Search

Background: Worst-case, typical, and best-case scenarios for survival, based on simple multiples of an individual's expected survival time (EST), estimated by their oncologist, are a useful way of formulating and explaining prognosis. We aimed to determine the accuracy and prognostic significance of oncologists' estimates of EST, and the accuracy of the resulting scenarios for survival time, in advanced gastric cancer., Materials and Methods: Sixty-six oncologists estimated the EST at baseline for each of the 152 participants they enrolled in the INTEGRATE trial. We hypothesized that oncologists' estimates of EST would be unbiased (∼50% would be longer or shorter than the observed survival time [OST]); imprecise (<33% within 0.67-1.33 times the OST); independently predictive of overall survival (OS); and accurate at deriving scenarios for survival time with approximately 10% of patients dying within a quarter of their EST (worst-case scenario), 50% living within half to double their EST (typical scenario), and 10% living three or more times their EST (best-case scenario)., Results: Oncologists' estimates of EST were unbiased (45% were shorter than the OST, 55% were longer); imprecise (29% were within 0.67-1.33 times observed); moderately discriminative (Harrell's C-statistic 0.62, p = .001); and an independently significant predictor of OS (hazard ratio, 0.89; 95% confidence interval, 0.83-0.95; p = .001) in a Cox model including performance status, number of metastatic sites, neutrophil-to-lymphocyte ratio ≥3, treatment group, age, and health-related quality of life (EORTC-QLQC30 physical function score). Scenarios for survival time derived from oncologists' estimates were remarkably accurate: 9% of patients died within a quarter of their EST, 57% lived within half to double their EST, and 12% lived three times their EST or longer., Conclusion: Oncologists' estimates of EST were unbiased, imprecise, moderately discriminative, and independently significant predictors of OS. Simple multiples of the EST accurately estimated worst-case, typical, and best-case scenarios for survival time in advanced gastric cancer., Implications for Practice: Results of this study demonstrate that oncologists' estimates of expected survival time for their patients with advanced gastric cancer were unbiased, imprecise, moderately discriminative, and independently significant predictors of overall survival. Simple multiples of the expected survival time accurately estimated worst-case, typical, and best-case scenarios for survival time in advanced gastric cancer., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2019.)

Introduction: Over time, the incidence of nephrolithiasis has risen significantly, and patient populations have become increasingly complex. Our study aimed to determine the impact of changes in patient demographics on percutaneous nephrolithotomy (PCNL) outcomes., Methods: A retrospective analysis of a prospectively collected database was carried out from 1990-2015. Patient demographics, comorbidities, stone and procedure characteristics were analyzed. Multivariate logistic regression was used to evaluate differences in operative duration, complications, stone-free rate, and length of stay., Results: A total of 2486 patients with a mean age of 54±15 years, body mass index (BMI) of 31±8, and stone surface area of 895±602 mm 2 were analyzed; 47% of patients had comorbidities, including hypertension (22%), diabetes mellitus (14%), and cardiac disease (13%). Complication rate was 19%, including a 2% rate of major complications (Clavien grade III-V). There was a statistically significant increase in patient age, BMI, and comorbidities over time, which was correlated with an increased complication rate (odds ratio [OR] 1.15; p=0.010). The overall transfusion rate was 1.0% and remained stable (p=0.131). With time, both OR duration (mean Δ 16 minutes; p<0.001) and hospital length of stay (mean Δ 2.4 days; p<0.001) decreased significantly. Stone-free rate of 1873 patients with available three-month followup was 87% and decreased significantly over time (OR 1.09; p<0.001), but was correlated with an increased use of computed tomography (CT) scans for followup imaging., Conclusions: Despite an increasingly complex patient population, PCNL remains a safe and effective procedure with a high stone-free rate and low risk of complications.

Background: Metastatic colorectal cancer (mCRC) patients with a right-sided primary (RC) have an inferior survival to mCRC arising from a left-sided primary (LC). Previous analyses have suggested multiple factors contribute., Methods: The Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) Registry prospectively captured data on consecutive mCRC patients. RC were defined as tumors proximal to the splenic flexure; LC were those at and distal to the splenic flexure and included rectal cancers. Patient, tumor, treatment, and survival data were analyzed stratified by side., Results: Of 2306 patients enrolled from July 2009-March 2018, 747 (32%) had an RC. Patients with RC were older, more likely to be female and have a Charlson score ≥3. RC were more frequently BRAF mutated, deficient in mismatch repair, associated with peritoneal metastases, and less likely to receive chemotherapy. Progression-free survival on first-line systemic therapy was inferior for RC patients (8.1 vs. 10.8 months, hazard ratio [HR] for progression in RC 1.38, P < 0.001). Median overall survival for all RC patients was inferior (19.6 vs. 27.5 months, HR for death in RC 1.44, P < 0.001), and inferior within the treated (21 vs. 29.5 months, HR 1.52, P < 0.001) and untreated subgroups (5.9 vs. 10.3 months, HR 1.38, P = 0.009). Primary side remained a significant factor for overall survival in multivariate analysis., Conclusion: Our data from a real-world population confirms the poorer prognosis associated with RC. Primary tumor location remains significantly associated with overall survival even when adjusting for multiple factors, indicating the existence of further side-based differences that are as yet undefined., (© 2019 John Wiley & Sons Australia, Ltd.)

Background: Emerging evidence on the optimal use of chemotherapy and biologics in patients with metastatic colorectal cancer should impact management in routine care. Recent studies have demonstrated benefits for initial triplet chemotherapy (5-fluorouracil, oxaliplatin and irinotecan, FOLFOXIRI) and for initial treatment with an epidermal growth factor receptor inhibitor (EGFRi) in patients with a RAS wild-type tumour and a left-sided primary tumour., Aim: To explore evolving pattern of metastatic colorectal cancer care over time in Australia., Methods: We analysed data from the Treatment of Recurrent and Advanced Colorectal Cancer registry., Results: From July 2009 to December 2017, 2552 metastatic colorectal cancer patients were entered into the Treatment of Recurrent and Advanced Colorectal Cancer registry. Of 1585 patients who initially underwent chemotherapy, treatment was with a doublet in 76%. FOLFOXIRI was given to 22 patients (1.4%), mostly young patients and those with potentially resectable disease. Along with first-line chemotherapy, 61% received bevacizumab, while 3.3% received an EGFRi, predominantly over the last 2 years. Within the KRAS wild-type left-sided tumour cohort, EGFRi use increased from 9% in 2015 to 37% in 2017. Across treatment sites, there was a wide variation in the utilisation of FOLFOXIRI and EGFRi therapy; bevacizumab use was more consistent. A clear impact on survival outcomes from these regimens is not evident, potentially due to multiple confounders., Conclusion: Doublet chemotherapy + bevacizumab remains the dominant initial strategy, with limited uptake of triplet chemotherapy and of EGFRi. Potential explanations include uncertainty about the significance of post hoc analyses for EGFRi and concerns regarding adverse events for both strategies., (© 2018 Royal Australasian College of Physicians.)

Background: Pattern of spread in patients with metastatic colorectal cancer (mCRC) is variable and may reflect different biology in subsets of patients. This is a retrospective study to explore the outcome of patients with mCRC based on their site of metastasis at diagnosis and to explore the association between tumor characteristics [KRAS/RAS, BRAF, mismatch repair (MMR) status, site of primary] and the site of metastasis., Methods: Patients from two Australian databases were divided into six groups based on site of metastasis at time of diagnosis of metastatic disease; lung-only, liver-only, lymph node-only or any patients with brain, bone or peritoneal metastases. Primary endpoint was overall survival (OS) of each cohort compared with the rest of the population. A Mantel-Haenszel chi-squared test used to explore the association between site of metastasis and selected tumor characteristics., Results: Five thousand nine hundred and sixty-seven patients were included. In a univariate analysis, median OS was significantly higher when metastases were limited to lung or liver and shorter for those with brain, bone or peritoneal metastases (p < .001) in both datasets. BRAF mutation was strongly associated with peritoneal metastases (relative risk = 1.8, p < .001) with lower incidence of lung (RR = 0.3, p = .004) and liver (RR = 0.7, p = .005) limited metastases. Lung-only metastases were more frequent with KRAS/RAS mutation (RR = 1.4, p = .007). Left colon tumors were associated with bone (RR = 1.6, p < .001) and lung-only metastases (RR = 2.3, p = .001) while peritoneal spread was less frequent compared with right colon tumors (RR = 0.6, p < .001). Rectal cancer was associated with brain, bone and lung metastases (RR = 1.7; p = .002, 1.7; p < .001, 2.0; p < .001). Liver-only metastases were less frequent in deficient MMR tumors (RR = 0.7, p = .01)., Conclusion: Survival duration with mCRC is related to the site of metastases with lung limited disease showing a more favorable survival outcome compared to other single metastatic site disease. The BRAF mutation and primary rectal cancer were associated with poor prognostic metastatic sites.

