Monday, December 29, 2014

Two Prostate Cancer Tests 'Not Clinically Useful,' Says National Institute for Health and Care Excellence (NICE) part 2

PHI Is Blood Serum Immunoassay
In contrast, the PHI is an in vitro diagnostic multivariate index assay that combines three blood serum PSA immunoassays — PSA, free PSA, and p2PSA — into a single calculation (p2PSA/free PSA) × √total PSA.
The test is simple and inexpensive and has performed better than conventional PSA and free PSA measures in several studies for predicting overall and high-grade prostate cancer.
For the current draft NICE guidance, researchers from the External Assessment Group conducted three systematic reviews of the evidence, identifying 6 studies that reported the analytical validity and 31 that reported the clinical validity of the tests. No studies that reported the clinical validity of the tests were identified.
In addition, the group conducted a systematic review of the existing economic analyses of the PCA3 and PHI tests. Because no published economic studies met the inclusion criteria, the group designed their own de novo economic model designed to assess the cost-effectiveness of the tests.
After reviewing the available evidence, the guidance committee considered whether more research into the two assays was advisable.

Noting that any potential improvements to the tests would be small, the guidance says: "If the potential benefits of using the PCA3 assay and the PHI were realised, they were unlikely to be sufficiently large to offset the costs of the test and make a substantial difference to the number of people having a second biopsy unnecessarily."

Two Prostate Cancer Tests 'Not Clinically Useful,' Says National Institute for Health and Care Excellence (NICE) part 1

Two tests designed to help identify prostate cancer in patients with negative or inconclusive results on prostate biopsy do not improve diagnosis enough to be recommended for clinical practice, says the United Kingdom (UK)'s healthcare watchdog.
In draft diagnostics guidance issued on December 17, the National Institute for Health and Care Excellence (NICE) recommends that the Progensa prostate cancer antigen 3 (PCA3) assay (Hologic GenProbe) and the Prostate Health Index (PHI) (Beckman Coulter) should not be used in the National Health Service in England.
PCA3 and PHI are both in vitro diagnostic tests for use in patients suspected of having prostate cancer who have negative or inconclusive findings on transrectal ultrasound prostate biopsy; these tests are used to determine the need for a second biopsy.
The appraisal was undertaken in the belief that the PCA3 or PHI may avoid second biopsies and associated complications by identifying patients unlikely to have a positive biopsy result and, thus, prostate cancer.
However, the draft guidance says that adding either of these tests to clinical assessment plus MRI is unlikely to improve diagnostic accuracy in clinical practice.
"Prostate biopsies are associated with discomfort and pain, as well as side effects including bleeding, problems with catheterization and possible infections," Carole Longson, PhD, NICE Health Technology Evaluation Centre director, commented in a statement.
"These tests would be of value if they were able to improve diagnostic certainty because it would reduce the number of prostate biopsies patients had to have, reducing patients' anxiety," she continued.
"However, the committee noted from the evidence that, although there were some improvements in diagnostic performance when PCA3 or PHI was added to clinical assessment alone, these improvements were very small."

PCA3 Test Performed on Urine Sample
The PCA3 assay is an in vitro nucleic acid amplification test for determining levels of PCA3 RNA in urine. The urine sample is obtained after digital rectal examination, which releases prostate cells and RNA into the urinary tract.
As reported by Medscape Medical News, the PCA3 assay was approved for use in Europe in 2006, and received US Food and Drug Administration approval in 2012, based on a study involving 495 men at 14 clinical sites that indicated the assay had a negative predictive value for prostate cancer of 90%.
A further study conducted in 233 men with persistently elevated serum prostate-specific antigen (PSA) levels and at least one previous negative biopsy result suggested that the PCA3 assay may help reduce the number of biopsies performed in men suspected of having prostate cancer. The assay performed significantly better than serum PSA in predicting prostate biopsy outcome.
Furthermore, an analysis of 1072 men from the REDUCE (REduction by DUasteride of prostate Cancer Events) study suggested that higher PCA3 scores not only predicted a positive biopsy result but was also associated with a higher biopsy Gleason score.

