(BQ) Part 2 book “Smith’s general urology” has contents: Chemotherapy of urologic tumors, renal parenchymal neoplasms, neoplasms of the prostate gland, genital tumors, urinary diversion & bladder substitution, neuropathic bladder disorders,…. And other contents.
Immunology & Immunotherapy of Urologic Cancers 18 Eric J Small, MD Both experimental and naturally occurring tumors are capable of stimulating a specific antitumor immune response This observation suggests that there are foreign proteins (antigens) on tumor cells that classically have been described as resulting in humoral and cellular immune responses However, experimental models suggest that a Tcell (cell-mediated) response may be more important in the killing of tumor cells than a B-cell (humoral) response A detailed description of the components of the immune system is beyond the scope of this chapter, but certain features of the immune system as they pertain to diagnostic and therapeutic issues will be reviewed to the specific antigen The mechanisms of tolerance are complex and may be due in part to the absence of other required costimulatory molecules (such as B7, a molecule required for T-cell stimulation) The development of monoclonal (hybridoma) technology has allowed the development of many antibodies against many tumor-associated antigens and has provided insight into the regulation and expression of these antigens The reexpression or upregulation of these tumorassociated antigens during carcinogenesis may lead to immune response (or loss of tolerance) Many novel therapeutic approaches have sought to break this tolerance, and approaches to enhance a patient’s immune response will be discussed Tumor Antigens Tumor antigens can be divided into tumor-specific antigens and tumor-associated antigens Tumor-specific antigens are not found on normal tissue, and they permit the host to recognize a tumor as foreign Tumor-specific antigens have been shown to exist in oncogenesis models utilizing chemical, physical, and viral carcinogens but appear to be less common in models of spontaneous tumor development The identification of tumor-specific antigens led to the theory of immune surveillance, which suggests that the immune system is continuously trolling for foreign (tumorspecific) antigens This theory is supported by the observation that at least some cancers are more common in immune-suppressed patients such as transplant patients or human immunodeficiency virus-infected individuals However, many cancers are not overrepresented in these patient populations Furthermore, spontaneous tumor models, which more closely resemble human carcinogenesis, appear to have a less extensive repertoire of tumor-specific antigens but instead have been found to express many tumorassociated antigens Tumor-associated antigens are found on normal cells but either become less prevalent in normal tissue after embryogenesis (eg, alpha-fetoprotein [AFP]) or remain present on normal tissue but are overexpressed on cancer cells (eg, prostate-specific antigen [PSA]) In either case, the more ubiquitous nature of these antigens appears to cause reduced immune reactivity (also known as tolerance) Humoral Immunity A large number of monoclonal antibodies have been developed against a variety of tumor-associated antigens Oncofetal antigens such as AFP and beta-human chorionic gonadotropin (β-hCG) are important markers in germ cell tumors β-hCG is also expressed in a small percentage of patients with bladder carcinoma Antibodies directed against specific targets such as vascular endothelial growth factor (vegF) have been correctly developed and are being tested for the treatment of both advanced prostate cancer of RCC Antibodies in Cancer Diagnosis & Detection A PROSTATE CANCER Immunoassays are used to test both body fluids and tissues for the presence of tumor-associated antigens In the urologic cancers, the most obvious example is the development of monoclonal antibodies against PSA The utility and limitations of PSA are described elsewhere in this volume Other antigens that have been tested in prostate cancer include prostatic acid phosphatase, which has largely been replaced by PSA in screening programs and in patients with low tumor burden Prostatic acid phosphatase may be of some use in detecting or following up bone 297 Copyright © 2008, 2004, 2001, 2000 by The McGraw-Hill Companies, Inc Click here for terms of use 298 / CHAPTER 18 metastases and as a predictive marker of response to therapy for metastatic disease, both hormone-sensitive andinsensitive More recently, antibodies to prostate-specific membrane antigen (PSMA) have been used, primarily for immunohistochemistry B RENAL CELL CARCINOMA Unfortunately, there are as yet no well-established antigens (or antibodies) that can be used to reliably evaluate and monitor renal cell carcinoma, although a variety of target antigens are being evaluated C BLADDER CANCER Two oncofetal antigens, β-hCG and carcinoembryonic antigen, are expressed by a minority (20% or less) of transitional cell carcinomas These markers are not routinely used, but in diagnostic dilemmas, measurement of serum levels of β-hCG or staining of tissue for this antigen may be useful D GERM CELL TUMORS As described in Chapter 23, antibodies to hCG and AFP are routinely used to detect shed antigen from germ cell tumors in the bloodstream These antigens can also be detected on tissue samples in the setting of some diagnostic dilemmas While the use of serum markers in germ cell tumors is reviewed elsewhere, it is worth noting that the presence of the oncofetoprotein AFP, either in serum or on tissue specimens, is pathognomic for a nonseminomatous germ cell tumor, regardless of results of routine pathologic evaluation In addition to their diagnostic utility, AFP and hCG can be used as markers of response to therapy and as predictive factors of outcome For example, the international germ cell tumor risk classification schema for patients with metastatic disease relies heavily on AFP and hCG levels as well as levels of a nonspecific marker, lactate dehydrogenase, to assign patients with nonseminomatous germ cell tumors to of risk levels (see Chapter 23) E RADIOIMMUNODETECTION Monoclonal antibodies to a specific antigen can be radiolabeled, and the preferential binding of the monoclonal antibody to tumor cells can be exploited Theoretically, such an approach could be used for the presurgical evaluation of disease, postsurgical evaluation for minimal residual disease, confirmation of cancer identified by other imaging modalities, and detection of recurrent disease There are several potential impediments to successful tumor radioimmunodetection These include dilution of antibody in the bloodstream; metabolism of the antibody; nonspecific binding in liver, reticuloendothelial system, bone marrow, and elsewhere; binding of antibody by circulating or shed antigen; and the development of neutralizing human antimouse antibodies The only radioimmunodetection system for urologic cancers at this time is 111 In-capromab pendetide (Prostascint), a murine monoclonal antibody to PSMA Its use has been hampered by a fairly laborious administration process, operator dependence in interpretation of scans, and a less than satisfactory positive predictive value The use of 111In-capromab pendetide is described in Chapter 10 Immunotherapy with Monoclonal Antibodies Immunotherapy with monoclonal antibodies alone (“naked antibodies”) has been fairly extensively evaluated The use of monoclonal antibodies against tumorassociated antigens has met with only limited success in patients with solid tumors In lymphoproliferative disorders such as leukemia and lymphoma, some antibodies to tumor-associated surface antigens appear to result in tumor cell death The mechanism for these effects is certainly multifactorial but may in part be mediated by resultant complement fixation Direct antiproliferative effects of antibodies on cancer cells can be achieved by antibodies against functionally important antigens Thus, the inhibition of growth factors and growth factor receptors and the activation or inhibition of signal transducing molecules are attractive therapeutic targets In the urologic cancers, while no approved monoclonal antibody therapy exists, trials of antibodies against growth factors, vascular endothelial growth factor (VEGF, an angiogenic molecule), and signal transduction molecules are being undertaken Kidney cancer is highly dependent on angiogenesis, and bevacizumab (an antibody agent against VEGF) has been shown to prolong time to progression in metastatic disease Results from a trial of interferon-alpha with and without bevacizumab are awaited There is, as well, an ongoing trial of chemotherapy with and without bevacizumab in patients with metastatic hormone refractory prostate cancer An alternative approach to naked antibodies is to conjugate any of a variety of cytotoxic agents to an antibody The advantage of this approach is a “bystander effect,” making it unnecessary to use an antibody that binds each and every cell This can be achieved in a variety of ways The most straightforward is to use the monoclonal antibody as a means of providing some targeting specificity for the cytotoxic agent used Cytotoxic agents used include radioisotopes, chemotherapy, and toxins such as ricin Other means of providing some specificity is to bind a prodrug (with an antibody) to the tumor site and then to activate the bound prodrug Finally, targeting with bispecific antibodies (eg, to antigen and to an effector T cell, or to antigen and toxin) has been undertaken These approaches have all been tested in prostate cancer, but all remain investigational at this point IMMUNOLOGY & IMMUNOTHERAPY OF UROLOGIC CANCERS / Cell-Mediated Immunity There is considerable evidence, both clinical and preclinical, that tumor-associated antigens can elicit a cellmediated immune response In some models, when carcinogen-induced tumors in mice are resected and the mouse is reinoculated with tumor cells, the tumor fails to regrow, suggesting the development of immunity to specific antigens Specific antigens that are rejected in immunized hosts are termed transplantation antigens The specificity of tumor rejection has since been demonstrated to reside in T lymphocytes (at a minimum) Lymphocytes of cancer patients can sometimes be stimulated in vitro to recognize specific tumor-associated antigens and consequently demonstrate properties of cytolytic T lymphocytes Unfortunately, the phenomenon of tumor rejection is by no means universal, either in the laboratory or clinically, and it is unusual to detect cytolytic-T-lymphocyte activity against many tumorassociated antigens Nevertheless, there are several clinical scenarios that suggest that cell-mediated antitumor responses exist These observations have promoted a broad search for the means of enhancing patients’ immune responses to tumor-associated antigens Renal cell carcinoma (RCC) is in many ways the prototypical immune-mediated tumor and, along with melanoma, has until recently been the primary target of immune manipulations A dramatic example of such an immune-mediated response is the phenomenon of spontaneous regression of metastatic RCC deposits after nephrectomy Classically this has been described in less than 1% of patients The impact of tumor debulking may also explain why a subset of RCC patients with lymph node or renal vein involvement that undergo resection are seemingly cured The exact mechanism of this phenomenon is not well understood but may involve elimination of inhibitors of cell-mediated immunity Indeed, tumor-infiltrating lymphocytes in RCC have been shown to exhibit mutant or faulty T-cell-receptor components, and it is not unreasonable to speculate that involvement in the tumor milieu in some fashion results in “deactivation” of such lymphocytes Immunotherapy Involving Cell-Mediated Immunity Additional evidence of cell-mediated immunity playing a role in tumor rejection lies in the results of a variety of immunotherapeutic interventions Immunotherapy can be broadly classified as active or passive This classification refers to the role the host’s immune system plays Thus, the passive transfer of preformed antibodies is contrasted to a vaccination program in which the host’s immune system must be capable of mounting an immune response Adoptive therapy refers to a middle ground in which efforts are made to reconstitute, modify, or bolster one of the effector cells involved ex vivo, followed by reinfusion 299 into the patient, where the rest of the immune cascade must then be recruited Active Immunotherapy: Vaccination Autologous vaccination programs (the vaccination of patients with their own tumor cells) have been extensively explored The advantage of autologous vaccination is that the vaccine bears the antigens of the patient’s tumor, although the distinct disadvantage is that not every patient has tumor available for vaccine preparation, and the preparation of each vaccine is tremendously labor intensive By contrast, allogeneic vaccines (the use of a generic vaccine or “off-the-shelf” antigen) have the benefit of mass production and ease of use, and the identification of specific tumor rejection antigens allows specific antigenic targeting However, this approach runs the risk of a more narrow shared antigenic spectrum with the patient’s tumor Both autologous and allogeneic vaccination strategies are under evaluation, both in RCC and prostate cancer Several means exist to undertake vaccination The simplest is to use intact but inactivated tumor cells Inactivation can be achieved with UV radiation, external beam (photon) radiation, or freeze-thawing Crude extracts of cells can also be used The advantage of using cell extracts is that inactivation is not necessary and small particles and proteins that might be more easily phagocytosed are available One can also enhance the immunogenicity