Ewing sarcoma is a highly aggressive small round cell malignant neoplasm of bone and soft tissue that typically is manifested in children and young adults. It is most commonly a primary bone tumor; however, extraosseous cases have been increasingly reported. We report a case of metastatic extraosseous Ewing sarcoma with the primary lesion occurring within a limb affected by primary lymphedema. Lymphedema, in this case, played a role not only in the genesis of the tumor because of the relative local immunosuppression but also in masking the development of the lower limb mass.

Aim: Current efforts to understand patient management in clinical practice are largely based on clinician surveys with uncertain reliability. The TRACC (Treatment of Recurrent and Advanced Colorectal Cancer) database is a multisite registry collecting comprehensive treatment and outcome data on consecutive metastatic colorectal cancer (mCRC) patients at multiple sites across Australia. This study aims to determine the accuracy of oncologists' impressions of real-word practice by comparing clinicians' estimates to data captured by TRACC., Methods: Nineteen medical oncologists from nine hospitals contributing data to TRACC completed a 34-question survey regarding their impression of the management and outcomes of mCRC at their own practice and other hospitals contributing to the database. Responses were then compared with TRACC data to determine how closely their impressions reflected actual practice., Results: Data on 1300 patients with mCRC were available. Median clinician estimated frequency of KRAS testing within 6 months of diagnosis was 80% (range: 20-100%); the TRACC documented rate was 43%. Clinicians generally overestimated the rates of first-line treatment, particularly in patients over 75 years. Estimate for bevacizumab in first line was 60% (35-80%) versus 49% in TRACC. Estimated rate for liver resection varied substantially (5-35%), and the estimated median (27%) was inconsistent with the TRACC rate (12%). Oncologists generally felt their practice was similar to other hospitals., Conclusions: Oncologists' estimates of current clinical practice varied and were discordant with the TRACC database, often with a tendency to overestimate interventions. Clinician surveys alone do not reliably capture contemporary clinical practices in mCRC., (© 2017 John Wiley & Sons Australia, Ltd.)

Background: Napabucasin is a first-in-class cancer stemness inhibitor that targets STAT3, which is a poor prognostic factor in colorectal cancer. This study aimed to test napabucasin in advanced colorectal cancer., Methods: This study was a double-blind randomised phase 3 trial done at 68 centres in Canada, Australia, New Zealand, and Japan. Patients with advanced colorectal cancer with a good Eastern Cooperative Oncology Group (ECOG) performance status (0-1) for whom all available standard therapies had failed were eligible for the study. Patients were randomly assigned (1:1) to receive placebo or napabucasin through a web-based system with a permuted block method, after stratification by ECOG performance status, KRAS status, previous VEGF inhibitor treatment, and time from diagnosis of metastatic disease. Napabucasin 480 mg or matching placebo was taken orally every 12 h. All patients received best supportive care. The primary endpoint was overall survival assessed in an intention-to-treat analysis. This is the final analysis of this trial, which is registered at ClinicalTrials.gov, number NCT01830621., Findings: Accrual began on April 15, 2013, and was stopped for futility on May 23, 2014, at which point 282 patients had undergone randomisation (138 assigned to the napabucasin group and 144 to the placebo group). Overall survival did not differ significantly between groups: median overall survival was 4·4 months (95% CI 3·7-4·9) in the napabucasin group and 4·8 months (4·0-5·3) in the placebo group (adjusted hazard ratio [HR] 1·13, 95% CI 0·88-1·46, p=0·34). The safety population included 136 patients in the napabucasin group and 144 patients in the placebo group. More patients who received napabucasin had any grade of treatment-related diarrhoea (108 [79%] of 136 patients), nausea (69 [51%]), and anorexia (52 [38%]) than did patients who received placebo (28 [19%] of 144 patients, 35 [24%], and 23 [16%], respectively). The most common severe (grade 3 or worse) treatment-related adverse events were abdominal pain (five [4%] patients receiving napabucasin vs five [3%] receiving placebo), diarrhoea (21 [15%] vs one [1%]), fatigue (14 [10%] vs eight [6%]), and dehydration (six [4%] vs one [1%]). 251 (89%) patients had data on pSTAT3 expression, of whom 55 (22%) had pSTAT3-positive tumours (29 in the napabucasin group, 26 in the placebo group). In a prespecified biomarker analysis of pSTAT3-positive patients, overall survival was longer in the napabucasin group than in the placebo group (median 5·1 months [95% CI 4·0-7·5] vs 3·0 months [1·7-4·1]; HR 0·41, 0·23-0·73, p=0·0025)., Interpretation: Although there was no difference in overall survival between groups in the overall unselected population, STAT3 might be an important target for the treatment of colorectal cancer with elevated pSTAT3 expression. Nevertheless, these results require validation., Funding: Canadian Cancer Society Research Institute and Boston Biomedical., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Debate continues regarding the benefits versus risks of initial resection of the primary tumor in metastatic colorectal cancer (mCRC) patients with an asymptomatic primary tumor. Although the benefit of the anti-vascular endothelial growth factor agent bevacizumab alongside first-line chemotherapy in mCRC is established, the impact of bevacizumab on the intact primary tumor (IPT) is less well understood., Methods: Data from an Australian mCRC registry were used to assess the impact of bevacizumab-based regimens in the presence of an IPT, to see if this differs from effects in resected primary tumor (RPT) patients and to understand the safety profile of bevacizumab in patients with IPT. Progression-free survival (PFS), overall survival (OS) and safety endpoints were analyzed., Results: Of 1204 mCRC patients, 826 (69%) were eligible for inclusion. Bevacizumab use was similar in both arms (IPT (64%) versus RPT (70%)); compared with chemotherapy alone, bevacizumab use was associated with significantly longer PFS (IPT: 8.5 months vs 4.7 months, P = 0.017; RPT: 10.8 months vs 5.8 months, P < 0.001) and OS (IPT: 20 months vs 14.8 months, P = 0.005; RPT: 24.4 months vs 17.3 months, P = 0.004)). 1 Bevacizumab use in an IPT was associated with more GI perforations (4.5% vs 1.8%, P = 0.210) but less frequent bleeding (1.5% vs 5.3%, P = 0.050) and thrombosis (1.5% vs 2.7%, P = 0.470), versus chemotherapy alone. Median survival was equivalent between patients that did or did not experience bevacizumab-related adverse events - 20.0 months versus 19.9 months, hazard ratio = 0.98, P = 0.623. 1 CONCLUSIONS: The addition of bevacizumab significantly improved survival outcomes in mCRC with an IPT. The occurrence of bevacizumab-related adverse events did not significantly impact survival outcomes., (© 2016 John Wiley & Sons Australia, Ltd.)

