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Introduction: Emotional and behavioral problems are growing among children ages birth to five, and racial/ethnic and socioeconomic disparities exist. Comprehensive, culturally responsive, family-driven systems of care, such as the one operated by California's diverse, urban Alameda County, offer one potential intervention., Methods: We used client-level service data ( n = 496 children) to calculate descriptive statistics and regression analyses (including multilevel models to account for observations for the same client at multiple points in time). We estimated the prevalence of mental health issues and assessed the association between the length of time using services and emotional and behavioral functioning., Results: Comprehensive mental health services and supports were associated with improved emotional and behavioral functioning outcomes for children over time, even after controlling for other risk factors., Discussion: Systems of care appear to support the multidimensional functioning of children and their families.

Thermal green protein (TGP) is an extremely stable, highly soluble synthetic green fluorescent protein. The quantum yield of TGP is lower than the closest related natural fluorescent protein, monomeric Azami-Green. We improved the thermal recovery of TGP through the introduction of a chromophore mutation, Q66E. Furthermore, we developed a yellow thermal protein (YTP) via mutation of histidine 193 to tyrosine. Incorporation of Q66E into YTP (YTP-E) improved chemostability and pH stability. Both YTP and YTP-E have superior thermostability compared to TGP or TGP-E. These proteins offer a new option for green or yellow fluorescence under harsh chemical or thermal conditions., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Purpose: To study how young adult college students are managing their health behaviors and risks related to spreading COVID-19., Methods: We created a national cohort of full-time college students in late April 2020 (n = 707), and conducted a follow-up survey with participants in July 2020 (n = 543). Participants reported COVID-19-related health risk behaviors and COVID-19 symptoms, and also responded to an open-ended prompt about how the COVID-19 pandemic has affected their lives. Quantitative data were analyzed in Stata and we conducted content analysis to identify themes in the qualitative data., Results: For most health protective behaviors (e.g., frequent handwashing, social distancing), participants were less compliant in summer 2020 than spring 2020, with the exception of face mask use, which increased. In each month of the first half of 2020, only approximately half of participants with any symptoms that could indicate COVID-19 stayed home exclusively while symptomatic (there was no meaningful change from pre-pandemic or over the course of the pandemic). In qualitative data, the participants who had gone to bars or clubs at least twice within a 4-week period this summer reported being bored and/or isolated, stressed, and/or taking pandemic safety measures seriously., Conclusions: These findings suggest multiple areas for intervention, including harm reduction and risk management education approaches for the students who are going to bars and clubs, and creating policies and programs to better incentivize young people with symptoms to stay home exclusively while symptomatic., (Copyright © 2021 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Maternal mortality remains a large concern in the United States (US), although other Western countries are making progress. In this scoping review, we identify four problems that may contribute to the maternal mortality burden in the US: inadequately investing in women's health, poor quality of care, increasing disparities, and poor data collection and monitoring of maternal health issues. Because maternal mortality is decreasing in California, we identify strategies implemented there that could improve maternal health outcomes nationwide: funding programs to address social determinants of maternal health; supporting health care strategies to improve maternal health (including national standards and goals for health care systems); and investing in maternal health monitoring and surveillance (including use of technology). We encourage researchers, practitioners, and policymakers to work together to develop evidence-based policies and practices to improve maternal health and reduce maternal. We conclude with recommendations for the United States and globally.

At the Canadian Testis Cancer Workshop, the multidisciplinary management of testis cancer care was discussed. The two-day workshop involved urologists, medical and radiation oncologists, pathologists, radiologists, physician's assistants, residents, fellows, nurses, patients, and patient advocacy group members.This review summarizes the discussion regarding clinical dilemmas in local and regional testis cancer. We present cases that highlight the need for a coordinated approach to individualize care. Overarching themes include the importance of a multidisciplinary approach to testis cancer, willingness to involve a high-volume experienced center, and given that the oncological outcomes are excellent, a reminder that clinical decisions need to prioritize selecting a strategy with the least treatment-related morbidity when safe.

At the Canadian Testis Cancer Workshop, the rationale and feasibility of regionalization of testis cancer care were discussed. The two-day workshop involved urologists, medical and radiation oncologists, pathologists, radiologists, physician's assistants, residents and fellows, and nurses, as well as patients and patient advocacy groups.This review summarizes the discussion and recommendations of one of the central topics of the workshop - the centralization of testis cancer in Canada. It was acknowledged that non-guideline-concordant care in testis cancer occurs frequently, in the range of 18-30%. The National Health Service in the U.K. stipulates various testis cancer care modalities be delivered through supra-regional network. All cases are reviewed at a multidisciplinary team meeting and aspects of care can be delivered locally through the network. In Germany, no such network exists, but an insurance-supported online second opinion network was developed that currently achieves expert case review in over 30% of cases. There are clear benefits to regionalization in terms of survival, treatment morbidity, and cost. There was agreement at the workshop that a structured pathway for diagnosis and treatment of testis cancer patients is required.Regionalization may be challenging in Canada because of geography; independent administration of healthcare by each province; physicians fearing loss of autonomy and revenue; patient unwillingness to travel long distances from home; and the inability of the larger centers to handle the ensuing increase in volume. We feel the first step is to identify the key performance indicators and quality metrics to track the quality of care received. After identifying these metrics, implementation of a "networks of excellence" model, similar to that seen in sarcoma care in Ontario, could be effective, coupled with increased use of health technology, such as virtual clinics and telemedicine.

Introduction: Social factors across one's lifespan may contribute to the relationship between low educational attainment and depression, but this relationship has been understudied. Previous studies assessing the association between educational attainment and depression did not fully account for prior common determinants across the life course and possible interactions by sex or race/ethnicity. It is also unclear whether the link between educational attainment and depression is independent of the role of aspired educational attainment or expected educational attainment., Methods: We used generalized linear log link models to examine the association between educational attainment at age 25 and depression at age 40 in the National Longitudinal Survey of Youth 1979 cohort, adjusting for confounders and mediators from childhood, adolescence, and adulthood., Results: Members of each educational attainment group were less likely to be depressed at age 40 than those with less education. After adjusting for educational aspirations and educational expectations, the risk ratios became closer to the null. Neither sex nor race/ethnicity interacted with educational attainment. Additionally, low educational expectations in adolescence, but not low educational aspirations, was associated with a higher risk of depression at age 40., Conclusion: Our study provides a nuanced understanding of the role of education, educational expectations, and educational aspirations as part of education's effect on risk of depression after controlling for a thorough set of confounders and mediators. Our findings may help advance the study of social determinants of depression.

