Antiadenovirus Antibodies Predict Response Durability to Nadofaragene Firadenovec Therapy in BCG-unresponsive Non-muscle-invasive Bladder Cancer: Secondary Analysis of a Phase 3 Clinical Trial.

A recent phase 3 trial of intravesical nadofaragene firadenovec reported a promising complete response rate for patients with bacillus Calmette-Guérin-unresponsive non-muscle-invasive bladder cancer. This study examined the ability of antiadenovirus antibody levels to predict the durability of therapeutic response to nadofaragene firadenovec. A standardized and validated quantitative assay was used to prospectively assess baseline and post-treatment serum antibody levels among 91 patients from the phase 3 trial, of whom 47 (52%) were high-grade recurrence free at 12 mo (responders). While baseline titers did not predict treatment response, 3-mo titer >800 was associated with a higher likelihood of durable response (p = 0.026). Peak post-treatment titers >800 were noted in 42 (89%) responders versus 26 (59%) nonresponders (p = 0.001; assay sensitivity, 89%; negative predictive value, 78%). Moreover, 22 (47%) responders compared with eight (18%) nonresponders had a combination of peak post-treatment titers >800 and peak antibody fold change >8 (p = 0.004; assay specificity, 82%; positive predictive value, 73%). A majority of responders continued to have post-treatment antibody titers >800 after the first 6 mo of therapy. In conclusion, serum antiadenovirus antibody quantification may serve as a novel predictive marker for nadofaragene firadenovec response durability. Future studies will focus on large-scale validation and clinical utility of the assay. PATIENT SUMMARY: This study reports on a planned secondary analysis of a phase 3 multicenter clinical trial that established the benefit of nadofaragene firadenovec, a novel intravesical gene therapeutic, for the treatment of patients with bacillus Calmette-Guérin (BCG)-unresponsive high-risk non-muscle-invasive bladder cancer. Prospective assessment of serum anti-human adenovirus type-5 antibody levels of patients in this trial indicated that a combination of post-treatment titers and fold change from baseline can predict treatment efficacy. While this merits additional validation, our findings suggest that serum antiadenovirus antibody levels can serve as an important predictive marker for the durability of therapeutic response to nadofaragene firadenovec.

Understanding the Ecological Validity of Relying Practice as a Basis for Risk Identification.

Understanding the reliability of hazardous organizations and their protective systems is central to understanding the risk they produce. Work on "high reliability organization" has done much to illuminate the conditions in which social organization becomes reliable in highly demanding conditions. But risk depends just as much on how relying entities do their relying as it does on the reliability of the entities they rely on. Patterns of relying are often opaque in sociotechnical systems, and processes of relying and being relied on are mutually influencing in complex ways, so the relationship between relying and risk may not be at all obvious. This study was an attempt to study relying as a social practice, in particular analyzing how it had ecological validity in a social organization-how practice was responsive to the conditions in which it took place. This involved observational fieldwork and inductive, qualitative analysis on an offshore oil and gas production platform that was nearing the end of its design life and undergoing refurbishment. The analysis produced four main categories of ecological validity: responsiveness to formal organization, responsiveness to situational contingency, responsiveness to information asymmetry, and responsiveness to sociomateriality. This ecological validity of relying practice should be a primary focus of risk identification, assessing how relying can become mismatched to reliability in certain ways, both when relying practice is responsive to circumstances and when it is not.

Angiotensin receptor blocker use and gastro-oesophageal cancer survival: a population-based cohort study.

BACKGROUND: Angiotensin receptor blockers (ARBs; including candesartan, losartan, olmesartan and valsartan) are widely used to treat hypertension, heart failure and diabetic neuropathy. There is considerable pre-clinical evidence that ARBs can reduce cancer progression, particularly for gastric cancer. Despite this, epidemiological studies have yet to assess the impact of ARB use on gastro-oesophageal cancer survival. AIM: To investigate the association between post-diagnosis ARB use and gastro-oesophageal cancer survival. METHODS: We selected a cohort of patients with newly-diagnosed gastro-oesophageal cancer between 1998 and 2012 from English cancer registries. We linked to prescription and clinical records from the Clinical Practice Research Datalink, and to death records from the Office for National Statistics. We used time-dependant Cox-regression models to calculate hazard ratios (HRs) comparing gastro-oesophageal cancer-specific mortality between post-diagnosis ARB users and non-users, after adjusting for demographics, comorbidities and post-diagnosis aspirin or statin use. RESULTS: Our cohort included 5124 gastro-oesophageal cancer patients, of which 360 used ARBs, and 3345 died due to their gastro-oesophageal cancer during follow-up. After adjustment, ARB users had moderately lower risk of gastro-oesophageal cancer mortality than the non-users (HR = 0.83, 95% CI 0.71-0.98). There was evidence of a dose-response relationship with the lowest HRs observed among patients receiving at least 2 years of prescriptions (HR = 0.42, 95% CI 0.25-0.72). CONCLUSIONS: In this large population-based gastro-oesophageal cancer cohort, we found moderately reduced cancer-specific mortality among ARB users. However, confirmation in further independent epidemiological studies with sufficient staging information is required.