Background: The survival impact of primary tumor resection in patients with metastatic colorectal cancer (mCRC) treated with palliative intent remains uncertain. In the absence of randomized data, the objectives of the present study were to examine the effect of primary tumor resection (PTR) and major prognostic variables on overall survival (OS) of patients with de novo mCRC., Patients and Methods: Consecutive patients from the Australian 'Treatment of Recurrent and Advanced Colorectal Cancer' registry were examined from June 2009 to March 2015. Univariate and multivariate Cox proportional hazards regression analyses were used to identify associations between multiple patient or clinical variables and OS. Patients with metachronous mCRC were excluded from the analyses., Results: A total of 690 patients de novo and 373 metachronous mCRC patients treated with palliative intent were identified. The median follow-up period was 30 months. The median age of de novo patients was 66 years; 57% were male; 77% had an Eastern Cooperative Oncology Group performance status of 0 to 1; and 76% had a colon primary. A total of 216 de novo mCRC patients treated with palliative intent underwent PTR at diagnosis and were more likely to have a colon primary (odds ratio [OR], 15.4), a lower carcinoembryonic antigen level (OR, 2.08), and peritoneal involvement (OR, 2.58; P < .001). On multivariate analysis, PTR at diagnosis in de novo patients was not associated with significantly improved OS (hazard ratio [HR], 0.82; 99% confidence interval [CI], 0.62-1.09; P = .068). PTR at diagnosis did not correlate with outcome in de novo patients with a colon primary (HR, 0.74; 99% CI, 0.54-1.01; P = .014) or a rectal primary (HR, 0.81; 99% CI, 0.27-2.44; P = .621)., Conclusion: For de novo mCRC patients treated with palliative intent, PTR at diagnosis does not significantly improve OS when adjusting for known major prognostic factors. The outcomes of randomized trials examining the survival impact of PTR are awaited., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: With an ever-increasing focus on personalized medicine, all factors known to affect treatment response need to be considered when defining optimal therapy for individual patients. While the prognostic impact of primary tumor site on colorectal cancer (CRC) outcomes is established, emerging data suggest potential differences in response to biologic therapies. We studied the impact of tumor site on bevacizumab efficacy in patients with metastatic CRC., Patients and Methods: We analyzed data of patients in an Australian prospective multicenter metastatic CRC (mCRC) registry who received first-line chemotherapy. Tumor site was defined as right colon, cecum to transverse; left colon, splenic flexure to rectosigmoid; and rectum. Kaplan-Meier and Cox models were used for survival analyses., Results: Of 926 patients, 297 had right colon, 354 left colon, and 275 rectum primary disease. Median age was 68.6, 65.9, and 63.3 years, respectively (P = .001). Right colon disease was significantly associated with intraperitoneal spread (P < .0001), while left colon and rectum disease preferentially metastasized to the liver and lungs, respectively (P < .0001 in both settings). A total of 636 patients (68.7%) received bevacizumab. Progression-free survival was superior for bevacizumab-treated patients in all groups but appeared greatest in right colon disease (hazard ratio, 0.46; 95% confidence interval, 0.36-0.60; P ≤ .001). Overall survival was longest in patients with disease of the rectum, followed by left colon and right colon (median, 26.2, 23.6, and 18.2 months, respectively; P = .0004)., Conclusion: Tumor site appears to be prognostic in mCRC, with rectum and right colon disease associated with the best and worst outcomes, respectively. Patients who received bevacizumab in addition to chemotherapy had superior outcomes, with the effect appearing greatest in patients with right colon disease., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Radiation lung injury usually develops 1-6 months after cessation of radiation therapy to the lung. Acute change in the previously irradiated lung after administration of antineoplastic agent is known as radiation recall pneumonitis. Erlotinib is a reversible epidemal growth factor receptor tyrosine kinase inhibitor, which is effective for patients with advanced lung cancer with epidermal growth factor receptor mutations. Here we report a rare case of radiation recall pneumonitis following treatment with erlotinib 4 months after palliative radiotherapy to the lung. A 76-year-old man with non-small cell lung cancer was treated with polychemotherapy, palliative thoracic irradiation (30 Gy in 12 fractions) and erlotinib thereafter. Two months after administration of erlotinib he developed of severe dyspnea, cough, anorexia and lack of energy. CT chest revealed extensive radiation pneumonitis. Erlotinib was ceased and high-dose steroids were started. The symptoms ultimately resolved and erlotinib was resumed cautiously after 11 weeks. On dosimetric analysis, lung V20 and the mean lung dose were 20.33% and 10.7 Gy, respectively, and hence, the risk of radiation pneumonitis is very low. These data indicate that systemic administration of erlotinib after low-dose palliative radiation therapy can be associated with unexpected toxicity when visceral organs are within the radiation field., (© 2016 John Wiley & Sons Australia, Ltd.)

Introduction: The primary objective of this study was to compare surgical management options for various urolithiasis scenarios that urologists would choose for themselves vs. the options they would recommend for their patients. The secondary objective was to identify the common recommended treatments for upper urinary tract stones of various sizes and locations., Methods: Two surveys were sent by the Clinical Research Office of the Endourological Society (CROES) to members of the Endourological Society. Standard demographic information was collected. The first survey asked the urologists to recommend treatment for urolithiasis in 10 different scenarios assuming that they were the patient with stone disease. The second survey, sent eight months later, asked urologists to recommend treatment for the same 10 scenarios for a theoretical patient. Only urologists who responded to the first and the second survey were included. Recommended treatment options were compared between the surveys. Agreement between the two scenarios was measured with Cohen's kappa. Surveys were conducted on the Internet using SurveyMonkey™. All statistical analyses were performed using R statistical program version 2.12.2., Results: The two surveys had response rates of 78% (160/205) and 84% (172/205), respectively with urologists from 38 countries. Median experience of respondents was seven years (range: 2-30). The majority of respondents, 117 (75%), were affiliated with academic hospitals. Recommended treatments for stone disease in different scenarios were not entirely consistent when the urologists considered themselves as the patients compared to the choice they might recommend for their patients. Cohen's kappa ranged from 0.292-0.534 for the different scenarios. Overall, shock wave lithotripsy (SWL) and ureteroscopy (URS) were the most commonly chosen treatment options, with medical expulsive therapy (MET) and laparoscopy being the least recommended by urologists for themselves, as well as for their patients., Conclusions: Although urologists were not entirely consistent in their recommendations for stone treatment, they generally followed the "golden rule" and treated their patients as they would want to be treated. The most commonly recommended treatments for upper urinary tract stones were SWL and URS.

Paragangliomas (or extra-adrenal paragangliomas) are rare neuroendocrine tumors that arise from the extra-adrenal autonomic paraganglia, small organs consisting mainly of neuroendocrine cells that are derived from the embryonic neural crest and have the ability to secrete catecholamines. This is in contrast to pheochromocytomas, where tumors occur in the adrenal gland. Malignant paraganglioma is a very rare presentation. We present a case report of a 56-year-old woman with acute foot drop with no previous significant background history. To the best of our knowledge, the current case represents the first case of malignant paraganglioma with acute foot drop presentation., Competing Interests: The authors have no conflicts of interests to declare.

Purpose: We sought to describe and evaluate the complications related to percutaneous nephrolithotomy and identify risk factors of morbidity according to the modified Clavien scoring system. We also sought to specify which perioperative factors are associated with minor and major complications., Materials and Methods: We retrospectively analyzed data on patients who underwent percutaneous nephrolithotomy from 1990 to 2013. Descriptive statistics were used to analyze patient characteristics, medical comorbidities and perioperative features. Complications were categorized according to the Clavien score for percutaneous nephrolithotomy. The Mann-Whitney and Fisher exact tests were used as appropriate. Logistic regression analysis was performed to look for prognostic factors associated with major complications., Results: A total of 2,318 surgeries were evaluated. Mean age of the population was 53.7 years. The stone-free rate at hospital discharge was 81.6%. The overall complication rate was 18.3%. Two deaths occurred. Patients with any postoperative complications were older, had more comorbidities, were more likely to have staghorn calculi and had longer operative time and hospital stay on univariate analysis (p<0.05). Age 55 years or older and upper pole access were independent predictors of major complications on multivariate analysis. Other factors such as a history of urinary tract infections, body mass index, stone composition, previous percutaneous nephrolithotomy and multiple tracts were not associated with a major complication., Conclusions: At our center percutaneous nephrolithotomy is an excellent option for complex kidney stone management with a low overall complication rate. Older patient age and upper pole access are significantly associated with an increased risk of a major complication., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objectives: The elderly accounts for a large proportion of patients with metastatic colorectal cancer (mCRC). This study reviews patterns of care and outcomes for elderly patients with mCRC in the community setting., Materials and Methods: Elderly patients (≥ 65 years) with mCRC on the TRACC (Treatment of Recurrent and Advanced Colorectal Cancer) registry were identified. Treatment, bevacizumab-related adverse events, and overall survival (OS) were analysed by age cohorts, comparing those aged 65-74 vs. 75-84 vs. ≥ 85 years and correlated with potential prognostic factors. Factors affecting chemotherapy and bevacizumab administration were analysed using logistic regression analysis., Results: Of 1439 patients, 363, 352, and 106 were aged 65-74, 75-84, and ≥ 85 years, respectively. 584 (71%) patients received first-line chemotherapy, with chemotherapy use declining with advancing age (84%, 69%, and 34% in 65-74-, 75-84- and ≥ 85-year-olds, respectively). Seven (10%) patients aged ≥ 85 years were not treated with chemotherapy on the basis of age alone. Only 10 of 36 very elderly patients who received chemotherapy also received bevacizumab. Factors affecting bevacizumab administration included age, treatment location, and comorbidities. There was no impact of age on bevacizumab-related adverse events. Resection of metastatic disease occurred in 173 (21%) patients overall, with rates declining with age (26% vs. 21% vs. 6%)., Conclusion: Chemotherapy usage and resection of metastatic disease decline with advancing age. A minority of patients are not treated with systemic therapy due to advanced age alone. Our cohort suggests underutilisation of bevacizumab in older patients, but where given, toxicity rates did not increase with age., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aims: Defining multidisciplinary quality of care indicators (QCIs) for metastatic colorectal cancer (mCRC) could improve understanding of variations in routine practice care. This may identify areas of below-average performance, which could then be addressed by clinicians to improve the quality of care delivered. This study aimed to define a panel of QCIs in mCRC and, based on these QCIs, to evaluate quality of care across multiple Australian sites., Methods: A panel of clinicians with expertise in colorectal cancer defined evidence-based or best practice-based QCIs relevant to the routine multidisciplinary management of mCRC patients through structured consensus discussion. Related data were extracted from the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry, a prospectively maintained database recording comprehensive details on consecutive mCRC patients across multiple Australian hospitals. Variations in QCIs across sites were explored., Results: Of 13 QCIs defined, data related to 10 were reliably extracted from TRACC. Analysis of data on 1276 patients across 10 sites demonstrated low rates of screening for hereditary nonpolyposis colorectal cancer in young patients and significant variation in surveillance-detected recurrences, lung resection rates and palliative chemotherapy use. Exploratory analyses suggested correlation between liver resection rates and survival., Conclusions: We have defined a novel set of mCRC QCIs and have demonstrated wide variation in the quality of care of mCRC across multiple Australian sites. With further validation to confirm a direct correlation between QCI and patient outcomes, these QCIs could be applied to improve the quality of care received by all mCRC patients., (© 2015 Wiley Publishing Asia Pty Ltd.)

