Hydroxychloroquine in the treatment of outpatients with mildly symptomatic COVID-19: a multi-center observational study.

BACKGROUND: Hydroxychloroquine has not been associated with improved survival among hospitalized COVID-19 patients in the majority of observational studies and similarly was not identified as an effective prophylaxis following exposure in a prospective randomized trial. We aimed to explore the role of hydroxychloroquine therapy in mildly symptomatic patients diagnosed in the outpatient setting. METHODS: We examined the association between outpatient hydroxychloroquine exposure and the subsequent progression of disease among mildly symptomatic non-hospitalized patients with documented SARS-CoV-2 infection. The primary outcome assessed was requirement of hospitalization. Data was obtained from a retrospective review of electronic health records within a New Jersey USA multi-hospital network. We compared outcomes in patients who received hydroxychloroquine with those who did not applying a multivariable logistic model with propensity matching. RESULTS: Among 1274 outpatients with documented SARS-CoV-2 infection 7.6% were prescribed hydroxychloroquine. In a 1067 patient propensity matched cohort, 21.6% with outpatient exposure to hydroxychloroquine were hospitalized, and 31.4% without exposure were hospitalized. In the primary multivariable logistic regression analysis with propensity matching there was an association between exposure to hydroxychloroquine and a decreased rate of hospitalization from COVID-19 (OR 0.53; 95% CI, 0.29, 0.95). Sensitivity analyses revealed similar associations. QTc prolongation events occurred in 2% of patients prescribed hydroxychloroquine with no reported arrhythmia events among those with data available. CONCLUSIONS: In this retrospective observational study of SARS-CoV-2 infected non-hospitalized patients hydroxychloroquine exposure was associated with a decreased rate of subsequent hospitalization. Additional exploration of hydroxychloroquine in this mildly symptomatic outpatient population is warranted.

Implementing a Review Process to Facilitate and Prioritize COVID-19 Research: Staying One Step Ahead of the Pandemic.

The first coronavirus disease 2019 (COVID-19) patient in the state of New Jersey (NJ) was admitted on March 2, 2020. With the number of hospitalized patients increasing exponentially in the following days and no established treatment approaches, research was to play a significant role in this fight. To facilitate review of all COVID-19 research proposals in a large health care network in NJ, we established the COVID-19 Research Review Committee (RRC) and implemented a peer-review process prior to the Institutional Review Board submission. The RRC was tasked with processing, soliciting, reviewing, and prioritizing research proposals and was comprised of a multidisciplinary group of reviewers. Within a 9-week period, three network-wide requests for proposals were released with 238 proposals submitted and 93 approved, an approval rate of 39%. The establishment of the RRC helped ensure scientific merit, better utilization of resources, collaborations across disciplines and network hospitals, and compliance with applicable regulatory and ethical standard.

Development and validation of a prognostic 40-day mortality risk model among hospitalized patients with COVID-19.

OBJECTIVES: The development of a prognostic mortality risk model for hospitalized COVID-19 patients may facilitate patient treatment planning, comparisons of therapeutic strategies, and public health preparations. METHODS: We retrospectively reviewed the electronic health records of patients hospitalized within a 13-hospital New Jersey USA network between March 1, 2020 and April 22, 2020 with positive polymerase chain reaction results for SARS-CoV-2, with follow-up through May 29, 2020. With death or hospital discharge by day 40 as the primary endpoint, we used univariate followed by stepwise multivariate proportional hazard models to develop a risk score on one-half the data set, validated on the remainder, and converted the risk score into a patient-level predictive probability of 40-day mortality based on the combined dataset. RESULTS: The study population consisted of 3123 hospitalized COVID-19 patients; median age 63 years; 60% were men; 42% had >3 coexisting conditions. 713 (23%) patients died within 40 days of hospitalization for COVID-19. From 22 potential candidate factors 6 were found to be independent predictors of mortality and were included in the risk score model: age, respiratory rate ≥25/minute upon hospital presentation, oxygenation <94% on hospital presentation, and pre-hospital comorbidities of hypertension, coronary artery disease, or chronic renal disease. The risk score was highly prognostic of mortality in a training set and confirmatory set yielding in the combined dataset a hazard ratio of 1.80 (95% CI, 1.72, 1.87) for one unit increases. Using observed mortality within 20 equally sized bins of risk scores, a predictive model for an individual's 40-day risk of mortality was generated as -14.258 + 13.460*RS + 1.585*(RS-2.524)^2-0.403*(RS-2.524)^3. An online calculator of this 40-day COVID-19 mortality risk score is available at www.HackensackMeridianHealth.org/CovidRS. CONCLUSIONS: A risk score using six variables is able to prognosticate mortality within 40-days of hospitalization for COVID-19. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT04347993.