Further improvements in the ability of the PCA3 assay to identify men with prostate cancer have been reported when used in combination with the TMPRSS2:ERG gene fusion, and with a panel of biomarkers.

Abiraterone acetate

Abiraterone acetate (ZYTIGA®, Janssen) with prednisone/prednisolone after androgen deprivation therapy failure in asymptomatic or mildly symptomatic metastatic castration-resistant prostate cancer (mCRPC) significantly extends life compared with prednisone/prednisolone alone.1
Statistically significant new data from the final analysis of the COU-AA-302 trial including 4 years of follow-up1 were reported at the 2014 Annual Meeting of the European Society for Medical Oncology.

The findings, presented by Charles Ryan, MD, show an unmatched overall survival of 34.7 months with ZYTIGA® plus prednisone/prednisolone compared with 30.3 months for prednisone/prednisolone alone, providing an unrivalled 4.4 months extension of life. The pre-specified final analysis was performed after 96% of expected deaths had occurred.1

Friday, December 26, 2014

microbiology and immunology

http://www.mediafire.com/download/jv4bhfojfxojj0w/Rapid+Review+Microbiology+and+Immunology_nodrm_2.pdf

Saturday, October 18, 2014

US Centers for Disease Control and Prevention (CDC) Ebola outbreak

The risk of an Ebola outbreak in the United States is very low. Currently, the US Centers for Disease Control and Prevention (CDC) recommends avoiding travel to the affected countries in West Africa. Travel to other countries in Africa has not been restricted. In general, the risk among travelers of getting Ebola virus disease is very low unless they are spending time inside a hospital having direct contact with infected patients.
The CDC has been working closely with US Customs and Border Protection, airlines, and cargo ships to help ensure that the chance of Ebola virus being brought into the United States is very low. According to the CDC, the current outbreak does not pose a major risk to the United States. For the latest updates on the current Ebola virus disease outbreak, visit the CDC website below.
http://jama.jamanetwork.com/article.aspx?articleid=1915432

Saturday, October 11, 2014

Obesity and Long-Term Survival After Radical Prostatectomy



ABSTRACT


The Journal of Urology
Obesity and Long-Term Survival After Radical Prostatectomy
J Urol 2014 Oct 01;192(4)1100-1104, HJ Chalfin, SB Lee, BC Jeong, SJ Freedland, H Alai, Z Feng, BJ Trock, AW Partin, E Humphreys, PC Walsh, M Han

Who Really Benefits From Nephron-Sparing Surgery?