Aim: To investigate the safety and efficacy of adding bevacizumab to first-line chemotherapy in metastatic colorectal cancer patients with peritoneal disease., Methods: We compared rates of gastrointestinal perforation in patients with metastatic colorectal cancer and peritoneal disease receiving first-line chemotherapy with and without bevacizumab in three distinct cohorts: (1) the AGITG MAX trial (Phase III randomised clinical trial comparing capecitabine vs capecitabine and bevacizumab vs capecitabine, bevacizumab and mitomycinC); (2) the prospective Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry (any first-line regimen ± bevacizumab); and (3) two cancer centres in New South Wales, Australia [Macarthur Cancer Therapy Centre and Liverpool Cancer Therapy Centre (NSWCC) from January 2005 to Decenber 2012, (any first-line regimen ± bevacizumab). For the AGITG MAX trial capecitabine was compared to the other two arms (capecitabine/bevacizumab and capecitabine/bevacizumab/mitomycinC). In the AGITG MAX trial and the TRACC registry rates of gastrointestinal perforation were also collected in patients who did not have peritoneal metastases. Secondary endpoints included progression-free survival, chemotherapy duration, and overall survival. Time-to-event outcomes were estimated using the Kaplan-Meier method and compared using the log-rank test., Results: Eighty-four MAX, 179 TRACC and 69 NSWCC patients had peritoneal disease. There were no gastrointestinal perforations recorded in either the MAX subgroup or the NSWCC cohorts. Of the patients without peritoneal disease in the MAX trial, 4/300 (1.3%) in the bevacizumab arms had gastrointestinal perforations compared to 1/123 (0.8%) in the capecitabine alone arm. In the TRACC registry 3/126 (2.4%) patients who had received bevacizumab had a gastrointestinal perforation compared to 1/53 (1.9%) in the chemotherapy alone arm. In a further analysis of patients without peritoneal metastases in the TRACC registry, the rate of gastrointestinal perforations was 9/369 (2.4%) in the chemotherapy/bevacizumab group and 5/177 (2.8%) in the chemotherapy alone group. The addition of bevacizumab to chemotherapy was associated with improved progression-free survival in all three cohorts: MAX 6.9 m vs 4.9 m, HR = 0.64 (95%CI: 0.42-1.02); P = 0.063; TRACC 9.1 m vs 5.5 m, HR = 0.61 (95%CI: 0.37-0.86); P = 0.009; NSWCC 8.7 m vs 6.8 m, HR = 0.75 (95%CI: 0.43-1.32); P = 0.32. Chemotherapy duration was similar across the groups., Conclusion: Patients with peritoneal disease do not appear to have an increased risk of gastrointestinal perforations when receiving first-line therapy with bevacizumab compared to systemic therapy alone.

Aim: The potential beneficial interaction between erlotinib and chemotherapy may require sequencing or pharmacodynamic separation. The aim of this study was to evaluate the efficacy and tolerance of sequential erlotinib and gemcitabine versus gemcitabine monotherapy as first-line therapy in elderly or ECOG PS-2 patients with advanced non-small cell lung carcinoma., Methods: The primary objective of this multicenter randomized Phase II study was progression-free survival (PFS). Secondary objectives were overall response rate (ORR), disease control rate, response duration, overall survival and safety. Patients were randomized to either gemcitabine (1250 mg/m2 Day 1, 8 q28 days) followed by erlotinib (150 mg/day on day 15 through day 28), (EG-arm), or gemcitabine monotherapy (1000 mg/m2 Days 1, 8, 15 q28 days), (G-arm) for up to six cycles., Results: Fifty-four patients were recruited, 28 G-arm and 26 EG-arm. Overall, efficacy results were not significantly different between study arms. Median PFS and ORR for the G- versus EG-arms were 8.0 versus 10.3 weeks (hazard ratio 1.3; 95% confidence interval [0.63;2.68]; P=0.48) and 7.1 versus 3.8 percent respectively (difference -3.30; 95% confidence interval [-17.5;10.9]). The majority of adverse events (AEs) in both arms were Grade 1-2. The commonest AEs recorded in the EG- and G-arms were rash-like events (65 percent) and nausea (42 percent) respectively. Four patients (17 percent) in EG-arm and five (16 percent) in G-arm experienced at least one treatment-related serious AE., Conclusions: In this study, patients with non-small cell lung carcinoma at ECOG PS-2 or aged ≥70 years derived no efficacy advantage from sequential erlotinib in combination with gemcitabine relative to gemcitabine alone. No unexpected safety findings were noted., (© 2014 Wiley Publishing Asia Pty Ltd.)

Background: Efficacy and safety of percutaneous nephrolithotomy (PCNL) have been demonstrated in obese individuals. Yet, there is a paucity of data on the outcomes of PCNL in morbidly obese patients (body mass index [BMI] >40)., Methods: Perioperative and stone-related outcomes following PCNL in morbidly obese patients was assessed using a prospective database administered by the Clinical Research Office of the Endourological Society (CROES). A multidimensional match of 97 morbidly obese patients with those of normal weight was created using propensity score matching. Student's t-test and Chi-square tests were used to assess for differences between the groups., Results: In total, 97 patients with a BMI >40 kg/m(2) were matched by stone characteristics with 97 patients of normal weight. The morbidly obese population demonstrated higher rates of diabetes mellitus (43% vs. 6%, p < 0.001) and cardiovascular disease (56% vs. 18%, (p < 0.001). Access was achieved more frequently by radiologists in the morbidly obese group (19% vs. 6%, p = 0.016). Mean operative duration was longer in the morbidly obese group (112 ± 56 min vs. 86 ± 43.5 min, p < 0.001). Stone-free rates were lower in the morbidly obese group (66% vs. 77%, p = 0.071). There was no significant difference in length of hospital stay or transfusion rate. Morbidly obese patients were significantly more likely to experience a postoperative complication (22% vs. 6%, p = 0.004)., Interpretation: PCNL in morbidly obese patients is associated with longer operative duration, higher rates of re-intervention and an increased risk of perioperative complications. With this knowledge, urologists should seek to develop strategies to optimize the perioperative management of such patients.

Background and Purpose: Shockwave lithotripsy (SWL) and ureteroscopy (URS) are minimally invasive treatment alternatives for kidney stones. Although less invasive, SWL subjects the renal parenchyma to a high level of energy and the potential to cause renal injury. The ability to detect renal injury post-SWL in a reliable and noninvasive way would be clinically beneficial. Kidney injury molecule 1 (KIM-1) and N-acetyl-β-D-glucosaminidase (NAG) are two proteins secreted by the kidney into the urine and have been found to be sensitive markers of acute kidney injury in transplant patients. The aim of this work was to measure urinary levels of KIM-1 and NAG in patients with kidney stone who were treated by SWL or URS and in nonstone volunteers., Patients and Methods: Patients with kidney stones who were treated by SWL (n = 50) or URS (n = 10) were recruited. Voided urine samples were collected before and 2 to 3 hours after URS and SWL. In addition, further urinary specimens were collected 2 days and 2 weeks post-SWL treatment. Voided urine samples from healthy volunteers were also collected., Results: Mean KIM-1 values were increased in patients with kidney stones when compared with volunteers. KIM-1 and NAG levels significantly increased post-SWL and returned to baseline within 2 weeks post-SWL. Poor kidney function was significantly associated with increased biomarker activity both in baseline and post-SWL measurements. There was no significant change in urinary KIM-1 and NAG concentrations before and after URS., Conclusions: Kim-1 and NAG levels significantly increased post-SWL treatment suggesting a potential role for these urinary markers in identifying patients at higher risk of tissue injury.

Purpose: This study evaluates the safety and efficacy of intravesical ropivacaine as part of a mulitimodal approach to the provision of analgesia after robot-assisted radical prostatectomy (RARP)., Patients and Methods: In this double-blind, placebo-controlled trial, 40 patients who were scheduled to undergo RARP for treatment of localized prostate cancer by a single surgeon (SP) were randomized 1:1 to receive either alkalinized intravesical ropivacaine or placebo (0.9% sodium chloride) at the completion of the vesicourethral anastomosis. A standardized general anesthetic was administered in each case. The primary outcome was a reduction in postoperative pain as assessed by a visual analogue scale (VAS). The need for alternate analgesic agents was recorded. Adverse events related to the administration of intravesical ropivacaine were documented prospectively., Results: No serious adverse events related to the administration of intravesical ropivacaine were identified. In the ropivacaine group, there was a significant reduction in the cumulative needed dose of ketoralac relative to placebo at 6 hours postoperatively. There was no statistically significant difference between the groups with regard to pain scores or narcotic use at any time point., Conclusions: Intravesical administration of ropivacaine may be used safely in the context of RARP and is associated with a significant, albeit modest reduction in the need for supplementary analgesic agents, but did not result in a decrease in postoperative pain scores.

