010, four groups of doctors specialized in the therapy of patients with mRCC were asked for their behaviour in the first-, second- and third-line or sequential therapy. Those questioned included urologists in private practice (n=40), oncologists in private practice (n=40), hospital urologists (n=35) and hospital oncologists (n=35). Further the reasons for a therapy decision should be stated or weighted. RESULTS: Altogether 92% of all patients with mRCC were treated. Urologists in private practice treat only 30% of their patients themselves. The earlier used immune therapies (IFN, IL-2) no longer play a role. Sunitinib is used most often in first-line therapy by urologists in private practice (50.4%) and oncologists in private practice (47.1%). In second- and third-line therapy everolimus is used by urologists in private practice (27.1%, 26.3%) and sorafenib (28.6%) or everolimus (26.4%) by oncologists in private practice. Hospital oncologists use primarily sunitinib (56.1%), in second-line sorafenib (45.5%) and in third-line above all everolimus (19.4%). Hospital urologists use sunitinib most often for first-line therapy (57.6%) and sorafenib for second-line treatment (37.3%), while in third-line therapy temsirolimus (49.6%) and also everolimus (30.4%) were used. CONCLUSIONS: The therapy of mRCC is determined very strongly by the substances sunitinib and sorafenib. The mTOR inhibitors have recently been increasingly included in the second- and third-line therapy. With the introduction of the new targeted therapies, the treatment of these special patients is performed less by urologists and increasingly more by oncologists. This trend is strengthened in comparison to the DGFIT study from 2008.

A clinical phase I/II trial with the monoclonal antibody cG250 (RENCAREX®) and interferon-alpha-2a in metastatic renal cell carcinoma patients.

PURPOSE: To evaluate the efficacy and safety of WX-G250, a chimeric monoclonal antibody that binds to carboxy anhydrase IX, combined with low-dose interferon-alpha (LD-IFNα) in patients with progressive metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: Thirty-one patients, nephrectomized for the primary tumor, clear cell progressive mRCC, were enrolled to receive weekly infusions of WX-G250 (20 mg i.v.; week 2-12) combined with LD-IFNα (3 MIU s.c. 3 times/week; week 1-12). At week 16, patients were evaluated for response and stratified into two groups: (a) responders into the extended treatment group for an additional 6 weeks of treatment or (b) the progressive group with no further study treatment. RESULTS: Of the 31 treated patients, 26 were evaluable for response to treatment. Two patients showed partial remission and 14 patients had stable disease as assessed in week 16. One patient experienced partial remission resulting in a complete remission lasting at least 17 months. Nine patients had durable stable disease of 24 weeks or longer. Clinical benefit was obtained in 42% (11/26) patients. The median overall survival achieved was 30 months and the 2-year survival was 57%. Patients receiving extended treatment showed a significantly longer 2-year survival rate than discontinued patients (79 vs. 30%; P=0.0083). In general, treatment was well tolerated with little toxicity. CONCLUSION: Treatment with the antibody WX-G250 in combination with LD-IFNα is safe, well tolerated, led to clinically meaningful disease stabilization and demonstrated clinical benefit in this progressive mRCC patient population.

[Impact of immunotherapy in metastatic kidney cancer in Germany after introduction of new target therapy--results of a telephone survey of the German Society of Immuno- and Targeted Therapy (DGFIT)]. / Welche Bedeutung hat die Immuntherapie beim metastasierten Nierenzell-karzinom nach Einführung der neuen Target-Substanzen in Deutschland--Ergebnisse einer repräsentativen Umfrage der DGFIT.

