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Purpose Rapid sequence intubation (RSI) drugs, such as propofol, affect clinical outcomes, but this has not been examined in the pediatric population. This descriptive study compares the outcomes associated with intubation drugs used in pediatric traumatic brain injury (TBI) patients. Methods A retrospective chart review and descriptive analysis of intubated TBI patients, ages 0–17, admitted to Children's Hospital London Health Sciences Centre (LHSC) from January 2006–December 2016 was performed. Results Out of 259 patients intubated, complete data was available for 107 cases. Average injury severity score was 28; 46 were intubated at LHSC, 55 at primary care site, and 6 on scene. Intubation attempts were recorded in 87 of 107 paper charts. First-pass intubation success rate was 88.5%. Propofol (n = 21), midazolam (n = 31), etomidate (n = 13), and ketamine (n = 7) were the most commonly used intubation drugs. Paralytics were used in 50% of patients. Following use of propofol, Pediatric Adjusted Shock Index was increased as a result of worsening hypotension. Mean total hospital length of stay was 21 days with 7.5 days in ICU. Survival was 87%. Conclusion Great variability exists in the use of induction agents and paralytics for RSI. Propofol was commonly used and is potentially associated with poorer clinical outcomes. Type of Study Retrospective. Level of Evidence IV

Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial. Background: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial. Objective: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management. Design: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts before voting during a consensus conference. Setting: Online Delphi survey and consensus conference. Participants: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management. Outcome measurements and statistical analysis: Statements were ranked by experts according to their level of agreement: 1–3 (disagree), 4–6 (equivocal), 7–9 (agree). A priori (level 1) consensus was defined as 70% agreement and 15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus). Results and limitations: Overall, 116 statements were included in the Delphi survey. Of these, 33 (28%) statements achieved level 1 consensus and 49 (42%) statements achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease and the evolving role of checkpoint inhibitor therapy in metastatic disease. Conclusions: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time where further evidence is available to guide our approach, The authors would like to thank Peter E. Clark from Atrium Health, Levine Cancer Institute, Charlotte, NC, USA, for his contribution to the Delphi survey. Angela Corstorphine of Kstorfin Medical Communications Ltd provided medical writing support with the preparation of this manuscript; this support was funded jointly by EAU and ESMO.

Background: Image-guided percutaneous core needle biopsy (PCNB) is increasingly utilized to diagnose solid tumors. The objective of this study is to determine whether PCNB is adequate for modern biologic characterization of neuroblastoma. Procedure: A multi-institutional retrospective study was performed by the Pediatric Surgical Oncology Research Collaborative on children with neuroblastoma at 12 institutions over a 3-year period. Data collected included demographics, clinical details, biopsy technique, complications, and adequacy of biopsies for cytogenetic markers utilized by the Children's Oncology Group for risk stratification. Results: A total of 243 children were identified with a diagnosis of neuroblastoma: 79 (32.5%) tumor excision at diagnosis, 94 (38.7%) open incisional biopsy (IB), and 70 (28.8%) PCNB. Compared to IB, there was no significant difference in ability to accurately obtain a primary diagnosis by PCNB (95.7% vs 98.9%, P =.314) or determine MYCN copy number (92.4% vs 97.8%, P =.111). The yield for loss of heterozygosity and tumor ploidy was lower with PCNB versus IB (56.1% vs 90.9%, P

The authors regret that a co-author was mistakenly missed from the authorship. The following co-author should have been included in the authorship: Peter-Paul M. Willemse Department of Oncological Urology, University Medical Center, Utrecht Cancer Center, Utrecht, The Netherlands