of inoculated cells by growing the cells in cytokines, coinjecting with cytokines (nonspecific active immunotherapy, described below), or transfecting these cells with the genes for immune stimulatory cytokines or the costimulatory molecule B7 Current clinical trials are underway that use prostate cancer cell lines transfected with the GM-CSF gene (GVAX, Cell Genesys, South San Francisco, CA) for vaccination in patients with metastatic hormone refractory prostate cancer Purified protein or peptides represent a second potential vaccination schema In prostate cancer, trials of vaccination with PSMA and PSA are under way Trials of PSA in a vaccina and fowlpox (ProstaVax) are also underway A third way of undertaking specific vaccination is to attempt to bypass the antigen-presenting function of the immune system and to directly stimulate professional antigen-presenting cells, such as dendritic cells, ex vivo These cells can be stimulated by pulsing them with protein or peptides of interest or by transfecting them with a gene encoding the antigenic peptide of interest before re-infusion Initial trials of PAP-pulsed dendritic cells (Provenge, Dendreon Corporation, Seattle, WA) have demonstrated preliminary activity Confirmatory trials are ongoing Nonspecific Active Immunotherapy: Cytokines & Biologic Response Modifiers BCG (Bacillus Calmette-Guérin) is a live attenuated form of tubercle bacillus that appears to have local activity against 300 / CHAPTER 18 some tumors but has been largely disappointing as systemic therapy The utility of BCG in the treatment of superficial bladder cancer is well described and is beyond the scope of this chapter The mechanism by which BCG can elicit a local immune response in the uroepithelium and thereby exhibit impressive anticancer activity is not well delineated However, possible mechanisms of action include macrophage activation, lymphocyte activation, recruitment of dendritic cells, and natural killer cells It is intriguing that this is strictly a local phenomenon and that BCG has no role in the treatment of muscle-invasive or metastatic disease Interleukin-2 (IL-2) is a naturally occurring cytokine that has multiple immunoregulatory properties The observation that exogenously administered IL-2 could result in tumor regression in patients with RCC and melanoma was the first unequivocal indication that cancer regression could be mediated by immune manipulations IL-2 stimulates lymphocyte proliferation, enhances cytolytic-T-cell activity, induces natural killer cell activity, and induces gamma-interferon and tumor necrosis factor production IL-2 has no direct cytotoxicity, but when administered endogenously will activate effector cells of the host immune system, including lymphocytes, natural killer cells, lymphokine-activated killer cells, and tumor-infiltrating lymphocytes The details of immunotherapy for RCC are beyond the scope of this chapter Nevertheless, in brief, IL-2 has been administered in RCC in several different schemas, including highdose intravenous bolus (IL-2 is U.S Food and Drug Administration [FDA] approved with this schedule), continuous intravenous infusion, and at lower doses subcutaneously The high-dose regimens must be administered on an inpatient basis and are characterized by significant, albeit manageable, toxicities, including fever; malaise; vascular leak syndrome; hypotension; and cardiac, renal, and hepatic dysfunction Subcutaneous IL-2 is self-administered by patients in the outpatient setting, and while clearly less toxic, still has associated malaise and constitutional symptoms The optimal dosing regimen is not well established, and overall response proportions rarely exceed 20% Durable complete responses of 5–8% have been reported with some of the high-dose regimens IL-2 has also been combined with other active agents such as alpha-interferon and chemotherapy, although it is not clear if these combinations provide additional benefit Alpha-interferon is a naturally occurring cytokine that has direct cytotoxic and possibly antiproliferative properties, but also has immunoregulatory properties It enhances major histocompatibility complex expression, thereby potentially increasing the efficiency of antigen processing and recognition Alpha-interferon has anticancer activity in both RCC and superficial bladder cancer Its primary toxicity is fever, malaise, and constitutional symptoms, although at higher doses it can result in bone marrow toxicity, central nervous system toxicity, and hepatic toxicity In RCC, as a single agent, alpha-interferon can result in clinical responses in up to 20% of patients In contradistinction to IL-2 as a single agent, durable complete responses are quite rare Nevertheless, in randomized trials, alpha-interferon appears to confer a modest survival advantage over other agents now known to be largely inactive Alpha-interferon is also used as an intravesicle treatment in superficial bladder cancer, where it has established activity, and is not infrequently used as second-line therapy after BCG Granulocyte macrophage-colony stimulating factor (GM-CSF) is perhaps the most important cytokine in eliciting cellular immune responses Administered systemically as a subcutaneous injection, GM-CSF has been shown to reduce PSA in patients with both hormonesensitive and hormone-resistant prostate cancer However, the use of GM-CSF is neither proven to be of clinical benefit, nor approved for this indication, and must be considered investigational Immunomodulation A myriad of immunosuppressive factors exist within cancer patients that may serve to dampen anti-tumor immune responses Some of these molecules represent natural pathways to inhibit autoimmunity, while some molecules may have been usurped by the tumor to evade immune recognition Novel approaches are now being developed to target these pathways For example, CTLA-4 is an inhibitory molecule that blocks binding of B7 to CD28, thereby preventing costimulation and downmodulating T-cell activation By preventing the action of CTLA-4, an anti-CTLA-4 antibody (ipilimumab) can augment and prolong T-cell immune responses In animal models, ipilimumab antibody can induce tumor rejection in immunogenic tumors, and in combination with antitumor vaccination, can induce rejection of minimally immunogenic tumors, including in the transgenic adeno carcinoma of mouse/prostate (TRAMP) prostate cancer model In a phase I study, 14 patients with androgen insensitive prostate cancer were treated with a humanized anti-CTLA-4 antibody (MDX-010, Medarex, Inc., Bloomsbury, NJ) There was no evidence of polyclonal T-cell activation, therapy was well tolerated, and patients had ≥50% decline in their PSA The combination of CTLA-4 blockade with vaccination is of interest and is under investigation Adoptive Immunotherapy Adoptive immunotherapy is the transfer of cellular products (effector cells) to the host or patient in an effort to develop an immune response The use of adoptive immunotherapy was prompted by the observation that T cells derived from patients with melanoma or RCC had the ability to recognize antigens on the primary tumor Thus, it was hoped that these cells could be harvested, activated IMMUNOLOGY & IMMUNOTHERAPY OF UROLOGIC CANCERS / ex vivo, and then reinfused into patients Lymphokineactivated killer cells and tumor-infiltrating lymphocytes have been used to treat patients with metastatic RCC in the investigational setting, frequently along with IL-2 However, randomized trials comparing IL-2 alone with IL-2 plus cellular products have failed to demonstrate an improvement in response proportions or survival Chapter 22 gives specific details of immunotherapy in RCC REFERENCES Agarwala SS, Kirkwood JM: Interferons in the treatment of solid tumors Oncology 1994;51:129 Anichini A, Fossati G, Parmiani G: Parmiani G: Clonal analysis of the cytolytic T-cell response to human tumors Immunol Today 1987;8:385 Berd D: Cancer vaccines: Reborn or just recycled? Semin Oncol 1998; 25:605 Berd D, Maguire HC Jr, Mastrangelo MJ: Induction of cell-mediated immunity to autologous melanoma cells and regression of metastases after treatment with a melanoma cell vaccine preceded by cyclophosphamide Cancer Res 1986;46:2572 Berd D et al: Treatment of metastatic melanoma with an autologous tumor-cell vaccine: Clinical and immunologic results in 64 patients J Clin Oncol 1990;11:1858 Bukowski RM: Natural history and therapy of metastatic renal cell carcinoma: The role of interleukin-2 Cancer 1997;80:1198 Fyfe G et al: Results of treatment of 255 patients with metastatic RCC who received high-dose recombinant interleukin-2 therapy J Clin Oncol 1995;13:688 Gitlitz BJ, Belldegrum A Figlin R: Immunotherapy and gene therapy Semin Urol Oncol 1996;14:237 Goedegebuure PS, Eberlen TJ: Vaccine trials for the clinician: Prospects for viral and non-viral vectors Oncologist 1997;2:300 Hewitt H, Blake E, Walder A: A critique of the evidence for active host defense against cancer based on personal studies of 27 murine tumors of spontaneous origin Br J Cancer 1976;33:241 Hoover HC Jr et al: Adjuvant active specific immunotherapy for human colorectal cancer: 6.5-year median follow-up of a phase III prospectively randomized trial J Clin Oncol 1993;11:390 301 Hsu FJ, Engleman EG, Levy R: Dendritic cells and their application in immunotherapeutic approaches to cancer therapy PPO Updates 1997;11:1 International Germ Cell Cancer Collaborative Group: International germ cell consensus classification: A prognostic factor-based staging system for metastatic germ cell cancers J Clin Oncol 1997; 15:594 Lamm DL: Long-term results of intravesical therapy for superficial bladder cancer Urol Clin North Am 1992;19:573 Morales A, Nickel JC: Immunotherapy for superficial bladder cancer Urol Clin North Am 1992;19:549 Morton DL et al: Prolongation of survival in metastatic after active specific immunotherapy with a new polyvalent melanoma vaccine Ann Surg 1992;216:463 Osanto S: Vaccine trials for the clinician: Prospects for tumor antigens Oncologist 1997;2:284 Rosenberg SA et al: Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin-2 JAMA 1994;271:907 Rosenberg SA et al: Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma N Engl J Med 1988;319:1676 Schlag P et al: Active specific immunotherapy with Newcastle-diseasevirus-modified autologous tumor cells following resection of liver metastases in colorectal cancer Cancer Immunol Immunother 1992;35:325 Shepard HM et al: Monoclonal antibody therapy of human cancer: Taking the HER2 protooncogene to the clinic J Clin Immunol 1991;11:117 Simons JW, Mikhak B: Ex vivo gene therapy using cytokine-transduced tumor vaccines: Molecular and clinical pharmacology Semin Oncol 1998;25:661 Texter JH Jr, Neal CE: The role of monoclonal antibody in the management of prostate adenocarcinoma J Urol 1998;160: 2393 Vanky F, Klein E: Specificity of auto-tumor cytotoxicity exerted by fresh, activated and propagated human T lymphocytes Int J Cancer 1982;29:547 Velders MP, Schreiber H, Kast WM: Active immunization against cancer cells: Impediments and advances Semin Oncol 1998; 25:697 Chemotherapy of Urologic Tumors 19 Eric J Small, MD If cure is the intent with systemic therapy, the relevant response criterion to consider is the percentage of patients achieving a complete response This number is less than 10% in patients with metastatic renal cell carcinoma and hormone-refractory prostate cancer, 25% or less in patients with metastatic transitional cell carcinoma, and up to 80% in patients with metastatic germ cell malignancies Under some circumstances, however (for example, in postchemotherapy residual masses in patients with germ cell carcinoma), an apparent partial response can be converted into a complete response with judicious resection (see Section A 3.) The second feature to consider in treating patients with potentially curative systemic therapy is the anticipated toxicity of such therapy In general, higher levels of toxicity are acceptable if a cure can be achieved, although care must be exercised to avoid a “cure worse than the disease.” This is particularly true in the case of fairly toxic therapies such as interleukin-2 or bone marrow transplantation These treatments can result in apparent cures of approximately 10% and 30%, respectively, of patients with metastatic renal cell carcinoma or refractory germ cell tumors (GCT) Patients undergoing these rigorous therapies must be carefully selected and must be as fully informed as possible about potential toxicities Treatment of patients with incurable metastatic cancer—When the goal of systemic therapy is palliation of symptoms rather than cure, the toxicity of the treatment to be offered must be balanced against the cancer-related symptoms the patient is experiencing, and in general, more toxic therapies are not indicated Nonetheless, an understanding of the potential capabilities of systemic therapy must be understood because even in otherwise incurable disease there may be a role for systemic therapy if there is a likelihood that the patient’s life can be prolonged with its use In addition, systemic chemotherapy can be associated with a control of pain, and an improvement in quality of life This appears to be the case for both mitoxantrone and docetaxel in patients with metastatic hormone refractory prostate cancer Systemic therapy used in conjunction with surgery: adjuvant and neoadjuvant therapy—Systemic therapy administered after a patient has been rendered free of disease surgically is termed adjuvant therapy Several The use of chemotherapy in the treatment of malignant tumors of the genitourinary system serves as a paradigm for a multidisciplinary approach to cancer The careful integration of surgical and chemotherapeutic treatments has resulted in impressive advances in the management of urologic cancer By definition, surgical interventions are directed at local management of urologic