Vaccines in urologic malignancies

The prospect of activating the immune system to combat neoplastic disease has stimulated the interest of clinicians and scientists for over 100 years. Despite a few notable exceptions (especially with urologic malignancies), immunotherapy has not fully reached its considerable therapeutic potential for the treatment of cancer. Tumors undoubtedly express antigens that may act as targets for antitumor immunity, and advances in molecular biology and tumor immunology have recently revived the possibility of a cancer vaccine. This improved understanding has resulted in numerous successes with active immunotherapy in animal models and has facilitated the clinical testing of cancer vaccines. Ongoing advances in the identification of unique, tumor-specific antigens and their presentation to stimulate T cells will be necessary for the emergence of these novel vaccine therapies for cancer patients. Herein we review the current concepts of tumor immunology, including observations on cell types probably involved with the immune surveillance of tumors, the presentation and recognition of “foreign” antigens, and possible mechanisms of tumor escape from the immune response, all of which are critical to the understanding of new initiatives for cancer vaccine therapy. Finally, we review some of the successes and limitations of vaccine therapy for urologic malignancies. Received: 28 October 2000 / Accepted: 9 February 2001     

The early history of arthroplasty in the United States

Arthroplasty is defined in the broadest sense as a reconstructive procedure that alters the structure or function of a joint. The first recorded procedures done in the United States in the early nineteenth century and the introduction of modern total joint replacement in the 1970s will be discussed. Although major surgical procedures occasionally were performed in the early 1800s, it was not until the introduction of general anesthesia and antiseptic techniques during the latter half of the nineteenth century that the field of surgery could be developed. Procedures involving the major joints of the upper and lower extremities are described. These procedures include resection and interposition arthroplasties, joint debridement, procedures done to correct complications of hip fractures and developmental dysplasia of the hip, cup arthroplasties, endoprosthetic replacement, hinge arthroplasties, resurfacing procedures, and early total joint replacement.     

The role of imaging in the surveillance of urologic malignancies

Urologic malignancies are common, accounting for approximately 25% of all new cancer cases in the United States. Patients with urologic malignancies require long-term surveillance to detect progression or recurrence as early as possible. The urologist is faced with the task of balancing patient safety and cost-effectiveness, while finding the most practical follow-up regimen. For each urologic malignancy, this article reviews the commonly used radiologic techniques for surveillance and offers recommended follow-up schedules.     

The E-cadherin cell-cell adhesion pathway in urologic malignancies

Summary Alterations in the E-cadherin-mediated cell-cell adhesion pathway are commonly observed in urologic malignancies. This issue has been addressed most thoroughly in prostate cancer. Whereas both cadherin and catenin dysfunction have been seen in human prostate cancers, only down-regulation of E-cadherin has been shown for bladder cancer and renal-cell carcinoma. Although studies in bladder cancer and renal-cell carcinoma are less mature than studies in prostate cancer, they support the hypothesis that immunostaining for E-cadherin may be of significance for both diagnostic and prognostic purposes. Finally, the E-cadherin-mediated cell-cell adhesion pathway may represent a novel chemotherapeutic target for bladder cancer, prostate cancer, and renal-cell carcinoma. Obviously, more work lies ahead to translate these important observations from the bench to the bedside.     

The impact of musculoskeletal disorders on the population of the United States.

Musculoskeletal disorders constitute such a large component of impairments of individuals in the working and geriatric population that good statistical data on them are essential for planning health care. We have collected the pertinent data, with references to recent source material, to determine the incidence, effect on the quality of life, and associated costs of these disorders in the United States.     

Percutaneous transperitoneal biopsy in urologic malignancies

A percutaneous transperitoneal thin needle aspiration biopsy was performed in 15 patients with urologic malignancies to determine the extent of disease and obviating in some cases exploratory surgery. No complications have resulted thus far. The technique is discussed.     

Tumor inhibitory factors in urologic malignancies

In this review, pathogenesis and genetic alterations of urologic malignancies and their therapeutic target molecule are summarized briefly. In bladder cancer, only a little has been revealed. Loss of heterozygosity of 9p/q is frequently observed in low grade, low stage tumors. In invasive or carcinoma in situ tumors, alteration of p53 and Rb tumor suppressor gene is frequently found. In prostate cancer, the process of carcinogenesis from normal epithelium to cancer hypothesized by Nelson et al. (N Engl J Med 24; 349 : 366-381) seems to be logic. Androgen independency of tumor cells is associated with androgen receptor gene mutation and amplification, however, the mechanism is not well clarified. It is a turning point, therapeutic strategy is changing from cytokine immunotherapy to molecular targeting therapy in metastatic renal cell carcinoma. The pathway from growth factors such as vascular endothelial growth factor and platelet derived growth factor, and their receptors to mTOR is a central controller of tumor angiogenesis and proliferation.     