Purpose Management of localized radio-recurrent prostate cancer is not standardized, partly due to the absence of long-term data on oncologic control and the toxicity of various treatment modalities. We analyzed the long-term oncologic outcomes and morbidity of salvage cryoablation for radio-recurrent prostate cancer. Materials and Methods Patients undergoing salvage cryoablation for biopsy proven, localized radio-recurrent prostate cancer from 1995 to 2004 were prospectively accrued. Preoperative characteristics, perioperative morbidity and postoperative data were reviewed from a prospectively maintained database or via telephonic contact with the patient. The primary outcome was overall survival. Secondary outcomes were metastasis-free and biochemical disease-free survival. The Kaplan-Meier method was used for survival analysis and multivariable Cox regression analysis was performed. Results Of 187 patients 157 (84%) had records available for followup. Mean ± SD age was 69.4 ± 5.8 years and mean presalvage prostate specific antigen was 6.6 ± 5.7 ng/ml. Median followup was 117 months (IQR 55–154). Five and 10-year overall survival was 93% and 76%, respectively. Biochemical disease-free survival at 10 and 15 years was 35% and 22.6% whereas metastasis-free survival at 10 and 15 years was 86% and 71%, respectively. On multivariable analysis precryoablation and nadir prostate specific antigen values were significant predictors of metastasis-free and biochemical disease-free survival. Age at salvage cryoablation (p = 0.008) and nadir prostate specific antigen (p = 0.015) were significant predictors of overall survival. There were 157 Clavien-Dindo grade 1-2 and 22 grade 3 complications. Conclusions A single center, long-term experience documented by a prospectively maintained database shows that cryoablation is a viable salvage option for radio-recurrent prostate cancer as it provides durable biochemical disease-free survival with acceptable morbidity.

BackgroundAlthough guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial.ObjectiveTo bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management.DesignA steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts prior to voting during a consensus conference.SettingOnline Delphi survey and consensus conference.ParticipantsThe European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management.Outcome measurements and statistical analysisStatements were ranked by experts according to their level of agreement: 1–3 (disagree), 4–6 (equivocal), and 7–9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus).Results and limitationsOverall, 116 statements were included in the Delphi survey. Of these statements, 33 (28%) achieved level 1 consensus and 49 (42%) achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease, and the evolving role of checkpoint inhibitor therapy in metastatic disease.ConclusionsThese consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time when further evidence is available to guide our approach.Patient summaryThis report summarises findings from an international, multistakeholder project organised by the EAU and ESMO. In this project, a steering committee identified areas of bladder cancer management where there is currently no good-quality evidence to guide treatment decisions. From this, they developed a series of proposed statements, 71 of which achieved consensus by a large group of experts in the field of bladder cancer. It is anticipated that these statements will provide further guidance to health care professionals and could help improve patient outcomes until a time when good-quality evidence is available.

Objectives To review the use of fiducial markers and spacers in prostate radiotherapy (RT). Materials and Methods We reviewed the literature on the use of fiducial markers to improve accuracy in delivery of RT for prostate cancer. We discuss the rationale for fiducials, the types available, the procedures and complications. We also reviewed the current literature on the novel use of spacers to reduce rectal toxicity during prostate irradiation. Results Prostate motion is a significant problem both during and between RT treatments. Intraprostatic fiducials allow accurate prostate localisation ensuring RT treatment accuracy. Insertion of gold fiducials are a cost-effective marker that can be easily and quickly implanted and at least three fiducials are recommended. Severe complications from fiducial implantation are uncommon and marker migration is very rarely clinically significant. Spacers are a novel method to distance the rectum from the prostate during RT, reducing acute rectal toxicity, and have no detrimental impact on health-related quality of life. Conclusions Intraprostatic fiducials are now standard of care when delivering prostate RT and early data shows benefit of spacers in reducing RT rectal toxicity.

Normal physiology relies on the organization of transmembrane proteins by molecular scaffolds, such as tetraspanins. Oncogenesis frequently involves changes in their organization or expression. The tetraspanin CD151 is thought to contribute to cancer progression through direct interaction with the laminin-binding integrins α3β1 and α6β1. However, this interaction cannot explain the ability of CD151 to control migration in the absence of these integrins or on non-laminin substrates. We demonstrate that CD151 can regulate tumor cell migration without direct integrin binding and that integrin-free CD151 (CD151free) correlates clinically with tumor progression and metastasis. Clustering CD151free through its integrin-binding domain promotes accumulation in areas of cell–cell contact, leading to enhanced adhesion and inhibition of tumor cell motility in vitro and in vivo. CD151free clustering is a strong regulator of motility even in the absence of α3 expression but requires PKCα, suggesting that CD151 can control migration independent of its integrin associations. The histologic detection of CD151free in prostate cancer correlates with poor patient outcome. When CD151free is present, patients are more likely to recur after radical prostatectomy and progression to metastatic disease is accelerated. Multivariable analysis identifies CD151free as an independent predictor of survival. Moreover, the detection of CD151free can stratify survival among patients with elevated prostate-specific antigen levels. Cumulatively, these studies demonstrate that a subpopulation of CD151 exists on the surface of tumor cells that can regulate migration independent of its integrin partner. The clinical correlation of CD151free with prostate cancer progression suggests that it may contribute to the disease and predict cancer progression. Cancer Res; 74(1); 173–87. ©2013 AACR.

