tag:blogger.com,1999:blog-47307825865483000342024-03-16T03:33:54.236-04:00Brady Urology at Johns Hopkins HospitalThe Brady is among the premier Urological Institutes in the world. The Johns Hopkins Hospital and The Brady have been ranked one of the top hospitals and Urology Departments in America by U.S. News & World Report. We write here to share the newest, exciting news in urology and from The Brady Urological Institute and Department of Urology at Johns Hopkins Hospital. Anonymoushttp://www.blogger.com/profile/05286847723206340868noreply@blogger.comBlogger207125tag:blogger.com,1999:blog-4730782586548300034.post-36900746078959240102015-09-14T09:00:00.000-04:002015-09-14T09:00:04.317-04:00Blue Light Cystoscopy for Bladder CancerBladder cancer is the fourth leading cause of cancer death in males and the most common site of cancer in the urinary system. An estimated 74,000 new cases of bladder cancer are expected to be diagnosed in the USA in 2015 and 16,000 deaths are estimated[1]. Non-muscle-invasive bladder cancer (NMIBC) has a high rate of recurrence and also a risk of progression that requires patients to undergo regular monitoring with cystoscopy after transurethral resection of the bladder tumor (TURBT). Current standard of care uses <strong>white-light cystoscopy (WLC)</strong> to map and resect all visible tumors. This blog will give an overview of the use of fluorescent cystoscopy in the management of NMIBC and review the evidence for its use.<br />
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<h2>
Product Overview</h2>
<strong>Blue-light cystoscopy (BLC),</strong> also referred to as fluorescent cystoscopy or photodynamic diagnosis (PDD), is a procedure in which a photosensitizer medication is instilled in the bladder prior to cystoscopy. This photosensitizer is part of the heme biosynthesis pathway (that makes red blood cells) and causes an accumulation of photoactive porphyrins in neoplastic cells. These porphyrins preferentially accumulate in neoplastic cells due to the increased metabolic activity in these cells. When excited with blue-light in the 360-450 nm wavelength, the porphyrins emit a red light that can easily be seen during cystoscopy (Figure 1). There are two main photosensitizers that have been used in studies looking at fluorescent cystoscopy: 5-aminolevulinic acid (5-ALA) and <strong>hexaminolevulinate (HAL).</strong> HAL is the only photosensitizer that has been approved for use in the USA and Europe. In the USA it is marketed under the brand name <em>Cysview</em>, and in Europe under the brand name <em>Hexvix</em>.<br />
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgrd5_IH00XBCfhar2lPsP7wQN0FT8y5RTZezTIJToeMoeWoBTzcUUPMb2PTKUYJO6InxeXZvZ_MEf9AJzZv9QIuBlDqKNbf7GZX20lc9vc1x_5bzsfJmfANXEKw9gU6WP4cVh53zkjPkQ/s1600/CYSVIEW1.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" height="318" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgrd5_IH00XBCfhar2lPsP7wQN0FT8y5RTZezTIJToeMoeWoBTzcUUPMb2PTKUYJO6InxeXZvZ_MEf9AJzZv9QIuBlDqKNbf7GZX20lc9vc1x_5bzsfJmfANXEKw9gU6WP4cVh53zkjPkQ/s400/CYSVIEW1.jpg" width="400" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Figure 1. 63 year old female with prior TURBT+BCG now with recurrence. (a) WLC of a prior resection site near a ureteral orifice. (b) Same site using BLC. Tumor was found to be high grade T1. (c) WLC showing an area of CIS that was missed upon repeat resection. (d) Same site using BLC. <br />
From: Daneshmand, et al.[2]</td></tr>
</tbody></table>
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<h2>
Increased Tumor Detection</h2>
Most studies are in agreement that more tumors are found when using BLC compared to WLC alone. Perhaps the best evidence for this is a meta-analysis published in 2013 which looked at the raw data from 6 prospective studies including a total of over 800 patients[3]. This meta-analysis found that a significant proportion of tumors were missed by WLC alone. In fact, an additional 14.7% of Ta tumors were detected with BLC, 10.8% of T1 tumors, and 40.8% of CIS (carcinoma in situ or flat tumors) (Figure 2). Another meta-analysis by Shen et al4. failed to show a statistically significant difference in tumor detection rates between BLC and WLC, however this study was limited by the inclusion of a large number of studies which used the photosensitizer 5-ALA, which is not FDA approved and has been shown to have less fluorescent properties than HAL.<br />
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjChrM7YOOBcyRjnvdQYbDnWRALlxFi7p1lCgV9Ov4OEuElR3J1nFLR0qcKrPfXwPUdXm23e3Tfu-u5-l7bzTYkg4T2Auqd3ldX-89zYv09yIweDftS1a7jgqUVNLWgmPCl9_VjRyfFcWE/s1600/CYSVIEW2.png" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" height="130" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjChrM7YOOBcyRjnvdQYbDnWRALlxFi7p1lCgV9Ov4OEuElR3J1nFLR0qcKrPfXwPUdXm23e3Tfu-u5-l7bzTYkg4T2Auqd3ldX-89zYv09yIweDftS1a7jgqUVNLWgmPCl9_VjRyfFcWE/s400/CYSVIEW2.png" width="400" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Figure 2. Increased detection of tumors using BLC alone when compared to WLC alone. <br />
From: Burger, et al.[3]</td></tr>
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<h2>
Recurrence Free Survival</h2>
While the data on increased detection are consistent, data on recurrence-free survival (RFS) are less clear-cut. Cysview gained FDA approval following a study by Stenzl et al5. published in 2010. This study was a prospective, randomized, multi-center study that looked at 551 patients with suspected Ta or T1 disease and were randomized to either WLC or WLC+BLC. During the 9-month surveillance period, 47% of patients in the BLC group and 56% of patients in the WLC group had tumor recurrences for a relative reduction of 16%. Interestingly, the following year Stenzl published another paper which randomized patients to either 5-ALA or placebo which failed to show a difference in recurrence-free survival 12 months after tumor resection6. However, as previously mentioned, this study used 5-ALA which is not the FDA approved photosensitizer.<br />
<br />
The study with the longest follow-up data is actually an extension to the original Stenzl study used for FDA approval. This study was published in 2012 by Grossman et al7. and showed that with a median follow-up for 53.0 months (WLC group) and 55.1 months (BLC group), 38% of the patients in the BLC group remained tumor free vs. 31.8% in the WLC group. The median time to recurrence was 16.4 months in the BLC group and 9.4 months in the WLC group. This study also looked at progression-free survival and cystectomy rates but was unable to show a statistical difference between the two groups, possibly due to the original study not being powered to look at differences in these outcomes.<br />
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Figure 3 summarizes additional studies that have looked at recurrence-free survival for BLC vs. WLC.<br />
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgRWfCTNQjdQ3PspNTRyyoG3JxZJrb6mslXDdywca6BO1Yzy0Ps66ZVn7fFDWup5ieLXKZzoThkC-R83V-MkYmllrE2FzEzHl439kZP5HJVOOOSB5h8s28QM4G7iNi1HpvmMzWny77wFvw/s1600/CYSVIEW3.png" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" height="187" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgRWfCTNQjdQ3PspNTRyyoG3JxZJrb6mslXDdywca6BO1Yzy0Ps66ZVn7fFDWup5ieLXKZzoThkC-R83V-MkYmllrE2FzEzHl439kZP5HJVOOOSB5h8s28QM4G7iNi1HpvmMzWny77wFvw/s400/CYSVIEW3.png" width="400" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Figure 3. Summary of studies that have looked at recurrence-free survival for BLC vs. WLC.</td></tr>
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<h2>
<br />Cost</h2>
Bladder cancer is one of the mostly costly cancers to treat on a per capita basis. Lifetime per capita costs have been estimated between $96,000 and $187,000 (2001 US dollars)8. Multiple analyses have looked at whether using BLC could reduce cost for bladder cancer treatments using the assumption that if a patient has a longer recurrence-free survival, they may require fewer or perhaps less frequent TURBTs. Garfield et al9. used a probabilistic decision-tree model and estimated that over 5 years, approximately $4,600 could be saved per patient by using BLC during diagnostic cystoscopy (excluding the cost of the equipment).<br />
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<h2>
Indications</h2>
The current AUA guidelines for bladder cancer were written in 2007, 3 years before Cysview was approved for use in the USA and therefore do not have an official recommendation for the use of fluorescent cystoscopy in the management of NMIBC. The NCCN guidelines acknowledge that BLC has been shown to decrease recurrence in NMIBC but has not been shown to reduce progression. They suggest that “BLC may have the greatest advantage in detecting difficult-to-visualize tumors (eg, CIS tumors)” and “the limitations of BLC require judicious application of this additional diagnostic tool”10.<br />
<br />
In 2013, an expert focus group convened in San Diego to create a consensus statement for appropriate use of BLC in the USA2. Based on the evidence reviewed, they recommend that BLC should be considered:<br />
- At initial TURBT on suspicion of NMIBC<br />
- In patients with positive urine cytology but negative WLC findings<br />
- In patients with intermediate-risk NMIBC<br />
- For assessment of disease recurrence<br />
<br />
These recommendations are similar to consensus statements and guidelines from Europe.<br />
<br />
<h2>
Summary</h2>
Blue-light cystoscopy has been shown to increase detection of NMIBC during TURBT. Whether this increased detection leads to a difference in recurrence or progression is less clear. Most studies to date, especially those with longer follow-up times, have shown a decrease in recurrence in patients who undergo TURBT with BLC. No study to date has shown a difference in progression. It is likely that to show a statistically significant difference in progression, larger studies with longer follow-up will need to be conducted.<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgCE61I6R9PB76STLqbhXHR5hM8MXZrVC5VOx-XIFwtoU_UO8E2kmKunzJAK-7HdvbYf0bMh-Nhsp1N17eRNjQ9WVCK_MfjBg-p3Y7bfFch23hUaUY9tl63pK06zkNUasW13B1ZrZh45TI/s1600/Curtiss_Kevin.jpg" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" height="200" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgCE61I6R9PB76STLqbhXHR5hM8MXZrVC5VOx-XIFwtoU_UO8E2kmKunzJAK-7HdvbYf0bMh-Nhsp1N17eRNjQ9WVCK_MfjBg-p3Y7bfFch23hUaUY9tl63pK06zkNUasW13B1ZrZh45TI/s200/Curtiss_Kevin.jpg" width="142" /></a></div>
<em>This blog was written by <strong>Kevin Curtiss</strong>, a medical student at Johns Hopkins School of Medicine. Kevin recently finished a four-week sub-internship at the Brady Urological Institute and gave a presentation to the department on "Blue Light Cystoscopy" from which this blog is inspired. Kevin is looking forward to a career in urology.</em><br />
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REFERENCES<br />
<span style="font-size: x-small;">1. Cancer of the Urinary Bladder - SEER Stat Fact Sheets. http://seer.cancer.gov/statfacts/html/urinb.html. Accessed September 2, 2015.<br />2. Daneshmand S, Schuckman AK, Bochner BH, et al. Hexaminolevulinate blue-light cystoscopy in non-muscle-invasive bladder cancer: review of the clinical evidence and consensus statement on appropriate use in the USA. Nat Rev Urol. 2014;11(10):589-596. doi:10.1038/nrurol.2014.245.<br />3. Burger M, Grossman HB, Droller M, et al. Photodynamic diagnosis of non-muscle-invasive bladder cancer with hexaminolevulinate cystoscopy: a meta-analysis of detection and recurrence based on raw data. Eur Urol. 2013;64(5):846-854. doi:10.1016/j.eururo.2013.03.059.<br />4. Shen P, Yang J, Wei W, et al. Effects of fluorescent light-guided transurethral resection on non-muscle-invasive bladder cancer: a systematic review and meta-analysis. BJU Int. 2012;110(6 Pt B):E209-E215. doi:10.1111/j.1464-410X.2011.10892.x.<br />5. Stenzl A, Burger M, Fradet Y, et al. Hexaminolevulinate guided fluorescence cystoscopy reduces recurrence in patients with nonmuscle invasive bladder cancer. J Urol. 2010;184(5):1907-1913. doi:10.1016/j.juro.2010.06.148.</span><br />
<span style="font-size: x-small;">6. Stenzl A, Penkoff H, Dajc-Sommerer E, et al. Detection and clinical outcome of urinary bladder cancer with 5-aminolevulinic acid-induced fluorescence cystoscopy : A multicenter randomized, double-blind, placebo-controlled trial. Cancer. 2011;117(5):938-947. doi:10.1002/cncr.25523.<br />7. Grossman HB, Stenzl A, Fradet Y, et al. Long-term decrease in bladder cancer recurrence with hexaminolevulinate enabled fluorescence cystoscopy. J Urol. 2012;188(1):58-62. doi:10.1016/j.juro.2012.03.007.<br />8. Botteman MF, Pashos CL, Redaelli A, Laskin B, Hauser R. The health economics of bladder cancer: a comprehensive review of the published literature. Pharmacoeconomics. 2003;21(18):1315-1330. http://www.ncbi.nlm.nih.gov/pubmed/14750899. Accessed September 2, 2015.<br />9. Garfield SS, Gavaghan MB, Armstrong SO, Jones JS. The cost-effectiveness of blue light cystoscopy in bladder cancer detection: United States projections based on clinical data showing 4.5 years of follow up after a single hexaminolevulinate hydrochloride instillation. Can J Urol. 2013;20(2):6682-6689. http://www.ncbi.nlm.nih.gov/pubmed/23587507. Accessed September 2, 2015.</span><br />
<span style="font-size: x-small;">10. NCCN Clinical Practice Guidelines in Oncology: Bladder Cancer. 2015;http://www. http://www.nccn.org/professionals/physician_gls/PDF/bladder.pdf. Accessed September 2, 2015. </span><br />
<br />Anonymoushttp://www.blogger.com/profile/05286847723206340868noreply@blogger.com96tag:blogger.com,1999:blog-4730782586548300034.post-28573461006072298072015-09-02T09:01:00.000-04:002015-09-02T09:01:00.143-04:00The Surgical Management of Large Prostatic Adenoma<h2>
<b><span style="font-family: "Arial",sans-serif;">Introduction</span></b></h2>
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<span style="font-family: "Arial",sans-serif;">Benign
prostatic hyperplasia (BPH) is a prevalent disease, affecting 22% of men <
60 years old, and 45% of men 70-80 years old [1]. When BPH symptoms are
refractory to medical management, surgical intervention is recommended. Optimal
surgical management for large prostatic adenoma, defined as prostate mass >
100 g or volume > 80 cc, is controversial. While open simple prostatectomy
(OSP) remains the gold-standard surgical management for severe BPH, the
procedure is associated with significant morbidity, encouraging the use of
other surgical options. This blog will discuss the surgical management of large
prostatic adenoma, with emphasis on several alternatives to OSP, including bipolar
TURP, holmium laser therapy, photoselective vaporization of the prostate (PVP),
and robot assisted laparoscopic simple prostatectomy (RASP).<o:p></o:p></span></div>
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<h2>
<b><span style="font-family: "Arial",sans-serif;">Open Simple Prostatectomy (OSP)</span></b></h2>
<br />
OSP is the gold standard surgical management for high volume (> 80 cc) prostatic adenoma. Advantages of this approach include more complete removal of prostatic adenoma under direct visualization, lower re-treatment rates, and no risk of TUR syndrome. A randomized controlled trial comparing transvesical open simple prostatectomy (TVP) with TURP for prostates > 80 cc demonstrated significant reduction in IPSS scores at 12 months post-op for the TVP group. Unfortunately, the peri-operative blood transfusion rate was 11% and 14% for the TVP and TURP arms, respectively (Figure 1) [2]. This morbidity associated with OSP has encouraged urologists to seek other alternatives for the management of large prostatic adenoma.<br />
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgkCEXuAW4ZUGDEwZSq702nhbb9UZrqniKvtCqDF04FF0zl5g4sDE3IgzZMqmLSyrH4pVSVeylpe7HaFiRnD42JsVXkhYc3p73eQ6KOnNIUf9720luj9Wv6FoSyJqc7kD6FLU-13evl0mo/s1600/Picture1.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" height="141" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgkCEXuAW4ZUGDEwZSq702nhbb9UZrqniKvtCqDF04FF0zl5g4sDE3IgzZMqmLSyrH4pVSVeylpe7HaFiRnD42JsVXkhYc3p73eQ6KOnNIUf9720luj9Wv6FoSyJqc7kD6FLU-13evl0mo/s400/Picture1.jpg" width="400" /></a></td></tr>
<tr><td class="tr-caption"><b>Figure 1: </b>Complications for both TURP (n= 35) and Transvesical Open <br />
Simple Prostatectomy (TVP) (n = 34). Ou et al. Urology 2010.<br />
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<h2>
<b><span style="font-family: "Arial",sans-serif;">TURP</span></b></h2>
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<span style="font-family: "Arial",sans-serif;">Monopolar TURP
has been the gold standard surgical management for prostates 30-80 mL, but
concerns regarding TUR syndrome and excessive bleeding prevent its routine use
in larger prostatic adenoma. For this reason, many studies have focused on
Bipolar TURP, which enables the use of normal saline irrigation with no risk of
TUR syndrome. In a recent prospective, randomized trial comparing Bipolar TURP
vs. OSP for prostates > 80 cc, Bipolar TURP was found to resect
significantly less prostatic adenoma mass despite having similar pre-operative
prostate size to the OSP arm. However, a significantly less hemoglobin drop,
blood transfusion rate, and hospital stay was found in the Bipolar TURP arm [3].<o:p></o:p></span></div>
<h2>
<b><span style="font-family: "Arial",sans-serif;"><br /></span></b></h2>
<h2>
<b><span style="font-family: "Arial",sans-serif;">Holmium Laser Therapy</span></b></h2>
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<span style="font-family: "Arial",sans-serif;">Holmium laser
therapy emits light at 2100 nm in pulses. This causes tissue water vaporization
with limited (0.4 mm) tissue penetration. Because the procedure uses normal
saline for irrigation, there is no risk for TUR syndrome manifested by
dilutional hyponatremia. Laser settings commonly cited in the literature
include 2-2.5 J and 40-50 Hz [4]. Several retrospective studies have found
significant 6 month post-op reduction in IPSS scores for prostates greater than
75, 125, and 175 g [4-6]. Furthermore, these studies reported low
peri-operative blood transfusion rates of 1.9-3.5%, which is significantly less
than the reported OSP average blood transfusion rate of 8.5% or greater. For
this reason, holmium laser therapy is often cited in the literature as having prostate
“size independent” effectiveness.<o:p></o:p></span></div>
<h2>
<b><span style="font-family: "Arial",sans-serif;"><br /></span></b></h2>
<h2>
<b><span style="font-family: "Arial",sans-serif;">Photoselective Vaporization of the
Prostate (PVP)</span></b></h2>
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<span style="font-family: "Arial",sans-serif;">Photoselective
Vaporization of the Prostate (PVP) is commonly referred to as the Greenlight
laser, as it vaporizes tissue at a wavelength of 532 nm. Because the laser is
selectively absorbed by hemoglobin, the relatively fibrous prostatic capsule is
resistant to absorption, making this procedure an attractive alternative to OSP.