Clinical stage I represents the most frequent presentation of both seminoma and nonseminoma testicular cancer. Despite a survival rate of close to 100%, the management of patients with this disease stage is controversial. The recurrence rate is 10% to 20% for patients with stage I seminoma and 15% to 50% for those with stage I nonseminoma. A highly sensitive and specific biomarker of relapse that is applicable to both seminoma and nonseminoma, and able to drive a definitive risk-adapted management of the patients, still is not available. Lymphovascular invasion (LVI) in the orchiectomy specimen has been used as a risk factor in patients with stage I nonseminoma. However, with a risk of recurrence of 50% for LVI-positive patients and 15% for LVI-negative patients, the discriminative power of LVI is modest at best. Various management options exist. In the absence of a predictive biomarker for recurrence, active surveillance avoids overtreatment in 50% to 85% of patients, with no risk of long-term side effects in nonrelapsing patients and a preserved overall survival of almost 100% after specific treatment for recurrent disease. However, although active surveillance has been accepted as the preferred option for stage I seminoma and low-risk stage I nonseminoma, its role in high-risk stage I nonseminoma remains controversial.

Introduction: Retroperitoneal lymph node dissection (RPLND) for the treatment of testicular cancer is a relatively rare and complex operation that may contribute to differences in utilization. We sought to characterize the use of RPLND between different categories of cancer center facilities in the United States., Materials and Methods: The National Cancer Database was queried for patients with germ cell tumors treated at different types of cancer centers between 1998 and 2011. The proportion of patients who underwent RPLND was stratified by stage and histology and then compared between treatment facilities. RPLND utilization was then compared between facility types as a function of time., Results: A total of 59,652 patients met inclusion criteria and 5,475 (9.2%) underwent RPLND. The proportion of patients treated with RPLND for non-seminomatous germ cell tumor (NSGCT) was significantly different between cancer center types for all stages (P<0.001) and used most often in academic comprehensive cancer centers. There was no difference in the proportion of RPLND utilization for stage II and III seminoma stratified by treatment facility. There was a significantly decreased trend in the utilization of RPLND for stage I (P = 0.032) NSGCT whereas utilization was increased for stage III NSGCT (P≤0.001) over the study period., Conclusions: The proportion of patients undergoing RPLND for NSGCT varies significantly by the type of cancer center and is used most often in academic cancer centers. Utilization of RPLND decreased for stage I NSGCT and increased for stage III NSGCTs during the study period., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: Sex cord stromal tumors of the testis comprise less than 5% of testicular neoplasms. Consequently, data regarding patterns of care and survival are sparse. Using a large national database, we sought to provide a more definitive analysis of outcomes and management of these malignancies., Materials and Methods: Data were obtained from the National Cancer Data Base. Patients diagnosed from 1998 to 2011 with 2 of the most frequent sex cord stromal tumors of the testis, including Leydig and Sertoli cell tumors, were selected for study. Overall survival estimates were assessed by the Kaplan-Meier method., Results: Of the 79,120 cases of testicular cancer between 1998 and 2011, 315 (0.39%) were primary malignant Leydig or Sertoli cell tumors. Median patient age was 43 years for both tumors. Of the 315 patients 250 (79%) had malignant Leydig cell tumors and 65 (21%) had malignant Sertoli cell tumors, of which 94% and 78%, respectively, were stage I. Overall survival at 1 and 5 years for stage I Leydig cell tumors was 98% (95% CI 96-100) and 91% (95% CI 85-96), and for stage I Sertoli cell tumors overall survival was 93% (95% CI 83-100) and 77% (95% CI 62-95), respectively (p = 0.015). Of patients with stage I Leydig and Sertoli cell tumors 94% and 84%, respectively, received no further treatment following orchiectomy., Conclusions: Five-year survival estimates of stage I Leydig and Sertoli cell tumors are significantly lower compared to those of stage I germ cell tumors with Sertoli cell tumors significantly worse than Leydig cell tumors. These differences in the survival of sex cord stromal tumors indicate the importance of large databases to evaluate the efficacy of treatment for rare neoplasms., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Adolescent and Young Adult Oncology (AYAO, including patients 15-39 years of age) is an emerging discipline in the field of cancer treatment and research. Poorer survival outcomes for this population and characteristic age-related challenges in care have called attention to the need for increased AYAO research. This chapter outlines pressing questions and reviews recent progress in AYAO research within the current organizational structure of the federal clinical trials enterprise, emphasizing how the United States National Cancer Institute's National Clinical Trials Network (NCTN) has created novel opportunities for collaborative AYAO research among the pediatric and adult NCTN groups. Potential strategies for expanding AYAO research, both within the NCTN and with other partners in the federal and advocacy domains are identified., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the performance of active surveillance as a management strategy in broad populations and to inform the development of surveillance schedules by individual patient data regarding timing and type of relapse., Methods: Retrospective study including data from 2,483 clinical stage I (CSI) patients, 1,139 CSI nonseminoma and 1,344 CSI seminoma managed with active surveillance, with the majority treated between 1998 and 2010. Clinical outcomes including relapse and death, time distribution, extent of relapse and method of relapse detection observed on active surveillance were recorded., Results: Relapse occurred in 221 (19%) CSI-nonseminoma and 173 (13%) CSI-seminoma patients. Median time to relapse was 4 months (range, 2-61 months), 8 months (range, 2-77 months) and 14 months (range, 2-84 months) for lymphovascular invasion-positive CSI nonseminoma, lymphovascular invasion-negative CSI nonseminoma and CSI seminoma. Most relapses were observed within the first 2 years/3 years after orchiectomy for CSI nonseminoma (90%)/CSI seminoma (92%). Relapses were detected by computed tomography scan/tumor-markers in 87%/3% of seminoma recurrences, in 48%/38% of lymphovascular invasion-negative and 41%/61% of lymphovascular invasion-positive patients, respectively. 90% of CSI-nonseminoma and 99% of CSI-seminoma relapses exhibited International Germ Cell Collaborative Group good-risk features. Three patients with CSI nonseminoma died of disease (0.3%). One patient with CSI seminoma and two patients with CSI nonseminoma died because of treatment-related events. Overall, advanced disease was seen in both early- and late-relapse patients. All late recurrences were cured with standard therapy. Five-year disease-specific survival was 99.7% (95% CI, 99.24% to 99.93%)., Conclusion: Active surveillance for CSI testis cancer leads to excellent outcomes. The vast majority of relapses occur within 2 years of orchiectomy for CSI nonseminoma and within 3 years for CSI seminoma. Late and advanced stage relapse are rarely seen. These data may inform further refinement of rationally designed surveillance schedules., (© 2014 by American Society of Clinical Oncology.)

