Urologic Oncology: Seminars and Original Investigations

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2012-05-01

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Masthead

2012-05-01

Editorial Board

2012-05-01

The Oncology Knowledge Assessment Test

Steven C. Campbell, Michael S. Cookson — 2012-03-16

In 2006, the leadership of the Society of Urologic Oncology (SUO) decided to pursue construction of an examination for its members to provide them with a tool that would allow for self-assessment with regards to their fund of knowledge in the field of urologic oncology. Under the SUO leadership, a small committee worked with the American Urologic Association/American Board of Urology (AUA/ABU) Examination Committee to construct a written examination in a format similar to an In-Service Examination. This test became known as the Oncology Knowledge Assessment Test (OKAT), and is currently administered annually for fellows in training and SUO members. It now serves as a valuable resource for all active surgeons and allied physicians in the field. Given the ongoing changes in the evaluation and management of urologic cancers and a research base that is continually adding to our understanding of the pathophysiology of these malignancies, keeping up to date with this knowledge base remains a challenge. The OKAT allows individuals to assess their progress relative to their peers, and provides feedback with respect to performance in each of the major content areas on the examination. As such, the OKAT represents an important resource for self-assessment and practice-based learning for SUO members and their trainees.

Update on the Society of Urologic Oncology fellowship programs

Jeffrey M. Holzbeierlein — 2012-03-16

The Society of Urologic Oncology Fellowship Programs officially began in 2001 and has now expanded to over 31 programs in the USA and Canada. The Match process was initiated in 2009 and has been very successful. There are 68 active fellows in the USA and Canada, and it is the most competitive fellowship in Urology. Future initiatives include exploring Accreditation Council for Graduate Medical Education (ACGME) accreditation of Fellowship Programs, integration of the Electronic Residency Application Service (ERAS) application for the Match application process, and the requirement of the Oncology Knowledge Assessment Test (OKAT) annually for each fellow and program director. In this brief update, we consider the history and development of the Society for Urologic Oncology (SUO) Fellowship Program and report on new initiatives.

The Outreach Committee of the Society of Urologic Oncology (SUO): Advancing the patient mission

Cheryl T. Lee — 2012-05-01

The Outreach Committee is an exploratory committee of the Society of Urologic Oncology (SUO) formed in 2010 to help advance the organization's mission as it relates to patient care. The committee aims to improve the management of patients with urologic malignancies by developing content-appropriate educational materials, advocating for greater patient resources and by establishing disease-specific survivorship programs that will ensure appropriate aftercare, surveillance, and attention to treatment-related impairments.

An update on targeted therapy in metastatic renal cell carcinoma

2010-04-26

Abstract: An improved understanding of the biological pathways deregulated in renal cell carcinoma has led to the development of various targeted agents, changing dramatically the therapeutic options for this disease. However, despite numerous opinions and guidelines, the optimal treatment still remains uncertain. In this review, we analyze the most recent published reports regarding the agents sunitinib, bevacizumab, sorafenib, temsirolimus, and everolimus. Moreover, we assess the novel targeted drugs pazopanib and axitinib. In addition, given the likely lack of cross-resistance between these targeting agents, we discuss sequential and combination targeted therapy in metastatic renal cell carcinoma, analyzing the most recent data.

Discrepancy between clinical staging through bimanual palpation and pathological staging after cystectomy