The current generation of the Greenlight laser is the 180 W XPS laser. The
power has been increased from previous generations in order to improve adenoma
removal and lower re-treatment rates. A multi-institutional prospective trial
that looked at nearly 1,200 patients (2/3 with > 80 cc prostates; 1/3 with
< 80 cc prostates) who underwent 180 W XPS laser therapy found that the
larger prostate cohort maintained a mean IPSS reduction of 19 points at 6, 12,
and 24 months post-op [7]. However, significantly more of the > 80 cc
prostate cases had to be converted to TURP, most commonly due to bleeding that
obscured the visual field. Therefore, PVP appears to be an effective, but
imperfect alternative to OSP for large prostatic adenoma.<o:p></o:p></span></div>
<h2>
<b><span style="font-family: "Arial",sans-serif;"><br /></span></b></h2>
<h2>
<b><span style="font-family: "Arial",sans-serif;">Robot assisted laparoscopic Simple
Prostatectomy (RASP)</span></b></h2>
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<span style="font-family: "Arial",sans-serif;">Robot assisted
simple prostatectomy (RASP) appears to be a very attractive alternative to OSP,
with the hope that it would produce the functional results of OSP while
reducing the associated morbidity, including hospital length of stay,
perioperative hemorrhage, and blood transfusion rates. The transvesical
approach provides excellent visualization of the extent of the prostatic
adenoma, while preventing injury to the ureteral orifices during incision of
the bladder mucosa (Figure 2).<o:p></o:p></span><br />
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiodkytQAMB2s515p95z1HoPD80yv6nthxj2mnOcUYjmpSh9my-uL2zNWo3QyHQuZQBa7fDIkQ4Pldxlv-A7YtMfUEQ3G6F4zZWn176Z6SdJD09Wf3-mLkJK5PIkjDl09zRc8nF0t27VLQ/s1600/2.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" height="226" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiodkytQAMB2s515p95z1HoPD80yv6nthxj2mnOcUYjmpSh9my-uL2zNWo3QyHQuZQBa7fDIkQ4Pldxlv-A7YtMfUEQ3G6F4zZWn176Z6SdJD09Wf3-mLkJK5PIkjDl09zRc8nF0t27VLQ/s400/2.jpg" width="400" /></a></td></tr>
<tr><td class="tr-caption"><br />
Figure 2: Transvesical RASP: Incision in bladder mucosa distal to the ureteral orifices. <br />
Screen shot credit: Misop Han, M.D. Brady Urological Institute at Johns Hopkins Hospital.<br />
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<span style="font-family: "Arial",sans-serif;">Data from the
Brady Urological Institute comparing RASP to OSP found reductions in estimated
blood loss, blood transfusions, and hospital length of stay for the RASP arm
(Figure 3). Although there was no significant difference in pre-operative
prostate volume by transrectal ultrasound measurements, RASP had similar
adenoma resection weights as compared to OSP. A review that looked at 13 RASP
studies found an overall blood transfusion rate of 3.5% [8].<o:p></o:p></span><br />
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh5u_BVTkA-QVqr9-M_8LiD6PqkvXASnsLxhu5zlo0q9L4ytMRUAXHCzWxBHsdOr5HzROYN3qBtJpXpBL4ywYU2BwZxtDDohkbS0TcXOoaYZiqTRJqprbPEfe1TodMbLLwzJ0-q2s2r1bQ/s1600/3.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" height="253" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh5u_BVTkA-QVqr9-M_8LiD6PqkvXASnsLxhu5zlo0q9L4ytMRUAXHCzWxBHsdOr5HzROYN3qBtJpXpBL4ywYU2BwZxtDDohkbS0TcXOoaYZiqTRJqprbPEfe1TodMbLLwzJ0-q2s2r1bQ/s400/3.jpg" width="400" /></a></td></tr>
<tr><td class="tr-caption"><br />
Figure 3. RASP vs. OSP Peri-operative Outcomes. <br />
Brady Urological Institute at Johns Hopkins Hospital.<br />
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<span style="font-family: "Arial",sans-serif;">An edited video
of a robot assisted laparoscopic simple prostatectomy performed at Johns
Hopkins Hospital can be found below.<o:p></o:p></span><br />
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<b><span style="font-family: "Arial",sans-serif;">Key Points</span></b></h2>
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<li>Open simple prostatectomy is the gold standard surgical management for large prostatic adenoma</li>
<li>Bipolar TURP may remove less adenoma than OSP</li>
<li>HoLEP has prostate “size independent” effectiveness</li>
<li>PVP is effective but bleeding my obscure visualization</li>
<li>RASP is an excellent alternative for severe BPH for those well versed in robotic radical prostatectomy</li>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj35HenV2S3Qlu6P-IagxYNQEQl01h_o9xFpRaFutNDQemA4vcnHbzlsVxMqK4DQQ4ksfGajHqyppkfFHCEVU5A_cf0MJyWWersgJoQaJ6cAxHrutiplnHdITVOVUczoCnFAcVfVGka9SU/s1600/Brady+Blog+Photo.jpg" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" height="200" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj35HenV2S3Qlu6P-IagxYNQEQl01h_o9xFpRaFutNDQemA4vcnHbzlsVxMqK4DQQ4ksfGajHqyppkfFHCEVU5A_cf0MJyWWersgJoQaJ6cAxHrutiplnHdITVOVUczoCnFAcVfVGka9SU/s200/Brady+Blog+Photo.jpg" width="181" /></a></div>
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<span style="background-color: white; color: #333333; font-family: Arial; font-size: 11pt; text-align: start;"><em>This blog was written by <b>Bijan W. Salari,</b> a medical student a</em></span><i>t Wright State University Boonshoft School of Medicine. Bijan recently finished a four-week sub-internship at the Brady Urological Institute and gave a presentation to the department on "The Surgical Management of Large Prostatic Adenoma" from which this blog is inspired. Bijan is looking forward to a career in urology.</i></div>
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<span style="font-size: x-small;">REFERENCES<br />1. Speakman et al. Burden of male lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) - focus on the UK. BJU Int. 2015 Apr;115(4):508-19. doi: 10.1111/bju.12745. Epub 2014 Oct 16.<br />2. Ou et al. A randomized trial of transvesical prostatectomy versus transurethral resection of the prostate for prostate greater than 80 mL. Urology. 2010 Oct;76(4):958-61. doi: 10.1016/j.urology.2010.01.079. Epub 2010 Apr 15.<br />3. Geavlete et al. Bipolar vaporization, resection, and enucleation versus open prostatectomy: optimal treatment alternatives in large prostate cases? J Endourol. 2015 Mar;29(3):323-31. doi: 10.1089/end.2014.0493. Epub 2014 Sep 17.</span></div>
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<span style="font-size: x-small;">4. Krambeck et al. Holmium laser enucleation of the prostate for prostates larger than 175 grams. J Endourol. 2010 Mar;24(3):433-7. doi: 10.1089/end.2009.0147.<br />5. Matlaga et al. Holmium laser enucleation of the prostate for prostates of >125 mL. BJU Int. 2006 Jan;97(1):81-4.<br />6. Kuo et al. Holmium laser enucleation of prostate (HoLEP): the Methodist Hospital experience with greater than 75 gram enucleations. J Urol. 2003 Jul;170(1):149-52. <br />7. Hueber et al. Photoselective Vaporization of the Prostate for Benign Prostatic Hyperplasia Using the 180 Watt System: Multicenter Study of the Impact of Prostate Size on Safety and Outcomes. J Urol. 2015 Aug;194(2):462-9. doi: 10.1016/j.juro.2015.03.113. Epub 2015 Apr 4.<br />8. Patel et al. Robotic-assisted Simple Prostatectomy: Is there Evidence to go Beyond the Experimental Stage? Curr Urol Rep (2014) 15:443.</span></div>
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Anonymoushttp://www.blogger.com/profile/05286847723206340868noreply@blogger.com47tag:blogger.com,1999:blog-4730782586548300034.post-44390035005291334742015-08-18T09:00:00.000-04:002015-08-18T09:00:06.480-04:00Diffusion of Robotics in Urology: Responsible Introduction of Surgical Innovation<span style="text-align: justify;">The use of robotic surgery in urology began in 2001 with the advent of robot assisted radical prostatectomy (RARP). Since then, it has diffused throughout the field, providing an alternative to the open approach in numerous urologic procedures. However, the evidence for the utility and added benefits of the robotic approach is limited and varies among procedures. Given the fact that robotic-assisted procedures cost the patient an additional $1000 and the hospital nearly $100,000 annually, it is necessary to investigate the benefits of this technology and to determine for which procedures and which patients it is worth this increased cost. Furthermore, it is critical to assess whether the early introduction of this technology is safe for patients. Not only is the data supporting the use of robotics unclear, but also, in retrospect, the introduction of robotics may have led to unfavorable patient outcomes in certain settings. </span><strong style="text-align: justify;">This blog will serve as overview of some of the early data regarding the use of robotics in the surgical management of three index cancers and will end with a brief discussion of safety during the initial diffusion of robotic prostatectomy.</strong><span xmlns=""></span><br />
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<span xmlns=""><strong>RADICAL PROSTATECTOMY</strong></span></h2>
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<span xmlns="">Most of the initial data regarding RARP came from small, retrospective, single-center studies, most of which reported less blood loss, lower rates of transfusion, shorter length of stay and fewer short term complications. A recent prospective, multi-center, controlled trial from Sweden showed that RARP was associated with 500cc less blood loss, shorter length of stay by one day, and lower rates of reoperation during the initial hospital stay <span style="font-family: Cambria;">[1]</span>. Therefore, at least in the short term, there seems to be good evidence for RARP improving perioperative outcomes. </span></div>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjyP5V87ahLbsnuRynlAsjFK6XRec-qXqImj7iRKJmpVbVoWYQ9TICR7BhwYRMeMHyQdoqt2CWAp14zTChQubN0yipncmFFNUzofTeFgGwg4OgFs3U4b_wcvCQ806ul5gESZLT8LR5Lijg/s1600/fig1.png" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" height="192" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjyP5V87ahLbsnuRynlAsjFK6XRec-qXqImj7iRKJmpVbVoWYQ9TICR7BhwYRMeMHyQdoqt2CWAp14zTChQubN0yipncmFFNUzofTeFgGwg4OgFs3U4b_wcvCQ806ul5gESZLT8LR5Lijg/s1600/fig1.png" width="400" /></a></td></tr>
<tr><td class="tr-caption">Figure 1. RARP is associated with better short-term outcomes including less blood loss, shorter length of stay, and less rates of reoperation. From <span style="font-size: xx-small; text-align: start;">Wallerstedt, et al. </span><span style="font-size: 12.8000001907349px;">[1].</span></td></tr>
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<span xmlns="">Data regarding long-term outcomes are more controversial. Based on numerous studies, it is difficult to interpret whether there is any benefit or drawback to achieving the "trifecta" of oncologic control, continence, and potency with robotic assistance. A recent prospective, non-randomized study from Sweden suggests that there may be some benefit to RARP with regard to potency, but no difference for oncologic control or continence <span style="font-family: Cambria;">[2]</span>. Of note, the only randomized trial that sought to investigate this was terminated due to slow patient enrollment. Therefore, some evidence points to the benefits of RARP, some to its detriment, but most suggest equivalence between open and robotic.</span></div>
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<span xmlns=""><strong>PARTIAL NEPHRECTOMY</strong></span></h2>
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<span xmlns="">The use of robotics in partial nephrectomy (PN) is a different story. PN is the preferred surgical management of small renal masses (when technically feasible) because of its ability to preserve kidney function (i.e. nephron-sparing) with equivalent oncologic control. Minimally invasive PN has been shown to be associated with less blood loss, shorter length of stay, faster recovery, and less post-operative pain compared to the open flank incision <span style="font-family: Cambria;">[3]</span>. Within the category of minimally invasive surgery, Pierorazio et al. showed that robotic assisted partial nephrectomy (RAPN) is associated with shorter operative time, less blood loss, and shorter warm ischemia time (WIT)<span style="font-family: Cambria;"> [4]</span>. Regarding complications, Mullins et al. found no difference in complication rates, but when stratified by Clavien grade, the RAPN cohort was more likely to have lower grade complications <span style="font-family: Cambria;">[5]</span>. A meta-analysis comparing robotic vs. laparoscopic PN found no differences in operative times, blood loss, conversion rates, complications, or length of stay. However, RAPN was associated with shorter WIT, the key to renal preservation, which ultimately is the primary goal of PN <span style="font-family: Cambria;">[6]</span>.</span></div>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhi_SS9pKqopLW35Cm6UstcMRc7D8KiOAmpLA1n8URwYRviIzMo-yAus60mZ-TpZDQKV-_WHOT-v9Cd3rdKpaVWpK7YXNG-sZK59lXf4ISmUhrZORjhhfsIpAKI1fRyNTarxEMb7s4yKxs/s1600/fig2.png" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" height="130" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhi_SS9pKqopLW35Cm6UstcMRc7D8KiOAmpLA1n8URwYRviIzMo-yAus60mZ-TpZDQKV-_WHOT-v9Cd3rdKpaVWpK7YXNG-sZK59lXf4ISmUhrZORjhhfsIpAKI1fRyNTarxEMb7s4yKxs/s1600/fig2.png" width="400" /></a></td></tr>
<tr><td class="tr-caption">Figure 2. RAPN is associated with shorter WIT. From <span style="font-size: xx-small; text-align: start;">Aboumarzouk, et al. </span><span style="font-size: 12.8000001907349px;">[6].</span></td></tr>
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Robotic technology has led to an increased use of PN, due in part to the superior range of motion that aids in tumor excision and reconstruction under ischemic time constraints. This has been shown to be a real phenomenon, with a demonstrable increase in PN compared to radical nephrectomy in the years of robotic diffusion.<span style="font-family: Cambria;"> [7]</span> In addition, robotics has allowed urologists to tackle more complex renal tumors, such as tumors invading the large veins of the kidney and retroperitoneum (i.e. IVC thrombectomies), intrarenal, and posterior tumors, with comparable functional outcomes and less risk of conversion to radical nephrectomy <span style="font-family: Cambria;">[8-10]</span>.</div>
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<span xmlns=""><strong>RPLND</strong></span></h2>
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<span xmlns="">Retroperitoneal lymph node dissection (RPLND) is a treatment option for men with stage I and select stage II nonseminomatous germ cell tumors and is particularly useful for men who want to avoid long term surveillance or chemotherapy. Laparoscopic RPLND has been shown to have comparable oncologic outcomes with superior perioperative outcomes compared to open <span style="font-family: Cambria;">[11, 12]</span>. The data regarding robotic RPLND is scant due to its nascency in the field, however a recent study shows that early on, robotic RPLND is comparable to laparoscopic in terms of perioperative outcomes <span style="font-family: Cambria;">[13]</span>. Given the increased cost and risk of serious complications due to the intimacy with the great vessels during this procedure, the role of robotics in RPLND remains largely unknown at this point.</span></div>
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<span xmlns=""><strong>DIFFUSION AND PATIENT SAFETY</strong></span></h2>
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<span xmlns="">Given the variable and unclear data, particularly regarding RARP, how did robotics diffuse so rapidly and widely among urologists? First, it is important to note that in order to introduce new technology, one only needs a 510(k) clearance from the FDA. In the case of RARP, da Vinci received FDA clearance in 2000, the first RARP was in 2001, and the first population-based outcomes study was published in 2009. So many were performing RARP blindly without any population based data on efficacy or safety. Parsons et al. sought to retrospectively investigate if there was an effect on patient safety during this diffusion period using patient safety indicators (PSI). They found that in the year before the "tipping point," a set point indicating when RARP diffused from centers of excellence to more general urologists, there was a two-fold increase in PSI [14].</span></div>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi13yN1Z_B8PUZmfN5yyZccNHOHrgSrPsQ-BmXuhGc_hvE5sJuCndxDqpvTzSVBvSJ0BMfi4wqh9ZuYXZoV0qqbxAhDTZ7fjbkq-9lNuCG-lYpAEaHLD9gIPEDS1ecScoofr4TNiwA8S_w/s1600/fig3.png" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" height="322" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi13yN1Z_B8PUZmfN5yyZccNHOHrgSrPsQ-BmXuhGc_hvE5sJuCndxDqpvTzSVBvSJ0BMfi4wqh9ZuYXZoV0qqbxAhDTZ7fjbkq-9lNuCG-lYpAEaHLD9gIPEDS1ecScoofr4TNiwA8S_w/s1600/fig3.png" width="400" /></a></td></tr>
<tr><td class="tr-caption">Figure 3. RARP during diffusion era is associated with a two-fold increase in PSI. From <span style="font-size: xx-small; text-align: start;">Parsons, et al.</span><span style="font-size: 12.8000001907349px;"> [14].</span></td></tr>
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<span xmlns="">These results highlight the importance of responsibility with regards to the introduction of new technology. Is a compromise to patient safety in the initial years of dissemination necessary? Does new technology always come with risk? How do we know when to stop pursuing a given technique? When is a reasonable time to assess whether it is inferior and causing more harm than good? Was RARP even worth this increased risk given its limited utility and increased cost? Finally, is the culprit here technology, or does innovation by nature have barriers at first?</span></div>
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<span xmlns=""><strong>SUMMARY</strong></span></h2>
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<span xmlns="">The role of robotics in urology today raises many questions regarding comparative efficacy, cost justification, and patient safety with innovation. Radical prostatectomy and partial nephrectomy illustrate a juxtaposition of results – RAPN seems to have succeeded while RARP has yet to show a demonstrable benefit other than less blood loss. It has also raised questions about patient safety during the dissemination of new technology and bears the question, how does an innovator responsibly report results while marketing and patient demand accelerate the innovation's diffusion? Moving forward, standardized training and credentialing programs as well as systematic reporting to non-industry groups could be instituted in order to diffuse innovation while keeping the patient first.</span></div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEif-_wQ5RXy8OEgMNcQG9dWWghLQoC0XA2HOm5eMjqm6xkKCniBmSTedv72o0XUIfk1EHQGBRFdlBy4cMF_cx-i3JxOyv9zi6orL3gttKsi2Hk7PMezMK_Sm06zNr-oMJo0sE_F2Cw1E4A/s1600/harris.jpg" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" height="200" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEif-_wQ5RXy8OEgMNcQG9dWWghLQoC0XA2HOm5eMjqm6xkKCniBmSTedv72o0XUIfk1EHQGBRFdlBy4cMF_cx-i3JxOyv9zi6orL3gttKsi2Hk7PMezMK_Sm06zNr-oMJo0sE_F2Cw1E4A/s200/harris.jpg" width="142" /></a><span style="background-color: white; color: #333333; font-family: Arial; font-size: 11pt; text-align: start;"><em>This blog was written by <b>Kelly Harris,</b> a medical student at Johns Hopkins Medical School. Kelly recently finished a four-week sub-internship at the Brady Urological Institute and gave a presentation to the department on "</em></span><span style="background-color: white; color: #333333; font-family: Arial; font-size: 11pt; text-align: start;"><em>The Diffusion of Robotic Surgery in Urology" from which this blog is inspired. Kelly is looking forward to a career in urology.</em></span></div>
<span style="font-size: x-small;"><br /><br /><br /><br /><br /><br />1. Wallerstedt A, Tyritzis SI, Thorsteinsdottir T, et al. Short-term Results after Robot-assisted Laparoscopic Radical Prostatectomy Compared to Open Radical Prostatectomy. Eur Urol 2015: 67:660-70<br />2. Haglind E, Carlsson S, Stranne J, et al. Urinary Incontinence and Erectile Dysfunction After Robotic Versus Open Radical Prostatectomy: A Prospective, Controlled, Nonrandomised Trial. Eur Urol 2015<br />3. Hung AJ, Cai J, Simmons MN, Gill IS. "Trifecta" in partial nephrectomy. J Urol 2013: 189:36-42<br />4. Pierorazio PM, Mullins JK, Eifler JB, et al. Contemporaneous comparison of open vs minimally-invasive radical prostatectomy for high-risk prostate cancer. BJU Int 2013: 112:751-7<br />5. Mullins JK, Feng T, Pierorazio PM, Patel HD, Hyams ES, Allaf ME. Comparative analysis of minimally invasive partial nephrectomy techniques in the treatment of localized renal tumors. Urology 2012: 80:316-21<br />6. Aboumarzouk OM, Stein RJ, Eyraud R, et al. Robotic versus laparoscopic partial nephrectomy: a systematic review and meta-analysis. Eur Urol 2012: 62:1023-33<br />7. Patel HD, Mullins JK, Pierorazio PM, et al. Trends in renal surgery: robotic technology is associated with increased use of partial nephrectomy. J Urol 2013: 189:1229-35<br />8. Ball MW, Gorin MA, Jayram G, Pierorazio PM, Allaf ME. Robot-assisted radical nephrectomy with inferior vena cava tumor thrombectomy: technique and initial outcomes. Can J Urol 2015: 22:7666-70<br />9. Harris KT, Ball MW, Gorin MA, Curtiss KM, Pierorazio PM, Allaf ME. Transperitoneal Robot-Assisted Partial Nephrectomy: A Comparison of Posterior and Anterior Renal Masses. J Endourol 2014: 28:655-9<br />10. Curtiss KM, Ball MW, Gorin MA, Harris KT, Pierorazio PM, Allaf ME. Perioperative outcomes of robotic partial nephrectomy for intrarenal tumors. J Endourol 2015: 29:293-6<br />11. Bhayani SB, Ong A, Oh WK, Kantoff PW, Kavoussi LR. Laparoscopic retroperitoneal lymph node dissection for clinical stage I nonseminomatous germ cell testicular cancer: a long-term update. Urology 2003: 62:324-7<br />12. Steiner H, Peschel R, Janetschek G, et al. Long-term results of laparoscopic retroperitoneal lymph node dissection: a single-center 10-year experience. Urology 2004: 63:550-5<br />13. Harris KT, Gorin MA, Ball MW, Pierorazio PM, Allaf ME. A Comparative Analysis of Robotic versus Laparoscopic Retroperitoneal Lymph Node Dissection for Testicular Cancer. BJU Int 2015<br />14. Parsons JK, Messer K, Palazzi K, Stroup SP, Chang D. Diffusion of surgical innovations, patient safety, and minimally invasive radical prostatectomy. JAMA Surg 2014: 149:845-51</span>Anonymoushttp://www.blogger.com/profile/05286847723206340868noreply@blogger.com27tag:blogger.com,1999:blog-4730782586548300034.post-82595312387834103752015-05-05T08:05:00.000-04:002015-05-05T08:05:06.563-04:00Historical Contribution: 1969, Schwarz, et al., UTI Correlation to Fecal Bacteria<span xmlns=""></span><br />
<span style="color: #660000; font-family: Georgia, Times New Roman, serif; font-size: x-large;" xmlns=""><b>1969</b></span><br />
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<span style="color: #660000; font-family: Georgia, Times New Roman, serif;" xmlns=""><b>Schwarz H, Schirmer HKA, Ehlers B, Post B. Urinary Tract Infections: Correlation between Organisms Obtained Simultaneously from the Urine and Feces of Patients with Bacteriuria and Pyuria. J Urol. 1969. 101:765-767.</b></span><br />
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<span xmlns="">It was well established that gram-negative bacteria caused approximately 80% of UTI (urinary tract infections) and the colon was believed to be the source of most of these bacteria. In a study of 148 hospitalized individuals with bacteria in their urine, researchers from Johns Hopkins correlated the urinary organism with stool cultures from the same patients. Limited by difficulties in bacterial culture and identification of the time period, Dr. Schwarz and colleagues were able to demonstrate that urinary and fecal organisms were correlated in 60% to 100% of cases, depending on the bacteria. The authors then postulated that the colon was the most likely source of urinary bacteria, and perhaps, treating colonic flora could control the spread of infectious urinary organisms. </span><br />
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<span xmlns="">While we now know that the relationship between the colon, urinary bacteria and antimicrobial agents is more complex than a simple causal relationshipWe now understand that each patient has risk factors for infection, each bacteria has different methods for causing infection and there is certainly a difference between bacteruria (bacteria in the urine) and a UTI. However , manuscripts like this 1969 historical contribution, paved the way for a better understanding of UTI. </span><br />
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<span xmlns=""><span style="color: #333333;"><span style="font-family: Arial;"><span style="background-color: white; font-size: 13pt;">Visit the <a href="http://urology.jhu.edu/centennial/"><span style="color: #771000; text-decoration: underline;"><strong>Centennial Website</strong></span></a> or click <a href="http://urology.jhu.edu/centennial/pdf/1964.pdf"><span style="color: #771000; text-decoration: underline;"><strong>here</strong></span></a> to see more about the first 100 years at the Brady.</span><span style="font-size: 13pt;"><br /><span style="background-color: white;"><br /> </span></span></span><span style="color: black; font-family: Times New Roman; font-size: 13pt;"><br /> </span></span></span><br />