Introduction: The aim of this study was to compare the metabolic profiles of diabetic and non-diabetic patients with uric acid stones to understand whether preventive strategies should be tailored to reflect different causative factors., Methods: The results of the metabolic evaluation of patients with uric acid stones identified prospectively from the Metabolic Stone Clinic at St. Joseph's Hospital, London, Canada were reviewed. Information included patients' clinical histories, 24 hour urine collections, blood chemistry and stone analysis., Results: Complete data were obtained from 68 patients with uric acid stones. Twenty-two patients had diabetes. There were no statistically significant differences in mean age, body mass index, or history of gout. Among diabetics, pure uric acid stones were identified in 14 patients (63%) and mixed uric acid in 8 (36%). Pure uric acid stones were more common in the diabetic cohort (63% vs. 46%, p = 0.16). Urine pH, serum and urine uric acid levels and 24-hour urine volumes were similar in both groups. The diabetic group had an increased average oxalate excretion (424 μmol/d vs. 324 μmol/d, p = 0.003)., Conclusion: The exact etiological basis for the higher oxalate excretion in diabetic uric acid stone formers is unclear. Whether this is a metabolic feature of diabetes, due to dietary indiscretion or the iatrogenic consequence of dietary advice requires further investigation.

Purpose: To determine the incidence of and evaluate the potential risk of a symptomatic perinephric hematoma (PNH) after shockwave lithotripsy (SWL) with the Storz Modulith SLX-F2 device., Patients and Methods: Patient and treatment-related data from 6172 SWL treatments for proximal ureteral and kidney stones were collected prospectively from April 2006 to August 2010. Patients in whom signs or symptoms of a PNH developed after SWL were investigated with imaging studies. Each patient identified with a PNH was matched with four controls using sex, age (±5 years), shockwave rate, energy and number, and no SWL within the previous 6 months as the matching variables. The baseline characteristics of the 21 cases and 84 controls were compared using the Student t test. The independent variables of hypertension (intraoperative value >140/90 mm Hg), anticoagulant/antiplatelet drugs, obesity (body mass index ≥30), and diabetes were compared using a conditional logistic regression analysis. The dependent variable was hematoma., Results: A PNH developed after SWL with the Storz Modulith SLX-F2 device in 21 (0.34%) adult patients (19 men, 2 women) with a mean age of 55.2 years. Significant risk factors identified included intraoperative hypertension (hazard ratio [HR] 3.302, 1.066-10.230, P=0.0384) and anticoagulant/antiplatelet medications (HR 4.198, 1.103-15.984, P=0.0355). Diabetes (P=0.1043) and obesity (P=0.1021) were not associated with PNH., Conclusions: A clinical PNH occurred in less than 1% of our population. This is consistent with reports from earlier generation devices. Risk factors identified for hematoma formation were intraoperative hypertension and the use of anticoagulant/antiplatelet drugs.

Unlabelled: What's known on the subject? and What does the study add? Infection, encrustation and ureteral-stent-related symptoms (USRS) including pain, urgency and frequency are all major problems associated with stent use. No current ureteral stent or exogenously applied therapy adequately deals with these problems and antibiotic use is ineffective once a bacterial biofilm forms on the device. Triclosan is a broad spectrum antibacterial agent widely used in numerous healthcare products and has been previously shown to reduce inflammation on the skin and in the oral cavity. This study tested a triclosan-impregnated ureteral stent for its ability to reduce infection, encrustation and USRS. This study shows that while a triclosan-impregnated ureteral stent cannot reduce infection rates alone compared with antibiotic use, the stent can reduce several USRS including pain during indwelling. This study suggests that the triclosan eluting stent may have a role in treating patients, perhaps in combination with standard antibiotic therapy., Objective: To evaluate the capacity of triclosan-loaded ureteral stents to reduce stent-associated bacterial attachment, biofilm formation and encrustation, thereby potentially reducing infection development and other device-related sequelae., Patients and Methods: Twenty subjects requiring short-term stenting (7-15 days) were randomized to receive either a Percuflex Plus(®) non-eluting stent (control) or a Triumph(®) triclosan eluting stent. Control-stented subjects received 3 days of levofloxacin prophylaxis (500 mg once daily) while Triumph(®)-stented subjects did not. All subjects were assessed for positive urine and stent cultures, stent biofilm development and encrustation. Following device removal, each subject completed an analogue-scale symptom assessment questionnaire., Results: Ureteral stenting was performed after nine ureteroscopic and one extracorporeal shock wave lithotripsy procedure in the control group and eight ureteroscopic and two shock wave lithotripsy procedures in the triclosan group. No significant differences were observed for culture, biofilm and encrustation between the two groups. Subjects in the triclosan group reported significant reductions in lower flank pain scores during activity (58.1% reduction, P = 0.017) and urination (42.6%, P = 0.041), abdominal pain during activity (42.1%, P = 0.042) and urethral pain during urination (31.7%, P = 0.049)., Conclusions: In this study, the use of the Triumph(®) triclosan eluting stent had no marked impact on biofilm formation, encrustation or infection development in short-term stented patients. The Triumph(®) device led to significant reductions in several common ureteral-stent-related symptoms, supporting its use in this patient population., (© 2012 BJU INTERNATIONAL.)

Purpose: In addition to more commonly forming stones, obese patients present a number of challenges when undergoing percutaneous nephrolithotomy. We evaluated percutaneous nephrolithotomy outcomes in 3,709 patients stratified by body mass index., Materials and Methods: A prospective database administered by CROES (Clinical Research Office of the Endourological Society) captured data on 5,803 patients treated with percutaneous nephrolithotomy between November 2007 and December 2009. Patients with known solitary kidney, previous percutaneous nephrolithotomy and congenital abnormalities were excluded from analysis. For statistical analysis patients were categorized as normal weight--body mass index 18.5 to 25 kg/m(2), overweight--25 to 30, obese--30 to 40 and super obese--greater than 40., Results: During the study period 5,803 patients underwent percutaneous nephrolithotomy, of whom 3,709 met the inclusion criteria. As expected, obesity was associated with significantly higher rates of comorbid conditions and anticoagulant use (p < 0.001). Operative time was significantly longer in obese patients and use of a balloon device for tract dilation was more common (each p < 0.001). The stone-free rate decreased with obesity (p = 0.009), corresponding to a significantly higher re-treatment rate in this group (p < 0.001). No difference was seen in length of stay or the transfusion rate. No significant difference was seen in the overall complication rate among the 4 groups (p = 0.707)., Conclusions: Percutaneous nephrolithotomy may be done safely in obese patients, although with a longer operative time, an inferior stone-free rate and a higher re-intervention rate., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: Monopolar transurethral resection of the prostate (TURP) is the gold standard surgical therapy for men with lower urinary tract symptoms due to benign prostatic hyperplasia. Although generally considered safer, TURP experience is limited in Canada., Methods: Forty-three patients from 5 Canadian centres were randomized to TURP with either bipolar or monopolar platforms. Patients underwent baseline determinations of American Urological Association (AUA) symptom score, peak urinary flow rate, post-void residual bladder volume and transrectal ultrasound prostate volume. Primary outcome measures were improvement in AUA symptom score, quality of life assessment and bother assessment. Secondary outcomes included procedural times, duration of catheterization, length of hospitalization, complications and the degree of thermal artifact in tissue specimens. Patients were followed for 6 months., Results: Twenty-two patients were treated with bipolar and 21 with monopolar TURP. Preoperative demographics were not statistically different between groups. Postoperative data collection times were equivalent in AUA symptom, quality of life, bother and sexual function assessments. No differences were observed in the procedure time (60.7 min, bipolar vs. 47.4, monopolar) or the duration of urethral catheterization (1.5 days, bipolar vs. 1.1, monopolar). More patients in the bipolar group were discharged on the same day of surgery. There were no differences in the degree of tissue thermal artifact or complication rate., Conclusion: This trial suggests equivalent short-term outcomes for men undergoing monopolar or bipolar TURP.

Background and Purpose: Caliceal diverticula are rare renal anomalies present in approximately 0.6% of the population. They are associated with calculi in 50% of cases. Therapeutic options include several minimally invasive techniques. We report a retrospective review of outcomes and complications from our series of patients who were treated with a percutaneous approach., Patients and Methods: A database of outcomes related to percutaneous nephrolithotomy (PCNL) has been maintained at our institution since 1992. Data on all patients with caliceal diverticular stones who underwent PCNL during a 17-year period from 1992 to 2009 were reviewed retrospectively. Our preferred approach to PCNL in these patients is to puncture directly into the diverticulum and to try to advance a guidewire through the infundibular neck. In cases where the caliceal neck could not be intubated, we performed a transdiverticular approach with creation of a neoinfundibulum as a salvage procedure. We evaluated the two techniques with regard to stone-free rates and early postoperative complications., Results: Seventy-six procedures were performed. The mean age was 43 years (range 17-72 y). The mean stone area was 583 mm(2). The surgical approach was direct puncture in 47, transdiverticular in 20, retrograde in 8, and unknown in 1 patient. Eight patients underwent lining fulguration. The average duration of surgery was 75 minutes (23-169 min) with an average hospital stay of 4.7 days. There were a total of 23 complications, of which 11 necessitated additional intervention. The overall stone-free rates were 77% and 89% for direct puncture and transdiverticular approaches, respectively., Conclusions: The percutaneous management of caliceal diverticular calculi is highly effective and can be accomplished with low morbidity.