2010-05-10

Abstract: Objectives: In muscle invasive bladder cancer (MIBC), careful clinical staging is essential for patient counseling and decision-making. Bimanual palpation (BP) is an integral part and guideline advice of clinical staging. Until now, however, the value of BP has never been studied. With this study, we aim to determine the accuracy of clinical staging through BP. Methods: Detailed clinical data were collected from a population-based series of 1,409 patients with MIBC, diagnosed between 1989 and 2005, in the region of the Comprehensive Cancer Centre East in The Netherlands. Selected were all patients who underwent BP (n = 738). Preoperative tumor-stage (cT-stage) determined through BP was compared with post-cystectomy pT-stage. Contingency tables were made to determine the correlation between cT-stage and pT-stage. Results: In 18 of 142 patients in whom BP showed an organ-confined tumor, the tumor was unresectable (pT4) at the time of surgery. Four out of 9 patients who had a suspected T4 tumor on BP but who underwent cystectomy anyway appeared to have operable tumors at cystectomy. In 87 patients (57.6%), accurate staging through BP was observed. In 17 patients (11.3%), clinical overstaging was found, and in 47 patients, (31.1%) clinical understaging. Conclusions: Frequently, pT-stage after cystectomy does not correlate with preoperative cT-stage based on BP. Discrepancy was observed in 42% of the patients: in 11%, clinical overstaging and in 31%, clinical understaging. Based on these data, some caution is suggested when interpreting the outcome of BP. Prospective data is needed for a more formal evaluation of the staging accuracy of BP.

Concomitant carcinoma in situ is a feature of aggressive disease in patients with organ confined urothelial carcinoma following radical nephroureterectomy

2010-05-10

Abstract: Objective: Carcinoma in situ (CIS) is associated with increased risk of progression when found with high-grade non-muscle-invasive bladder cancer, yet its impact is less clear in the upper urinary tract. In the current study, we evaluated the impact of concomitant CIS on recurrence-free survival and cancer-specific survival following radical nephroureterectomy for upper tract urothelial carcinoma (UTUC). Materials and methods: A multi-institutional retrospective cohort of 1,387 patients undergoing radical nephroureterectomy was identified. Concomitant CIS was defined as the presence of CIS in association with another pathologic stage; patients with CIS alone were excluded from the analysis. The presence of concomitant CIS served as the exposure variable with disease recurrence and cancer-specific mortality as the outcomes. Organ-confined disease was defined as AJCC/UICC stage II or lower. Results: Concomitant CIS was identified in 371 of 1,387 (26.7%) patients and was significantly more common in patients with a previous bladder cancer history, high grade, and high stage tumors. In a multivariable analysis, concomitant CIS was a predictor of disease recurrence (HR = 1.25, P = 0.04) and cancer specific mortality (HR = 1.34, P = 0.05) for patients with organ-confined UTUC, but not in the entire cohort. Other prognostic variables, such as grade, stage, lymphovascular invasion, and lymph node status, were associated with poorer overall and recurrence-free survival for all patients. Conclusion: The presence of concomitant CIS in patients with organ-confined UTUC is associated with a higher risk of recurrent disease and cancer-specific mortality. This information may be useful in refining surveillance protocols and in more appropriate selection of patients for adjuvant chemotherapy.

Results of long-term follow-up of patients with superficial bladder carcinoma treated with intravesically applied bacillus Calmette-Guerin vaccine according to the schedule of 6 weekly + 6 monthly instillations

Davor Librenjak, Marijan Šitum, Eduard Vrdoljak, Kazimir Milostić, Josip Gotovac — 2010-09-15

Abstract: Background: The efficacy of bacillus Calmette-Guerin (BCG) immunotherapy in the prevention of local recurrence and disease progression in patients with superficial bladder cancer is very well documented. This study reports the effect of BCG on disease-specific and overall survival. Patients and methods: In this retrospective trial, we have analyzed 170 patients with stage Ta and T1 superficial bladder cancer. Patients in the control group (87 patients) we followed-up only (median follow-up of 119 months) and treated surgically or with other oncologic modalities when progression of disease was diagnosed. The BCG group consisted of 83 patients treated with 6 weekly followed by 6 monthly instillations, and they have been followed-up of median 124 months. Results: Patients receiving BCG had statistically significant better 10-year disease specific survival (83% vs. 69%, P = 0.03). At the same time point, the local recurrence rate was 48 % and the progression rate 19% for patients treated with BCG, while 77% (P < 0.001) and 38% (P = 0.007) were results in control group. Despite numerically better in the BCG group, overall survival is not significantly different in the 2 groups (P = 0.14). Conclusion: BCG immunotherapy significantly increases the disease-specific survival in patients with superficial bladder carcinoma.