We assessed and compared the survival outcomes between cryoablation and external beam radiation therapy in patients with locally advanced prostate cancer (cT2c-cT3b).Patients with locally advanced prostate cancer, recruited from 1999 to 2002, were randomized to primary cryoablation or external beam radiotherapy. All patients received neoadjuvant hormonal therapy for 3 months before and 3 months after the procedures. Patients underwent followup transrectal ultrasound guided biopsy (at 3, 6, 12, 18 and 24 months for cryoablation, and at 18 and 24 months for external beam radiotherapy) and as clinically indicated thereafter. Biochemical failure was based on the Phoenix criterion (prostate specific antigen nadir +2 ng/dl).A total of 62 patients completed the trial. Median followup was 105.2 months (SD ±35.8). Accrual was limited due to newer data favoring longer neoadjuvant hormonal therapy and higher external beam radiotherapy dose for locally advanced prostate cancer. There was a greater reduction in prostate volume in the cryoablation group after intervention (-54% vs -34%, p ≤0.01). Disease specific survival and overall survival were comparable between the groups. However, the 8-year biochemical disease-free survival rate was significantly lower in the cryoablation group (17.4% vs 59.1%) (p = 0.01).This randomized trial with median followup approaching 9 years showed that cryoablation was inferior in attaining biochemical disease-free survival in patients with locally advanced prostate cancer (cT2c-T3). Cryoablation may be more suited for less bulky prostate cancer. Longer duration neoadjuvant hormonal therapy or a multimodal approach may provide optimal biochemical disease-free survival in this patient population.

BACKGROUND: Whole-gland high-intensity focused ultrasound (HIFU) has been used as salvage therapy for local recurrence following external beam radiation therapy for decades. This article describes the use of the Sonablate 500 HIFU system in the salvage setting. METHODS: An evaluation was performed of a consecutive group of men with biochemical failure after external beam radiation therapy with histologically proven local recurrence and bone-scan and pelvic magnetic resonance imaging to exclude macroscopic metastases, and who chose to have whole-gland salvage HIFU (Sonablate 500) at 2 centers (3 expert HIFU surgeons at each center). The modified Clavien system was used to categorize adverse events and validated questionnaires for functional outcomes. Progression following HIFU treatment was defined as ASTRO-Phoenix criteria (prostate serum antigen [PSA] >nadir+2 ng/mL) and/or a positive biopsy and/or start of hormone therapy. RESULTS: Eighty-four men underwent whole-gland salvage HIFU (2004-2009). Median age, pretreatment serum PSA, and biopsy Gleason score was 68 years (range, 64-72 years), 4.3 ng/mL (range, 1.9-7.9 ng/mL), and 7 (range, 6-7), respectively. Mean follow-up was 19.8 months (range, 3.0-35.1 months). After salvage HIFU, 62% of the men were pad-free and leak-free. Mean International Index of Erectile Function-5 point score fell from 8.8 to 4.7 (P < .001). International Prostate Symptoms Score and RAND-SF36 scores were not affected. Two men developed rectourethral fistulae after 1 salvage procedure. A further 2 fistulae occurred in the 6 men undergoing a second salvage HIFU. Intervention for bladder outlet obstruction was needed in 20% (17 of 84 patients). If PSA nonresponders were included, 1- and 2-year progression-free survival rates were 59% (50 of 84 patients) and 43% (36 of 84 patients), respectively. If PSA nonresponders were excluded, 1- and 2-year progression-free survival rates were 62% (48 of 77 patients) and 48% (37 of 77 patients), respectively. CONCLUSIONS: Salvage whole-gland HIFU is a high-risk procedure. Although its use in early cancer control is promising, strategies to better identify metastatic disease prior to salvage therapy and reduce local toxicity are needed to improve on this. Cancer 2012;118: 3071–78. © 2011 American Cancer Society.