In the last 15 years, new information has fundamentally changed our approach to the management of renal masses. Previously, all renal masses, regardless of size, in the presence of a normal contralateral kidney were managed by radical nephrectomy (RN). The fundamental belief then was that this was akin to kidney donation for transplantation. Now we know that young, healthy, and carefully selected kidney donors sit in contradistinction to most sporadic renal tumor patients, who are 25 years older, and many of whom suffer from common medical comorbidities that affect renal function, including hypertension, diabetes, obesity, and cigarette smoking–induced vascular disease.1
The recent understanding that chronic kidney disease (CKD)—renal function below an estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73 m2 but above that of end-stage renal disease (<15 mL/min/1.73 m2)—is associated with cardiovascular morbidity and mortality2 has led to many studies evaluating whether nephrectomy for renal masses induces similar adverse renal functional and cardiovascular events. Although most studies, such as this one, are retrospective reviews of institutional or multi-institutional databases and are subject to all of the usual weaknesses of such studies, key observations have been consistently made. First, up to 30% of patients with renal tumors have preexisting CKD (stage 3 or worse), even if their serum creatinine is within normal limits. Second, partial nephrectomy (PN) effectively prevents or delays the onset of CKD and is associated with less cardiovascular morbidity and better overall survival.3-7
As demonstrated by Woldu and colleagues, within their pool of patients undergoing renal tumor surgery from 1992 to 2012, there is a range of presurgical renal function, yet the majority (80%) had eGFR >60 mL/min/1.73 m2 (CKD stage 1 and 2, considered "normal" by most nephrologists), and 20.1% had an eGFR <60 mL/min/1.73 m2 (CKD stage 3).The authors report that PN was associated with a significantly lower rate of annual eGFR decline in patients with a starting eGFR >60 mL/min/1.73 m2, but not in patients with a starting eGFR <60 mL/min/1.73 m2. The group at the greatest risk for developing "significant" renal impairment (defined as eGFR <45 mL/min/1.73 m2 or 30 mL/min/1.73 m2) was restricted to those with CKD stage 2 (eGFR between 60 and 89 mL/min/1.73 m2).
Certain factors in this dataset could influence these results. The study covers a 20-year period. Initially PN was used sparingly (18.8%); however, PN became the predominant procedure (53.6%) in the latter part of the study as the surgeons became more comfortable executing this complex operation. Many unaccounted for technical factors, including estimated blood loss, intraoperative hypotension, ischemia type (ie, warm, cold, or none), percentage of kidney preserved, and degree of surgical difficulty (nephrometry) could also influence these results. Notably, higher-stage tumors were treated with RN across the board. Assuming that these higher-stage tumors were larger, the possibility of contralateral renal compensation leading to a greater renal reserve and lesser impact of RN exists.
Despite the limitations implicit in this kind of surgical research, this study and others like it clearly indicate that kidney preservation for the management of renal masses is now front and center in contemporary urology. For healthy patients with excellent preexisting kidney function, the impact of PN on overall renal function may not be as great as in patients with moderate to severe preexisting renal impairment. All groups benefit from the equivalent local tumor control of PN to RN, with the added benefit of facing the low but real possibility of a contralateral tumor in their lifetime with much more than a solitary kidney. For elderly, comorbidly ill, and otherwise vulnerable patients with small renal masses, the other rational approach to kidney preservation is active surveillance, with only rare patients outliving their medical problems to experience significant renal cancer progression.8
References
  1. Russo P. The role of surgery in the management of early-stage renal cancer. Hematol Oncol Clin North Am2011;25(4):737-752.http://www.hemonc.theclinics.com/article/S0889-8588%2811%2900051-7/abstract
  2. Go AS, Chertow GM, Fan D, et al. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Eng J Med. 2004;351(13):1296-1305. http://www.nejm.org/doi/full/10.1056/NEJMoa041031
  3. Huang WC, Levey AS, Serio AM, et al. Chronic kidney disease after nephrectomy in patients with renal cortical tumors: a retrospective cohort study. Lancet Oncol. 2006;7(9):735-740.http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2806%2970803-8/abstract
  4. Thompson HR, Boorjian SA, Lohse CM, et al. Radical nephrectomy for pT1a renal masses may be associated with decreased overall survival compared to partial nephrectomy. J Urol. 2008;179(2):468-473.http://www.urosa.co.za/images/RadicalNephrectomyT1aRenalmassesOverall.pdf
  5. Huang WC, Elkin EB, Levey AS, et al. Partial nephrectomy versus radical nephrectomy in patients with small renal tumors–is there a difference in mortality and cardiovascular outcomes. J Urol. 2009;181(1):55-62.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2748741/
  6. Tan HJ, Norton EC, Ye Z, et al. Long-term survival following partial vs. radical nephrectomy among older patients with early-stage kidney cancer. JAMA. 2012;307(15):1629-1635. http://jama.jamanetwork.com/article.aspx?articleid=1148150
  7. Kim SP, Thompson H, Boorjian SA, et al. Comparative effectiveness for survival and renal function of partial and radical nephrectomy for localized renal tumors: A systematic review and meta-analysis. J Urol. 2012;188(1):51-57.http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0049517/
  8. Jewett MAS, Zuniga A. Renal tumor natural history: The rationale and role for active surveillance. Urol Clin North Am. 2008;35(4):627-634.http://www.urologic.theclinics.com/article/S0094-0143%2808%2900059-1/abstract


