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Testicular tumors can be divided into germ cell tumors and sex cord stromal tumors. Malignant testicular germ cell tumors (TGCT) represent about 90-95 % of all testicular tumors and are the most common solid neoplasms in young men aged 20-40 years with an increasing incidence in industrialized countries. Treatment of TGCT is performed by an individual and risk-adapted approach taking primary tumor histology, histopathlogical and molecular prognostic risk factors, tumor stage and for metastasized tumors the response to systemic chemotherapy into consideration. Knowledge of the specific histopathology of the primary tumor and the prognostic factors is of utmost importance for the treating urologist and oncologist in order to avoid undertreatment or overtreatment. Established risk factors which have been validated in retrospective and prospective studies for clinical stage I non-seminomatous TGCT are the presence of vascular invasion and the percentage of embryonal carcinoma. In clinical stage I seminomas tumor size (> 4 cm) and presence of rete testis infiltration have been identified as risk factors in retrospective but not in prospective studies. Quantitative histopathology of the primary tumor is also important for the management of small residual masses following chemotherapy: if the masses are ≤ 1 cm, postchemotherapy retroperitoneal lymph node dissection is only indicated if the primary tumor contains ≥ 50 % teratoma. Quantitative pathohistology of the resected residual masses is of importance for the decision-making process of a consolidating chemotherapy which is only of benefit if the amount of vital cancer tissue is > 10 %. Resection of residual hepatic and thoracic masses is indispensable. For gonadal stromal tumors knowledge of atypical nuclear forms, increased rate of mitosis and increased growth fractions are important for therapy planning.

For improved tumor staging and therapy control, imaging biomarkers are of great interest allowing a noninvasive characterization of invasiveness. In squamous epithelial skin and cervix lesions, transition to invasive stages is associated with enhanced matrix metalloproteinase (MMP) activity, increased angiogenesis, and worsened prognosis. Thus, we investigated MMP activity as imaging biomarker of invasiveness and the potential of optical tomography in characterizing the angiogenic and invasive behavior of skin squamous cell carcinoma (SCC) xenografts. MMP activity was measured in vivo in HaCaT-ras A-5RT3 tumors at different angiogenic and invasive stages (onset of angiogenesis, intermediate and highly angiogenic, invasive stage) and after 1 week of sunitinib treatment by fluorescence molecular tomography-microcomputed tomography imaging using an activatable probe. Treatment response was additionally assessed morphologically by optical coherence tomography (OCT). In vivo MMP activity significantly differed between the groups, revealing highest levels in the highly angiogenic, invasive tumors that were confirmed by immunohistochemistry. At the onset of angiogenesis with lowest MMP activity, fibroblasts were detected in the MMP-positive areas, whereas macrophages were absent. Accumulation of both cell types occurred in both invasive groups, again to a significantly higher degree at the most invasive and angiogenic stage. Sunitinib treatment significantly reduced the MMP activity and accumulation of fibroblasts and macrophages and blocked tumor invasion that was additionally visualized by OCT. Human cervical SCCs also showed high MMP activity and a similar stromal composition as the HaCaT xenografts, whereas normal tissue was negative. This study strongly suggests MMP activity as imaging biomarker and demonstrates the high sensitivity of optical tomography in determining tumor invasiveness that can morphologically be supported by OCT., (Copyright © 2014 Neoplasia Press Inc. Published by Elsevier Inc. All rights reserved.)

Results of molecular pathology have supported changes in the 2004 WHO classification of urothelial cancer. Since then new molecular data such as the distribution pattern of the fibroblast growth factor receptor 3 (FGFR3) has further supported the principle of low and high grade entities of urothelial carcinoma. Animal experiments with knockout mice and conditional knockout systems reveal important parallels to humans and results emphasize the cellular context as a trigger for malignancy. One special feature of the urothelium is its high protection of the urothelial cells by members of the retinoblastoma gene family, efficiently inhibiting invasion even in the presence of p53 mutations. In search of the tumor stem cell phenotype the basal cell phenotype is the focus of attention providing a high clonogenic potential. At the same time detailed analysis of the distribution of mutations in the mitochondrial genome within the urothelium will help to gain insight into the spreading of normal cell or tumor cell clones. The overall data in urological oncology provide evidence that diagnostic and prognostic tools for urothelial cancer can only be reached with multiparametric approaches.

