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Urology news 17 April 2014
Perioperative chemotherapy for muscle-invasive bladder cancer: A population-based outcomes study
Christopher M. Booth MD1,2,*, D. Robert Siemens MD2,3, Gavin Li MD1, Yingwei Peng PhD1,4, Ian F. Tannock MD, PhD5, Weidong Kong MD1, David M. Berman MD, PhD6 andWilliam J. Mackillop MB, ChB1,2,/14 APR 2014/DOI: 10.1002/cncr.28510
Division of Cancer Care and Epidemiology, Queen's University Cancer Research Institute,Department of Oncology, Queen's University, Kingston, Ontario, Canada,Department of Urology, Queen's University, Kingston, Ontario, Canad,Department of Public Health Sciences, Queen's University, Kingston, Ontario, Canad,Princess Margaret Hospital, Toronto, Ontario, Canada,Department of Pathology and Molecular Medicine, Queen's University, Kingston, Ontario, Canada
Practice guidelines recommend neoadjuvant chemotherapy (NACT) for bladder cancer. However, the evidence in support of adjuvant chemotherapy (ACT) is less robust. Here we describe whether the evidence of efficacy for NACT/ACT was sufficient to change clinical practice and whether the efficacy demonstrated in clinical trials was translated into effectiveness in the general population.
Electronic records of treatment were linked to the population-based Ontario Cancer Registry to identify all patients with bladder cancer treated with cystectomy in Ontario 1994-2008. Utilization of NACT/ACT was compared across 1994-1998, 1999-2003, and 2004-2008. Logistic regression was used to analyze factors associated with NACT/ACT. Cox model and propensity score analyses were used to explore the association between ACT and survival.
Two thousand forty-four patients underwent cystectomy for muscle-invasive bladder cancer (MIBC). Use of NACT remained stable (mean, 4%), whereas utilization of ACT increased over time (16%, 18%, 22%; P = .001). Advanced stage (T3/T4; OR, 1.83; 95% CI, 1.38-2.46) and node-positive disease (OR, 8.10; 95% CI, 6.20-10.7) were associated with greater utilization of ACT. Five-year overall survival (OS) and cancer-specific survival (CSS) for all patients was 29% (95% CI, 28%-31%) and 33% (95% CI, 31%-35%), respectively. Utilization of ACT was associated with improved OS (HR, 0.71; 95% CI, 0.62-0.81) and CSS (HR, 0.73; 95% CI, 0.64-0.84). Results were consistent in propensity score analyses.
NACT remains substantially underutilized in routine clinical practice. Our results suggest that perioperative chemotherapy is associated with a substantial survival benefit in the general population. Patients who are planning to undergo cystectomy for bladder cancer should be reviewed by a multidisciplinary team. Cancer 2013. © 2013 American Cancer Society.
10 Prognostic and predictive value of plasma testosterone levels in patients receiving first-line chemotherapy for metastatic castrate-resistant prostate cancer British Journal of Cancer, April 14, 2014
15 Effect of perioperative electroacupuncture as an adjunctive therapy on postoperative analgesia with tramadol and ketamine in prostatectomy: a randomised sham-controlled single-blind trial Acupuncture in Medicine, April 14, 2014
17 Blood type influences prostate cancer relapse, study shows, Prostate Cancer News,Healthcare Industry Today by EIN Newsdesk
18 Gene linked to pediatric kidney cancer suggests new strategies for kidney regeneration,Journal reference: Genes & Development
14 Apr 2014 MNT
20 Ejaculatory Problems Linked to BPH Drugs , Renal&Urology news
Urology news 13 April 2014
Penile traction therapy reduced curvature and significantly improved function and hardness. Penile traction therapy (PTT) is an effective treatment for the acute phase of Peyronie's disease (PD).
Juan Martínez-Salamanca, MD, PhD, of the Department of Urology at the Autonomous University of Madrid and colleagues studied 55 patients who underwent PTT, a novel penile extender device therapy, for 6 months for acute phase (AP) of Peyronie's. These patients were compared with 41 patients in the acute phase of Peyronie's disease who received no active treatment.
