Friday, December 5, 2014

The Brady Centennial: 100 Years of Leadership


As the Brady enters its second century, it is wise to reflect on the title that Thomas Turner, the revered Dean of the Johns Hopkins School of Medicine from 1957-1968, gave to his book, Heritage of Excellence, which summarizes the contributions made by the early leaders of Johns Hopkins. These words serve as a constant reminder of the continuing responsibility to honor and respect these men and women whose shoulders the current generation stands, and to live up to their legacy as the Brady enters the next 100 years.

The Brady can be explored by the four directors who have led the institution since 1915. This blog will reflect on the contributions of each of these leaders.

 

HUGH HAMPTON YOUNG 1897-1941

"The Father of Modern Urology," recognized for transforming the field into a major surgical specialty.

Selected at age 27 by Halsted and Welch to run the genitourinary clinic, Young rapidly transformed a diagnostic and endoscopic outpatient field into a full-fledged branch of highly specialized major surgery. His pioneering contributions such as radical perineal prostatectomy for the cure of prostate cancer, and the simple perineal prostatectomy and the transurethral "punch" procedure for the treatment of prostatic obstruction, brought Young great fame and a new patient. "Diamond" Jim Brady was so grateful for Young's care that he funded the Institute that bears his name. Young is also credited with the discovery of mercurochrome, the first use of interstitial radiotherapy for prostate and bladder cancer, surgical correction of disorders of sexual differentiation, and surgery for posterior urethral valves. Young developed the first urology residency training program, founded the Journal of Urology and wrote the major textbook of his time. It has been said that, "The prostate makes most men old, but it made Hugh Young."

 

WILLIAM W. SCOTT 1946-1974

Revolutionized academic Urology by introducing basic research into residency training.

Scott, who trained at the University of Chicago with the future Nobel Prize-winning Urologist Charles Huggins, was appointed tat age 33 to be Young's successor. At the Brady, Scott introduced basic science into the field and made one year of laboratory research a mandatory part of residency training. This move was critical: in the absence of a comparable medical specialty, Urologists also had to become surgeon-scientists. Scott's contribution could not have been better timed. At the end of World War II, there were many outstanding candidates for residency positions, and soon many influential chairs would need to be filled. Sixteen of Scott's residents became chairs of those departments. One of Scott's greatest gifts to the field was recognizing and encouraging the brilliant scientist, Donald S. Coffey, PhD, the legendary director of research at the Brady for three decades. Coffey went on to educate, inspire, and mentor scores of the future leaders in the field.

 

PATRICK C. WALSH 1974-2004

Pioneered nerve-sparing radical prostatectomy, which rejuvenated scientific discovery in the field.

When Walsh became Director at age 36, he faced two major challenges: radical prostatectomies were rarely performed, because of excessive blood loss and unacceptable side effects; and the antiquated Brady Building needed to be replaced. After painstaking anatomic studies, Walsh developed a nerve-sparing procedure that reduced blood loss, improved continence, and made it possible to preserve potency. By 1992, radical prostatectomy became the most common treatment for localized prostate cancer in the US, and over the next decade deaths from prostate cancer declined by 40 percent. This surgical advance also provided abundant tissue for scientific investigation, galvanizing research in the field. in 1982, the Brady Institute was relocated to the newly renovated Marburg Building, a state-of-the-art facility where surgeons and scientists could work side by side. Over the next two decades, the Brady gained national recognition for excellence in research, patient care, and teaching. Eighty-five percent of Walsh's residents entered careers in academic medicine and seventeen became chairs of departments.

 

ALAN W. PARTIN 2004-PRESENT

Inventor of the nomogram that predicted curability and leader of the Brady as it enters its second century.

An Academic All-American in football and Valedictorian of his class at the University of Mississippi, Partin came to Hopkins in 1983 and never left. He received his MD and PhD in Pharmacology and Molecular Sciences under the mentorship of Don Coffey in 1989. As a Brady resident, Partin developed a nomogram, the Partin Tables, which launched a new field in prognostic prediction, helping countless patients to estimate whether they had curable disease. In 1995, he joined the faculty, and in 2004, at the age of 43, he was appointed the fourth Director of the Brady Institute. During the next decade, Partin oversaw initiation of robotic surgical programs in prostate, kidney and bladder cancer, expansion of the residency training program to three residents per year, creation of fellowships in Oncology and Sexual Medicine and Reconstruction, construction of a Woman's Pelvic Health Center at the Bayview Campus, and dedication of the Christina and Robert C. Baker Prostate Cancer Treatment Center on the eleventh floor of the Zayed Tower, the new home for the Brady inpatients.