tumors, whereas chemotherapy and biologic therapy are systemic in nature While there is no question that there are times in the natural history of genitourinary tumor when only one therapeutic method is required, a multidisciplinary approach is always called for This chapter details the importance of a joint surgical-medical approach to patients with urologic cancer A practicing urologist should collaborate closely with a medical oncologist and should feel comfortable speaking with patients about the uses, risks, and benefits of chemotherapy PRINCIPLES OF SYSTEMIC THERAPY A CLINICAL USES OF CHEMOTHERAPY Systemic therapy is indicated in the treatment of disseminated cancer when either cure or palliation is the goal Additionally, chemotherapy may be used as part of a multimodality treatment plan in an effort to improve both local and distant control of the tumor An understanding of the goals and limitations of systemic therapy in each of these settings is essential to its effective use Curative intent of metastatic disease—In considering the role of potentially curative chemotherapy in patients with metastatic disease, several factors must be taken into account The first is the responsiveness of the tumor Responsiveness is generally defined by the observed partial, complete, and overall responses It is important to note that a complete response implies complete resolution of abnormal serum tumor markers, if any, and complete radiographic resolution of any abnormalities This makes the assessment of neoplasms with frequent bony metastases such as prostate cancer, renal cell carcinoma, and transitional cell carcinoma difficult, as a persistently abnormal bone scan does not necessarily imply residual cancer Patients in whom the only site of disease is bone generally must be considered non-assessable by conventional measures, and if available, intermediate markers of response (such as prostate-specific antigen [PSA]) are required 302 Copyright © 2008, 2004, 2001, 2000 by The McGraw-Hill Companies, Inc Click here for terms of use CHEMOTHERAPY OF UROLOGIC TUMORS / important criteria must be met if adjuvant therapy is to be used outside of a research setting First, an assessment must be undertaken of known risk factors predictive of relapse or development of distant metastases Patients at low risk of relapse generally should not receive adjuvant therapy because they are unlikely to derive a benefit and will be unnecessarily exposed to the toxicity of therapy Second, the proposed therapy must have been shown to decrease the rate of relapse and increase the disease-free interval (and, it is hoped, survival) in a randomized, phase III trial Finally, because patients who are being treated with adjuvant therapy are free of disease and presumably asymptomatic, toxicity must be kept at a minimum This opens the way to a tailored approach in which patients with high-risk disease, as determined by pathologic review of the surgical specimen, are treated in order to decrease the risk of micrometastatic disease By contrast, neoadjuvant therapy is administered before definitive surgical resection Here, the potential advantages include early therapy of micrometastatic disease and tumor debulking to allow a more complete resection Patients with known metastatic disease generally not exhibit high enough response rates to systemic therapy to warrant local surgery following chemotherapy, with the clear exception of patients with GCT Whether or not patients with metastatic renal cell carcinoma who exhibit a partial response to systemic therapy may benefit from resection of residual masses is not known As with adjuvant therapy, 303 the proposed therapy must have been demonstrated to impact favorably on rate of relapse, disease-free interval, and survival in a randomized phase III trial B CHEMOTHERAPEUTIC AGENTS AND THEIR TOXICITY The usefulness of antineoplastic agents lies in their therapeutic index or preferential toxicity to malignant cells over normal, nonmalignant cells The mechanism of action of most chemotherapeutic drugs is based on their toxicity to rapidly dividing cells Thus, in general, malignancies that have relatively rapid growth, such as GCT, are relatively chemosensitive, whereas slower growing neoplasms such as renal cell carcinoma are less sensitive Toxicity from chemotherapeutic agents is seen primarily in normal, nonmalignant cells that are also rapidly dividing, such as hematopoietic cells in the bone marrow, gastrointestinal mucosa, and hair follicles, and is manifested in cytopenias, mucositis, and alopecia Other common toxicities observed with agents frequently used in the treatment of genitourinary malignancies include nephrotoxicity, neurotoxicity, hemorrhagic cystitis, pulmonary fibrosis, and cardiotoxicity Table 19–1 summarizes the spectrum of activity and primary toxicities of commonly used chemotherapeutic agents The development of chemotherapy drug resistance remains an important clinical problem in the field of oncology Malignant cells develop resistance in a variety of ways, including the induction of transport pumps, which Table 19–1 Commonly Used Chemotherapeutic Agents in Urologic Oncology, and Their Toxicity Agent Cisplatin Carboplatin Bleomycin Doxorubicin Etoposide (VP-16) 5-Fluorouracil Floxuridine (FUdR) Methotrexate Ifosfamide Vinblastine Estramustine Paclitaxel (Taxol) Docetaxel (Taxotere) Gemcitabine (Gemzar) Activity Common Toxicities Bladder cancer, germ cell tumors, prostate cancer Bladder cancer, germ cell tumors Germ cell tumors Bladder cancer, prostate cancer Germ cell tumors, prostate cancer† Renal cell carcinoma, bladder cancer, prostate cancer Renal cell carcinoma Germ cell tumors, bladder cancer Germ cell tumors Renal cell carcinoma, bladder cancer, germ cell tumors, prostate cancer† Prostate cancer Bladder cancer, germ cell tumors, prostate cancer† Bladder cancer, germ cell tumors, prostate cancer Bladder cancer Renal insufficiency, peripheral neuropathy, auditory toxicity, myelosuppression* Myelosuppression Fever, chills, pulmonary fibrosis Myelosuppression, mucositis, cardiomyopathy Myelosuppression Mucositis, diarrhea, myelosuppression Mucositis, diarrhea Mucositis, myelosuppression, renal toxicity Myelosuppression, neurologic (CNS) toxicity, cystitis Peripheral, autonomic neuropathy; myelosuppression Nausea, thromboembolic events Myelosuppression, neuropathy Myelosuppression, neuropathy Myelosuppression *Because of recent advances in the treatment of chemotherapy-induced nausea and vomiting, even the most emetogenic agents, such as cisplatin, have virtually no associated nausea and vomiting † In combination with estramustine 304 / CHAPTER 19 actively pump the drug out of the cell and through increased activity of enzymes necessary to inactivate the particular chemotherapeutic agent While there are several experimental methods of circumventing these mechanisms of drug resistance, one practical approach to this problem is the use of multiagent chemotherapy Increased tumor cell killing is achieved by exposing neoplastic cells to multiple agents with different mechanisms of action Furthermore, this approach allows the selection of agents with nonoverlapping toxicity profiles The use of increased dose intensity (higher doses of a drug administered over the same time period) as a means of overcoming drug resistance remains experimental in urologic malignancies with one clear exception A subset of patients with otherwise incurable GCT appear to be curable with high-dose chemotherapy and autologous bone marrow transplant support (see the section Germ Cell Malignancies, following) C UNIQUE FEATURES OF GENITOURINARY MALIGNANCIES The systemic therapy of urologic malignancies offers unique challenges to the practitioner Renal insufficiency due to obstructive uropathy from local extension of the tumor or postsurgical or postradiotherapy changes is not infrequent and may alter antineoplastic drug clearance In patients with renal cell carcinoma, previous nephrectomy also may impact on drug clearance Furthermore, the common use of the nephrotoxic chemotherapeutic agent cisplatin in the treatment of urologic malignancies (most prominently, in bladder and testicular neoplasms) may further diminish renal function Careful attention must be paid, therefore, to renal function throughout the course of systemic therapy, with appropriate dose adjustments made Dosing adjustments also must be considered in patients who have undergone cystectomy because ileal conduits or neobladders have the capacity to resorb chemotherapeutic agents that are excreted in the urine in active form (most notably, methotrexate) Frequent local extension in the pelvis presents additional unique problems Patients with previous pelvic radiotherapy have markedly diminished bone marrow reserves, which may limit the use of myelosuppressive drugs Furthermore, local pelvic relapses have the potential to be symptomatic and painful Particularly in patients who have already received radiotherapy, systemic therapy may be important for palliation GERM CELL MALIGNANCIES A OVERVIEW The evolution of therapy for GCT has been deliberate and thoughtful, and has resulted in cures of 80–85% of men with GCT, serving as a model for the treatment of curable cancers Nonetheless, challenges in the management of GCT remain Because of their young age, patients who have been cured are at risk of delayed, treatment-induced toxicity Furthermore, an 80–85% cure rate also implies that 15–20% of patients with GCT will not be cured and ultimately will succumb to their disease An understanding of staging and risk assessment is crucial if (1) patients with good risk features are not to be overtreated and exposed to undue toxic risks, and (2) patients with poor risk features are to receive adequate (curative) therapy The most common multiagent chemotherapy regimen for the treatment of GCT is a 3-drug combination consisting of bleomycin, etoposide, and cisplatin (BEP) The treatment is repeated every 21 days One cycle consists of cisplatin 20 mg/m2 IV day 1–5, etoposide 100 mg/m2 IV day 1–5, and bleomycin, 30 units IV, day 2, 9, and 16 Frequently the first days of treatment require hospitalization The deletion of bleomycin from this regimen results in the PE regimen The substitution of ifosfamide for bleomycin yield the VIP regime (UP-16, ifosfamide, platinum) B USE OF CHEMOTHERAPY FOR PATIENTS WITH STAGE I AND II DISEASE The standard of care for patients with stage I GCT remains orchiectomy followed by retroperitoneal lymphadenectomy (nonseminoma), radiation therapy (seminoma), or in selected patients, careful surveillance The use of chemotherapy in stage I GCT in lieu of lymphadenectomy or irradiation remains investigational despite encouraging early results Patients with stage II nonseminomatous microscopic disease identified at lymphadenectomy (stage IIA) or patients with low-volume clinical stage II disease (stage IIB) who have undergone retroperitoneal lymphadenectomy may benefit from cycles of adjuvant PE or PEB chemotherapy The use of adjuvant therapy results in a 96% long-term disease-free survival While the relapse rate for patients who not receive adjuvant therapy approaches 40%, the vast majority of relapsing patients can also be cured with either or cycles of chemotherapy, yielding an identical long-term survival rate The decision about adjuvant chemotherapy after lymphadenectomy must be individualized Patients at high risk for relapse may choose to undergo cycles of chemotherapy at that point in order to avoid the possibility of 3–4 cycles in the future C USE OF CHEMOTHERAPY IN PATIENTS WITH ADVANCED DISEASE Patients with advanced GCT should be treated with systemic therapy after completion of their orchiectomy This group includes some stage IIB nonseminomatous tumors and all stage IIC or higher tumors, both seminomas and nonseminomas A variety of chemotherapy regimens will result in approximately 80% of patients with advanced GCT achieving a complete response and 70% achieving CHEMOTHERAPY OF UROLOGIC TUMORS / long-term apparent cures (good prognosis) By the same token, however, 20–30% of patients have a poor prognosis and will still ultimately die from their disease Studies of pretreatment clinical characteristics have sought to identify prognostic features that can be prospectively used to segregate this diverse group of advanced GCT patients into poor- and good-prognostic subsets A common classification system has been developed by the International Germ Cell Cancer Collaborative Group (IGCCC) In this system, good-prognosis patients with nonseminomatous GCT have a testis or retroperitoneal primary tumor, no nonpulmonary visceral metastases, and low-serum tumor markers Intermediate-prognosis patients are the same as good-prognosis patients but have intermediate serum tumor markers Poor-prognosis patients have a mediastinal primary tumor or nonpulmonary visceral metastases (liver, bone, brain) or high levels of serum tumor markers Five-year overall survival for the good-, intermediate-, and poor-prognosis categories with current regimens is 92%, 80%, and 48%, respectively By definition, seminomas are never in the poor-prognosis category Seminomas are segregated into good-prognosis cases (any primary site, but no nonpulmonary visceral metastases), with an 86% 5year survival, and intermediate-prognosis cases (any primary site but with the presence of nonpulmonary visceral metastases), with a 72% 5-year survival Because it is not likely that the extraordinarily high cure rate for good-prognosis patients can be improved upon, most efforts in the treatment of these patients have been aimed at optimizing treatment with less toxic regimens that will have equal efficacy Trials evaluating (1) the elimination of bleomycin, (2) a reduction in the number of chemotherapy cycles administered, or (3) the substitution of carboplatin for cisplatin have been undertaken The outlook for poor-prognosis