Upper tract urothelial carcinoma: Impact of time to surgery

2010-09-28

Abstract: Objective: Patients diagnosed with upper tract urothelial carcinoma (UTUC) sometimes experience a delay from diagnosis to extirpative surgery (nephroureterectomy or ureterectomy) as a result of attempted endoscopic management and/or neoadjuvant chemotherapy. The purpose of this analysis is to examine the impact of such delay on survival outcomes. Methods: An IRB-approved retrospective review identified consecutive patients undergoing extirpative surgery for UTUC treated at a single institution between 1990 and 2007. 240 patients with non-metastatic disease represented both primarily-presenting and referred patients. Patients in the “early” surgery group underwent extirpative surgery <3 months after diagnosis and patients in the “delayed” surgery group underwent surgery ≥3 months after diagnosis. Timing to surgery was at the discretion of individual patient-surgeon decision-making. Analyses and measurements were univariate and multivariate models correlating death from disease with clinico-pathologic parameters, recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) in the “early” and “delayed” surgery groups. Results: 186 patients underwent early surgery and 54 patients underwent delayed surgery. Median follow-up for all patients was 29 months. The 5-year CSS were 72% and 71% for the early versus late groups, respectively (P = 0.39) and corresponding 5-year OS rates were 60% and 69%, respectively (P = 0.69). Delay in surgery was not associated with a worse outcome, even following adjustment for potential confounders. The most common factor contributing to delayed surgery in our cohort was administration of neoadjuvant chemotherapy (50%), which did not impact survival. Limitations included a median follow-up of 19 months in the neoadjuvant group; and the requirement to analytically group pathologic high-stage and low-stage disease, which reflects challenges inherent to current clinical staging. Conclusions: Our results show no difference in survival between patients undergoing early versus delayed extirpative surgery for UTUC, suggesting the feasibility of delayed surgery in appropriately selected patients. Only prospective validation of delayed surgery can guarantee its safety.

Role of fluorescence in situ hybridization in bladder cancer surveillance of patients with negative cytology

2010-05-10

Abstract: Objectives: The clinical utility of urine markers in urothelial cancer (UC) surveillance is not established. We previously evaluated the use of fluorescence in situ hybridization (FISH) in managing patients with atypical cytology at risk for UC. This study evaluates its role in patients with negative cytology with a history of UC. Materials and methods: Between June 2007 and January 2009, every patient with a history of UC who underwent cystoscopy and cytology with UroVysion test were identified. A comprehensive chart review was performed on each patient with negative cytology. Results: The population comprised 142 patients undergoing cancer surveillance; 111 patients with negative cystoscopy, 19 with equivocal cystoscopy, and 12 with positive cystoscopy. In patients with negative cystoscopy, there was cancer in only 1 of 111 patients. UroVysion could detect the only patient with UC with sensitivity of 100% and had a negative predictive value (NPV) of 100%. In patients with equivocal cystoscopy, it detected 2 tumors that would be missed by cytology. There were 4 false negative results (sensitivity 33.3% and NPV 66.7%). In patients with obvious lesion on cystoscopy, there were 9 false negative results (sensitivity 10% and NPV 18.2%). Conclusions: Few patients with negative cystoscopy and negative cytology have cancer. Patients with equivocal and positive cystoscopy and negative cytology frequently have cancer and the UroVysion FISH assay was not helpful in these cases. The cost-effectiveness of the FISH assay needs to be assessed prior to widespread use in patients with negative cytology.