INTRODUCTION: Until recently, the standard therapy for metastatic renal cell carcinoma (mRCC) in Germany consisted of interleukin-2 (IL-2), interferon-alfa (IFN) as single agents or in combination, with or without chemotherapy. Since 2005, new drugs (target drugs) in the therapy for mRCC are available. The aim of this study was to analyse the current therapy standard in Germany. METHODS: By representative telephone interviews (GFK-Nürnberg by order of DGFIT) the following colleagues were contacted A: urologists in private practice (n = 40), B: oncologists in private practice (n = 40), C: hospital urologists (n = 35) and D: hospital oncologists (n = 35). Screening criteria were 1) responsibility for therapy in mRCC; 2) therapy of at least 10 patients with mRCC per year. RESULTS: Patients/year: A: n = 19, B: n = 17, C: n = 43, D: n = 21. 98% of patients with mRCC were treated: A: the most frequent therapy was sunitinib (43%, 42%, 33% as first-, second-, third-line), B: the most frequent therapy was sunitinib (45% as first-line, 37% as second-line), the most frequent third-line therapy was sorafenib (35%); C: the most frequent therapy were sorafenib and sunitinib (first-line 26% vs. 27%, second-line 46% vs. 42%), in third-line therapy additionally temsirolimus 24%; D: primary sorafenib and sunitinib (first-line 33% vs. 40%, second-line 46% vs. 42%), in third-line therapy additionally temsirolimus 23%. Immunotherapy (IL-2, IFN with or without chemotherapy) in mRCC plays in Germany for the second- and third-line therapy in A-D no major role (less than 10%). Otherwise, for first-line therapy immunotherapy has some relevance: A: 25%, B: 37%, C: 33%, D: 16%. The most important criteria for therapy decision making in A-D were: efficacy, toxicity, drug approval status. CONCLUSIONS: Most patients with mRCC in Germany were seen by hospital urologists. Sunitinib (in first-line) and sorafenib (in second-line) are currently the most frequent prescribed drugs in mRCC. Temsirolimus is used mostly for third-line therapy (followed by sunitinib/sorafenib). Treatment of mRCC in Germany is increasingly being performed by oncologists.

Interleukin-2- and interferon alfa-2a-based immunochemotherapy in advanced renal cell carcinoma: a Prospectively Randomized Trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN).

PURPOSE: We conducted a prospectively randomized clinical trial to compare the efficacy of three outpatient therapy regimens in 341 patients with progressive metastatic renal cell carcinoma. PATIENTS AND METHODS: Patients were stratified according to known clinical predictors and were subsequently randomly assigned. Treatment arms were: arm A (n = 132), subcutaneous interferon alfa-2a (sc-IFN-alpha-2a), subcutaneous interleukin-2 (sc-IL-2), and intravenous (IV) fluorouracil; arm B (n = 146): arm A treatment combined with per oral 13-cis-retinoic acid; and arm C (n = 63), sc-IFN-alpha-2a and IV vinblastine. RESULTS: Treatment (according to the standard 8-week Hannover Atzpodien regimen) arms A, B, and C yielded objective response rates of 31%, 26%, and 20%, respectively. Arm B, but not arm A, showed a significantly improved progression-free survival (PFS) compared with arm C (P =.0248). Both arm A (median overall survival, 25 months; P =.0440) and arm B (median overall survival, 27 months; P =.0227) led to significantly improved overall survival (OS) compared with arm C (median OS, 16 months). All three sc-IFN-alpha-2a-based therapies were moderately or well tolerated. CONCLUSION: Our results established the safety and improved long-term therapeutic efficacy of sc-IL-2 plus sc-INF-alpha-2a-based outpatient immunochemotherapies, compared with sc-INF-alpha-2a/IV vinblastine.

[Surgical treatment of pulmonary metastases from renal cancer]. / Lungenmetastasenchirurgie beim Nierenzellkarzinom.

Based on a large single-center follow-up database, we evaluated the long-term results after curative resection of pulmonary metastases from renal cancer. During a 20-year period, 105 patients underwent a total of 150 resections with curative intention. Hospital mortality was 0.95%, 5- and 10-year survival rates were 40% and 33%, respectively. Significant prognostic relevance was shown for complete pulmonary resection, lymph node involvement upon primary resection as well as size of the resected lung metastasis. Our findings of low perioperative morbidity and mortality rates lead us to propose that in patients without additional metastases curative resection of pulmonary lesions should be considered. Moreover, recurrent pulmonary metastases should also be considered for surgical treatment since resection for cure significantly improves survival in these patients.