 


The blog is extracted from 100 Years of Leadership at the Brady Urological Institute by Patrick C. Walsh, MD.


For more information of the upcoming centennial visit the Centennial Website.

Wednesday, December 3, 2014

Urologic Oncology in the Middle East


The Emirates Oncology Conference and Pan-Arab Cancer Congress 2014 was held in Abu Dhabi, UAE as a joint program of the SEHA Health System in conjunction with Johns Hopkins International and its affiliate Tawam Hospital. While the conference covered a wide range of malignancies, there was a palpable focus on cancer care in the Middle East. In urologic oncology, the prevalence of renal cell, prostate and bladder cancers is different depending on the country and region – therefore, the treatments and outcomes can vary dramatically.

This blog will discuss differences in Renal Cell Carcinoma, Prostate Cancer and Bladder Cancer in countries of the Middle East. 



The incidence and mortality of urologic malignancies in the Middle East (Western Asia) and the more developed regions of the world including the United States and Europe.

RENAL CELL CARCINOMA

According to the WHO GLOBOCAN program, the annual incidence of RCC (renal cell carcinoma) is 213,924 people, with 90,802 deaths per year leaving a 5-year prevalence of 580,700 people. RCC is age-related (i.e. more common in older patients) and is most common in the more developed countries of the world like the United States and countries of Europe. In the United States, the ASR (age-specific rate) of RCC is 12.0 per 100,000 people (see Table below). While Israel has an ASR for RCC of 10.0, most Arab countries of the Middle East have rates between 2.0 and 3.0. Turkey has the highest ASR of 5.6 for RCC. 

The 20 highest age-specific rates of kidney cancer (per 100,000) in the countries of Western Asia from WHO GLOBOCAN.
Most of the figures are likely inaccurate and underestimate the true incidence of RCC as data in not consistently shared among countries and institutions within countries.  To address the shortcomings of systematic data collection in these countries, the Africa Middle-East Collaborative RCC Epidemiology Project was started as a cancer registry, collecting data from a number of countries including Algeria, Egypt, Jordan, Lebanon, Libya, Morocco, and Saudi Arabia. For instance, GLOBOCAN estimates the incidence of RCC in Lebanon to be approximately 2 per 100,000, while the actual data from the collaborative registry indicates the incidence in Lebanon is closer to 4.3 per 100,000.

Similar to other countries around the world, most RCC are low-grade, early stage tumors, however the significant proportion of patients that present with high-stage or metastatic disease mirrors the 20-30% seen globally.

 

PROSTATE CANCER

The prostate cancer data mirrors the data for RCC. The US has an ASR of 98.2 per 100,000 men; Turkey has the highest ASR of 40.6 in the Middle East. 

The 20 highest age-specific rates of prostate cancer (per 100,000) in the countries of Western Asia from WHO GLOBOCAN.
Interestingly, Lebanon has seen a dramatic rise in the incidence of prostate cancer due to a national screening campaign using PSA several years ago.

The increasing trends in prostate cancer in Lebanon coincide with a national PSA screening campaign.
From Shamseddine etal. [1]


In the United Arab Emirates, prostate cancer is the 3rd most common malignancy. Most patients (77%) present with advanced disease and only approximately 20% receive radical local treatment (16.6% radiation treatment, 5.5% radical prostatectomy).[2] However, over the past decade there has been a tremendous shift toward a multidisciplinary approach to prostate cancer including oncology, urologic oncologists, robotic surgery, radiation oncology and cancer nursing. There are now approximately 30 daVinci Robotic Surgery Systems in the Middle East, with 12 in Saudi Arabia.

 

BLADDER CANCER

The ASR trends in bladder cancer are similar to those observed in RCC and prostate cancer. 

The 20 highest age-specific rates of bladder cancer (per 100,000) in the countries of Western Asia from WHO GLOBOCAN.
One of the more interesting trends in bladder cancer are the decreasing rates of schisosomiasis related squamous cell carcinomas of the bladder in Egypt (read more about schistosomiasis-related cancer of the bladder in our previous blog or click here). Control of schistosomiasis through antibilharzial campaigns have led to dramatic decreases in infestation rates and subsequent bladder cancer incidence. For instance, in Egypt the overall prevalence of schistosomiasis infection decreased from 37-48% to 3%, with a subsequent decrease in the proportion of bladder cancers from 31% to 12% of total cancers in the country.[3,4]

The second interesting trend in bladder cancer is the increasing incidence of cancers related to increasing rates of tobacco smoke. For instance, in Lebanon, the incidence of bladder cancer (13.7%) approaches that of prostate cancer (16.4%) – unheard of in most other countries! Recent data indicate that differences in the prevalence of drug metabolizing enzymes (S-transferases, N-acetyltransferases, and cytochromes P-450) in a number of ethnic groups may explain the susceptibility to bladder cancer in this population.[5]