Splicing variants of carbonic anhydrase IX in bladder cancer and urine sediments

2010-09-28

Abstract: Objective: In human cancers, carbonic anhydrase IX (CAIX) influences cell proliferation and tumor progression, maintaining intracellular and extracellular pH under hypoxic conditions. An alternative CAIX isoform, lacking of exons 8–9 (AS) and independent from the levels of hypoxia, was recently demonstrated in cancer cells. AS-CAIX competes with the full-length (FL) isoform in the regulation of the extracellular pH, mainly in a mild hypoxic status. In the present study, we evaluated mRNA expression of the 2 CAIX isoforms and their clinical relevance in bladder cancers and urine sediments. Materials and methods: We measured mRNA expression of FL- and AS-CAIX isoforms in tumor tissues and benign mucosa from 45 patients with bladder transitional cell carcinoma. The expression of the 2 isoforms was also measured in urine sediment of 81 bladder cancer patients and 93 control subjects. Results: Expression of FL-CAIX mRNA was lower than AS-CAIX in benign mucosa (P = 0.006) whereas in paired bladder cancers FL-CAIX mRNA was higher (P = 0.007). Consequently, the percentage of FL-CAIX in bladder cancers [median: 62.6%] was significantly higher than in benign mucosa [15.0%] (P < 0.0001). In the urinary sediments of bladder cancer patients FL-CAIX mRNA was significantly higher in comparison with normal controls (P = 0.003). FL-CAIX percentage appeared dramatically higher in urine sediments of bladder cancer patients [64.5%] in comparison with controls [7.5%] (P < 0.0001). In addition, FL-CAIX% was significantly different in sediments from pTa-pT1 and ≥pT2 patients [51.5% and 91.7%, respectively] (P = 0.016). Stratification according tumor grade indicated that FL-CAIX% was significantly lower in G1 bladder cancers [33.3%] in comparison with G2-G3 [88.6%] (P = 0.005) The clinical sensitivity for FL-CAIX% in urine sediments was 0.93, with a 0.76 specificity. Using the same cut-off positive predictive value (PPV) was 0.78, whereas negative predictive value (NPV) was 0.93. Conclusions: Our results seem to indicate that in bladder cancers and related urine sediments, FL-CAIX is the prevalent and is the most accurate clinically relevant variant surrogate of hypoxic stress.

Fluorescence and white light cystoscopy for detection of carcinoma in situ of the urinary bladder

Seth P. Lerner, Hao Liu, Meng-Fen Wu, Yngvil K. Thomas, J. Alfred Witjes — 2011-03-14

Abstract: Objectives: To understand the additional benefits of HAL compared with conventional cystoscopy at the patient level and to explore relationships of urine cytology and CIS. Methods: We reanalyzed pooled data from 3 phase III studies comparing hexaminolevulinate (HAL, Hexvix) fluorescence cystoscopy with white light (WL) cystoscopy for detecting CIS. Results: Of 551 patients, 174 had at least one CIS lesion detected by HAL, WL, or random biopsy. The CIS detection rate of HAL was 0.87 vs. 0.75 for WL (P = 0.006). By multivariate Poisson regression, female patients had fewer CIS lesions (P < 0.0001) while older patients (≥65) had a higher number of CIS lesions detected by HAL (P = 0.04). HAL was less likely to detect CIS in patients previously treated with chemotherapy or BCG (P = 0.01 and 0.03, respectively), after adjusting for age. CIS was unifocal in 44% and multifocal in 56%. Multifocal CIS was associated with positive cytology more frequently than unifocal (65% vs. 45%; P = 0.016) whereas a negative cytology was more frequently associated with unifocal CIS. Patients with positive urine cytology had twice as many CIS lesions detected by HAL as patients with negative urine cytology (P = 0.02). Conclusions: HAL cystoscopy had a higher CIS detection rate than WL cystoscopy. The average number of CIS lesions detected was associated with baseline clinical characteristics. Cytology was positive more frequently in multifocal CIS suggesting that HAL may be particularly useful in this setting to optimize detection of the extent of CIS.

