Peter Albers

Positron emission tomography in the clinical staging of patients with Stage I and II testicular germ cell tumors.

OBJECTIVES To evaluate the accuracy of fluorodeoxyglucose positron emission tomography (PET) compared with computed tomography (CT) staging in patients with Stage I and II testicular germ cell tumors (GCTs). METHODS From January 1995 to July 1997, in 37 patients with clinical Stage (CS) I (n = 25) and CS II (n = 12) GCT (24 nonseminomas, 13 seminomas), PET and CT were compared in the initial staging. After PET, the patients with nonseminomatous GCT were staged surgically by retroperitoneal lymph node dissection and the patients with seminomatous GCT were followed up clinically. RESULTS Correct staging by PET was achieved in 34 of 37 patients compared with correct CT staging in 29 of 37 patients. Of 10 metastatic lesions, 7 and 4 were detected by PET and CT, respectively. PET did not show false-positive signals. PET was unable to detect vital cancer with a maximal diameter less than 0.5 cm or teratoma at any size. CONCLUSIONS PET was useful for detecting viable tumor in lesions that are visible on CT scan and, thus, it may omit false-positive CS II lesions. However, PET was not able to identify mature teratoma. In this study, PET did not improve the staging in patients with CS I tumor.

Long-Term Results of Internal Urethrotomy

PURPOSE A retrospective analysis was done of long-term results of internal urethrotomy to evaluate risk factors of stricture recurrence. MATERIALS AND METHODS Followup studies were performed of 937 patients with urethral strictures treated with internal urethrotomy. Of the patients 357 were treated at Mainz University between 1977 and 1989 (mean followup 4.6 years) and 580 were treated at Bonn University between 1974 and 1986 (mean followup 3.2 years). RESULTS Strictures recurred in 96 of 357 (26.9%) and 260 of 580 (44.8%) patients, respectively. Risk factors for recurrence were etiology (post-transurethral resection and inflammation), stricture longer than 1 cm. and postoperative catheter drainage for longer than 3 days. CONCLUSIONS Urethroplasty should be considered in patients at high risk for stricture recurrence and with more than 1 treatment failure after urethrotomy.

Therapeutic vaccination against metastatic renal cell carcinoma by autologous dendritic cells: preclinical results and outcome of a first clinical phase I/II trial

Abstract. In this study we have presented in vitro data and results of a preliminary clinical trial using dendritic cells (DC) in patients with progressive metastatic renal cell carcinoma. DC precursor cells were obtained from peripheral blood mononuclear cells (PBMC). DC were pulsed with autologous tumor cell lysate if available. In total, 15 patients were treated with a median of 3.95×106 DC administered and ultrasound-guided into a lymph node or into adjacent tissue. Seven patients remained with progressive disease (PD), 7 patients showed stable disease (SD), and one patient displayed a partial response (PR). Most interestingly, the patient who was treated with the highest number of DC (14.4×106 DC/vaccine) displayed a PR. Delayed-type hypersensitivity (DTH) reaction using autologous tumor lysate was positive in 3 out of 13 patients, including the patient with PR. Two out of 3 patients receiving additional treatment with keyhole limpet hemocyanin (KLH) showed reactivity to KLH after vaccination. CD3+CD4+ and CD3+CD28+ cells as well as the proliferation rate of peripheral blood lymphocytes (PBL) increased significantly in the blood of patients during therapy. In conclusion, our observations confirm the capability of tumor-lysate pulsed autologous DC vaccines to stimulate an immune response in patients with metastatic renal cell carcinoma even in the presence of a large tumor burden. The lack of adverse effects together with immunologic effects support further investigation of this novel therapeutic approach. Further studies are necessary to demonstrate clinical effectiveness in cancer patients, in particular in patients with less advanced disease.

SALVAGE SURGERY OF CHEMOREFRACTORY GERM CELL TUMORS WITH ELEVATED TUMOR MARKERS

PURPOSE We evaluated the prognostic criteria for salvage surgery in patients with persistent marker elevation after chemotherapy for metastatic germ cell tumors. MATERIALS AND METHODS Of 125 men who underwent post-chemotherapeutic resection of residual tumors 30 had persistent marker elevation at surgery. This group was subdivided into 17 patients with no evidence of disease, 7 dead of disease and 6 others. Outcome analysis was performed in the subgroups with regard to preoperative and postoperative parameters. Mean followup was 120.3 months (range 1 to 228) after surgery. RESULTS Of the 30 patients 17 (57%) with persistently elevated tumor markers after chemotherapy were long-term survivors after salvage surgery. Overall persistent viable cancer and teratomatous elements were identified in 64% and 11% of cases, respectively. Significantly more patients died of disease who had a poor prognosis according to International Germ Cell Cancer Collaborative Group guidelines. Embryonal carcinoma was the predominant initial histology in this group and residual disease was more often located at various sites, for example the viscera, with a lower chance of complete surgical resection. Marker status before surgery, and chemotherapeutic pretreatment and postoperative histological findings did not differ significantly in patients with no evidence of disease and those dead of disease. CONCLUSIONS Salvage surgery results in long-term success in greater than 50% of patients. Complete resection is the most important single parameter for a favorable outcome. Even patients with visceral metastasis benefit from surgery. Our data do not justify omitting surgery in certain subgroups.