Analysis of Affordance, Time, and Adaptation in the Assessment of Industrial Control System Cybersecurity Risk.

Industrial control systems increasingly use standard communication protocols and are increasingly connected to public networks-creating substantial cybersecurity risks, especially when used in critical infrastructures such as electricity and water distribution systems. Methods of assessing risk in such systems have recognized for some time the way in which the strategies of potential adversaries and risk managers interact in defining the risk to which such systems are exposed. But it is also important to consider the adaptations of the systems' operators and other legitimate users to risk controls, adaptations that often appear to undermine these controls, or shift the risk from one part of a system to another. Unlike the case with adversarial risk analysis, the adaptations of system users are typically orthogonal to the objective of minimizing or maximizing risk in the system. We argue that this need to analyze potential adaptations to risk controls is true for risk problems more generally, and we develop a framework for incorporating such adaptations into an assessment process. The method is based on the principle of affordances, and we show how this can be incorporated in an iterative procedure based on raising the minimum period of risk materialization above some threshold. We apply the method in a case study of a small European utility provider and discuss the observations arising from this.

Can urinary PCA3 supplement PSA in the early detection of prostate cancer?

PURPOSE: Given the limited sensitivity and specificity of prostate-specific antigen (PSA), its widespread use as a screening tool has raised concerns for the overdiagnosis of low-risk and the underdiagnosis of high-grade prostate cancer. To improve early-detection biopsy decisions, the National Cancer Institute conducted a prospective validation trial to assess the diagnostic performance of the prostate cancer antigen 3 (PCA3) urinary assay for the detection of prostate cancer among men screened with PSA. PATIENTS AND METHODS: In all, 859 men (mean age, 62 years) from 11 centers scheduled for a diagnostic prostate biopsy between December 2009 and June 2011 were enrolled. The primary outcomes were to assess whether PCA3 could improve the positive predictive value (PPV) for an initial biopsy (at a score > 60) and the negative predictive value (NPV) for a repeat biopsy (at a score < 20). RESULTS: For the detection of any cancer, PPV was 80% (95% CI, 72% to 86%) in the initial biopsy group, and NPV was 88% (95% CI, 81% to 93%) in the repeat biopsy group. The addition of PCA3 to individual risk estimation models (which included age, race/ethnicity, prior biopsy, PSA, and digital rectal examination) improved the stratification of cancer and of high-grade cancer. CONCLUSION: These data independently support the role of PCA3 in reducing the burden of prostate biopsies among men undergoing a repeat prostate biopsy. For biopsy-naive patients, a high PCA3 score (> 60) significantly increases the probability that an initial prostate biopsy will identify cancer.

Organizational sensemaking about risk controls: the case of offshore hydrocarbons production.

In the same way that individuals' risk perceptions can influence how they behave toward risks, how organizational members make sense of risk controls is an important influence on how they apply and maintain such controls. In this article, we describe an analysis of sensemaking about the control of risk in offshore hydrocarbons production, an industry that continues to produce disasters of societal significance. A field study of 80 interviews was conducted in five offshore oil and gas companies and the agency that regulates them. The interviews were analyzed using qualitative template analysis. This provided a categorization of the many ways of acting through which informants made sense of the risk control task, and indicated that the organizations placed substantially different emphases on different ways of acting. Nevertheless, this sensemaking fell into two broad classes: that which tended to limit or be pessimistic about organizational controls, and that which tended to extend or be optimistic about organizational controls. All the participating organizations collectively placed a balanced emphasis on these two classes. We argue that this balanced sensemaking is an adaptation rather than a deliberate choice, but that it is an important element of controlling risk in its own right.

Uptake of carotid artery stenting in England and subsequent vascular admissions: an appropriate response to emerging evidence?