Purpose: To report on our recent experience with peri- and postoperative morbidity of radical cystectomy in patients 75 years and older compared to younger patients., Patients and Methods: Medical records of 326 consecutive patients undergoing radical cystectomy from May 2004 through April 2008 were reviewed., Results: Eighty-five of 326 patients (26%) were > or =75 years (75-95) old. ASA score was equal 3 or greater in 51% of patients > or =75 years and 32% of patients <75 years. Ileal conduit was performed in 83% of patients > or =75, 16% received an ileal neobladder compared to 46 and 51%, respectively, in patients <75. A total of 33 patients (39%) in the older patient group received blood transfusions intraoperatively compared to 76 patients (32%) in the younger age group. In 6 patients > or =75 years (7.1%) and 17 patients <75 (7.1%) open surgical revision was necessary, perioperative complication rate was 22 and 21%, respectively. The most common complications were wound dehiscence (5.9 vs. 7.5%), infections (4.7 vs. 4.6%), and pulmonary embolism (3.5 vs. 2.1%). Perioperative mortality was 1.2% (1 patient) in the elderly versus 0.4% (1 patient) in the younger age group., Conclusion: Our data show that radical cystectomy can be offered to the elderly patient with acceptable morbidity. Because of higher comorbidity rate in the elderly, therapeutic decision for radical cystectomy in elderly patients should be made carefully and individually. Nevertheless our results demonstrate that age itself is not a main criterion which has to be considered strongly in decision making for radical cystectomy.

Background: Surgical margin status after radical prostatectomy (RP) is a significant risk factor for tumour recurrence. It is an intriguing concept to find a fluorescence marker for photodynamic diagnosis (PDD) to make tumour margins visible during surgery., Objective: To investigate the feasibility of identification of positive surgical margins (PSM) during open retropubic or endoscopic extraperitoneal RP by 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) to enhance surgical radicality., Design, Setting, and Participants: Thirty-nine patients (Gleason score 6-10, prostate-specific antigen [PSA] 2.3-120 ng/ml) received 20 mg/kg of body weight of 5-ALA orally and underwent RP (24 endoscopic extraperitoneal, 15 open retropubic)., Measurements: A PDD-suitable laparoscopy optic (Karl-Storz GmbH, Tuttlingen, Germany) with a yellow long-pass filter was coupled to a fibre-optic light cord with an excitation light source (380-420 nm, D-Light, Karl-Storz GmbH, Tuttlingen, Germany) for fluorescence excitation of PpIX and to a PDD-suitable camera for video and photo documentation by the AIDA DVD system (Karl-Storz GmbH, Tuttlingen, Germany)., Results and Limitations: There were more false-negative cases in the open group (four vs two) than in the endoscopic group but more false-positive cases in the endoscopic group (two vs none) than in the open group. The overall sensitivity and specificity were 56% and 91.6%, respectively. The sensitivity of the endoscopic cases was much higher (75% vs 38%) than for the open cases, while the specificity was higher for the open group (88.2% vs 100%)., Conclusions: PDD with 5-ALA-induced PpIX during RP might be a feasible and effective method for reducing the rate of PSM. The technique seems to be more practicable during endoscopic RP rather than open RP. Further clinical studies with higher patient volumes and further development of the technique seem justified., Trial Registration: EudraCT: 2005-004406-93.