Introduction: Clinical stage I seminoma can be managed with surveillance, chemotherapy or radiotherapy with similar survival rates. However, costs and side effects vary among these treatment modalities. We created a model to estimate the direct and indirect costs during the first 5 years of treatment for the 3 treatment strategies., Methods: Markov model based analyses were conducted to compare the costs of the 3 management strategies during the first 5 years. In this model clinicians and patients were assumed to be 100% compliant with the 2012 NCCN Guidelines ® for testicular cancer. Model parameters were collected from the Washington State CHARS (Comprehensive Hospital Abstract Reporting System), published literature and Medicare reimbursement amounts. A 5% annual health inflation rate was assumed., Results: The model predicts an initial cost premium for carboplatin (1 cycle-$9,199.49; 2 cycles-$10,613.85) and radiotherapy ($9,532.80) compared with surveillance ($9,065.31). Radiotherapy (145.8 hours) and surveillance (123.0 hours) require more patient time than carboplatin (1 cycle-93.2 hours, 2 cycles-106.3 hours). When the direct and indirect costs are considered, the least expensive management strategy is surveillance., Conclusions: Surveillance is the most cost-effective management strategy for clinical stage I seminoma during the first 5 years of treatment. Although not evaluated in this analysis, costs of late side effects associated with radiotherapy and chemotherapy should be considered. Due to potentially minimal late side effects and superior cost-effectiveness, surveillance represents a safe, cost-effective and time effective option for the management of stage I seminoma.

In approximately 25% of patients with testicular germ cell tumor (GCT), the cancer metastasizes to lymph nodes and distant organs. The initial lymphatic drainage site of GCTs is the retroperitoneum. GCTs rarely involve mesenteric lymph nodes. In this study, we report a case of a 32-year-old male patient with GCT and associated mesenteric lymphadenopathy., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Safe, effective interventions to improve cancer-related fatigue (CRF) are needed because it remains a prevalent, distressing, and activity-limiting symptom. Based on pilot data, a phase III trial was developed to evaluate the efficacy of American ginseng on CRF., Methods: A multisite, double-blind trial randomized fatigued cancer survivors to 2000mg of American ginseng vs a placebo for 8 weeks. The primary endpoint was the general subscale of the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) at 4 weeks. Changes from baseline at 4 and 8 weeks were evaluated between arms by a two-sided, two-sample t test. Toxicities were evaluated by self-report and the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) provider grading., Results: Three hundred sixty-four participants were enrolled from 40 institutions. Changes from baseline in the general subscale of the MFSI-SF were 14.4 (standard deviation [SD] = 27.1) in the ginseng arm vs 8.2 (SD = 24.8) in the placebo arm at 4 weeks (P = .07). A statistically significant difference was seen at 8 weeks with a change score of 20 (SD = 27) for the ginseng group and 10.3 (SD = 26.1) for the placebo group (P = .003). Greater benefit was reported in patients receiving active cancer treatment vs those who had completed treatment. Toxicities per self-report and CTCAE grading did not differ statistically significantly between arms., Conclusions: Data support the benefit of American ginseng, 2000mg daily, on CRF over an 8-week period. There were no discernible toxicities associated with the treatment. Studies to increase knowledge to guide the role of ginseng to improve CRF are needed.

This paper presents a practical method for the development of spectral reflectance libraries under sub-optimal sky conditions. Although there are commercially available spectrometers which simultaneously measure both downwelling and upwelling radiance to mitigate the impact of sub-optimal sky conditions, these spectrometers only record in the visible and near infra-red. There are presently no commercially available spectrometers with this capability that can record the visible through short-wave infra-red. This paper presents a practical method of recording and processing data using coordinated measurements from two full-range spectrometers and discusses potential pitfalls and solutions required to achieve accurate reflectance spectra. Results demonstrate that high-quality spectral reflectance libraries can be developed with this approach.

Testicular cancer represents the most curable solid tumor, with a 10-year survival rate of more than 95%. Given the young average age at diagnosis, it is estimated that effective treatment approaches, in particular, platinum-based chemotherapy, have resulted in an average gain of several decades of life. This success, however, is offset by the emergence of considerable long-term morbidity, including second malignant neoplasms, cardiovascular disease, neurotoxicity, nephrotoxicity, pulmonary toxicity, hypogonadism, decreased fertility, and psychosocial problems. Data on underlying genetic or molecular factors that might identify those patients at highest risk for late sequelae are sparse. Genome-wide association studies and other translational molecular approaches now provide opportunities to identify testicular cancer survivors at greatest risk for therapy-related complications to develop evidence-based long-term follow-up guidelines and interventional strategies. We review research priorities identified during an international workshop devoted to testicular cancer survivors. Recommendations include 1) institution of lifelong follow-up of testicular cancer survivors within a large cohort setting to ascertain risks of emerging toxicities and the evolution of known late sequelae, 2) development of comprehensive risk prediction models that include treatment factors and genetic modifiers of late sequelae, 3) elucidation of the effect(s) of decades-long exposure to low serum levels of platinum, 4) assessment of the overall burden of medical and psychosocial morbidity, and 5) the eventual formulation of evidence-based long-term follow-up guidelines and interventions. Just as testicular cancer once served as the paradigm of a curable malignancy, comprehensive follow-up studies of testicular cancer survivors can pioneer new methodologies in survivorship research for all adult-onset cancer.