OBJECTIVE: We report the uptake, length of stay and vascular readmission rates of carotid endarterectomy (CEA) and CAS among patients with symptomatic or asymptomatic carotid artery disease in the English National Health Service (NHS). METHODS: Retrospective cohort study based on routinely collected Hospital Episode Statistics (HES) inpatient data. We identified individual admissions for CEA (n = 15996) or CAS (n = 632) between 2006 and 2009. Summary data were used to describe procedure volumes between 2009 and 2012. We analysed trends in procedure use over time and used ordinary least squares regression to evaluate patient, clinical and organisational characteristics associated with longer length of stay for revascularisation. RESULTS: CAS made up less than 5% of carotid revascularisation procedures; there was no trend for increasing use between 2006 and 2012. Patients treated with CAS were on average younger, lived in areas of higher deprivation and were more likely to have amaurosis fugax or a comorbidity of heart disease. CAS patients had a 19% (95% CI 14-24) shorter stay in hospital than CEA patients. CONCLUSION: Despite the early promise of CAS and numerous randomised controlled trials evaluating efficacy, it has not been rapidly adopted in England. Cautious adoption may be appropriate given the higher periprocedural risk of stroke or death after CAS, particularly in recently symptomatic patients.

A pragmatic randomised controlled trial of the effectiveness and cost-effectiveness of 'PhysioDirect' telephone assessment and advice services for physiotherapy.

BACKGROUND: As a result of long delays for physiotherapy for musculoskeletal problems, several areas in the UK have introduced PhysioDirect services in which patients telephone a physiotherapist for initial assessment and treatment advice. However, there is no robust evidence about the effectiveness, cost-effectiveness or acceptability to patients of PhysioDirect. OBJECTIVE: To investigate whether or not PhysioDirect is equally as clinically effective as and more cost-effective than usual care for patients with musculoskeletal (MSK) problems in primary care. DESIGN: Pragmatic randomised controlled trial to assess equivalence, incorporating economic evaluation and nested qualitative research. Patients were randomised in 2 : 1 ratio to PhysioDirect or usual care using a remote automated allocation system at the level of the individual, stratifying by physiotherapy site and minimising by sex, age group and site of MSK problem. For the economic analysis, cost consequences included NHS and patient costs, and the cost of lost production. Cost-effectiveness analysis was carried out from the perspective of the NHS. Interviews were conducted with patients, physiotherapists and their managers. SETTING: Four community physiotherapy services in England. PARTICIPANTS: Adults referred by general practitioners or self-referred for physiotherapy for a MSK problem. INTERVENTIONS: Patients allocated to PhysioDirect were invited to telephone a senior physiotherapist for initial assessment and advice using a computerised template, followed by face-to-face care when necessary. Patients allocated to usual care were put on to a waiting list for face-to-face care. MAIN OUTCOME MEASURES: Primary outcome was the Short Form questionnaire-36 items, version 2 (SF-36v2) Physical Component Score (PCS) at 6 months after randomisation. Secondary outcomes included other measures of health outcome [Measure Yourself Medical Outcomes Profile, European Quality of Life-5 Dimensions (EuroQol health utility measure, EQ-5D), global improvement, response to treatment], wait for treatment, time lost from work and usual activities, patient satisfaction. Data were collected by postal questionnaires at baseline, 6 weeks and 6 months, and from routine records by researchers blind to allocation. RESULTS: A total of 1506 patients were allocated to PhysioDirect and 743 to usual care. Patients allocated to PhysioDirect had a shorter wait for treatment than those allocated to usual care [median 7 days vs 34 days; arm-time ratio 0.32, 95% confidence interval (CI) 0.29 to 0.35] and had fewer non-attended face-to-face appointments [incidence rate ratio 0.55 (95% CI 0.41 to 0.73)]. The primary outcome at 6 months' follow-up was equivalent between PhysioDirect and usual care [mean PCS 43.50 vs 44.18, adjusted difference in means -0.01 (95% CI -0.80 to 0.79)]. The secondary measures of health outcome all demonstrated equivalence at 6 months, with slightly greater improvement in the PhysioDirect arm at 6 weeks' follow-up. Patients were equally satisfied with access to care but slightly less satisfied overall with PhysioDirect compared with usual care. NHS costs (physiotherapy plus other relevant NHS costs) per patient were similar in the two arms [PhysioDirect £ 198.98 vs usual care £ 179.68, difference in means £ 19.30 (95% CI -£ 37.60 to £ 76.19)], while QALYs gained were also similar [difference in means 0.007 (95% CI -0.003 to 0.016)]. Incremental cost per QALY gained was £ 2889. The probability that PhysioDirect was cost-effective at a £ 20,000 willingness-to-pay threshold was 88%. These conclusions about cost-effectiveness were robust to sensitivity analyses. There was no evidence of difference between trial arms in cost to patients or value of lost production. No adverse events were detected. CONCLUSIONS: Providing physiotherapy via PhysioDirect is equally clinically effective compared with usual waiting list-based care, provides faster access to treatment, appears to be safe, and is broadly acceptable to patients. PhysioDirect is probably cost-effective compared with usual care.