From baseline, mean curvature in patients treated with PTT had decreased from 33° to 15° at 6 months and 13° at 9 months, with a mean decrease of 20°. Erectile function and hardness improved significantly, and the proportion of patients unable to achieve penetration decreased from 62% to 20%.
The need for surgery was reduced in 40% of patients who would otherwise have been eligible, and the complexity of surgical procedures was further simplified in 1 out of 3 patients. PTT was associated with the removal of sonographic plaques in 48% of patients treated.The non-active treatment group had a significant increase in penile deformity, where function and hardness worsened and stretched flaccid penile length had decreased.“PTT seems an effective treatment for the AP of PD in terms of pain reduction, penile curvature decrease, and improvement in sexual function,” the authors concluded.
The Journal of Sexual Medicine (2014;11:506-515).
Case Report 13 April 2014
1Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Nehru Hospital, 4th Floor, F Block, Chandigarh 160012, India2Department of Urology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India3Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India4Department of Laboratory Medicine and Surgical Pathology, St. Michael’s Hospital, Room 2-101V, 30 Bond Street, Toronto, ON, Canada M5B 1W8/8 April 2014
A 63-year-old male, known to be hypothyroid for the past three years, on treatment with 100 μg of L-thyroxine presented to his primary care physician with history of 3 episodes of syncopal attacks 8 months back. He was a smoker with history suggestive of chronic bronchitis. He was also hypertensive for the last 4 years. His blood pressure was stable on 100 mg of losartan per day. Electrocardiogram and 24-hour holter revealed runs of ill sustained ventricular tachycardia and he was started on 100 mg of amiodarone per day 8 months back.
He had history of prostatism since 2008 and was on tamsulosin 0.4 mg once daily. He had some relief, but in 2010 there was recurrence of symptoms. His ultrasound revealed enlarged prostate of size 5.2 × 4.8 × 5.4 cm with a residual urine volume of 75 mL. The serum prostate specific antigen (PSA) was found to be elevated (152 ng/mL, normal <5). MRI of prostate reconfirmed the same and showed ill-defined low intensity signal in peripheral zone of prostate and adjacent portion of bilateral seminal vesicles suggestive of stage III disease .
Biopsy showed adenocarcinoma of the prostate (Gleason’s Grade 3 + 3). Bone scan was normal and he had normal serum electrolyte at that time. The patient was started on goserelin acetate (Zoladex 10.8 mg) once every three monthly as he refused orchidectomy. The PSA level decreased to 6 ng/mL in mid-2012. In May 2013, he was hospitalized elsewhere with acute urinary retention requiring catheterization followed by hematuria. His sonogram of the prostate showed the same findings and PSA was 23.16 ng/mL at this juncture. He was subjected to bilateral orchidectomy, cystoscopy, and transurethral prostate resection .
Two months later he presented with generalized tiredness and disorientation. His hemoglobin was 8.8 gm/dL, urea 20 mg/dL, creatinine 0.8 mg/dL, sodium 124 mmol/L, potassium 3.9 mmol/L, uric acid 2.2 mg/dL, protein 5.4 g/dL, and serum albumin 3.6 g/dL. His liver function test was normal. He was started on fluid restriction, 10–15 gms of added salt per day, and tolvaptan 60 mg per day without much improvement in his symptoms. This time he was admitted to our hospital for further evaluation and treatment.
On evaluation, his hemoglobin was 8.6 mg/dL, and he had normal renal function, sodium 109 mmol/L, serum cortisol 738 nmol/L (N: 350–540), T3 1.2 ng/mL (N: 0.8–2.0), T4 10.2 μg/dL (N: 4.8–12.7), TSH 4.64 mIU/mL (N: 0.27–4.2), plasma osmolality 242 mOsm/kg (N: 275–295), urine osmolality 504 mOsm/kg (N: 50–1200), and spot urine sodium 105 mmol/L (N > 20). Follow-up bone scan revealed increased osteoblastic activity in right fifth rib suggestive of metastatic process. Fluorodeoxyglucose-positron emission tomography (FDG PET) showed avid lesions in the prostate, pelvic bones, abdominal lymph nodes, left transverse abdominal muscles, and liver. Tolvaptan was continued and patient was advised liberal oral salt (15 gms/day) and to restrict his fluid intake.