BACKGROUND Ghrelin is a natural growth hormone secretagogue (GHS) that is co-expressed with its receptor GHSR in human prostate cancer (PCa) cells. Imaging probes that target receptors for ghrelin may delineate PCas from benign disease. The specificity of a novel ghrelin-imaging probe for PCa over normal tissue or benign disease was assessed. METHODS A fluorescein-bearing ghrelin analogue was synthesized (fluorescein-ghrelin(1–18)), and its application for imaging was evaluated in a panel of PCa cell lines and human prostate tissue. Prostate core biopsy samples were collected from fresh surgery specimens of 13 patients undergoing radical prostatectomy. Ghrelin probe signal was detected and quantified in each sample using a hapten amplification technique and associated with pathological features. RESULTS The ghrelin probe was taken up by GHSR-expressing LNCaP and PC-3 cells, and not in BPH cells that express low levels of GHSR. Binding was blocked by competition with excess unlabeled probe. The ghrelin probe signal was 4.7 times higher in PCa compared to benign hyperplasia tissue (P = 0.0027) and normal tissue (P = 0.0093). Furthermore, while the ghrelin probe signal was 1.9-fold higher in PIN compared to benign hyperplasia (P = 0.0022) and normal tissue (P = 0.0047), there was no significant difference in the signal of benign hyperplasia compared to normal tissue. CONCLUSION The imaging probe fluorescein-ghrelin(1–18) is specific for PCa, and did not associate significantly with benign hyperplasia or normal prostate tissue. This data suggests that ghrelin analogues may be useful as molecular imaging probes for prostatic neoplasms in both localized and metastatic disease. Prostate 72:825–833, 2012. © 2011 Wiley Periodicals, Inc.

Background The optimum treatment of prostate cancer recurrence following radiation therapy (RT) remains controversial due to the lack of long-term data. Objective Our aim was to review the survival of patients who underwent salvage cryotherapy to the prostate gland for biopsy-proven recurrent prostate cancer and establish prognostic indicators. Design, setting, and participants A retrospective analysis was performed on all patients undergoing salvage cryotherapy at an academic urology unit for biopsy-proven locally recurrent prostate cancer after RT from 1995 to 2004. Patients' preoperative, perioperative, and postoperative data were reviewed and recorded. Intervention Two freeze-thaw cycles of transperineal cryotherapy were performed under transrectal ultrasound guidance by a single surgeon. Measurements The primary outcome was survival. Secondary outcomes were disease-free survival (DFS), metastasis-free survival, and progression to androgen-deprivation therapy. Results and limitations Of 187 patients, 176 had records available for follow-up (follow-up rate: 94%). Mean follow-up was 7.46 yr (range: 1-14 yr). Fifty-two patients were followed for >10 yr. DFS at 10 yr was 39%. Risk factors for recurrence were presalvage prostate-specific antigen (PSA), preradiation, and presalvage Gleason score. A PSA nadir >1.0 ng/dl was highly predictive of early recurrence. Conclusions Salvage cryotherapy led to an acceptable 10-yr DFS. Presalvage PSA and Gleason score were the best predictors of disease recurrence. A PSA nadir >1 ng/dl following cryotherapy indicated a poor prognosis, and recurrence of disease was universal in these patients.

Objective • To explore the usefulness of cumulative summation (CUSUM) graphs for monitoring positive surgical margin (PSM) rates during a surgeon's transition from open to robot-assisted radical prostatectomy (RARP). Patients and methods • Data were prospectively collected from patients undergoing RARP by a single surgeon. • Preoperatively all patients were either low or moderate risk under the D'Amico classification system. • A CUSUM graph was charted retrospectively to analyse the PSM rate in patients undergoing RARP for pathological stage T2 (pT2) disease. • Acceptable and unacceptable PSM rates were set at 10% and 15% respectively. Results • From a cohort of 226 patients, 158 patients with pT2 disease were selected. The mean (range) age of these patients was 59.2 (39-73) years, the median (range) Gleason score was 6 (4-9), the mean (range) PSA was 6.43 (0.52-17.5) ng/mL and the mean (range) prostate volume was 44 (18-120) cm(3). In all, 21 patients had PSMs (13%). • CUSUM graphs were produced and clearly demonstrated the change in PSM rate over time. Conclusion • CUSUM graphs are a novel and useful visual representation of the learning curve for surgeons. • PSM rates in patients with pT2 disease are a good outcome to monitor using CUSUM graphs as they are binary and lack the confounding factors associated with other outcomes such as continence and erectile dysfunction. • We advocate the use of CUSUM graphs as a method of quality assurance with the introduction of a robotics programme.