Managing the social amplification of risk: a simulation of interacting actors.

A central problem in managing risk is dealing with social processes that either exaggerate or understate it. A longstanding approach to understanding such processes has been the social amplification of risk framework. But this implies that some true level of risk becomes distorted in social actors' perceptions. Many risk events are characterised by such uncertainties, disagreements and changes in scientific knowledge that it becomes unreasonable to speak of a true level of risk. The most we can often say in such cases is that different groups believe each other to be either amplifying or attenuating a risk. This inherent subjectivity raises the question as to whether risk managers can expect any particular kinds of outcome to emerge. This question is the basis for a case study of zoonotic disease outbreaks using systems dynamics as a modelling medium. The model shows that processes suggested in the social amplification of risk framework produce polarised risk responses among different actors, but that the subjectivity magnifies this polarisation considerably. As this subjectivity takes more complex forms it leaves problematic residues at the end of a disease outbreak, such as an indefinite drop in economic activity and an indefinite increase in anxiety.

Prostate cancer, Version 3.2012: featured updates to the NCCN guidelines.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prostate Cancer provide multidisciplinary recommendations for the clinical management of patients with prostate cancer. These NCCN Guidelines Insights highlight notable recent updates. Abiraterone acetate is a first-in-class hormonal agent that represents a new standard of care for patients with metastatic castration-recurrent prostate cancer who have previously received docetaxel (category 1 recommendation). Abiraterone acetate also received category 2B recommendations in the prechemotherapy setting for asymptomatic patients or symptomatic patients who are not candidates for docetaxel. The NCCN Prostate Cancer Panel also added new indications for existing agents, including the option of sipuleucel-T as second-line therapy. In addition, brachytherapy in combination with external beam radiation therapy with or without androgen deprivation therapy is now an alternative for patients with high-risk localized tumors or locally advanced disease.

A phase 2 cancer chemoprevention biomarker trial of isoflavone G-2535 (genistein) in presurgical bladder cancer patients.

The soy compound genistein has been observed preclinically to inhibit bladder cancer growth with one potential mechanism being the inhibition of epidermal growth factor receptor phosphorylation (p-EGFR). A phase 2 randomized, placebo-controlled trial investigated whether daily, oral genistein (300 or 600 mg/d as the purified soy extract G-2535) for 14 to 21 days before surgery alters molecular pathways in bladder epithelial tissue in 59 subjects diagnosed with urothelial bladder cancer (median age, 71 years). G-2535 treatment was well tolerated; observed toxicities were primarily mild to moderate gastrointestinal or metabolic and usually not attributed to study drug. Genistein was detected in plasma and urine of subjects receiving G-2535 at concentrations greater than placebo subjects' but were not dose-dependent. Reduction in bladder cancer tissue p-EGFR staining between the placebo arm and the combined genistein arms was significant at the protocol-specified significance level of 0.10 (P = 0.07). This difference was most prominent when comparing the 300-mg group with placebo (P = 0.015), but there was no significant reduction in p-EGFR staining between the 600-mg group and placebo. No difference in normal bladder epithelium p-EGFR staining was observed between treatment groups. No significant differences in tumor tissue staining between treatment groups were observed for COX-2, Ki-67, activated caspase-3, Akt, p-Akt, mitogen-activated protein kinase (MAPK), or p-MAPK. No significant differences in urinary survivin or BLCA-4 levels between treatment groups were observed. Genistein displayed a possible bimodal effect (more effective at the lower dose) on bladder cancer tissue EGFR phosphorylation that should be evaluated further, possibly in combination with other agents.

Multi-institutional analysis of robotic radical cystectomy for bladder cancer: perioperative outcomes and complications in 227 patients.