Purpose: To compare the operative techniques and perioperative outcomes of patients with urinary intestinal diversions undergoing percutaneous nephrolithotripsy (PCNL), to a control cohort of patients without diversions., Patients and Methods: The medical records of all patients who were treated with PCNL from 1990 to 2009 were retrospectively reviewed. Each urinary diversion patient's first PCNL was age-matched with four controls who were undergoing PCNL. The perioperative outcomes were compared between the diversion and control cohorts., Results: Twenty-five patients with a urinary diversion who had undergone 33 PCNLs were identified. The mean age was 49.3 (8-85) years for the diversion group and 48.9 (4-84) for the control group. Urinary tract infection (64% vs 15% patients, P<0.0001), neurologic disease (64% vs 2%, P<0.0001), previous procedure for the same calculus (24% vs 4%, P=0.0004), urinary tract abnormalities (56% vs 14%, P<0.0001), solitary kidney (20% vs 3%, P=0.0081), and struvite stones (80% vs 12.5%, P=0.0006) were more commonly observed in the diversion group. Percutaneous access gained by a radiologist (40% vs 0%, P<0.0001), second-look nephroscopy (36% vs 16%, P=0.0466), and an increase in the frequency of fever or sepsis (8% vs 0%, P=0.0387) were identified more frequently in the diversion group., Conclusions: Patients with upper tract calculi and urinary diversions are challenging to the endourologist because of anatomic factors that can make percutaneous access more difficult; ultrasonography-guided access can be helpful in this setting. Patients with urinary diversions can be treated as safely and effectively by PCNL as nondiverted patients.

Introduction: The cost of surveillance strategies in patients after radical nephrectomy for localized primary renal cell carcinoma (RCC) has not been evaluated. We compared the costs of 2 different surveillance strategies, the new Canadian Urological Association (CUA) guidelines and the old strategy implemented in our institution., Methods: Seventy-five patients who underwent radical nephrectomy for primary non-metastatic renal cancer were retrospectively reviewed. The direct cost of surveillance was determined and compared with the theoretical cost which would have been accrued using the CUA guidelines., Results: Our mean follow-up was 31.1 (SD ± 20.4) months. The overall and disease-free survival endpoints were 87.7% and 85.2%, respectively. Total medical costs were higher for our old institutional surveillance strategy than the CUA guidelines ($181 861 vs. $135 054). For the complete follow-up of 75 patients, a cost-savings of $46 806 could have been achieved following the CUA guidelines (p = 0.002). Of recurrences, 7 of 8 were detected by routine screening, only 1 recurrence was identified by symptoms. The cost per recurrence detected in our old protocol was $9 812.92. The increased cost of our institution was due to more visits with basic testing, symptomatic investigation, and follow-up of imaging tests. The median percent cost attributable to these extra tests was 15% (range 0 to 59)., Conclusion: Based on our results, we endorse the new CUA surveillance strategy in RCC follow-up as appropriate and cost effective in comparison with previous follow-up strategies used at our institution.

Background and Purpose: Robot-assisted pyeloplasty (RAP) has been established recently as an option in the management of ureteropelvic junction obstruction (UPJO). We present the first Canadian experience with RAP with respect to operative results and outcomes. We compare the surgical outcomes between experienced and trainee surgeons, with respect to operating room times and success rates., Patients and Methods: Eighty-eight patients underwent transperitoneal RAP for UPJO using the da Vinci robotic platform. Two surgeons performed Anderson-Hynes dismembered pyeloplasty in 85 cases and YV-plasty in 5 cases. Five patients had RAP for secondary UPJO after failure of other treatments. Diuretic renography was performed at 6 weeks, and 6, 12, 18, 24, and 36 months postpyeloplasty. The mean follow-up was 14.1 ± 8.5 months., Results: The mean operative time was 167.7 ± 43.2 minutes, and the mean anastomotic time was 41.9 ± 14.1 minutes. The mean operative duration significantly decreased with time (P < 0.05). Ten patients needed simultaneous nephroscopic stone management via the pyelotomy incision. The mean blood loss was 56.6 ± 55.4 mL, and the mean hospital stay was 2.5 ± 0.5 days. There were five major postoperative (stent migration, urinoma) and three minor complications that were associated with the RAP procedures. Postoperative renal scintigraphy demonstrated only four cases with persistent obstruction. Eighty-three (94.3%) patients experienced improvement of symptoms whereas 5 continued to be symptomatic. Two patients needed secondary procedures to relieve persisting obstruction. There were no statistical differences in outcomes between the experienced surgeons and trainees (P = 0.28)., Conclusions: In the first large case series of RAP from Canada, we demonstrate that RAP can be performed with relatively short operative times and is safe and effective, achieving similar long-term results with standard open repair. We show that robot-assisted surgery can be safely transitioned to surgical trainees. With its cost and availability, its role in the Canadian system needs further study.

Background and Purpose: Widespread introduction of robot-assisted laparoscopic radical prostatectomy (RALRP) has led to multiple surgeons going through the learning curve (LC). One of the recommendations for surgeons on the LC for RALRP is to choose patients with smaller glands. We evaluated our LCs to determine whether prostate size influenced intraoperative outcomes and positive surgical margin rates., Patients and Methods: Data were obtained from a prospective database for the first 154 cases of RALRP performed by a single surgeon. Patients were divided into three groups based on prostate volume (PV): <40 cc (group 1), 40 to 60 cc (group 2), or >60 cc (group 3). PV was estimated by preoperative transrectal ultrasonography (TRUS) and correlated with pathologic weight (PW). Perioperative and immediate postoperative outcomes were evaluated., Results: A statistically significant difference in total operative times between the groups (206 minutes vs 201 minutes vs 233 minutes for groups 1, 2, and 3, respectively) was noted. With regard to individual intraoperative steps, the bladder neck reconstruction and anastomosis time was longer in group 3. No other statistically significant differences were noted. The Pearson correlation coefficient between PV estimation by TRUS and PW was r = 0.785, and an additional analysis based on PW supports the results of our study., Conclusions: Prostate size influenced total operative times and the bladder neck reconstruction and anastomosis time. Our data support the use of preoperative TRUS to estimate PV and recommendations for surgeons starting on their LC to choose glands less than 60 cc.

Background and Purpose: Percutaneous nephrolithotomy (PCNL) for staghorn calculi is one of the more challenging endourologic procedures. Although excellent stone-free rates are universally reported in the literature, complication rates vary widely, especially related to the need for blood transfusion. The purpose of this study was to evaluate the outcomes of PCNL for patients with staghorn calculi in a large series of patients at a single, tertiary referral, endourologic stone center., Patients and Methods: Between July 1990 and December 2005, 1338 patients underwent PCNL for renal stone disease at our institution. Among this group, 509 procedures were performed for patients with a partial or complete staghorn calculus. Data analysis included procedure time, length of hospital stay, number of access tracts, transfusion rates, other early and late complications, and stone-free status., Results: Mean patient age was 53.8 years (range 4-84 yrs). The average procedure time was 104 minutes. Sixteen percent of the cases needed multiple access tracts (range 2-5), with the lower calix being the most commonly used in 64.1%, followed by the upper calix in 18.5% and the middle calix in 17.4%. Various intracorporeal lithotriptors were used, including ultrasound, pneumatic, electrohydraulic, and holmium:yttrium-aluminium-garnet laser. The transfusion rate among this group was 0.8%. There was no statistically significant difference in transfusion rates (0.7%-1.2% P = 0.24) or other major complications in patients who were treated with either a single tract or among those needing multiple tracts. Stone-free rates at hospital discharge and at 3 months follow-up were 78% and 91%, respectively., Conclusion: PCNL is a safe and effective procedure in the management of staghorn calculi, with outcomes similar to those reported for percutaneous management of smaller volume nonstaghorn stones. Attention to accurate tract selection and placement as well as possession of the full array of endourologic equipment are essential to achieving an excellent outcome.