Background: With treatment leading to nearly uniform cure in clinical stage I nonseminomatous testicular cancer (CSI-NSGCT), diminishing treatment-related morbidity has become the primary concern. This study examined feasibility and outcome of active surveillance as treatment in an unselected CSI patient population., Materials and Methods: All patients with CSI-NSGCT referred from 1998 to 2007 to the British Columbia Cancer Agency and the Oregon Testis Cancer Program were retrospectively reviewed. A total of 233 patients were identified, of which 223 chose active surveillance., Results: Vascular invasion (VI) was absent, present and unknown in 66%, 27% and 7% of cases, respectively. Overall, 49% of patients had embryonal predominant disease. Fifty-nine patients (26%) relapsed, all but one with good prognosis disease. VI was present in 30 relapsed patients. Most patients relapsed within 2 years (88%). Only 7 of 223 patients (3%) relapsed beyond 2 years. All relapses were in long-term remission following chemotherapy with or without retroperitoneal lymph node dissection (RPLND). Only 17 of 223 patients (8%) required postorchiectomy surgery. Disease-specific survival is 100% after a median follow-up of 52 months (3-136). No patient has required second-line chemotherapy., Conclusions: Active surveillance for all CSI-NSGCT patients is associated with excellent outcomes comparable with the best results reported with primary RPLND or adjuvant chemotherapy. Nearly 75% of patients are spared any therapy after orchiectomy.

Testicular cancer is the most common solid tumor among males in the 20- to 39-year age range. Moreover, testicular cancer has unique biological associations, clinical features, and psychosocial impacts that establish this tumor as a prototypic malignancy of young adults. The biology of testicular germ cell tumors after puberty is distinctive. Epidemiologic patterns of testicular cancer suggest etiologic factors that may be congenital, racial, and geographic. The clinical management of a cancer common among young adults, but rare among adults in general, requires expertise so as not to jeopardize the high rates of survivorship associated with modern therapy. The concurrent but separate development of staging, prognostic systems, and treatment recommendations between the fields of pediatric and adult oncology highlights the need for increased integration and cooperation across these subspecialties. The high rate of survival, combined with the need for long-term monitoring for relapse or late effects, demonstrates the challenge of delivering longitudinal care in this mobile and active young adult population.

Purpose: The purpose of this study was to characterize the activity and toxicity of irinotecan in metastatic platinum-refractory urothelial carcinoma., Patients and Methods: In a prospective multi-institutional phase II clinical trial, we evaluated the activity and safety of irinotecan 350 mg/m2 (300 mg/m2 in patients with previous radiation therapy to the pelvis) intravenously given every 21 days in patients with metastatic urothelial carcinoma and evidence of progression following one previous systemic chemotherapy regimen for metastatic disease that included cisplatin or carboplatin. The primary goal of this study was to evaluate the probability of confirmed complete or partial response., Results: Forty eligible patients were registered between December 2003 and December 2006. One patient had a complete response, and 1 had a partial response (overall response rate, 5%; 95% CI, 1%-17%). Median progression-free survival was 2.1 months (95% CI, 1.8-2.3 months). Median overall survival was 5.4 months (95% CI, 3.4-7.1 months). Toxicity was similar to that reported previously for this schedule of irinotecan., Conclusion: The response rate seen in this study is insufficient to recommend further evaluation of irinotecan in urothelial cancer that relapsed following initial platinum based chemotherapy. Investigation of novel agents for this patient population remains a priority.

Goals of Work: The aims of this study were to assess the safety and antiemetic efficacy of multiple-day dosing of palonosetron plus dexamethasone in patients receiving highly emetogenic multiple-day cisplatin-based chemotherapy for germ cell tumors., Materials and Methods: Forty-one men undergoing 5-day cisplatin-based chemotherapy for testicular cancer received palonosetron 0.25 mg IV once daily 30 min before chemotherapy on days 1, 3, and 5 plus IV dexamethasone 20 mg before chemotherapy on days 1 and 2, and 8 mg PO bid on days 6 and 7 and 4 mg bid on day 8. Safety and efficacy were assessed in 24-h intervals for 9 days. Efficacy endpoints included emesis, intensity of nausea and its interference with patient functioning, and rescue antiemetic use. A subset of patients (n = 11) was studied for electrocardiograph effects and pharmacokinetic evaluation., Main Results: This multiple-day antiemetic regimen was safe, with headache and constipation the most common treatment-related adverse events, mostly mild. Neither adverse events nor electrocardiographic changes appeared to increase in frequency, duration, or intensity over time despite a 1.42-fold systemic accumulation of palonosetron with repeated doses. The majority of patients had no emesis at any time throughout days 1-5 (51%) or days 6-9 (83%), had no moderate-to-severe nausea, and did not require rescue medication. Most patients reported that nausea had no significant effect on daily functioning on days 1-4 (72%) and days 5-9 (85%)., Conclusions: Palonosetron on days 1, 3, and 5, along with a regimen of dexamethasone, was safe and well tolerated and effectively controlled both nausea and emesis in patients undergoing 5-day cisplatin-based chemotherapy for testicular cancer.

Carboplatin/docetaxel chemotherapy was evaluated in advanced squamous cell carcinoma of the head and neck (SCCHN). Eligibility included patients with recurrent, persistent, or metastatic SCCHN with Zubrod performance status 0-2. Docetaxel 65 mg/m(2) and carboplatin (AUC of 6) were given IV in a 21-day cycle to 68 patients. Response probability was 25 percent (95%CI: 15-38). The major toxicity observed was neutropenia, with 36 patients (61 percent) experiencing Grade 3 or worse. Median progression-free survival was 3.8 months (95%CI, 3.1-4.8) Median overall survival was 7.4 months (95%CI, 6.2-8.9). The results of this study suggest this regimen is active for outpatient treatment of recurrent SCCHN patients with good performance status.

Although testicular cancer is a rare disease accounting for only 1% of all male neoplasms, it represents a paradigm for cancer curability. Overall, more than 95% of patients can expect to be cured of their disease with minimal long-term toxicity. Given these expectations, it is critical that cancer care providers are familiar with the diagnostic and therapeutic challenges encountered in these rare patients. In particular, clinicians managing these patients should be aware of some of the pitfalls encountered when determining relapse. In a series of case presentations, we review the evaluation and management of patients with persistent elevation of serum tumor markers and postchemotherapy residual radiographic abnormalities.

Breast cancer during pregnancy is increasingly common as women delay childbearing until later in life. Safe administration of adjuvant chemotherapy during pregnancy has been reported. Physiologic and metabolic changes during pregnancy could alter the pharmacokinetics of these agents. This is a pilot study to prospectively study the pharmacokinetics of chemotherapeutic agents during pregnancy. Herein, we report the initial results with paclitaxel in the first patient.

