Radiotherapy for spermatic cord sarcoma.

OBJECTIVES: Spermatic cord sarcomas are rare paratesticular tumors affecting older men. Current management is based on small series, case reports, and literature reviews, with surgery still the mainstay of treatment. Local-regional recurrence is common after definitive surgery (~50%), but patients treated with adjuvant radiotherapy may have improved outcomes. METHODS: We reviewed the outcomes of 15 patients with intermediate-grade to high-grade spermatic cord sarcomas treated with radiation at our institution from 1974 to 2009. Patients were treated to 40 to 60 Gy using conformal opposed anterior-posterior/posterior-anterior ports to the scrotum, inguinal canal, and lower pelvic wall with various beam energies. Some patients were managed with surgical exploration and resection, followed by radiotherapy and/or definitive surgery. More recently treated patients had an initial biopsy, followed by preoperative radiation or planned resection with postoperative radiation therapy. RESULTS: No patient experienced a local recurrence. Two patients had regional nodal recurrences and 1 had distant metastases. All recurrences were in patients who had initial "exploration" with unexpected findings of sarcoma during surgery versus planned, definitive resection with planned adjuvant radiotherapy. At 5 years, overall survival was 53%, but cause-specific survival was 80%. Complications were minimal, with only 4 grade 2 or 3 toxicities and no grade 4 toxicities. CONCLUSIONS: Although most patients die from causes other than disease progression, this sarcoma carries grave morbidity. Optimizing the primary management is of utmost importance. Unplanned treatments complicate definitive therapy and increase the risk of local-regional contamination and recurrence. Proactive management is therefore consistent with sarcomas of other primary sites, ideally with preoperative radiotherapy and definitive resection.

Circulating and tumor-infiltrating myeloid cell subsets in patients with bladder cancer.

Both cancer-related inflammation and tumor-induced immune suppression are associated with expansion of myeloid cell subsets including myeloid-derived suppressor cells. However, little known regarding characteristics of myeloid cells in patients with bladder cancer. In this study, we analyzed myeloid cells from peripheral blood (PBMC) and tumor tissue that were collected from patients with superficial noninvasive and invasive urothelial carcinomas. Our results demonstrate that PBMC from bladder cancer patients contain two major CD11b myeloid cell subsets: granulocyte-type CD15(high) CD33(low) cells and monocyte-type CD15(low) CD33(high) cells. The number of circulating granulocytic but not monocytic myeloid cells in cancer patients was markedly increased when compared to healthy individuals. Both myeloid cell subsets from cancer patients were highly activated and produced substantial amounts of proinflammatory chemokines/cytokines including CCL2, CCL3, CCL4, G-CSF, IL-8 and IL-6. Granulocytic myeloid cells were able to inhibit in vitro T cell proliferation through induction of CD4(+) Foxp3(+) T regulatory cells. Analysis of bladder cancer tissues revealed that tumors were infiltrated with monocyte-macrophage CD11b(+) HLA-DR(+) and granulocytic CD11b(+) CD15(+) HLA-DR(-) myeloid cells. Collectively, this study identifies myeloid cell subsets in patients with bladder cancer. We demonstrate that these highly activated inflammatory myeloid cells represent a source of multiple chemokines/cytokines and may contribute to inflammation and immune dysfunction in bladder cancer.

Combination therapy for renal cell cancer: what are possible options?

Antiangiogenic therapy has shown promise in the treatment of patients with renal cell carcinoma (RCC). Two classes of antiangiogenic drugs, the anti-vascular endothelial growth factor antibody bevacizumab and the tyrosine kinase inhibitors sorafenib, sunitinib and pazopanib, have shown efficacy in patients with RCC and are approved by the US Food and Drug Administration for treatment of this cancer. In practice, the clinical benefit of antiangiogenic drugs in RCC has been heterogeneous, and in patients who do respond, benefits are modest and/or short-lived. To improve efficacy, combination targeted therapy has been attempted, but with either very limited additional efficacy or nontolerable toxicities. Recent advances in the molecular understanding of tumor angiogenesis and mechanism of resistance, along with the rapid development of targeted drug discovery, have made it possible to further explore novel combination therapy for RCC.