Age-specific Rate (per 100,000 population)
Renal Cancer Prostate Cancer Bladder Cancer Testis Cancer
United States of America 12.0 98.2 11.6 5.0
State of Palestine 3.1   15.2   7.6   1.6  
Iraq 2.9   8.7   11.4   1.1  
Israel 10.0   84.3   12.6   4.9  
Jordan 3.2   15.3   7.1   1.7  
Kuwait 2.2   14.5   5.5   0.6  
Lebanon 3.2   37.2   16.6   2.4  
Oman 2.1   10.2   4.8   0.4  
Qatar 3.5   13.2   5.3   0.5  
Saudi Arabia 2.3   9.5   3.6   0.6  
Syrian Arab Republic 3.1   11.9   9.6   1.4  
Turkey 5.6   40.6   15.2   3.2  
United Arab Emirates 2.3   10.0   4.3   0.4  
Yemen 0.6   2.7   1.8   0.1  

 

SUMMARY


  • The most common urologic malignancies (RCC, prostate and bladder cancer) are disease of older populations and more common in the most developed countries of the world.
  • The incidence of these cancers is lower in all countries of the Middle East, although the true incidence may be underestimated by difficulties in gathering and sharing cancer data.
  • A number of interesting trends in the incidence of urologic malignancies make the Middle East a fascinating frontier for investigating cancers of the genitourinary system.


 

This blog was inspired by the lecture, "Overview of Genito Urinary Malignancies in The MENA Region," by Professor Marwan Ghosn of Lebanon.
 

[1] Shamseddine A, Saleh A, Charafeddine M, Seoud M, Mukherji D, Temraz S, Sibai AM. Cancer trends in Lebanon: a review of incidence rates for the period of 2003-2008 and projections until 2018. Popul Health Metr. 2014 Mar 4;12(1):4. doi: 10.1186/1478-7954-12-4.
[2] Ghafoor M, Schuyten R, Bener A. Epidemiology of prostate cancer in United Arab Emirates. Med J Malaysia. 2003 Dec;58(5):712-6.
[3] Ministry of Health and Population, Department of Endemic Diseases, Prevalence of schistosomiasis in Egypt over time, Egypt, 2004.
[4] I. Gouda, N. Mokhtar, D. Bilal, T. El-Bolkainy, N.M. El-Bolkainy. Bilharziasis and bladder cancer: a time trend analysis of 9843 patients. J Egypt Natl Canc Inst, 19 (2) (2007), pp. 158–162
[5] Dhaini HR, Kobeissi L. Toxicogenetic profile and cancer risk in Lebanese. J Toxicol Environ Health B Crit Rev. 2014;17(2):95-125. doi: 10.1080/10937404.2013.878679.

 

Tuesday, December 2, 2014

Historical Contribution: 1946, Jewett & Strong, Bladder Cancer Staging


1946
Hugh J. Jewett and George H. Strong. Infiltrating Carcinoma of the Bladder: Relation of Depth of Penetration of the Bladder Wall to Incidence of Local Extension and Metastases.  The Journal of Urology, 1946: 55, 366-372.


 

Hugh J. Jewett, MD
Hugh J. Jewett III (1903-1990) finished the Brady Residency at Johns Hopkins Hospital under Hugh Hampton Young in 1936, became a Professor in the School of Medicine, reaching emeritus in 1969.  His work on the prognostication and evaluation of urological malignancies earned him the Barringer Medal by the American Association of Genitourinary Surgeons and the Ramon Guiteras Award by the American Urological Association.  The theme of that body of work is epitomized in this 1946 manuscript.

---

In this paper, Dr. Jewett reviewed the autopsies of 127 patients with infiltrating bladder cancer from 1919-1944. The depth of penetration of tumor into the bladder wall was documented in 107 cases and related to the incidence of 1) metastases, 2) lymphatic capillary invasion and 3) perivesical fixation. From this data, Dr. Jewett was able to stratify patients into three groups: those with submucosal invasion, those with invasion into the detrusor muscle and those with invasion through the detrusor. These groups served as the basis for and correspond to today's modern staging categories of non-muscle invasive (pTa, pT1), muscle invasive (pT2) and locally invasive (pT3, pT4) urothelial cancer.
 




Importantly, Dr. Jewett demonstrated that the number of lymph node and distant metastases, as well as the likelihood of pelvic fixation increased as the tumor grew into and through the bladder wall. He therefore deduced that 100% of patients with submucosal invasion were potentially curable and only 26% of those with perivesical fixation were potentially curable.