High-intensity focused ultrasound (HIFU) has evolved significantly from early work treating cerebral lesions. The ability to treat deep soft-tissue lesions without damaging superficial structures led to it being used for prostate cancer treatment both in the primary and salvage setting. Primary HIFU treatment for prostate cancer leads to 5-year disease free survival rates of up to 70-80% in selected patients with little morbidity; however, comparative studies with established treatment modalities are lacking. Salvage treatment with HIFU leads to significantly more morbidity than primary treatment yet the morbidity appears the same or less than other salvage treatments following external-beam radiation treatment. We believe that with the development of more advanced imaging techniques combined with multimodality prostate imaging that HIFU's future lies in focal treatment of prostate cancer.

Background/Purpose: Recent work has shown that apoptosis is a key component of the normal development of the foregut. This study was designed to compare the patterns of apoptosis in the normal foregut with those in the fetus developing esophageal atresia and tracheoesophageal fistula (EA-TEF) using 3-dimensional reconstructive techniques. Methods: Timed pregnant rats that received no treatment (control group) or received Adriamycin intraperitoneally (experimental group) had their embryos removed between days 11 and 14 of gestation. The embryos were sectioned serially and stained with H&E. Three-dimensional reconstructions were made of the foregut and areas of apoptosis were marked on them to facilitate analysis of apoptotic patterns. Results: Apoptosis was evident in control embryos in the region in which tracheoesophageal separation occurs from days 12 and 12.5. Experimental embryos showed no apoptosis until day 13 when apoptosis was observed immediately posterior to the foregut within the esophageal mesenchyme and in the laryngeal mesenchyme ventral to the foregut. Conclusions: The pattern, timing and location of apoptosis in rats developing EA-TEF is abnormal. Our work indicates that it is actually a complete lack of apoptosis at the crucial stage of development that leads to this abnormality rather than an alteration in the patterning of apoptosis at this crucial time. The observation of apoptosis only within the mesenchyme raises the possibility that apoptosis in the foregut developing EA-TEF may be a reaction to that abnormal development rather than its cause. J Pediatr Surg 35:1617-1620. Copyright © 2000 by W.B. Saunders Company.

INTRODUCTION AND OBJECTIVES: Early diagnosis of prostate cancer is conventionally done with serum prostate specific antigen (PSA) test and digital rectal examination, but these tests lack specificity. Many men worldwide undergo repeated, sometimes unnecessary prostate biopsies due to suspicious or rising PSA levels. A urine test PCA3 is gaining popularity, predominantly in the field of managing patients with suspicious PSA and previous benign biopsies. In this multinational study we assessed the performance of the PCA3 urine test in patients who were candidates for prostate biopsies due to high or rising PSA’s. METHODS: The PCA3 scores were determined in urine samples in these men A PCA3 scores of 35 or higher were considered higher probability of cancer. Subsequent biopsy was performed as per current best practice and at the discretion of the urologist in concert with the patient. To retrospectively assess the performance of PCA3, we used multiple logistic regression analysis and receiver operating characteristic (ROC) curves were constructed to evaluate PCA3 as a prognostic factor compared with PSA and evaluated the influence of PCA3 testing on the decision making. RESULTS: 401 patients had PCA3 score available. The most common indication was rising or high PSA after previous negative biopsies -in 256 patients (63.8%), followed by the finding of high grade prostatic intraepithelial neoplasia (HGPIN) or atypical small acinar proliferation (ASAP) on previous biopsy in 101 patients (25.2%). Forty four subjects (11%) did not undergo prostate biopsy prior to PCA3 testing. PCA3 scores were significantly lower in patients without malignancy using a cutoff score of 35 (OR 2.99 (95%CI) (1.42, 6.30), p 0.004). On ROC curve analysis PCA3 area under the curve of 0.722 was significantly greater than PSA (0.4837). Sensitivity and specificity of PCA3 score using the 35 cutoff were 63.6% and 63.0%, respectively. When a cutoff score of 20 was used, the sensitivity and specificity of PCA3 score were 86.4% and 41.3%, respectively. The PCA3 test influenced the clinical course of the patient in 73.5% of cases. The follow-up PSA values in patients who did not perform biopsy after PCA3 testing had, without exception, remained stable or dropped (7.86 vs. 6.22, p 0.003) with follow-up of at least 6 months. CONCLUSIONS: In this multinational study we demonstrate that urine PCA3 score test out-performs PSA in decision making in men facing possibility of repeat prostate biopsy. We recommend that the PCA3 results should be integrated with other relevant data and rather be used in continuous fashion, and not with certain cutoff value.

