Historical Contribution: 1969, Schwarz, et al., UTI Correlation to Fecal Bacteria

1969

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.

 
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.

 
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.

 
Visit the Centennial Website or click here to see more about the first 100 years at the Brady.

 

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! 

Historical Contribution: 1966: Gibbons, Transurethral Freezing of the Bladder

1966
Gibbons RP. Transurethral Freezing of the Bladder: An Experimental Study. J Urol. 1966. 95;33-44.

 
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.

 
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. 

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.

 
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.

 
Visit the Centennial Website or click here to see more about the first 100 years at the Brady.

 

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! 

Historical Contribution: 1971, Chung and Coffey, The Prostate Nuclei

1971
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

 
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 Historical Contribution: 1968). 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:

1. Magnesium levels and the nuclear membranes are affected by testosterone levels. Aberrations in these normal cellular processes resulted in lower nuclei yield.
2. 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.
3. Nuclear protein to DNA content (as measured by nuclear proteins and nuclear membrane proteins) is decreased with low testosterone levels and,
4. … can be restored to normal after testosterone supplementation.

This series of elegant experiments can be found in Biochimica et Biophysica Acta. It is a wonderful example of Dr. Coffey's thoughtful and inventive approach to deciphering the prostate.

 
Visit the Centennial Website or click here to see more about the first 100 years at the Brady.

 

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! 

Historical Contribution: 1968, Coffey et al, DNA, Androgens and Prostate Growth

1968
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.


 

Donald S. Coffey, PhD

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.

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 "the enhancement of "DNA synthesis" by intact prostatic cells."

 
Follow the link here to access the manuscript from Archives of Biochemistry and Biophysics.


Visit the Centennial Website or click here to see more about the first 100 years at the Brady.

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! 

 

 

Historical Contribution: 1967, Schirmer and Scott, Prostate Cancer and Irradiation

1967
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.

HKA Schirmer (2nd from left, last row) 
and WW Scott (2nd from right, 1st row), 1986-87.

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.

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.

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.

Follow the link here to access the Southern Medical Journal.

 

Historical Contribution: 1965, Williams-Ashman, Androgens, Nucleic Acid & Protein Synthesis in Male Organs

1965
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.


 
Howard Guy Williams-Ashman, PhD, 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).

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:

"…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."

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.

 
Follow the link here to access the Journal of Cellular Physiology.

Historical Contribution: 1964, Schirmer & Walton, Hypothermia and Kidney Function

1964
Schirmer HKA, Walton K. The Effet of Hypothermia upon Respiration and Anerobic Glycolysis of Dog Kidney. Invest Urol. 1964. 1;6:604-9.

 
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] 

Horst Schirmer, MD

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:

• With decreasing temperature, the reduction in glycolysis associated with ischemia was tempered (33% at 27C, 17% at 17C and near zero at 7C).
• After achieving hypothermia of 7C, normal function returned after 1 hour.
• Interruption of blood flow for 4 hours resulted in:
  • 75% reduction in function in the normothermic kidney
  • Unchanged function in the cooled (7C) kidney
• 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.

 
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! 

[1] Herr HW.A history of partial nephrectomy for renal tumors.J Urol. 2005 Mar;173(3):705-8.

Historical Contribution: 1963, King et al, The Bladder Neck in Childhood

1963
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.


 
In the Transcripts of the American Association of Genitourinary Surgeons, 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:

• 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.
• Of boys with outlet obstruction, about half of the patients had meatal stenosis and the other half had posterior urethral valves (PUV).
• 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.

In conclusion, King, Mellins and Scott found that there was a characteristic appearance of the bladder neck in pediatric patients with obstruction. However, "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."

 
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! 

Historical Contribution: 1962, Hypophysectomy for Prostate Cancer, Scott & Schirmer.

1962
Scott WW, Schirmer HKA. Hypophysectomy for Disseminated Prostatic Cancer. Cancer and Hormones. 1962. 175-203.


 

WW Scott

Believing that the metastatic progression of prostate cancer was related to exogenous testosterone after castration,[What makes the Prostate Grow, WW Scott] 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^st hypophysectomy) and 1961, 17 patients underwent hypophysectomy for the treatment of their prostate cancer.

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

"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."

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.

 
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! 