In addition, this manuscript defined the lymphatic drainage of the bladder in relation to the peritoneum and abdominal wall and detailed the principle sites of invasion of urothelial metastases (regional lymph nodes, liver, lungs and vertebral column).

This manuscript was a landmark paper, in that it described the basis for our modern-day staging of bladder cancer and developed a prognostic model that could be easily shared among physicians and patients. It has been cited over 400 times since its original publication.
 

To read the entire manuscript: follow the link above, visit the Centennial Website or click here.

HISTORICAL CONTRIBUTIONS 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! 


Monday, December 1, 2014

The Importance of Testicular Self-Examination

Testicular Cancer is the most common malignancy in men aged 15-34 years old. While there are less than 10k cases of testicular cancer diagnosed every year, the cure rate is greater than 95% for all new cases – leaving hundreds of thousands of survivors in the US at any given moment.[1]  Men with cancer confined to the testicle are almost guaranteed a cure – the long-term survival is approximately 99%. While the cure rate for men with metastatic disease (or cancer spread from the testicle) is still 75%, these men are often subjected to chemotherapy and/or surgery. Read our prior blog on the life-saving additional of Platinum-based Chemotherapy to the Treatment of Metastatic Testicular Cancer.

While most men present with a painless testicular mass, upwards of 15-60% of men will still present with testicular cancer that has spread.[2]  One of the challenges in treating this disease is therefore trying to get more men to present with early-stage, confined testicular cancer before they develop metastatic disease. In the US, on average, men wait 4-6 months prior to seeking a professional opinion for an abnormality in their scrotum and this can lead to higher rates of chemotherapy and worse survival rates.[3,4]

The best means for early-diagnosis and treatment is Testicular Self-Examination (TSE). It is recommended that men examine themselves in a shower once per month for any lumps, bumps, firmness or abnormalities in their testicles. TSE is advocated for by a number of Testicular Cancer advocacy groups including the Testicular Cancer Awareness Foundation (TCAF, www.tcafinfo.org). The TCAF describes how to perform TSE:
  • The best time to self-exam is after a warm bath or shower when the scrotal skin is relaxed.
  • Examine each testicle gently with both hands by rolling the testicle between the thumb a forefingers.
  • Find the epididymis, the soft tube-like structure behind the testicle that collects and carries sperm. If you are familiar with this structure, you won't mistake it for an abnormal mass.

  • Look for any lumps or irregularities. Remember that lumps or bumps may also present themselves as painless.
  • Look for any changes in size, shape, or texture. Remember it's normal for one testicle to be slightly larger.
The most important step in TSE is to seek a medical opinion if something abnormal is felt.



 

Testicular cancer can grow and spread incredibly quickly and seeking a timely opinion from a testicular cancer expert is of utmost importance – a timely diagnosis can help diagnose the disease early and prevent the need for chemotherapy or extensive surgery. 
For any man with a testicular abnormality - especially those 15-35 - the first thought should be testicular cancer. 
These men should be evaluated immediately with a scrotal ultrasound; if an abnormality, tumor markers (see our prior blog on Testicular Tumor Markers); and should be referred to an urologist or testicular cancer expert. Men should not be treated with antibiotics or anti-inflammatories without an ultrasound or evaluation by an expert.

Of note, the US Preventive Services Task Force (USPSTF) recommends against TSE, citing "moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits". A future blog will address the shortcomings of the USPSTF recommendation and the evidence supporting TSE.


 

This blog was written by Phillip M. Pierorazio, MD; Assistant Professor of Urology and Oncology and Director of the Division of Testicular Cancer at the Brady Urological Institute at Johns Hopkins.










[1] SEER Stat Fact Sheets: Testis Cancer, http://seer.cancer.gov/statfacts/html/testis.html
[2] Stephenson, A. J., and T. D. Gilligan. 2012. Neoplasms of the testis. Pp. 837–870 in A. J. Wein, L. R. Kavoussi, A. C. Novick, A. W. Partin and C. A. Peters, eds. Campbell-Walsh urology. Chapter 31, vol. 1, 10 ed. Elsevier Saunders, Philadelphia, PA.
[3] Moul JW, Paulson DF, Dodge RK, et al: Delay in diagnosis and survival in testicular cancer: impact of effective therapy and changes during 18 years. J Urol 1990; 143: pp. 520-523
[4] Stephenson AJ, Russo P, Kaplinsky R, et al: Impact of unnecessary exploratory laparotomy on the treatment of patients with metastatic germ cell tumor. J Urol 2004; 171: pp. 1474-1477