[Ambulatory radiosurgery in cerebral metastatic renal cell carcinoma. 5-year outcome in 58 patients]. / Ambulante Radiochirurgie bei zerebral metastasiertem Nierenzellkarzinom. Fünfjahresergebnisse von 58 Patienten.

Brain metastases (BM) indicate an advanced stage of renal cell cancer (RCC). They pose an increasing challenge to urologists as a result of improved survival due to modern therapy. Median survival of untreated patients with BM who often suffer from neurological deficits is 3 months. Radiosurgery with the Gamma Knife (GK) has increased in use as an alternative to whole brain radiation therapy (WBRT) and/or surgery. This study reports the results of a consecutive series of RCC patients treated for BM by GK radiosurgery during a 5-year period. Between 1994 and 1999, 58 patients with a total of 277 BM and 3.0 (1-19) BM/patient were treated. Because of recurrent BM, 23 (40%) patients received repeated (multiple) GK sessions. The median tumor volume was 3.4 cm3 (0.1-19.1). The median interval between diagnosis of RCC and GK treatment was 2.2 years (0.1-17.2). Symptomatic side effects were detected in 9 (16%) of 58 patients. The median actuarial survival time was 9.9 months. Local tumor control could be achieved in 95% of patients. The GK therapy induced a significant tumor remission accompanied by rapid neurological improvement in 70% of patients. Compared to standard radiotherapy, GK radiosurgery is more effective, less time consuming, and can be repeated. Compared to surgery, radiosurgery is less invasive and better suited to treat multiple metastases in one single session. Surgery and radiosurgery, however, are supplementary methods that are highly effective to control intracerebral metastasizing RCC.

[Telerobotic surgery between Baltimore and Munich]. / Telerobotische Chirurgie zwischen Baltimore und München.

The rapid development of laparoscopy in urology necessitates the training of specialists to guarantee the high standard of patient care. The real-time data communication of medical information between physicians in different locations is known as telemedicine. Telementoring describes the assistance of an experienced surgeon, while telerobotics requires the use of robots. Two robots, the established AESOP and the PAKY + RCM developed at the Johns Hopkins Hospital (JHH), were used to perform a telerobotic laparoscopic renal cyst ablation in cooperation between Baltimore and Munich. The telementor maneuvered the robots over a distance of 8000 km using eight ISDN lines and a PC. AESOP moved the camera, while PAKY allowed the use of a fan retractor in the abdomen. The telerobotic operation was performed without complications or system and communication failures. Telementoring can be used for training purposes but also for consultation between specialists in emergency settings.

Application of Photofrin II as a specific radiosensitising agent in patients with bladder cancer--a report of two cases.

BACKGROUND: The effect of ionizing radiation on tumour tissues can be optimised by adding radiosensitising agents to enhance tumour inactivation. Photofrin II has been approved as a photosensitising agent for the photodynamic therapy (PDT) of selected solid tumours. At present, no chemical modifier has been found to act as a selective radiosensitiser. We report here the first use of Photofrin II as a radiosensitising agent to enhance radiation therapy. PATIENTS: Two patients, one female with unresectable bladder cancer and one male with recurrent inoperable bladder cancer, were treated with radiation therapy (44.8 Gy + 14 Gy boost) of the pelvic region. 24 hours before initiation of therapy the patients were intravenously injected with 1 mg kg(-1) Photofrin II (Axcan, Canada). RESULTS: Magnetic resonance imaging of the pelvis with a standardized protocol demonstrated a reduction in tumour volume of approximately 40% in the female patient and 35% in the male patient. The female patient was operated upon after conclusion of radiotherapy, the male patient refused the operation. No severe side effects were observed. CONCLUSION: Photofrin II is a promising radiosensitising agent in the treatment of patients with advanced solid tumours.

Use of hydro-jet cutting for laparoscopic partial nephrectomy in a porcine model.