National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for use of tumor markers in liver, bladder, cervical, and gastric cancers.

BACKGROUND: Updated National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for the use of tumor markers in the clinic have been developed. METHODS: Published reports relevant to use of tumor markers for 4 cancer sites--liver, bladder, cervical, and gastric--were critically reviewed. RESULTS: Alpha-fetoprotein (AFP) may be used in conjunction with abdominal ultrasound for early detection of hepatocellular carcinoma (HCC) in patients with chronic hepatitis or cirrhosis associated with hepatitis B or C virus infection. AFP concentrations >200 microg/L in cirrhotic patients with typical hypervascular lesions >2 cm in size are consistent with HCC. After a diagnosis of HCC, posttreatment monitoring with AFP is recommended as an adjunct to imaging, especially in the absence of measurable disease. Although several urine markers have been proposed for bladder cancer, none at present can replace routine cystoscopy and cytology in the management of patients with this malignancy. Some may, however, be used as complementary adjuncts to direct more effective use of clinical procedures. Although carcinoembryonic antigen and CA 19-9 have been proposed for use gastric cancer and squamous cell carcinoma antigen for use in cervical cancer, none of these markers can currently be recommended for routine clinical use. CONCLUSIONS: Implementation of these recommendations should encourage optimal use of tumor markers for patients with liver, bladder, cervical, or gastric cancers.

Female sexual dysfunction in urological patients: findings from a major metropolitan area in the USA.

OBJECTIVE: To determine the prevalence of and risk factors for female sexual dysfunction (FSD) in a practice focused mainly on female urology. PATIENTS AND METHODS: A modified version of the Female Sexual Function Index (FSFI) was used to assess the prevalence of FSD in 587 patients who completed the questionnaire. Logistic regression was used to identify risk factors. RESULTS: The prevalence of FSD was 63%; age, menopausal status and usage of selective serotonin reuptake inhibitors were statistically significant risk factors for FSD. CONCLUSIONS: FSD is highly prevalent in this population of patients and screening female urological patients for FSD should be considered.

Hydroxychloroquine and tocilizumab therapy in COVID-19 patients-An observational study.

Hydroxychloroquine has been touted as a potential COVID-19 treatment. Tocilizumab, an inhibitor of IL-6, has also been proposed as a treatment of critically ill patients. In this retrospective observational cohort study drawn from electronic health records we sought to describe the association between mortality and hydroxychloroquine or tocilizumab therapy among hospitalized COVID-19 patients. Patients were hospitalized at a 13-hospital network spanning New Jersey USA between March 1, 2020 and April 22, 2020 with positive polymerase chain reaction results for SARS-CoV-2. Follow up was through May 5, 2020. Among 2512 hospitalized patients with COVID-19 there have been 547 deaths (22%), 1539 (61%) discharges and 426 (17%) remain hospitalized. 1914 (76%) received at least one dose of hydroxychloroquine and 1473 (59%) received hydroxychloroquine with azithromycin. After adjusting for imbalances via propensity modeling, compared to receiving neither drug, there were no significant differences in associated mortality for patients receiving any hydroxychloroquine during the hospitalization (HR, 0.99 [95% CI, 0.80-1.22]), hydroxychloroquine alone (HR, 1.02 [95% CI, 0.83-1.27]), or hydroxychloroquine with azithromycin (HR, 0.98 [95% CI, 0.75-1.28]). The 30-day unadjusted mortality for patients receiving hydroxychloroquine alone, azithromycin alone, the combination or neither drug was 25%, 20%, 18%, and 20%, respectively. Among 547 evaluable ICU patients, including 134 receiving tocilizumab in the ICU, an exploratory analysis found a trend towards an improved survival association with tocilizumab treatment (adjusted HR, 0.76 [95% CI, 0.57-1.00]), with 30 day unadjusted mortality with and without tocilizumab of 46% versus 56%. This observational cohort study suggests hydroxychloroquine, either alone or in combination with azithromycin, was not associated with a survival benefit among hospitalized COVID-19 patients. Tocilizumab demonstrated a trend association towards reduced mortality among ICU patients. Our findings are limited to hospitalized patients and must be interpreted with caution while awaiting results of randomized trials. Trial Registration: Clinicaltrials.gov Identifier: NCT04347993.