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<span xmlns=""><span style="color: #660000;"><span style="font-family: Arial; font-size: 13pt;"><em><strong>HISTORICAL CONTRIBUTIONS </strong>highlight the greatest academic manuscripts from the Brady Urological Institute over the past 100 years. As the Brady Urological Institute approaches its centennial, we will present a HISTORICAL CONTRIBUTION from each of the past 100 years. In the most recent experience, the most highly cited article from each year is selected; older manuscripts were selected based on their perceived impact on the field. We hope you enjoy!</em> </span><span style="color: black; font-family: Times New Roman; font-size: 13pt;"><br /> </span></span></span></div>
Anonymoushttp://www.blogger.com/profile/05286847723206340868noreply@blogger.com12tag:blogger.com,1999:blog-4730782586548300034.post-33531099383216749722015-04-28T07:15:00.000-04:002015-04-28T07:15:00.394-04:00Historical Contribution: 1966: Gibbons, Transurethral Freezing of the Bladder<span xmlns=""></span><br />
<span style="color: #660000; font-family: Georgia, Times New Roman, serif; font-size: x-large;" xmlns=""><strong>1966</strong></span><br />
<span xmlns=""><strong><span style="color: #660000; font-family: Georgia, Times New Roman, serif;">Gibbons RP. Transurethral Freezing of the Bladder: An Experimental Study. J Urol. 1966. 95;33-44.</span></strong></span><br />
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<span xmlns="">Presented at the Urological Research Forum at the annual American Urological Association in New Orleans, 1965, Dr. Robert Gibbons presented early experiments to treat non-invasive urothelial cancers of the bladder. The proposed hypothesis was that by circumferentially destroying the mucosa of the bladder, the risk of subsequent, recurrent non-invasive cancers could be eliminated. Therefore Gibbons set out to find an acceptable freezing material and device to deliver a treatment that could treat these non-invasive bladder cancers. </span><br />
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<span xmlns="">Using a specially designed transurethral cooling device, Gibbons was able to deliver coolant to the entire surface of the bladder – effectively destroying the urothelial layer. </span><br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg6uHPc6KiOnrCpPF8ruKAhW8r61eMls_cw4QUQ_gdkVO8XAYxfVJ8kJ5ysLlBf-9l4qMF2BnEaXZz-IbzubMLsclj5JPnBTcAng_mYXuTG_d-DpOED_iAfwK3rGcdcqXR2yj9Mnm6cDds/s1600/1966.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg6uHPc6KiOnrCpPF8ruKAhW8r61eMls_cw4QUQ_gdkVO8XAYxfVJ8kJ5ysLlBf-9l4qMF2BnEaXZz-IbzubMLsclj5JPnBTcAng_mYXuTG_d-DpOED_iAfwK3rGcdcqXR2yj9Mnm6cDds/s1600/1966.jpg" height="357" width="400" /></a></div>
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<span xmlns="">The experiments were carried out in 30 dogs, and anatomic and pathological evaluation was carried out of the bladders at varying time points following treatment. By carefully tuning the cooling apparatus, Gibbons was able to achieve greater than 75% mucosal slough in many of the experiments. Importantly, Gibbons was never able to achieve 100% mucosal destruction, nor could he create reproducible outcomes by standardizing the coolant and methods to cool the bladder. Anatomic examination demonstrated reduced bladder capacity, new onset hydronephrosis and abdominal adhesions in many animals. Pathological evaluation demonstrated involvement of the submucosa in most specimens and often noticed full-thickness necrosis of the bladder wall in a number of cases. Unfortunately, this corresponded to peritoneal infections and death in a number of the experiments. </span><br />
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<span xmlns="">While this experiment could be considered a failure, this was an outstanding attempt to treat non-invasive bladder cancers. In 1965, there was no BCG or other intravesical treatment for the management of non-invasive urothelial cancers. Thermal ablation, or "freezing" of cancers was en vogue and being attempted in gastric, esophageal, retinal, brain and kidney cancers. </span><br />
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<span xmlns=""><span style="color: #333333; font-family: Arial;"><span style="background-color: white; font-size: 13pt;">Visit the <a href="http://urology.jhu.edu/centennial/"><span style="color: #771000; text-decoration: underline;"><strong>Centennial Website</strong></span></a> or click <a href="http://urology.jhu.edu/centennial/pdf/1964.pdf"><span style="color: #771000; text-decoration: underline;"><strong>here</strong></span></a> to see more about the first 100 years at the Brady.</span><br /><span style="background-color: white;"><br /> </span></span><span style="font-family: Times New Roman; font-size: 12pt;"><br /> </span></span><br />
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<span xmlns=""><span style="color: #660000; font-family: Arial;"><span style="font-size: 13pt;"><em><strong>HISTORICAL CONTRIBUTIONS </strong>highlight the greatest academic manuscripts from the Brady Urological Institute over the past 100 years. As the Brady Urological Institute approaches its centennial, we will present a HISTORICAL CONTRIBUTION from each of the past 100 years. In the most recent experience, the most highly cited article from each year is selected; older manuscripts were selected based on their perceived impact on the field. We hope you enjoy!</em> </span><span style="color: #333333;"><br /> </span></span></span></div>
Anonymoushttp://www.blogger.com/profile/05286847723206340868noreply@blogger.com9tag:blogger.com,1999:blog-4730782586548300034.post-28271446347052993502015-04-22T07:30:00.000-04:002015-04-22T07:30:00.745-04:00Is Testosterone Replacement Therapy "Feeding the Fire" of Prostate Cancer?<span xmlns=""></span><br />
<span xmlns=""><b>Testosterone replacement therapy (TRT)</b> is the administration of testosterone to men with abnormally low testosterone, termed hypogonadism, or "low T," Men with symptoms of low testosterone, can often benefit from TRT. Common symptoms of hypogonadism in post-pubertal men commonly include decreased muscle mass, decreased energy, depressed mood, decreased libido, decreased spontaneous erections, and erectile dysfunction [Wang et al., 2008, Basaria, 2014]. </span><br />
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<span xmlns="">While TRT has been used for decades the last decade has seen a dramatic increase in the use of TRT. The percentage of men in the Unites States over 40 years of age prescribed TRT increased from less than 1% in 2001 to nearly 3% in 2011 [Baillargeon et al., 2013]. The increase in TRT and lack of data from large, long term <b>randomized controlled trials (RCT)</b> has raised concern for unrecognized adverse health risks, including potential increases in cardiovascular disease and <b>prostate cancer (PC)</b>.</span><br />
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<tr><td class="tr-caption">Changes in androgen use over time. From Baillargeon et al., 2013.</td></tr>
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<span style="color: #660000;" xmlns=""><strong>There is large body of both historic and modern data supporting a role for androgens in PC pathogenesis and progression.</strong></span></h2>
<span xmlns="">In 1941, Huggins and Hodges proposed that PC growth was driven by androgens, after observing benefits of castration in PC patients [Huggins et al., 1941]. Current laboratory data demonstrate that many PC cell lines depend on testosterone for growth and spread. [Kyprianou et al., 1990, Webber et al., 1996, Schwab et al., 2000]. In animal models, testosterone promotes PC tumor growth [Bladou et al., 1996, Ahmad et al., 2008].</span><br />
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The data supporting the androgen hypothesis has led to the dogma that TRT in PC patients is like <i>"feeding the fire." </i>Historically, there is data supporting this concept. In 1982 Fowler et al. reported on 52 men with metastatic PC patients who recieved testosterone. 38% of men had elevations in prostatic acid phosphatase (a blood test used to monitor PC), 2 men had measurable metastatic progression, and ther were 4 deaths [Fowler et al., 1982]. Importantly, these patients had advanced disease, and many had prior androgen deprivation [Fowler et al., 1982]. Thus, it would not be appropriate to apply these observations to men with clinically localized disease who receive early primary treatment and PSA monitoring.<br />
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<span style="color: #660000;" xmlns=""><strong>There is currently no reliable data indicating an increase in PC in men without PC undergoing TRT. </strong></span></h2>
<span xmlns="">The majority of studies on TRT and PC are small, and to date, there have been no prospective studies on TRT with sufficient patient numbers to determine increased PC risk. By one estimate, 6,000 patients receiving 5 years of TRT would be needed to detect a 30% increase in PC incidence [Bhasin et al., 2003]. In a systematic review of 40 prospective studies, there was no study which demonstrated an association between TRT and PC risk in men without prior PC. In addition, a meta-analysis of 19 studies, there was no significant increase in PC or significant PSA increases necessitating prostate biopsy. [Calof et al., 2005].</span><br />
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<span style="color: #660000;" xmlns=""><strong>TRT in patients with localized PC appears safe, based on limited data </strong></span></h2>
<span xmlns="">Using Medicare data, Kaplan and colleagues reported on 149,354 men, including 1,181 men who received TRT after a diagnosis with PC. Overall, TRT was not associated with PC deaths [Kaplan et al., 2014]. Similarly, Pastuszak and colleagues reported on 103 men who after prostatectomy were treated with TRT. There was an overall increase serum PSA, but no evidence of increased cancer recurrence over 36 months [Pastuszak et al., 2013]. In a smaller study, Morgentaler et al. examined 13 patients with untreated PC, enrolled in an active surveillence program and receiving TRT. After a median follow-up of 2.5 years, 2 men had worse pathology on subsequent biopsy, but no cases of disease or PSA progression were seen [Morgentaler et al., 2011].</span><br />
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<span style="color: #660000;" xmlns=""><strong>Summary</strong></span></h2>
Overall, there remains no clear answer to the question <i>"Does testosterone promote prostate cancer development in humans?"</i> Thus, TRT in men with prostate cancer remains controversial. There is clear evidence that androgens can promote PC in animal models. It is clear that the influence of testosterone on PC disease progression is of paramount importance to both patients and providers as they weight the potential benefits of TRT. Currently, there is a growing amount of evidence that TRT is safe in well-selected men with clinically localized PC. However, these results are based on TRT in a small number of patients. Furthermore, the heterogeneity in PC progression and aggressiveness may give rise to heterogeneity in the responsiveness of tumors to TRT. Thus, until the results of future RCTs are available, TRT should only be offered to select patients who are carefully monitored and well-informed about the potential risks and benefits.<br />
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<span xmlns=""><i>This blog was written by <b>Jason E. Michaud M.D., Ph.D</b>., urology resident at the Brady Urological Institute, currently in his laboratory research year.</i></span><br />
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<span style="font-size: x-small;" xmlns="">Ahmad, I., Sansom, O.J., and Leung, H.Y. (2008) Advances in Mouse Models of Prostate Cancer. Expert Rev Mol Med 10: e16.</span><br />
<span style="font-size: x-small;" xmlns="">Al-Khazaali, A., Arora, R., and Muttar, S. (2015) Controversial Effects of Exogenous Testosterone on Cardiovascular Diseases. Am J Ther: </span><br />
<span style="font-size: x-small;" xmlns="">Andriole, G., Bruchovsky, N., Chung, L.W., Matsumoto, A.M., Rittmaster, R., Roehrborn, C. et al. (2004) Dihydrotestosterone and the Prostate: The Scientific Rationale for 5alpha-Reductase Inhibitors in the Treatment of Benign Prostatic Hyperplasia. J Urol 172: 1399-1403.</span><br />
<span style="font-size: x-small;" xmlns="">Andriole, G.L., Crawford, E.D., Grubb, R.L., Buys, S.S., Chia, D., Church, T.R. et al. (2009) Mortality Results from a Randomized Prostate-Cancer Screening Trial. New England Journal of Medicine 360: 1310-1319.</span><br />
<span style="font-size: x-small;" xmlns="">Araujo, A.B., O'donnell, A.B., Brambilla, D.J., Simpson, W.B., Longcope, C., Matsumoto, A.M. et al. (2004) Prevalence and Incidence of Androgen Deficiency in Middle-Aged and Older Men: Estimates from the Massachusetts Male Aging Study. J Clin Endocrinol Metab 89: 5920-5926.</span><br />
<span style="font-size: x-small;" xmlns="">Baillargeon, J., Urban, R.J., Ottenbacher, K.J., Pierson, K.S., and Goodwin, J.S. (2013) Trends in Androgen Prescribing in the United States, 2001 to 2011. JAMA Intern Med 173: 1465-1466.</span><br />
<span style="font-size: x-small;" xmlns="">Basaria, S. (2014) Male Hypogonadism. Lancet 383: 1250-1263.</span><br />
<span style="font-size: x-small;" xmlns="">Bhasin, S., Singh, A.B., Mac, R.P., Carter, B., Lee, M.I., and Cunningham, G.R. (2003) Managing the Risks of Prostate Disease During Testosterone Replacement Therapy in Older Men: Recommendations for a Standardized Monitoring Plan. J Androl 24: 299-311.</span><br />
<span style="font-size: x-small;" xmlns="">Bladou, F., Vessella, R.L., Buhler, K.R., Ellis, W.J., True, L.D., and Lange, P.H. (1996) Cell Proliferation and Apoptosis During Prostatic Tumor Xenograft Involution and Regrowth after Castration. Int J Cancer 67: 785-790.</span><br />
<span style="font-size: x-small;" xmlns="">Botelho, F., Pina, F., Figueiredo, L., Cruz, F., and Lunet, N. (2012) Does Baseline Total Testosterone Improve the Yielding of Prostate Cancer Screening? Eur J Cancer 48: 1657-1663.</span><br />
<span style="font-size: x-small;" xmlns="">Bremner, W.J., Vitiello, M.V., and Prinz, P.N. (1983) Loss of Circadian Rhythmicity in Blood Testosterone Levels with Aging in Normal Men. J Clin Endocrinol Metab 56: 1278-1281.</span><br />
<span style="font-size: x-small;" xmlns="">Calof, O.M., Singh, A.B., Lee, M.L., Kenny, A.M., Urban, R.J., Tenover, J.L. et al. (2005) Adverse Events Associated with Testosterone Replacement in Middle-Aged and Older Men: A Meta-Analysis of Randomized, Placebo-Controlled Trials. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 60: 1451-1457.</span><br />
<span style="font-size: x-small;" xmlns="">D'amico, A.V., Moul, J.W., Carroll, P.R., Sun, L., Lubeck, D., and Chen, M.H. (2003) Surrogate End Point for Prostate Cancer-Specific Mortality after Radical Prostatectomy or Radiation Therapy. J Natl Cancer Inst 95: 1376-1383.</span><br />
<span style="font-size: x-small;" xmlns="">Dai, B., Qu, Y., Kong, Y., Ye, D., Yao, X., Zhang, S. et al. (2012) Low Pretreatment Serum Total Testosterone Is Associated with a High Incidence of Gleason Score 8-10 Disease in Prostatectomy Specimens: Data from Ethnic Chinese Patients with Localized Prostate Cancer. BJU Int 110: E667-672.</span><br />
<span style="font-size: x-small;" xmlns="">Endogenous, H., Prostate Cancer Collaborative, G., Roddam, A.W., Allen, N.E., Appleby, P., and Key, T.J. (2008) Endogenous Sex Hormones and Prostate Cancer: A Collaborative Analysis of 18 Prospective Studies. J Natl Cancer Inst 100: 170-183.</span><br />
<span style="font-size: x-small;" xmlns="">Fowler, J.E. and Whitemore, W.F. (1982) Considerations for the Use of Testosterone with Systemic Chemotherapy in Prostate Cancer. Cancer 49: 1373-1377.</span><br />
<span style="font-size: x-small;" xmlns="">Gann, P.H., Hennekens, C.H., Ma, J., Longcope, C., and Stampfer, M.J. (1996) Prospective Study of Sex Hormone Levels and Risk of Prostate Cancer. J Natl Cancer Inst 88: 1118-1126.</span><br />
<span style="font-size: x-small;" xmlns="">Garcia-Cruz, E., Piqueras, M., Ribal, M.J., Huguet, J., Serapiao, R., Peri, L. et al. (2012) Low Testosterone Level Predicts Prostate Cancer in Re-Biopsy in Patients with High Grade Prostatic Intraepithelial Neoplasia. BJU Int 110: E199-202.</span><br />
<span style="font-size: x-small;" xmlns="">Haider, A., Zitzmann, M., Doros, G., Isbarn, H., Hammerer, P., and Yassin, A. (2014) Incidence of Prostate Cancer in Hypogonadal Men Receiving Testosterone Therapy: Observations from 5-Year Median Followup of 3 Registries. J Urol 193: 80-86.</span><br />
<span style="font-size: x-small;" xmlns="">Handelsman, D.J. (2013) Global Trends in Testosterone Prescribing, 2000-2011: Expanding the Spectrum of Prescription Drug Misuse. Med J Aust 199: 548-551.</span><br />
<span style="font-size: x-small;" xmlns="">Harman, S.M., Metter Ej Fau - Tobin, J.D., Tobin Jd Fau - Pearson, J., Pearson J Fau - Blackman, M.R., and Blackman, M.R. (2001) Longitudinal Effects of Aging on Serum Total and Free Testosterone Levels in Healthy Men. Baltimore Longitudinal Study of Aging. </span><br />
<span style="font-size: x-small;" xmlns="">Howden, L., Meyer, J. (2011) Age and Sex Composition: 2010, 2010 Census Briefs, Vol. 2015. United States Census Bureau.</span><br />
<span style="font-size: x-small;" xmlns="">Huggins, C. (1947) The Etiology of Benign Prostatic Hypertrophy. Bulletin of the New York Academy of Medicine 23: 696-704.</span><br />
<span style="font-size: x-small;" xmlns="">Huggins, C. and Hodges, C.V. (1941) Studies on Prostatic Cancer: I. The Effect of Castration, of Estrogen and of Androgen Injection on Serum Phosphatases in Metastatic Carcinoma of the Prostate. 1941. Cancer Res 1: 293-297.</span><br />
<span style="font-size: x-small;" xmlns="">Imamoto, T., Suzuki, H., Fukasawa, S., Shimbo, M., Inahara, M., Komiya, A. et al. (2005) Pretreatment Serum Testosterone Level as a Predictive Factor of Pathological Stage in Localized Prostate Cancer Patients Treated with Radical Prostatectomy. Eur Urol 47: 308-312.</span><br />
<span style="font-size: x-small;" xmlns="">Kaplan, A.L., Trinh, Q.D., Sun, M., Carter, S.C., Nguyen, P.L., Shih, Y.C. et al. (2014) Testosterone Replacement Therapy Following the Diagnosis of Prostate Cancer: Outcomes and Utilization Trends. J Sex Med 11: 1063-1070.</span><br />
<span style="font-size: x-small;" xmlns="">Kyprianou, N., English, H.F., and Isaacs, J.T. (1990) Programmed Cell Death During Regression of Pc-82 Human Prostate Cancer Following Androgen Ablation. Cancer Res 50: 3748-3753.</span><br />
<span style="font-size: x-small;" xmlns="">Lane, B.R., Stephenson, A.J., Magi-Galluzzi, C., Lakin, M.M., and Klein, E.A. (2008) Low Testosterone and Risk of Biochemical Recurrence and Poorly Differentiated Prostate Cancer at Radical Prostatectomy. Urology 72: 1240-1245.</span><br />
<span style="font-size: x-small;" xmlns="">Leibowitz, R.L., Dorff, T.B., Tucker, S., Symanowski, J., and Vogelzang, N.J. (2010) Testosterone Replacement in Prostate Cancer Survivors with Hypogonadal Symptoms. BJU Int 105: 1397-1401.</span><br />
<span style="font-size: x-small;" xmlns="">Massengill, J.C., Sun, L., Moul, J.W., Wu, H., Mcleod, D.G., Amling, C. et al. (2003) Pretreatment Total Testosterone Level Predicts Pathological Stage in Patients with Localized Prostate Cancer Treated with Radical Prostatectomy. J Urol 169: 1670-1675.</span><br />
<span style="font-size: x-small;" xmlns="">Matsumoto, A.M. (2003) Fundamental Aspects of Hypogonadism in the Aging Male. Reviews in Urology 5: S3-S10.</span><br />
<span style="font-size: x-small;" xmlns="">Mearini, L., Zucchi, A., Nunzi, E., Villirillo, T., Bini, V., and Porena, M. (2013) Low Serum Testosterone Levels Are Predictive of Prostate Cancer. World J Urol 31: 247-252.</span><br />
<span style="font-size: x-small;" xmlns="">Miner, M., Barkin, J., and Rosenberg, M.T. (2014) Testosterone Deficiency: Myth, Facts, and Controversy. Can J Urol 21 Suppl 2: 39-54.</span><br />
<span style="font-size: x-small;" xmlns="">Morgentaler, A., Lipshultz, L.I., Bennett, R., Sweeney, M., Avila, D., Jr., and Khera, M. (2011) Testosterone Therapy in Men with Untreated Prostate Cancer. J Urol 185: 1256-1260.</span><br />
<span style="font-size: x-small;" xmlns="">Morgentaler, A. and Rhoden, E.L. (2006) Prevalence of Prostate Cancer among Hypogonadal Men with Prostate-Specific Antigen Levels of 4.0 Ng/Ml or Less. Urology 68: 1263-1267.</span><br />
<span style="font-size: x-small;" xmlns="">Morote, J., Ramirez, C., Gomez, E., Planas, J., Raventos, C.X., De Torres, I.M. et al. (2009) The Relationship between Total and Free Serum Testosterone and the Risk of Prostate Cancer and Tumour Aggressiveness. BJU Int 104: 486-489.</span><br />
<span style="font-size: x-small;" xmlns="">Muller, M., Den Tonkelaar, I., Thijssen, J.H., Grobbee, D.E., and Van Der Schouw, Y.T. (2003) Endogenous Sex Hormones in Men Aged 40-80 Years. Eur J Endocrinol 149: 583-589.</span><br />
<span style="font-size: x-small;" xmlns="">Muller, R.L., Gerber L Fau - Moreira, D.M., Moreira Dm Fau - Andriole, G., Andriole G Fau - Castro-Santamaria, R., Castro-Santamaria R Fau - Freedland, S.J., and Freedland, S.J. (2012) Serum Testosterone and Dihydrotestosterone and Prostate Cancer Risk in the Placebo Arm of the Reduction by Dutasteride of Prostate Cancer Events Trial. </span><br />
<span style="font-size: x-small;" xmlns="">Mulligan, T., Frick, M.F., Zuraw, Q.C., Stemhagen, A., and Mcwhirter, C. (2006) Prevalence of Hypogonadism in Males Aged at Least 45 Years: The Him Study. International Journal of Clinical Practice 60: 762-769.</span><br />
<span style="font-size: x-small;" xmlns="">Neaves Wb Fau - Johnson, L., Johnson L Fau - Porter, J.C., Porter Jc Fau - Parker, C.R., Jr., Parker Cr Jr Fau - Petty, C.S., and Petty, C.S. (1984) Leydig Cell Numbers, Daily Sperm Production, and Serum Gonadotropin Levels in Aging Men. </span><br />
<span style="font-size: x-small;" xmlns="">Pastuszak, A.W., Pearlman, A.M., Lai, W.S., Godoy, G., Sathyamoorthy, K., Liu, J.S. et al. (2013) Testosterone Replacement Therapy in Patients with Prostate Cancer after Radical Prostatectomy. J Urol 190: 639-644.</span><br />
<span style="font-size: x-small;" xmlns="">Pierorazio, P.M., Ferrucci L Fau - Kettermann, A., Kettermann a Fau - Longo, D.L., Longo Dl Fau - Metter, E.J., Metter Ej Fau - Carter, H.B., and Carter, H.B. (2010) Serum Testosterone Is Associated with Aggressive Prostate Cancer in Older Men: Results from the Baltimore Longitudinal Study of Aging. </span><br />
<span style="font-size: x-small;" xmlns="">Rhoden, E.L. and Morgentaler, A. (2003) Testosterone Replacement Therapy in Hypogonadal Men at High Risk for Prostate Cancer: Results of 1 Year of Treatment in Men with Prostatic Intraepithelial Neoplasia. J Urol 170: 2348-2351.</span><br />
<span style="font-size: x-small;" xmlns="">Rove, K.O. and Crawford, E.D. (2014) Traditional Androgen Ablation Approaches to Advanced Prostate Cancer: New Insights. Can J Urol 21: 14-21.</span><br />
<span style="font-size: x-small;" xmlns="">Rubens R Fau - Dhont, M., Dhont M Fau - Vermeulen, A., and Vermeulen, A. (1974) Further Studies on Leydig Cell Function in Old Age. </span><br />
<span style="font-size: x-small;" xmlns="">Salonia, A., Gallina, A., Briganti, A., Abdollah, F., Suardi, N., Capitanio, U. et al. (2010) Preoperative Hypogonadism Is Not an Independent Predictor of High-Risk Disease in Patients Undergoing Radical Prostatectomy. Cancer 117: 3953-3962.</span><br />
<span style="font-size: x-small;" xmlns="">San Francisco, I.F., Rojas, P.A., Dewolf, W.C., and Morgentaler, A. (2014) Low Free Testosterone Levels Predict Disease Reclassification in Men with Prostate Cancer Undergoing Active Surveillance. BJU Int 114: 229-235.</span><br />
<span style="font-size: x-small;" xmlns="">Schroder, F.H., Hugosson, J., Roobol, M.J., Tammela, T.L.J., Ciatto, S., Nelen, V. et al. (2012) Prostate-Cancer Mortality at 11 Years of Follow-Up. New England Journal of Medicine 366: 981-990.</span><br />
<span style="font-size: x-small;" xmlns="">Schwab, T.S., Stewart, T., Lehr, J., Pienta, K.J., Rhim, J.S., and Macoska, J.A. (2000) Phenotypic Characterization of Immortalized Normal and Primary Tumor-Derived Human Prostate Epithelial Cell Cultures. Prostate 44: 164-171.</span><br />
<span style="font-size: x-small;" xmlns="">Shaneyfelt, T., Husein, R., Bubley, G., and Mantzoros, C.S. (2000) Hormonal Predictors of Prostate Cancer: A Meta-Analysis. Journal of Clinical Oncology 18: 847.</span><br />
<span style="font-size: x-small;" xmlns="">Shin, B.S., Hwang, E.C., Im, C.M., Kim, S.O., Jung, S.I., Kang, T.W. et al. (2010) Is a Decreased Serum Testosterone Level a Risk Factor for Prostate Cancer? A Cohort Study of Korean Men. Korean J Urol 51: 819-823.</span><br />
<span style="font-size: x-small;" xmlns="">Siiteri Pk Fau - Wilson, J.D. and Wilson, J.D. (1974) Testosterone Formation and Metabolism During Male Sexual Differentiation in the Human Embryo. </span><br />
<span style="font-size: x-small;" xmlns="">Spitzer, M., Huang, G., Basaria, S., Travison, T.G., and Bhasin, S. (2013) Risks and Benefits of Testosterone Therapy in Older Men. Nat Rev Endocrinol 9: 414-424.</span><br />