Primary mucinous cystadenocarcinoma of the retroperitoneum isan extremely rare malignancy with only 2 male patients reportedin the literature. We describe an unusual case presenting as a pelvicmass in a male with previous pan-proctocolectomy and endileostomy for Crohn’s disease and review the available literature.

Introduction: Surgical wait times have been shown to be of significance in other malignancies, but limited studies exist in renal cell cancer (RCC). We analyzed surgical waiting time for RCC patients to see if there was an adverse impact on pathological characteristics. Methods: Our centre triages RCC patients on the basis of perceived tumour risk. The waiting time for surgery is adjusted stage for stage: clinical T1 at 90 days, T2 at 40 days, T3 and T4 at 30 days. We retrospectively reviewed the charts of 354 patients who underwent surgery for RCC. Patients were assessed for pathological upstaging, positive lymph nodes, tumour recurrence and tumour size within each stage. Analysis was performed, using surgical waiting time as a categorical variable, to test for associations with disease recurrence or adverse pathological characteristics. Results: The median time from the first consultation to surgery was 41 days and the mean follow-up was 26.6 months. Waiting time stage for stage was: clinical T1 at 57.12 days, clinical T2 at 36.8 days, clinical T3 and T4 at 30.32 days. On multivariate analysis, pathological tumour size was associated with progression, whereas no significant association was found between waiting time and upstaging. Higher stage tumours, sarcomatoid pathology and clinical evidence of progression were associated with shorter waiting times for early interventions. Conclusions: There was no statistically significant evidence for upstaging or progression during the waiting period for our group of patients. The data reinforce previous studies reporting a “safe” period of active surveillance in T1 RCC without affecting their final pathological outcome. Introduction : Il a ete montre que les temps d’attente en chirurgie ont de l’importance avec d’autres tumeurs malignes, mais il existe peu d’etudes concernant l’hypernephrome. Nous avons analyse le temps d’attente avant une intervention chirurgicale des patients atteints d’hypernephrome pour voir si ce temps d’attente avait un effet negatif sur les caracteristiques pathologiques. Methodes : Notre centre trie les patients atteints d’hypernephrome sur la base du risque percu lie a la tumeur. Le temps d’attente pour la chirurgie est ajuste en fonction du stade : stade clinique T1, 90 jours, stade T2, 40 jours, stades T3 et T4, 30 jours. Nous avons examine de facon retrospective les dossiers de 354 patients ayant subi une chirurgie pour traiter un hypernephrome. Les patients ont ete evalues pour cerner la presence d’une progression du stade pathologique ou de ganglions lymphatiques positifs, et la recidive et la taille de la tumeur pour chaque stade. L’analyse a ete effectuee en utilisant le temps d’attente avant l’intervention comme variable categorique, afin de verifier son lien avec la recurrence de la maladie ou des caracteristiques pathologiques nefastes. Resultats : Le delai median entre la premiere consultation et l’intervention etait de 41 jours, et le suivi moyen etait de 26,6 mois. Le temps d’attente en fonction du stade allait comme suit : stade clinique T1, 57,12 jours, stade clinique T2, 36,8 jours, stades cliniques T3 et T4, 30,32 jours. Lors de l’analyse multivariee, une correlation a ete etablie entre la taille de la tumeur et la progression, alors qu’aucun lien significatif n’a ete observe entre les temps d’attente et la progression du stade pathologique. Un stade tumoral superieur, des caracteristiques sarcomatoides a l’examen pathologique et des preuves cliniques de progression ont ete associes a des temps d’attente plus courts pour les interventions precoces. Conclusions : Il n’y avait aucune donnee statistiquement significative montrant une progression du stade pathologique au cours de la periode d’attente pour notre groupe de patients. Les donnees confirment les resultats d’etudes anterieures signalant une periode « sans danger » de surveillance active dans les cas d’hypernephrome de stade T1 sans que cela n’affecte le resultat pathologique final.