 

Historical Contribution: 1961, Stamey, Renovascular Hypertension

1961
Stamey TA, Nudelman IJ, Good PH, Schwentker FN, Hendricks F. Functional Characteristics of Renovascular Hypertension. Medicine. 1961. 40(4):347-94.


 

Thomas A. Stamey, MD

Shortly before leaving the Brady for Stamford University, where he served as chairman of urology for 26 years, Thomas A. Stamey, MD, wrote authored a 50 page manuscript summarizing the state-of-the-art of renovascular hypertension (RVH). Early in his career, Dr. Stamey was recognized as one of the world's experts on RVH and renal physiology.

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.

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.


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! 

 

Historical Contribution: 1960, Jewett, Bladder Cancer Mechanisms of Invasion

1960
Jewett HJ, Eversole Jr. SL. Carcinoma of the Bladder: Characteristic Modes of Local Invasion. J Urol. 1960. 83;4:383-89.

 
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.

Jewett and Eversole arrived at three "characteristic modes of local invasion" in bladder cancer:
"1) as a fairly compact mass (70%)
2) as finger-like projections represented frequently as isolated masses (27%)
3) as intramural lymphatic metastases traveling in a direction more or less perpendicular to the plane of the overlying bladder mucosa (3%)"

To reach these conclusions, Jewett and Eversole first characterized the 300 specimens (from autopsy, cystectomy and transurethral resections) using Jewett's staging system: A, submucosa only; B1, less than halfway through the muscle; B2, halfway or more through the muscle; C, 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.

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 missed 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).

 
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! 

 

 

Historical Contribution: 1959, Colston, Radical Perineal Prostatectomy

1959
Colston JAC. Radical Perineal Prostatectomy for Early Cancer: Follow-up Study of One Hundred Eight Personal Cases. JAMA. 1959;169(7):700-703.

 
In 1959, Dr. JAC Colston delivered his experience of over 100 radical perineal prostatectomies for the treatment of prostate cancer at the Southeastern Section of the American Urological Association. The transcript of his talk was published in the Journal of the American Medical Association (JAMA).

Prior to the advent of PSA testing, the diagnosis of prostate cancer relied on physical examination (digital rectal examination) as symptoms do not present until an advanced stage. Colston explains,

"Unfortunately, the progress of prostatic carcinoma is a slow and insidious one, as is well known, and symptoms from a neoplasm usually do not occur until the growth has progressed beyond the capsule of the gland, making a complete eradication of the disease impossible."

The diagnostic rate for curable prostate cancer was reported as low as 5% in the general population. Over the same time period, >40% of men diagnosed at Walter Reed Army Hospital were diagnosed with curable disease – as all men >40 years old were subjected to annual digital rectal examination. At the Brady Urological Institute, the rate of curable disease was 22%.

During this time period, there were no reliable diagnostic biopsies available. Transurethral resections were unreliable as most cancers were found peripherally. Perineal needle biopsy yielded insufficient amounts of tissue for analysis (and tumor seeding through the perineum was observed). Transrectal biopsies were just being undertaken, but at this time involved an incision into the rectal mucosa to reach the prostate. The paradigm at Johns Hopkins involved perineal exposure of the prostate, excisional biopsy and confirmation of carcinoma to be followed by radical prostatectomy in the same setting if cancer was present. Preoperative evaluation included: (1) metastatic survey (serum acid phosphatase and xray), (2) discussion of impotence and possible incontinence following surgery and (3) evaluation of life expectancy. As early as the 1950's, Colston and others recognized that the benefit to treating men over 70 years old, unless in the best of health, was limited.

Colston briefly reviews the existing literature regarding survival following treatment for "curable" prostate cancer:

• Jewett, Johns Hopkins, 1954: 401 radical perineal prostatectomies (starting with HH Young in 1904), 50% 10-year survival approximates that of the general population. [1]
• Turner and Belt, 1957: 274 radical perineal prostatectomies: 47% 10-year survival. [2]
• Barnes, 1953: 31 patients with "resectable" disease treated with hormone therapy only, 50% 5-year survival, 22% 10-year survival. [3]

Colston then presents his experience with 108 patients over a 15-year period. Not only does this demonstrate his "learning curve," but interestingly highlights a phenomenon of survival bias – "After the first 5 years the incidence of death from the disease progressively diminished, and if a patient has survived 10 years his chances of death from carcinoma are minimal."