OBJECTIVES: To evaluate whether a laparoscopic hydro-jet device can provide a safe and effective partial nephrectomy. Partial nephrectomy is still one of the most challenging operations in urologic laparoscopy. The control of hemorrhage is very difficult to achieve with laparoscopic techniques. In open surgery, hydro-jet resection is used to cut the renal parenchyma selectively, avoiding damage to the vascular structures or collecting system.Methods. Laparoscopic wedge, as well as pole, resections of the kidney were performed in 5 pigs under general anesthesia. After exposure of the kidney, the renal capsule was incised using electrocautery. The hydro-jet was then used to dissect the renal parenchyma. In pole resections, the collecting system and central vessels were divided using an Endo-GIA. Hemostasis was achieved by electrocoagulation or clips. The dissection time and intraoperative complications were evaluated.Results. The operations were performed successfully in all animals without temporary ischemia. The hydro-jet generator allowed precise and effective tissue dissection without significant hemorrhage. The parenchymal vessels were selectively coagulated. The collecting system and central vessels remained intact and could be divided after application of the Endo-GIA. The mean dissection time was 42 +/- 6 minutes for the wedge resections and 54 +/- 8 minutes for the pole resections. CONCLUSIONS: These experimental results demonstrate the suitability of hydro-jet dissection for safe laparoscopic partial nephrectomy without temporary ischemia and with reduction of the operative trauma to the kidney. On the basis of our own experiences with other techniques, including electrocautery and laser technology for partial nephrectomy, we conclude that laparoscopic hydro-jet resection represents an interesting alternative to other techniques.

Endoscopic detection of transitional cell carcinoma with 5-aminolevulinic acid: results of 1012 fluorescence endoscopies.

OBJECTIVES: The initial encouraging results using 5-aminolevulinic acid (5-ALA) induced fluorescence endoscopy (AFE) have promised a procedure with an outstanding sensitivity for the detection of early stage bladder cancer. Summarized here is our clinical experience and data comprising 1012 fluorescence endoscopies. METHODS: Two hours, 30 minutes before endoscopy, 1.5 g 5-ALA dissolved in 50 mL of 5.7% sodium monohydrogen phosphate was instilled in patients intravesically. Before AFE, all patients underwent white light endoscopy, and a bladder washing cytologic specimen was obtained. A special light source provided blue light (375 to 440 nm) for fluorescence excitation. Suspicious sites were identified by their red fluorescence contrasting against backscattered blue light when observed through the long pass filter (445 nm) integrated into the telescope eyepiece. RESULTS: Two thousand four hundred seventy-five specimens were obtained (2.4 biopsies per AFE). In 552 AFEs (54.5%), neoplastic urothelial lesions were detected, in 34.2% only because of their positive fluorescence; 38.7% of these additionally detected neoplastic foci had poorly differentiated histologic features. CONCLUSIONS: AFE has proved to be a clinically feasible procedure with an outstanding detection rate for flat, urothelial, high-risk lesions.

Immunomagnetic cell enrichment detects more disseminated cancer cells than immunocytochemistry in vitro.

PURPOSE: We describe a method to improve tumor cell detection compared to currently available immunocytochemical methods by using immunomagnetic cell enrichment. MATERIALS AND METHODS: Two different methods of immunomagnetic cell enrichment using antibody coated magnetic beads were tested and compared with unenriched immunocytochemistry. One method was positive selection of epithelial cells from mononuclear cells with the antiepithelial antibody BER-EP4 and the other was depletion of mononuclear cells with the antileukocyte antibody CD45. Mononuclear cells were isolated from peripheral blood by density centrifugation and various numbers of tumor cells were added. The 5 different cell lines from urological malignancies used in the study were DU-145, RT-4, CAKI-2, KTCTL-2 and KTCTL-30. Following incubation of cell suspensions with the beads, cell separation was performed in a magnetic field. After centrifugation on glass slides immunocytochemical staining for cytokeratin was performed. A total of 112 experiments were completed and negative controls were obtained. RESULTS: The number of tumor cells detected by positive selection and depletion was significantly higher than by immunocytochemistry (p <0.001). The median enrichment factor and tumor cell recovery rate for positive selection and depletion were 15.3 and 61.2%, and 13.0 and 57.3%, respectively (not significant). With less than 1 tumor cell suspended in 106 mononuclear cells, the probability of tumor cell detection was 23% for immunocytochemistry alone and 93.3% for both enrichment methods (p <0.01). No false-positive results were observed. CONCLUSIONS: Compared to immunocytochemistry, immunomagnetic cell enrichment significantly improves the sensitivity of detection of epithelial cells added to mononuclear cells. Both methods of enrichment were equally effective and may be important for clinical practice in the future.