Background and Purpose: Long-term use of ureteral stents is prevented by biofilm-related infection and encrustation mandating stent changes every few months. Triclosan is a broad-spectrum antimicrobial in numerous consumer and medical products and has been incorporated into a ureteral stent. We sought to determine the clinical effects of the triclosan-eluting stent in patients who needed long-term ureteral stenting., Patients and Methods: Eight patients with long-term stents were enrolled prospectively. All received a control stent for 3 months along with preoperative and postoperative antibiotics. After 3 months, the control stent was removed, and a triclosan-eluting stent was placed for 3 months with no antibiotics administered. For both indwelling periods, urine cultures were obtained weekly and biweekly for the first and last 6 weeks, respectively, and antibiotics were prescribed when patients had both a positive urine culture and symptoms of urinary tract infection. On removal, stents were assessed for microorganisms and encrustation., Results: Overall, similar microorganisms were isolated during each indwell period, although Staphylococcus and Enterococcus strains were isolated more frequently during control and triclosan stenting, respectively. Significantly fewer antibiotics were used during triclosan stenting, coinciding with a slightly higher number of positive urine cultures and significantly fewer symptomatic infections. No bacterial isolates developed antibiotic resistance during triclosan stent placement., Conclusions: Antibiotic use with control stents resulted in bacterial antibiotic resistance, which was not the case with the triclosan-eluting stents. Although triclosan-eluting stents did not show a clinical benefit in terms of urine and stent cultures or overall subject symptoms compared with controls, their use did result in decreased antibiotic usage and significantly fewer symptomatic infections. The triclosan-eluting stent alone is not sufficient to reduce device-associated infections in this difficult patient population.

Purpose: To compare the surgical outcomes in a cohort of patients with diabetes who were undergoing percutaneous nephrolithotripsy (PCNL) for renal stone disease to a nondiabetic group of patients at a single center., Patients and Methods: Between July 1990 and December 2005, all patients scheduled for PCNL were prospectively included in a single-center database. Preoperative, intraoperative, and postoperative data were prospectively collected and analyzed. Primary outcomes evaluated were stone-free rates and complications, including the need for blood transfusion, while the secondary outcome was length of hospital stay. This report specifically reviews these outcomes in patients known to have diabetes at the time of surgery. Both outcomes were compared with those obtained in our nondiabetic patient population., Results: Analysis of the data from 183 (13.7%) patients with diabetes of the 1338 patients undergoing PCNL revealed that patient age (63.1 years), surgical time (90.8 minutes), and complications (major 2.2%), including need for transfusion (0.5%) and stone-free rate (94.5%), were not significantly different from those observed in our nondiabetic patients. The average length of hospital stay was significantly longer in the diabetic group (4.4 days vs 3.9 days, P = 0.022). Uric acid stone composition was found to be the most common stone composition among the patients with diabetes in this study (41%)., Conclusions: PCNL can be performed with excellent stone-free rates and with an acceptable complication risk in the diabetic population. The incidence of uric acid stone disease appears to be significantly higher than previously reported and warrants heightened efforts directed toward stone prevention in this population.

Background and Purpose: Ureteral stents may cause significant morbidity, including pain, dysuria, hematuria, and infection. New biomaterials, coatings, and designs have been studied in an attempt to reduce stent-related symptoms, but to date, the ideal comfortable stent has not been developed. In order to facilitate development of a stent that will mold and change with patient movement, we examined stent and ureteral movement with changes in patient body position., Patients and Methods: Four women and two men with a median age of 60.5 +/- 7.7 years who underwent shockwave lithotripsy and insertion of a ureteral stent were enrolled. Static radiographs were performed with the patients in four positions: supine, standing, sitting, and bending forward. Differences in stent position were analyzed digitally relative to fixed bony reference points to determine ureteral movement., Results: The renal stent curl was most cephalad when the patient was supine and moved caudally an average of 2.5 +/- 1.5 cm when the patient stood up. The absolute vertical length of the stent was greatest when the patient was supine (31.1 +/- 1.2 cm) and shortened with standing (28.3 +/- 2.3 cm) and sitting (26.6 +/- 1.5 cm). The bladder curl moved an average of 2.3 +/- 1.2 cm vertically with patient movement., Conclusions: By measuring stent position, we were able to quantify the range of motion of the ureter during changes in body position. Stent movement appears to be a combination of bowing in the proximal ureter and moving within the bladder. Future stent designs may take this into account to decrease stent-related symptoms.

Idiopathic hyperammonemic encephalopathy is an uncommon but frequently fatal complication of chemotherapy. It is characterised by abrupt alteration in mental status with markedly elevated plasma ammonia levels in the absence of obvious liver disease or any other identifiable cause, and frequently results in intractable coma and death. It usually occurs in patients with haematologic malignancies during the period of neutropenia following cytoreductive therapy or bone marrow transplantation, and in solid organ malignancies treated with 5-fluorouracil. Although the aetiology of this syndrome is yet to be determined, it appears to be multi-factorial in nature. Optimal management remains to be formally established, and the critical step is increased awareness of the syndrome by measurement of plasma ammonium levels in patients with neurological symptoms, leading to early diagnosis and the prompt implementation of therapy.

Background and Purpose: The approach to urinary-stone disease has changed dramatically over the last three decades with a transition from open surgery to minimally invasive procedures. Percutaneous nephrolithotripsy (PCNL) is a cornerstone of the treatment of kidney and selected upper-ureteral stones and continues to evolve with advances in techniques and instrumentation. The purpose of this study was to assess outcomes and trends prospectively in a large contemporary group of patients undergoing PCNL., Patients and Methods: Between July 1990 and December 2005, all 1338 patients at a single center scheduled for PCNL (N = 1585 procedures) were enrolled. Their mean age was 53 years (range 4-89 years). Data including comorbidities, stone burden, stone location, surgical time, hospital length of stay, rate of secondary procedures, and adverse events were collected prospectively. The primary outcome measures were stone-free rate and complications., Results: There was a substantial incidence of comorbid medical conditions (48.8%) and anatomic renal abnormalities (25.3%), demonstrating the diverse and challenging patient population in this contemporary series. The overall stone-free rate at 3 to 6 months of follow-up was 94.8%., Conclusions: Percutaneous nephrolithotripsy is a highly effective procedure and may be performed in a diverse group of patients with comorbid conditions and renal abnormalities. Improved intracorporeal lithotripters, balloon dilation of the tract, use of flexible instruments, and liberal use of secondary nephroscopy result in excellent stone-free rates with low morbidity.

Purpose: To study the long-term outcomes of men with moderately severe symptomatic benign prostatic hyperplasia (BPH) who were treated with transurethral microwave thermotherapy (TUMT) with the Dornier Urowave machine., Patients and Methods: A total of 220 patients (mean age 66.2 years) with clinical BPH, an American Urological Association (AUA) Symptom Score of >or=13, and a peak urinary flow rate (Qmax) of

Human telomerase reverse transcriptase (hTERT) mRNA expression has been considered a surrogate marker for telomerase activity based on its parallel detection in urological malignancies, including transitional cell carcinoma (TCC) of the bladder. The objective of this study was to prospectively evaluate the diagnostic performance of urine hTERT mRNA marker and urine cytology in the detection of bladder cancer. The multiplex hTERT/GAPDH (glyceraldehyde-3-phosphate dehydrogenase) reverse transcription polymerase chain reaction (RT-PCR) assay was employed to assess hTERT mRNA expression in urine sediments from 43 patients with clinically apparent TCC undergoing transurethral resection. Tumor grade and pathological stage were determined. The results of urine cytology were compared with urine hTERT mRNA expression. The control group consisted of 46 age-matched healthy volunteers without known urinary tract disease. The sensitivity of hTERT mRNA expression marker in the detection of bladder cancer was significantly better than urine cytology (95% versus 65%, p<0.001). The hTERT mRNA was detected with high sensitivity in both low and high grade tumors, and in superficial and invasive phenotypes. No correlation was seen between hTERT mRNA and the histopathological grade and stage. The specificity of urinary hTERT mRNA marker was 93.5%. The detection of hTERT mRNA expression in urine was a highly sensitive marker for the diagnosis of TCC of the bladder in this study. This urine-based marker shows promise as a non-invasive adjunct to cystoscopy in patients undergoing bladder tumor surveillance.

Background and Purpose: Ureteral stents are a significant source of pain and discomfort for many urologic patients. A novel approach to addressing this problem is the intravesical instillation of a selected pharmacologic agent after stent insertion. The purpose of this study was to assess the safety and efficacy of intravesical instillation of various agents in reducing ureteral stent-associated discomfort in patients requiring a stent after extracorporeal shockwave lithotripsy (SWL)., Patients and Methods: In this double-blind prospective trial, 42 patients were randomized to receive intravesical instillation of one of three agents (oxybutynin, alkalinized lidocaine, or ketorolac) or a control solution (0.9% sodium chloride) immediately after stent insertion at time of SWL. The four groups of patients were demographically similar. Preoperative, intraoperative, and postoperative data were collected prospectively and analyzed statistically. The primary outcome measure was reduction in ureteral stent symptoms, and the secondary outcome measure was the safety of intravesical instillation of each agent through assessment of drug-related adverse events., Results: There were no intraoperative or postoperative complications, nor were there any serious side effects attributable to any of the intravesically instilled agents. There was a statistically significant decrease in stent-related discomfort at the 1-hour time point in the group of patients who received intravesical ketorolac compared with the control group., Conclusions: Intravesical instillation represents a novel approach to the problem of ureteral stent-related discomfort. From our results, ketorolac appears to be the most effective intravesical agent in reducing stent-related patient discomfort, and we have established that intravesical instillation of ketorolac is safe in humans.