Tocilizumab among patients with COVID-19 in the intensive care unit: a multicentre observational study.

BACKGROUND: Tocilizumab, a monoclonal antibody directed against the interleukin-6 receptor, has been proposed to mitigate the cytokine storm syndrome associated with severe COVID-19. We aimed to investigate the association between tocilizumab exposure and hospital-related mortality among patients requiring intensive care unit (ICU) support for COVID-19. METHODS: We did a retrospective observational cohort study at 13 hospitals within the Hackensack Meridian Health network (NJ, USA). We included patients (aged ≥18 years) with laboratory-confirmed COVID-19 who needed support in the ICU. We obtained data from a prospective observational database and compared outcomes in patients who received tocilizumab with those who did not. We applied a multivariable Cox model with propensity score matching to reduce confounding effects. The primary endpoint was hospital-related mortality. The prospective observational database is registered on ClinicalTrials.gov, NCT04347993. FINDINGS: Between March 1 and April 22, 2020, 764 patients with COVID-19 required support in the ICU, of whom 210 (27%) received tocilizumab. Factors associated with receiving tocilizumab were patients' age, gender, renal function, and treatment location. 630 patients were included in the propensity score-matched population, of whom 210 received tocilizumab and 420 did not receive tocilizumab. 358 (57%) of 630 patients died, 102 (49%) who received tocilizumab and 256 (61%) who did not receive tocilizumab. Overall median survival from time of admission was not reached (95% CI 23 days-not reached) among patients receiving tocilizumab and was 19 days (16-26) for those who did not receive tocilizumab (hazard ratio [HR] 0·71, 95% CI 0·56-0·89; p=0·0027). In the primary multivariable Cox regression analysis with propensity matching, an association was noted between receiving tocilizumab and decreased hospital-related mortality (HR 0·64, 95% CI 0·47-0·87; p=0·0040). Similar associations with tocilizumab were noted among subgroups requiring mechanical ventilatory support and with baseline C-reactive protein of 15 mg/dL or higher. INTERPRETATION: In this observational study, patients with COVID-19 requiring ICU support who received tocilizumab had reduced mortality. Results of ongoing randomised controlled trials are awaited. FUNDING: None.

A single-institution experience with induction and maintenance intravesical docetaxel in the management of non-muscle-invasive bladder cancer refractory to bacille Calmette-Guérin therapy.

OBJECTIVE: To analyse the durability of response for patients with non-muscle-invasive bladder cancer (NMIBC) refractory to bacille Calmette-Guérin (BCG) therapy and treated with intravesical docetaxel in a combined induction and maintenance regimen. PATIENTS AND METHODS: A previous phase I trial showed docetaxel to be safe for intravesical therapy, with no systemic absorption and minimal toxicity after six weekly instillations for patients with BCG-refractory NMIBC. In that trial, docetaxel gave a 56% complete response (CR) rate at 12 weeks, but the durability was only 22%. Thus a second group of patients was treated with a 6-week induction and then given monthly maintenance therapy with intravesical docetaxel. Thirteen patients with BCG-refractory Ta, T1, or Tis transitional cell carcinoma were treated. Induction therapy was administered as six weekly intravesical instillations of 75 mg followed by single-dose monthly maintenance therapy for nine additional instillations in patients who had a CR. The initial response at 12 weeks from the start of induction therapy was evaluated by cystoscopy with biopsy, and urine cytology. The follow-up consisted of quarterly cystoscopy with biopsy and cytology, and periodic imaging. RESULTS: The median follow-up was 13 months; 10 of 13 patients had a CR after induction, and six have remained disease-free during the follow-up. Of those in who the treatment failed, six had transurethral resection of the tumour and one a cystectomy. All 10 initial responders completed at least three instillations of maintenance therapy to date (median nine instillations), of whom six have remained recurrence-free. CONCLUSION: Monthly maintenance therapy with intravesical docetaxel appears to extend the durability of response to induction treatment for a selected group of patients with BCG-refractory NMIBC, and might decrease the overall risk of recurrence in high-risk NMIBC.

Quality of life of men treated for localized prostate cancer: outcomes at 6 and 12 months.