Colston also delivers very important perioperative and functional outcomes. There are no operative mortalities in his series (typically in the range of 4-5% for this operation), and no instances of serious hemorrhage. Ten patients were completely incontinent after the operation (all were impotent) – a high proportion by today's standards but low for that era of prostate surgery! Colston indicated that avoiding muscles of the external sphincter helped restore continence in many of his patients – an observation that would later be confirmed and exploited by Dr. Patrick C. Walsh to usher in the modern era of radical prostatectomy with minimal risk of incontinence.

Colston concluded:

The postoperative course and follow-up studies on 108 patients subjected to radical perineal prostatectomy have been analyzed. There has been no operative mortality in this series. Perineal exposure and frozen section biopsy were found to be superior to other methods of early diagnosis. The 10-year survival rate in this series is 47%, which closely approximates the life expectancy in normal individuals in this age group.

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! 

 
[1] Jewett, H. J.: Radical Perineal Prostatectomy for Carcinoma: Analysis of Cases at Johns Hopkins Hospital, 1904-1954, J. A. M. A. 156:1039-1041 (Nov. 13) 1954.
[2] Turner, R. D., and Belt, E.: Study of 229 Consecutive Cases of Total Perineal Prostatectomy for Cancer, J. Urol. 77:62-77 (Jan.) 1957.
[3] Barnes, R. W.: Results of Palliative Treatment of Early Carcinoma of Prostate, J. Urol. 70:489-490 (Sept.) 1953.

Historical Contribution: 1958, Jewett, Surgical Treatment of Bladder Cancer

1958
Jewett HJ. The Surgical Treatment of Carcinoma of the Bladder. J Urol. 1958. 79; 1: 87-93.


 
In the follow-up to his 1946 manuscript on the staging of bladder cancer, Dr. Hugh Jewett reviews the surgical management of bladder cancer stratified into the staging system he proposed. The purpose of this 1958 manuscript was to determine who most benefits from radical cystectomy, or as Jewett puts it,

"to steer a course between what may prove excessively radical on the one hand and ineffectually conservative on the other."

Jewett provides a wonderful summation and timeline of the understanding of bladder cancer in the first half of the 20^th century. Investigators at that time realized that tumor grade provided valuable information and a mechanism for invasive disease, but stage (i.e. depth of invasion) was most correlated with the presence of metastases. In 1951, the first update of his 1946 manuscript, Jewett reviews 80 cystectomy cases and demonstrates an extremely poor survival rate for advanced, infiltrative disease.

Jewett was quick to point out, "that intramural or even extravesical metastasis cannot occur until infiltration is well along. Such a concept would be naive since it is well known that metastasis can occur at any stage of infiltration…" Recognizing that superficial tumors were potentially curable through local excision he came up with the following criteria:

SUPERFICIAL INVASION

• Absence of palpable induration

• Only a "sprinkling" of carcinoma cells only

• Cancer involving only the submucosa, or superficial muscle layer

DEEP INVASION

• Palpable induration after resection

• Massive, invasion of the muscle bundles

Jewett used these criteria to define his staging system (and related survival statistics):
O: Mucosa
A: Submucosa
B1: Superficial muscle
B2: Deep muscle
C: Perivesical fat

Note the similar survival rates for patients with superficial disease undergoing segmental resection and cystectomy. Conversely, observe the potential survival benefit for patients undergoing cystectomy with invasive disease.

Therefore Jewett urged,

"A conscientious attempt to use this classification will prove rewarding. It will enable one-to avoid radical and mutilating surgery when it is unnecessary, to employ more effective instead of less effective measures when the tumor is deeper, and to compare intelligently the results of different kinds of treatment for tumors having roughly the same degree of potential curability."

 

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! 


 

 

Historical Contribution: 1951, Hodges, Gilbert & Scott, Renal Trauma

1951
Hodges CV, Donald RG, Scott WW. Renal Trauma: A Study of 71 Cases. J Urol. 1951;56;5:627-37.


In 1951, axial imaging was not available for the diagnosis and staging of renal trauma. Given shortcomings in diagnostics, the invasiveness of existing diagnostics (i.e. retrograde pyelogram), and the, in general, favorable outcomes associated with renal trauma, the consensus of most general surgeons and urologists was to manage renal trauma conservatively. Expert opinion at the time stated:

"the majority of patients with renal trauma may be treated conservatively with the expectation that the injured kidney will recover sufficient function to be a useful and serviceable organ."