<span style="font-size: x-small;" xmlns="">Swerdloff, R. and Wang, C. (2011) Testosterone Treatment of Older Men: Why Are Controversies Created? The Journal of Clinical Endocrinology and Metabolism 96: 62-65.</span><br />
<span style="font-size: x-small;" xmlns="">Swyer, G.I.M. (1944) Post-Natal Growth Changes in the Human Prostate. Journal of Anatomy 78: 130-145.</span><br />
<span style="font-size: x-small;" xmlns="">Tenover, J.S., Matsumoto, A.M., Clifton, D.K., and Bremner, W.J. (1988) Age-Related Alterations in the Circadian Rhythms of Pulsatile Luteinizing Hormone and Testosterone Secretion in Healthy Men. J Gerontol 43: M163-169.</span><br />
<span style="font-size: x-small;" xmlns="">Vermeulen, A. and Kaufman, J.M. (1995) Ageing of the Hypothalamo-Pituitary-Testicular Axis in Men. Horm Res 43: 25-28.</span><br />
<span style="font-size: x-small;" xmlns="">Wang, C., Nieschlag, E., Swerdloff, R., Behre, H.M., Hellstrom, W.J., Gooren, L.J. et al. (2008) Investigation, Treatment and Monitoring of Late-Onset Hypogonadism in Males: Isa, Issam, Eau, Eaa and Asa Recommendations. Eur J Endocrinol 159: 507-514.</span><br />
<span style="font-size: x-small;" xmlns="">Webber, M.M., Bello, D., and Quader, S. (1996) Immortalized and Tumorigenic Adult Human Prostatic Epithelial Cell Lines: Characteristics and Applications. Part I. Cell Markers and Immortalized Nontumorigenic Cell Lines. Prostate 29: 386-394.</span><br />
<span style="font-size: x-small;" xmlns="">Wu, F.C., Tajar, A., Beynon, J.M., Pye, S.R., Silman, A.J., Finn, J.D. et al. (2010) Identification of Late-Onset Hypogonadism in Middle-Aged and Elderly Men. N Engl J Med 363: 123-135.</span><br />
<span style="font-size: x-small;" xmlns="">Xylinas, E., Ploussard, G., Durand, X., Fabre, A., Salomon, L., Allory, Y. et al. (2011) Low Pretreatment Total Testosterone (< 3 Ng/Ml) Predicts Extraprostatic Disease in Prostatectomy Specimens from Patients with Preoperative Localized Prostate Cancer. BJU Int 107: 1400-1403.</span><br />
<span style="font-size: x-small;" xmlns="">Yano, M., Imamoto, T., Suzuki, H., Fukasawa, S., Kojima, S., Komiya, A. et al. (2007) The Clinical Potential of Pretreatment Serum Testosterone Level to Improve the Efficiency of Prostate Cancer Screening. Eur Urol 51: 375-380.</span><br />
Anonymoushttp://www.blogger.com/profile/05286847723206340868noreply@blogger.com36tag:blogger.com,1999:blog-4730782586548300034.post-27288149288380998302015-03-31T07:00:00.000-04:002015-03-31T07:00:05.688-04:00Historical Contribution: 1971, Chung and Coffey, The Prostate Nuclei<span xmlns=""></span><br />
<span style="color: #660000; font-family: Georgia, Times New Roman, serif; font-size: x-large;" xmlns=""><b>1971</b></span><br />
<span style="color: #660000; font-family: Georgia, Times New Roman, serif;" xmlns=""><b>Biochemical characterization of prostatic nuclei. I. Androgen-induced changes in nuclear proteins L. W. Chung and D. S. Coffey Biochim Biophys Acta 1971 247: 570-83</b></span><br />
<span xmlns=""><br /> </span><br />
<span xmlns="">Based on prior work, Dr. Coffey and colleagues demonstrated that the DNA, RNA and protein synthesis of the prostate gland varied with androgen levels (see the <a href="http://bradyurology.blogspot.com/2015/03/historical-contribution-1968-coffey-et.html">Historical Contribution: 1968</a>). In this 1971 investigation (written in two parts), Drs. Chung and Coffey analyzed the nuclei and DNA content of rats following castration. They found that nuclei from prostate cells could easily be recovered in rats who were castrate (approximately 60%). However, in normal rats and those who received testosterone replacement (after castration) – the proportion of nuclei recovered was dramatically lower (13-15%). Thorough investigation determined a number of factors that contributed to the difference in prostate nuclei:</span><br />
<ol>
<li><span xmlns="">Magnesium levels and the nuclear membranes are affected by testosterone levels. Aberrations in these normal cellular processes resulted in lower nuclei yield. </span></li>
<li><span xmlns="">Testosterone levels also affect the size of the nuclei (it had previously been demonstrated that testosterone affected the size of the whole prostate cell). Just as the prostate cell shrinks under castrate levels, so too does the prostate cell nucleus.</span></li>
<li><span xmlns="">Nuclear protein to DNA content (as measured by nuclear proteins and nuclear membrane proteins) is decreased with low testosterone levels and,</span></li>
<li><span xmlns="">… can be restored to normal after testosterone supplementation. </span></li>
</ol>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjsWxcA5TMNervE8zZHCyH1UOTcpItnhZj-U8sNQ3wF9b10i7iUg_oO0ET81gi_fVMNlk5-aCSRZRiHTxpw5vVRkwgHVcjDmpu026jOZFDJt4zAwDWG0Mmp-LXrR_cQIFrTsRf7L23hPuo/s1600/1971.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjsWxcA5TMNervE8zZHCyH1UOTcpItnhZj-U8sNQ3wF9b10i7iUg_oO0ET81gi_fVMNlk5-aCSRZRiHTxpw5vVRkwgHVcjDmpu026jOZFDJt4zAwDWG0Mmp-LXrR_cQIFrTsRf7L23hPuo/s1600/1971.jpg" height="400" width="348" /></a></div>
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<span xmlns="">This series of elegant experiments can be found in <a href="http://www.sciencedirect.com/science/journal/00052736/241/2"><em>Biochimica et Biophysica Acta</em></a>. It is a wonderful example of Dr. Coffey's thoughtful and inventive approach to deciphering the prostate. </span><br />
<span xmlns=""><br /> </span><br />
<span xmlns=""><span style="color: #333333; font-family: Arial;"><span style="background-color: white; font-size: 13pt;">Visit the <a href="http://urology.jhu.edu/centennial/"><span style="color: #771000; text-decoration: underline;"><strong>Centennial Website</strong></span></a> or click <a href="http://urology.jhu.edu/centennial/pdf/1964.pdf"><span style="color: #771000; text-decoration: underline;"><strong>here</strong></span></a> to see more about the first 100 years at the Brady.</span><br /><span style="background-color: white;"><br /> </span></span><span style="font-family: Times New Roman; font-size: 12pt;"><br /> </span></span><br />
<div style="background: white;">
<span xmlns=""><span style="color: #660000; font-family: Arial;"><span style="font-size: 13pt;"><em><strong>HISTORICAL CONTRIBUTIONS </strong>highlight the greatest academic manuscripts from the Brady Urological Institute over the past 100 years. As the Brady Urological Institute approaches its centennial, we will present a HISTORICAL CONTRIBUTION from each of the past 100 years. In the most recent experience, the most highly cited article from each year is selected; older manuscripts were selected based on their perceived impact on the field. We hope you enjoy!</em> </span><span style="color: #333333;"><br /> </span></span></span></div>
Anonymoushttp://www.blogger.com/profile/05286847723206340868noreply@blogger.com39tag:blogger.com,1999:blog-4730782586548300034.post-31205609650031845442015-03-24T08:09:00.003-04:002015-03-24T08:09:30.981-04:00Historical Contribution: 1968, Coffey et al, DNA, Androgens and Prostate Growth<span xmlns=""></span><br />
<span style="color: #660000; font-family: Georgia, Times New Roman, serif; font-size: x-large;" xmlns=""><b>1968</b></span><br />
<span xmlns=""><a href="http://ac.els-cdn.com/0003986168903196/1-s2.0-0003986168903196-main.pdf?_tid=fe40d416-d21d-11e4-afba-00000aacb35e&acdnat=1427198879_984abf7755685cf466510f66cfeda7cc"><b><span style="color: #660000; font-family: Georgia, Times New Roman, serif;">Coffey DS, Shimazaki J, Williams-Ashman HG. Polymerization of Deoxyribonucleotides in Realtion to Androgen-Induced Prostatic Growth. Ach Biochem Biophys. 1968. 124(1):184-98.</span></b></a><br /> </span><br />
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjHbqXZPaPEJhdMODueYR7u5xx4-rAHVHCn6TvCKHT_nsSzQcjlCvZ2h_50Av2xL5J2Z4ZL2uxgJeCplQMwYgzg1d_jmc8tEKSJSpC-Y3oGVdwBqLNFx4a1JjYq8owfAzBsKVdID9IOpPg/s1600/coffey3_cov.jpg" imageanchor="1" style="clear: right; margin-bottom: 1em; margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjHbqXZPaPEJhdMODueYR7u5xx4-rAHVHCn6TvCKHT_nsSzQcjlCvZ2h_50Av2xL5J2Z4ZL2uxgJeCplQMwYgzg1d_jmc8tEKSJSpC-Y3oGVdwBqLNFx4a1JjYq8owfAzBsKVdID9IOpPg/s1600/coffey3_cov.jpg" height="190" width="200" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Donald S. Coffey, PhD</td></tr>
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<span xmlns="">Long before becoming the Director of the Research Laboratories in the Department of Urology in 1974, Dr. Donald Coffey started a long career of investigation and discovery in the realm of benign and malignant prostatic growth. Based on observations that restoration of androgens after castration often results in regrowth of androgen-sensitive tissues, Coffey postulated that hyperplastic and hypertrophic changes in prostatic tissue could be detected in changes in DNA content. </span><br />
<span xmlns=""><br /></span>
<span xmlns="">In this 1968 manuscript, Dr. Coffey found that large doses of testosterone, when given to normal rats, only resulted in small increases in prostatic DNA content and DNA polymerase activity, and high levels of prostatic DNA activity and DNA polymerase levels are only present when the cells undergo active proliferation. The data supporting these conclusions demonstrates that following castration, the rat prostate decreases in size and DNA content. With exogenous testosterone, the prostate will grow and DNA content restored to normal levels… for some time. Even if excessive amounts of testosterone are administered, eventually the prostatic DNA content will plateau. DNA polymerase activity mirrored this effect, paralleling <em>"the enhancement of "DNA synthesis" by intact prostatic cells</em>." </span><br />
<span xmlns=""><br /> </span><br />
<span xmlns="">Follow the link <a href="http://ac.els-cdn.com/0003986168903196/1-s2.0-0003986168903196-main.pdf?_tid=fe40d416-d21d-11e4-afba-00000aacb35e&acdnat=1427198879_984abf7755685cf466510f66cfeda7cc">here</a> to access the manuscript from <a href="http://ac.els-cdn.com/0003986168903196/1-s2.0-0003986168903196-main.pdf?_tid=fe40d416-d21d-11e4-afba-00000aacb35e&acdnat=1427198879_984abf7755685cf466510f66cfeda7cc"><em>Archives of Biochemistry and Biophysics</em></a><em>. </em><br /> </span><br />
<span xmlns=""><em><br /></em></span>
<span xmlns=""><span style="color: #333333; font-family: Arial;"><span style="background-color: white; font-size: 13pt;">Visit the <a href="http://urology.jhu.edu/centennial/"><span style="color: #771000; text-decoration: underline;"><strong>Centennial Website</strong></span></a> or click <a href="http://urology.jhu.edu/centennial/pdf/1964.pdf"><span style="color: #771000; text-decoration: underline;"><strong>here</strong></span></a> to see more about the first 100 years at the Brady.</span></span><em style="background-color: white; color: #660000; font-family: Arial; font-size: 13pt;"><strong><br /></strong></em></span><br />
<span xmlns=""><em style="background-color: white; color: #660000; font-family: Arial; font-size: 13pt;"><strong>HISTORICAL CONTRIBUTIONS </strong>highlight the greatest academic manuscripts from the Brady Urological Institute over the past 100 years. As the Brady Urological Institute approaches its centennial, we will present a HISTORICAL CONTRIBUTION from each of the past 100 years. In the most recent experience, the most highly cited article from each year is selected; older manuscripts were selected based on their perceived impact on the field. We hope you enjoy!</em><span style="background-color: white; color: #660000; font-family: Arial; font-size: 13pt;"> </span></span><br />
<span xmlns=""><br /> </span><br />
<span xmlns=""><br /> </span><br />
Anonymoushttp://www.blogger.com/profile/05286847723206340868noreply@blogger.com9tag:blogger.com,1999:blog-4730782586548300034.post-19948287403767486132015-03-10T07:56:00.002-04:002015-03-10T07:56:24.876-04:00Historical Contribution: 1967, Schirmer and Scott, Prostate Cancer and Irradiation<span xmlns=""></span><br />
<b><span style="color: #660000; font-family: Georgia, Times New Roman, serif;"><span style="font-size: x-large;">1967</span><br /><a href="http://sma.org/southern-medical-journal/article/prostatic-cancer-and-irradiation-its-possible-mode-of-action-and-its-clinical-indication/">Schirmer HKA, Scott WW. Prostatic Cancer and Irradiation: Its Possible Mode of Action and its Clinical Indication. Southern Med Journal. 1967. 60;6:578-82.</a></span></b><br />
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiT1u4kZwxaqjxMVqSzGjo0H21AmatS-BkBQshdd82hSEQ_VKbIAP0TGXWzfCXc9ExJGhTIqrtT2ohJybLoLCHsXS_5gRUFP1vZmYtp5w8VirGIpc6QBcWDuKMphxO1kHxezjB3m-gwOQQ/s1600/1986-1987.jpg" imageanchor="1" style="clear: right; margin-bottom: 1em; margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiT1u4kZwxaqjxMVqSzGjo0H21AmatS-BkBQshdd82hSEQ_VKbIAP0TGXWzfCXc9ExJGhTIqrtT2ohJybLoLCHsXS_5gRUFP1vZmYtp5w8VirGIpc6QBcWDuKMphxO1kHxezjB3m-gwOQQ/s1600/1986-1987.jpg" height="203" width="320" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;"><span style="font-size: 12.8000001907349px;">HKA Schirmer (2nd from left, last row) </span><br />
<span style="font-size: 12.8000001907349px;">and WW Scott (2nd from right, 1st row), 1986-87.</span></td></tr>
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<span xmlns="">The Brady Urological Institute is well known for its advances in surgical treatment of prostatic disease, dating back to Hugh Hampton Young's perineal prostatectomy in 1904. The Brady was also a pioneer in radiation treatment for prostate cancer. In 1917, in the first Journal of Urology, HH Young demonstrated interstitial radiation (brachytherapy) for the treatment of prostate cancer. In this week's Historical Contribution, Horst Schirmer and William Scott embarked upon experimentation in freshly retrieved prostate cancer tissue to examine the possible effects of radiation therapy upon the tissue.</span><br />
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<span xmlns="">Based on the observations that (1) cancer cells derive chemical energy from lactic acid fermentation rather than oxidative metabolism (i.e. the Warburg effect; see FIGURE 2), (2) radiation preferentially affects cells undergoing aerobic metabolism, and (3) the catalase enzyme can attenuate the response of cells to radiation by reducing hydroxyl radical and molecular oxygen; Schirmer and Scott investigated the levels of catalase in normal prostate, well- and poorly-differentiated prostate cancers. They found that the catalase activity of normal prostate was 35 fold higher than catalase activity in prostate cancer. In addition, they found that well-differentiated prostate cancers had 6-fold higher catalase activity than poorly-differentiated cancers. They found corresponding decreases in oxygen consumption (i.e. respiration) and increases in glycolysis. </span><br />
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<span xmlns="">In the second part of this manuscript, Schirmer and Scott review three patients (of 16 treated at Hopkins) treated with prostate irradiation. Interestingly, all three patients had poorly differentiated prostate cancer and were treated with between 4500 and 5000 rads (a dose we now know to be biologically inadequate for prostate cancer). However, all three men experienced clinical improvement in prostate size and urinary symptoms. However, oncologic follow-up was short and the one patient who died of diffuse metastatic disease had residual, viable prostate cancer on histologic examination of the gland after his death. </span><br />
<span xmlns=""><br /></span>
<span xmlns="">Follow the link <a href="http://sma.org/southern-medical-journal/article/prostatic-cancer-and-irradiation-its-possible-mode-of-action-and-its-clinical-indication/">here</a> to access the <a href="http://sma.org/southern-medical-journal/article/prostatic-cancer-and-irradiation-its-possible-mode-of-action-and-its-clinical-indication/"><em>Southern Medical Journal</em></a>.</span><br />
<span xmlns=""><br /> </span>Anonymoushttp://www.blogger.com/profile/05286847723206340868noreply@blogger.com10tag:blogger.com,1999:blog-4730782586548300034.post-60701324033141709142015-03-03T07:00:00.000-05:002015-03-03T07:00:08.704-05:00Historical Contribution: 1965, Williams-Ashman, Androgens, Nucleic Acid & Protein Synthesis in Male Organs<span xmlns=""></span><br />
<span style="color: #660000; font-family: Georgia, Times New Roman, serif; font-size: x-large;" xmlns=""><b>1965</b></span><br />
<span xmlns=""><a href="http://onlinelibrary.wiley.com/doi/10.1002/jcp.1030660411/abstract"><b><span style="color: #660000; font-family: Georgia, Times New Roman, serif;">Williams-Ashman HG. Androgenic Control of Nucleic Acid and Protein Synthesis in Male Accessory Genital Organs. Jour of Cellular and Comp Physiology. 1965. 66;2:111-24.</span></b></a><br /> </span><br />
<span xmlns=""><br /> </span><br />
<span xmlns=""><a href="http://urology.jhu.edu/about/ashman.php"><b>Howard Guy Williams-Ashman, PhD</b></a>, was an internationally recognized authority on sex hormones and the biochemistry, biosynthesis, regulation and mode of action in both normal reproduction and malignant conditions. Dr. Williams-Ashman trained under Charles Huggins at the University of Chicago. For five years (1964-1969), he served as the Director of the Brady Laboratory for Reproductive Physiology at Johns Hopkins before returning to the University of Chicago. In this manuscript from 1965, Williams-Ashman discusses the reactions between RNA (ribonucleic acid) and protein synthesis in the prostate and seminal vesicle (SV). </span><br />
<span xmlns=""><br /></span>
<span xmlns="">Dr. Williams-Ashman starts by highlighting a number of important clinical observations: natural estrogens exert effects at much lower doses than androgens, physiologic actions of estrogens are quicker than those to androgens, sex genotype has little influence of reactivity to androgens and estrogens, and determining target tissues for androgens and estrogens can be challenging. He then reviews the scientific discoveries leading to the current understanding of androgens and development of the prostate and SV. He finishes by summarizing these data, stating:</span><br />
<span xmlns=""><br /></span>
<br />
<blockquote class="tr_bq">
<span xmlns="">"…androgenic hormones initiate and maintain the functional differentiation of the prostate gland and seminal vesicles… [through] primary changes in the ribosomal population density and in the levels of template RNA's."</span></blockquote>
<span xmlns=""><br /></span>
<span xmlns="">The changes in RNA polymerase activity may be among the first detectable metabolic changes following castration. In addition, although they were not yet discovered, he hypothesized that the androgen receptor would be "proteinaceous" and the resulting discussion between Drs. Williams-Ashman and several leading researchers in the field provides wonderful, historical insight into the understanding of sex hormones, sex hormone receptors and the interplay in extragenital tissues. </span><br />
<span xmlns=""><br /> </span><br />
<span xmlns="">Follow the link <a href="http://onlinelibrary.wiley.com/doi/10.1002/jcp.1030660411/abstract">here</a> to access the <a href="http://onlinelibrary.wiley.com/doi/10.1002/jcp.1030660411/abstract"><em>Journal of Cellular Physiology</em></a>.</span>Anonymoushttp://www.blogger.com/profile/05286847723206340868noreply@blogger.com6tag:blogger.com,1999:blog-4730782586548300034.post-81251232747129999582015-03-02T07:00:00.000-05:002015-03-02T14:55:22.022-05:00MRI-Robot Helps Target Cancer<b>MRI (magnetic resonance imaging) </b>has recently been demonstrated to help in the diagnosis of prostate cancer, especially in men with a prior negative biopsy or those meeting criteria for active surveillance (See our prior blog on <a href="http://bradyurology.blogspot.com/2015/01/mri-improves-misclassification-of-men.html">MRI and Active Surveillance</a>). Traditionally prostate biopsies are performed with ultrasound imaging – which is great at targeting the prostate, but not necessarily for finding prostate cancer. Fusing MRI and ultrasound imaging is a recent advance that has helped urologists make use of the precision of MRI for finding tumors and the targeting of ultrasound to sample them.<br />
<br />
Fusing MRI and ultrasound images can be complex and does not always work perfectly. If the tumor could be targeted with MRI, the extra step of fusion could be avoided. However, MRI machines make use of extremely strong magnets and metal instruments cannot be near the machine when it is turned on. This makes it impossible to use metal needles or machines with any metal components (including electrical wiring). <br />
<br />
Researchers at Johns Hopkins, led by <a href="http://urology.jhu.edu/danstoianovici/"><b>Dan Stoianovici, PhD</b>,</a> Director of the Urology Robotics Program, have developed a completely MRI-compatible robot to target the prostate and cancers within it. The robot makes use of pneumatic system composed of rubber and plastic tubing, screws and gears to manipulate a MRI-compatible needle to target the prostate. "The robotic device mounts on the MRI table alongside the patient. The physician selects a suspicious region that the MRI has shown, and the robot automatically guides the needle to target and presets the depth of insertion."<br />
<br />
<blockquote class="tr_bq">
<b><i><span style="color: #660000;">"To the best of our knowledge, this is the only robot approved by the FDA to operate in the MR environment in general, not only for the prostate." </span></i></b></blockquote>
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The <a href="http://urobotics.urology.jhu.edu/projects/MrBot/">MR-bot</a> (MRI-robot) has been approved by the Food and Drug Administration (FDA) and Insitutional Review Board (IRB) of Johns Hopkins for a clinical trial in humans. Urologists <a href="http://urology.jhu.edu/mohamadallaf/">Mohamad Allaf, MD </a>and <a href="http://urology.jhu.edu/ashleyross/">Ashley Ross, MD, PhD</a>, perform the biopsies. The first few cases indicate that robotic biopsy is safe and feasible. <br />
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<br />
With more precise imaging and techniques, urologists may continue to improve the precision of prostate biopsies. This work was awarded best paper of the Engineering and Urology Society of the American Urological Association. <br />
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Read more about the MrBOT at: <a href="http://urobotics.urology.jhu.edu/projects/MrBot/">http://urobotics.urology.jhu.edu/projects/MrBot/</a><br />
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<span style="background-color: white; color: #333333; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: 14.8500003814697px; line-height: 20.7900009155273px;" xmlns=""><span style="font-family: Arial;"><span style="font-size: 11pt;">Portions of this story were extracted from </span></span></span><a href="http://urology.jhu.edu/newsletter/2015/detecting_prostate_cancer_2.php">"First-Ever MRI Robot Targets Potential Cancer Sites for Biopsy"</a><span style="background-color: white; color: #333333; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: 14.8500003814697px; line-height: 20.7900009155273px;"> in </span><a href="http://urology.jhu.edu/newsletter/2015/" style="background-color: white; color: #771000; font-family: Arial; font-size: 14.8500003814697px; line-height: 20.7900009155273px; text-decoration: none;"><em>Discovery: Volume XI, Winter 2015</em></a><span style="background-color: white; color: #333333; font-family: Arial; font-size: 14.8500003814697px; line-height: 20.7900009155273px;"> by the Patrick C. Walsh Prostate Cancer Research Fund.</span>Anonymoushttp://www.blogger.com/profile/05286847723206340868noreply@blogger.com16tag:blogger.com,1999:blog-4730782586548300034.post-18679596311402444842015-02-04T07:00:00.000-05:002015-02-04T07:00:11.581-05:00Penile Cancer: Carcinoma in situ<span xmlns=""></span><br />
<span xmlns="">Carcinoma in situ (CIS) of the penis refers to a squamous cell cancer limited to the most superficial layers of the penile skin. This cancer is also known as <em>Erythroplasia of Queyrat</em> if on the glans (head) of the penis or <em>Bowen Disease</em> if on the shaft of the penis and was covered in a <a href="http://bradyurology.blogspot.com/search/label/Penile%20Cancer">previous blog</a>. While CIS is technically a non-invasive cancer and believed to have low metastatic potential, it has features of high-grade (potentially aggressive) cancer that warrants careful management.</span><br />
<br />
<h2>
<span xmlns="">History</span></h2>
<span xmlns="">CIS was inititally described by Queyrat in 1911 as a red, velvety, well-marginated lesion of the glans penis or prepuce (of uncircumcised men). Bowen described a similar lesion of the penile skin in 1912. The original description of Bowen disease related to subsequent internal malignancy, however subsequent studies have demonstrated that this relationship was nothing more than coincidence.[1] </span><br />
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<h2>
<span xmlns="">Presentation and Prognosis</span></h2>
<span xmlns="">CIS has a similar clinical presentation whether on the glans penis or shaft. As described above, CIS can appear as a red, velvety, well-marginated lesion on the penis. Alternatively the lesion can be scaly, crusted or ulcerated – similar in appearance to eczema or psoriasis. Development of metastasis for CIS is incredibly rare – however 10-33% of CIS on the glans and 5% of CIS on the shaft can progress to more invasive, dangerous disease.[2,3]</span><br />