Feasibility and effects of high-dose hypofractionated radiation therapy and simultaneous multi-kinase inhibition with sunitinib in progressive metastatic renal cell cancer

2010-09-02

Abstract: Objectives: Radiotherapy (RT) is considered oncologically ineffective in metastatic renal cell cancer (mRCC). Inhibition of angiogenetic pathway may lead to radiosensitization in mRCC. The aim of this study was to evaluate the efficacy of the simultaneous combination of RT with systemic treatment of bulky (mRCC) using sunitinib. Methods and materials: We included 22 patients with progressive mRCC between 04/2007 and 08/2008 at the University Hospital Munich Großhadern. All patients underwent high-dose hypofractionated RT while they were simultaneously treated systemically with sunitinib 50 mg. Results: Median age was 63.0 years (range 26.7–84.4). Median dose of radiation was 40 Gy (range 25–50) in a median of 8 fractions (range 5–30). Treatment sites were brain, retroperitoneal and mediastinal lymph nodes, spinal cord, bones, liver, and kidney. Median follow-up was 14.3 months. After 3 months, 2 patients had complete remission (CR), 9 patients showed partial remission (PR) as measured by response evaluation criteria in solid tumors (RECIST) criteria, 2 patients had minor response (MR), and 8 patients had stable disease (SD). Only 1 patient did not respond to therapy. Toxicity was very low with only 1 grade 4 hypertension. Skin toxicities were manageable with no grade 3 event during the combination period. Conclusions: The combination of RT with simultaneous systemic treatment using sunitinib is effective in patients with progressive mRCC. With high dose RT, complete response seems to be possible. Further evaluation should be based upon combination of RT with systemic therapy, rather than sequential RT regiments.

Clinical features and prognosis of patients with renal cancer and a second malignancy

2010-09-15

Abstract: Objective: To evaluate the epidemiologic aspects, the clinical features, and the prognosis of patients with renal cancer affected by a second malignancy. Materials and methods: Since 1983, at our institution, a database concerning all the patients who underwent surgery for renal neoplasia has been prospectively compiled. In the present study, we compared patients with renal cancer and a second primary malignancy, diagnosed before, at the same time, or after the renal cancer, to those affected only by a renal malignancy. Results: Out of 1,673 patients with renal cancer, 285 (17%) were diagnosed with a second malignancy. The follow-up lasted on average 71 months after the treatment of renal neoplasia. The second neoplasia was antecedent in 115 patients (average latency period 8.5 years), synchronous in 97 patients, and subsequent in 103 patients (average latency period 4.4 years). The sites of associated neoplasia were, in descending order of frequency, prostate, bladder, and bowel for men and breast, gynecologic organs, thyroid, and bladder for women. Compared with the patients not affected by a second neoplasm, those with multiple malignancies generally were older and had a smaller, low-grade, low-stage, and asymptomatic renal tumor. Comparing patients with associated neoplasia with a group without associated neoplasia matched for gender, mode of diagnosis, dimension, grade, stage, and histologic subtype of renal cancer, at survival analysis, no significant differences were noticed in renal cancer-related survival. However, among patients with multiple malignancies, the contemporaneous diagnosis of renal and associated cancer had an independent negative impact on survival. Conclusions: The association between renal cancer and other malignancies is a frequent event with an unremarkable impact on prognosis, and it shall not limit surgical indication to treat renal cancer, even if the negative prognostic impact of synchronous occurrence of multiple neoplasias should be regarded, especially in older or unhealthy patients, since ablative therapies or active surveillance could be considered as viable alternative options.

Endorectal T2-weighted MRI does not differentiate between favorable and adverse pathologic features in men with prostate cancer who would qualify for active surveillance