In order to evaluate the molecular heterogeneity of prostate cancer, this study examined the expression of Akt-pathway related parameters within the cancerous prostate gland. PTEN, p-Akt and p27kip1 are known to be altered in prostate cancer. Tissue samples from malignant, tumor adjacent benign and benign areas of 25 whole mounted prostate cancer specimens were processed to 583 tissue microarray cores. Immunohistochemically determined biomarker expression was correlated to the different localizations. p-Akt and p27kip1 showed increased staining in malignant tissue compared to the respective benign tissue (p < 0.01 and p < 0.05). The adjacent but histologically benign tissue had increased levels (p < 0.05 and p < 0.01), whereas no significant difference was found between the adjacent and malignant regions. A highly significant correlation of p-Akt and p27kip1 in benign tissue (p < 0.001) was lost in the adjacent areas and in the malignant tissue (p = 0.054 and p = 0.12). In tendency, PTEN expression was decreased in the malignant regions and revealed the highest staining in the adjacent zone. According to the results obtained, the expression of p-Akt and p27kip1 was increased in both the adjacent microscopically benign tissue as well as the primary tumors when compared with the histologically benign tissue specimens that served as biological control. The increased expression of PTEN indicates its regulatory function in the initial steps of a deteriorated cell cycle control as well as uncontrolled cellular proliferation, for example, which seem to be present in the normal prostatic tissue surrounding the primary malignant lesion. The addition of molecular markers to a 'classical' histopathological approach might contribute to an enhanced sensitivity of analytical approaches aimed at the detection of malignant or premalignant lesions within prostatic biopsies.

Increasing knowledge in molecular genetic research on urinary bladder carcinoma has allowed us to classify the morphological picture on the basis of a better understanding. But this new knowledge will only be ground-breaking if it can be correlated with the clinical outcome of urinary bladder tumours and with histopathological findings. The use of the new 2004 WHO classification results in a standardized diagnosis of urothelial tumours by means of an exact definition of the subgroups. In the future, trials can thus be compared worldwide and risk profiles can be stratified. Further research in molecular genetics and correlation with the current classification together with molecular biological techniques may allow refinement of this scheme, e.g. by immunohistochemical subclassifications, enabling identification of potentially genetically unstable tumours. In this paper we present the new 2004 WHO classification of urinary bladder tumours emphasizing the changes in relation to the former classifications focusing on histological typing, grading and molecular characterization. Until the new classification is finally validated, and those working in the field have become familiar with it, the WHO classification of 1973 should be mentioned additionally in the histopathological report.

Background and Aims: Depending on their physico-chemical characteristics, bile acids can be potent inducers of apoptosis in colon cancer cells. This observation contrasts with bile acids being promoters of colorectal cancer carcinogenesis. Our recent observation of caspase activation in deoxycholate (DC)-treated colon cancer cell lines prompted us to analyze the mechanisms of bile acid-induced colon cancer cell death., Methods: CD95 expression was correlated to DC-induced cell death in four colon cancer cell lines. Mitochondrial transmembrane potential (MTP) was determined in whole cells as well as in isolated mitochondria., Results: On 2 of the 4 human colon cancer cell lines investigated, no CD95 was detected. These data were supported by a lack of CD95 mRNA in those cell lines that did not express CD95 on their surface. The apoptotic response to bile acids did not correlate with CD95 receptor expression on the respective cell lines. Therefore, we analyzed the MTP after the addition of toxic bile acids. MTP was destabilized early after the addition of deoxycholate to SW480 cells. These data were confirmed in isolated mitochondria, which showed strong swelling after the addition of DC. Accordingly, release of cytochrome-c from the mitochondrial intermembrane space into the cytosol, indicating dissipation of the MTP, and subsequent caspase-3 cleavage were detectable as early as 3 min after the addition of DC., Conclusion: In contrast to hepatocytes and hepatic carcinoma cell lines, DC induces apoptosis in colon cancer cell lines via a CD95 receptor-independent mechanism. Direct induction of the mitochondrial permeability transition by toxic bile acids is suggested as the apoptosis-inducing mechanism in colon cancer cells.