Tumor-associated macrophages mediate immunosuppression in the renal cancer microenvironment by activating the 15-lipoxygenase-2 pathway.

Renal cell carcinoma (RCC), the most common human kidney cancer, is frequently infiltrated with tumor-associated macrophages (TAM) that can promote malignant progression. Here, we show that TAMs isolated from human RCC produce substantial amounts of the proinflammatory chemokine CCL2 and immunosuppressive cytokine IL-10, in addition to enhanced eicosanoid production via an activated 15-lipoxygenase-2 (15-LOX2) pathway. TAMs isolated from RCC tumors had a high 15-LOX2 expression and secreted substantial amounts of 15(S)-hydroxyeicosatetraenoic acid, its major bioactive lipid product. Inhibition of lipoxygenase activity significantly reduced production of CCL2 and IL-10 by RCC TAMs. In addition, TAMs isolated from RCC were capable of inducing in T lymphocytes, the pivotal T regulatory cell transcription factor forkhead box P3 (FOXP3), and the inhibitory cytotoxic T-lymphocyte antigen 4 (CTLA-4) coreceptor. However, this TAM-mediated induction of FOXP3 and CTLA-4 in T cells was independent of lipoxygenase and could not be reversed by inhibiting lipoxygenase activity. Collectively, our results show that TAMs, often present in RCCs, display enhanced 15-LOX2 activity that contributes to RCC-related inflammation, immunosuppression, and malignant progression. Furthermore, we show that TAMs mediate the development of immune tolerance through both 15-LOX2-dependent and 15-LOX2-independent pathways. We propose that manipulating LOX-dependent arachidonic acid metabolism in the tumor microenvironment could offer new strategies to block cancer-related inflammation and immune escape in patients with RCC.

Smoothelin immunohistochemistry is a useful adjunct for assessing muscularis propria invasion in bladder carcinoma.

AIMS: To prospectively evaluate the utility of smoothelin immunohistochemical expression for the evaluation of muscularis propria (MP) in diagnostic transurethral resection of bladder tumour (TURBT) specimens and cystectomies. METHODS AND RESULTS: Smoothelin immunohistochemistry was performed on a total of 26 TURBT and cystectomy specimens. All but two cases (24/26) demonstrated strong (3+) or moderate (2+) immunoreactivity of the MP with smoothelin. Muscularis mucosae (MM) never displayed strong (3+) reactivity, and in only one case did the MM have moderate (2+) reactivity; in this case the MP had strong (3+) reactivity. MM intensity mirrored the intensity of reactivity of blood vessels in all cases (26/26). Using moderate or strong immunoreactivity as a cut-off, smoothelin had a sensitivity of 92% for detecting MP and a specificity of 97% for distinguishing between MP and MM. In all unequivocal MP-invasive and lamina proporia-invasive cases by haematoxylin and eosin (H&E), smoothelin immunohistochemistry confirmed the original light microscopic diagnosis. In four cases in which there was equivocal MP involvement by H&E, smoothelin helped establish MP invasion. CONCLUSIONS: Smoothelin immunohistochemistry has diagnostic utility in the evaluation of MP invasion in urothelial carcinoma. Smoothelin could be used as an adjunct to traditional H&E-stained light microscopy and may help reduce the number of equivocal diagnoses.

Metastatic epithelioid trophoblastic tumor in a male patient with mixed germ-cell tumor of the testis.

This report describes a rare case of a concurrent epithelioid trophoblastic tumor (ETT) and a teratoma in a para-aortic lymph node from a 39-year-old male patient with the initial diagnosis of testicular malignant mixed germ-cell tumor. The metastatic lesion was excised 2 years after orchiectomy and chemotherapy. Microscopically, the metastatic lesion contained a teratoma component and dispersed small nests of cohesive chorionic-type intermediate trophoblastic cells, closely resembling gestational ETT in female patients. The diagnosis of ETT in this case was confirmed by stepwise immunohistochemistry. Demonstration of ETT as one of the histologic manifestations of recurrent testicular germ-cell tumors should encourage pathologists to recognize this unique feature in assessing posttreatment mixed germ-cell neoplasm. Furthermore, this case represents a unique opportunity to understand the pathobiology of trophoblastic neoplasms arising from germ-cell tumors.