Resistance responses that plants deploy in defence against pathogens are often triggered following a recognition event mediated by resistance (R) genes. The encoded R proteins usually contain a nucleotide-binding site (NB) and a leucine-rich repeat (LRR) domain. They are further classified into those that contain an N-terminal coiled coil (CC) motif or a Toll interleukin receptor (TIR) domain. Such R genes, when transferred into a susceptible plant of the same or closely related species, usually impart full resistance capability. We have used map-based cloning and mutation analysis to study the recognition of Peronospora parasitica (RPP)2 (At) locus in Arabidopsis accession Columbia (Col-0), which is a determinant of specific recognition of P. parasitica (At) isolate Cala2. Genetic mapping located RPP2 to a 200-kb interval on chromosome 4, which contained four adjacent TIR:NB:LRR genes. Mutational analysis revealed three classes of genes involved in specifying resistance to Cala2. One class, which resulted in pleiotropic effects on resistance to other P. parasitica (At) isolates, was unlinked to the RPP2 locus; this class included AtSGT1b. The other two classes were mapped within the interval and were specific to Cala2 resistance. Representatives of each of these classes were sequenced, and mutations were found in one or the other of two (RPP2A and RPP2B) of the four TIR:NB:LRR genes. RPP2A and RPP2B complemented their specific mutations, but failed to impart resistance when present alone, and it is concluded that both genes are essential determinants for isolate-specific recognition of Cala2. RPP2A has an unusual structure with a short LRR domain at the C-terminus, preceded by two potential but incomplete TIR:NB domains. In addition, the RPP2A LRR domain lacks conserved motifs found in all but three other TIR:NB:LRR class proteins. In contrast, RPP2B has a complete TIR:NB:LRR structure. It is concluded that RPP2A and RPP2B cooperate to specify Cala2 resistance by providing recognition or signalling functions lacked by either partner protein.

Objectives: To assess the long-term efficacy of percutaneous antegrade endopyelotomy for the treatment of ureteropelvic junction (UPJ) obstruction performed at a single institution during a 10-year period. We provide alterations in investigation and management strategies on the basis of the results., Methods: From July 1990 to June 2001, 80 patients with clinical and radiographic evidence of UPJ obstruction underwent percutaneous endopyelotomy for the treatment of primary (n = 61) or secondary (n = 19) UPJ obstruction. The mean patient age was 35 years (range 4 to 76). Percutaneous endopyelotomy was performed in a standard fashion using either a hooked-knife (n = 77) or holmium laser (n = 3)., Results: With a mean patient follow-up of 55 months (range 16 to 138), the overall success rate was 67% (53 of 79). The success rate for primary and secondary UPJ obstruction was 65% (39 of 60) and 74% (14 of 19), respectively. The mean time to failure was 15 months (range 1 to 79). Operative intervention for 24 of 26 patients with failure included open pyeloplasty (n = 18, 75%), indwelling ureteral stenting (n = 2, 8%), retrograde balloon dilation (n = 1, 4%), and nephrectomy (n = 3, 13%). Two asymptomatic patients with recurrent radiographic evidence of obstruction elected conservative follow-up. Significant crossing vessels were encountered at open pyeloplasty in 15 (83%) of 18 patients., Conclusions: Our long-term results of percutaneous endopyelotomy demonstrated somewhat lower success rates than that reported in published studies. Long-term follow-up is critical in identifying late failures. The high prevalence of crossing vessels encountered at open pyeloplasty provided further evidence to support its role in endopyelotomy failure. Routine preoperative helical computed tomography to detect significant crossing vessels is recommended. Patients with crossing vessels are likely better served with operative techniques that specifically address this issue, namely open or laparoscopic pyeloplasty.

Introduction/objective: Advances in ureteroscope design and refinements of ancillary instrumentation have resulted in an expanded role for ureteroscopy in the management of urinary calculi. Technological enhancements coupled with improved endourologic skills have also been associated with a reduction in procedural-related complications. Historically, postoperative imaging with ultrasound (U/S) or intravenous pyelogram (IVP) had been advocated to rule out persistent obstruction due to retained stone fragments or ureteral stricture. The purposes of this study were to evaluate the incidence of postoperative ureteral obstruction in a contemporary series of patients undergoing ureteroscopic holmium:YAG laser lithotripsy without basket extraction of fragments and to identify patient, stone and operative factors predictive of which patients will benefit from postoperative imaging., Materials and Methods: The charts and imaging studies of 89 consecutive patients undergoing a total of 94 holmium:YAG ureteroscopic lithotripsy procedures between December 1998 and December 2000 were retrospectively reviewed. Preoperative, intraoperative and postoperative data were collected and analyzed. The primary outcome measure was the incidence of postoperative ureteral obstruction documented on upper tract imaging. Secondary outcome measures included interventions required for postoperative obstruction and other nonobstructive postoperative complications., Results: Twenty-eight females and 61 males were studied, with a mean patient age of 54 (range 13-80) years. Fifty-five percent of patients underwent related procedures prior to referral to our tertiary endourology centre. Complete clinical and radiological follow-up is available for 68 of 89 (76.4%) patients, with a mean follow-up duration of 24.2 weeks. Overall stone-free rate was 97%. Six patients had evidence of urinary tract obstruction on follow-up radiological assessment, two from residual stone fragments and four from ureteral stricture. Each of these four patients had at least one preoperative risk factor for ureteral stricture., Conclusions: Routine postoperative upper tract imaging is not necessary in all patients undergoing uncomplicated ureteroscopic holmium:YAG laser lithotripsy. Indications for upper tract imaging include chronic stone impaction, significant ureteral trauma, pre-existing renal function impairment, endoscopic evidence of stricture and postoperative flank pain or fever.

Objectives: To review the results of holmium laser lithotripsy in a cohort of patients who presented with symptomatic urolithiasis in pregnancy. Symptomatic urolithiasis in pregnancy that does not respond to conservative measures has traditionally been managed with ureteral stent insertion or percutaneous nephrostomy. Holmium:yttrium-aluminum-garnet (YAG) laser lithotripsy using state-of-the-art ureteroscopes represents an emerging strategy for definitive stone management in pregnancy., Methods: A retrospective analysis was conducted at two tertiary stone centers from January 1996 to August 2001 to identify pregnant patients who were treated with ureteroscopic holmium laser lithotripsy for symptomatic urolithiasis or encrusted stents. Eight patients with a total of 10 symptomatic ureteral calculi and two encrusted ureteral stents were treated. The mean gestational age at presentation was 22 weeks. The mean stone size was 8.1 mm. The stones were located in the proximal ureter/ureteropelvic junction (n = 3), midureter (n = 1), and distal ureter (n = 6)., Results: Complete stone fragmentation and/or removal of encrusted ureteral stents were achieved in all patients using the holmium:YAG laser. The overall procedural success rate was 91%. The overall stone-free rate was 89%. No obstetric or urologic complications were encountered., Conclusions: Ureteroscopy and holmium laser lithotripsy can be performed safely in all stages of pregnancy, providing definitive management of symptomatic ureteral calculi. The procedure can be done with minimal or no fluoroscopy and avoids the undesirable features of stents or nephrostomy tubes.

Purpose: We assessed the safety and efficacy of ureteroscopy and holmium:YAG laser lithotripsy for treating upper urinary tract calculi in patients with known and uncorrected bleeding diathesis., Materials and Methods: We retrospectively reviewed the charts at 2 tertiary stone centers to identify patients with known bleeding diathesis who were treated with holmium:YAG laser lithotripsy for upper urinary tract calculi. A total of 25 patients (29 upper urinary tract calculi) underwent ureteroscopic holmium laser lithotripsy. Bleeding diathesis involved warfarin administration for various conditions in 17 patients, liver dysfunction in 3, thrombocytopenia in 4 and von Willebrand's disease in 1. The mean international normalized ratio, platelet count and bleeding time were 2.3, 50 x 109/l. and greater than 16 minutes in patients on warfarin and in those with liver dysfunction, thrombocytopenia and von Willebrand's disease, respectively., Results: Overall the stone-free rate was 96% (27 of 28 cases) and 29 of 30 procedures were completed successfully without significant complication. In a patient treated concomitantly with electrohydraulic lithotripsy significant retroperitoneal hemorrhage required blood transfusion., Conclusions: Upper tract urinary calculi in patients with uncorrected bleeding diathesis can be safely managed by contemporary small caliber ureteroscopes and the holmium laser as the only modality of lithotripsy. Ureteroscopic holmium laser lithotripsy without preoperatively correcting hemostatic parameters limits the risk of thromboembolic complications and costs associated with an extended hospital stay. Avoiding electrohydraulic lithotripsy is crucial for decreasing bleeding complications in this cohort of patients.