Urology
Who Really Benefits From Nephron-Sparing Surgery?
Urology 2014 Oct 01;84(4)860-868, SL Woldu, AC Weinberg, R Korets, R Ghandour, MR Danzig, A RoyChoudhury, SD Kalloo, MC Benson, GJ DeCastro, JM McKiernan

Kidney Preservation in the Management of Renal Masses

In the last 15 years, new information has fundamentally changed our approach to the management of renal masses. Previously, all renal masses, regardless of size, in the presence of a normal contralateral kidney were managed by radical nephrectomy (RN). The fundamental belief then was that this was akin to kidney donation for transplantation. Now we know that young, healthy, and carefully selected kidney donors sit in contradistinction to most sporadic renal tumor patients, who are 25 years older, and many of whom suffer from common medical comorbidities that affect renal function, including hypertension, diabetes, obesity, and cigarette smoking–induced vascular disease.1
The recent understanding that chronic kidney disease (CKD)—renal function below an estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73 m2 but above that of end-stage renal disease (<15 mL/min/1.73 m2)—is associated with cardiovascular morbidity and mortality2 has led to many studies evaluating whether nephrectomy for renal masses induces similar adverse renal functional and cardiovascular events. Although most studies, such as this one, are retrospective reviews of institutional or multi-institutional databases and are subject to all of the usual weaknesses of such studies, key observations have been consistently made. First, up to 30% of patients with renal tumors have preexisting CKD (stage 3 or worse), even if their serum creatinine is within normal limits. Second, partial nephrectomy (PN) effectively prevents or delays the onset of CKD and is associated with less cardiovascular morbidity and better overall survival.3-7
As demonstrated by Woldu and colleagues in an article recently published in Urology,8within their pool of patients undergoing renal tumor surgery from 1992 to 2012, there is a range of presurgical renal function, yet the majority (80%) had eGFR >60 mL/min/1.73 m2 (CKD stage 1 and 2, considered "normal" by most nephrologists), and 20.1% had an eGFR <60 mL/min/1.73 m2 (CKD stage 3).The authors report that PN was associated with a significantly lower rate of annual eGFR decline in patients with a starting eGFR >60 mL/min/1.73 m2, but not in patients with a starting eGFR <60 mL/min/1.73 m2. The group at the greatest risk for developing "significant" renal impairment (defined as eGFR <45 mL/min/1.73 m2 or 30 mL/min/1.73 m2) was restricted to those with CKD stage 2 (eGFR between 60 and 89 mL/min/1.73 m2).
Certain factors in this dataset could influence these results. The study covers a 20-year period. Initially PN was used sparingly (18.8%); however, PN became the predominant procedure (53.6%) in the latter part of the study as the surgeons became more comfortable executing this complex operation. Many unaccounted for technical factors, including estimated blood loss, intraoperative hypotension, ischemia type (ie, warm, cold, or none), percentage of kidney preserved, and degree of surgical difficulty (nephrometry) could also influence these results. Notably, higher-stage tumors were treated with RN across the board. Assuming that these higher-stage tumors were larger, the possibility of contralateral renal compensation leading to a greater renal reserve and lesser impact of RN exists.
Despite the limitations implicit in this kind of surgical research, this study and others like it clearly indicate that kidney preservation in the management of renal masses is now front and center in contemporary urology. For healthy patients with excellent preexisting kidney function, the impact of PN on overall renal function may not be as great as in patients with moderate to severe preexisting renal impairment. All groups benefit from the equivalent local tumor control of PN to RN, with the added benefit of facing the low but real possibility of a contralateral tumor in their lifetime with much more than a solitary kidney. For elderly, comorbidly ill, and otherwise vulnerable patients with small renal masses, the other rational approach to kidney preservation is active surveillance, with only rare patients outliving their medical problems to experience significant renal cancer progression.9