Wednesday, November 26, 2014

Robotics in Urologic Oncology: Partial Nephrectomy for Kidney Cancer

Robotic surgery is the latest evolution in laparoscopic surgery. Traditional laparoscopic surgery was and is performed with rigid instruments, a two-dimensional view with the surgeon at the patient's bedside and an assistant controlling the camera (or view) of the operation. Robotic surgery makes use of a three-dimensional, dual-camera system; instruments that mimic natural hand motions leading to improved ergonomics, and while the surgeon sits at a console away from the patient, he or she has full control of the camera and view of the operation. The robotic systems used today are termed "master-slave" systems where the robot transforms human movements into scaled robotic movements, but the robotic instruments cannot function independently or autonomously.

The most widely-used robotic system is the daVinci system by Intuitive Surgical. This system was first cleared by the FDA in 1997 for surgical assistance, for radical prostatectomy in 2001 and broad urological surgery in 2005. There are currently over 2,000 daVinci units in use in the United States and nearly 1,000 additional units worldwide. Urology and urologic oncology as specialties represent a major proportion of the utilization of robotic surgery. For many diseases and operations, robotic technology has improved perioperative and long-term outcomes – for other operations the benefit is marginal at best. In this series of blog entries, we will review the utilization and impact of robotic technology on a number of urologic oncology disease states.

The first blog in this series will focus on kidney cancer and the use of robotic partial nephrectomy.

 

THE HISTORY OF LAPAROSCOPIC NEPHRECTOMY AND PARTIAL NEPHRECTOMY

The first laparoscopic radical nephrectomy was performed in 1991 by Dr. Clayman and colleagues at the Washington University School of Medicine, St Louis.[1] Unlike appendectomy (appendix removal) and cholecystectomy (gallbladder removal) in general surgery, the adoption of laparoscopic nephrectomy was slow in the US with only 30% of nephrectomies being performed laparoscopically by 2005.[2] In comparison, 70% of gallbladders were removed laparoscopically 15 years after the first laparoscopic cholecystectomy. During the same time period, partial nephrectomy (PN, or removal of just a kidney tumor and the surrounding normal kidney tissue) was historically underutilized in the US. In the 1990's and early 2000's, only approximately 10% of kidney surgeries were PN – and most of these were performed at large, academic, urban and teaching hospitals.[3] While the rates oif both laparoscopy and PN increased during the 2000's, the majority of PN were performed through an open incision, once again in large urban and teaching hospitals.[4]

 

In the late 2000's, a number of national and worldwide trends changed the way kidney surgery was performed. First, robotic technology was taking off – the daVinci system was approved for radical prostatectomy in 2001 and over the next decade hospitals all over the US were acquiring robots. As the number of robotic prostatectomies and surgeries increased nationwide, surgeons became more comfortable with robotic technology and began looking for more uses. In addition, in 2009, the AUA (American Urological Association) released the "Guidelines for the Management of the Clinical Stage 1 Renal Mass." The Guideline states that "Nephron-sparing surgery should be considered in all patients with a clinical T1 renal mass as an overriding principle," and within a year of releasing the Guidelines, the utilization of PN increased from 27% to 32% nationwide.[5]

 

Data from Johns Hopkins and the State of Maryland indicate that the rate of PN increased from 9% to 27% from 2000 to 2010. The proportion of open PN decreased by 1/3rd and robotic and other minimally-invasive PN increased to nearly 60% of all PN. Importantly, after 2008 (a time period which robotic technologies were widely disseminated), being treated at a university hospital was no longer a predictor of PN – PN was finally becoming widespread!![6] 


The increasing using of robotic and minimally-invasive partial
nephrectomy in the State of Maryland. From Patel et al. [6]

This local trend was reflected in national data, indicating modest increases in open PN (8%) but dramatic increases in robotic PN (45%) in the National Inpatient Sample (a large all-payer inpatient care database cataloguing over 7 million inpatient hospitalizations).[7]

 

COMPARATIVE OUTCOMES FOR ROBOTIC PARTIAL NEPHRECTOMY: 

DO THE DATA SUPPORT THIS TREND?

In general, the increasing use of robotic PN is supported by data and represents one of the true "success stories" for robotic surgery. Robotic surgery is beneficial to patients undergoing PN as the wristed robotic instruments and three-dimensional views facilitate better and faster removal of tumors and reconstruction of the kidney.  The video below is a representative example of a robotic PN: the artery is temporarily clamped to facilitate a bloodless resection and reconstruction (ischemia time), the tumor is resected and the kidney is reconstructed.