Hyponatremia persisted despite these measures. It was thought to be because of SIADH due to ectopically secreted vasopressin from prostatic malignancy, which was negated by immunohistochemistry. A literature review at this juncture made us suspect the possibility of amiodarone induced hyponatremia. Amiodarone was stopped and on the third day of the discontinuation of the drug, serum sodium improved to 122 mmol/L. Metoprolol was introduced replacing amiodarone; however, patient succumbed to refractory ventricular tachycardia in the next five days. Autopsy could not be performed.
Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is one of the most common causes of hyponatremia. The usual causes are malignancies, central nervous system, pulmonary disorders, and drugs.
Amiodarone is a broad spectrum antiarrhythmic agent widely used in the management of arrhythmias. The different side effects include thyroid dysfunction, visual disturbances, pulmonary infiltrates, ataxia, cardiac conduction abnormalities, drug interactions, corneal microdeposits, skin rashes, and gastrointestinal disturbances. SIADH is a rare but lethal side effect of amiodarone.
Case Reports in Urology
Volume 2014 (2014), Article ID 136984, 6 pages
Urology news 13 April 2014
Anthony E Rizzardi12, Nikolaus K Rosener2, Joseph S Koopmeiners34, Rachel Isaksson Vogel3, Gregory J Metzger5, Colleen L Forster6, Lauren O Marston2, Jessica R Tiffany2, James B McCarthy2, Eva A Turley78, Christopher A Warlick9, Jonathan C Henriksen126 and Stephen C Schmechel126*
1 Department of Pathology, University of Washington, Mailcode 359791, 908 Jefferson St, Seattle, WA 98104, USA 2 Department of Laboratory Medicine and Pathology and Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA 3 Biostatistics and Bioinformatics Core, Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA 4 Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, USA 5 Department of Radiology, University of Minnesota, Minneapolis, MN, USA 6 BioNet, Academic Health Center, University of Minnesota, Minneapolis, MN, USA 7 Department of Biochemistry, London Health Sciences Center, University of Western Ontario, London, Ontario, Canada 8 Department of Oncology, London Health Sciences Center, University of Western Ontario, London, Ontario, Canada 9 Department of Urology, University of Minnesota, Minneapolis, MN, USA
BMC Cancer 2014, 14:244 doi:10.1186/1471-2407-14-244
Background ---Prognostic multibiomarker signatures in prostate cancer (PCa) may improve patient management and provide a bridge for developing novel therapeutics and imaging methods. Our objective was to evaluate the association between expression of 33 candidate protein biomarkers and time to biochemical failure (BF) after prostatectomy.
Methods ---PCa tissue microarrays were constructed representing 160 patients for whom clinicopathologic features and follow-up data after surgery were available. Immunohistochemistry for each of 33 proteins was quantified using automated digital pathology techniques. Relationships between clinicopathologic features, staining intensity, and time to BF were assessed. Predictive modeling using multiple imputed datasets was performed to identify the top biomarker candidates.
Results ---In univariate analyses, lymph node positivity, surgical margin positivity, non-localized tumor, age at prostatectomy, and biomarkers CCND1, HMMR, IGF1, MKI67, SIAH2, and SMAD4 in malignant epithelium were significantly associated with time to BF. HMMR, IGF1, and SMAD4 remained significantly associated with BF after adjusting for clinicopathologic features while additional associations were observed for HOXC6 and MAP4K4 following adjustment. In multibiomarker predictive models, 3 proteins including HMMR, SIAH2, and SMAD4 were consistently represented among the top 2, 3, 4, and 5 most predictive biomarkers, and a signature comprised of these proteins best predicted BF at 3 and 5 years.