patients is grim, with only 38–62% of patients achieving a complete response Thus, whereas the major concern in goodprognosis patients has been the reduction of toxicity, the major objective of clinical investigation in poor-prognosis patients has been to improve efficacy, with less concern for reducing toxicity Clinical trials in poor-prognosis patients have by and large relied on one or both of two approaches The first has been to exploit agents that have been demonstrated to be efficacious in the salvage setting, and the second has been to evaluate the role of dose escalation Currently acceptable regimens for good-prognosis patients are fairly well defined and include cycles of PEB or cycles of PE By contrast, optimal therapy for poorprognosis patients continues to be investigational Four cycles of PEB or cycles of VIP (are appropriate options D ADJUNCTIVE SURGERY AND “SALVAGE” THERAPY Postchemotherapy adjunctive surgery must be integrated into the treatment plan of patients with advanced GCT Between 10% and 20% of patients with nonseminoma- 305 tous tumors have residual masses after systemic therapy, and up to 80% of patients with seminomas have residual radiographic abnormalities The role of adjunctive surgery in patients with GCT with postchemotherapy residual masses has been reviewed Except in rare circumstances, adjunctive surgery is not indicated in the presence of persistently elevated serum tumor markers Adjunctive surgery usually can be undertaken safely within 1–2 months of completion of chemotherapy It must be noted, however, that all patients who have received bleomycin, whether or not there is clinical evidence of pulmonary fibrosis, are at risk of development of oxygen-related pulmonary toxicity The anesthesiologist must be made aware of the patient’s previous exposure to bleomycin and every effort must be taken to maintain the FiO2 as low as possible throughout the surgical procedure Patients who are found to have active carcinoma in their resected specimens are frequently treated with further “salvage” chemotherapy, generally with a different regimen, although compelling evidence supporting this procedure is still forthcoming Patients who appear to benefit from postsurgical chemotherapy are patients with incomplete resections, patients whose resected specimen contains more than 10% viable cancer cells, and patients who were in the IGCCC high-risk group prior to beginning frontline chemotherapy While approximately 80% of patients with GCT can currently be cured with platinum-based therapy, 20% ultimately die of their disease, either because a complete response is not achieved with induction therapy or because they relapse after becoming disease-free with primary therapy Before the initiation of salvage therapy, the diagnosis of relapsed or primary, refractory GCT must be clearly established In particular, falsely elevated human chorionic gonadotropin or alpha-fetoprotein values and false-positive radiographic studies of the chest due to previous bleomycin use must be ruled out Persistent or slowly growing masses, particularly in the absence of serologic progression, may represent benign teratoma Therapies based on ifosfamide, paclitaxel, or high-dose chemotherapy with autologous bone marrow transplant provide a salvage rate of approximately 25% in patients with relapsed or refractory GCT TRANSITIONAL CELL CARCINOMA OF THE UROEPITHELIUM A NONMETASTATIC DISEASE The development of effective chemotherapy regimens for the treatment of metastatic transitional cell carcinoma (TCC) has resulted in more widespread use of these regimens in combination with other modes for the treatment of locally advanced but nonmetastatic disease In bulky inoperable invasive bladder tumors (T3b, T4, N+), chemotherapy has been used as a means of cytoreduction in order to make surgery possible Chemotherapy before sur- 306 / CHAPTER 19 gery, termed neoadjuvant therapy, has also been used in muscle-invasive cancers that are resectable, in an effort to treat micrometastatic disease before cystectomy It must be borne in mind that the pathologic complete response rate in the bladder after neoadjuvant chemotherapy is probably in the 30–40% range; therefore, definitive surgical resection after chemotherapy is usually required A modest survival advantage has been demonstrated with neoadjuvant MVAC chemotherapy (see below) Other investigators believe that adjuvant therapy administered after radical cystectomy should be the means of treating patients with invasive bladder cancer at risk for relapse Adjuvant trials generally have been used to treat only patients found to have pathologic T3 and T4 lesions Several small randomized trials have shown a benefit to various adjuvant chemotherapy regimens; a large randomized multi-institution trial remains to be done Chemotherapy in combination with radiation therapy has been advocated by some as a bladder-preserving approach for muscle-invasive tumors Patients are usually treated with cycles of chemotherapy, followed by radiation therapy and concomitant cisplatin as a radiosensitizer If follow-up cystoscopy reveals no cancer, consolidative multiagent systemic chemotherapy is administered This approach appears to be particularly useful for smaller, lower-stage tumors The presence of hydronephrosis or hydroureter is a contradiction to this approach, as these patients less well with a bladder sparing approach While longer follow-up is required, it appears that approximately 30–50% of patients can attain long-term diseasefree status with a functional bladder with this approach B METASTATIC DISEASE The development of successful therapy of metastatic bladder TCC has been based on the use of cisplatin Until recently, two common cisplatin-based regimens are in wide use: (1) cisplatin, methotrexate, and vinblastine (CMV) and (2) the same drugs in a slightly different schedule and dose along with doxorubicin (Adriamycin), in a regimen known as MVAC These regimens result in overall response rates of approximately 50–60% and complete remission rates in the 20–35% range Median overall survival for patients with metastatic disease treated with these regimens is in the 8- to 14-month range Despite early promise, however, long-term survival after MVAC or CMV remains in the single digits Both CMV and MVAC are intensive regimens, with myelosuppression occurring commonly The use of hematopoietic growth factors has made it easier to administer full doses on schedule, although this improvement in dose intensity does not appear to translate into a clinical benefit More recently, the combination of gemcitabine and cisplatin has been compared to MVAC This new regimen is far less toxic, is better tolerated, and appears to be equivalent in efficacy to MVAC As a consequence, gemcitabine/ cisplatin can be considered the new standard of care for the treatment of advanced TCC However, it should be noted that the gemcitabine/cisplatin regime has been tested in a randomized study only in patients with metastatic disease, and its utility as an adjuvant or neoadjuvant has not been tested For patients with impaired renal function, agents such as carboplatin and paclitaxel have been utilized RENAL CELL CARCINOMA The treatment of metastatic renal cell carcinoma with chemotherapy remains largely unsatisfactory The general lack of active agents and the excessive toxicity of many of the agents that exhibit some activity have contributed to the absence of adjuvant or neoadjuvant trials The only such trials used adjuvant interferon-alpha for patients considered at high risk for relapse after nephrectomy and failed to show an advantage of the adjuvant therapy Nephrectomy prior to systemic therapy is recommended, particularly in patients in whom the bulk of disease is in the renal mass, and who have a good performance status Metastatic renal cell carcinoma is relatively resistant to chemotherapy The fluoropyrimidines floxuridine, 5fluorouracil, and capecitabine have modest activity, as does gemcitabine, with response proportions of 10–15% reported Renal cell carcinoma is one of very few neoplasms that clearly are responsive to biologic response modifiers The utility of biologic response modifiers and anti-angiogenic agents in renal cell carcinoma is discussed elsewhere in Chapter 20 In general, these agents are used prior to using chemotherapy HORMONE-REFRACTORY PROSTATE CANCER The systemic therapy of patients with metastatic prostate cancer in whom hormonal therapy has failed generally consists of secondary hormonal manipulations followed by chemotherapy Approximately 15% of patients who have had progressive disease despite therapy with combined androgen blockade will have a fall in PSA when their antiandrogen is discontinued This maneuver is mandated, therefore, before initiating other systemic therapy Furthermore, second-line hormonal maneuvers such as adrenal androgen deprivation with ketoconazole, estrogens, or secondary antiandrogens such as nilutamide clearly have activity and, particularly in asymptomatic patients, should be considered As noted previously, the evaluation of responses in patients with bone disease only is difficult at best The use of the PSA in this setting has been fairly extensively evaluated, and it appears to be a reasonable intermediate endpoint Thus, a decline in PSA of 35–50% appears to be predictive of longer survival for these patients Several agents or combinations of agents show promise in the therapy of HRPC Not only can a significant 742 / INDEX Intersex disorders (cont.) mixed, 657t, 672–673, 673f pure, 658t, 672 XY, 673f male pseudohermaphroditism, 668–669 clinical findings, 72f, 670f complete androgen insensitivity in, 668 differential diagnosis, 666t, 669f partial androgen insensitivity in, 669 micropenis, 625, 676–677, 677f, 677t persistent Müllerian duct, 661t, 671–672, 671f surgical management, 677–683 clitoroplasty, 678–679 phallic reconstruction, 679, 683 vaginoplasty, 679, 681f, 682f true hermaphroditism, 657t, 674–675, 674f Turner syndrome, 656t, 672 Interstitial cystitis, 576–577 clinical findings, 576–577 complications, 577 differential diagnosis, 577 vs neuropathic bladder, 447 pathogenesis, 576 pathology, 576 prognosis, 577 treatment, 577 Interstitial nephritis, 526 Intertrigo, 645 Interventional radiology percutaneous See Percutaneous endourology vascular See Vascular interventional radiology Intracavernous injection, for erectile dysfunction, 605–607, 606t adverse effects, 607 alprostadil, 606 contraindications, 607 dosage and administration, 607 drug combinations, 606–607 papaverine, 606 patient acceptance and drop-out rate, 607 phentolamine methylate, 606 Intracytoplasmic sperm injection, 713f, 714 Intrauterine insemination, 713 Isoniazid, for renal tuberculosis, 224 Itraconazole, for tinea cruris, 646 Juxtaglomerular cell tumor, 330 Kallmann syndrome, 699 Kaposi’s sarcoma of penis, 386 of scrotum, 387 Kartagener syndrome, 706 Kayexalate, for acute renal failure, 531 Ketoconazole for candidiasis/candidemia, 226 for Cushing’s syndrome, 495 for prostate cancer, 368, 368t Kidney(s) See also Genitourinary tract; renal entries; specific disorders anatomy blood supply, 3–4, 6f calices, 4, 5f gross appearance, 1, 2f, 3f, 4f histology, 1–3 lymphatics, renal pelvis, 4, 5f CT scans, 85–88f fetal development congenital anomalies, 19–20, 20f See also Kidney disorders, congenital developmental stages, 17–19, 18f, 19f magnetic resonance angiography, 94f MRI, 90–93f normal laboratory values, 729 physical examination, 39–40, 40f ultrasonography, 78–79, 78–80f, 115, 115f Kidney disorders See also Renal failure acquired lesions adenoma, 328 angiomyolipoma See Angiomyolipoma arteriovenous aneurysm, 519, 519f arteriovenous fistulas/malformations See Renal arteriovenous fistulas/ malformations calculi See Calculi, renal and ureteral cysts See Renal cysts hemangioma, 330 hydronephrosis See Hydronephrosis juxtaglomerular cell tumor, 330 leiomyoma, 330 lipoma, 330 medullary tubular ectasia, 62f oncocytoma, 328, 329f renal artery aneurysm, 111–112, 515–516, 517f renal infarcts, 517 renal vein thrombosis, 517–518, 518f renoalimentary fistula, 519 renobronchial fistula, 519 retroperitoneal fibrosis, 65f clinical presentation gastrointestinal symptoms, 34 pain, 30, 31f congenital anomalies abnormal rotation, 515 abnormalities of vessels, 515 agenesis, 506 cysts See Renal cysts dysplasia and multicystic, 506–507 ectopic kidney, 19, 63f, 515 fusion See Renal fusion hypoplasia, 506 malrotation, 20 solitary kidney, 20 supernumerary kidneys, 20, 506 infections See Kidney infections malignant adenocarcinoma See Renal cell carcinoma angiomyolipoma, 80f, 86f neuroblastoma, 86f sarcoma, 101f, 343 secondary tumors, 343 squamous cell carcinoma, 64f transitional cell carcinoma, 63f, 64f, 87f ultrasonography, 80f Wilms’ tumor See Wilms’ tumor medical diseases, 521–530 analgesic nephropathy, 526–527 clinical findings history, 521 imaging, 521 laboratory findings, 521 physical examination, 521 renal biopsy, 521–522 in collagen diseases, 526 distal tubule anomalies, 529 glomerulonephritis See Glomerulonephritis hereditary chronic hereditary nephritis, 527 medullary cystic disease, 528 medullary sponge kidney, 515, 516f, 528 polycystic kidney disease See Polycystic kidney disease idiopathic hypercalciuria, 530 interstitial nephritis, 526 myelomatosis, 527 nephrotic syndrome See Nephrotic syndrome obstructive uropathy, 527 INDEX / proximal tubule anomalies, 528–529 uric acid nephropathy, 527 Kidney infections actinomycosis, 227 bacterial See Pyelonephritis; Urinary tract infections, bacterial candidiasis, 226–227 echinococcosis, 232–233, 233f fungal, 64f tuberculosis See Renal tuberculosis Kidney injuries, 281–287 classification, 282–283f clinical findings, 284–285, 285f, 286f complications, 286 differential diagnosis, 285 lacerations, 86f mechanisms, 281, 281f pathology, 281–284, 284f prognosis, 287 treatment, 286 Kidney transplantation See Renal