2011-08-19

Abstract: Objective: With the increased diagnosis of low grade, low volume, potentially non-lethal disease, active surveillance (AS) has become an increasingly popular alternative for select men with low-risk prostate cancer. The absence of precise clinical staging modalities currently makes it difficult to predict which patients are most appropriate for AS. The goal of our study was to evaluate the ability of endorectal MRI (eMRI) to predict adverse pathologic features in patients who would otherwise qualify for an AS program. Materials and methods: We retrospectively reviewed our institution's radical prostatectomy (RP) database from 1991 to 2007 and identified 172 patients who would have qualified for AS and underwent preoperative staging eMRI with T2-weighted (T2W) sequences. MRI findings were correlated to final pathology in order to assess the ability of staging eMRI to predict adverse pathologic features in patients suitable for AS. Results: The mean age of our cohort was 59.8 ± 6.2 years. The mean PSA at the time of diagnosis was 5.2 ± 2.2 ng/ml. In 51% of patients, no discrete tumor was visualized on eMRI and in 49% of patients a discrete tumor was detected. At the time of RP, Gleason score upgrading, extracapsular extension, and a positive surgical margin occurred in 17%, 6%, and 5% of cases, respectively. Patients with documented tumor on eMRI did not have an increased incidence of adverse pathologic findings with regard to tumor volume (P = 0.31), extra-capsular extension (P = 0.82), Gleason upgrading (P = 0.92), seminal vesicle invasion (P = 0.97), or positive surgical margin rate (P = 0.95) compared with those in whom no tumor was seen. Conclusion: Discrete tumor identification on eMRI is not predictive of adverse pathologic features in patients who would otherwise qualify for AS. eMRI likely does not provide additional information when prospectively evaluating patients for AS protocols.

High matrix metalloproteinase-to-E-cadherin ratio measured by bicolor fluorescent in situ hybridization is associated with lymphangiogenesis and lymph node metastasis in prostate cancer

2010-09-15

Abstract: Objective: The colorimetric in situ hybridization (CISH)-based matrix metalloproteinase (MMP)-to-E-cadherin (ECD) ratio (MER) has been revealed as an excellent marker for the disease stage in prostate cancer. The one aim of this study was investigating a new method for estimation of MER by bicolor fluorescent ISH (bicolor FISH) with a computerized fluorescence detector-based system. Another aim was examination of relation of MER by bicolor FISH with expression of vascular endothelial growth factor-C (VEGF-C). Methods: The bicolor FISH technique used cyanin 5 (cy5)-labeled MMP-2 and −9 probes, and a cyanin 3 (cy3)-labeled ECD probe on needle biopsy specimens from 67 prostate cancer cases. The ISH was followed by computerized detection of the signal intensities and cy5-to-cy3 ratios using a fluorescence detector. VEGF-C expression was examined using cy5-labeled VEGF-C by computerized detection. Results: The bicolor FISH-based MER was well correlated with CISH-based MER (P < 0.0001). The bicolor FISH-based MER correlated with Gleason score and pathologic stage of the cases. VEGF-C mRNA expression was associated with the pathologic stage and maximum lymph vessel density (LVD). The LVD was associated with VEGF-C expression at the tumor area where the maximum MER was detected (P < 0.0001). Conclusion: The MER was correlated with the VEGF-C expression and LVD, indicating lymph node metastasis of prostate cancer. Therefore, this computer-assisted MER is a useful marker for preoperative prediction of disease stage, especially lymph node metastasis, of prostate cancer.

Effective enrichment of prostate cancer stem cells from spheres in a suspension culture system

Xinlan Fan, Shanying Liu, Fang Su, Qiuhui Pan, Tianxin Lin — 2010-09-15

Abstract: Background: Stem-like prostate cancer cells are also called prostate cancer stem cells (PrCSCs). These rare cells are supposed to be highly tumorigenic and to be involved in maintenance of tumor homeostasis and mediation of tumor metastasis. Methods for sorting PrCSCs are mainly based on sorting cells with the marker (CD133+/CD44+) or side population cells. However, CD133+/CD44+ cells or side population cells are very rare or even undetectable. The scarcity of approaches for isolation and purification of PrCSCs is the main obstacle to studying PrCSCs. Methods: In the present study, suspension culture was used for enrichment of PrCSCs. And PrCSCs were verified by side population technology, drug sensitivity assays, and the molecular marker analysis of prostate cancer stem cell. Results: PC3 cells survived and formed spheres in nonadherent suspension culture. The percentage of CD44+/CD133+ cells was 18-fold higher in the nonadherent sphere-forming cell population than in the adherent PC3 cell population (13.94% vs. 0.77%, respectively). This side population was increased to 3.1% in the nonadherent population but undetectable in adherent population. Resistance to cisplatin was higher in the nonadherent cells than adherent cells. Conclusion: Suspension culture can be used to enrich for PrCSCs. This approach will aid prostate stem cell biology research and facilitate identification of novel therapeutic agents for prostate cancer.