Clinical Relevance of AR-V7 in Castrate-Resistant Prostate Cancer

Androgen receptor splice variants (AR-Vs) have been described for a number of years, but their clinical relevance has been unclear until now. In an article recently published inThe New England Journal of Medicine,1 Antonarakis and colleagues demonstrated that patients with metastatic castrate-resistant prostate cancer (mCRPC) expressing AR-V7 in circulating tumor cells (CTCs) have a 0% response rate to newer androgen axis-targeting agents such as enzalutamide and abiraterone. This is an important observation that indicates that AR-V7 is a predictive biomarker for an important class of drugs.
AR-V7 lacks the C-terminal androgen receptor ligand–binding domain and functions as a constitutively active ligand-independent transcription factor. Simply stated, that means that AR-V7 is fully functional in terms of DNA binding and transcriptional activity despite a complete lack of testosterone and dihydrotestosterone binding. Enzalutamide and abiraterone can only block the androgen-signaling axis when the androgens initiate the signaling cascade. They are ineffective therapies in the presence of ligand-independent androgen receptor variants.
The assays were performed on CTCs derived from blood of men with advanced cancers. If there were no circulating CTCs, there was no assay to perform. Patients examined by these assays all had advanced cancer; all had mCRPC, and most had undergone multiple therapies when the assays were performed. Men with earlier-stage prostate cancer are less likely to have CTCs.
The number of patients treated was small, but the clinical relevance is clear. Abiraterone and enzalutamide are important new agents in the clinician’s armamentarium. Men with CTCs positive for AR-V7 do not respond to these agents; further, they progress rapidly and die quickly. There is much more to learn, but the implications of AR-V7 detection in CTCs are important in the management of advanced prostate cancer patients.

Venous Thromboembolism After Major Urologic Oncology Surgery: High Rate for Radical Cystectomy

http://www.practiceupdate.com/journalscan/13058

Article of the Week: Assessing prostate cancer brachytherapy using patient-reported outcomes

http://www.bjuinternational.com/article-of-the-week/using-patient-reported-outcomes-to-assess-and-improve-prostate-cancer-brachytherapy/

Patient-reported outcomes in prostate cancer brachytherapy

http://www.youtube.com/watch?v=UAjCiQqIxHg&list=UUInXkfY9yLXsBtYnJDQblTg

BJUI - BJU International

http://www.bjuinternational.com/

The 'Big Data' challenge

https://www.youtube.com/watch?v=5FbX1S2bZcU


Published on Jun 6, 2014
Amplify your content using video and maximise your impact.
For more information, read the June 2014 editorial at http://www.bjuinternational.com/?p=14248


Guideline of guidelines: prostate cancer screening

You have free access to this content

BJU InternationalVolume 114, Issue 3, Article first published online: 25 AUG 2014






http://onlinelibrary.wiley.com/doi/10.1111/bju.12854/pdf

Bracco gets FDA nod for ultrasound contrast agent

October 10, 2014 -- A third contestant has joined the U.S. market for ultrasound contrast agents: Bracco Diagnostics today received U.S. Food and Drug Administration (FDA) approval for its Lumason ultrasound contrast agent.
Known previously as SonoVue, Lumason (sulfur hexafluoride lipid microbubbles) is indicated for patients whose echocardiography images are hard to see with ultrasound, according to the FDA. The agency noted that three clinical trials involving 191 patients with suspected cardiac disease were used to establish Lumason's safety and efficacy

http://www.auntminnie.com/index.aspx?sec=sup&sub=ult&pag=dis&itemid=108760&wf=6196

Superb Micro-Vascular Imaging (SMI)

Toshiba's innovative Superb Micro-Vascular Imaging (SMI) technology expands the range of visible blood flow and provides visualization of low velocity microvascular flow never before seen with ultrasound.
SMI's level of vascular visualization, combined with high frame rates, advances diagnostic confidence when evaluating lesions, cysts and tumors, improving patient outcomes and experience.

http://medical.toshiba.com/products/ul/general/aplio-500/clinical-applications/advanced-applications.php?utm_source=Aunt+Minnie+UL+Community&utm_medium=Banner&utm_term=0814&utm_content=Banner&utm_campaign=SMI