GOALS OF WORK: Treatments for early-stage prostate cancer (PCa) are highly effective; therefore, research studies that explore quality of life (QOL) issues associated with different treatments are important. The purposes of this study were to (a) examine differences among treatment groups of men treated with either radiation therapies or radical prostatectomy for PCa and (b) examine quality of life outcomes over time. PATIENTS AND METHODS: We report outcomes 6 and 12 months after 159 men began treatment for PCa with either one of two types of radiation treatment (intensity-modulated radiation therapy plus high dose rate or intensity-modulated radiation therapy plus seed implantation) or radical prostatectomy. MAIN RESULTS: Significant differences among groups are described. Significant predictors of QOL at 6 months included urinary, bowel, and sexual symptoms, anxiety, depression, problem-focused coping, and physiological self-efficacy. Significant predictors of QOL at 12 months were urinary and bowel symptoms, stress, depression, problem-focused coping, and physiological self-efficacy. Demographic variables, race, and living status were significant predictors of quality of life at 12 months. CONCLUSIONS: Physiological symptoms and psychological symptoms were both significant predictors of QOL. The psychological factors that predicted quality of life in this study have potential for intervention and point to the next stage of the research.

Vascular anomalies during laparoscopic renal surgery: incidence and management of left-sided inferior vena cava.

BACKGROUND: Left-sided inferior vena cava (IVC) is an unusual abnormality that may be clinically significant during renal surgery. METHODS: We report the unique case of a patient with a centrally located left renal mass who underwent laparoscopic radical nephrectomy. During the hilar dissection, unusual vascular anatomy was encountered. The patient was noted to have a left-sided inferior vena cava with multiple renal veins and anomalous tributaries. Laparoscopic radical nephrectomy was performed without complication. DISCUSSION: The embryology of a left-sided inferior vena cava is reviewed, and the safety and feasibility of a laparoscopic approach is discussed.

Prostate HDR radiation therapy: a comparative study evaluating the effectiveness of pain management with peripheral PCA vs. PCEA.

INTRODUCTION: High dose rate (HDR) brachytherapy is considered one of the most advanced treatment technologies currently available for treatment of localized prostate cancer. It gives the advantage of applying higher dose radiation, with greater precision, directly to the tumor while sparing healthy tissue and surrounding organs, thereby resulting in fewer side effects. In this facility, the treatment requires an overnight stay in the hospital, in a supine position, with a perineal template sutured to the perineum to prevent catheter movement or dislodgement. PURPOSE: To compare the effectiveness of pain management for men with prostate cancer being treated with HDR brachytherapy using a peripheral patient controlled analgesia (PCA) or patient controlled epidural analgesia (PCEA). METHOD: A comparative study was conducted evaluating the effectiveness of two pain management methods for men with prostate cancer receiving HDR brachytherapy. Pain assesments were conducted by scoring pain from the Foley catheter, interstitial catheter (perineal) and back (lumbosacral), using the Brief Pain Inventory Scale. RESULTS: Patients receiving pain management with the PCEA experienced significantly less pain. CONCLUSIONS: These finding suggest that use of PCEA with bupivacaine and fentanyl is more effective in managing pain related to HDR brachytherapy for prostate cancer, and results in a positive patient outcome thereby improving patient satisfaction.

The role of carbonic anhydrase IX overexpression in kidney cancer.

Carbonic anhydrase IX (CA IX) is a membrane isoenzyme, the overexpression of which is associated with clear cell carcinoma of the kidney. Its overexpression is restricted mainly to cancer, as it is absent in corresponding normal tissues making it a potential cancer biomarker. Several recent studies have shown that CA IX, apart from its classical enzyme activity of reversibly hydrating carbon dioxide extracellularly to facilitate the net extrusion of protons from inside to outside the cell, it can also be a key player in the modulation of cell adhesion processes and participate in the regulation of cell proliferation in response to hypoxic environment to ultimately contribute to tumour progression. Here, we have shown that the sole tyrosine moiety of CA IX present in its intracellular domain can be phosphorylated in an epidermal growth factor dependent manner, suggesting that it can feed into the growth factor receptor dependent signalling pathways. Our studies suggest that the tyrosine phosphorylated CA IX can interact with the regulatory subunit of PI-3-Kinase, contributing to Akt activation. These studies have revealed a positive feed back loop that can form the basis of a vicious cycle that could contribute to the progression of clear cell renal carcinoma and poor prognosis. These studies show that CA IX signalling may be a part of both the hypoxia driven and hypoxia independent pathways that occur in the cancer cell. Finally, our studies emphasize the need for a more refined strategy using signal transduction therapeutics to inhibit the cell surface carbonic anhydrases for the management of this malignancy.