The incidence and management of metachronous testicular germ cell tumors in patients with extragonadal germ cell tumors

2010-05-17

Abstract: Objectives: The optimal management of extragonadal germ cell tumor (EGGCT) and metachronous testicular germ cell tumor (MTGCT) has not been determined. Patients and methods: Fifty-one consecutive patients with EGGCT were identified. Testicular palpation or ultrasonography to rule out a primary testicular tumor was performed. Pretreatment testicular biopsies were not performed. The incidence and outcome of MTGCT, and the prognosis of EGGCT were evaluated. Results: Twenty-five and 26 patients, respectively, had mediastinal and retroperitoneal EGGCT. Fourteen and 37 patients, respectively, had seminoma and nonseminoma. Five patients developed MTGCT in patients with retroperitoneal EGGCT. The median interval from the primary treatment for EGGCT to MTGCT diagnosis was 64 months (range 15–120). The cumulative risk of developing MTGCT was 8.3% at 6 y. Five patients underwent an orchiectomy and have survived in the 16-months median follow-up period (range 4–30). Among the patients with seminomatous and nonseminomatous EGGCT, the 5-year survival rate was 84.6% and 78.3%, respectively. Among the patients with retroperitoneal and mediastinal nonseminomatous EGGCT, the 5-year survival rate was 94.7% and 58.8%, respectively. Conclusions: The prognosis of EGGCT without testicular biopsies was sufficient. EGGCT patients, especially retroperitoneal EGGCT, need long-term follow-up for MTGCT.

Microvessel density as a prognostic factor in penile squamous cell carcinoma

2010-06-21

Abstract: Objective: To examine the potential effect of tumor-induced angiogenesis in squamous cell carcinoma of the penis as a possible prognostic factor. Patients and methods: Immunohistochemistry was preformed to detect microvessels in tumor samples of 64 patients with squamous cell carcinoma of the penis. We used a monoclonal mouse antibody directed against CD34 antigen. Only 61 (30 with and 31 without metastasis) patients had good staining properties and were included. After immunostaining, the entire tumor section was scanned microscopically at low power (×40) to identify hot spots within the tumor and at its periphery. Individual tumor microvessels were then counted under high power (×200) to obtain a vessel count in a defined area, and the mean of the 3 highest microvessel counts was taken as the microvessel density (MVD). Microvessel counting was performed using a computer-aided image analysis system. The nodal status was based on histopathologic examination or an uneventful follow-up ≥2 years. Results: The 5-year overall survival (OAS) was 75% and 30 % for those with high and low peritumoral MVD, respectively (log rank P = 0.01). No difference was noticed within the tumor with regard to high (5-year OAS of 65.03%) and low (5-year OAS of 60.56%) intratumoral MVD (log rank P = 0.99). The mean intratumoral MVD was 32.35 (3.16), 37.94 (3.35), and 62.66 (5.47) in T1, T2, and T3 respectively (ANOVA P = 0.0006), with increasing tendency. The mean peritumoral MVD was 55.91 (5.60), 56.8 (4.00), and 78.86 (8.71), respectively (P = 0.06). No correlation between MVD lymph node status and tumor grade was seen (P > 0.05). Conclusion: In our group of patients, a high peritumoral MVD was associated with a better 5-year OAS. However, for a reliable and reproducible assessment of tumor angiogenesis in penile squamous cell carcinoma, validation procedures and quality control protocols are mandatory.