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<h2>
<span xmlns="">Management</span></h2>
<span xmlns="">As CIS rarely metastasizes, treatment is focused on (1) confirmation of a non-invasive lesion, (2) resection of lesions with an adequate microscopic margin and (3) penis-sparing techniques if the lesion is on the glans. Confirmation of non-invasive malignancy may require multiple biopsies or complete excision of the area of concern. A 5mm margin if often adequate for lesions on the shaft, while circumcision will cure most cases of CIS on the prepuce. Lymph node dissection is only performed in cases suspicious for invasion or enlarged lymph nodes. </span><br />
<span xmlns=""><br /></span>
<h4>
<span xmlns="">Penis-sparing treatments</span></h4>
<span xmlns="">Lesions of the glans penis can be difficult to treat surgically without distorting normal penile anatomy or sensation. A number of topical treatments including 5-fluorouracil, 5% imiquimod, laser ablation (YAG or KTP lasers) and radiation therapy have all been used with success.[4-10] For patients with large tumors or lesions refractory to topical treatment, local skin excision can be performed with skin grafting as needed. </span><br />
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<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg4S9ihhqHOB1WCOJA-9y3ueB8Sde98a2eGFoFVLbwSumEsy1Q83Lh8RqC8f3_wVOyRhWfI5v4GsCpSPaf1AtDenKFxG_zQxDj8CSY0dX4Y9SvV5znSYCDaUXIFbuxSByabHhtvLv_GgoU/s1600/penisgraft.png" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg4S9ihhqHOB1WCOJA-9y3ueB8Sde98a2eGFoFVLbwSumEsy1Q83Lh8RqC8f3_wVOyRhWfI5v4GsCpSPaf1AtDenKFxG_zQxDj8CSY0dX4Y9SvV5znSYCDaUXIFbuxSByabHhtvLv_GgoU/s1600/penisgraft.png" height="220" width="400" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Penile lesion (CIS) completely excised (left) and with a skin graft using non-hair bearing skin of the groin (right).</td></tr>
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<span xmlns="">For patients with CIS involving the glans, partial or complete excision with partial or complete resurfacing can be performed.[11,12] </span><br />
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjIqO8ylFwl5zQubK2zlFpKwXEcBsU8FFlvbQ4ZHSW2ofnYt-NfJ1uUHofb7_fVbxlmR5BlcJwDuRfTHd8hy2T_3wfMmL3MGZ4j9-qUPB15QUQRvX1vyrvagGKqnoi9W0mjt-3F9WKUfWE/s1600/cis_resurface.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjIqO8ylFwl5zQubK2zlFpKwXEcBsU8FFlvbQ4ZHSW2ofnYt-NfJ1uUHofb7_fVbxlmR5BlcJwDuRfTHd8hy2T_3wfMmL3MGZ4j9-qUPB15QUQRvX1vyrvagGKqnoi9W0mjt-3F9WKUfWE/s1600/cis_resurface.jpg" height="281" width="400" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">A. CIS on the glans penis, B. Glanular skin removed, C. Skin graft placed on the glans, D. Final, cosmetically pleasant result. From Palminteri etal. [12]</td></tr>
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<span xmlns=""><br /></span>
<span xmlns="">These penile surgeries often involve a multidisciplinary approach including a urologic oncologist, plastic (reconstructive) surgeon and excellent pathologists to ensure eradication of the disease. Penile cancer is a rare disease and balancing the risks of cancer with penile reconstruction and function is best done at a center with experience treating this disease.</span><br />
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<span xmlns=""></span><br />
<ol>
<li><span xmlns=""><span style="font-size: x-small;">Anderson SL, Nielson A, and Reymann F: Relationship between Bowen disease and internal malignant tumors. Arch Dermatol 1973; 108: pp. 367.</span></span></li>
<li><span xmlns=""><span style="font-size: x-small;">Buechner SA: Common skin disorders of the penis. BJU Int 2002; 90: pp. 498-506.</span></span></li>
<li><span xmlns=""><span style="font-size: x-small;">Bleeker MCG, Heideman DAM, Snijders PJF, et al: Penile cancer: epidemiology, pathogenesis, and prevention. World J Urol 2009; 27: pp. 141-150.</span></span></li>
<li><span xmlns=""><span style="font-size: x-small;">Harrington KJ, Price PM, Fry L, Witherow RO. Erythroplasia of Queyrat treated with isotretinoin. Lancet. Oct 16 1993;342(8877):994-5. </span></span></li>
<li><span xmlns=""><span style="font-size: x-small;">Micali G, Nasca MR, De Pasquale R. Erythroplasia of Queyrat treated with imiquimod 5% cream. J Am Acad Dermatol. Nov 2006;55(5):901-3. </span></span></li>
<li><span xmlns=""><span style="font-size: x-small;">Conejo-Mir JS, Munoz MA, Linares M, Rodriguez L, Serrano A. Carbon dioxide laser treatment of erythroplasia of Queyrat: a revisited treatment to this condition. J Eur Acad Dermatol Venereol. Sep 2005;19(5):643-4. </span></span></li>
<li><span xmlns=""><span style="font-size: x-small;">Arlette JP. Treatment of Bowen's disease and erythroplasia of Queyrat. Br J Dermatol. Nov 2003;149 Suppl 66:43-9. </span></span></li>
<li><span xmlns=""><span style="font-size: x-small;">Orengo I, Rosen T, Guill CK. Treatment of squamous cell carcinoma in situ of the penis with 5% imiquimod cream: a case report. J Am Acad Dermatol. Oct 2002;47(4 Suppl):S225-8. </span></span></li>
<li><span xmlns=""><span style="font-size: x-small;">Micali G, Lacarrubba F, Dinotta F, Massimino D, Nasca MR. Treating skin cancer with topical cream. Expert Opin Pharmacother. Jun 2010;11(9):1515-27. </span></span></li>
<li><span xmlns=""><span style="font-size: x-small;">Grabstald H, and Kelley CD: Radiation therapy of penile cancer. Urology 1980; 15: pp. 575-576.</span></span></li>
<li><span xmlns=""><span style="font-size: x-small;">Pompeo AC, Zequi Sde C, Pompeo AS. Penile cancer: organ-sparing surgery. Curr Opin Urol. 2015 Mar;25(2):121-8. doi: 10.1097/MOU.0000000000000149.</span></span></li>
<li><span xmlns=""><span style="font-size: x-small;">Palminteri E, Berdondini E, Lazzeri M, Mirri F, Barbagli G. Resurfacing and reconstruction of the glans penis. Eur Urol. 2007 Sep;52(3):893-8. Epub 2007 Jan 22.</span></span></li>
</ol>
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Anonymoushttp://www.blogger.com/profile/05286847723206340868noreply@blogger.com113tag:blogger.com,1999:blog-4730782586548300034.post-88247423085663506112015-02-03T07:00:00.000-05:002015-02-03T07:00:07.434-05:00Historical Contribution: 1964, Schirmer & Walton, Hypothermia and Kidney Function<span xmlns=""></span><br />
<span style="color: #660000; font-family: Georgia, Times New Roman, serif; font-size: x-large;" xmlns=""><b>1964</b></span><br />
<span style="color: #660000; font-family: Georgia, Times New Roman, serif;" xmlns=""><b><a href="http://urology.jhu.edu/centennial/pdf/1964.pdf">Schirmer HKA, Walton K. The Effet of Hypothermia upon Respiration and Anerobic Glycolysis of Dog Kidney. Invest Urol. 1964. 1;6:604-9.</a></b></span><br />
<span xmlns=""><br /> </span><br />
<span xmlns="">The first deliberate partial nephrectomy for the excision of a tumor was credited to Vincenz Czerny in 1887. Numerous studies over the next decades defined the surgical anatomy and feasibility of partial nephrectomy for a variety of localized kidney processes (including cancer). Lack of early diagnostics and technical challenges prevented the operation from being widely utilized in the early 1900's. While these early researchers investigated repair mechanisms of the kidney, advances in the understanding of segmental blood supply and renal hypothermia to prevent ischemic damage were not introduced until the 1950's and 1960's.[1] </span><br />
<table cellpadding="0" cellspacing="0" class="tr-caption-container" style="float: right; margin-left: 1em; text-align: right;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEieGnXMJnihRqfWBwBu13j7E3arF5v3TLg-Cu3UUSKinEpS9w_TfFc-qNTHkmtHIZNsLBWbef9Bv6Uuq-9cLvxdu81I_KbHVJgW95ZNOCFMqqLKS9fqw6mMHOE3IDzFHY6irFY0MgdZHUg/s1600/schirmer.png" imageanchor="1" style="clear: right; margin-bottom: 1em; margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEieGnXMJnihRqfWBwBu13j7E3arF5v3TLg-Cu3UUSKinEpS9w_TfFc-qNTHkmtHIZNsLBWbef9Bv6Uuq-9cLvxdu81I_KbHVJgW95ZNOCFMqqLKS9fqw6mMHOE3IDzFHY6irFY0MgdZHUg/s1600/schirmer.png" height="195" width="200" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Horst Schirmer, MD</td></tr>
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<span xmlns=""><br />In 1964, Horst Schirmer and Kenneth Walton of the Brady Urological Institute investigated the effects of hypothermia on the kidney. Prior work demonstrated that, with local cooling, renal function would only be temporarily depressed and irreversible damage (under normothermic conditions) could be limited. They investigated ox'ygen consumption and glycolysis in the kidneys of dogs. They found:</span><br />
<ul>
<li><span xmlns="">With decreasing temperature, the reduction in glycolysis associated with ischemia was tempered (33% at 27C, 17% at 17C and near zero at 7C).</span></li>
<li><span xmlns="">After achieving hypothermia of 7C, normal function returned after 1 hour. </span></li>
<li><div>
<span xmlns="">Interruption of blood flow for 4 hours resulted in:</span></div>
<ul>
<li><span xmlns="">75% reduction in function in the normothermic kidney</span></li>
<li><span xmlns="">Unchanged function in the cooled (7C) kidney</span></li>
</ul>
</li>
<li><span xmlns="">By examining both tissue from the cortex and medulla of the kidney, the cortex is nearly 7x more active than the medulla – providing evidence that cortical cooling is sufficient to provide effective hypothermia.</span></li>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi1WJKP8fEo282ac_UolAre-ZTGvcFiMIIVLagHM_avai3zhqDU1cizwHdhFD1-DW7DDtwlZqWFRSQ1fMluH3qouXVTMyrF-otbPCE366QUqdGjmKNW0Mn6s5WZ-8Kaan3X2omDvtSwZBM/s1600/1964.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi1WJKP8fEo282ac_UolAre-ZTGvcFiMIIVLagHM_avai3zhqDU1cizwHdhFD1-DW7DDtwlZqWFRSQ1fMluH3qouXVTMyrF-otbPCE366QUqdGjmKNW0Mn6s5WZ-8Kaan3X2omDvtSwZBM/s1600/1964.jpg" height="400" width="240" /></a></div>
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<span xmlns=""><span style="color: #333333; font-family: Arial;"><span style="background-color: white; font-size: 13pt;">To read the entire manuscript: follow the link above, visit the <a href="http://urology.jhu.edu/centennial/"><span style="color: #771000; text-decoration: underline;"><strong>Centennial Website</strong></span></a> or click <a href="http://urology.jhu.edu/centennial/pdf/1964.pdf"><span style="color: #771000; text-decoration: underline;"><strong>here</strong></span></a>.</span><br /><span style="background-color: white;"><br /> </span></span><span style="font-family: Times New Roman; font-size: 12pt;"><br /> </span></span><br />
<div style="background: white;">
<span xmlns=""><span style="color: #660000; font-family: Arial;"><span style="font-size: 13pt;"><em><strong>HISTORICAL CONTRIBUTIONS </strong>highlight the greatest academic manuscripts from the Brady Urological Institute over the past 100 years. As the Brady Urological Institute approaches its centennial, we will present a HISTORICAL CONTRIBUTION from each of the past 100 years. In the most recent experience, the most highly cited article from each year is selected; older manuscripts were selected based on their perceived impact on the field. We hope you enjoy!</em> </span><span style="color: #333333;"><br /> </span></span></span></div>
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<span style="font-size: x-small;">[1] Herr HW.A history of partial nephrectomy for renal tumors.J Urol. 2005 Mar;173(3):705-8.</span><div style="background: white;">
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Anonymoushttp://www.blogger.com/profile/05286847723206340868noreply@blogger.com2tag:blogger.com,1999:blog-4730782586548300034.post-12090018841871522622015-02-02T07:00:00.000-05:002015-02-02T07:00:04.584-05:00Getting closer to an “quantitative” diagnosis of prostate cancer<span xmlns=""></span><br />
<span xmlns=""><strong><em>Histomorphometry</em></strong> is the study of the microscopic organization and structure of tissue in a quantitative manner under the microscope. This process was briefly described in a <a href="http://bradyurology.blogspot.com/2014/09/looking-to-identify-men-with-high-risk.html">prior blog</a>, and often involves computer-assisted technology to provide objective measures cellular architecture to aide in diagnosis – a process that is often based on subjective classification of microscopic features. </span><br />
<span xmlns=""><br />Most cancers, prostate cancer included, are diagnosed by a pathologist – who examines tissue under a microscope to determine the presence and aggressiveness of a cancer. The future of digital pathology will likely use <span style="text-decoration: underline;"><strong>prostate cancer quantitative histomorphometry</strong></span> using computer-assisted scanned image features and may serve as a new and innovative predictive tool to improve determination of aggressive phenotypes of cancer. In prior work, <b><a href="http://urology.jhu.edu/robertveltri/">Dr. Robert Veltri, PhD</a></b>, of the Brady Urological Institute, demonstrated that a special "spectrophotometer" microscope was accurate and capable of predicting stage, recurrence and progression of prostate cancer when examining portions of prostate cancer slides.[1] </span><br />
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<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjF4m-bfMTFc2bEhSjHju8mnRYjVRb60l429Ym5z7VAUA1dhmrwqP2XLGeCWIAgzwMWiuqaYyzjXmjKVNXfqp-aeDvoCCALcz9NwHXNUw0xkXCZQXyPa64b1GFuvOrhqRKCoqN3IMwOGbk/s1600/image1.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjF4m-bfMTFc2bEhSjHju8mnRYjVRb60l429Ym5z7VAUA1dhmrwqP2XLGeCWIAgzwMWiuqaYyzjXmjKVNXfqp-aeDvoCCALcz9NwHXNUw0xkXCZQXyPa64b1GFuvOrhqRKCoqN3IMwOGbk/s1600/image1.jpg" height="106" width="400" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">An original, high-powered image of prostate cancer (a) is segmented into areas of individual nuclei (b), classified into individual sets (c) and segmented by the computer-alogorithm. From Ali <i>etal</i> [2].</td></tr>
</tbody></table>
<span xmlns=""><br /></span>
With collaborator, Anant Madabhushi, PhD, and his team at Case Western Reserve University, Dr. Veltri is working to develop new techniques to examine the entire slide image in a high-throughput process. These novel tools could form the basis of future software tools to conduct, in cooperation with the pathologist, automated, rapid and reproducible identification and quantification of tissue histology morphologic and molecular events – enabling machine-based predictions of tumor aggressiveness and outcomes such as recurrence, metastasis and survival.<br />
<span xmlns=""><br /> </span><br />
<span xmlns="">In a recent experiment, Drs. Veltri and Madabhushi examined 80 prostate cancers looking at a variety of cellular features. Through a complex computer algorithm termed <span style="text-decoration: underline;"><strong>adaptive active contour scheme (AdACM)</strong></span>, they were able to distinguish features of nuclei, gland architecture, and texture and then identify the best features to discriminate Gleason grade patterns. Using these features, AdACM was able to distinguish Gleason score patterns with an accuracy of 86%.[2]</span><br />
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<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhDQLTTViNIiZ4-uK1ePJM0KORpro46_MoqXxrIBNCV6E16dOJAj6z_CUXTWCchQs8zFiGs_KyaCmlO_ipH5HK1EIphZX3VT1Dp-kx3sTsGX2xr5TrvZWUtCoLxOEpP00o3V7TsqSQfapg/s1600/1-s2.0-S0895611114001761-gr4.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhDQLTTViNIiZ4-uK1ePJM0KORpro46_MoqXxrIBNCV6E16dOJAj6z_CUXTWCchQs8zFiGs_KyaCmlO_ipH5HK1EIphZX3VT1Dp-kx3sTsGX2xr5TrvZWUtCoLxOEpP00o3V7TsqSQfapg/s1600/1-s2.0-S0895611114001761-gr4.jpg" height="226" width="400" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Different computer-generated features to model architecture of prostate cancer in a core of tissue from a prostate biopsy. From Ali <i>etal</i> [2].</td></tr>
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<span xmlns=""><br /></span>
This is just some of the exciting research ongoing at the Brady Urological Institute at Johns Hopkins that will improve the way we diagnose and treat prostate cancer.<br />
<span xmlns=""><br /> </span><br />
<span style="font-size: x-small;" xmlns="">[1] </span><span style="font-size: x-small;">Ali S, Veltri R, Epstein JI, Christudass C, Madabhushi A.</span><span style="font-size: x-small;">Adaptive energy selective active contour with shape priors for nuclear segmentation and gleason grading of prostate cancer.</span><span style="font-size: x-small;">Med Image Comput Comput Assist Interv. 2011;14(Pt 1):661-9.</span><br />
<span style="font-size: x-small;" xmlns=""></span><br />
<span style="font-size: x-small;" xmlns="">[2] </span><span style="font-size: x-small;">Ali S, Veltri R, Epstein JI, Christhunesa Christudass CS, Madabhushi A. Selective Invocation of Shape Priors for Deformable Segmentation and Morphologic Classification of Prostate Cancer Tissue Microarrays. CMIG, December, 2014. dx.doi.org/10.1016/j.compmedimag.2014.11.001</span><br />
Anonymoushttp://www.blogger.com/profile/05286847723206340868noreply@blogger.com53tag:blogger.com,1999:blog-4730782586548300034.post-67669751968666023142015-01-30T07:00:00.000-05:002015-01-30T07:00:03.305-05:00A new trial down the “Hedgehog” pathway for men with high-risk prostate cancer<span xmlns=""></span><br />
<span xmlns="">Nearly ten years ago, Johns Hopkins researchers David Berman and Philip Beachy discovered the <strong>hedgehog pathway</strong> in mice with prostate cancer.[1] This molecular pathway is turned on in the embryologic development of lung, pancreas, prostate, brain and other organs during normal development. In prostate cancer, this pathway is abnormally turned "on" as prostate cancer grows and spreads. Patrick C. Walsh, MD, describes the pathway, <em>"It's like soil and seeds. The soil is the stroma of the prostate — the connective tissue that serves as its framework — and the cancer cells are the seeds."</em> And the Hedgehog protein is compost, sunlight and water — everything the seeds need to grow. <em>"If these cells spread but try to grow in poor soil, they can't survive. But if they can manufacture the Hedgehog signal, they can make the soil that they need — they can pack their lunch and take it with them."</em></span><br />
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<span xmlns="">In their original study, published in <em>Nature</em>,[1] Drs. Berman and Beachy demonstrated that giving drugs that could block the Hedgehog pathway, could shrink human prostate cancer tumors in animals. That model is now ready for prime-time testing in humans. <a href="http://urology.jhu.edu/ashleyross/"><strong>Dr. Ashley Ross, MD, PhD</strong></a>, Assistant Professor in Urology, Oncology, and Pathology, is partnering with Emmanuel Antonarakis, MD, medical oncologist, are opening a randomized, placebo-controlled clinical trial of a highly selective Hedgehog pathway inhibitor, called <strong>LDE225</strong> and made by Novartis. Dr. Ross explains the hypothesis of the trial:</span><br />
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<tr><td class="tr-caption" style="text-align: center;"><b>Ashley E. Ross, MD, PhD</b></td></tr>
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<blockquote class="tr_bq">
<span xmlns=""><em>"By looking at gene expression patterns, we and others have found that the Hedgehog pathway appears up-regulated in men with disease that metastasizes after local therapy. Also, in men with advanced prostate cancer, Itraconazole, which inhibits the Hedgehog pathway, appears to slow the disease by a mechanism independent of the androgen receptor. Itraconazole is an antifungal drug. Recently, new, Hedgehog pathway specific drugs with much more favorable toxicity profiles are available."</em></span></blockquote>
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Men with high-risk prostate cancer are badly in need of a drug that could potentially prevent cancer growth and metastasis. In these patients, there is always the possibility that, even after surgery or radiation therapy, some cancer cells have already escaped the prostate, are hiding somewhere in the body, and will repopulate. Use of a systemic Hedgehog inhibitor may help wipe out these "micrometastatic" cells. Dr. Ross explains,<br />
<blockquote class="tr_bq">
<span style="color: #660000;" xmlns=""><em><b>"We need to start thinking of high-risk disease as a different type of cancer, a systemic disease, and we have to start treating them like we treat other cancers, with a systemic approach in addition to surgery and/or radiation."</b></em></span></blockquote>
<span xmlns=""><br />The trial is open to radical prostatectomy patients at Johns Hopkins with <b>high-risk prostate cancer: men with a Gleason score of 8 to 10, a PSA of 20 or greater, or clinical stage T3 disease</b>. The men who receive the drug will take the pill for four weeks before radical prostatectomy. All of the men will undergo a repeat biopsy and will have a molecular profile done on their cancer cells before surgery, and then will have the radical prostatectomy specimens examined afterward. Dr. Ross explains, <em>"It's a pharmacodynamic trial, to see if this new drug actually gets into the prostate and inhibits the Hedgehog pathway as we expect it should. Of course, men will be followed closely following prostatectomy and we will also monitor whether superior cancer control results are achieved in those who received LDE225."</em></span><br />
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<span xmlns="">This blog and quotations are extracted from:</span><br />
<span xmlns=""><a href="http://urology.jhu.edu/newsletter/2015/prostate_cancer_clinical_trials1.php">Target: Hedgehog Pathway, New Trial Opens for Men with High-Risk Prostate Cancer</a> in <a href="http://urology.jhu.edu/newsletter/2015/">Discovery, Volume XI, Winter 2015.</a><br /> </span><br />
<span xmlns=""><a href="http://urology.jhu.edu/newsletter/prostate_cancer811.php">Hedgehog Blockers:Can They Stop Advanced Prostate Cancer? Scientists One Step Closer To Finding Out</a> in <a href="http://urology.jhu.edu/newsletter/prostate_cancer_update_2005_II.php">Prostate Cancer Discovery, Volume II, Autumn 2005</a>.</span><br />
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<span style="font-size: x-small;" xmlns="">[1] Karhadkar SS, Bova GS, Abdallah N, Dhara S, Gardner D, Maitra A, Isaacs JT, Berman DM, Beachy PA. Hedgehog signalling in prostate regeneration, neoplasia and metastasis. Nature. 2004 Oct 7;431(7009):707-12. Epub 2004 Sep 12.</span><br />
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Anonymoushttp://www.blogger.com/profile/05286847723206340868noreply@blogger.com7tag:blogger.com,1999:blog-4730782586548300034.post-84114752030499925072015-01-27T07:00:00.000-05:002015-01-27T07:00:01.142-05:00Historical Contribution: 1963, King et al, The Bladder Neck in Childhood <span xmlns=""></span><br />
<span style="color: #660000; font-family: Georgia, Times New Roman, serif; font-size: x-large;" xmlns=""><b>1963</b></span><br />
<span style="font-family: Georgia, Times New Roman, serif;" xmlns=""><b><a href="http://urology.jhu.edu/centennial/pdf/1963.pdf"><span style="color: #660000;">King LR, Mellins HZ, Scott WW. Radiographic Evaluation of the Bladder Neck in Childhood. Trans of Amer Assoc of Genito-urinary Sugeons. 1963. 55:7-12.</span></a><br /> </b></span><br />
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<span xmlns="">In the <em>Transcripts of the American Association of Genitourinary Surgeons</em>, Lowell King, Harry Mellins and William Wallace Scott detail the anatomy of voiding in 121 pediatric patients. Children ranged from one day to 17 years old. They found a number of interesting observations they describe in the manuscript:</span><br />
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<li><span xmlns="">Approximately 40% of normal girls will have a narrowed proximal urethra – this has no bearing on incidence of vesicoureteral reflux or clinical outcomes and can therefore be considered normal.</span></li>
<li><span xmlns="">Of boys with outlet obstruction, about half of the patients had meatal stenosis and the other half had posterior urethral valves (PUV). </span></li>
<li><span xmlns="">Of boys with recurrent urinary tract infections (UTI), approximately half had a congenital abnormality of the outlet – either PUV or an ureterocele. The rest had normal anatomy but functional deficits that led to residual urine and UTI.</span></li>
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<span xmlns="">In conclusion, King, Mellins and Scott found that there was a characteristic appearance of the bladder neck in pediatric patients with obstruction. However, <em>"A narrow bladder neck relative to the proximal urethra as seen in the AP view is a common finding, and is certainly not a specific sign of bladder neck contracture."</em></span><br />
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<span xmlns=""><span style="background-color: white; color: #333333; font-family: Arial; font-size: 13pt;">To read the entire manuscript: follow the link above, visit the <a href="http://urology.jhu.edu/centennial/"><span style="color: #771000; text-decoration: underline;"><strong>Centennial Website</strong></span></a> or click <a href="http://urology.jhu.edu/centennial/pdf/1963.pdf"><span style="color: #771000; text-decoration: underline;"><strong>here</strong></span></a>.</span></span><br />