Prostate cancer is the leading malignancy in North American men and despite improvements in treatments 20 - 30% of patients will relapse. Immunotherapy using activated mononuclear cells is a way to harness the body's adaptive immune response to fight metastatic prostate cancer.In 2005, at least 10 therapeutic cancer vaccines, designed to confer active, specific immunotherapy against tumor-associated antigens, were in clinical trials. These covered potential fields of immunological strategy to overcome castration-resistant prostate cancer.A literature review was performed using the search terms sipuleucel-T, Provenge and APC8015 or APC-8015, and restricted to English language articles from 2000 to 2010. The immunological design and development of sipuleucel-T are summarized. The efficacy and safety of sipuleucel-T are discussed based on current data from clinical trials. Ongoing clinical trials involving sipuleucel-T are summarized.Efficacy and safety with sipuleucel-T has been demonstrated in Phase I/II trials. The latest data from a Phase III trial shows that sipuleucel-T has met the primary endpoint of survival benefit. Further work is needed to understand the mechanisms behind cancer vaccine failure and elucidate the population for whom this vaccine will be suitable.

The pathogenesis of the alimentary tract duplications, including foregut duplications (FgD) remains speculative. The accidental finding of FgD in fetal rats with esophageal atresia and tracheoesophageal fistula (EA-TEF) induced by Adriamycin provided an animal model to investigate a possible relationship between these two entities. Timed-pregnant rats were intraperitoneally injected with Adriamycin (1.75 mg/kg) on gestational Days 6 to 9. Their embryos were harvested by Caesarean section from gestational Days 14 to 21. Forty-six of embryos were processed and serially sectioned in the transverse or sagittal planes. EA-TEF occurred in 43/46 (93%) embryos of which 11 (24%) were found to have an associated FgD located at the level where the esophagus was absent. Six FgDs communicated with the foregut or the trachea. Five noncommunicating FgDs were located between the foregut and the vertebral column. In the control embryo, the notochord was located in the centre of the vertebral column from Day 11 of the gestation. In Day 14, 15 and 16, however, embryos exposed to Adriamycin, an abnormal notochord or branch frequently was located within the mesenchyme of the maldeveloped foregut or attached to the duplication cyst. In some, it appeared that the notochord was drawing the cyst-like structure away from the foregut. The present study confirms that duplications adjacent to the esophagus arise from the foregut and that failure of the foregut to detach from the notochord at the normal time may contribute to the development of foregut duplications. Anat Rec 264:93–100, 2001. © 2001 Wiley-Liss, Inc.

The histological changes (both macroscopic and microscopic) in the prostate following the combination of external beam radiotherapy and salvage high intensity focused ultrasound (HIFU) have not been previously described. This article describes the case of a 65-year-old male who presented with recurrent localized prostate cancer after undergoing external beam radiotherapy for low-risk prostate cancer. He was treated with salvage HIFU, and 4 weeks later presented with symptoms and signs consistent with a prostatorectal fistula. During a period of conservative management, his serum prostate-specific antigen levels started rising after having reached a nadir. A radical cystoprostatectomy and repair of fistula were performed after conservative management failed. Histological changes of dense fibrosis were noted in the region where the prostate should have been located. A literature review of the histological findings in the prostate after HIFU is discussed in this article, as well as the available evidence for the management of patients with local failure after the combination of external beam radiotherapy and salvage HIFU.