PURPOSE: Recently, some surgeons have begun to describe single-institution case series with less invasive surgical approaches to bladder cancer such as laparoscopic or robotic-assisted techniques. We report on a multi-institutional, multi-surgeon experience with robotic radical cystectomy with regard to operative and pathologic outcomes and complications to evaluate the feasibility and reproducibility of this technique in a large cohort of patients. SUBJECTS AND METHODS: Two hundred twenty-seven patients (178 males and 49 females) underwent a robotic cystectomy and urinary diversion at one of four institutions. Operative outcomes, pathological results, and complications of this combined case series are herein reported. RESULTS: Mean age of this cohort was 67.1 years (range, 33-86 years) with a mean American Society of Anesthesiologists score of 2.7 (range, 2-4). One hundred sixty-eight patients (74%) underwent ileal conduit diversion, 58 (26%) underwent orthotopic ileal neobladder, and 1 patient (<1%) had no diversion (end-stage renal disease). The urinary diversion was performed extracorporeally in 97% cases, with 7 patients (3%) undergoing an intracorporeal diversion. Mean operating room time of all patients was 5.5 hours, and mean surgical blood loss was 256 mL. On surgical pathology, 120 (53%) patients had pT2 or less disease, 35 (15%) had pT3/T4 disease, and 46 (20%) had N+ disease. The mean number of lymph nodes removed was 18 (range, 3-52). There was a positive surgical margin in 5 cases--all with pT3-4 disease. Mean time to discharge was 5.5 days (median, 5 days), with 70% of patients discharged on postoperative day 5 or sooner. Sixty-eight patients (30%) experienced complications, with 7% having Clavien grade 3 or higher. On multivariate analysis, decreased age and increased American Society of Anesthesiologists score were predictors of higher Clavien complication score, with younger patients more likely to undergo neoadjuvant chemotherapy prior to surgery. CONCLUSION: A multi-institutional experience with robotic radical cystectomy appears to demonstrate acceptable operative and pathologic outcomes, thus helping to validate the previously reported single-institution case series. Ultimately, oncologic follow-up of these patients will remain as the most important measure of therapeutic success.

Outcome of hand assisted laparoscopic bilateral native nephrectomy in transplant recipients.

PURPOSE: We explored the safety and reproducibility of hand assisted laparoscopic bilateral native nephrectomy. We also present our improvements to the surgical technique. MATERIALS AND METHODS: We retrospectively reviewed the charts of 36 patients who underwent hand assisted laparoscopic bilateral nephrectomy at our institution between 2003 and 2010. In all cases the 2 kidneys were removed transperitoneally via a hand assisted laparoscopic technique. RESULTS: Mean operative time was 222 minutes. Pathological kidney size was 20 to 34 cm. Mean hospital stay was 3 days (range 1 to 13). Average estimated blood loss was 175 cc (range 50 to 200). No patient required intraoperative blood transfusion. There were no intraoperative complications and no conversions to open surgery. Postoperatively complications developed in 8 patients (22%), including temporary adrenal insufficiency and pulmonary embolism in 1 each, and myocardial infarction, superficial wound infection and loss of arteriovenous fistula function in 2 each. According to the Clavien-Dindo classification complications were grades 1, 2, 3 and 4a in 2, 3, 1 and 2 patients, respectively. A total of 18 patients with kidney transplants continued to have normal graft function after surgery. CONCLUSIONS: Simultaneous hand assisted bilateral nephrectomies are safe and reproducible. The complication rate is low and postoperative hospital stay is short compared to those in published open surgery series. Graft function was preserved in patients who underwent renal transplantation before native kidney removal.

Association between lymph node density and disease specific survival in patients with penile cancer.

PURPOSE: We assessed the value of lymph node density for predicting disease specific survival after lymphadenectomy for penile cancer. MATERIALS AND METHODS: Data were collected retrospectively in 75 and prospectively in 88 consecutive patients with squamous cell carcinoma of the penis treated at M. D. Anderson Cancer Center between 1979 and 2007. We identified 45 patients with penile cancer and nodal metastasis who underwent lymphadenectomy with curative intent. Lymph node density was analyzed as a categorical variable by grouping patients into 2 or 3 categories based on equal percents. We explored the prognostic value of lymph node density for predicting disease specific survival in this cohort. RESULTS: Median followup was 23.7 months in all patients. By the time of analysis 22 patients had died, including 18 (82%) of penile cancer and 4 (18%) of other causes. Median lymph node density in patients alive or dead of other causes was 3.4% (IQR 2.9-5.9) compared to 43.3% (IQR 15.6-80) in those dead of disease (p <0.001). Median lymph node density in all patients was 6.7%. Estimated 5-year disease specific survival in patients with lymph node density 6.7% or less was significantly better than that in patients with lymph node density greater than 6.7% (91.2%, 95% CI 53.9-98.8 vs 23.3%, 95% CI 7.0-45.1, p <0.001). In models comparing lymph node density to known prognostic features lymph node density remained statistically significant, while the other factors were no longer statistically associated with disease specific survival. CONCLUSIONS: Lymph node density proved to be a significantly better prognosticator of disease specific survival than the current TNM nodal staging system in patients with penile cancer and nodal involvement. Further independent validation is required to determine the clinical usefulness of lymph node density in this patient population.