Conclusions ---This study provides rationale for investigation of HMMR, HOXC6, IGF1, MAP4K4, SIAH2, and SMAD4 as biomarkers of PCa aggressiveness in larger cohorts.
News 13 April 2014
A University of Colorado Cancer Center study recently published in the journal Cell Reports and presented today at the American Association for Cancer Research (AACR) Annual Conference 2014 shows that the cellular process of autophagy in which cells "eat" parts of themselves in times of stress may allow cancer cells to recover and divide rather than die when faced with chemotherapies.
Autophagy, from the Greek "to eat oneself," is a process of cellular recycling in which cell organelles called autophagosomes encapsulate extra or dangerous material and transport it to the cell's lysosomes for disposable. Like tearing apart a Lego kit, autophagy breaks down unneeded cellular components into building blocks of energy or proteins for use in surviving times of low energy or staying safe from poisons and pathogens (among other uses).
"What we showed is that if this mechanism doesn't work right, for example if autophagy is too high or if the target regulated by autophagy isn't around, cancer cells may be able to rescue themselves from death caused by chemotherapies," says Andrew Thorburn, PhD, deputy director of the CU Cancer Center.
A movie that accompanies the study online shows a cancer cell dying. In the first few frames, mitochondrial cell walls break down and the cell's mitochondria can be seen releasing proteins in a process abbreviated as MOMP, which is considered a common marker of cell death. But then high autophagy allows the cell to encapsulate and "digest" these released proteins before MOMP can keep the cell well and truly dead. Later in the movie, the cancer cell recovers and goes on to divide.
"The implication here is that if you inhibit autophagy you'd make this less likely to happen, i.e. when you kill cancer cells they would stay dead," Thorburn says.
Thorburn and colleagues including postdoctoral researcher Jacob Gump, PhD, show that autophagy depends on the target PUMA to regulate cell death. Specifically, when PUMA is absent, it doesn't matter if autophagy is inhibited because without the communicating action of PUMA, cancer cells continue to survive.
The finding has important implications. First, it demonstrates a mechanism whereby autophagy controls cell death. And second, the study further reinforces the clinical potential of inhibiting autophagy to sensitize cancer cells to chemotherapy.
"Autophagy is complex and as yet not fully understood," Thorburn says. "But now that we see a molecular mechanism whereby cell-fate can be determined by autophagy, we hope to discover patient populations that could benefit from drugs that inhibit this action."
Source: University of Colorado Denver/ April 6, 2014
Urology news 13 April 2014
Arno Therapeutics enrolls first patient in a Phase I/II trial evaluating onapristone in men with advance CRPC
Arno Therapeutics, Inc., a clinical stage biopharmaceutical company focused on the development of oncology therapeutics, has announced that it has enrolled the first patient in a Phase I/II trial (NCT02049190) evaluating its lead compound onapristone in men with advanced castration-resistant prostate cancer (CRPC) after failure of abiraterone or enzalutamide. Patient enrollment of this study follows approval of an Investigational Medicinal Product Dossier from the United Kingdom (UK) Health Authority, Medicines and Healthcare products Regulatory Agency, ethics committee authorization and subsequent site authorization.
Glenn Mattes, President and Chief Executive Officer of Arno Therapeutics, remarked, "Globally, prostate cancer is the second most common cancer in men, and the fifth leading cause of death from cancer in men, with an estimated 1.1 million new cases diagnosed and 307,000 deaths during 2012 alone, according to the International Agency for Research on Cancer. These numbers are staggering, and our ultimate goal is to evaluate onapristone in the subset of advanced CRPC patients who are more likely to respond to this personalized treatment, for which there is an immense unmet medical need. The trial marks Arno's second Phase I study actively enrolling this year and we are excited by the momentum generated thus far."