"extensive urologic investigation, including cystoscopy and retrograde pyelography, immediately after renal injury is usually unnecessary and often undesirable"

"in the majority of cases, medical treatment will be followed by functional results which are satisfactory, although various types of anatomic abnormalities may persist."

"most kidney injuries should be left alone. If the renal· pelvis is reasonably intact, the patient will soon recover. If the contour of the pelvis is blasted beyond recognition, nephrectomy is necessary."

The authors of this manuscript poke a number of holes in the argument for conservative treatment:

1. The favorable outcomes of patients managed "conservatively" is biased by the inherent self-selection of severe renal trauma – those patients with the most severe injuries succumb to those injuries, those left for "conservative" management have an inherently improved chance at survival.
2. Late complications (abscess, hydronephrosis, pyonephrosis, etc.) can cause complete loss of renal function.
3. Unassociated renal diseases (hydronephrosis, malignancy of cortex or renal pelvis, cysts or polycystic kidney disease) are unrecognized in the setting of trauma and may have implications for future management.
4. Patients undergoing "conservative" management can undergo protracted convalescence for weeks or years.

The authors therefore created a diagnostic and therapeutic algorithm based stratification of 71 renal injuries seen at the Johns Hopkins Hospital (1930-1948). They classified injuries as (1) minor, (2) major and (3) critical injuries.

Minor Injuries

Definition: Parenchymal damage without rupture of the capsule of extension of the defect into the collecting system.
Prevalence: 66.2%
Presentation: Do not present in shock, may have hematuria that resolves within 48-72 hours. Pain, when present, also improves within 72 hours.
Most importantly, excretory and retrograde pyelogram demonstrates integrity of the collecting system (– "the greatest single criterion for placing injuries in the minor group").
Management: Urography.
Average Hospitalization: 8 days

Major Injuries

Definition: Parenchymal damage with rupture of the capsule or calyces.
Prevalence: 32.4%
Presentation: Often presents as mass around the kidney and hematuria. Shock may or may not be present (and may be delayed for hours or days). Hematuria and symptoms persist for several days.
Extravasation on excretory or retrograde pyelogram indicates a "major" injury.
Management:

• Immediate Surgery: 39% for repair or nephrectomy
• Delayed Surgery: 48% (21 days to 35 years after trauma) for incapacitating sequelae of injury.
• Conservative Management: 13%; of which 85.7% developed renal disease of "severe proportions" requiring future nephrectomy.

Average Hospitalization: 19.1 days (if operated on), 20 days (if conservative management)

Critical Injuries

Definition: Extension into or disruption of the renal vessels.
Prevalence: 1.4%
Presentation: Exquisite pain, early and profound shock; urography is not necessary nor does it yield valuable information if the vasculature is disrupted.
Management: Immediate surgery.
Average Hospitalization: 11 days

 
While our grading of renal trauma has developed into a more complex system, many of the principles outlined in this 1951 manuscript hold true today.

AAST (American Association for the Surgery of Trauma): 
http://www.aast.org/library/traumatools/injuryscoringscales.aspx


Also of interest are images of lower and upper pole heminephrectomy to preserve kidney function on the injured side (below).

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! 

Historical Contribution: 1949, Haines & Grabstald, Xylocaine

1949
Haines JS, Grabstald H. Xylocaine: A New Topical Anesthetic in Urology. J Urol. 1949;62;6:901-2.


 
Xylocaine (2-(diethylamino)-N-(2,6-dimethylphenyl)acetamide), more commonly known as Lidocaine, was first described by Swedish scientists Lofgren and Lundquist in 1943. Interestingly, Lundquist performed the first local anesthetic experiments using xylocaine on himself.[1] A number of subsequent studies demonstrated, "high degrees of anesthetic potency both for surface and infiltration purposes."

In this 1949 manuscript published in the Journal of Urology, Haines and Grabstald describe the use of xylocaine in 250 transurethral procedures varying from passage of sounds to fulguration of bladder tumors. They used approximately 10cc in men and a xylocaine-soaked applicator (placed in the urethra) in women. They describe no untoward effects and tolerability in a wide range of applications including transurethral fulguration of multiple tumors and recurrent dilations of urethral strictures in soldiers who suffered pelvic injuries. Xylocaine became widely marketed as a topical and local anesthetic in 1949 – around the time of this report – and continues to be one of the most widely used topical and local anesthetics around the world!