Experimental orthotopic prostate tumor in nude mice: Techniques for local cell inoculation and three-dimensional ultrasound monitoring

2010-05-10

Abstract: Objectives: Orthotopic prostate cancer models are of great importance for cancer research. Orthotopic models in mice have been described previously. However, these studies lack a detailed methodological description and fail to define standards for local cell inoculation. Herein, we studied the effect of different protocols on tumor growth and report for the first time the use of high resolution ultrasound for monitoring of tumor growth. Materials and methods: Orthotopic inoculation of DU 145 MN1 prostate cancer cells was performed in 30 nude mice varying (1) the amount of cells (5 × 105 vs. 5 × 104), (2) the number of puncture sites, and (3) the addition of matrigel. Surgical complications such as recoil of cells through the injection canal and rupture of the prostatic capsule were monitored. Animals were tracked by ultrasound imaging after 4, 5, and 6 weeks. Autopsy and histology confirmed local tumor growth. Results: A take rate of 27/30 (90%) was observed. Growth of orthotopic prostate tumors was increased after inoculation of a large amount of cells under the capsule of 1 dorsal prostate lobe, but inoculation of small amounts of cells still induced local tumors. Noninvasive ultrasound examination allowed to identify orthotopic tumor formation and to monitor tumor growth in vivo. Addition of matrigel did not accelerate tumor growth. Complications like recoil (6.8%) or rupture of the prostate capsule (1.4%) were rare. Conclusions: Inoculation of DU 145 MN1 cells under the prostate capsule with a defined procedure results in very high take rates. Ultrasound screening is feasible to repetitively monitor tumor growth.

13-Methyltetradecanoic acid induces mitochondrial-mediated apoptosis in human bladder cancer cells

2010-09-15

Abstract: Objective: 13-Methyltetradecanoic acid (13-MTD), a saturated branched-chain fatty acid purified from soy fermentation products, is known to induce apoptosis in many types of human cancer cells. This study was designed to investigate the molecular mechanisms involved in 13-MTD-induced apoptosis in human bladder cancer cells. Methods and materials: MTT assay was used to investigate the potential effects of 13-MTD on the growth and viability of human bladder cancer cells. To find out whether anti-proliferation and cell death were associated with apoptosis, we used flow cytometry to quantify the extent of apoptosis and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay to measures DNA degradation of apoptotic cells. The proteins involved in the 13-MTD induced apoptosis were examined using Western blot. Results: We show that 13-MTD inhibits cellular proliferation and viability in human bladder cancer cells, which has been attributed to apoptosis. 13-MTD down-regulates Bcl-2 and up-regulates Bax. This promotes mitochondrial dysfunction, leading to the release of cytochrome c from the mitochondria to the cytoplasm, as well as the proteolytic activation of caspases. Moreover, 13-MTD down-regulates AKT phosphorylation and activates phosphorylation of p38 and c-Jun N-terminal kinase (JNK). Up-regulating AKT phosphorylation and down-regulating JNK and P38 phosphorylation could attenuate the13-MTD-induced apoptosis. Conclusion: Taken together, these data indicate that 13-MTD induces mitochondrial-mediated apoptosis through regulation of the AKT and MAPK pathways, suggesting 13-MTD is a potential candidate for treatment of human bladder cancer.

Survey Section Editorial Board

2012-05-01

Commentary on “70 Gy vs. 80 Gy in localized prostate cancer: 5-Year results of GETUG 06 randomized trial.” Beckendorf V, Guerif S, Le Prisé E, Cosset JM, Bougnoux A, Chauvet B, Salem N, Chapet O, Bourdain S, Bachaud JM, Maingon P, Hannoun-Levi JM, Malissard L, Simon JM, Pommier P, Hay M, Dubray B, Lagrange JL, Luporsi E, Bey P, Centre Alexis Vautrin, Vandoeuvre les Nancy, France: Int J Radiat Oncol Biol Phys 2011;80:1056–63