transplantation Klebsiella, in urinary tract infections, 195, 198t Klinefelter syndrome characteristics, 656t clinical findings, 656t, 695f, 701 male infertility in, 701 treatment, 656t Kock pouch urinary reservoir, 393, 394f L-Q (linear-quadratic) equation, 405 Labial fusion, 639 Laboratory examination in elderly, 56, 56t normal values, 727–730 blood, serum and plasma, 727–729 cerebrospinal fluid, 730 hematology, 727 hormones, serum and plasma, 729 miscellaneous, 730 urologic See Urologic laboratory examination Lactobacillus vaginal suppositories, for chronic cystitis, 207 Laparoscopy complications cardiovascular, 135–136 pulmonary, acid–base, and insufflant-related, 136–137, 137f training and, 152 future developments, 152, 152f instrumentation, 140f, 141 physiology cardiovascular, 135, 136f pulmonary, acid–base, and insufflant-related, 136 postoperative care, 142 preoperative preparation, 137–138, 138f specific procedures adrenalectomy, 150, 150f cystectomy/cystoprostatectomy with urinary diversion, 152 nephrectomy See Nephrectomy nephroureterectomy, 147–148, 148f orchidopexy, 144, 144f pelvic lymph node dissection, 142–143, 142f, 143f, 144f pyeloplasty, 149–150, 150f radial prostatectomy, 151–152 renal cyst decortication, 144–145, 145f retroperitoneal lymph node dissection, 150–151, 151f varicocelectomy, 143–144, 144f techniques exiting the abdomen, 141, 142f extraperitoneal approach, 140, 141f hand assistance, 140–141, 141f insufflation methods, 138–139, 139f port placement, 139–140, 140f Lasers endoscopic use, 136 for intraureteral lithotripsy, 130 for prostate resection, 354 Leflunomide, in renal transplantation, 550 Leiomyoma epididymis, 383 renal, 330 Leukemia, testicular infiltration in, 382 Leukocyte esterase test, 48 Leukocytes, in urine, 49 Leukocytospermia, 692–693, 693t Leukoplakia, penis, 384 Leuprolide acetate, for prostate cancer, 367, 368t Levofloxacin, for epididymitis, 238t Leydig cells age-related changes, 717 tumors, 381 LHRH agonists, for prostate cancer, 367–368, 368t Lice, pubic, 646 Lichen planus, 646 Lichen sclerosus, 646 Lichen simplex chronicus, 645 Lindane, for pediculosis pubis, 646 743 Linear-quadratic (L-Q) equation, 405 Lipoma, renal, 330 Lipomatosis pelvic, 67f perivesical, 583 Lithotripsy See Extracorporeal shock wave lithotripsy Liver cirrhosis, male infertility and, 703 Living donors See Renal transplantation, living donor Luteinizing hormone (LH) in male infertility, 692, 693t, 699 in male reproductive physiology, 685–686 Luteinizing hormone–releasing hormone (LHRH) agonists, for prostate cancer, 367–368, 368t Lymph nodes laparoscopic dissection pelvic, 142–143, 142f, 143f retroperitoneal, 150–151, 151f physical examination, 44 at risk for metastases in testicular tumors, 417–418, 417f Lymphangiography, 66, 73f Lymphangioleiomyomatosis, 329 Lymphocele, retroperitoneal, 125–126, 125f Lymphogranuloma venereum, 240t, 241–242 Lymphoma, testicular, 382 Macrogenitosomia, 495 Magnesium, urinary calculi formation and, 250 Magnetic resonance angiography (MRA), renal, 94f Magnetic resonance imaging (MRI), 85–94, 91–97f See also specific disorders and organs advantages and disadvantages, 94 clinical applications, 87–88, 94 comparison with other methods, 94, 98f, 101f principles, 85 Major histocompatibility complex (MHC), 546 Malacoplakia, 207–208 Male infertility See Infertility, male Male reproductive physiology See Reproductive physiology, male Massage, prostate, 44 Maximum closure pressure, 466 Maximum flow rate, 456, 457f Maximum flow time, 456, 457f Medications See Drugs Medullary cystic disease, 528 744 / INDEX Medullary sponge kidney, 515, 516f, 528 Medullary tubular ectasia, kidney, 62f Megalopenis, 625 Megaureter, obstructed, 568, 568f Meiosis and mitosis basic processes, 687, 687t differences between, 688f, 688t in sperm production, 687–688 Melanoma penis, 386 scrotum, 387 Membranoproliferative glomerulonephritis, 525 Membranous nephropathy, 525 Mercaptopropionylglycine, for urinary calculi, 253, 264, 272 Mesonephros, 17, 18f Metanephros, 17–18, 18f Methantheline bromide for enuresis, 580 for spastic bladder, 449 Methotrexate for bladder transitional cell carcinoma, 306 toxicity, 303t Metrifonate, for schistosomiasis, 230 Metronidazole, for persistent urethritis, 237t Metyrapone, for Cushing’s syndrome, 495 Metyrosine, for pheochromocytoma, 501 Micropenis, 625, 676–677, 677f, 677t Micturition frequent, 35 neural control, 426–429 afferent pathways, 427, 439, 440f afferent signaling from the urothelium/suburothelium, 427–428 of bladder emptying, 428–429 of bladder filling, 428 parasympathetic pathways, 426–427 somatic pathways, 427 sympathetic pathways, 427 pharmacologic targets, 429–434 central nervous system dopamine mechanisms, 431 GABA mechanisms, 430–431 noradrenaline mechanisms, 431 opioid receptors, 429–430 serotonin mechanisms, 430 peripheral adrenergic receptors, 432–433 botulinum toxin-sensitive mechanisms, 434–435 ion channels, 433–434 muscarinic receptors, 431–432 vanilloid receptors, 434 symptoms related to, 35–37 urgent, 35 urodynamic studies See Urodynamic studies Minimal-change nephropathy, 524 Mitomycin C for bladder cancer, 316 for upper urinary tract cancer, 323 Mitosis See Meiosis and mitosis Mitotane, for Cushing’s syndrome, 495 Mitoxantrone, for hormone-refractory prostate cancer, 307 Mixed gonadal dysgenesis, 657t Molluscum contagiosum, 647–648 Monobactams, in pregnancy, 212t Monoclonal antibodies for immunotherapy of urologic cancer, 298 radioimmunodetection, 298 in renal transplantation, 552 Morphine, for detrusor overactivity/overactive bladder, 429 MRI See Magnetic resonance imaging Mucopurulent cervicitis, 238 Müllerian duct(s) cyst, 72f fetal development, 21, 23f, 25, 26 persistent, 661t, 671–672, 671f Mumps, male infertility and, 689–690 Munchausen syndrome, 254, 274 Muromonab-CD3, in renal transplantation, 552 Muscarinic receptors, in micturition, 431–432 Mycobacterium infections, 213 See also Tuberculosis, urinary tract Mycophenolate mofetil, in renal transplantation, 550 Mycoplasma spp., urethritis caused by, 235 Myelolipoma, adrenal, 502, 502f Myelomatosis, 527 Myotonic dystrophy, 702 Neisseria gonorrhoeae, 198t, 235 See also Gonorrhea Neoarsphenamine, for amicrobic cystitis, 226 Nephrectomy laparoscopic approaches, 145 complications, 147 living donor, 148–149, 547 outcomes, 147 partial, 148–149 techniques, 145–147, 146f, 147f open, for living donor, 547 partial, for renal stones, 270 for renal cell carcinoma, 336–337, 336f transplant allograft, 542 Nephric system See also Kidney(s) congenital anomalies, 19–20, 20f, 63f fetal development, 17–19, 18f, 19f Nephritis See also Glomerulonephritis; Pyelonephritis chronic hereditary, 527 interstitial, 526 Nephroblastoma See Wilms’ tumor Nephrolithiasis See Calculi, renal and ureteral Nephrolithotomy anatrophic, 269–270 percutaneous, 269 Nephropathy analgesic, 526–527 membranous, 525 reflux, 187 See also Vesicoureteral reflux uric acid, 527 Nephroscopy, percutaneous, 121–124 instrumentation, 121, 121f large-bore dilation, 121–122, 122f for nephrolithotomy, 114, 122–123, 122f, 123f for renal pelvis tumor, 124 for ureteropelvic stenosis, 123–124 Nephrotic syndrome, 524–526 clinical findings differential diagnosis, 526 laboratory findings, 525 signs and symptoms, 525 diagnosis, 524 diseases associated with, 524–525 focal glomerulosclerosis, 524–525 membranoproliferative glomerulonephritis, 525 membranous nephropathy, 525 minimal glomerular lesions, 524 prognosis, 526 treatment, 526 Nephrotomy, radial, 270 Nephroureterectomy, laparoscopic, 147–148, 148f Neuroblastoma, 86f, 503–504 Neurologic examination, 44 Neuropathic bladder, 442–453 classification, 442–443, 442t clinical findings flaccid bladder, 446 imaging, 68f mildly spastic neuromuscular dysfunction, 445–446 INDEX / spastic bladder, 444–445, 445f complications autonomic dysreflexia, 453 calculi, 452–453 hydronephrosis, 452 infection, 452 renal amyloidosis, 453 sexual dysfunction, 453 differential diagnosis, 447 etiology injury causing poor detrusor distensibility, 443 injury to afferent feedback pathways, 443 injury to detrusor motor nucleus, 443 injury to external sphincter, 443 lesions above sacral micturition center, 442–443 lesions at or below sacral micturition center, 443 prognosis, 453 treatment flaccid bladder, 450 spastic bladder, 448–449 in spina bifida, 450–451 spinal shock, 447–448 urinary incontinence control, 451 See also Urinary incontinence, neuropathic vesical function after spinal cord injury, 443–444 Neurostimulation for neuropathic incontinence, 489 for spastic bladder, 449 for urinary incontinence control, 451 Neurotransmitters, erectile function and, 592 Nifedipine, for autonomic dysreflexia, 453 Nilutamide, for prostate cancer, 368t Niridazole, for schistosomiasis, 231 Nitric oxide, erectile function and, 592 Nitrite reductase test, 48 Nitrofurantoin for bacterial urinary tract infections, 199 for candidiasis/candidemia, 226 for chronic prostatitis, 209 in pregnancy, 212t prophylactic regimen, 199t Nitroprusside test, 53 Nocturnal penile tumescence test, 600–601 Noonan syndrome, 702 Nuclear magnetic resonance, 85 See also Magnetic resonance imaging Nuclear matrix protein 22 test, 53 Nystatin for candidiasis, 647 for intertrigo, 645 Obesity renal transplantation and, 541–542 urinary calculi in, 258–259 Obstruction and stasis, urinary, 166–177 See also specific organs and types, e.g., Calculi classification, 166 clinical findings, 173–176 imaging, 174–176, 175f instrumental examination, 176 interventional uroradiology, 176 isotope scanning, 176 laboratory findings, 174 signs and symptoms, 173–174 complications, 176 differential diagnosis, 176 etiology, 166, 569–570 in malignant disease, 65f, 571 pathogenesis and pathology, 166–173 bladder neck obstruction compensation phase, 173 decompensation phase, 173 lower tract, 166 mid tract, 166–168, 167f upper tract, 168–173 kidney, 168–173, 169–172f ureter, 130–131, 168, 169f, 569–570, 570f prognosis, 177 treatment, 176–177 vesicoureteral reflux and, 188 Ofloxacin, for epididymitis, 238t Oliguria, 36, 531 See also Renal failure, acute Omega-3 fatty acids, for IgA nephropathy, 524 Omniport, 141f Oncocytoma, renal, 328, 329f Oncocytomatosis, 328 Opioid receptors, in micturition, 429–430 Opioids, for detrusor overactivity/overactive bladder, 429–430 Orange juice, for urinary alkalinization, 263 Orchidometer, 690, 690f Orchidopexy, 144, 144f, 711 Orchiectomy, for prostate cancer, 368t Orchitis, 704 Orgasm, male disorders, 609 physiology, 608 Ormond disease, 570–571, 570f 745 Orthophosphate, for urinary calculi, 250 Oval fat bodies, 521 Ovarian vein varices, transcatheter embolization, 109, 110f Ovary(ies) descent, 25 fetal development, 23–25, 24f Overactive bladder, pharmacologic targets adrenergic receptors, 432–433 botulinum toxin-sensitive mechanisms, 434–435 dopamine mechanisms, 431 GABA mechanisms, 430–431 ion channels, 433–434 muscarinic receptors, 431–432 noradrenaline mechanisms, 431 opioid receptors, 429–430 serotonin mechanisms, 430 vanilloid receptors, 434 Oxalate, urinary, 248 Oxamniquine, for schistosomiasis, 230 Oxybutynin chloride for neuropathic incontinence, 488 for spastic bladder, 449 for urge incontinence, 485 Oxychlorosene sodium, for interstitial cystitis, 577 Paclitaxel, 303t Pain in genitourinary tract disorders, 30–34, 31f from renal and ureteral calculi, 254–256, 255f renal vs radicular, 40 P450aldo block, 496 Palpation of female genitalia, 42 of kidneys, 39, 40f of penis, 41 Papaverine, for erectile dysfunction, 606 Papilloma bladder, 310 ureter, 320 Paraneoplastic syndromes, in renal cell carcinoma, 332–333 Paranephric abscesses, 202 Paraphimosis, 633 Parasympathetic pathways, micturition, 426–427 Parathyroid hormone studies, 55 Paternal age, birth defects and, 720 P450c11 block, 496 P450c17 block, 496 P450c21 block, 496 See also 21α-Hydroxylase deficiency 746 / INDEX PEB regimen for germ cell tumors, 304–305 for seminoma, 420 Pediculosis pubis, 646 Pelvic congestion syndrome, 109 Pelvic lymph node dissection, laparoscopic, 142–143, 142f, 143f Pelvic organ prolapse, 611–620 anatomic factors bony pelvis, 611, 612f innervation, 613 musculofascial support, 611–613, 612f, 613f, 614f classification, 614, 615f, 616f diagnosis physical examination, 615 symptoms, 614–615 evaluation cystourethrography, 615–616, 616f cystourethroscopy, 617–618 laboratory, 618 MRI, 616–617, 617f ultrasonography, 616f upper urinary tract, 618 video urodynamic study, 617 vs neuropathic bladder, 447 pathophysiology, 613 treatment nonsurgical, 618 surgical repair anterior compartment, 618–619, 618f apical compartment, 619, 619f posterior compartment, 619–620 Pelvic-to-hypogastric reflex, 428 Pelvic-to-pudendal reflex, 428 D-Penicillamine for urinary calculi, 253, 264, 272 for Wilson’s disease, 528 Penicillin(s) for bacterial urinary tract infections, 199 in pregnancy, 212t for syphilis, 240t, 241 Penicillin G, for actinomycosis, 227 Penicillin V, for actinomycosis, 227 Penile fibrosis, 77f Penile thermal sensory testing, 600 Penis acquired disorders paraphimosis, 633 Peyronie’s disease, 632–633 phimosis, 633 phlebothrombosis and lymphatic occlusion, 636 priapism See Priapism anatomy, 14, 589–590, 590f circumcision, 633 congenital anomalies, 22, 625 apenia, 625 megalopenis, 625 micropenis, 625, 676–677, 677f, 677t erectile dysfunction See Erectile dysfunction erectile function See Erectile function fetal development, 27, 650–652, 651–655f injuries, 295 physical examination, 40–41 size, infancy to adulthood, 625, 626t, 663t tumors, 383–386 clinical findings, 384–385 differential diagnosis, 385 epidemiology, 383 pathology carcinoma in situ, 384 invasive carcinoma, 384 precancerous dermatologic lesions, 384 patterns of metastatic spread, 384 prognosis, 386 risk factors, 383–384 staging, 384, 384t treatment algorithm, 386f lymph node dissection, 385–386, 385f primary lesion, 385 radiotherapy, 416–417 systemic disease, 