In a systematic review of eight studies comparing robotic PN to open PN, robotic PN was associated with:
  • Longer operative time (+40.89 minutes ; p = 0.002)
  • Lower perioperative complication rate (19.3% for RPN and 29.5% for OPN)
    • Odds ratio: 0.53; 95%CI, 0.42–0.67; p<0.001
  • Shorter hospital stay (−2.78 days; p<0.00001)
  • Less estimated blood loss (−106.83mL; p = 0.003)
There was no difference observed in transfusions, conversion to radical nephrectomy, ischemia time, estimated GFR change (kidney function), surgical margin status, or overall cost.[8]
Comparing robotic to laparoscopic PN in a systematic review of 12 studies and over 700 patients, demonstrated no difference in operative times, estimated blood loss, conversion rates, length of hospital stay, complications, or positive margins between the surgeries. In fact, the only notable difference was that robotic PN was associated with less warm ischemic time (quicker removal of the tumor and reconstruction of the kidney). It should be noted that laparoscopic surgery was performed by fewer, but expert surgeons while robotic PN was performed by a greater variety of surgeons of varying experience level.[9]

When comparing our data at Johns Hopkins, we found that robotic PN was associated with improved operative parameters (operative time, blood loss, ischemia time) and fewer serious complications.[10] In addition, we determined that the learning curve for robotic PN was much quicker than laparoscopic surgery – about 25 patients.[11]

While long-term oncologic data is lacking, surrogate oncologic measure (i.e. surgical margin status) and short-term recurrence and survival data indicate that robotic PN is equivalent to open and laparoscopic surgery with regards to oncology outcomes, and likely superior with regard to perioperative outcomes.

 

SUMMARY


  • The emergence of robotic technology dramatically changed the management of kidney cancer in the United States, with more patients undergoing partial nephrectomy now than ever before.
  • The comparative data demonstrates improved outcomes for many peri-operative and surrogate oncologic outcomes. Longer-term data will likely confirm robotic PN as the standard-of-care for small renal masses requiring treatment.


 


 

This blog was adapted from a lecture titled "Robotics in Urologic Oncology," given by Phillip M. Pierorazio, MD, Assistant Professor of Urology and Oncology, at the Emirates Oncology Conference, 2014 in Abu Dhabi.

 


 







  1. Clayman et al. Laparoscopic Nephrectomy. N Engl J Med 1991; 324:1370-1371May 9, 1991. http://www.nejm.org/doi/full/10.1056/NEJM199105093241918
  2. Miller, D. C. et al. JAMA 2006;295:2480-2482
  3. Hollenbeck, Urology, Volume 67, Issue 2, 2006, 254 - 259
  4. Patel et al., J Urol, Volume 187, Issue 3, 2012, 816 - 821
  5. Bjurlin et al., Urology, Volume 82, Issue 6, 2013, 1283 - 1290
  6. Patel et al., J Urol, 2013 Apr;189(4):1229-35.
  7. Ghani et al., J Urol, Volume 191, Issue 4, 2014, 907 - 913
  8. Wu etal. PLoS One. 2014; 9(4): e94878.
  9. Aboumarzouka etal. Eur Urol. 2012 Dec;62(6):1023-33.
  10. Mullins etal. Urology. 2012 Aug;80(2):316-21.
  11. Pierorazio et al., Urology, 78 (2011), p. 813

Tuesday, November 25, 2014

Historical Contribution: 1945, Lewis, Bladder Dysfunction after Trauma


1945
Lewis LG. Treatment of Bladder Dysfunction after Neurologic Trauma. J Urol. 1945; 54; 3: 284-95.    

 

Lloyd G. Lewis, MD
LLoyd G. Lewis graduated the Brady Residency in 1933. He was remembered as a superb surgeon and co-author of The Physiology of Micturation, 1940 after undertaking a number of laboratory experiments involving the innervation of the feline bladder. During World War II, Lewis served as Chief of Urology at Walter Reed General Hospital in Washington, DC and succeeded in having Walter Reed approved for residency training during his time there. This manuscript was written while Chief of Urology at Walter Reed.