Background: Akt is an ubiquitous signaling molecule that is associated with a wide array of biological effects including cell growth and proliferation. The dysregulation of Akt has been associated with cancer cell transformation, invasion and metastasis. While the roles of mutations in FGFR3, p53 and Ras have been the focus of the majority of studies of Transitional cell carcinoma (TCC) of the bladder, recent evidence suggests a link between the Akt pathway and the progression of TCC. Mutations in Akt pathway members have been identified in subsets of bladder TCCs, and Akt activation in TCC cell lines confers resistance to chemotherapeutics and promotes invasion in vitro. This led us to hypothesize that activated Akt may be an important biomarker in the progression of muscle invasive TCC. Methods: Tissue was obtained from 67 patients who had undergone radical cystectomy procedures for treatment of muscle invasive TCC. Tissue sections were taken from paraffin embedded samples and subjected to immunohistochemical analysis with anti Akt antibody to detect the activated form of Akt. A database of patient demographics, disease, treatment and survival parameters was generated and used to correlate 4, 12, 24 and 36 month disease-free intervals (DFI). Results: 53 of the 67 patients had sufficient follow-up to allow for DFI analysis. Of these 53 patients, 48 stained positively for pAkt, while 5 stained negatively. None of the pAkt negative patients had recurrent disease, while the pAkt negative patients suffered cumulative recurrence in 10, 19, 24, and 25 of the 48 patients at 4, 12, 24 and 36 months respectively. Chi square analysis reveals statistically significant differences in recurrence rates between pAkt negative and negative patients at 24 (p=0.0235) and 36 months (p=0.016). Tumor stage and nodal status were also strong predictors of recurrence. Conclusions: pAkt negative patients were found to have a significantly better prognosis for TCC recurrence, which indicates that pAkt status could be useful in helping to determine the prognosis for patients with muscle invasive TCC. These results lead us to speculate that the use of a serine threonine kinase inhibitor may prove to be therapeutically beneficial for TCC patients undergoing concurrent chemotherapy for their disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4187. doi:10.1158/1538-7445.AM2011-4187

Background: One in seven men will be diagnosed with prostate cancer (PCa) during their lifetime and nearly 25% of those will die as a result of metastatic disease. Current diagnostic methods for PCa fail to predict which patients harbor occult metastases and although Epstein's criteria are useful in establishing relative risk, a significant number of patients diagnosed with “low risk” PCa develop metastasis. Clearly, there is a need for more accurate prognostic tools to determine which patients are at higher risk of suffering metastasis. We have previously demonstrated that tetraspanin CD151 plays a role in tumor cell motility and metastasis that is dependent upon an extracellular epitope recognized by the monoclonal antibody 1A5 (mAb 1A5). We surmised that this antibody might specifically recognize a pool of CD151 that is relevant for clinical metastasis. In this study, we evaluate the role of CD151 as detected by mAb 1A5 as a molecular prognostic factor for PCa disease progression and metastasis. Methods: Specimens from 99 patients who underwent radical prostatectomy (RP) between 1994-1998 with pathological pT2 and pT3 were assessed by immunohistochemistry using mAb 1A5 with a mean follow up of 12.1 years ± 1.6 SD. After deparaffinization, immunohistochemical analysis was carried out and protein expression was categorized as negative (score=0); or positive in weak (1), moderate (2) and strong (3). CD151 analysis was also performed in benign tissue around and away from the tumor as internal negative control. Additionally, 36 diagnostic biopsy specimens of patients who had documented metastasis during their follow up were assessed for CD151 immunoreactivity. A database of patient demographic factors, disease factors and relevant survival information was generated and correlated with disease-free progression and survival. Results: CD151 immunoreactivity was higher in malignant tissue than in either benign tissue around (p=0.01) or away from the tumor (p Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2260. doi:10.1158/1538-7445.AM2011-2260

Ganglioneuromas are rare benign tumors originating from the sympathetic nervous system and neural crest cells. A 4-year-old girl presented with numerous urinary tract infections. Ultrasound and computed tomography revealed a large mass within the right kidney. A right nephrectomy and sampling of surrounding lymph nodes were performed. Pathology confirmed that the mass was a mature ganglioneuroma. The patient remains disease-free, more than 2 years after surgery. We present this rare case of renal ganglioneuroma as well as a review of the literature.