Background: To the authors' knowledge, no satisfactory therapy is available for patients with refractory germ cell neoplasms. The activity and safety of arsenic trioxide in refractory germ cell tumors was assessed., Methods: Twenty patients were treated with arsenic trioxide at a dose of 0.25 mg/kg/day and administered intravenously over 1 to 2 hours on Days 1-5 and repeated every 28 days., Results: There were no complete or partial responses. The median progression-free survival was 1 month and the median overall survival was 2 months. Three patients died as a result of adverse events believed to be possibly related to treatment: ventricular arrhythmia, adult respiratory distress syndrome, and pneumonitis., Conclusions: In the current study, arsenic trioxide in the dose regimen and schedule employed was found to have no activity in men with refractory germ cell malignancies. Treatment was associated with severe toxicity. Dismal overall survival reflects the poor outcome in this patient group and highlights the acute need for new agents with activity in refractory germ cell neoplasms., (Copyright 2006 American Cancer Society.)

Although higher dietary intake of lutein/zeaxanthin has been associated with reduced risk for cataracts, the impact of dietary supplements on lens lutein (L) or zeaxanthin (Z) has not been examined. If higher lens carotenoids do reduce risk for cataract, it would be essential to know whether dietary carotenoids can elevate carotenoids in the adult vertebrate lens. In this study, a covey of Japanese quail were hatched and raised 6 months on carotenoid-deficient diet, then switched to deficient diet supplemented with low or high 3R,3R'-zeaxanthin (5 or 35 mgkg(-1) food) or beta-carotene (50 mgkg(-1) food). Controls included a group of covey-mates that remained on the deficient diet and another raised from birth on the high Z (35 mg Zkg(-1)) diet. At 1 year of age, carotenoids and tocopherols in the lens and in the serum were analysed by HPLC, and compared by analysis of variance. Serum Z was significantly elevated in deficient birds fed the lower or higher Z supplement for 6 months (P<0.0001 for each). Serum Z in birds maintained on the higher Z supplement for 1 year was much higher than that in deficient birds (P<0.0001), but not different from deficient birds given the higher Z supplement. As in humans, the predominant lens carotenoids were lutein (L) and zeaxanthin (Z), and the total carotenoid concentration was of lower magnitude than the concentration of alpha-tocopherol. Responses to Z supplementation were sex-related. Female quail had 5-10 times higher serum concentrations of both Z and L than males (P<0.0001, <0.001), and they also had higher lens Z concentrations than males (P<0.0006); possible effects of estrogen on lens carotenoids are discussed. Lens Z concentration was strongly and positively correlated with serum Z in females (r=0.77; P<0.002). Deficient adult females supplemented with the 35 mgkg(-1) dose of Z for 6 months had a mean lens Z concentration (0.252+/-0.06 microgg(-1) protein) close to that in females fed with the supplement from birth (0.282+/-0.15 microgg(-1) protein). Birds fed with the higher dietary Z supplement for 6 or 12 months had significantly higher lens Z than birds fed lower or no dietary Z (P<0.0001). Lens L was not altered by dietary supplementation with either Z or beta-carotene. beta-Carotene supplements did not result in detectable lens beta-carotene, and had no effect on lens Z. Neither Z nor beta-carotene supplementation had a significant effect on serum or lens tocopherol concentrations. These studies in quail provide the first experimental evidence that lens carotenoids in adult vertebrates can be manipulated by dietary Z supplements.

Antioxidant component alterations in the aorta during atherogenesis were examined in atherosclerosis-susceptible (SUS) Japanese quail fed a cholesterol-supplemented (0.5% w/w) diet. Birds fed a non-supplemented diet provided information on the effects of aging on endogenous antioxidants. One hundred adult SUS males were used. Birds were sacrificed after 0, 4, 8 and 12 weeks on the diets and were examined for plaque development and corresponding antioxidant component alterations in aorta and myocardium. With aging, superoxide dismutase (SOD) activity was increased in both tissues, whereas aortic glutathione peroxidase (GPx) activity and myocardial glutathione reductase (GRd) activity decreased. Myocardial ascorbate levels increased with aging, with a reciprocal decrease in myocardial tocopherol levels. Following 4 weeks of cholesterol supplementation, aortic GRd decreased, SOD activity increased, but activities of GPx and catalase were unchanged. This same qualitative pattern of antioxidant enzyme changes was also found in myocardium. Thus, although aortic antioxidant enzyme changes produced by cholesterol feeding and aging showed some similarities, the early phase of atherogenesis does not simply reflect accelerated aging. In the late stages of atherogenesis, SOD activity returned to baseline, but other antioxidant enzymes remained unaltered from levels characterizing the early phase of lesion development. There was no detectable functional coupling between changes in GPx and GRd, nor between SOD (which produces hydrogen peroxide) and GPx or catalase (which utilize hydrogen peroxide as substrate). Previously reported alterations in erythrocyte antioxidant enzyme components during atherogenesis in quail were not predictive of changes in the corresponding enzymes in the aorta and myocardium.

As the number of elderly patients receiving oncologic therapies increases, the need for better outcome predictors for the critically ill elderly with cancer increases. Physicians should not view age as an indicator of poor ICU outcome, as many elderly patients with cancer will derive the same benefit from intensive care as their younger counterparts. Such a gain can be accomplished without overuse of valuable resources. Similar prognostic factors that are applied to the younger cancer patients should also be applied to the elderly. These parameters, in addition to clinical judgment, can be helpful in deciding who will benefit from ICU care regardless of age. Oncologists and critical care physicians will need to collaborate and change the paradigm of ICU care for the elderly.