To understand the neurogenic bladder, one must first understand the normal mechanisms of bladder function. Therefore, Dr. Lewis begins this manuscript with a thorough description of the normal anatomy and neurophysiology of bladder storage and micturition as it was understood in the 1940's. Interestingly, the pathophysiology for abnormal bladder function came from studies of advanced syphilis patients (with tabes dorsalis) and pelvic surgery patients. Through careful observation and meticulous attention to detail, Lewis noted neurologic consistencies among patients with similar neurologic diseases or injuries, and tabulated the following observations:

  • The immediate effect of severe injury to the brain or spinal cord is urinary retention (a concept called spinal shock).
    • Spinal shock was believed to be relieved within 48 hours.
    • Failure to decompress the spinal cord within 48 hours would lead to permanent disability.
    • Lewis demonstrates 10 circumstances where bladder function was restored weeks to months following surgical decompression of the spinal cord.
  • Until the permanent neurourologic state is determined, treatment should focus on:
    • Prevention of ascending urinary tract infections (UTI).
    • Protection of paralyzed muscles.
    • Restoration of function.
  • To prevent UTI, HH Young preached "no instrumentation" of the urinary tract. Lewis noted that failure to drain the urinary system would lead to permanent dysfunction of the bladder, likely due to overstretching. Therefore, Lewis recommended:
    • No instrumentation for 24 hours.
    • If no voiding after 24 hours, a one-time, straight urethral catheter should be employed.
    • If the patient is unable to void, a second, indwelling urethral or suprapubic drainage should be instituted. 
    • Changing of the urinary catheter every 5 days in the acute setting.
      • Chronic catheter changes at 6 week intervals if needed. 
    • Use of acidic-solution irrigation if needed to prevent encrustation and infection of the catheter.
    • Perineal urethrostomy with catheter drainage (performed under local anesthetic) if periurethral abscesses.
  • Lewis described the outcomes of 16 patients with a variety of complete and incomplete spinal cord injuries resulting in urinary retention. From these observations, he concluded that:
    • Permanent drainage is indicated for complete injuries below L1.
    • Outlet obstruction cannot be relieved with surgical operations.
    • Presacral neurectomy (surgical transection of the parasympathetic nerves to the bladder) can be considered as an experimental treatment in patients with residual urine and no concern for ejaculatory function.
    • Patients are more comfortable with permanent cystostomy tubes than permanent incontinence.
    • Surgery to decompress or treat the neurologic injury should be instituted immediately; any surgery to treat bladder dysfunction should be delayed for months to years, as adequate neurologic function may return.
Interestingly, many of the principles laid forth by Lewis in 1945 remain the standard principles practiced by urologists today.

To read the entire manuscript: follow the link above, visit the Centennial Website or click here.

HISTORICAL CONTRIBUTIONS 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! 


Monday, November 24, 2014

Acute Kidney Injury: Understanding the Causes


Acute kidney injury (AKI), previously known as acute renal failure, is a rapid reduction in kidney function that can represent a spectrum of injuries that involve failure to maintain fluid, electrolyte and acid-base balances. A variety of patients suffering from a variety of medical conditions can develop AKI. Patients with urological issues often experience AKI as a result of their disease, or occasionally treatments thereof. 

A prior blog reviewed the "Basics of Renal Failure and Acute Kidney Injury," click here to read the prior blog.

This blog will review the causes of AKI, specifically as they may affect urological patients.

In general, AKI is grouped into three categories that describe the etiology (cause) and subsequent management:

  • Pre-renal
  • Intra-renal
  • Post-renal
Most patients who develop AKI in the community do so as a result of a pre-renal etiology. In contrast, of the patients who develop AKI in the hospital, upwards of 45%, do so as a result of acute tubular necrosis (ATN) – a form of intra-renal AKI. For surgical patients, there are 11 established pre-operative predictors of AKI following surgery:
  • Age ≥ 56 years
  • Male Sex
  • Congestive Heart Failure (CHF)
  • Diabetes Mellitus on oral medications or requiring insulin
  • Hypertension
  • Emergency Surgery
  • Intraperitoneal (Abdominal) Surgery
  • Ascites (fluid in the abdomen)
  • Mild or moderate renal insufficiency preoperatively
The strongest predictors of post-operative AKI are intraperitoneal (abdominal) surgery, pre-existing renal insufficiency and abdominal ascites.[1]

From Kheterpal etal. [1]