Monday, September 22, 2014

PDF- An Update of the International Society of Sexual Medicine’s Guidelines for the Diagnosis and Treatment of Premature Ejaculation (PE)

PDF

http://onlinelibrary.wiley.com/doi/10.1002/sm2.28/pdf

An Update of the International Society of Sexual Medicine's Guidelines for the Diagnosis and Treatment of Premature Ejaculation (PE)

http://onlinelibrary.wiley.com/enhanced/doi/10.1002/sm2.28#Survey

Wednesday, September 17, 2014

Venous Thromboembolism After Urological Surgery

http://www.practiceupdate.com/journalscan/12330

Choosing Amongst the Available Therapies for mCRPC

http://prostatecancer.urologiconcology.org/Content/jplayer/jplayer-therapies.html#video0

Cabazitaxel Rechallenge at Prostate-Specific Antigen Relapse After Previous Cabazitaxel and Docetaxel Chemotherapy: Case Report

http://prostatecancer.urologiconcology.org/Content/PDFs/Perry-Cabazitaxel.pdf

Intracranial Meningeal Carcinomatosis in Metastatic Castration Resistant Prostate Cancer: Will Extension of Survival Increase the Incidence?

http://prostatecancer.urologiconcology.org/Content/PDFs/Gupta-Intracranial.pdf

Case Report: Responses to Cabazitaxel in Metastatic Castration-Resistant Prostate Cancer After Extensive Docetaxel Treatment

http://prostatecancer.urologiconcology.org/Content/PDFs/Guancial-Responses.pdf

A case report

http://prostatecancer.urologiconcology.org/Content/PDFs/Bilen-Prolonged.pdf

Individualized Decision-Making for Older Men With Prostate Cancer: Balancing Cancer Control With Treatment Consequences Across the Clinical Spectrum

http://prostatecancer.urologiconcology.org/Content/PDFs/Sajid-Individualized.pdf

Update on Metastatic Castration- Resistant Prostate Cancer An official center of the journal Urologic Oncology, an Elsevier publication

http://prostatecancer.urologiconcology.org/

Saturday, September 13, 2014

Urology Department Ain Shams University



Dear Doctor :

Greeting,

It is an honor to cooperate with the Department of Urology at the University of AinShams.

We very pleased to Invite You For actively participate in Prof.Rizwen workshop's entitled (Role Of BOTOX in Mangment of The Over Active Bladder).

WorkShop will be Thursday 16/9/2014 at 9 am ( Agenda Attached).

For Any Clarification Please Don't Hesitate to Contact Me.

Thanks,

Mark Micheal
Product Specialist
BOTOX
01226213831
Mark_micheal@neuro-team.net


ورشة عمل الثلاثاء
.docx
https://us-mg5.mail.yahoo.com/neo/launch?.rand=8f40fp6821upi#7875261223

Coming soon - Look out for the Abstracts from the NS-AUA Annual Meeting in Amelia Island, Florida*

http://nsaua.org/i4a/pages/index.cfm?pageid=3278


NSAUA Preliminary Program 2014 Amelia Island

http://issuu.com/auamarketing/docs/3567nsauapreliminaryprogram

Friday, September 5, 2014

Hypospadias GOALS

Hypospadias is defined by the three major anatomic defects:
(1) the abnormal location of the urethral meatus, 
(2) penile curvature, and 
(3) abnormalities of the foreskin.

The objective in treating patients with hypospadias is to
reconstruct a straight penis for normal coitus and place
the new urethral meatus on the terminal aspect of the glans
to allow a forward directed stream. 
There are five basic steps for a successful hypospadias outcome: 
(1) orthoplasty (straightening), 
(2) urethroplasty, 
(3) meatoplasty and glanuloplasty,
(4) scrotoplasty, and 
(5) skin coverage. 
These various elements of surgical technique can be applied either sequentially

or in various combinations to achieve a surgical success.