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<span xmlns=""><span style="color: #660000;"><span style="font-family: Arial; font-size: 13pt;"><em><strong>HISTORICAL CONTRIBUTIONS </strong>highlight the greatest academic manuscripts from the Brady Urological Institute over the past 100 years. As the Brady Urological Institute approaches its centennial, we will present a HISTORICAL CONTRIBUTION from each of the past 100 years. In the most recent experience, the most highly cited article from each year is selected; older manuscripts were selected based on their perceived impact on the field. We hope you enjoy!</em> </span><span style="color: black; font-family: Times New Roman; font-size: 13pt;"><br /> </span></span></span></div>
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Anonymoushttp://www.blogger.com/profile/05286847723206340868noreply@blogger.com3tag:blogger.com,1999:blog-4730782586548300034.post-39866678471286947882015-01-26T07:00:00.000-05:002015-01-27T11:36:17.823-05:00The Brady Centennial: “Diamond Jim” Brady<span xmlns=""></span><br />
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<tr><td class="tr-caption" style="text-align: center;">James "Diamond Jim" Buchanan Brady</td></tr>
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<span xmlns="">One hundred years ago, the Brady Urological Institute opened its doors to patients. The funding for the institute came to Hugh Hampton Young as a gift from James "Diamond Jim" Buchanan Brady. Brady was a wealthy railroad tycoon who sought treatment for prostatic disease at Johns Hopkins. His story is told in this blog.</span><br />
<span xmlns=""><br />Diamond Jim was born in New York City in 1856 to a modest household. Through a number of employment opportunities he worked himself into the railroad industry, starting first with the New York Central Railroad and gaining prominence with Manning, Maxwell and Moore (a railroad supply company), the Pressed Steel Car Company, and Vice President of the Standard Steel Company.</span><br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiuUtEyl4kfJMEbRFy7mpM2N3iLO31TEyLg0x7PWcAMdJwdtpZypvc7BUoj1CVjr3CaIaPzLRJTMDfqStKpa00YtgOHdvxA-WHZ6bwIn9fambrJwmKswxUVPpfOAzFPVIL2AdZCZvR-s-4/s1600/diam_graphic_full.jpg" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiuUtEyl4kfJMEbRFy7mpM2N3iLO31TEyLg0x7PWcAMdJwdtpZypvc7BUoj1CVjr3CaIaPzLRJTMDfqStKpa00YtgOHdvxA-WHZ6bwIn9fambrJwmKswxUVPpfOAzFPVIL2AdZCZvR-s-4/s1600/diam_graphic_full.jpg" height="640" width="99" /></a><span xmlns="">Diamond Jim had a passion for fine clothes, expensive jewelry, women and food. A <a href="http://www.nytimes.com/2008/12/31/dining/31diam.html?pagewanted=all&_r=0">NY Times article in 2008</a> detailed the enormity of a typical Brady diet (see picture). He is rumored to have been the first owner of an automobile in New York City (1895). His long time girlfriend was Lillian Russell, a well-known actress and singer of the times. He garnished himself and Lillian in an extensive jewelry collection – conservatively estimated to be worth $2 million at that time! </span><br />
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<span xmlns="">Diamond Jim also suffered from obstructive uropathy. As Diamond Jim was obese, diabetic and in poor general health, a number of hospitals in Boston, New York, and Philadelphia turned him away from open prostate surgery (the treatment of choice at the time for benign prostatic hyperplasia, BPH). Hugh Hampton Young had developed his "punch" procedure, a transurethral surgery for BPH and precursor to the modern TURP (transurethral resection of the prostate), and successfully treated Diamond Jim. Diamond Jim was so grateful he contributed $200k <i>"for a building in which the laboratory and experimental side should play a very important role, and in which clinical material, public and private, outpatient and inpatient could be used for study, research and advancement in the field of urology."</i></span><br />
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The legacy of Diamond Jim lives on in the Brady Urological Institute which turns 100 years old this month.</b><br />
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Read more about Diamond Jim at:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjgMXk5pBPJhlF4jJnaU8D7Yr4gIdh3ubn3z6fbcFMGfMJzpJBcBk__DD4VkLdvUOsB9apQgYED708vaDomeLLvdIOPU3gutscpR9pmp_pNjnVR2rmXdWx1erNrF6QRspp7jfBig3aYaqo/s1600/centennial.gif" imageanchor="1" style="clear: right; float: right; margin-bottom: 1em; margin-left: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjgMXk5pBPJhlF4jJnaU8D7Yr4gIdh3ubn3z6fbcFMGfMJzpJBcBk__DD4VkLdvUOsB9apQgYED708vaDomeLLvdIOPU3gutscpR9pmp_pNjnVR2rmXdWx1erNrF6QRspp7jfBig3aYaqo/s1600/centennial.gif" height="160" width="200" /></a><b><span style="color: #073763;">The Brady Centennial Website</span></b>:<br />
<a href="http://urology.jhu.edu/centennial/">http://urology.jhu.edu/centennial/</a><br />
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<a href="http://topics.nytimes.com/top/reference/timestopics/people/b/diamond_jim_brady/index.html">Diamond Jim Brady, The New York Times.</a><br />
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<a href="http://diamond%20jim%20brady/">Diamond Jim Brady, Wikipedia.</a></div>
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<a href="http://www.gourmandizer.com/ezine/brady/">James "Diamond Jim" Brady: Honored Gourmandizer</a><br />
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<a href="http://www.nytimes.com/2008/12/31/dining/31diam.html?pagewanted=all&_r=0">"Whether True or False, a Real Stretch," by DAVID KAMP. New York Times, Published: December 30, 2008</a><span xmlns=""><br /></span>
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Anonymoushttp://www.blogger.com/profile/05286847723206340868noreply@blogger.com3tag:blogger.com,1999:blog-4730782586548300034.post-60931248017388833332015-01-21T07:00:00.000-05:002015-01-21T07:00:07.671-05:00Centralizing Care for Testicular Cancer<span xmlns=""></span><br />
<span xmlns="">A number of studies and a growing body of evidence indicates that high hospital and surgeon volume can be associated with improved outcomes for a number of surgical diseases. Research involving the Institute of Medicine[1] and a number of large, national databases including SEER (Surveillance, Epidemiology, and End Results) Cancer Program,[2] National Inpatient Sample [3] and others [4,5] indicate associations between hospital volume and outcome for a variety of cardiovascular and oncologic surgeries. While not specifically focused on urologic oncology, these studies demonstrate modest but significant improvements in mortality for radical cystectomy and nephrectomy.[3,5] </span><br />
<span xmlns="">In the urologic literature, significant improvements have been demonstrated for the treatment of prostate,[6-11] bladder,[3,5,12-16] and kidney cancer[3,17-18] at high-volume centers and by high-volume surgeons. There is less, well-established literature in the treatment of testicular cancer (TC) and this blog will focus on the relationship between hospital volume and outcomes for TC.</span><br />
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<span xmlns="">A study of the <b>Irish Testicular Tumor Registry</b> (1980-1985) evaluated 246 patients over 41 hospitals. Inferior survival outcomes were associated with patients who received incomplete orchiectomy, were not staged by tumor markers, did not receive appropriate chemotherapy, had less frequent imaging or marker surveillance and did not have a urologist and/or oncologist involved in their care.[19] In an early study from the <b>SWENOTECA</b> (Swedish Norweigan Testicular Cancer) Project (1981-1986), high-volume cancer centers were associated with improved care – especially in patients with large volume, advanced disease.[20] Of 440 men treated in <b>Scotland</b>, 87% of 235 men treated at the highest volume center were alive at 5 years. Of the 194 treated at other, smaller centers, only 73% were alive at 5 years – much of this difference was attributed to various treatment protocols independent of other prognostic variables.[21]</span><br />
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<span xmlns="">In the <b>United States</b>, 172 men with advanced testicular cancer in the national, <b>SEER database</b> were matched to 133 men from <b>MSKCC</b> (Memorial Sloan Kettering Cancer Center) in New York (1978-1984). Survival rates were higher at MSKCC despite similar treatment regimens. The benefit at MSKCC was highest in men with minimal to moderate disease and therefore attributed to the combination of surgery and chemotherapy at this tertiary care center.[22] This relationship was validated in 380 patients with metastatic TC enrolled in an <b>EORTC </b>(European Organization for Research and Treatment of Cancer) Trial. The trial was conducted over 49 sites, and patients treated at the 26 sites with the fewest patients (five or fewer) had inferior survival outcomes.[23]</span><br />
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<span xmlns="">More recent studies from <b>Japan </b>have investigated the volume-outcome relationship, demonstrating increasing volume of treatment to be associated with improved survival.[24] However the rates did not achieve the survival rates demonstrated in western countries like the US or countries of Europe. Based on these data, efforts have been made to centralize TC care in a risk-adapted algorithm – as severity of disease increases, patients are referred to more centralized, specialized referral centers. One study evaluating this "centralization" demonstrated markedly improved and excellent survival in patients receiving induction chemotherapy, with the majority of patients receiving care at one, large center.[25]</span><br />
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<span xmlns="">While much of the data regarding hospital volume and outcome for TC patients is dated, the argument for centralization of care is poignant. As outcomes for a variety of urologic malignancies including prostate, bladder and kidney cancer are established to be improved in high-volume centers, it is rational that TC care could also be better served by centralized care – TC is a rare disease that often requires multi-disciplinary care and a thorough understanding of management options and outcomes (especially for men with advanced disease). A risk-adapted centralization, where following a diagnosis of TC patients are referred to an increasingly experienced center for the stage of their disease, may help improve outcomes for patients. For instance, a man with early stage disease who is a candidate for active surveillance can be followed by his local urologic oncologist, and the man with high-volume metastatic disease should be referred to a large, tertiary care center with extensive experience treating men in the region. </span>In addition, while this blog does not discuss the costs associated with the treatment of advanced TC, centralization may provide improved population-based outcomes in a cost-effective manner and this is a disease where reimbursements may reinforce quality care.<br />
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<span xmlns=""><em style="background-color: white; color: #333333; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: 15px; line-height: 20.7900009155273px;">This blog was written by <a href="http://urology.jhu.edu/phillippierorazio/" style="color: #771000; text-decoration: none;"><strong>Phillip M. Pierorazio, MD</strong></a>, Assistant Professor of Urology and Oncology and Director of the Division of Testicular Cancer.</em></span><br />
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<span style="font-size: x-small;"><ol>
<li>E.A. Halm, C. Lee, M.R. Chassin. Is volume related to outcome in health care? A systematic review and methodologic critique of the literature. Ann Intern Med, 137 (2002), p. 511</li>
<li>C.B. Begg, L.D. Cramer, W.J. Hoskins, M.F. Brennan. Impact of hospital volume on operative mortality for major cancer surgery. JAMA, 280 (1998), p. 1747</li>
<li>J.D. Birkmeyer, A.E. Siewers, E.V. Finlayson, T.A. Stukel, F.L. Lucas, I. Batista,et al. Hospital volume and surgical mortality in the United States. N Engl J Med, 346 (2002), p. 1128</li>
<li>R.A. Dudley, K.L. Johansen, R. Brand, D.J. Rennie, A. Milstein. Selective referral to high-volume hospitals: estimating potentially avoidable deaths. JAMA, 283 (2000), p. 1159</li>
<li>J.D. Birkmeyer, T.A. Stukel, A.E. Siewers, P.P. Goodney, D.E. Wennberg, F.L. Lucas. Surgeon volume and operative mortality in the United States. N Engl J Med, 349 (2003), p. 2117</li>
<li>F.J. Bianco Jr, P.T. Scardino, M.W. Kattan, A.C. Rhee, J.A. Eastham. Surgeon volume is predictor of improved outcomes in radical prostatectomy patients. J Urol, 171 (suppl.) (2004), p. 211 abstract 796</li>
<li>C.B. Begg, E.R. Riedel, P.B. Bach, M.W. Kattan, D. Schrag, J.L. Warren, et al. Variations in morbidity after radical prostatectomy. N Engl J Med, 346 (2002), p. 1138</li>
<li>J.A. Eastham, M.W. Kattan, E. Riedel, C.B. Begg, T.M. Wheeler, C. Gerigk, et al. Variations among individual surgeons in the rate of positive surgical margins in radical prostatectomy specimens. J Urol, 170 (2003), p. 2292</li>
<li>L.M. Ellison, J.A. Heaney, J.D. Birkmeyer. The effect of hospital volume on mortality and resource use after radical prostatectomy. J Urol, 163 (2000), p. 867</li>
<li>J.C. Hu, K.F. Gold, C.L. Pashos, S.S. Mehta, M.S. Litwin. Role of surgeon volume in radical prostatectomy outcomes. J Clin Oncol, 21 (2003), p. 401</li>
<li>S.L. Yao, G. Lu-Yao. Population-based study of relationships between hospital volume of prostatectomies, patient outcomes, and length of hospital stay. J Natl Cancer Inst, 91 (1999), p. 1950</li>
<li>L.S. Elting, C.A. Pettaway, H.B. Grossman, B.N. Bekele, K.R. Saldin, C.P.N. Dinney. Relationship between postoperative in-hospital mortality and annual hospital volume of cystectomies: the effect of centres of experience. J Urol, 169 (suppl.) (2003), p. 336 abstract 1301</li>
<li>H.W. Herr, J.R. Faulkner, H.B. Grossman, R.B. Natale, R. DeVere White, M.F. Sarosdy, et al. Surgical factors influence bladder cancer outcomes: a cooperative group report. J Clin Oncol, 22 (2004), p. 2781</li>
<li>H.W. Herr, J.A. Smith, J.E. Montie. Standardization of radical cystectomy: time to count and be counted. BJU Int, 94 (2004), p. 481</li>
<li>B.R. Konety, V. Dhawan, V. Allareddy, S.A. Josyln. Impact of hospital and surgeon volume on in-hospital mortality from radical cystectomy: data from the Health Care Utilization Project. J Urol, 173 (2005), p. 1695</li>
<li>B.R. Konety, V. Dhawan, V. Allareddy, M.A. O'Donnell. Association between volume and charges for most frequently performed ambulatory and nonambulatory surgery for bladder cancer is more cheaper? J Urol, 172 (2004), p. 1056</li>
<li>E.V. Finlayson, P.P. Goodney, J.D. Birkmeyer. Hospital volume and operative mortality in cancer surgery: a national study. Arch Surg, 138 (2003), p. 721</li>
<li>D.A. Taub, D.C. Miller, J.A. Cowan, J.B. Dimick, J.E. Montie, J.T. Wei. Impact of surgical volume on mortality and length of stay after nephrectomy. Urology, 63 (2004), p. 862</li>
<li>J.A. Thornhill, A. Walsh, R.M. Conroy, J.J. Fennelly, D.G. Kelly, J.M. Fitzpatrick. Physician-dependent prognostic variables in the management of testicular cancer. Br J Urol, 61 (1988), p. 244</li>
<li>N. Aass, O. Klepp, E. Cavallin-Stahl, O. Dahl, H. Wicklund, B. Unsgaard, et al. Prognostic factors in unselected patients with nonseminomatous metastatic testicular cancer: a multicenter experience. J Clin Oncol, 9 (1991), p. 818</li>
<li>M.J. Harding, J. Paul, C.R. Gillis, S.B. Kaye. Management of malignant teratoma: does referral to a specialist unit matter? Lancet, 341 (1993), p. 999</li>
<li>E.J. Feuer, C.M. Frey, O.W. Brawley, S.G. Nayfield, J.B. Cunningham, N.L. Geller, et al. After a treatment breakthrough: a comparison of trial and population-based data for advanced testicular cancer. J Clin Oncol, 12 (1994), p. 368</li>
<li>L. Collette, R.J. Sylvester, S.P. Stenning, S.D. Fossa, G.M. Mead, R. de Wit, et al. Impact of the treating institution on survival of patients with "poor-prognosis" metastatic nonseminoma. European Organization for Research and Treatment of Cancer Genito-Urinary Tract Cancer Collaborative Group and the Medical Research Council Testicular Cancer Working Party. J Natl Cancer Inst, 91 (1999), p. 839</li>
<li>Suzumura S, Ioka A, Nakayama T, Tsukuma H, Oshima A, Ishikawa O. Hospital procedure volume and prognosis with respect to testicular cancer patients: a population-based study in Osaka, Japan. Cancer Sci. 2008 Nov;99(11):2260-3. doi: 10.1111/j.1349-7006.2008.00920.x.</li>
<li>Inai H, Kawai K, Kojima T, Joraku A, Shimazui T, Yamauchi A, Miyagawa T, Endo T, Fukuhara Y, Miyazaki J, Uchida K, Nishiyama H. Oncological outcomes of metastatic testicular cancers under centralized management through regional medical network. Jpn J Clin Oncol. 2013 Dec;43(12):1249-54. doi: 10.1093/jjco/hyt152. Epub 2013 Oct 6.</li>
</ol>
</span>Anonymoushttp://www.blogger.com/profile/05286847723206340868noreply@blogger.com8tag:blogger.com,1999:blog-4730782586548300034.post-6510890018131178052015-01-20T07:00:00.000-05:002015-01-20T07:00:02.648-05:00Historical Contribution: 1962, Hypophysectomy for Prostate Cancer, Scott & Schirmer.<span xmlns=""></span><br />
<span style="color: #660000;" xmlns=""><strong><span style="font-size: x-large;">1962</span></strong></span><br />
<span style="color: #660000;" xmlns=""><a href="http://urology.jhu.edu/centennial/pdf/1962.pdf"><strong>Scott WW, Schirmer HKA. Hypophysectomy for Disseminated Prostatic Cancer. Cancer and Hormones. 1962. 175-203.</strong></a><strong><br /> </strong></span><br />
<span xmlns=""><br /> </span><br />
<table cellpadding="0" cellspacing="0" class="tr-caption-container" style="float: right; margin-left: 1em; text-align: right;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjXndJVVdlw8T4mH2vd_jRY-Sb-_sZVw9JThB4zBFRpEJFvK65URfEdALIN62lRCXi5H9-43OGaqrRRqkZxscOLyicfjJ7gBdD5rqHvnINS9Wy6_x59SBroXCpjDvtlPJzKsXtDs416LSA/s1600/wws.jpg" imageanchor="1" style="clear: right; margin-bottom: 1em; margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjXndJVVdlw8T4mH2vd_jRY-Sb-_sZVw9JThB4zBFRpEJFvK65URfEdALIN62lRCXi5H9-43OGaqrRRqkZxscOLyicfjJ7gBdD5rqHvnINS9Wy6_x59SBroXCpjDvtlPJzKsXtDs416LSA/s1600/wws.jpg" height="200" width="158" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">WW Scott</td></tr>
</tbody></table>
<span xmlns="">Believing that the metastatic progression of prostate cancer was related to exogenous testosterone after castration,[<a href="http://bradyurology.blogspot.com/2014/09/historical-contribution-what-makes.html"><em>What makes the Prostate Grow, WW Scott</em></a>] Scott and other embarked on experimentation with hypophysectomy (removal of the pituitary) in the treatment of advanced prostate cancer with mixed results – the first patient died 11 days after surgery, but two of the next five patients had a tangible response to surgery. Between 1948 (the 1<sup>st</sup> hypophysectomy) and 1961, 17 patients underwent hypophysectomy for the treatment of their prostate cancer. </span><br />
<span xmlns=""><br /></span>
<span xmlns="">In a detailed description of the 17 cases, Scott and Schirmer arrived at the following conclusions. While the intention of hypophysectomy was palliative (i.e. not intended to extend life), it could not be demonstrated to improve survival outcomes of these patients. Instead Scott and Schimer recognized that grade, timing of metastases and castration had the largest influence on survival times. While hypophysectomy could improve the subjective (symptoms) and objective (lab values) progression of many of these patients, they recognized that </span><br />
<span xmlns=""><br /></span>
<blockquote class="tr_bq">
<span style="color: #660000;" xmlns=""><em>"these comparisons are probably meaningless… they point out our lack of reliable criteria on which to base an evaluation as well as the fact that the degree of palliation depends to a great extent on when in the course of the disease any hormonal therapy is instituted." </em></span></blockquote>
<span xmlns=""><em><br /></em></span>
<span xmlns="">Nevetheless, Scott and Schirmer were able to demonstrate effects of serum acid phosphatase, ketosteroids, and osseous lesions on x-ray – demonstrating some effect of hypophysectomy on these patients. They concluded that patients with (1) a previous favorable response to castration therapy and (2) evidence of persistent androgen production may benefit from this surgery. </span><br />
<span xmlns=""><br /> </span><br />
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjgMXk5pBPJhlF4jJnaU8D7Yr4gIdh3ubn3z6fbcFMGfMJzpJBcBk__DD4VkLdvUOsB9apQgYED708vaDomeLLvdIOPU3gutscpR9pmp_pNjnVR2rmXdWx1erNrF6QRspp7jfBig3aYaqo/s1600/centennial.gif" imageanchor="1" style="clear: right; float: right; margin-bottom: 1em; margin-left: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjgMXk5pBPJhlF4jJnaU8D7Yr4gIdh3ubn3z6fbcFMGfMJzpJBcBk__DD4VkLdvUOsB9apQgYED708vaDomeLLvdIOPU3gutscpR9pmp_pNjnVR2rmXdWx1erNrF6QRspp7jfBig3aYaqo/s1600/centennial.gif" height="160" width="200" /></a><span xmlns=""><span style="color: #333333; font-family: Arial;"><span style="background-color: white; font-size: 13pt;">To read the entire manuscript: follow the link above, visit the <a href="http://urology.jhu.edu/centennial/"><span style="color: #771000;"><b>Centennial Website</b></span></a> or click <a href="http://urology.jhu.edu/centennial/pdf/1962.pdf"><span style="color: #771000;"><b>here</b></span></a>.</span><span style="background-color: white; font-size: 11pt;"><br /></span></span></span><br />
<div style="background: white;">
<span xmlns=""><span style="color: #333333; font-family: Arial;"><span style="color: #660000;"><span style="font-size: 13pt;"><em><strong>HISTORICAL CONTRIBUTIONS </strong>highlight the greatest academic manuscripts from the Brady Urological Institute over the past 100 years. As the Brady Urological Institute approaches its centennial, we will present a HISTORICAL CONTRIBUTION from each of the past 100 years. In the most recent experience, the most highly cited article from each year is selected; older manuscripts were selected based on their perceived impact on the field. We hope you enjoy!</em> </span><span style="color: #333333; font-size: 11pt;"><br /> </span></span></span></span></div>
<span xmlns=""><br /> </span><br />
Anonymoushttp://www.blogger.com/profile/05286847723206340868noreply@blogger.com4tag:blogger.com,1999:blog-4730782586548300034.post-88062145609829970612015-01-14T07:00:00.000-05:002015-01-14T07:00:03.721-05:00MRI Improves the “Misclassification” of Men with Prostate Cancer Undergoing Active Surveillance<span xmlns=""></span><br />
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<span xmlns="">While prostate cancer remains one of </span><br />
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<b><span style="color: #333333; font-family: "Arial",sans-serif; font-size: 10.0pt; mso-fareast-font-family: "Times New Roman";">Active
surveillance for prostate cancer: <o:p></o:p></span></b></div>
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<b><span style="color: #333333; font-family: "Arial",sans-serif; font-size: 10.0pt; mso-fareast-font-family: "Times New Roman";">What
is it and is it right for me?<o:p></o:p></span></b></div>
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<b><u><span style="color: #666666; font-family: "Arial",sans-serif; font-size: 8.0pt; mso-fareast-font-family: "Times New Roman"; text-transform: uppercase;"><a href="http://bradyurology.blogspot.com/2014/10/active-surveillance-for-prostate-cancer.html">PART
ONE<span style="font-weight: normal; mso-bidi-font-weight: bold;"> ALL
CANCERS ARE NOT CREATED EQUAL</span></a><o:p></o:p></span></u></b></div>
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<b><u><span style="color: #666666; font-family: "Arial",sans-serif; font-size: 8.0pt; mso-fareast-font-family: "Times New Roman"; text-transform: uppercase;"><a href="http://bradyurology.blogspot.com/2014/10/active-surveillance-for-prostate-cancer_8.html">PART
TWO <span style="font-weight: normal; mso-bidi-font-weight: bold;">WHAT DOES IT
ENTAIL</span></a></span></u></b><span style="color: #333333; font-family: "Arial",sans-serif; font-size: 10.0pt; mso-fareast-font-family: "Times New Roman";"><o:p></o:p></span></div>
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<span xmlns="">the most common cancers in men in the US, many patients are diagnosed with <strong>indolent (or benign-behaving)</strong> prostate cancer – cancers that will not affect a man's longevity and do not require treatment. This blog has previously covered the basics of active surveillance (see inset). Over a ten year period of active surveillance, approximately one third of men will undergo a treatment for their prostate cancer. The majority of those men, approximately 70%, elected treatment due to an increased volume of cancer or Gleason score > 6 – indicating the presence of more aggressive cancer.[1] Determining who has high-grade or aggressive prostate cancer at the outset can be challenging based on traditional biopsy techniques. <strong>Dr. H. Ballentine Carter, MD</strong>, Professor of Urology and Director of the Active Surveillance Program at the Brady Urological Institute explains, </span><br />