Laparoscopic radical nephrectomy in renal cell carcinoma.

Historically, the only surgical option for removal of a renal mass was through a large incision in the abdomen. Recently, many urologists have adopted new innovations in the removal of renal masses including laparoscopic radical nephrectomy. The laparoscopic approach to radical nephrectomy has been associated with improved patient outcomes including decreased pain, shorter hospital stay, rapid recovery, and improved aesthetic cosmetic appearance. Laparoscopic radical nephrectomy may be performed in three different types of surgical procedures including laparoscopic hand-assisted radical nephrectomy, transperitoneal radical nephrectomy, and retroperitoneal radical nephrectomy. Understanding the procedure, preoperative instructions, and recovery will assist nurses in counseling patients considering laparoscopic radical nephrectomy.

Bacillus Calmete-Guérin plus interferon-alpha2B intravesical therapy maintains an extended treatment plan for superficial bladder cancer with minimal toxicity.

Bacillus Calmette-Guérin (BCG) and interferon-alpha2B (IFN-alpha2B) have both been individually used for the intravesical treatment of superficial bladder cancer. We report our experience on the therapeutic efficacy and toxicity of combined intravesical BCG plus IFN-alpha2B for treating superficial bladder cancer, including patients failing previous BCG therapy. Thirty-two patients with superficial bladder cancer underwent 6 weekly treatments with full-, one-third, or one-tenth-dose of BCG plus 50 or 100 MU of IFN-alpha2B based on prior BCG exposure and tolerance. Patients with no evidence of disease proceeded onto maintenance therapy of 3 weekly treatments at 3 months followed by 2 additional maintenance cycles given 6 months apart. Response was assessed by cystoscopy/biopsy every 3 months after treatment. Before BCG plus IFN-alpha2B treatment, 20 patients (63%) had previously failed intravesical BCG therapy, 27 (84%) had aggressive disease (stage T1, grade 3, or carcinoma in situ), 27 (84%) had recurrent disease, 14 (44%) had multifocal disease, and 6 (19%) had disease of over 4 years duration. At median follow-up of 22 months, 21 patients (66%) remain disease-free and 11 patients (34%) had disease-recurrence. Nineteen of 32 patients (59%) were disease-free after the initial induction cycle. Six of 11 patients 55% ultimately failing combination therapy did so at the first 3 to 4 month evaluation. Four of 7 patients (57%) benefited from salvage re-induction therapy. Of the 20 patients previously treated with BCG, 12 patients (60%) remain disease-free. Combination BCG plus IFN-alpha2B intravesical therapy was well tolerated. Combination intravesical BCG plus IFN-alpha2B is an effective and tolerable alternative for patients with superficial bladder cancer, including those patients in whom intravesical BCG therapy had previously failed. Benefits of this combination therapy may include potentially less morbidity, improved clinical efficacy, and in the long term, fewer patients undergoing radical therapy. However, radical treatment options should be pursued for early failures of this combination regimen in those patients with risk factors for recurrence and progression.

DD23 Biomarker: a prospective clinical assessment in routine urinary cytology specimens from patients being monitored for TCC.

BACKGROUND: A prospective clinical study was conducted to assess the ability of the DD23 murine monoclonal antibody to enhance detection of bladder cancer in routine alcohol fixed urine cytology samples. METHODS: Prospectively, 308 bladder cytology specimens were obtained from patients with a history of bladder cancer with a mean age of 71.4+/-11.9 (27% female, 73% male). Data included 121 biopsy-confirmed results and 187 cystoscopy results to assess presence or absence of cancer. Thirty-five normal cytology specimens were obtained from asymptomatic men and women between 55-85 years of age. Separate slides from the alcohol fixed cytology specimens were stained using the Papanicolaou (Pap) and Feulgen staining procedures. The DD23 assay was performed using an avidin-biotin alkaline phosphatase immunocytochemical procedure, with a single urothelial cell exhibiting intense immunostaining sufficient to make a positive call. RESULTS: Pap-Feulgen cytopathology for the 308 cases yielded an overall sensitivity of 65.5% and a specificity of 85.1%, and the DD23 biomarker alone yielded a sensitivity of 80.5% and a specificity of 59.7%. Analysis of the voided urines only (n=164) yielded sensitivities of 61.0% and 73.2% and specificities of 86.2% and 67.5% for cytopathology and DD23 alone, respectively. Results in 49 bladder wash urine cytology cases produced a sensitivity of 70.2% and 100% and specificities of 92.3% and 61.5% for cytopathology and DD23 alone, respectively. In 133 patients that underwent biopsy or had positive cystoscopy results, cytopathology yielded a sensitivity of 65.5% and a specificity of 69.6% while DD23 yielded a sensitivity of 80.5% and a specificity of 58.7%. In 25 biopsy-confirmed low-grade cancers, DD23 improved cancer detection from 32% to 72% when compared to cytopathology. The DD23 biomarker had a specificity of 85.7% in 35 age-matched normal asymptomatic control specimens. CONCLUSIONS: The DD23 biomarker is an adjuvant test that provides improved detection of bladder cancer in cytology specimens and enhances the sensitivity of the cytopathology diagnosis, especially in low-grade cancers.