Onapristone is an oral, anti-progestin hormone blocker that has been shown in previous Phase II clinical trials to exhibit anti-tumor activity in patients with breast cancer. In pre-clinical testing, onapristone has been shown to block the activation of the progesterone receptor (PR), which is believed to be a mechanism that inhibits the growth of APR-driven breast, endometrial and other tumors. Tests for the activated form of the progesterone receptor (APR) have the potential to function as a biomarker of anti-progestin activity, as detected by a companion diagnostic under development.
The randomized, open-label trial is currently enrolling patients and is designed to evaluate the safety and anti-cancer activity of onapristone in the select patient population. This single-site trial is taking place at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust in the UK and additional UK sites are planned. The study is expected to enroll a total of 60 patients. Arno has engaged Biotrial, a drug evaluation and pharmacology research company, as its contract research organization for this trial.
Professor Johann de Bono, MD, PhD, MSc, FRCP, Professor of Experimental Cancer Medicine at The Institute of Cancer Research (ICR) and Honorary Consultant in Medical Oncology at The Royal Marsden, and an investigator for the trial, said, "Advanced prostate cancer remains a difficult disease to treat due to the development of various resistance mechanisms. We are very interested in developing new personalized therapies to improve treatment outcomes for these patients. Through Arno Therapeutics' early trial in advanced castration-resistant prostate cancer, we hope to gain a deeper understanding of the safety profile and potential anti-cancer activity of onapristone with the goal of accelerating the development of the APR biomarker and this targeted anti-progestin."
Onapristone is also being developed for other indications including breast and endometrial cancers. The potential treatment is concurrently being evaluated in a Phase I clinical trial in France in women who have progesterone receptor expressing tumors. This targeted therapy has the potential to be the first approved anti-progestin for oncology indications and provide chemotherapy-sparing treatment to cancer patients who express a specific biomarker.
The Phase I/II study will evaluate onapristone in extended-release tablet formulations in up to five dose levels (10-50 mg BID) in patients with advanced CRPC in which PR may be contributing to tumor progression. Study subjects will be evaluated for whether their tumors express APR, which may help identify patients who are more likely to respond to onapristone. A second cohort of patients will be included at the recommended Phase II dose to gain additional understanding of the onapristone safety profile and potential anti-cancer activity.
Alex Zukiwski, MD, Chief Medical Officer of Arno Therapeutics, commented, "Tolerance to chemotherapy and various targeted therapies is known to be different in males undergoing androgen deprivation treatment. While the percentage of castration-resistant prostate cancer that is APR positive remains to be determined, the initial series of preclinical tumor specimens we examined has demonstrated evidence of APR, and we are looking forward to evaluating the safety and anti-cancer activity of onapristone in this patient population."
Apr. 7, 2014 — Each year prostate tissue samples are taken from over a million men around the world -- in most cases using 12 large biopsy needles -- to check whether they have prostate cancer.
Apr. 7, 2014 — Men circumcised after the age of 35 were 45% less at risk of later developing prostate cancer than uncircumcised men. Prostate cancer is rare amongst Jewish or Muslim men,
Apr. 6, 2014 — Men with prostate cancer that is small and confined to the prostate gland but that is at risk of growing and spreading, do better if they are treated with radiotherapy combined with androgen ...
Apr. 6, 2014 — A novel method to 'manipulate the lipid metabolism in the cancer cell to trick them to use more radiolabeled glucose, the basis of PET scanning' is being described by researchers. The ...
Apr. 4, 2014 — A new genetic “signature” to identify prostate cancer patients who are at high risk of their cancer recurring after surgery or radiotherapy has been ...
Apr. 4, 2014 — The use of permanent brachytherapy, a procedure where radioactive sources are placed nside
Apr. 3, 2014 — Results from laboratory experiments carried out by a team of molecular biologists have identified a strategy for overcoming resistance to a new therapeutic opportunity for prostate cancer patients ...
Apr. 1, 2014 — Among men undergoing radiation therapy for prostate cancer, daily use of the erectile dysfunction drug tadalafil, compared with placebo, did not prevent loss of erectile function, according to a ..