Salvage therapy for prostate cancer recurrence after radiation therapy.

Radiotherapy has been successful in treating localized prostate cancer; however, a subset of patients will experience disease recurrence. Determination of the recurrence location must be made using pretreatment and posttreatment clinical variables, imaging, and postradiotherapy biopsy. Patients presumed to have local-only recurrence, optimal clinical risk factors, and an extended life expectancy may be considered for salvage local treatment. Current options include salvage surgery, cryoablation, and brachytherapy. Although they are associated with higher morbidity than primary therapy, salvage treatments can be effective and can still provide patients with a good oncologic and functional outcome. As these modalities continue to improve and patient selection is optimized, better results will evolve.

Aberrant activation of androgen receptor in a new neuropeptide-autocrine model of androgen-insensitive prostate cancer.

Treatment of advanced prostate cancer with androgen deprivation therapy inevitably renders the tumors castration-resistant and incurable. Under these conditions, neuroendocrine differentiation of prostate cancer (CaP) cells is often detected and neuropeptides released by these cells may facilitate the development of androgen independence. Exemplified by gastrin-releasing peptide (GRP), these neuropeptides transmit their signals through G protein-coupled receptors, which are often overexpressed in prostate cancer, and aberrantly activate androgen receptor (AR) in the absence of androgen. We developed an autocrine neuropeptide model by overexpressing GRP in LNCaP cells and the resultant cell line, LNCaP-GRP, exhibited androgen-independent growth with enhanced motility in vitro. When orthotopically implanted in castrated nude mice, LNCaP-GRP produced aggressive tumors, which express GRP, prostate-specific antigen, and nuclear-localized AR. Chromatin immunoprecipitation studies of LNCaP-GRP clones suggest that GRP activates and recruits AR to the cognate promoter in the absence of androgen. A Src family kinase (SFK) inhibitor, AZD0530, inhibits androgen-independent growth and migration of the GRP-expressing cell lines, and blocks the nuclear translocation of AR, indicating the involvement of SFK in the aberrant activation of AR and demonstrating the potential use of SFK inhibitor in the treatment of castration-resistant CaP. In vivo studies have shown that AZD0530 profoundly inhibits tumor metastasis in severe combined immunodeficient mice implanted with GRP-autocrine LNCaP cells. This xenograft model shows autocrine, neuropeptide- and Src kinase-mediated progression of androgen-independent CaP postcastration, and is potentially useful for testing novel therapeutic agents.

Comparing lymphadenectomy during radical nephroureterectomy: open versus laparoscopic.

OBJECTIVES: Laparoscopic nephroureterectomy (LNU) is an accepted treatment for tumors of the ureter and renal pelvis, although the ability to perform a regional lymphadenectomy has been criticized. We compared the quality of lymphadenectomy with LNU with that involving open nephroureterectomy (ONU) to determine whether oncologic principles are maintained. METHODS: We searched our institutional database for patients who had undergone ONU from 1990 to 2005. These were compared with a series of patients from January 2003 to April 2007 who underwent LNU. From each patient's medical records, we assessed the number of lymph nodes removed, the number of positive nodes removed, and the density of positive nodes. The differences between groups were analyzed using the Wilcoxon rank sum statistical test. RESULTS: We identified 106 patients who underwent ONU with lymphadenectomy and 28 who underwent LNU with lymphadenectomy. The median number of nodes removed, median number of positive nodes, and median density of positive nodes were, respectively, 3, 0, and 0 for the ONU group; and 6, 0, and 0, for the LNU group. There was a statistically significant difference between groups with respect to the number of nodes removed (P = 0.01) but not with respect to the number of positive nodes removed (P = 0.61) or the lymph node density (P = 0.42). CONCLUSIONS: Offsetting the benefits of laparoscopy could be a flawed oncologic technique. We have demonstrated that lymphadenectomy, which is a potentially important component of nephroureterectomy, can be performed as well during LNU as it is with ONU when a dedicated effort is made.