Treatment of penile strangulation caused by constricting devices

Constricting devices placed on the penis present a challenge to urologists. Various nonmetallic and metallic objects are placed on the penis to increase sexual performance or because of autoerotic intentions. We describe five different cases of strangulating objects (wedding ring, metal plumbing cuff, bull ring, hammer- head, and plastic bottle neck) and demonstrate that each case needs individual handling in removing the object. The treatment of penile strangulation is decompression of the constricted penis to facilitate free blood flow and micturition. It requires no particular skill but does require resourcefulness to perform the removal simply and effectively, and with as little discomfort for the patient as possible.

Randomised phase II trial of gemcitabine and paclitaxel second-line chemotherapy in patients with transitional cell carcinoma (AUO trial AB 20/99)

The objectives are to evaluate and compare the response and toxicity of a 3‐weekly and a 2‐weekly regimen of gemcitabine (Gem) and paclitaxel (Pac) second‐line treatment in patients with transitional cell carcinoma (TCC).

Eukaryotic initiation factor 3 p110 mRNA is overexpressed in testicular seminomas

Testicular germ cell tumors are important neoplasms and seminoma accounts for 40 to 50% of these tumors. Little is known concerning the molecular events underlying the development of these malignancies. In the present study we used a modified differential display approach to compare gene expression between seminoma and normal testicular parenchyma, both of which are mixed tissues. We first analyzed mRNA (cDNA) expression by differential display and then directly used differentially expressed cDNAs for the synthesis of radiolabeled riboprobes to attribute differential expression to specific cell types in tissue sections by in situ hybridization. Using this approach along with real-time quantitative reverse transcriptase-polymerase chain reaction analysis we found an overexpression of eukaryotic initiation factor 3 p110 mRNA (EIF3S8) in seminoma cells compared to normal germ cells of testicular tubules. The elF3-p110 subunit may promote seminoma development by generally increasing translation leading to enhanced cellular growth and division rates.

MIB-1 immunohistochemistry in clinical Stage I nonseminomatous testicular germ cell tumors predicts patients at low risk for metastasis†

The clinical Stage I of nonseminomatous germ cell tumors (NSGCT) is inaccurate in 30% of patients. In previous studies on tumor biologic risk factors, low tumor proliferation rates predicted a group of patients at low risk for occult metastatic disease. The goal of this study was to confirm the immunohistochemical assessment of tumor proliferation using MIB‐1 (Ki‐67 receptor) in a different patient cohort with different investigators to prove the methods reliability.

Surgery in Metastatic Testicular Cancer

Surgery in advanced testicular tumors is an integral part of the multimodality treatment. However, the indications for surgery in testis cancer have changed over the last 10 years. Patients with advanced seminoma only rarely will need surgery after chemotherapy whereas patients with advanced non-seminoma need to undergo the resection of residual disease in most of the cases. Surgery in metastatic disease may even be beneficial for patients with recurrent tumors, patients with persisting marker elevations during chemotherapy, or patients with late relapse of the disease. In view of late relapse, the extent and completeness of the primary resection is an important issue and, therefore, surgery should be performed in specialized centers. Most of the procedures are technically demanding and, therefore, individualized perioperative precautions are necessary to reduce morbidity of surgery. Nevertheless, in individual cases nerve-sparing techniques and laparoscopic approaches may be applicable to reduce surgery-related morbidity. This review will update the current indications and recommendations for post-chemotherapy surgery in advanced testis cancer.

Bladder cancer cells acquire competent mechanisms to escape Fas-mediated apoptosis and immune surveillance in the course of malignant transformation

Mechanisms of resistance against Fas-mediated cell killing have been reported in different malignancies. However, the biological response of immune escape mechanisms might depend on malignant transformation of cancer cells. In this study we investigated different mechanisms of immune escape in 2 well-differentiated low-grade (RT4 and RT112) and 2 poorly differentiated high-grade (T24 and TCCSUP) bladder cancer cell lines. Fas, the receptor of Fas-ligand, is expressed and shedded by human transitional bladder carcinoma cell lines RT4, RT112, T24 and TCCSUP. Cytotoxicity and apoptosis assays demonstrate that in spite of the Fas expression, poorly differentiated T24 and TCCSUP cells are insensitive towards either recombinant Fas-ligand or agonistic apoptosis-inducing monoclonal antibody against Fas. In poorly differentiated T24 and TCCSUP cell lines we were able to detect marked Fas-ligand protein by flow cytometry and Western blot analysis. In grade 1 RT4 and RT112 cells only minor expression of Fas-ligand possibly because of proteinase action. Fas-ligand mRNA translation or post-translational processing seems to be regulated differentially in the cancer cell lines depending on malignant transformation. In co-culture experiments we show that poorly differentiated cells can induce apoptosis and cell death in Jurkat cells and activated peripheral blood mononuclear cells. This in vitro study suggests that bladder cancer cells can take advantage of different mechanisms of immune evasion and become more competent in avoiding immune surveillance during transformation to higher-grade malignant disease.