Allogeneic vaccination for renal cell carcinoma: development and monitoring.

An allogeneic tumor cell vaccine should display a natural immunogenicity that allows the stimulation of tumor-reactive effector cells in patients. Furthermore, the vaccine should express antigens that are shared by many tumors to which patients are not tolerant. A variety of tumor peptides should be presented by different HLA-molecules due to limited MHC matching with recipients and last but not least, the vaccine should have a strong growth potential in vitro to allow adequate amounts of vaccine to be generated for long-term usage. In vitro and in situ studies with the renal cell carcinoma cell line RCC-26 demonstrate: (1) RCC-26 can induce complex allospecific responses through direct priming; (2) RCC-26 can not only reactivate cytotoxic T lymphocytes (CTL) of a memory phenotype but they also can induce de novo tumor-antigen associated responses in normal donors; (3) these cells present epitopes restricted by several MHC molecules, allowing the vaccination of patients matched for different HLA alleles; and (4) they stimulate HLA-A*0201-restricted T cells bearing characteristic T cell receptors (TCR). Thus, in addition to using limiting dilution killer and ELISPOT assays, molecular tracking of a tumor-specific TCR can be used to judge the development of antitumor reactivity and vaccine efficiency.

Growth hormone has no direct effect on human adrenal steroid and insulin-like growth factor-binding protein secretion.

Although it is known that growth hormone (GH) exerts its growth-promoting effects mainly via Insulin-like growth factor-I (IGF-I), an increasing number of direct effects of GH has been described in many tissues. In vivo, mice transgenic for human growth hormone (hGH) show significantly elevated levels of corticosterone, enlarged adrenal glands, and altered levels of insulin-like growth factor binding proteins (IGF-BPs). Recently, we have shown that IGF's induce the secretion of cortisol and IGF-BP's in adult human adrenocortical cells. However, since human adrenal glands express the intact GH-receptor, the objective of this study was to investigate whether GH exerts a direct effect on the steroidogenesis and IGF-BP synthesis in adult human adrenocortical cells. Primary cell cultures in monolayer were incubated under serum-free conditions with human growth hormone and/or ACTH for up to 72 hours. Cortisol was measured by specific RIA and the secretion of insulin-like growth factor binding proteins was analyzed by Western ligand blotting. hGH alone was unable to stimulate basal or ACTH-induced cortisol secretion. Additionally, neither hGH alone or in combination with ACTH did significantly alter the secretion of IGF-BP's. Therefore we conclude that hGH is unable to directly stimulate cortisol secretion and IGF-BP secretion in cultured human adrenocortical cells.

Expression of plakoglobin in renal cell carcinoma.

Little is known about the role of molecules involved in cell-cell interactions during the progression of renal cell carcinoma (RCC). We investigated the expression of plakoglobin (a component of the cadherin-catenin adhesion system) in 94 samples of normal kidney tissue from patients with RCC, in 109 primary renal cell carcinomas and in 16 metastases by immunohistochemistry. Expression of plakoglobin was significantly diminished in tumor tissue, particularly in metastatic lesions, as compared to normal kidney tissue (p < 0.001). Follow-up data were available from 87 patients. Patients with a diffuse plakoglobin expression (91-100% positive cells) in primary tumor tissue had a significant better survival rate than patients with a disturbed plakoglobin expression (p < 0.05) as determined by the log rank test. These results indicate that loss of plakoglobin may play an important role in malignant transformation of renal cells. Plakoglobin expression status could give additional information about the individual prognosis.