386 venography, 76, 77f Percussion, of kidneys, 39 Percutaneous endourology, 114–128 antegrade pyelography, 117 aspiration and biopsy, 124–128 differential diagnosis, 124t indications, 124t renal and retroperitoneal tumors, 126, 126f renal biopsy, 128 renal cysts, 125 retroperitoneal fluid collections, 125–126, 125f catheter placement, 118–121.7, 119f contraindications, 114 imaging and puncture techniques, 114–117, 115–117f indications, 115t instruments, 116f nephroscopy, 121–124 instrumentation, 121, 121f large-bore dilation, 121–122, 122f for nephrolithotomy, 114, 122–123, 122f, 123f for renal pelvis tumor, 124 for ureteropelvic stenosis, 123–124 perfusion-chemolysis of renal stones, 120–121, 120f pressure/perfusion studies, 117–118, 118f Percutaneous nephrolithotomy (PNL), 114, 122–123, 122f, 123f Perfusion-chemolysis, of renal stones, 120–121, 120f Perinephric abscesses, 202, 203f Peritoneal dialysis, 537 Permethrin for pediculosis pubis, 646 for scabies, 646 Persistent Müllerian duct, 661t, 671–672, 671f Pessary, vaginal, 618 Peyronie’s disease, 632–633 pH, urine, 47–48 Phenoxybenzamine for benign prostatic hyperplasia, 352t, 353 in pheochromocytoma, 501 in urethral pressure profile study, 467 Phentolamine methylate, for erectile dysfunction, 606 Phenylpropanolamine hydrochloride, for retrograde ejaculation, 609 Phenytoin, or enuresis, 580 Pheochromocytoma, 498–501 clinical findings, 499, 499t diagnostic strategy, 500 extra-adrenal, 99f, 500 imaging, 500, 502f malignant, 501 treatment, 500–501 tumor localization, 499–500, 500f Phimosis, 633 Phosphate, urinary, 248 Phosphate supplementation, for urinary stone prevention, 271 Phosphodiesterase inhibitors, 603–605 adverse events, 604 clinical efficacy, 603–604 mechanism of action, 603 period of efficacy, 604 starting doses, 605 time of onset, 604 warnings and drug interactions, 604–605 Phosphorus, reabsorption defects, 529 INDEX / Phytotherapy, for benign prostatic hyperplasia, 353 Pituitary ablation, 711 Pituitary disease, male infertility and, 700–701 Plasma laboratory examination, 55–56 normal laboratory values, 727–729 Pneumaturia, 36 Pneumoperitoneum for laparoscopy, 138–139, 139f tension, 135 Podofilox, for genital warts, 243, 243t Podophyllin resin, for genital warts, 243, 243t Podophyllotoxin, for genital warts, 647 Pollen extract, for benign prostatic hyperplasia, 353 Polyclonal antibodies, in renal transplantation, 551 Polycystic kidney disease, 507–510 clinical findings imaging, 90f, 508 laboratory findings, 508 signs and symptoms, 507–508, 528 complications, 508–510 differential diagnosis, 508 etiology, 507 infantile, 63f male infertility in, 705–706 pathology, 507, 507f, 528 prognosis, 510, 528 treatment, 510 Poplar, trembling, for benign prostatic hyperplasia, 353 POPQ system, for pelvic organ prolapse quantification, 614, 615f, 616f Ports, for laparoscopy, 139–140, 140f Posterior colporrhaphy, 619–620 Poststreptococcal glomerulonephritis, 522–523 Potassium channels, in micturition, 433–434 Potassium citrate, for urinary calculi, 251, 271 Potassium secretion excess, 529 reduced, 529 Prader orchidometer, 690f Prader-Willi syndrome, 699–700 Pramoxine hydrochloride, for circumscribed neurodermatitis, 645 Praziquantel, for schistosomiasis, 230 Prazosin, for benign prostatic hyperplasia, 352t, 353 Prednisone with docetaxel, for hormone-refractory prostate cancer, 307 for interstitial cystitis, 577 Pregnancy urinary calculi in, 257, 258f urinary tract changes in, 212 urinary tract infections in, 212, 212t Preimplantation genetic diagnosis, 714 Premature ejaculation, 593, 608–609 Preputial calculi, 274–275 Pressure, urethral See Urethral pressure profile Pressure/perfusion studies, 117–118, 118f Priapism, 632 causes, 632 classification, 632 high-flow, transcatheter embolization for, 109, 111f treatment, 607, 632 Probenecid, for syphilis, 240t Procaine penicillin, for syphilis, 240t Profilometry, 464 See also Urethral pressure profile Prolactin in male infertility, 692, 693t in male reproductive physiology, 686 Pronephros, 17, 18f Propantheline bromide, for spastic bladder, 449 ProstaScint, 363 Prostate anatomy, 348, 349f blood supply, 11–12 gross appearance, 11, 11f, 12f histology, 10f, 11 lymphatics, 12 nerve supply, 12 relations, 11 calculi, 273–274 fetal development, 21–22 MRI, 96f physical examination consistency, 43, 43f massage and prostatic smear, 44 mobility, 43 size, 43 ultrasonography, 164 Prostate biopsy, 361 Prostate cancer, 355–369 antigens, 297–298 chemoprevention, 359 clinical findings combined modality risk assessment, 361, 362t imaging antibody imaging, 363 747 bone scan, 359f, 362–363 CT scan, 362 endorectal MRI, 362 MRI, 362 transrectal ultrasonography, 361–362 laboratory findings, 360 prostate biopsy, 361 signs and symptoms, 359–360 tumor markers, 360–361, 361t See also Prostate-specific antigen differential diagnosis, 363 epidemiology, 355 grading, 357–358 immunotherapy, 300 incidence, 355 molecular genetics, 356 pathology, 356–357, 357f progression patterns, 359, 359f risk factors, 355–356 screening, 363 staging, 358–359, 358t testosterone replacement therapy and, 603 treatment hormone-refractory, 306–307, 369 localized disease brachytherapy, 366 cryosurgery and high-intensity focused ultrasound, 366 external beam radiotherapy, 365–366 general considerations, 364 radial prostatectomy, 364–365 watchful waiting/active surveillance, 364 metastatic disease, 367–369, 368t radiotherapy, 406–412 brachytherapy, 409–411 complications, 412 conventional EBRT, 406–408, 407t, 408t 3D conformal radiotherapy, 409, 410f, 410t hormonal therapy and, 408 intensity-modulated radiotherapy, 409, 409f, 410t, 411t neutrons, protons, and heavycharged particles, 411–412 postoperative, 412 recurrent disease, 367 vaccination, 299 Prostate disorders benign prostatic hyperplasia See Benign prostatic hyperplasia cancer See Prostate cancer congenital, 584 748 / INDEX Prostate disorders (cont.) infections See Prostate infections pain in, 34 rhabdomyosarcoma, 69f Prostate infections abscess, 210, 211f prostatitis acute, 208–209 chronic, 209, 209t granulomatous, 209–210 in HIV/AIDS, 213 treatment, 198t, 208–209 tuberculosis, 219, 221, 224–225 See also Tuberculosis, urinary tract Prostate-specific antigen (PSA) age-adjusted reference ranges, 360–361, 361t density, 360 detection, 360 for detection of recurrent prostate cancer, 367 molecular forms, 361 for prostate cancer screening, 55, 363 racial variations, 361 velocity, 360 Prostatectomy complications, 184, 365 open simple, 354 radical laparoscopic, 151–152 for prostate cancer, 364–365 radiotherapy following, 412 transurethral laser, 354 urinary incontinence following, 468–469 Prostatic hyperplasia, benign See Benign prostatic hyperplasia Prostatitis See Prostate infections Proteinuria, 48, 521 Proteus, in urinary tract infections, 195, 198t Prune belly (Eagle-Barrett) syndrome, 184 P450scc block, 496 Pseudohermaphroditism See also Intersex disorders female, 665–668, 667f, 668t congenital adrenal hyperplasia and, 495–497, 665–668, 667f differential diagnosis, 666t maternal medications and, 668, 668t maternal tumors and, 668 male, 668–669 clinical findings, 72f, 670f complete androgen insensitivity in, 668 differential diagnosis, 666t, 669f partial androgen insensitivity in, 669 Pseudomonas spp., in urinary tract infections, 195, 198t Psoriasis, 645–646 Psychosexual therapy for erectile dysfunction, 602 for female sexual dysfunction, 622 Pubic lice, 646 Pure gonadal dysgenesis, 658t Pyelolithotomy, 269 Pyelonephritis, 200–206 acute, 198t, 200 after urinary diversion, 400–401 bilateral staghorn calculi in, 60f chronic, 201–202, 202f clinical presentation, 30, 200 in diabetes mellitus, 213–214 emphysematous, 62f, 200–201 imaging, 200 CT scan, 87f, 200, 201f, 205f DMSA scan, 202f voiding cystourethrogram, 202f in polycystic kidney disease, 508 vesicoureteral reflux and, 183–184, 187 xanthogranulomatous, 204, 205f, 257 Pyeloplasty laparoscopic, 149–150, 150f Pyonephrosis clinical findings, 204, 206f treatment, 206 urinary calculi and, 257, 257f Pyospermia, 711 Pyrazinamide, for renal tuberculosis, 224 QUANTICYT System, 53 Quinolones See Fluoroquinolones Racial/ethnic differences, in prostate cancer detection, 361 Radial nephrotomy, 270 Radiation cystitis, 583 Radiation sensitivity, 404 Radiation therapy See Radiotherapy Radiation tolerance, 404 Radiofrequency ablation, renal lesions, 127 Radiography, 58–76 See also specific disorders and organs advantages and disadvantages, 59 angiography aortorenal and renal, 66, 74, 74f inferior venacavography and venography, 74, 75–76f, 76 miscellaneous urologic, 76, 77f contrast media, 58–59 cystography and voiding cystourethrography, 61, 66–69f equipment and techniques, 58–59 lymphangiography, 66, 73f plain film, abdomen, 59, 60–62f urethrography, 66, 70–72f urography, 59–61, 62–65f vasography, 66, 73f Radioimmunodetection, 298 Radiology, 58–45 See also specific disorders comparison of methods, 94 CT scanning See Computed tomography MRI See Magnetic resonance imaging (MRI) in percutaneous endourology See Percutaneous endourology radiography See Radiography ultrasonography See Ultrasonography in ureterorenoscopy See Ureterorenoscopy vascular interventional See Vascular interventional radiology Radiotherapy, 404–420 for bladder cancer, 318–319, 413–415 altered fractionation schedules, 415 brachytherapy, 415 combined with chemotherapy, 414–415, 414t conventional EBRT, 413–415 image-guided conformal, 415 toxicity, 415 general principles altered fractionation schedules, 405 brachytherapy, 405, 406f dose per fraction considerations, 405 mechanisms of cytotoxicity, 404 radiation sensitivity and tolerance, 404 history of, 404 for penile cancer, 416–417 for prostate cancer, 406–412 brachytherapy, 409–411 complications, 412 conventional EBRT, 406–408, 407t, 408t 3D conformal radiotherapy, 409, 410f, 410t hormonal therapy and, 408 intensity-modulated radiotherapy, 409, 409f, 410t, 411t in localized disease, 365–366 neutrons, protons, and heavycharged particles, 411–412 postoperative, 412 for renal cell carcinoma, 338, 415–416 INDEX / sperm production and, 702–703 for testicular germ cell tumors, 417–420 conventional EBRT, 417–418 limited-field EBRT, 419–420 toxicity, 420 for ureteral carcinoma, 416 for urethral carcinoma female, 406f, 416 male, 416–417 Rectal examination, male, 42–43 Rectocele See Pelvic organ prolapse 5α-reductase deficiency male infertility and, 703–704 type 2, 660t, 669–671, 670f, 671f 5α-reductase inhibitors, for benign prostatic hyperplasia, 352t, 353 Reflux, vesicoureteral See Vesicoureteral reflux Reflux nephropathy, 187 Reifenstein syndrome, 661t Rejection, in renal transplantation acute, 83f, 548–549 chronic, 549, 549f treatment, 553 Renal abscess clinical presentation, 202–203 imaging, 203–204, 203f treatment, 204 Renal agenesis, 506 Renal amyloidosis, in neuropathic bladder, 453 Renal arteriovenous fistulas/malformations clinical findings, 518–519 etiology, 518 in renal trauma, 284 transcatheter embolization, 105, 106f Renal artery aneurysms, 111–112, 515–516, 517f angioplasty and stenting, 109–111, 112f congenital abnormalities, 515 stenosis angiography, 74f bilateral, 74f magnetic resonance angiography, 94f transcatheter embolization before excision of renal cell carcinoma, 107, 108f Renal biopsy, 128, 522 Renal calculi See Calculi, renal and ureteral Renal cell carcinoma, 330–339 clinical findings fine-needle aspiration, 335 imaging angiography, 334, 334f comparison of methods, 98f CT scans, 86f, 87f, 334, 334f MRI, 92–93f, 334–335, 335f PET, 335f plain films, 60f radiographic tomography, 63f radionuclide imaging, 334 ultrasonography, 80f, 333–334, 333f instrumental and cytologic examination, 335 laboratory findings, 333 paraneoplastic syndromes, 332–333 signs and symptoms, 332 differential diagnosis, 335–336 etiology, 330–331 grading, 331–332 incidence, 330 pathogenesis, 331 pathology, 331, 331f prognosis, 339 staging, 331, 332t treatment biologic response modifiers, 300, 338–339 chemotherapy, 306 disseminated disease, 337–339 follow-up care, 339 local disease, 336–337, 336f radiotherapy, 338, 415–416 transcatheter embolization of renal artery in, 107, 108f venal caval involvement, 337f venal caval thrombi, 336–337 Renal cysts, 510–512 clinical findings laboratory findings, 511 percutaneous aspiration and biopsy, 125 signs and symptoms, 511 complications, 512 differential diagnosis, 124t, 511–512 etiology, 510–511 imaging, 511 CT scans, 85f, 510f, 511 excretory urogram, 509f infusion nephrotomogram, 509f ultrasonography, 80f, 511 pathology, 511 prognosis, 512 treatment, 512 laparoscopic decortication, 144–145, 145f percutaneous drainage, 125, 125f Renal disease See Kidney disorders Renal dysplasia, 506–507 749 Renal failure acute, 531–534 after urinary diversion, 401 causes, 531, 532t intrarenal, 532–534 postrenal, 534 prerenal, 531–532, 532t vascular, 532 chronic, 535–537 clinical findings, 535–536 etiology, 535 historical background, 535 overview, 535 stages, 535, 536t treatment, 536–537 male infertility and, 703 Renal function tests blood urea nitrogen, 55 endogenous creatinine clearance, 55 serum creatinine, 54 urine specific gravity, 54 Renal fusion, 512–515 clinical findings, 513 complications, 513 differential diagnosis, 513 etiology, 20, 512–513 imaging, 91f pathology, 513, 514f prognosis, 515 treatment, 515 Renal hamartoma See Angiomyolipoma Renal hypoplasia, 506 Renal infarcts, 517 Renal lesions cryotherapy, 127 percutaneous aspiration biopsy, 126, 126f radiofrequency ablation, 127 Renal parenchymal neoplasms, 328–330 adenocarcinoma See Renal cell carcinoma benign tumors adenoma, 328 angiomyolipoma See Angiomyolipoma hemangioma, 330 juxtaglomerular cell tumor, 330 leiomyoma, 330 lipoma, 330 oncocytoma, 328, 329f sarcoma, 101f, 343 secondary, 343 Wilms’ tumor See Wilms’ tumor Renal pelvis tumors, 320–323 cancer clinical findings, 321–322, 322f etiology, 320 750 / INDEX Renal pelvis