Study characteristics of abstracts presented at the annual meetings of the southeastern section of the American Urological Association (1996-2005).

PURPOSE: We determined study characteristics, authorship and institutional origin of studies presented in abstract form at the Southeastern Section of the American Urological Association annual meetings and identified predictors of full text publication. MATERIALS AND METHODS: All abstracts of poster and podium presentations from the Southeastern Section of the American Urological Association annual meetings from 1996 to 2005 were reviewed. A standardized evaluation form was developed and tested in 2 subsets of 50 abstracts, and then applied by 2 individual reviewers with specific coding instructions. Predictor variables analyzed included study origin, design, topic, domain, presentation form, number of patients, reporting of statistical analysis and gender. Univariate and multivariate analysis was applied using SPSS version 14.0. RESULTS: A total of 1,195 abstracts were found eligible for review. The mean number of abstracts presented per year was 120 +/- 16 (range 107 to 146). In clinical studies (1,068) approximately three-quarters of the abstracts reported case series (801, 75.0%). Cohort studies accounted for 11.2% of the abstracts and 4.0% were randomized controlled trials or systematic reviews/meta-analyses. Median followup was 64 months (range 17 to 126) and the overall publication rate was 33.5%. First and senior female authorship were identified in 6.2% (74) and 5.4% (64) of abstracts presented, respectively. CONCLUSIONS: A majority of studies presented at the Southeastern Section of the American Urological Association annual meetings continue to represent small case series that may not be well suited to guide clinical decision making. Only a third of studies are subsequently published in the peer reviewed literature. The percentage of abstracts with female authorship remains low suggesting that increased efforts to involve women in urological research are indicated.

Physical and emotional predictors of depression after radical prostatectomy.

Radical prostatectomy commonly results in urinary, sexual, and bowel dysfunction that bothers men and may lead to depressive symptomatology (hereafter depression) that occurs at a rate 4 times greater for men with prostate cancer than healthy counterparts. The purpose of this study was to assess depressive symptoms in men shortly after radical prostatectomy and to identify associated risk factors. Seventy-two men were interviewed 6 weeks after surgery. Measured were depression (Geriatric Depression Scale), self-efficacy (Stanford Inventory of Cancer Patient Adjustment), social support (Modified Inventory of Socially Supportive Behaviors), physical and emotional factors (UCLA Prostate Cancer Index), and social function (SF-36 subscale). Results indicate that men with high self-efficacy and less sexual bother were 45% and 55% less likely to have depressive symptoms, respectively. Findings from this study add to the limited amount of information on the complex relationship between prostate cancer treatment and depression in men.

Dyadic support and quality-of-life after radical prostatectomy.

BACKGROUND: Treatment side effects after radical prostatectomy include urinary, sexual, and bowel dysfunction. These functional declines, coupled with the bother associated with these dysfunctions, lead to a complicated pattern of change in quality-of-life and decreased self-efficacy. METHODS: In this study, 72 men who underwent radical prostatectomy 6-weeks prior were randomly assigned to usual health care control group or peer-to-peer support (dyadic support) group. The dyadic meetings were held once a week for 8 weeks. Measured pre- and post-test was general health-related quality-of-life (SF-36), prostate cancer-specific quality-of-life (UCLA Prostate Cancer Index), and self-efficacy (Stanford Inventory of Cancer Patient Adjustment). RESULTS: By 8 weeks, self-efficacy significantly improved for men in the experimental group, but not for men in the control group. A series of logistic regression analyses showed that the dyadic intervention significantly accounted for changes in physical role functioning, bowel function, mental health, and social function. Age, education, and self-efficacy had significant interaction effects and increased the effects of the dyadic intervention on several outcomes. CONCLUSIONS: The intervention had a significant impact on how men react socially and emotionally to the side effects of radical prostatectomy.