Aim: We determine the efficacy of unilateral nerve-sparing radical perineal prostatectomy in preserving the sexual function., Patients and Methods: Ninety-two patients with histologically confirmed unilateral prostate cancer were scheduled for contralateral nerve preservation. The perioperative morbidity was assessed using the patients' chart reviews. Postoperative health-related quality of life, urinary continence, and potency were evaluated prospectively with questionnaires provided before surgery and then after 6, 12, and 24 months., Results: Unilateral nerve preservation was performed in 88 of the 92 patients. Due to extensive scarring or prostatic size, the procedure was terminated as regular radical prostatectomy in 4 other patients. The perioperative complication rate was low and of minor significance, except in 1 patient who experienced a significant myoglobulinuria due to a prolonged procedure. Blood transfusions were necessary in 5 (5.4%) patients. Ureteral reimplantation was performed in 1 patient because of ureteral stricture. Positive surgical margins were present in 12 (18%) of 67 pT2 patients and in 8 (35%) of 23 pT3 patients. A proportion of 48% (15/31) of the patients followed for more than 24 months and who had a good erectile function prior to surgery reported unassisted sexual intercourse. However, only 4 of these patients were completely satisfied with all aspects of sexual performance, as asked in a short version of the International Index of Erectile Function questionnaire., Conclusions: Unilateral nerve-sparing radical perineal prostatectomy is technically feasible and yields excellent results in terms of potency preservation for prostates <60 ml. However, the quality of erections is decreased, even in patients with erections sufficient for intercourse. Hence, appropriate sexual counseling in conjunction with medical therapy should be offered to all patients., (Copyright 2005 S. Karger AG, Basel)

We present a 2-year-old boy with a red, cutaneous-subcutaneous, nodule on the right elbow and a 2.5 year-old girl with an red-brown, indurated plaque on the left knee. Colour-coded doppler sonography of the boy's lesion showed vascular structures. A biopsy established the diagnosis of tufted angioma in both patients. Tufted angioma is clinically characterized by slowly spreading erythematous macules and plaques preferentially located on the upper trunk and neck in children. It is a benign tumor, malignant transformation has not been reported. The case history, clinical and histological findings contribute to the diagnosis. Tufted angioma has to be distinguished from Kaposi's sarcoma, angiosarcoma, hemangioma of infancy, sometimes bacillary angiomatosis and other cutaneous capillary malformations. Treatment of tufted angioma is difficult, various modalities like glucocorticosteroids, Interferon-alpha, flashlamp-pumped pulsed dye laser, excision and spontaneous regression have been described with varying results.

Intraoperative autotransfusion is contraindicated in tumor surgery because of the danger of tumor cell dissemination. We have tested the elimination of tumor cells in blood by irradiation for safe retransfusion. Tumor cells of various origin were mixed to washed red blood cells from volunteer blood donations. The blood was irradiated with 50 Gy. After isolation of the tumor cells by density gradient centrifugation they were tested for colony formation. While with different tumor cell lines (n = 12) 10 cells were sufficient to yield several colonies, as many as 10(10) cells did not result in any colony after irradiation of the blood. Similar results were obtained with cells cultured from blood salvaged during tumor surgery (n = 3), and with tumor cells prepared from various carcinomas (n = 10). Flow cytometric DNA analysis showed the irradiated cells in mitotic arrest. None of these cells had residual DNA metabolism expressed as incorporation of BrdUrd. We were able to demonstrate a rate of reduction in dividing cells of up to 10(9). With the typical irradiation sensitivity of tumor cells, with D0 values between 1 and 2 Gy, a dose of 50 Gy results in an effective log 12 reduction, sufficient for safe elimination of tumor cells found in shed blood. No adverse effects of the gamma-irradiation on the blood cells are to be expected, especially since the blood is retransfused without storage.