Background: Various staging systems have been proposed for disseminated germ cell neoplasms. The Indiana University staging system was based on clinical and radiographic findings only, whereas the newly created International Germ Cell Cancer Collaborative Group (IGCCCG) staging system also utilized serum markers as a prognostic factor. This study updated the intergroup trial that compared the standard therapy of bleomycin, etoposide, and cisplatin (BEP) with etoposide, ifosfamide, and cisplatin (VIP) in advanced germ cell tumors and reanalyzed the results using the IGCCCG staging system., Methods: From October 1987 to April 1992, 304 patients with advanced-stage germ cell tumors (using the Indiana University staging system) were randomized to receive four cycles of BEP or VIP. Two hundred and eighty-six patients were eligible and fully evaluable. With a median follow-up of 7.3 years, 283 of the 286 evaluable patients from the Eastern Cooperative Oncology Group protocol, E3887, were reclassified using the IGCCCG staging system. Progression-free survival (PFS), overall survival (OS), and toxicity were assessed for the treatment arms., Results: With a longer follow-up of 7.3 years and using the Indiana University staging system, the PFS rates were 64% versus 58% and the OS rates were 69% versus 67% in the VIP and BEP arms, respectively. For patients reclassified with the IGCCCG staging system, the PFS rates were 81%, 72%, and 54% and the OS rates were 89%, 81%, and 60% for good, intermediate, and poor-risk patients, respectively. Differences in OS (VIP, 62%; BEP, 57%) and PFS (VIP, 56%; BEP, 49%) for the subset of patients reclassified as poor risk by the IGCCCG staging system were not significantly different. More toxicity, primarily hematologic toxicity, occurred on the VIP arm., Conclusions: With a median follow-up of 7.3 years and with a reclassification based on the IGCCCG, OS and PFS rates were comparable between BEP and VIP. Toxicity, primarily hematologic, was modestly greater with the ifosfamide-containing arm. The VIP regimen may be considered a treatment alternative for patients with underlying pulmonary disease. In most patients with poor and intermediate-risk germ cell tumors, four cycles of BEP remain the standard therapy., (Copyright 2003 American Cancer Society.)

An unselected population of 635 consecutive extragonadal GCT patients (EGCT) treated between 1975 through 1996 at 11 cancer centers was retrospectively evaluated for clinical prognosis and biological features of this disease. Five hundred twenty-four patients (83%) had a nonseminomatous GCT, and 104 patients (16%) a seminomatous histology; 341 (54%) patients had a primary mediastinal EGCT, and 283 patients (45%) a retroperitoneal EGCT. Following platinum based induction chemotherapy+/-secondary surgery, 141 patients (49%) with mediastinal nonseminomas (median follow up period: 19 months) and 144 patients (63%) with retroperitoneal nonseminoma (median follow up period: 29 months) are alive [p=0.0006]. In contrast, the overall survival rate for patients with seminomatous EGCT is 88% with no difference between patients with mediastinal or retroperitoneal tumor location (median follow up period: 49 months). Multivariate analysis revealed nonseminomatous histology, the presence of non-pulmonary visceral metastases, primary mediastinal GCT location, and elevated beta-HCG as independent prognostic factors for shorter survival. Sixteen patients (4.1%) developed a metachronous testicular cancer despite the use of platinum based chemotherapy. The cumulative risk of developing a MTC 10-years after a diagnosis of EGCT was 10.3% (95% CI=4.9 to 15.6%), but higher among patients with nonseminomatous EGCT (14.3%; 95% CI=6.7 to 21.9%) or retroperitoneal EGCT location (14.2%; 95% CI=5.6 to 22.8%) than among patients with seminomatous EGCT (1.4%; 95% CI=0.0 to 4.2) or mediastinal EGCT location (6.2%; 95% CI=0.1 to 12.2). After a median follow-up of 51 months (range=1 to 154 months), all 16 MTC patients were alive without disease. Patients with pure seminomatous EGCT histology have a long term chance of cure of almost 90% irrespective of the primary tumor site. Patients with mediastinal nonseminomas have a five-years survival rate of 45%. This outcome is clearly inferior compared to patients with nonseminomatous retroperitoneal primaries who have a five-year survival rate of 62%.

The purpose of these studies was to evaluate the effects of light damage on Japanese quail whose retinal carotenoids had been experimentally manipulated through altered diets. The birds were raised 6 months on a commercial turkey diet (T), on a custom carotenoid-deficient diet (C-) containing 90% less carotenoid than the T diet, or on Z+ diet [the C- diet supplemented with natural zeaxanthin (35mgkg(-1) food)]. Equal numbers of males and females on each diet were exposed to nine intervals (1hr on, 2hr off) of 3200lux cool white light, then placed in the dark for 14hr before tissue collection. One retina was immediately frozen for HPLC analysis; the other eye was immediately fixed and processed for microscopy. There were no significant differences in the retinal carotenoid concentrations in hatch-mates that were and were not exposed to light. Supplementation resulted in three- to four-fold increases in retinal zeaxanthin and no change in retinal lutein or alpha-tocopherol, but the C- diet did not reduce the retinal carotenoid concentration in C- birds below that in T birds. The light-exposed retinas had significant numbers of apoptotic photoreceptors and photoreceptor ghosts. The number of ghosts was negatively correlated with the number of dying photoreceptors (P<0.05), and with retinal concentrations of zeaxanthin, alpha-tocopherol or gamma-tocopherol (P<0.04, 0.02, 0.04, respectively), but not with lutein. The number of dying photoreceptors was positively correlated with alpha-tocopherol and the sum alpha-tocopherol plus zeaxanthin (P<0.1; P0.04). Photoreceptor death was semi-quantitatively scored, assuming that ghosts were formed by removal of apoptotic photoreceptors with nuclear condensation. Stepwise regression produced a good model (r(2)=0.67;P <0.0001) for predicting death scores from retinal concentrations of zeaxanthin (Standard Coefficient=-0.76) and lutein (Standard Coefficients=+0.43). Absence of lutein in gender-specific analyses suggests lutein served as surrogate marker for gender. Combined analysis of the C- and T birds also demonstrated that dying photoreceptors were negatively correlated with retinal zeaxanthin. These data confirm our previous report that retinal carotenoids prevent photoreceptor cell death, and provide the first direct evidence that retinal zeaxanthin protects photoreceptors from light-induced death.

Purpose: Inferential evidence indicates that macular pigments (lutein and zeaxanthin) protect photoreceptors and/or retard age-related macular degeneration. These experiments tested the hypothesis that retinal zeaxanthin prevents light-induced photoreceptor cell death., Methods: Retinal damage was assessed in quail fed a carotenoid-deficient (C-) diet for 6 months. Groups of 16 birds (8 male, 8 female) were fed a C- diet supplemented with 35 mg 3R,3'R-zeaxanthin for 1, 3, or 7 days; one group was continued on C- diets. Half of each group was exposed to intermittent 3200-lux white light (10 1-hour intervals separated by 2 hours in dark). After 14 additional hours in the dark, one retina of each quail was collected for HPLC analysis, and the contralateral retina was embedded in paraffin for counts of apoptotic nuclei., Results: After 7 days' supplementation, concentrations of zeaxanthin in serum, liver, and fat had increased by factors of 50.8, 43.2, and 6.5, respectively (all P < 0.001). In contrast, retinal zeaxanthin fluctuated significantly upward on day 3, but there was no net change on day 7. The number of apoptotic rods and cones in light-damaged eyes correlated significantly and inversely with zeaxanthin concentration in the contralateral retina (r = -0.61; P < 0.0001 and r = -0.54; P < 0.002), but not with serum zeaxanthin. Similar correlations were observed with retinal lutein, which correlated strongly with retinal zeaxanthin (r = 0.95; P < 0.0001)., Conclusions: Retinal zeaxanthin dose dependently reduced light-induced photoreceptor apoptosis; elevated serum levels did not. These data provide the first experimental evidence that xanthophyll carotenoids protect photoreceptors in vivo.