Limitations of reverse-transcriptase polymerase chain reaction analyses for detection of micrometastatic epithelial cancer cells in bone marrow.

PURPOSE: This study was designed to evaluate the potential of reverse-transcriptase polymerase chain reaction (RT-PCR) analyses for the detection of micrometastatic carcinoma cells in bone marrow (BM). PATIENTS AND METHODS: The specificity of RT-PCR assays with primers specific for various tumor-associated and organ-specific mRNA species was examined by analysis of 53 BM aspirates from control patients with no epithelial malignancy. In addition, BM samples from 63 patients with prostate cancer (n = 53) or breast cancer (n = 10) were analyzed by RT-PCR with primers specific for prostate-specific antigen (PSA) mRNA. As a reference method, all samples were analyzed simultaneously by an established immunocytochemical assay, using monoclonal antibodies (mAbs) against cytokeratins (CK) for tumor-cell detection. RESULTS: Seven of eight marker species could be detected in a considerable number of BM samples from control patients: epithelial glycoprotein-40 (EGP-40; 53 of 53 samples), desmoplakin I (DPI I; five of five), carcinoembryonic antigen (CEA; five of 19), erb-B2 (five of seven), erb-B3 (six of seven), prostate-specific membrane antigen (PSM; four of nine), and CK18 (five of seven). Only PSA mRNA was not detected in any of the 53 control BM samples. In serial dilution experiments, the PSA RT-PCR assay was able to detect five LNCaP prostate carcinoma cells in 4 x 10(6) BM cells. CK-positive cells were found in 20 patients (37.7%) with prostate cancer, while PSA mRNA was found in only 15 (28.3%; P = .04). Moreover, despite the recent observation that PSA is also expressed in mammary carcinomas, none of the 10 CK-positive BM samples were PSA mRNA-positive. CONCLUSION: Limiting factors in the detection of micrometastatic tumor cells by RT-PCR are (1) the illegitimate transcription of tumor-associated or epithelial-specific genes in hematopoietic cells, and (2) the deficient expression of the marker gene in micrometastatic tumor cells.

Cellular and molecular analyses of major histocompatibility complex (MHC) restricted and non-MHC-restricted effector cells recognizing renal cell carcinomas: problems and perspectives for immunotherapy.

Renal cell carcinomas belong to the small group of tumors that are able to induce antitumor responses. Here we describe two general types of cytotoxic effector lymphocytes that can eliminate autologous tumor cells and discuss the role that major histocompatibility complex encoded molecules play in governing their specificities. Improved understanding of the cellular and molecular basis of renal cell carcinoma recognition opens new avenues of research with the potential to develop better immunotherapies for patients with metastatic disease.

[Immunotherapy of metastatic renal cell carcinoma. Is clinical use justified in view of outcome, side effects and costs?]. / Immuntherapie des metastasierten Nierenzellkarzinoms. Ist der klinische Einsatz in Anbetracht der Ergebnisse, Nebenwirkungen und Kosten gerechtfertigt?

The immunogenic potential of renal cell carcinoma and the resistance of its metastases against chemotherapy, radiation and hormonal treatment have led to the development of a great number and variety of different strategies, summarized under the term immunotherapy. Objective remissions can be expected in about 20-40% of patients. Another 30-40% show stable disease for a limited time, only occasionally for longer. Most results are from uncontrolled phase II studies. A cancer cure can usually not be expected, long-term remissions are rare (5%), and high remission rates are only observed in studies with strong patient selection. Some authors have reported a higher survival rate in patients treated with IL-2 or IFN. Survival of patients with objective remissions is significantly improved. A standard therapy cannot be defined. Even presuming an increased survival rate, the toxicity, which can lead to a dramatic reduction in quality of life, and the high costs have to be considered carefully. We think that in view of the lack of therapeutic alternatives, the improving efficacy, the potential survival benefit, the reduction of toxicity and the perspectives, immunotherapy is essential in the treatment of metastatic renal cell carcinoma. Its use should be confined to clinical studies.