A contemporary evaluation of cytoreductive nephrectomy with tumor thrombus: Morbidity and long-term survival.

BACKGROUND: Metastatic renal cell carcinoma (RCC) is an aggressive entity that frequently invades the venous system. We evaluated the morbidity and survival of patients with tumor thrombus who undergo cytoreductive nephrectomy. MATERIALS AND METHODS: We identified 56 patients from our institution's database who had a primary renal tumor in place and documented metastases at the time of surgery. We reviewed demographic and pathologic characteristics from these patients as well as complications and overall survival. RESULTS: Median age was 58 (37-77). There were 33 patients (59%) who had tumor thrombus with 21 (64%) involving the renal vein, 10 (30%) involving the infradiaphragmatic inferior vena cava (IVC), and 2 (6%) involving the supradiaphragmatic IVC. Median tumor size for thrombus patients was 12 cm (5-29). There were 8 (14.2%) who had complications, including 1 death. Thrombus patients were significantly more likely to have a complication (P = 0.008). Median survival for all patients was 10.7 months (0.3-61). There was no significant difference in overall survival between patients with and without thrombus (P = 0.76). CONCLUSIONS: Patients who undergo cytoreductive nephrectomy with a tumor thrombus have a higher rate of complications as compared to patients undergoing cytoreductive nephrectomy without tumor thrombus. The long-term survival, however, was not statistically different and thus aggressive surgery for select metastatic RCC patients is warranted.

Shifting gene expression profiles during ex vivo culture of renal tumor cells: implications for cancer immunotherapy.

The use of cultured tumor cells rather than original tumor tissue for the preparation of therapeutic cancer vaccines represents an obvious solution to the problem of availability of adequate quantities of autologous tumor. In this study we investigated possible changes in gene expression accompanying the transition of renal cell carcinoma cells from the original tissue to cell populations in culture. In our study we employed cDNA microarray technology to compare the gene expression pattern of ex vivo cultured renal carcinoma cells to that of the original solid tumor tissue from which the cells were derived. Using this approach we detected changes in the expression of many genes mostly related to the cell lines' physiological properties. Some of the products of those genes showing differential expression between tumor-derived cell line and original tumor are known human autoantigens or tumor-associated antigens. Furthermore, analysis of overexpressed genes revealed the presence of several transcripts with restricted normal tissue distribution, representing self-antigens with potential to elicit autoimmunity. Our results suggest that adapting tumor tissue to culture can result in changes in the level of transcripts specific for known antigens and that more information regarding the composition of tumor cells and their byproducts used in vaccine trials is needed before the efficacy and safety of such procedures can truly be determined.

Review of vitamin E and selenium in the prevention of prostate cancer: implications of the selenium and vitamin E chemoprevention trial.

The National Cancer Institute in cooperation with the Southwest Oncology Group has begun one of the largest prostate cancer prevention studies to date, the Selenium and Vitamin E Chemoprevention Trial (SELECT). The purpose of this article is to review the evidence and discuss the individual antioxidant compounds under study. The authors comprehensively reviewed the peer-reviewed literature on the chemoprevention of prostate cancer with emphasis on the antioxidants vitamin E and selenium. The credible leads for the primary prevention of prostate cancer using selenium and vitamin E have emerged as secondary findings from randomized controlled trials with corroborative evidence from observational and in vitro studies. Selenium and vitamin E are widely available compounds that are safe if taken in moderation, with relatively few adverse effects. The evidence in support of the antioxidants in the primary prevention of prostate cancer is promising, and the next step in definitively answering the question has been addressed by the investigators of SELECT. The SELECT study will define the role of the antioxidants selenium and vitamin E in the prevention of prostate cancer; complete data from the study will be available in 12 years.