Background: Prostate cancer is the most common malignancy in American men, and as many as 70% of those initially treated for localized disease will ultimately progress and be considered candidates to receive therapy for metastatic cancer [Fuks et al.: Int J Radiat Oncol Bio Phys 21:537-547, 1991; Chodak et al.: N Engl J Med 330:246-248, 1994]. Although most will respond initially to hormone manipulation, essentially all will fail and require additional therapy. No standard chemotherapy approach has been shown to prolong survival significantly, and new agents are desperately needed. Topotecan is a new topoisomerase-1 inhibitor whose early investigation suggested possible activity in hormone-refractory prostate cancer., Methods: In this phase II trial, patients having failed one or two prior androgen ablative therapies were treated with 21-day continuous intravenous infusions of topotecan at a dose of 0.5 mg/m(2) per day every 28 days., Results: Twenty-six eligible patients were entered on the study. There were no confirmed tumor responses. Median survival was 9 months. The most common toxicities were hematologic, with 8 of 24 assessable patients experiencing grade 4 toxicity., Conclusion: Topotecan infusions at this dose are ineffective in the management of hormone-refractory prostate cancer., (Copyright 2002 Wiley-Liss, Inc.)

Background: This investigation evaluates prognostic variables in patients with seminomatous and non-seminomatous extragonadal germ-cell tumors (EGCT) in order to identify relevant factors for long-term outcome following cisplatin-based chemotherapy., Patients and Methods: Patients from six countries treated at 11 centers in Europe and the USA from 1975 to 1996 were evaluated retrospectively. Uni- and multivariate analyses of prognostic variables for survival and for response to chemotherapy were performed., Results: Data were available for 635 EGCT patients, 104 with seminomatous and 524 with non-seminomatous EGCT (n = 7 not specified). For non-seminomatous EGCT the following independent adverse factors were identified: presence of either liver, lung or central nervous system metastases, primary mediastinal tumor or elevation of pretreatment beta-human gonadotropin; for extragonadal seminoma (only univariate) adverse factors were: presence of liver metastases, two or greater metastatic sites or International Germ Cell Cancer Collaborative Group (IGCCCG) grouping (intermediate versus good). Integration of these variables produced the following prognostic risk groupings: 'excellent prognosis', all seminomatous EGCT (89% 5-year survival rate); 'intermediate low', 'intermediate high' and 'poor', all non-seminomatous EGCT with a 69, 55 and 17% 5-year survival rate, respectively. The decreased survival among the different groups was due to a lower rate of favorable objective remissions and a higher rate of relapses. Classification and regression tree (CART) modeling confirmed histology and location of primary tumor as the major prognosticators. For the subgroup of patients with mediastinal non-seminoma, the 2-year survival rate ranged from 34 to 84%. Multivariate testing for the probability to respond to chemotherapy revealed non-seminomatous histology, primary mediastinal tumor site, and the presence of liver, lung or CNS metastases as independent adverse factors., Conclusions: In EGCT, prognostic variables for the outcome and for the response to chemotherapy could be identified, which in part differ from gonadal GCT. The proposed model might help to better understand the specific prognosis of EGCT and to tailor risk-adapted treatment strategies. In addition, CART analysis demonstrated the heterogenous prognosis of patients with mediastinal non-seminoma.

Purpose: To characterize the clinical and biologic features of extragonadal germ cell tumor (EGCT) and to determine the overall outcome with currently available treatment strategies., Patients and Methods: Of an unselected population of 635 consecutive patients treated from 1975 through 1996 at 11 cancer centers, 341 patients (54%) had primary mediastinal EGCT, and 283 patients (45%) had retroperitoneal EGCT. Five hundred twenty-four patients (83%) had a nonseminomatous germ cell tumor (GCT), and 104 patients (16%) had a seminomatous histology., Results: After platinum-based induction chemotherapy with or without secondary surgery, 141 patients (49%) with mediastinal nonseminomas (median follow-up, 19 months; range, 1 to 178 months) and 144 patients (63%) with retroperitoneal nonseminoma (median follow-up, 29 months; range, 1 to 203 months) are alive (P =.0006). In contrast, the overall survival rate for patients with a seminomatous EGCT is 88%, with no difference between patients with mediastinal or retroperitoneal tumor location (median follow-up, 49 months; range, 4 to 193 months; respective 70 months; range, 1 to 211 months). A significantly lower progression-free survival rate was found in seminoma patients treated with initial radiotherapy alone compared with chemotherapy. Nonseminomatous histology, presence of nonpulmonary visceral metastases, primary mediastinal GCT location, and elevated beta-human chorionic gonadotropin were independent prognostic factors for shorter survival. Hematologic malignancies (n = 17) occurred without exception in patients with primary mediastinal nonseminoma. Sixteen patients developed a metachronous testicular cancer despite the use of platinum-based chemotherapy., Conclusion: Whereas patients with pure seminomatous EGCT histology have a long-term chance of cure of almost 90% irrespective of the primary tumor site, 45% of patients with mediastinal nonseminomas are alive at 5 years. This outcome is clearly inferior compared with patients with nonseminomatous retroperitoneal primary tumors.