PRE-RENAL ACUTE KIDNEY INJURY

All causes of pre-renal AKI result from decreased perfusion of the kidney. Common causes include decreased blood volume, dehydration, heart failure and other disease states that decrease blood flow to the kidneys. Most commonly, pre-renal AKI is due to transient hypoperfusion (or decreased blood flow to the kidney over a short period of time). Pre-renal AKI can be further classified into three causes of hypoperfusion:
  • Volume depletion: not enough blood volume to perfuse the kidney
    • Traumatic or surgical blood loss
    • Gastrointestinal losses (dehydration) from vomiting, diarrhea, etc.
    • Dehydration due to kidney disease (overdiuresis, salt-wasting diseases)
  • Cardiac: blood volume is normal, but the heart cannot "pump" the blood effectively
    • Acute causes: myocardial infarction (heart attack), arrhythmia
    • Chronic causes: valvular disease, cardiomyopathy
  • Redistribution of fluid: blood volume is normal, the hear can pump effectively, but the body cannot keep fluid in the blood vessels
    • Hypoalbuminemia (low body protein): liver disease, malnutrition/starvation
    • Physical injury: burns, crush injury
    • Vascular:
      • Vasodilation (opening of blood vessels all over the body, preventing blood from reaching the kidneys): serious infections, sepsis, anti-hypertensive medications
      • Obstruction of the renal blood vessels: artherosclerotic disease, renal artery stenosis
Hallmarks of pre-renal AKI include a reversible state, lack of structural damage to the kidney or the nephron (microscopic filtering apparatus of the kidney), and response to replacement of fluids. Often patients will return to normal kidney function within 24-72 hours of fluid replacement.

 

INTRA-RENAL ACUTE KIDNEY INJURY

Intra-renal AKI can be further classified into diseases that affect either: (1) the microscopic blood vessels of the kidney, (2) the glomerulus, or filtering mechanism of the kidney), (3) the tubules of the kidney that resorb fluids and electrolytes, or (4) the interstitium (the space between strictures) in the kidney.
Microscopic blood clots and a number of diseases termed microangiopathies can affect the small blood vessels in the kidney. The glomerulus is most often affected by a number of autoimmune disease states including: anti-glomerular basement membrane disease, glomerulonephritis (inflammation of the glomerulus) related to SLE (systemic lupus erythematosus) or Wegener's (ANCA-associated). In addition, glomerulonephritis can occur after a number of serious bacterial infections – termed post-infectious glomerulonephritis.
The most common cause of tubular injury is ATN (Acute Tubular Necrosis) caused by a combination of renal hypoperfusion and ischemic (no blood flow) injury, usually in combination with a toxic exposure to medication, prolonged surgery or disease-state that makes the kidney more sensitive to injury. ATN usually presents as oliguria (very low urine output, 150-300cc/day; normal is 800-2,000cc/day). During the early phases of ATN, the serum creatinine will rise (see "Basics of Renal Failure and Acute Kidney Injury" for description of serum creatinine and its relationship to AKI) while the patient continues to make an unconcentrated form of urine. Most patients will recover from ATN, however due to the tubular injuries patients can experience serious fluid and electrolyte abnormalities – about 25% of deaths related to AKI occur in the initial phases of ATN.
Interstitial diseases of the kidney are often caused by medications, infections and autoimmune diseases (similar to glomerulonephritis). AIN (Acute Interstitial Nephritis) is a rare but serious cause of drug-induced AKI. The most common meidcations to cause AIN are antibiotics, non-steroidal anti-inflammtory medications (ibuprofen, aspirin), diuretics and proton-pump inhibitors for gastroesophageal reflux. Patients may develop a fever, demonstrate white blood cells (specifically eosinophils, inflammatory cells associated with allergy-like reactions) in their urine without infection, and have a rising serum creatinine.

 

POST-RENAL ACUTE KIDNEY INJURY

Post-renal AKI refers to any obstruction of the urinary system. Obstructions can occur in the kidney, ureter(s) or at the level of the bladder, prostate (in men) or urethra. The obstruction is usually mechanical in nature and can be caused by a variety of benign and malignant conditions. Kidney stones, blood clots, stricture disease and malignancy can obstruct the ureters. Obstruction should involve both ureters to cause AKI; however in some circumstances, when pre-existing renal insufficiency is present, obstruction of one ureter can cause AKI. Similar causes including bladder stones, urethral strictures, benign growth (benign prostatic hyperplasia in men, uterine disease or prolapse in women) and pelvic malignancies can cause obstruction of the bladder and/or urethra. Post-renal AKI is easily treated with resolution of the obstruction. The obstruction can be relieved with a catheter in the bladder or nephrostomy tubes in the kidneys until the offending cause can be treated.

 

SUMMARY

  • AKI can be grouped into three etiologies that describe the cause and management of the injury:
    • Pre-renal
    • Intra-renal
    • Post-renal
  • Pre-renal AKI refers to hyoperfusion or not enough blood flow to the kidney.
  • Intra-renal AKI is usually due to disease states that affect the kidney and its micropscopic filtering unit, the nephron.
  • Post-renal AKI is caused by mechanical obstruction of the urinary system and is treated by drainage until the offending obstruction can be removed.

 


 


 


 

[1] Kheterpal S et al. Development and validation of an acute kidney injury risk index for patients undergoing general surgery: Results from a national data set. Anesthesiology 2009; 110 (3): 505-15.