<blockquote class="tr_bq">
<i><b><span style="color: #660000;">"Misclassification is the problem of relying on a prostate biopsy, which samples only a small fraction of the prostate, to reflect the biology of the entire gland. If a diagnosis of low-grade prostate cancer is made on the prostate biopsy and the patient chooses active surveillance, the risk that a higher-grade, more aggressive cancer is present within the prostate can range from 10 to 30 percent."</span></b></i></blockquote>
<strong>MRI (Magnetic resonance imaging)</strong> makes use of high-powered magnets and their influence on molecules like water (H2O) to image the body. <strong>Multi-parametric MRI (mpMRI)</strong> uses complex computer algorithms to differentiate benign from malignant tissue and has demonstrated promise in better identifying patients suitable for active surveillance. This technology relies on three characteristics of prostate cancer cells:<br />
<ol>
<li><span xmlns="">Prostate cancer cells are abnormal and can emit MRI signals different than normal tissue</span></li>
<li><span xmlns="">Because cancer cells are disorganized relative to normal prostate tissue, surrounding water diffuses through cancerous tissue differently than through normal prostate</span></li>
<li><span xmlns="">Cancers form with new blood vessels, these new blood vessels create abnormal diffusion of contrast materials through cancer and normal tissue</span></li>
</ol>
<span xmlns="">In addition, some prostate cancers can hide in areas of the prostate difficult to reach with a standard, transrectal ultrasound-guided biopsy. By assessing all of these characteristics and viewing these "hard to reach places," mpMRI can detect prostate cancers missed on biopsy.</span><br />
<span xmlns=""><br />In a recent study of 96 men on active surveillance at Johns Hopkins, Carter, with radiology colleagues Sayed Dianat and Kasia Macura, found that men with a mpMRI abnormality had a cancer 41% of the time, compared to 8% of men with a normal mpMRI. This resulted in a 65% lower risk of adverse pathology on subsequent biopsy if an active surveillance patient had a normal mpMRI.[2] </span><br />
<span xmlns=""><i>"Our group demonstrated that when mpMRI suggested the absence of prostate cancer in a particular area of the prostate, there was a high probability that cancer was absent on multiple biopsies taken from these negative mpMRI areas."</i></span><br />
<span xmlns=""><br /></span>
<blockquote class="tr_bq">
<span style="color: #660000;" xmlns=""><i><b>"We are now using mpMRI routinely to help select the most appropriate candidates for active surveillance, and to help reduce the frequency of biopsies."</b></i></span></blockquote>
Therefore, mpMRI can help identify men who truly have low-risk prostate cancer, reducing the "misclassification" of these men and decreasing the number of biopsies needed in the future.<br />
<span xmlns=""><br /><span style="color: #333333; font-family: Arial;"><span style="background-color: white; font-size: 11pt;">Portions of this story were extracted from <a href="http://urology.jhu.edu/newsletter/2015/active_surveillance.php">"</a></span></span></span><a href="http://urology.jhu.edu/newsletter/2015/active_surveillance.php">Making Active Surveillance Safer"</a> in <a href="http://urology.jhu.edu/newsletter/2015/" style="font-family: Arial;"><span style="color: #771000;"><em>Discovery: Volume XI, Winter 2015</em></span></a><span style="color: #333333; font-family: Arial;"> by the Patrick C. Walsh Prostate Cancer Research Fund.</span><br />
<span xmlns=""><br /> </span><br />
<span style="font-size: x-small;"><span style="background-color: white; color: #333333; font-family: Arial;">[1] Tosoian JJ, Trock BJ, Landis P, Feng Z, Epstein JI, Partin AW, Walsh PC, Carter HB. Active surveillance program for prostate cancer: an update of the Johns Hopkins experience. J Clin Oncol. 2011 Jun 1;29(16):2185-90. doi: 10.1200/JCO.2010.32.8112. Epub 2011 Apr 4. </span><a href="http://jco.ascopubs.org/content/29/16/2185.long" style="font-family: Arial;"><span style="color: #771000;">http://jco.ascopubs.org/content/29/16/2185.long</span></a></span><br />
<span style="font-size: x-small;" xmlns="">[2] Dianat SS, Carter HB, Pienta KJ, Schaeffer EM, Landis PK, Epstein JI, Trock BJ, Macura KJ. Magnetic Resonance-invisible Versus Magnetic Resonance-visible Prostate Cancer in Active Surveillance: A Preliminary Report on Disease Outcomes. Urology. 2015 Jan;85(1):147-54. doi: 10.1016/j.urology.2014.06.085. Epub 2014 Oct 16. <a href="http://www.goldjournal.net/article/S0090-4295(14)00915-7/abstract">http://www.goldjournal.net/article/S0090-4295(14)00915-7/abstract</a></span><br />
Anonymoushttp://www.blogger.com/profile/05286847723206340868noreply@blogger.com5tag:blogger.com,1999:blog-4730782586548300034.post-88730474239243310082015-01-13T07:00:00.000-05:002015-01-13T07:00:08.402-05:00Historical Contribution: 1961, Stamey, Renovascular Hypertension<span xmlns=""></span><br />
<span style="color: #660000; font-family: Georgia, Times New Roman, serif; font-size: x-large;" xmlns=""><b>1961</b></span><br />
<span xmlns=""><a href="http://urology.jhu.edu/centennial/pdf/1961.pdf"><b><span style="color: #660000; font-family: Georgia, Times New Roman, serif;">Stamey TA, Nudelman IJ, Good PH, Schwentker FN, Hendricks F. Functional Characteristics of Renovascular Hypertension. Medicine. 1961. 40(4):347-94.</span></b></a><br /> </span><br />
<span xmlns=""><br /> </span><br />
<table cellpadding="0" cellspacing="0" class="tr-caption-container" style="float: left; margin-right: 1em; text-align: left;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgFrBoea6vbzrV4nCPJmU1TP9XtjFTOvcMGGvjnphmZcBSLgTeVVHh4rPrg-4BEDJbAZhtVNA-GquVVJFCLfxQdn11s3RpnKqw8wx7-NwgXmTWD1TPODA65t5eAPY2OGRVn3ilISdOSWPA/s1600/StameyThomas_pic.jpg" imageanchor="1" style="clear: left; margin-bottom: 1em; margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgFrBoea6vbzrV4nCPJmU1TP9XtjFTOvcMGGvjnphmZcBSLgTeVVHh4rPrg-4BEDJbAZhtVNA-GquVVJFCLfxQdn11s3RpnKqw8wx7-NwgXmTWD1TPODA65t5eAPY2OGRVn3ilISdOSWPA/s1600/StameyThomas_pic.jpg" height="175" width="200" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Thomas A. Stamey, MD</td></tr>
</tbody></table>
<span xmlns="">Shortly before leaving the Brady for Stamford University, where he served as chairman of urology for 26 years, <a href="http://www.urologichistory.museum/content/collections/uropeople/stamey/p1.cfm"><strong>Thomas A. Stamey, MD</strong></a>, wrote authored a 50 page manuscript summarizing the <em>state-of-the-art </em>of renovascular hypertension (RVH). Early in his career, Dr. Stamey was recognized as one of the world's experts on RVH and renal physiology.</span><br />
<span xmlns=""><br /></span>
<span xmlns="">This wonderfully written manuscript summarizes the existing literature regarding on RVH and comprehensively covers the range of diseases that encompass RVH from unilateral to bilateral disease, characteristics of treatable disease and the evaluation and management of many patients. Marrying the scientific literature with his clinical experience, Stamey enables the reader to understand the concepts and clinical significance of RVH as they relate to renal physiology. </span><br />
<span xmlns=""><br /> </span><br />
<div class="separator" style="clear: both; text-align: center;">
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhBK_hsBgnfQf7UFs6XlsqFEK0P4oSQC00knXsaLPnoc_BAzy2SzJatT-tk1tnNofI0VZdnpQU8T6ZXaX18uMlKfemTaTzSLfKXA573zh8zRdK5kTJrVtfE5LtAL62Cqmo4UqZF46jaucc/s1600/1961.png" imageanchor="1" style="clear: right; float: right; margin-bottom: 1em; margin-left: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhBK_hsBgnfQf7UFs6XlsqFEK0P4oSQC00knXsaLPnoc_BAzy2SzJatT-tk1tnNofI0VZdnpQU8T6ZXaX18uMlKfemTaTzSLfKXA573zh8zRdK5kTJrVtfE5LtAL62Cqmo4UqZF46jaucc/s1600/1961.png" height="320" width="264" /></a></div>
<span xmlns="">While the diagnostic options and management strategies for RVH have changed dramatically from the 1960's, this manuscript offers a fascinating insight into the disease at this time period. Importantly, Stamey offers an algorithmic approach to the diagnosis and treatment of patients to assist practitioners in deciphering this complex disease state.</span><br />
<span xmlns=""><br /></span>
<span xmlns=""><br /></span>
<span xmlns=""><span style="color: #333333;"><span style="background-color: white; font-family: Arial; font-size: 13pt;">To read the entire manuscript: follow the link above, visit the <a href="http://urology.jhu.edu/centennial/"><span style="color: #771000;">Centennial Website</span></a> or click <a href="http://urology.jhu.edu/centennial/pdf/1961.pdf"><span style="color: #771000;">here</span></a>.</span><span style="background-color: white;"><br /></span></span><br /> </span><br />
<div style="background: white;">
<span xmlns=""><span style="color: #333333; font-family: Arial;"><span style="font-size: 11pt;"><br /> </span><span style="color: #660000;"><span style="font-size: 13pt;"><em><strong>HISTORICAL CONTRIBUTIONS </strong>highlight the greatest academic manuscripts from the Brady Urological Institute over the past 100 years. As the Brady Urological Institute approaches its centennial, we will present a HISTORICAL CONTRIBUTION from each of the past 100 years. In the most recent experience, the most highly cited article from each year is selected; older manuscripts were selected based on their perceived impact on the field. We hope you enjoy!</em> </span><span style="color: #333333; font-size: 11pt;"><br /> </span></span></span></span></div>
<div class="separator" style="clear: both; text-align: center;">
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<span xmlns=""><br /> </span>Anonymoushttp://www.blogger.com/profile/05286847723206340868noreply@blogger.com4tag:blogger.com,1999:blog-4730782586548300034.post-77961250617204632992015-01-12T07:00:00.000-05:002015-01-12T07:00:01.240-05:00Quality of Life in the Treatment of Clinically-Localized, Small Renal Masses<span xmlns=""></span><br />
<span xmlns="">There are a number of management strategies for patients with <u>clinically-localized, small renal masses (SRM, clinical stage T1)</u> including <b>radical nephrectomy (RN)</b>, <b>nephron-sparing surgery (NSS</b>; includes partial nephrectomy, PN, and ablative technologies), and <b>active surveillance</b>. Fortunately survival rates are excellent regardless of treatment [1]. And with recent level I evidence indicating no difference in oncologic or renal-functional outcomes for healthy patients undergoing PN and RN,[2,3] <b>quality-of-life (QOL)</b> is becoming an increasingly important consideration for these patients. </span><br />
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<span xmlns=""><b>This blog will review what is known regarding QOL in the management of SRM. </b></span><br />
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<h2>
<span style="color: #660000;" xmlns="">Radical Nephrectomy versus Nephron-Sparing Surgery</span></h2>
<span xmlns="">Most of the studies evaluating QOL in patients undergoing RN and NSS evaluate patients undergoing open surgery (in fact, there are no studies evaluating patients undergoing minimally-invasive PN). In addition, most of these studies employ a <em>cross-sectional survey</em> in which all patients from a given institution were sent a QOL questionnaire at some time period after surgery. Very few studies evaluate patients undergoing surgery in the more ideal, <em>prospective</em> fashion.</span><br />
<h3>
<span xmlns="">Cross-Sectional Studies</span></h3>
<span xmlns="">It is generally understood that patients undergoing RN and PN are very different patient populations. RN patients are often older, have more comorbidities and larger tumors. Patients undergoing PN are subjected to a higher risk surgery, but have the benefit of preservation of a kidney. </span><br />
<span xmlns="">Despite these differences, a study of the baseline QOL in patients undergoing RN and PN found no difference in general perceived health or QOL among the groups.[4] A more in-depth analysis indicating that patients undergoing PN had better QOL scores related to physical health, while patients undergoing RN had better mental health QOL scores at baseline. </span><br />
<span xmlns="">A number of studies indicate that overall QOL is similar following RN and PN.[5-7] The study by <i>Poulakis et al.</i> indicated that patients undergoing PN had higher physical health QOL scores [7], and while the study by <i>Clark </i><em>et al.</em> did not demonstrate a difference in QOL between RN and PN, those patients with more renal parenchyma (tissue) saved had higher QOL scores.[6] In general, these studies found that while NSS did not predict QOL, comorbidities, tumor size and renal function after surgery related strongly to overall QOL. </span><br />
<span xmlns="">In contrast, a study by <i>Ficarra </i><em>et al.</em> found that patients undergoing PN had improved QOL. Specifically they found lower rates of anxiety and depression in patients undergoing PN; and fewer patients had an impairment of their general health.[8] </span><br />
<h3>
<span xmlns="">Prospective Studies</span></h3>
<span xmlns="">In a study comparing radio-frequency ablation (RFA) to laparoscopic RN, <i>Onishi </i><em>et al. </em>found that patients undergoing RFA were older and sicker with resultant lower QOL scores at baseline. However, over the course of six months following surgery, patients undergoing RFA had improvements in QOL while those undergoing RN had a significant detriment to physical functioning, physical health, pain and general health.[9] In the study by <i>Parker </i><em>et al.</em>, patients undergoing RN had improved cancer-related QOL (indicating less fear of cancer recurrence). However, many domains of QOL (including physical health and fear of recurrence) were related to renal function – which was significantly better in patients undergoing PN.[10] </span><br />
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<h2>
<span style="color: #660000;" xmlns="">Minimally-Invasive versus Open Surgery</span></h2>
<span xmlns="">As stated above, most studies evaluate open RN and NSS. Studies evaluating laparoscopic and open surgery indicate that patients undergoing laparoscopic surgery have a quicker return to baseline QOL, but at one year both groups achieve similar QOL.[10] A recent systematic review of this literature indicates that: </span><br />
<ul>
<li><span xmlns="">With regard to RN, laparoscopic surgery has improved perioperative outcomes and related QOL.</span></li>
<li><span xmlns="">With regard to NSS, PN results in better preservation of renal function and related QOL regardless of approach. [11] </span></li>
</ul>
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<h2>
<span style="color: #660000;" xmlns="">Active Surveillance and Watchful Waiting</span></h2>
<span xmlns="">Little QOL data exists in the SRM literature regarding active surveillance (AS) or watchful waiting (WW) programs. Analogous data from prostate cancer AS programs suggest that men do not fare worse in terms of their mental and physical wellbeing compared to those that choose to undergo active intervention [12-15], however there may be increased anxiety, particularly if tumor growth or progression is found.[16] </span><br />
<span xmlns="">In a two-year study of patients undergoing WW, greater illness uncertainty was related to poorer general health, cancer-related QOL and higher distress. While physical health-related QOL decreased over the two-year period, intrusive thoughts and avoidance behaviors improved; and mental health-related QOL did not change with time.[17] </span><br />
<span xmlns="">In an ongoing prospective study of AS and surgery for SRM, early data indicates that physical health-related QOL is significantly higher at baseline for patients who undergo surgery. While this difference persists throughout follow-up, mental health-related QOL (including depression and anxiety) is not adversely affected for patients undergoing AS over time and when compared to surgery patients.[18]</span><br />
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<h2>
<span xmlns="">SUMMARY</span></h2>
<span xmlns="">While there are many shortcomings in the data regarding QOL in the management of SRM, the little data that exists indicates that:</span><br />
<ul>
<li><span xmlns="">There is likely little difference in QOL for healthy patients undergoing RN and PN.</span></li>
<li><span xmlns="">A perceived QOL benefit to PN (and other NSS) may be related to preservation of renal function and tissue.</span></li>
<li><span xmlns="">While there is no long-term difference in QOL related to open or laparoscopic surgery, patients undergoing laparoscopic surgery may have a quicker return to baseline QOL on average.</span></li>
<li><span xmlns="">WW and AS for SRM does not appear to adversely affect mental health-related QOL.</span></li>
</ul>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEic2200k29GyrzBkCYS7NZfSRtdU6Q4h2blCZN34dCB5I4sjYg4NZEJViMLv3K6gl_ixYAFFxU1OxvmDO26ikEcPpyV-_akd88BOUl7qeqZsnNj95EdXz5KYrCuwHEkJWz-4jtiLkcbnfo/s1600/PHILLIP+PIERORAZIO.jpg" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEic2200k29GyrzBkCYS7NZfSRtdU6Q4h2blCZN34dCB5I4sjYg4NZEJViMLv3K6gl_ixYAFFxU1OxvmDO26ikEcPpyV-_akd88BOUl7qeqZsnNj95EdXz5KYrCuwHEkJWz-4jtiLkcbnfo/s1600/PHILLIP+PIERORAZIO.jpg" height="200" width="143" /></a><span xmlns=""><em style="background-color: white; color: #333333; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: 15px; line-height: 20.7900009155273px;">This blog was written by <a href="http://urology.jhu.edu/phillippierorazio/" style="color: #771000; text-decoration: none;"><strong>Phillip M. Pierorazio, MD</strong></a>, Assistant Professor of Urology and Oncology.</em><br /> </span><br />
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<span style="font-size: x-small;" xmlns="">[1] Patel HD, Kates M, Pierorazio PM, Hyams ES, Gorin MA, Ball MW, Bhayani SB, Hui X, Thompson CB, Allaf ME. Survival after diagnosis of localized T1a kidney cancer: current population-based practice of surgery and nonsurgical management. Urology. 2014 Jan;83(1):126-32. doi: 10.1016/j.urology.2013.08.088. Epub 2013 Nov 16.</span><br />
<span style="font-size: x-small;" xmlns="">[2] Van Poppel H, Da Pozzo L, Albrecht W, Matveev V, Bono A, Borkowski A, Colombel M, Klotz L, Skinner E, Keane T, Marreaud S, Collette S, Sylvester R. A prospective, randomised EORTC intergroup phase 3 study comparing the oncologic outcome of elective nephron-sparing surgery and radical nephrectomy for low-stage renal cell carcinoma. Eur Urol. 2011 Apr;59(4):543-52. doi: 10.1016/j.eururo.2010.12.013. Epub 2010 Dec 22.</span><br />
<span style="font-size: x-small;" xmlns="">[3] Scosyrev E, Messing EM, Sylvester R, Campbell S, Van Poppel H. Renal function after nephron-sparing surgery versus radical nephrectomy: results from EORTC randomized trial 30904. Eur Urol. 2014 Feb;65(2):372-7. doi: 10.1016/j.eururo.2013.06.044. Epub 2013 Jul 2.</span><br />
<span style="font-size: x-small;" xmlns="">[4] Arnold ML, Thiel DD, Diehl N, Wu KJ, Ames S, Parker AS. Comparison of baseline quality of life measures between renal cell carcinoma patients undergoing partial versus radical nephrectomy. BMC Urol. 2013 Oct 22;13:52. doi: 10.1186/1471-2490-13-52.</span><br />
<span style="font-size: x-small;" xmlns="">[5] Clark PE, Schover LR, Uzzo RG, Hafez KS, Rybicki LA, Novick AC. Quality of life and psychological adaptation after surgical treatment for localized renal cell carcinoma: impact of the amount of remaining renal tissue. Urology. 2001 Feb;57(2):252-6.</span><br />
<span style="font-size: x-small;" xmlns="">[6] Gratzke C, Seitz M, Bayrle F, Schlenker B, Bastian PJ, Haseke N, Bader M, Tilki D, Roosen A, Karl A, Reich O, Khoder WY, Wyler S, Stief CG, Staehler M, Bachmann A. Quality of life and perioperative outcomes after retroperitoneoscopic radical nephrectomy (RN), open RN and nephron-sparing surgery in patients with renal cell carcinoma. BJU Int. 2009 Aug;104(4):470-5. doi: 10.1111/j.1464-410X.2009.08439.x. Epub 2009 Feb 23.</span><br />
<span style="font-size: x-small;" xmlns="">[7] Poulakis V, Witzsch U, de Vries R, Moeckel M, Becht E. Quality of life after surgery for localized renal cell carcinoma: comparison between radical nephrectomy and nephron-sparing surgery. Urology. 2003 Nov;62(5):814-20.</span><br />
<span style="font-size: x-small;" xmlns="">[8] Ficarra V, Novella G, Sarti A, Novara G, Galfano A, Cavalleri S, Artibani W. Psycho-social well-being and general health status after surgical treatment for localized renal cell carcinoma. Int Urol Nephrol. 2002-2003;34(4):441-6.</span><br />
<span style="font-size: x-small;" xmlns="">[9] Onishi T, Nishikawa K, Hasegawa Y, Yamada Y, Soga N, Arima K, Yamakado K, Hoshina A, Sugimura Y. Assessment of health-related quality of life after radiofrequency ablation or laparoscopic surgery for small renal cell carcinoma: a prospective study with medical outcomes Study 36-Item Health Survey (SF-36). Jpn J Clin Oncol. 2007 Oct;37(10):750-4. Epub 2007 Oct 17.</span><br />
<span style="font-size: x-small;" xmlns="">[10] Parker PA, Swartz R, Fellman B, Urbauer D, Li Y, Pisters LL, Rosser CJ, Wood CG, Matin SF. Comprehensive assessment of quality of life and psychosocial adjustment in patients with renal tumors undergoing open, laparoscopic and nephron sparing surgery. J Urol. 2012 Mar;187(3):822-6. doi: 10.1016/j.juro.2011.10.151. Epub 2012 Jan 15.</span><br />
<span style="font-size: x-small;" xmlns="">[11] MacLennan S, Imamura M, Lapitan MC, Omar MI, Lam TB, Hilvano-Cabungcal AM, Royle P, Stewart F, MacLennan G, MacLennan SJ, Dahm P, Canfield SE, McClinton S, Griffiths TR, Ljungberg B, N'Dow J; UCAN Systematic Review Reference Group; EAU Renal Cancer Guideline Panel. Systematic review of perioperative and quality-of-life outcomes following surgical management of localised renal cancer. Eur Urol. 2012 Dec;62(6):1097-117. doi: 10.1016/j.eururo.2012.07.028. Epub 2012 Jul 20.</span><br />
<span style="font-size: x-small;" xmlns="">[12] Vasarainen H, Lokman U, Ruutu M, Taari K, Rannikko A. Prostate cancer active surveillance and health-related quality of life: results of the Finnish arm of the prospective trial. BJU international. Jun 2012;109(11):1614-1619.</span><br />
<span style="font-size: x-small;" xmlns="">[13] Wilcox CB, Gilbourd D, Louie-Johnsun M. Anxiety and health-related quality of life (HRQL) in patients undergoing active surveillance of prostate cancer in an Australian centre. BJU international. Mar 2014;113 Suppl 2:64-68. </span><br />
<span style="font-size: x-small;" xmlns="">[14] Daubenmier JJ, Weidner G, Marlin R, et al. Lifestyle and health-related quality of life of men with prostate cancer managed with active surveillance. Urology. Jan 2006;67(1):125-130.</span><br />
<span style="font-size: x-small;" xmlns="">[15] van den Bergh RC, Essink-Bot ML, Roobol MJ, et al. Anxiety and distress during active surveillance for early prostate cancer. Cancer. Sep 1 2009;115(17):3868-3878.</span><br />
<span style="font-size: x-small;" xmlns="">[16] Johansson E, Steineck G, Holmberg L, et al. Long-term quality-of-life outcomes after radical prostatectomy or watchful waiting: the Scandinavian Prostate Cancer Group-4 randomised trial. The lancet oncology. Sep 2011;12(9):891-899.</span><br />
<span style="font-size: x-small;" xmlns="">[17] Parker PA, Alba F, Fellman B, Urbauer DL, Li Y, Karam JA, Tannir N, Jonasch E, Wood CG, Matin SF. Illness uncertainty and quality of life of patients with small renal tumors undergoing watchful waiting: a 2-year prospective study. Eur Urol. 2013 Jun;63(6):1122-7. doi: 10.1016/j.eururo.2013.01.034. Epub 2013 Feb 9.</span><br />
<span style="font-size: x-small;" xmlns="">[18] Pierorazio PM, McKiernan JM, Allaf ME. Quality of Life on Active Surveillance for a Small Renal Masses versus Immediate Intervention: Interim Analysis of the DISSRM (Delayed Intervention And Surveillance For Small Renal Masses) Registry. <em>AUA Annual Meeting, 2013</em>. <a href="https://www.auanet.org/university/abstract_detail.cfm?id=633&meetingID=13SAN">https://www.auanet.org/university/abstract_detail.cfm?id=633&meetingID=13SAN</a></span><br />
Anonymoushttp://www.blogger.com/profile/05286847723206340868noreply@blogger.com6tag:blogger.com,1999:blog-4730782586548300034.post-35259952047125592892015-01-07T07:00:00.000-05:002015-01-07T07:00:02.190-05:00“Lighting up” Prostate Cancer<span xmlns=""></span><br />
<span xmlns="">Prostate cancer is notoriously difficult to image. In fact, traditional imaging technologies like <b>CT </b>(computerized tomography) and <b>ultrasound </b>are useless for <em>clinically-localized</em> disease (cancer still in the prostate). These technologies can find the prostate, but cannot reliably distinguish cancer from normal prostate gland. Recently, improvements in <b>MRI </b>(magnetic resonance imaging) have made this technology more useful for the diagnosis of localized prostate cancer. While the role of MRI in localized prostate cancer is being determined, the only useful imaging technologies are for patients with advanced and metastatic disease. For instance, CT scan (or MRI) can detect enlarged lymph nodes and <b>nuclear medicine (bone) scans</b> can find cancer that has spread to bones. </span><br />