Wednesday, September 3, 2014

Laser Prostate Surgery

Holmium Laser Enucleation of the Prostate

http://www.camurology.org.uk/laser-prostate-surgery/

Incontinence Treatment

http://www.camurology.org.uk/incontinence-treatment/

Saturday, August 30, 2014

Analysis of Robot-Assisted Versus Laparoscopic Live Donor Nephrectomy

http://www.practiceupdate.com/ExpertOpinion/1128/1/3/?elsca1=emc_enews_expert-insight&elsca2=email&elsca3=practiceupdate_uro&elsca4=urology&elsca5=newsletter&rid=OTU1MjQ4MzA0MTgS1&lid=10332481

Efficacy and Safety of Local Steroids for Urethra Strictures

http://www.practiceupdate.com/journalscan/11948

Urologic Problems in Spina Bifida Patients Transitioning to Adult Care

http://www.practiceupdate.com/journalscan/11818

Approaches to Pediatric and Adolescent Varicocele

http://www.practiceupdate.com/journalscan/11817

MCRPC Featured Articles

http://prostatecancer.urologiconcology.org/

Individualized Decision-Making for Older Men With Prostate Cancer: Balancing Cancer Control With Treatment Consequences Across the Clinical Spectrum

http://prostatecancer.urologiconcology.org/Content/PDFs/Sajid-Individualized.pdf

Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: fi nal overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study

http://prostatecancer.urologiconcology.org/Content/PDFs/Fizazi-Abiraterone.pdf

A Wealth of New Options: A Case Presentation of the Management of Castration-Recurrent Prostate Cancer

http://prostatecancer.urologiconcology.org/Content/PDFs/Beach-Wealth.pdf

ORIGINAL ARTICLE Interleukin 6 downregulates p53 expression and activity by stimulating ribosome biogenesis: a new pathway connecting inflammation to cancer

http://www.nature.com/onc/journal/v33/n35/pdf/onc20141a.pdf


Chronic inflammation is an established risk factor for the onset of cancer, and the inflammatory cytokine IL-6 has a role in tumorigenesis by enhancing proliferation and hindering apoptosis. As factors stimulating proliferation also downregulate p53 expression by enhancing ribosome biogenesis, we hypothesized that IL-6 may cause similar changes in inflamed tissues, thus activating a mechanism that favors neoplastic transformation. Here, we showed that IL-6 downregulated the expression and activity of p53 in transformed and untransformed human cell lines. This was the consequence of IL-6-dependent stimulation of c-MYC mRNA translation, which was responsible for the upregulation of rRNA transcription. The enhanced rRNA transcription stimulated the MDM2-mediated proteasomal degradation of p53, by reducing the availability of ribosome proteins for MDM2 binding. The p53 downregulation induced the acquisition of cellular phenotypic changes characteristic of epithelial–mesenchymal transition, such as a reduced level of E-cadherin expression, increased cell invasiveness and a decreased response to cytotoxic stresses. We found that these changes also occurred in colon epithelial cells of patients with ulcerative colitis, a very representative example of chronic inflammation at high risk for tumor development. Histochemical and immunohistochemical analysis of colon biopsy samples showed an upregulation of ribosome biogenesis, a reduced expression of p53, together with a focal reduction or absence of E-cadherin expression in chronic colitis in comparison with normal mucosa samples. These changes disappeared after treatment with anti-inflammatory drugs. Taken together, the present results highlight a new mechanism that may link chronic inflammation to cancer, based on p53 downregulation, which is activated by the enhancement of rRNA transcription upon IL-6 exposure.

Friday, August 29, 2014

This CT was performed 2 days after resection of a bladder tumour. What does it show?












































































It shows extravasation of urine with a significant leak from the bladder extending posteriorly and intra-peritoneally

This is a CT scan with contrast in a middle-aged man with gross haematuria. Cystoscopy had shown no abnormality in the bladder. What does the CT show?
































































The left kidney is normal. Contrast medium in the right kidney outlines a large, irregular filling defect in the renal pelvis. Cytology showed malignant transitional cells and ureterorenoscopy confirmed a papillary, transitional cell tumour of the renal pelvis which was removed by nephroureterectomy (see macroscopic pathology below).




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