Purpose: The xanthophyll carotenoids (lutein and zeaxanthin) are hypothesized to delay progression of age-related macular degeneration. The quail has a cone-dominant retina that accumulates carotenoids. The purpose of these experiments was to characterize the carotenoid composition of retina, serum, liver, and fat in quail and to determine whether dietary enrichment with zeaxanthin alters zeaxanthin or lutein concentrations in these tissues., Methods: Quail were fed for 6 months with a commercial turkey diet (T group; n = 8), carotenoid-deficient diet (C- group; n = 8), or a carotenoid-deficient diet supplemented with 35 mg 3R,3'R-zeaxanthin per kilogram of food, (Z+ group; n = 8). Zeaxanthin was derived from Sphingobacterium multivorum (basonym Flavobacterium). Carotenoids in serum, retina, liver, and fat were analyzed by HPLC., Results: As in the primate fovea, the retina accumulated zeaxanthin, lutein, and cryptoxanthin, and preferentially absorbed zeaxanthin (P < 0.005). In contrast, lutein was preferentially absorbed by liver (P < 0.01) and fat (P < 0.0001). In supplemented females, zeaxanthin increased approximately 4-fold in retina, and 74-, 63- and 22-fold in serum, liver, and fat, respectively. In males, zeaxanthin was elevated approximately 3-fold in retina, and 42-, 17-, and 12-fold in serum, liver, and fat, respectively. Birds fed the Z+ diet absorbed a higher fraction of dietary lutein into serum, but lutein was reduced in the retina (P < 0.05)., Conclusions: Xanthophyll profiles in quail mimic those in primates. Dietary supplements of zeaxanthin effectively increased zeaxanthin concentrations in serum, retina, liver, and fat. The robust response to zeaxanthin supplementation identifies the quail as an animal model for exploration of factors regulating delivery of dietary carotenoids to the retina.

Background: The frequency of subsequent testicular cancer (referred to as metachronous testicular cancer) in men who have had previous testicular cancer is relatively high. The rate of metachronous testicular cancer in men with extragonadal germ cell tumors (EGCTs), however, is largely unknown. We conducted a retrospective study of EGCT patients to determine the incidence, cumulative risk, and specific risk factors for metachronous testicular cancers., Methods: A standardized questionnaire about patient characteristics, the extent of EGCT disease, any second malignancies, and treatments received was completed for 635 patients with EGCTs identified from the medical records of 11 cancer centers in Europe and the United States from 1975 through 1996. Comparisons with age group-specific data from the Saarland, Germany, population-based cancer registry were used to calculate the standardized incidence ratio (SIR). The Kaplan-Meier method was used to analyze survival data and cumulative risk. All statistical tests were two-sided., Results: Sixteen EGCT patients (4.1%) developed metachronous testicular cancers, with a median time between diagnoses of 60 months (range, 14-102 months). The risk of developing metachronous testicular cancers was statistically significantly increased in patients with EGCTs (observed = 16; expected = 0.26; SIR = 62; 95% confidence interval [CI] = 36 to 99) and in subsets of EGCT patients with mediastinal location (SIR = 31; 95% CI = 8 to 59), retroperitoneal location (SIR = 100; 95% CI = 54 to 172), and nonseminomatous histology (SIR = 75; 95% CI = 43 to 123). The cumulative risk of developing a metachronous testicular cancer 10 years after a diagnosis of EGCT was 10.3% (95% CI = 4.9% to 15.6%) and was higher among patients with nonseminomatous EGCTs (14.3%; 95% CI = 6.7% to 21.9%) and retroperitoneal EGCTs (14.2%; 95% CI = 5.6% to 22.8%) than among patients with seminomatous EGCTs (1.4%; 95% CI = 0.0% to 4.2%) and mediastinal EGCTs (6.2%; 95% CI = 0.1% to 12.2%)., Conclusions: Patients with EGCTs, particularly those with retroperitoneal or nonseminomatous tumors, but also those with primary mediastinal EGCTs, are at an increased risk of metachronous testicular cancer.

Background: Creutzfeldt-Jakob disease (CJD) in humans and chronic wasting disease (CWD) in deer and elk occur in the United States. Recent reports of 3 unusually young patients with CJD who regularly consumed deer or elk meat created concern about the possible zoonotic transmission of CWD., Objective: To examine the possible transmission of CWD to humans., Patients: Three unusually young patients (aged 28, 28, and 30 years) with CJD in the United States during 1997-2000., Methods: We reviewed medical records and interviewed family members and state wildlife and agriculture officials. Brain tissue samples were tested using histopathologic, immunohistochemical, immunoblot, or prion protein gene analyses., Main Outcome Measures: Presence or absence of established CJD risk factors, deer and elk hunting in CWD-endemic areas, and comparison of the evidence for the 3 patients with that of a zoonotic link between new variant CJD and bovine spongiform encephalopathy., Results: None of the patients had established CJD risk factors or a history of travel to Europe. Two patients hunted game animals and 1 was a daughter of a hunter. Unlike patients with new variant CJD, the 3 patients did not have a unique neuropathologic manifestation, clinicopathologic homogeneity, uniformity in the codon 129 of the prion protein gene, or prion characteristics different from those of classic variants., Conclusions: Although the occurrence of 3 unusually young patients with CJD who consumed venison suggested a possible relationship with CWD, our follow-up investigation found no strong evidence for a causal link. Ongoing CJD surveillance remains important for continuing to assess the risk, if any, of CWD transmission to humans.

Disseminated germ cell tumors (GCT) have come to represent the model for a curable malignancy, as cure rates with cisplatin-based chemotherapy coupled with appropriate surgery are 70% to 80%. For patients with favorable prognostic factors who achieve and maintain a complete response, the outlook is good. However, despite advances in the treatment of this disease, a significant number of patients with metastatic GCT fail to respond either primarily or secondarily. Being able to identify poor-risk patients up front would allow for appropriate selection of candidates for high-risk trials. Several different classification systems were previously developed at several treatment centers in the United States and Europe. These models recognized different clinical variables as prognosticators and had unique functional properties. However, these served as precursors to the International Germ Cell Consensus Classification that was developed to establish a universally accepted standard. The development of this system has allowed for valid comparisons of ongoing and future trials. Furthermore, this system will serve to encourage international collaboration for the study of high-risk GCT.

The success of management of germ cell tumors puts an extraordinary burden on the physician and health care system to assure that cure is achieved in all patients except the small proportion that present with advanced refractory disease. New prognostic systems can define groups of patients who have excellent outcomes with treatment and a group of patients for whom treatment less reliably results in cure. Good risk disseminated disease should be treated with three cycles of bleomycin, etoposide, and cisplatin, whereas those with more advanced disease should receive four cycles. Postchemotherapy resection of residual disease is commonly required. In patients who recur after primary chemotherapy, salvage treatments can result in cure in 30% to 40% of patients.