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<span xmlns="">Even <b>PET </b>(positron emission tomography) imaging – which can detect many other cancers – is useless in prostate cancer. PET imaging makes use of a labelled glucose molecule that is taken up by rapidly dividing and growing cancer cells. Unfortunately prostate cancer is slow growing and does not pick up the glucose molecule to make it detectable. </span><br />
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<table cellpadding="0" cellspacing="0" class="tr-caption-container" style="float: right; margin-left: 1em; text-align: right;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjZaNqj0crO99ogDZ8EAb5xUL3L-rKIeuqAsyG_FlfAKmkDweCnxvVgyCbgluPL63sKYlJOJvjbeeNs5gKh3DW459DYR2LFpEa59FBE-2W8ycMUuoXFh9xN165wMWEl5zKMgjKo-czOJqw/s1600/pomper.jpg" imageanchor="1" style="clear: right; margin-bottom: 1em; margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjZaNqj0crO99ogDZ8EAb5xUL3L-rKIeuqAsyG_FlfAKmkDweCnxvVgyCbgluPL63sKYlJOJvjbeeNs5gKh3DW459DYR2LFpEa59FBE-2W8ycMUuoXFh9xN165wMWEl5zKMgjKo-czOJqw/s1600/pomper.jpg" height="163" width="200" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Martin Pomper, MD, PhD</td></tr>
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<span xmlns="">Researchers at the Brady Urological Institute and Johns Hopkins may be onto a new way to image prostate cancer using <em>molecular genetics</em> and PET imaging. <b><a href="http://www.hopkinsmedicine.org/pharmacology_molecular_sciences/faculty/bios/pomper.html">Martin Pomper, MD, PhD</a>,</b> works with nanoparticle imaging technologies that preferentially bind to prostate cancer cells and emit a signal that can be detected. Instead of using a glucose pathway, Dr. Pomper has developed a nanoparticle that binds to PSMA (prostate specific membrane antigen), a protein overexpressed on prostate cancer cells. The nanoparticle sensor <i>"only becomes activated when it encounters malignant cells, but not normal tissue, so that cancer and its metastases can be detected anywhere in the body." </i></span><br />
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<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEivTIX8Bo5gWM04_C6O65gbsD9Ykz0Vs84rQVH55q7xD6vuUoOuO1jqCHT4wZro3Knprs3JvqrEhpzOlAU7RcQsHgTdtP-9G4P5UYYJcOJxRHMzQMH73ZcdoToTSwCcYJcmVEaUJEKk2TA/s1600/psma_PETimaging.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEivTIX8Bo5gWM04_C6O65gbsD9Ykz0Vs84rQVH55q7xD6vuUoOuO1jqCHT4wZro3Knprs3JvqrEhpzOlAU7RcQsHgTdtP-9G4P5UYYJcOJxRHMzQMH73ZcdoToTSwCcYJcmVEaUJEKk2TA/s1600/psma_PETimaging.jpg" height="230" width="400" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">PSMA-based PET imaging of a mouse model with prostate cancer tumor (yellow arrow) implanted <br />in the forearm of the mouse. The urinary system (kidneys, kid; bladder, bl) are also visualized in the <br />early imaging as the molecule is filtered by the urine. From Chen et al. [1]</td></tr>
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Over several years, Dr. Pomper has worked to refine the molecule and technology used to image prostate cancer in the prostate and around the body. His work has been published in <em>Nature Medicine</em> and <em>Cancer Research</em>. Stay tuned as in human studies are in progress.<br />
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<span xmlns=""><span style="background-color: white; color: #333333; font-family: Arial;">Portions of this story were extracted from <a href="http://urology.jhu.edu/newsletter/2015/detecting_prostate_cancer_1.php"><span style="color: #771000; font-size: 11pt;">"Molecular-Genetic Imaging Shows Individual Prostate Cancer Cells"</span></a><span style="font-size: 11pt;"> in <a href="http://urology.jhu.edu/newsletter/2015/"><span style="color: #771000;"><em>Discovery: Volume XI, Winter 2015</em></span></a> by the Patrick C. Walsh Prostate Cancer Research Fund.</span></span><br /> </span><br />
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<span style="font-size: x-small;" xmlns="">[1] Chen Y, Pullambhatla M, Foss CA, Byun Y, Nimmagadda S, Senthamizhchelvan S, Sgouros G, Mease RC, Pomper MG. 2-(3-{1-Carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid, [18F]DCFPyL, a PSMA-based PET imaging agent for prostate cancer. Clin Cancer Res. 2011 Dec 15;17(24):7645-53. doi: 10.1158/1078-0432.CCR-11-1357. Epub 2011 Oct 31.</span><br />
Anonymoushttp://www.blogger.com/profile/05286847723206340868noreply@blogger.com35tag:blogger.com,1999:blog-4730782586548300034.post-71162567903604258092015-01-06T07:00:00.000-05:002015-01-06T07:00:09.417-05:00Historical Contribution: 1960, Jewett, Bladder Cancer Mechanisms of Invasion<a href="http://urology.jhu.edu/centennial/pdf/1960.pdf" style="font-family: Georgia, 'Times New Roman', serif;"><b><span style="font-size: x-large;">1960</span></b></a><span xmlns=""></span><br />
<span style="color: #660000; font-family: Georgia, Times New Roman, serif;" xmlns=""><b><a href="http://urology.jhu.edu/centennial/pdf/1960.pdf">Jewett HJ, Eversole Jr. SL. Carcinoma of the Bladder: Characteristic Modes of Local Invasion. J Urol. 1960. 83;4:383-89.</a></b></span><br />
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<span xmlns="">This 1960 manuscript is the transcript of a talk given by Dr. Jewett at the 1960 Annual Meeting of the American Association of Genitourinary Surgeons. Drs. Jewett and Eversole review the pathology from 303 infiltrating bladder cancers and made the following observations.</span><br />
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<span xmlns="">Jewett and Eversole arrived at three <i>"characteristic modes of local invasion" </i>in bladder cancer:</span><br />
<span xmlns="">"1) as a fairly compact mass (70%)</span><br />
<span xmlns="">2) as finger-like projections represented frequently as isolated masses (27%)</span><br />
<span xmlns="">3) as intramural lymphatic metastases traveling in a direction more or less perpendicular to the plane of the overlying bladder mucosa (3%)"</span><br />
<span xmlns=""><br /></span>To reach these conclusions, Jewett and Eversole first characterized the 300 specimens (from autopsy, cystectomy and transurethral resections) using Jewett's staging system: <strong>A</strong>, submucosa only; <strong>B1</strong>, less than halfway through the muscle; <strong>B2</strong>, halfway or more through the muscle; <strong>C,</strong> perivesical fat or prostate. They immediately found that the majority of cases of lymphatic invasion were stage B2 or C. In addition, well-differentiated tumors (low-grade) remained low-stage; and poorly differentiated, squamous and anaplastic tumor types were much more likely to reach the lymphatics at earlier-stages. <br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjk3pvtpatUIxwTZoatfZ7tB2Z6t4fuTXX_2rfd1NXYEfrYpS5l9054lLHUs-S9xpplZ-iEEyr8LNbQebkqfr5gOa48gyuJI2AmUlz5GU-BeAQvVSegxLPO-Z7ogZifQsnNqqGYlZRANZ4/s1600/1960.1.png" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjk3pvtpatUIxwTZoatfZ7tB2Z6t4fuTXX_2rfd1NXYEfrYpS5l9054lLHUs-S9xpplZ-iEEyr8LNbQebkqfr5gOa48gyuJI2AmUlz5GU-BeAQvVSegxLPO-Z7ogZifQsnNqqGYlZRANZ4/s1600/1960.1.png" height="203" width="400" /></a></div>
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<span xmlns="">Using these observations, Jewett and Eversole looked closely at pathologic specimens to determine modes on invasion. They determined that many of the "early-stage" tumors were actually <em>missed</em> invasive tumors that invaded deeply into the bladder lymphatics as finger-like projections or perpendicularly into the bladder wall – both difficult to assess with the constraints of serial sectioning and two-dimensional pathologic analysis. While these finger-like and perpendicular growth patterns were relatively uncommon, they were more common in deeply invasive tumors (Stage B2 and C).</span><br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgOkPDK4bmJLxhjQO4V3EcuPPRU5-cGsrV2Qj5co-vQ7Yl4ihPF4L9V_lDx-tVFF2EfqkfCj1OMIfpB2cZlf7f7hVs-Yc4Q1NTV0oPBlaPEQQiiHv4BXvjJRB8_JwAJCdGZ7RFZPNFMZoA/s1600/1960.2.png" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgOkPDK4bmJLxhjQO4V3EcuPPRU5-cGsrV2Qj5co-vQ7Yl4ihPF4L9V_lDx-tVFF2EfqkfCj1OMIfpB2cZlf7f7hVs-Yc4Q1NTV0oPBlaPEQQiiHv4BXvjJRB8_JwAJCdGZ7RFZPNFMZoA/s1600/1960.2.png" height="275" width="400" /></a></div>
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<span xmlns=""><span style="background-color: white; color: #333333; font-family: Arial; font-size: 13pt;">To read the entire manuscript: follow the link above, visit the <a href="http://urology.jhu.edu/centennial/"><span style="color: #771000;">Centennial Website</span></a> or click <a href="http://urology.jhu.edu/centennial/pdf/1960.pdf"><span style="color: #771000;">here</span></a>.</span><span style="font-family: Times New Roman; font-size: 12pt;"><br /> </span></span><br />
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<span xmlns=""><br /> </span><em style="color: #660000; font-family: Arial; font-size: 13pt;"><strong>HISTORICAL CONTRIBUTIONS </strong>highlight the greatest academic manuscripts from the Brady Urological Institute over the past 100 years. As the Brady Urological Institute approaches its centennial, we will present a HISTORICAL CONTRIBUTION from each of the past 100 years. In the most recent experience, the most highly cited article from each year is selected; older manuscripts were selected based on their perceived impact on the field. We hope you enjoy!</em><span style="color: #660000; font-family: Arial; font-size: 13pt;"> </span></div>
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<span xmlns=""><br /> </span>Anonymoushttp://www.blogger.com/profile/05286847723206340868noreply@blogger.com7tag:blogger.com,1999:blog-4730782586548300034.post-55509288823155557152015-01-05T07:00:00.000-05:002015-01-05T07:00:01.728-05:00Journal Spotlight: Laser vs. TURP for BPH, The GOLIATH Trial<span xmlns=""></span><br />
<span xmlns="">For men with bothersome <strong>lower urinary tract symptoms (LUTS)</strong> related to <strong>benign prostatic hyperplasia (BPH),</strong> transurethral surgery can improve urinary flow and symptoms for men who are not helped by medications. <strong>Transurethral resection of the prostate (TURP)</strong> is the traditional method for removing the obstructive tissue of a large, benign prostate. This involves using electrocautery to resect tissue, which is then collected from the bladder and removed from the patient. Historically, TURP is associated with a significant and excellent improvements in LUTS with a complication rate of approximately 10%.[1]</span><br />
<span xmlns=""><br /></span>
<span xmlns="">Over the past two decades a number of technologies have emerged to improve TURP including laser vaporization, bipolar TURP or vaporization, and laser enucleation of the prostate. Laser vaporization technologies are the most widely used as they were among the first <em>new</em> technologies introduced, are relatively easy to use and are believed the have less bleeding and improved visualization. However, no rigorous, head-to-head study has evaluated laser technology compared to the <em>gold standard</em> TURP – which has the benefits of being a faster operation with well-established, long-term benefits. </span><br />
<span xmlns=""><br />The <strong>GOLIATH Trial</strong>, a European multicenter, randomized study of laser vaporization versus TURP for BPH was recently published in <em>European Urology </em>and the 12-month update in the <em>Journal of Urology.</em></span><br />
<br />
<span style="color: #990000;" xmlns=""><i><a href="http://www.europeanurology.com/article/S0302-2838%2813%2901135-4/abstract/180-w-xps-greenlight-laser-vaporisation-versus-transurethral-resection-of-the-prostate-for-the-treatment-of-benign-prostatic-obstruction-6-month-safety-and-efficacy-results-of-a-european-multicentre-randomised-trial-the-goliath-study">Bachmann A, Tubaro A, Barber N, etal. 180-W XPS GreenLight laser vaporisation versus transurethral resection of the prostate for the treatment of benign prostatic obstruction: 6-month safety and efficacy results of a European Multicentre Randomised Trial--the GOLIATH study. Eur Urol. 2014 May;65(5):931-42. doi: 10.1016/j.eururo.2013.10.040. Epub 2013 Nov 11.</a><br /> </i></span><br />
<a href="http://www.jurology.com/article/S0022-5347(14)04377-8/abstract"><i><span style="color: #990000;">Bachmann A, Tubaro A, Barber N, etal. A European Multicenter Randomized Noninferiority Trial Comparing 180 W GreenLight XPS Laser Vaporization and Transurethral Resection of the Prostate for the Treatment of Benign Prostatic Obstruction: 12-Month Results of the GOLIATH Study. J Urol. 2014 Sep 16. pii: S0022-5347(14)04377-8. doi: 10.1016/j.juro.2014.09.001. [Epub ahead of print]</span></i></a><br />
<span xmlns=""><br /> </span><br />
<span xmlns="">Vital statistics of the GOLIATH Study:</span><br />
<ul>
<li><span xmlns="">291 patients</span></li>
<li><span xmlns="">29 centers in 9 European countries</span></li>
<li><span xmlns="">Laser vaporization: <a href="http://americanmedicalsystems.com/en/professionals/products/greenlight-xps-laser-therapy-system.html">180 Watt Greenlight-XPS™</a><br /> </span></li>
<li><span xmlns="">TURP: monopolar or bipolar (42%) technology</span></li>
</ul>
<span xmlns="">Important results from this trial include:</span><br />
<ul>
<li><div>
<span xmlns="">No difference between laser vaporization and TURP with regard to <span style="text-decoration: underline;">urinary outcomes</span> (see table):</span></div>
<ul>
<li><span xmlns="">IPSS (International Prostate Symptom Score)</span></li>
<li><span xmlns="">IPSS Quality of life score (IPSS QOL)</span></li>
<li><span xmlns="">Maximum flow rate (Qmax)</span></li>
<li><span xmlns="">Post-void residual urine</span></li>
<li><span xmlns="">Both treatments were associated with <em>short-term dysuria </em>(discomfort with voiding that resolved spontaneously) in approximately 18% of men.</span></li>
</ul>
</li>
<li><div>
<span xmlns="">Decreases in PSA and prostate volume were also similar among treatments.</span></div>
<ul>
<li><span xmlns="">Six men undergoing TURP were found to have prostate cancer; tissue is not analyzed after laser vaporization.</span></li>
</ul>
</li>
<li><div>
<span xmlns="">Outcomes that <em>favored</em> laser vaporization included:</span></div>
<ul>
<li><span xmlns="">Length of stay</span></li>
<li><span xmlns="">Catheterization time </span></li>
<li><span xmlns="">Return to stable health status </span></li>
<li><span xmlns="">Fewer 30-day re-operations</span></li>
</ul>
</li>
<li><div>
<span xmlns=""><span style="text-decoration: underline;">Adverse events</span> and re-operative rates were similar at 12 months:</span></div>
<ul>
<li><span xmlns="">Laser vaporization patients were more likely to undergo re-operation for bladder neck contractures and urethral strictures</span></li>
<li><span xmlns="">TURP patients were more likely to undergo re-operation for bleeding</span></li>
</ul>
</li>
<li><span xmlns="">No difference between monopolar and bipolar TURP for any outcome.</span></li>
</ul>
<span xmlns=""><br /> <table border="0" style="border-collapse: collapse;"><colgroup><col style="width: 115px;"></col><col style="width: 79px;"></col><col style="width: 86px;"></col><col style="width: 68px;"></col><col style="width: 72px;"></col><col style="width: 72px;"></col><col style="width: 68px;"></col></colgroup><tbody valign="top">
<tr style="height: 20px;"><td style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"></td><td colspan="3" style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><div style="text-align: center;">
<span style="color: black; text-decoration: underline;">Baseline</span></div>
</td><td colspan="3" style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><div style="text-align: center;">
<span style="color: black; text-decoration: underline;">12 Months</span></div>
</td></tr>
<tr style="height: 20px;"><td style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><span style="color: black;">(Mean Value)</span></td><td style="border-bottom: solid 0.5pt; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><div style="text-align: center;">
<span style="color: black;">GL-XPS</span></div>
</td><td style="border-bottom: solid 0.5pt; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><div style="text-align: center;">
<span style="color: black;">TURP</span></div>
</td><td style="border-bottom: solid 0.5pt; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><div style="text-align: center;">
<span style="color: black;">p Value</span></div>
</td><td style="border-bottom: solid 0.5pt; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><div style="text-align: center;">
<span style="color: black;">GL-XPS</span></div>
</td><td style="border-bottom: solid 0.5pt; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><div style="text-align: center;">
<span style="color: black;">TURP</span></div>
</td><td style="border-bottom: solid 0.5pt; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><div style="text-align: center;">
<span style="color: black;">p Value</span></div>
</td></tr>
<tr style="height: 20px;"><td style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><span style="color: black;">I-PSS:</span></td><td style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><div style="text-align: center;">
<span style="color: black;">21.2±5.9</span></div>
</td><td style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><div style="text-align: center;">
<span style="color: black;">21.7±6.4</span></div>
</td><td style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><div style="text-align: center;">
<span style="color: black;">0.541</span></div>
</td><td style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><div style="text-align: center;">
<span style="color: black;">7.0±6.0</span></div>
</td><td style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><div style="text-align: center;">
<span style="color: black;">5.7±5.3</span></div>
</td><td style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><div style="text-align: center;">
<span style="color: black;">0.079</span></div>
</td></tr>
<tr style="height: 20px;"><td style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><span style="color: black;">I-PSS-QOL:</span></td><td style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><div style="text-align: center;">
<span style="color: black;">4.6±1.1</span></div>
</td><td style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><div style="text-align: center;">
<span style="color: black;">4.5±1.4</span></div>
</td><td style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><div style="text-align: center;">
<span style="color: black;">0.721</span></div>
</td><td style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><div style="text-align: center;">
<span style="color: black;">1.4±1.4</span></div>
</td><td style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><div style="text-align: center;">
<span style="color: black;">1.2±1.3</span></div>
</td><td style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><div style="text-align: center;">
<span style="color: black;">0.287</span></div>
</td></tr>
<tr style="height: 20px;"><td style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><span style="color: black;">Qmax (ml/sec):</span></td><td style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><div style="text-align: center;">
<span style="color: black;">9.5±3.0</span></div>
</td><td style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><div style="text-align: center;">
<span style="color: black;">9.9±3.5</span></div>
</td><td style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><div style="text-align: center;">
<span style="color: black;">0.266</span></div>
</td><td style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><div style="text-align: center;">
<span style="color: black;">23.0±10.7</span></div>
</td><td style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><div style="text-align: center;">
<span style="color: black;">24.7±10.1</span></div>
</td><td style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><div style="text-align: center;">
<span style="color: black;">0.221</span></div>
</td></tr>
<tr style="height: 20px;"><td style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><span style="color: black;">PVR (ml):</span></td><td style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><div style="text-align: center;">
<span style="color: black;">110.1±88.5</span></div>
</td><td style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><div style="text-align: center;">
<span style="color: black;">109.8±103.9</span></div>
</td><td style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><div style="text-align: center;">
<span style="color: black;">0.453</span></div>
</td><td style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><div style="text-align: center;">
<span style="color: black;">43.0±57.1</span></div>
</td><td style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><div style="text-align: center;">
<span style="color: black;">33.7±43.8</span></div>
</td><td style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><div style="text-align: center;">
<span style="color: black;">0.107</span></div>
</td></tr>
<tr style="height: 20px;"><td style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><span style="color: black;">PSA (ng/ml):</span></td><td style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><div style="text-align: center;">
<span style="color: black;">2.7±2.1</span></div>
</td><td style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><div style="text-align: center;">
<span style="color: black;">2.6±2.1</span></div>
</td><td style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><div style="text-align: center;">
<span style="color: black;">0.816</span></div>
</td><td style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><div style="text-align: center;">
<span style="color: black;">1.3±1.3</span></div>
</td><td style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><div style="text-align: center;">
<span style="color: black;">1.1±1.0</span></div>
</td><td style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><div style="text-align: center;">
<span style="color: black;">0.116</span></div>
</td></tr>
<tr style="height: 20px;"><td style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><span style="color: black;">Prostate vol (ml):</span></td><td style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><div style="text-align: center;">
<span style="color: black;">48.6±19.2</span></div>
</td><td style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><div style="text-align: center;">
<span style="color: black;">46.2±19.1</span></div>
</td><td style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><div style="text-align: center;">
<span style="color: black;">0.301</span></div>
</td><td style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><div style="text-align: center;">
<span style="color: black;">21.9±11.0</span></div>
</td><td style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><div style="text-align: center;">
<span style="color: black;">21.0±12.8</span></div>
</td><td style="border-bottom: none; border-left: none; border-right: none; border-top: none; padding-left: 7px; padding-right: 7px;" valign="bottom"><div style="text-align: center;">
<span style="color: black;">0.574</span></div>
</td></tr>
</tbody></table>
</span><br />
<span xmlns=""><br /> </span><br />
Proponents of laser technology claim this study as a victory for laser technology given economic and quality of life implications of decreased length of stay, catheterization time, return to stable health and lower, 30-day reoperation rate. However, this should be balanced with a higher rate of urethral stricture disease – which not only requires re-operation but may have serious implications for cost, quality of life and urinary continence with longer follow-up – and inability to diagnose prostate cancer (as tissue is destroyed rather than evaluated) in select patients.<br />
<span xmlns=""><br /></span>
<span xmlns=""><span style="text-decoration: underline;"><strong>Take-home</strong></span>: Both laser vaporization and TURP are excellent procedures for the management of LUTS due to BPH. Both result in marked improvements in symptoms at 1 year. Both are associated with short-term dysuria. Patients undergoing TURP have a higher likelihood of re-operation within 30 days due to bleeding from surgery. Patients undergoing laser vaporization have a higher likelihood of requiring a secondary procedure for bladder neck contracture or stricture disease. No one surgery is right for all patients and a surgeon may have a preference to the technology they use. The decision on type of surgery should not rely on technology, but should take into account patient characteristics and preferences as well as surgeon experience and skill set.</span><br />
<span xmlns=""><br /> </span><br />
<span style="font-size: x-small;" xmlns="">[1] Wasson JH, Reda DJ, Bruskewitz RC, Elinson J, Keller AM, Henderson WG. A comparison of transurethral surgery with watchful waiting for moderate symptoms of benign prostatic hyperplasia. The Veterans Affairs Cooperative Study Group on Transurethral Resection of the Prostate. N Engl J Med. 1995 Jan 12;332(2):75-9.</span><br />
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