Radiation therapy for urologic malignancies in the elderly

Radiotherapy is a commonly employed modality in the treatment of older men with urologic malignancies. The treatment recommendations should not be solely based on age even though optimal therapy for older patients continues to evolve. Radiotherapy is well tolerated by elderly prostate cancer patients and comparisons with other modalities should incorporate validated health-related quality of life measures, which is an important consideration in this age group. Due to lack of quality data, there is a need to optimize decision making process for older prostate cancer patients with more robust evidence-based measures. The new and emerging radiotherapeutic technologies are likely to benefit older patients with improvement in therapeutic ratio resulting from reduced dose delivery to normal tissues. The use of novel techniques, such as intensity modulated radiation therapy, image guidance and proton beam therapy, and their potential benefits for older population are discussed. This article also reviews the role of radiotherapy in older patients with other urologic malignancies, such as testicular tumor, bladder cancer, renal carcinoma, and penile cancer.     

The impact of laparoscopy on modern urologic practice

The original concept of laparoscopy developed as a branch of cystoscopy. Since the use of the Nitze cystoscope at its inception, laparoscopy has kept pace with the innovations in our cystoscopic inventory. The recently emerging interest of urologists in utility of the laparoscope for a variety of urologic surgery is a welcome renascence of this procedure, which has been used mainly by our gynecologic colleagues, in part because of our own lack of pursuit in its development. Laparoscopy should now become an integral part of our urologic teaching and practice.     

Notes on the early development of pediatric surgery in the United States

This lecture addresses the leadership roles in American surgery.     

The impact of regulatory policy on the development of somatic cell therapies in the United States

Cellular therapies offer new promise for the treatment of a variety of diseases. In order to protect patients and donors, the Food and Drug Administration in the USA has been developing specific regulations. These have undergone several iterations, however, a broad-based strategy has recently emerged. These proposals are reviewed and their impact on academic institutions is assessed.     

The impact of race and ethnicity on the outcome of carotid interventions in the United States

ObjectivePrevious studies have demonstrated an adverse impact of African American race and Hispanic ethnicity on the outcomes of carotid endarterectomy (CEA), although little is known about the influence of race and ethnicity on the outcome of carotid angioplasty and stenting (CAS). The present study was undertaken to examine the influence of race and ethnicity on the outcomes of CEA and CAS in contemporary practice.MethodsThe nationwide inpatient sample (2005–2008) was queried using International Classification of Diseases-9 codes for CEA and CAS in patients with carotid artery stenosis. The primary outcomes were postoperative death or stroke. Multivariate analysis was performed adjusting for age, gender, race, comorbidities, high-risk status, procedure type, symptomatic status, year, insurance type, and hospital characteristics.ResultsOverall, there were 347,450 CEAs and 47,385 CASs performed in the United States over the study period. After CEA, Hispanics had the greatest risk of mortality (P < 0.001), whereas black patients had the greatest risk of stroke (P = 0.02) compared with white patients on univariate analysis. On multivariable analysis, Hispanic ethnicity remained an independent risk factor for mortality after CEA (relative risk 2.40; P < 0.001), whereas the increased risk of stroke in black patients was no longer significant. After CAS, there were no racial or ethnic differences in mortality. On univariate analysis, the risk of stroke was greatest in black patients after CAS (P = 0.03). However, this was not significant on multivariable analysis.ConclusionHispanic ethnicity is an independent risk factor for mortality after CEA. While black patients had an increased risk of stroke after CEA and CAS, this was explained by factors other than race. Further studies are warranted to determine if Hispanic ethnicity remains an independent risk factor for mortality after discharge.     

Mechanisms of disease: angiogenesis in urologic malignancies

Angiogenesis is critical for growth of tumors and their metastasis. In this article we review the literature on studies of angiogenesis pathways and markers for renal cancer, prostate cancer and bladder cancer. Overall, there is clear evidence that markers of angiogenesis and expression of angiogenic factors are associated with adverse outcomes in each of these tumor types. Relatively few angiogenic pathways have been investigated so far, although over 50 factors are known to be involved, and little has been studied on the antiangiogenic pathways and their suppression. The failing in many of the studies is small size and lack of suitable statistical analysis. Nevertheless, this review demonstrates the importance of these pathways and the need to develop selection criteria for patients who are candidates for antiangiogenic therapies. On the basis of the expression profiles reported so far, therapies that target vascular endothelial growth factor should be considered for the treatment of renal, prostate and bladder cancers. As most tumors express factors that are involved in multiple angiogenic pathways, further research is needed to determine which are coregulated and what the most common patterns are.     

Treatment of skeletal metastases from urologic malignancies

Metastases from genitourinary tumors frequently involve the skeletal system and often produce the most disabling symptoms. Judicious early orthopedic management may prevent paralysis and maintain ambulation, thus significantly improving the quality of life. The role of prophylactic surgery for impending fractures and the symptomatic therapy of painful metastatic foci are discussed.     

The impact of health literacy on urologic oncology care

Health literacy is the ability to access, comprehend, and act upon medical information to make health care decisions. In the United States, 12% of adults have proficient health literacy. Low health literacy has been associated with worse outcomes in several chronic medical conditions. In addition, low health literacy has been associated with longer hospital stays. In the urologic oncology literature low health literacy is associated with increased minor complications following radical cystectomy. There remains sparse data on health literacy and its impacts on prostate, kidney, testicular and penile cancer care. Going forward, in order to provide the best urologic oncology care to our patients it is critical to account for patients' health literacy status.