Urothelial carcinoma recurrence in ileal orthotopic neobladder: urethrectomy and creation of ileal conduit.

A patient who had previously undergone radical cystoprostatectomy and ileal neobladder with the Studer technique presented with a recurrence of urothelial carcinoma in the neobladder and urethra. Surgical treatment consisted of resection of the neobladder, urethrectomy, and creation of an ileal conduit using a separately isolated segment of ileum. Pathologic analysis revealed high-grade urothelial carcinoma implants to the Studer pouch and urethra, with spread to the mesenteric lymph nodes draining the pouch. Intraluminal tumor cell seeding appears to be an important mechanism of metachronous transitional cell carcinoma recurrence in the urethra and ileal mucosa of a neobladder.

Urinary, sexual, and bowel dysfunction and bother after radical prostatectomy.

INTRODUCTION: Radical prostatectomy results in greater persistence of urinary and sexual dysfunction (and to a minor degree, bowel dysfunction) than other forms of prostate cancer treatment. These physical side effects create bother, which is the degree of annoyance, dysfunction, or discomfort associated with treatment aftermath. OBJECTIVE: The purpose of this study was to assess the relationships between post-radical prostatectomy urinary, sexual, and bowel dysfunction, and the resultant bother to determine which of the physical dysfunctions bothers men the most. METHOD: Seventy-two men were recruited and surveyed 6 weeks after radical prostatectomy. Outcome measures included self-efficacy (Stanford Inventory of Cancer Patient Adjustment), social support (Modified Inventory of Socially Supportive Behaviors), uncertainty (Uncertainty in Illness Scale), and physical function and bother (UCLA Prostate Cancer Index). RESULTS: Sexual dysfunction had the highest prevalence among treatment side effects caused by radical prostatectomy. However, it was urinary dysfunction in terms of incontinence that was the most bothersome. CONCLUSIONS: Given various treatment options for prostate cancer, men who undergo radical prostatectomy initially decide that the physical dysfunction is worth the benefits of improved likelihood of survival; however, they do so without firsthand knowledge of the associated bother. Patients should be informed of the transient and unrelenting physical symptoms and associated bother that are produced after radical prostatectomy.

Postoperative adjuvant and salvage radiotherapy for prostate cancer: impact on freedom from biochemical relapse and survival.

OBJECTIVES: To determine the therapeutic outcomes in patients with high-risk prostate cancer treated with adjuvant or salvage radiotherapy (RT) after radical prostatectomy. METHODS: Between 1982 and 2000, 163 patients were treated with RT after radical prostatectomy. Adjuvant therapy was administered to 107 consecutive node-negative patients (T2-T4N0) referred to our institution less than 1 year after surgery for postoperative RT. Salvage treatment was delivered to 56 patients for a persistently elevated prostate-specific antigen level, biochemical relapse after surgery, or local recurrence. RESULTS: The median follow-up was 70 months (range 2 to 167) from the initiation of RT. Patients treated with adjuvant RT were less likely than those treated with salvage RT to experience biochemical relapse. At 5 and 10 years, the rate of freedom from biochemical relapse was 80% and 66% in the adjuvant cohort compared with 39% and 22% for patients treated with salvage intent, respectively (P <0.0001). This did not translate into a statistically significant improvement in absolute survival (72% versus 70%) or cause-specific survival (93% versus 86%) at 10 years. On multivariate analysis, neoadjuvant hormonal therapy (P = 0.0187), presence of seminal vesicle involvement (P = 0.0002), and referral indication for postoperative RT (salvage versus adjuvant RT; P <0.001) were predictors of biochemical relapse. CONCLUSIONS: In this single-institution experience, patients at high risk of disease recurrence after radical prostatectomy realized a greater biochemical relapse-free survival benefit when treated with adjuvant RT than with salvage RT. Neoadjuvant hormonal therapy and seminal vesicle involvement predicted for inferior treatment outcome.