tumors (cont.) incidence, 320 pathology, 320 staging and natural history, 321, 321t treatment, 323 percutaneous endoscopic treatment, 124 Renal sarcoma, 101f, 343 Renal transplantation, 539–555 complications bacterial infections, 554 cancer, 555 diabetes, 555 fungal infections, 555 urologic, 554 vascular, 553–554 viral infections, 554–555 wound problems, 554 deceased donor cardiac death vs brain death, 544, 544–545 dual, 545, 545t extended criteria, 544, 545t extracorporeal renal preservation, 545 organ retrieval procedure, 547 pediatric en-bloc, 545 standard criteria, 544 imaging of transplant kidney, 548 immunosuppressive drugs, 549–552 azathioprine, 550 calcineurin inhibitors, 550–551 corticosteroids, 549–550 cyclophosphamide, 550 leflunomide, 550 monoclonal antibodies, 551 mycophenolate mofetil, 550 polyclonal antibodies, 551 regimens, 552 for rejection, 552 target-of-rapamycin inhibitors, 551 incidence, 539 indications, 537, 539 living donor, 542–547 altruistic, 543 deceased donor exchange, 543 directed, 542–543 evaluation, 546–547, 547t immunologic hierarchy, 543t laparoscopic nephrectomy for, 149, 547 nondirected, 543 open nephrectomy for, 547 paired exchange, 543 safety, 543–544 sources, 544f major histocompatibility complex in, 546 postoperative care graft function, 548 hemodynamic management, 548 urine output, 548 recipient selection and preparation, 539–542 blood transfusion, 542 cardiovascular status, 541 gastrointestinal disease, 541 genitourinary tract evaluation, 539–540 infection, 540–541 malignant disease, 541 modifiable risk factors, 541–542 systemic and metabolic disease, 541 rejection acute, 83f, 548–549 chronic, 549, 549f treatment, 553 results, 539, 540f, 542f, 553, 553t surgical technique, 547 transplant allograft nephrectomy, 542 urinary calculi in, 257, 258f Renal tuberculosis complications, 224 differential diagnosis, 223–224 imaging, 60f, 62f, 222–223, 223f pathogenesis, 219, 220f pathology, 221 treatment, 224 Renal tubular acidosis, 529 bilateral nephrocalcinosis with, 60f pathophysiology, 529 treatment, 529 urinary calculi in, 259 Renal vascular hypertension magnetic resonance angiography, 94f in renal trauma, 284 Renal vein thrombosis, 517–518, 518f tumor thrombus in, 76f Renoalimentary fistula, 519 Renobronchial fistula, 519 Reproductive physiology, male, 684–688 fertilization, 688 hypothalamic-pituitary-gonadal axis, 684–686, 685f anterior pituitary, 685–686 feedback loops, 684 hormone classes, 684, 685f hypothalamus, 684–685, 685t testis, 686 spermatogenesis, 686–688 cycles and saves, 687 germ cells, 687 meiosis and mitosis, 687, 687t, 688f Sertoli cells, 686–687 sperm maturation, 688 sperm production, 687–688 Resectoscope, transurethral, 161, 162f Resiniferatoxin for detrusor overactivity, 434 for spastic bladder, 449 Retrograde ejaculation, 593, 609 Retrograde instrumentation, urinary tract, 155–164 cystoscopy, 157–158 lasers, 163 lower tract calculi removal, 163 for transurethral surgery, 161–163, 162f ultrasonography, 163–164, 164f ureteral catheterization, 158–161, 158–161f urethral catheterization, 155–156, 157f urethroscopy, 156–157 Retroperitoneal fibrosis, 65f, 570–571, 570f Retroperitoneal lymph node dissection, laparoscopic, 150–151, 151f Rhabdomyosarcoma, prostate, 69f Rifampin, for renal tuberculosis, 224 Rituximab, in renal transplantation, 552 Saccule, ureteral, 183, 184f Sacral nerve stimulation, for urge incontinence, 485 Sacrocolpopexy, abdominal, 619, 619f Sarcoma, renal, 101f, 343 Saw palmetto, for benign prostatic hyperplasia, 353 Scabies, 646 Schistosoma, 227, 310 See also Schistosomiasis Schistosomiasis, 227–231 clinical findings imaging, 61f, 228, 229f, 230f instrumental examination, 228 laboratory findings, 228 signs, 228 symptoms, 228 complications, 231 differential diagnosis, 228–229, 577 epidemiology, 227 etiology, 227 pathogenesis, 227 pathology, 228, 310 prognosis, 231 treatment, 229–231 INDEX / Scrotum anatomy, 9f, 13–14 injuries, 295 MRI, 97f physical examination, 41 tumors, 387 ultrasonography, 694, 696f Seborrheic dermatitis, 646 Selective serotonin reuptake inhibitors (SSRIs) for detrusor overactivity/overactive bladder, 430 erectile dysfunction and, 595 female sexual dysfunction and, 622 for premature ejaculation, 609 Semen age-related changes, 718–720, 719f, 719t analysis computer assisted, 692 findings in infertile men, 692t fructose, 692 leukocytes, 10t, 692–693 normal values, 691t physical characteristics and measured variables, 691–692 sample collection, 691 culture, 698–699, 699f Seminal vesicles anatomy, 7f, 9f, 12 calculi, 273–274 disorders congenital, 584 vesiculitis, 73f fetal development, 26 MRI, 96f obstruction, 706 physical examination, 44 tuberculosis See Tuberculosis, urinary tract Seminoma See also Germ cell tumors, testicular CT scan, 89f pathology, 376 surveillance guidelines, 419t treatment, 379, 419–420, 419f Serotonin (5-HT) mechanisms, in micturition, 430–431 Serratia sp., antibiotics for, 198t Sertoli-cell-only syndrome, 702 Sertoli cells age-related changes, 718, 718t exocrine functions, 686 in spermatogenesis, 686 tumors, 381–382 Serum creatinine, 54 Serum screening, 546 Sexual determination and differentiation, 649–655 chromosomal sex and, 649 disorders See Intersex disorders female genitalia development, 650, 651f, 652f gonadal differentiation, 649, 650f hormones and, 649–650 male genitalia development, 650–652, 651–655f Sexual difficulty/dysfunction, female, 38, 620–622 definitions, 620, 620t evaluation, 621, 621t physiology, 621 recommendations and conclusions, 622–623 treatment hormonal, 622 nonhormonal, 622 pharmacologic, 622 psychologic, 622 Sexual difficulty/dysfunction, male, 38 definitions, 593 ejaculation, emission, and orgasmic disorders, 608–609 erectile dysfunction See Erectile dysfunction Sexually transmitted diseases, 235–244, 236t epididymitis, 238, 238t genital ulcer diseases chancroid, 240t, 241 diagnostic testing, 239 granuloma inguinale, 240t, 242 herpes simplex virus infection, 239–240, 240t lymphogranuloma venereum, 240t, 241–242 syphilis, 240–241, 240t warts, 242–243, 243t gonorrhea etiology, 235 laboratory testing, 236 treatment, 198t, 236–237, 237t HIV infection, 243–244 mucopurulent cervicitis, 238 syndromes, 236t urethritis in men See Urethritis Shock wave lithotripsy See Extracorporeal shock wave lithotripsy Sickle cell disease, male infertility and, 703 Sildenafil, 603–605, 622 Silicate stones, 254 Sirolimus, in renal transplantation, 551 Smoking bladder cancer and, 308 751 erectile dysfunction and, 596 renal transplantation and, 542 Sodium, urinary calculi formation and, 248 Sodium bicarbonate for acute renal failure, 531 for urinary calculi, 264 for urinary tract candidiasis, 226 Sodium oxychlorosene, 226 Sodium pentosanpolysulfate, for interstitial cystitis, 577 Solifenacin for neuropathic incontinence, 488 for urge incontinence, 485 Solubility product (K sp), 246 Somatic pathways, micturition, 427 Somatic storage reflex, 428 Sonography See Ultrasonography Spastic neuropathic bladder See also Neuropathic bladder clinical findings, 444–445 treatment, 448–449 Specific gravity, urine, 47, 54 Sperm See also Spermatogenesis aspiration, 710–711, 710f, 710t chromatin structure, 694 disorders of function or motility, 706–707 hypoosmotic swelling test, 693 penetration assay, 693 Spermatic cord anatomy, 8f, 12–13 physical examination, 41 tuberculosis, 221 See also Tuberculosis, urinary tract tumors, 383 Spermatogenesis, 686–688 age-related changes chromosomal anomalies, 719, 719f fertility, 719 genetic mutations, 719–720, 719t production, 718, 719t semen quality, 718–719 cycles and waves, 687 germ cells in, 687 Sertoli cells in, 686–687 sperm production in, 687–688 Sphincter/detrusor dyssynergia See Detrusor/sphincter dyssynergia Sphincteric function urodynamic studies, 464–16 dynamic changes in pressure profile, 466–467, 467f electromyography, 464–465, 465f profilometry, 464 urethral pressure profile, 441 components, 465–466, 466f, 467f 752 / INDEX Sphincteric function (cont.) in detrusor/sphincter dyssynergia, 469 dynamic changes, 466–467, 467f normal, 468, 468f in urinary incontinence, 468–469, 469f Sphincterotomy, for neuropathic incontinence, 489 Spina bifida, neuropathic bladder treatment in, 450–451 Spinal cord disease erectile dysfunction in, 594 vesicoureteral reflux in, 188 Spinal shock treatment, 447–448 vesical function recovery after, 443–444 Squamous cell carcinoma bladder, in schistosomiasis, 230f, 231, 310 kidney, 64f penis, 384 renal pelvis, 320 scrotum, 387 Staghorn calculi, 60f Staphylococcus aureus in external genital infections, 647 in urinary tract infections, 195, 198t Staphylococcus epidermidis, in urinary tract infections, 198t Staphylococcus saprophyticus, in urinary tract infections, 195, 198t Step system port, 140, 140f Stoma, for urinary diversion complications, 399, 400t location selection, 388 Streptomycin for amicrobic cystitis, 226 for renal tuberculosis, 224 Stress incontinence See Urinary incontinence, stress Struvite calculi, 251–252 See also Calculi, renal and ureteral Submucous fibrosis See Interstitial cystitis Subureteric transurethral injection (STING), 191 Suby’s G solution, for urinary calculi, 264 Sulfate, urinary calculi formation and, 250 Sulfonamides for actinomycosis, 227 in pregnancy, 212t Sunitinib, for renal cell carcinoma, 339 Supernumerary kidney, 506 Sympathetic pathways, micturition, 427 Sympathetic storage reflex, 428 Synechia vulvae, 639 Syphilis, 240–241, 240t T pouch urinary reservoir, 393, 395f Tacrolimus, in renal transplantation, 551 Tadalafil, 603–605 Tamsulosin, for benign prostatic hyperplasia, 352t, 353 Tension-free vaginal tape, 483 Tension pneumoperitoneum, 135 Teratoma, testicular, 376 See also Germ cell tumors, testicular Terazosin, for benign prostatic hyperplasia, 352t, 353 Terbinafine, for tinea cruris, 646 Testicular disorders germ cell tumors See Germ cell tumors, testicular non–germ cell tumors gonadoblastomas, 382 Leydig cell tumors, 381 Sertoli cell tumors, 381–382 orchitis, 704 pain in, 34 secondary tumors leukemic infiltrations, 382 lymphoma, 382 metastatic tumors, 382 torsion, 704 Testicular feminization, 660t Testis age-related changes Leydig cells, 717 Sertoli cells, 718, 718t testosterone production, 717–718, 718f anatomy, 8f, 13 biopsy and vasography, 696–698 descent, 25 disorders See Testicular disorders ectopic, 25 endocrine functions, 686 exocrine functions, 686 fetal development, 23–25, 24f fine-needle aspiration “mapping,” 698, 698f injuries, 295, 704 in male hypothalamic-pituitarygonadal axis, 686 MRI, 97f physical examination, 41, 42, 690–691, 690f volume in relation to age, 691f Testosterone age-related changes in production, 717–718, 718f anabolic effects, 720–721, 720f, 721t for female sexual dysfunction, 622 in genitalia development, 650 laboratory tests, 722, 729 in male infertility, 692, 693t for micropenis, 625 physiology, 686 replacement therapy in aging male See also Androgen, deficiency in aging male contraindications and precautions, 724 formulations, 723, 723t patient monitoring, 724, 724t risks, 723–724 for male infertility, 712 sexual function and, 591–592 Tetracycline for amicrobic cystitis, 226 for nongonococcal urethritis, 210 in pregnancy, 212t Thiazide diuretics, for urinary calculi, 250, 271 Thiotepa, for bladder cancer, 316 Thymoglobulin, in renal transplantation, 551 Thyroid, normal laboratory values, 729 Tiagabine, for micturition control, 430 Tinea cruris, 646 Tissue typing, 546 Tolterodine for neuropathic incontinence, 488 for spastic bladder, 449 for urge incontinence, 485 Torsion, testicular, 704 Total flow time, 456, 457f Tramadol, for detrusor overactivity/overactive bladder, 429–430 Transcatheter embolization, 105–109 for angiomyolipoma, 107–108 for high-flow priapism, 109, 111f of ovarian vein varices, 109, 110f preoperative, in renal cell carcinoma, 107, 108f of primary varicocele, 109 for renal arteriovenous fistulas and malformations, 105, 106f for total renal ablation, 108–109 for urinary tract hemorrhage, 105–107 Transillumination, of kidneys, 39–40 Transitional cell carcinoma of bladder chemotherapy, 305–306 histopathology, 310, 310f imaging CT scans, 89f cystogram, 68f INDEX / of kidney, 63f, 64f, 87f of ureter, 65f Transrectal ultrasound in male infertility evaluation, 694–695, 696f in prostate cancer, 164, 361–362 Transsphenoidal resection, pituitary, 494 Transurethral electrovaporization of the prostate, 355 Transurethral needle ablation of the prostate, 355 Transurethral resection of the ejaculatory ducts (TURED), 709, 709f Transurethral resection of the prostate (TURP), 162–163, 162f, 354 Trauma, genitourinary tract See Genitourinary tract, injuries Trichloroacetic acid, for genital warts, 243, 243t Trichomonas vaginalis, 235 Trigone anatomy, 179, 180f dysfunction See Vesicoureteral reflux histology, 181f physiology, 180–181 Trimethoprim-sulfamethoxazole (TMPSMX) for bacterial urinary tract infections, 197 for chronic prostatitis, 209 for cystitis, 207 for granuloma inguinale, 240t for malacoplakia, 208 in pregnancy, 212t prophylactic regimen, 199t Tripelennamine, for interstitial cystitis, 577 Triptorelin pamoate, for benign prostatic hyperplasia, 352t Tromethamine, for urinary calculi, 264 Tromethamine-E, for urinary calculi, 264 Trospium for neuropathic incontinence, 488 for urge incontinence, 485 True hermaphroditism, 657t, 666t, 674–675, 674f Tuberculosis, urinary tract, 219–225 clinical findings imaging, 223–224 CT scans, 223f plain films, 60f, 222 urography, 62f, 222–223, 223f instrumental examination, 223 laboratory findings, 53, 222 signs, 222 symptoms, 221–222 complications, 224 differential diagnosis, 223–224, 577 etiology, 219 in HIV/AIDS, 213 pathogenesis, 219, 220f pathology, 221 treatment, 224–225 Tuberous sclerosis, 508 Tumor antigens, 297 Turner syndrome, 656t, 672 Ultrasonography, 76–80, 78–83f See also specific disorders and organs advantages and disadvantages, 79–80, 94 clinical applications, 78–79 principles, 76, 78 scrotal, 694, 696f transrectal, 164, 694–695, 696f Ultrasound characteristics, 76 high-intensity focused, 355, 366–367 Urachus, persistent, 575, 575f Ureaplasma urealyticum, 235, 640 Uremia, in vesicoureteral reflux, 187 Ureter(s) anatomy, 4, 5f, 7f congenital anomalies See Ureteral disorders, congenital fetal development, 17–19, 20f Ureteral calculi See Calculi, renal and ureteral Ureteral cancer, 320–323 clinical findings imaging, 321–322, 321f laboratory findings, 321 signs and symptoms, 321 ureteropyeloscopy, 322 etiology, 320 future directions, 323 imaging, 65f incidence, 320 pathology, 320 staging and natural history, 321 treatment, 323 Ureteral catheterization, 158–161, 158–161f Ureteral disorders acquired obstruction See Obstruction and stasis, urinary retroperitoneal fibrosis, 570–571, 570f schistosomiasis calcification, 61f stones See Calculi, renal and ureteral 753 tuberculosis See Tuberculosis, urinary tract tumors See also Ureteral cancer fibroepithelial polyps, 320 fibroepithelioma, 131f ureterorenoscopy for, 131, 131f congenital, 559–569 abnormal position, 563–564 atresia, 559 bifid, 20 dilatation without obstruction, 568–569, 569f duplication, 559–560 characteristics, 20, 182, 183f, 559, 560f clinical findings, 559–560 imaging, 560, 561f treatment, 560 ectopic orifice, 183, 562–563, 564–565f obstructed megaureter, 568, 568f obstruction of uteropelvic junction See Uteropelvic junction obstruction ureterocele See Ureterocele pain from, 31, 31f Ureteral injuries, 287–288 clinical findings, 287, 288f complications, 288 differential diagnosis, 288 etiology, 287 pathogenesis and pathology, 287 prognosis, 288 treatment, 288 Ureterocele, 560–562 characteristics, 560, 562f clinical findings, 562 imaging, 67f, 561f, 563f pathophysiology, 562 treatment, 562 vesicoureteral reflux and, 181, 181f, 183 Ureterolithotomy, 270 Ureteropelvic stenosis, 130 Ureteropyeloscopy, 322 Ureterorenoscopy, 128–131 diagnostic, 129 indications, 128t instruments, 128, 128f technique, 128, 129f for ureteral stones, 129–130, 268–269 for ureteral strictures, 130–131 for ureteral tumors, 131 for ureteropelvic stenosis, 130 Ureterosigmoidostomy, 392–393, 393f 754 / INDEX Ureterovesical junction anatomy, 179, 180f histology, 181f physiology, 179–180 Ureterovesicoplasty, 190 Urethra female, 10f, 14–15 fetal development, 651, 652f, 653f male, 9f, 14 Urethral calibration, 188 Urethral carcinoma imaging, 71f radiotherapy for female, 406f, 416 male, 416–417 Urethral catheterization, 155–156, 156f Urethral discharge, 41, 54 See also Urethritis Urethral disorders acquired calculi, 274–275 carcinoma See Urethral carcinoma caruncle, 641–642 condylomata acuminata, 636 diverticulum, 70f, 642–643, 643f meatal stenosis, 636 prolapse, 642 strictures, 633–636 causes, 633 clinical findings, 633–634 complications, 634 differential diagnosis, 634 imaging, 71f prognosis, 635–636 treatment, 634–635, 635f in women, 643 urethritis See Urethritis urethroscrotal fistula, 70f urethrovaginal fistula, 642 congenital anterior urethral valves, 629 chordee without hypospadias, 631 distal stenosis, 41.638–639, 639f duplication, 626 epispadias, 22, 630f, 631–632 hypoplastic anterior urethra, 72f hypospadias See Hypospadias labial fusion, 639 posterior urethral valves, 69f, 626–629 clinical findings, 626–628, 628f prognosis, 629 treatment, 628–629 stricture, 626, 627f urethrorectal fistula, 629 vesicorectal fistula, 629 ultrasonography, 82f Urethral injuries, 278–295 anterior clinical findings, 70f, 294, 294f complications, 294 etiology, 293, 293f imaging, 70f pathogenesis and pathology, 294 prognosis, 295 treatment, 294–295 posterior clinical findings, 291–292, 292f differential diagnosis, 292 etiology, 291, 291f prognosis, 293 treatment, 292–293, 293f Urethral pressure profile, 441, 465–469 components, 465–466, 466f, 467f in detrusor/sphincter dyssynergia, 469 dynamic changes, 466–467, 467f normal, 468, 468f in urinary incontinence, 468–469, 469f, 474–477, 475–478f Urethritis acute, 640 chronic clinical findings, 640 differential diagnosis, 447, 640 treatment and prognosis, 447 clinical presentation, 210 complications, 235 etiology, 210, 235 gonococcal, 198t, 236–237, 237t in HIV/AIDS, 213 imaging, 210 laboratory tests, 236 nongonococcal, 237, 237t recurrent and persistent, 237–238 senile, 640–641 treatment, 198t, 210, 236–238, 237t Urethrography, 66, 70–72f, 278 Urethrorectal fistulas, 629 Urethroscopy, 156–157 Urethrotomy, 634 Urethrovaginal fistulas, 642 Urgency, urinary, 35 Uric acid, 248 Uric acid nephropathy, 527 Uric acid stones, 252 See also Calculi, renal and ureteral Urinalysis See Urine, laboratory examination Urinary diversion, 388–401 complications calculi, 401 continence and urinary function, 399–400 early, 396–397 metabolic and nutritional disorders, 397–399 pyelonephritis and renal deterioration, 400–401 stoma, 399, 400t continent general considerations, 388–392 reservoirs large intestine, 394–395, 397f, 398f small intestine, 393–394, 394f, 395f, 396f uterosigmoidostomy, 392–393, 393f intestinal conduit colon, 389, 391f, 392f ileal, 389, 390f jejunal, 389 postoperative care, 395–396 preoperative counseling and preparation, 388 for vesicoureteral reflux, 190 Urinary flow rate, 441, 455–460 measurement, 174 mechanical factors, 456 nomenclature, 456 outlet resistance in, 456 pattern measurement, 456–460, 457–459f variations in, 456 Urinary incontinence, 36, 473–489, 578 artificial sphincter for, 578 definition, 473–474 diagnosis, 480 false (overflow), 36, 473, 486 fistulous communication, 473 mixed, 485–486 neuropathic, 451, 486–489 active, 486, 487f classification, 486–488 diagnosis, 488 passive, 486 pathophysiology, 473 treatment, 488–489 overflow, 36, 473, 486 pathophysiology, 473–475, 474–477f postprostatectomy, 468–469 stress, 36, 476–483 anatomy, 476, 479–481f cystography, 479–481f pathophysiology, 473 treatment, 483, 484f, 485f urodynamic characteristics functional urethral length, 477, 480, 482f INDEX / pressure profile, 477, 482f response to bladder distension and change in position, 480, 483f response to stress, 480, 482f urethral pressure profile, 468, 475–476, 478f, 482–483f voluntary increase in urethral closure pressure, 480 traumatic, 473 true, 36 urge, 36 definition, 483–484 diagnosis, 484 treatment, 484–485 urethral pressure profile in, 468–469, 469f Urinary obstruction and stasis See Obstruction and stasis, urinary Urinary stones See Calculi Urinary tract infections See also Bladder infections; Kidney infections; Prostate infections; Urethritis actinomycosis, 227 amicrobic cystitis, 225–226 bacterial, 193–214 antibiotics for, 197–200 aminoglycosides, 199 cephalosporins, 199 dosage adjustments in liver and renal disease, 197t fluoroquinolones, 197–199 nitrofurantoin, 199 by pathogen, 198t penicillins, 199 prophylactic regiments, 199t resistance to, 199–200 trimethoprim-sulfamethoxazole, 197 by type of infection, 198t bladder cystitis See Cystitis malacoplakia, 207–208 in diabetes mellitus, 213–214 diagnosis, 195–196 localization studies, 196, 197f urinalysis, 196, 196t urine culture, 196, 196t epidemiology, 193, 194t in HIV/AIDS, 213 incidence, 193 kidney abscess, 202–204, 203f pyelonephritis See Pyelonephritis pyonephrosis, 204, 206, 206f pathogenesis bacterial entry, 193–194 bacterial pathogenic factors, 195 host defenses, 194–195 pathogens, 195, 198t in pregnancy, 212, 212t prostate abscess, 210 prostatitis See Prostate infections recurrent, 207 renal transplantation and, 540, 554 candidiasis, 226–227 echinococcosis, 232–233, 233f filariasis, 231–232 in neuropathic bladder, 452 schistosomiasis See Schistosomiasis tuberculosis See Tuberculosis, urinary tract urinary calculi and, 256–257 Urination See Micturition Urine bloody See Hematuria cloudy, 36 laboratory examination, 46–53 chemical tests, 47–48 collection of specimen, 46–47 color and appearance, 47 cultures, 196, 196t fistula diagnosis, 53 hormonal studies, 53 in male infertility evaluation, 691, 692 in medical renal disease, 521 microscopic, 48–50.7, 49f, 50f, 51f specific gravity, 47 stone constituents, 53 in urinary tract infections, 13t, 52–53, 196 urothelial cancer tests, 53, 53t Urinoma, traumatic, 284 Urodynamic studies bladder function (cystometry), 441, 460–464 capacity, accommodation, and sensation, 460, 460f, 461–463, 463–464t contractility and voluntary control, 461 intravesical pressure recording, 461–463, 462–463f responses to drugs, 461 functions relevant to, 455 micturition, 440–441 sphincteric function, 464–16 755 dynamic changes in pressure profile, 466–467, 467f electromyography, 441–442, 464–465, 465f profilometry, 464 urethral pressure profile, 441, 465–469 components, 465–466, 466f, 467f in detrusor/sphincter dyssynergia, 469 dynamic changes, 466–467, 467f normal, 468, 468f in urinary incontinence, 468–469, 469f, 474–477, 475–478f urinary flow rate (uroflowmetry), 441, 455–460 mechanical factors, 456 nomenclature, 456 outlet resistance in, 456 pattern measurement, 456–460, 457–459f variations in, 456 value of simultaneous recordings, 469–16 Uroflowmetry See Urinary flow rate Urography, 59–61, 62–65f excretory, 175f intravenous, 59–60, 62–63f percutaneous, 61 retrograde, 61, 64–65f, 100f Urologic laboratory examination, 46–56 See also specific disorders blood, serum and plasma, 55–56 in elderly, 56, 56t renal function tests, 54–55 urethral discharge, 54 urine, 46–53 See also Urine, laboratory examination vaginal exudate, 54 Usher’s syndrome, 706 Uteropelvic junction obstruction, 564–568 characteristics, 565f clinical findings, 566 etiology, 566 imaging, 567f prognosis, 566 treatment laparoscopic pyeloplasty, 149–150, 150f percutaneous, 568 surgical, 566 Uteropelvic stenosis, 123–124 Utricle, 72f 756 / INDEX Vaccination, for urologic cancers, 299 Vacuum constriction device, 607 Vaginal examination, 42 Vaginal exudate, laboratory examination, 54 Vaginal prolapse See Pelvic organ prolapse Vaginoplasty, 679, 681f, 682f Valacyclovir, for genital herpes virus infection, 240t, 648 Vancomycin, for renal abscess, 204 Vanilloid receptor, in micturition, 434 Vanishing testis syndrome, 702 Vardenafil, 603–605 Varices, penoscrotal, 77f Varicocele clinical findings, 691 infertility and, 704–705 surgical treatment, 707, 708t transcatheter embolization, 109 venography, 77f Varicocelectomy, laparoscopic, 143–144, 144f Vas deferens fetal development, 26 obstruction, 706 physical examination, 41–42 Vascular interventional radiology, 105–113 catheter-directed fibrinolysis, 112–113 for renal artery aneurysms, 111–112 renal artery angioplasty and stenting, 109–111, 112f transcatheter embolization for angiomyolipoma, 107–108 for high-flow priapism, 109, 111f of ovarian vein varices, 109, 110f preoperative, in renal cell carcinoma, 107, 108f of primary varicocele, 109 for renal arteriovenous fistulas and malformations, 105, 106f for total renal ablation, 108–109 for urinary tract hemorrhage, 105–107 Vasectomy, 706 Vasectomy reversal, 707–709, 708f Vasography, 66, 73f Vasovasotomy, 707–709, 708f Vena cava thrombus, in renal cell carcinoma, 336–337, 337f Venography in male infertility evaluation, 694 renal, 76f urologic, 76, 77f Venous gas embolism, 136–137 Veress needle, 138–139, 139f Verrucous carcinoma, penis, 384 Vesicoadnexal fistula, 583 Vesico-bulbo-vesical micturition reflex, 428–429 Vesicointestinal fistula, 581, 582, 582f Vesicorectal fistulas, 629 Vesico-spinal-vesical micturition reflex, 429 Vesicoureteral reflux causes congenital familial reflux, 182 trigonal weakness, 181–182, 181f, 182f ureteral abnormalities, 182–183, 183f contracted bladder, 184 edema of vesical wall, 183–184 iatrogenic, 184 vesical trabeculation, 183, 184f voiding dysfunction, 183 clinical findings instrumental examination, 188–189, 189f laboratory findings, 188 physical findings, 188 radiographic findings, 185f, 186f, 188 symptoms related to reflux, 187–188 symptoms related to underlying disease, 188 complications hydroureteronephrosis, 185–187, 185f, 186f pyelonephritis, 184 differential diagnosis, 189 incidence, 187 prognosis, 191 treatment medical, 189–190 surgical, 190–191 Vesicourethral unit congenital anomalies, 22, 61f fetal development, 21–22, 22f, 23f Vesicovaginal fistula, 581, 582 Vesiculography, 73f Vinblastine for bladder transitional cell carcinoma, 306 toxicity, 303t Viral infections, renal transplantation and, 540–541, 554–555 Voiding cystourethrography, 61, 66, 66f, 69f Voiding dysfunction, vesicoureteral reflux and, 183 von Hippel-Lindau disease, 330, 508 Waldeyer’s sheath, 179, 180f Water absorption, defects of, 529 Whitaker test, 117–118, 118f, 569 Wilms’ tumor, 339–343 clinical findings imaging, 86f, 341 laboratory findings, 341 needle biopsy, 341 signs and symptoms, 341 differential diagnosis, 341–342, 503 etiology, 340 incidence, 339–340 pathogenesis and pathology, 340, 340f prognosis, 343 staging, 341 treatment chemotherapy, 342 radiotherapy, 342–343 surgical, 342 Wilson’s disease, 528 Wolffian duct, 25 Wuchereria bancrofti, 231 See also Filariasis X-rays See Radiography Xanthine stones, 253–254 See also Calculi, renal and ureteral Xanthogranulomatous pyelonephritis, 204, 205f XX male syndrome, 656t, 701 XYY syndrome, 701 Y chromosome microdeletions, 694, 696f, 702 Yohimbine, for erectile dysfunction, 605 Young syndrome, 705 ... NPV (%) 35–61 28 –100 47–100 57–83 62 78 80–97 62 80 33–83 91 45–59 92 100 96 45– 72 93–100 40–96 61–99 33–95 51–98 73–86 60–99 66–91 85 71–93 93 89 100 80–87 – 33–80 29 –65 20 –56 62 72 81 84 79 95... evaluate the 3 12 / CHAPTER 20 Table 20 –1 Exfoliated Markers for the Detection of Bladder Cancer Marker Cytology BTA NMP 22 BTA stat BTA TRAK Lewis X antigen Telomerase FDP Cytoberatin 20 Quantiant... nucleoli (Figure 20 –2C) D NONTRANSITIONAL CELL CARCINOMAS Figure 20 2 A: Normal urothelium ( 125 ×) B: Moderately well-differentiated, papillary bladder cancer (60×) C: Carcinoma in situ (20 0×) Adenocarcinoma—Adenocarcinomas