As an interesting side note, the authors make an important disclosure in the footnotes - the xylocaine in this report was supplied by Astra Pharmaceuticals (a Swedish company founded in 1913, which would later merge with the British, Zeneca Group in 1999 to form AstraZeneca).

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! 


 

 

1. Löfgren N (1948). Studies on local anesthetics: Xylocaine: a new synthetic drug(Inaugural dissertation). Stockholm, Sweden: Ivar Heggstroms.

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! 

Historical Contribution: 1929, Young, Posterior Urethral Valves

1929
Posterior urethral valves: Congenital valve obstruction of the prostatic urethra. Young HH, McKay RW. Surg Gynecol Obstret 1929; 48:509.


 
Within this manuscript is the "classic" description of posterior urethral valves (PUV) and the first classification system taught to urologists to define the disease. PUV, or congenital valvular obstruction of the prostatic urethra, was described as a medical entity in the late-1700's and was first described in the medical literature by Dr. Conrad Johann Martin Langenbeck in 1802. In the first portion of this manuscript, Young and McKay detail the history of PUV from Langenbeck to their description including thoughtful descriptions of autopsy series, case reports and clinical outcomes from around the world. Common among all these reports was that all cases were found at autopsy or incidental discoveries during other genitourinary operations.

From Tolmatschew in 1870.

The etiology of PUV was unknown with a number of hypotheses put forward including: persistence of the urogenital membrane, or anomalous development of the Wolffian and Muellerian ducts. Young recognized that PUV was a clinical heterogeneous entity, with patients having a variety of clinical presentations and outcomes. Part of the objectives of this manuscript was to present a unifying theory of PUV – a challenging feat that Young recognized, "Apparently no single theory, as stated previously, will explain satisfactorily the formation of [PUV]."

 

The History of PUV at Johns Hopkins

The first cystoscopic diagnosis of PUV was at Johns Hopkins in 1912. The first curative, transurethral surgery was performed one year later, in 1913, by HH Young. By 1915, with a combination of cystoscopic evaluation and cystogram, Young and colleagues were able to demonstrate the clinical association between PUV and significant vesicoureteral reflux (VUR) often seen in the disease. In 1916, Young modified his famous "punch" operation for the prostate to the treatment of PUV in two patients. By 1919, Young, Frontz and Baldwin from Johns Hopkins reported 12 cases of PUV, of which 8 were treated transurethrally. The four patients who did not undergo treatment died of complications of urinary obstruction and renal failure.

Description of Cases and Clinical Outcomes from Hopkins

In this manuscript from 1929, Young added 21 cases from the Brady Urological Institute to the world's literature of 41 treated cases of PUV. This can be considered a very early, systematic review of PUV before that concept existed. In typical HH Young fashion, the clinical circumstances and outcomes of each case are recorded and reported with meticulous detail. Young reviews the "Symptomatology" or clinical presentation of patients, the diagnostic algorithm including differential diagnosis, treatment strategies including the prepatory treatment, and prognosis.
Importantly, incorporating all these concepts with careful attention to detail, Young was able to classify PUV into three main types (figure below):

• Type I: valves of the distal verumontanum, classified into (a) two separate valves, (b) two fused valves, and (c) and unilateral single valve.
• Type II: a bifurcated valve from the distal verumontanum to the more proximal prostatic urethra.
• Type III: an "iris-like" valve above the verumontanum.

 
When describing the clinical outcomes the first nine patients treated with the modified "punch procedure," HH Young demonstrated: six curative treatments, one curative treatment with resulting incontinence and two deaths (one due to sepsis following treatment, one death due to sepsis prior to treatment). Young was extremely selective in choosing patients for an operation, as he recognized many patients had end-stage renal disease – a terminal condition at the time. According to Young, "These results show conclusively that the punch operation was the method of choice but should always be preceded by thorough prepatory drainage until functional tests show sufficient improvement in renal function to warrant an operation."

The "punch procedure" modified for posterior urethral valves (PUV).

 
In summation, Young stressed the following points in the work-up and treatment of PUV – much of which are still relevant today!

• Initial evaluation should involve:
  • Anatomic investigation of the upper tracts
  • Investigation of renal function
• Initial management can involve insertion of small catheters to gain adequate drainage of the bladder and evaluate subsequent renal function.
• Cystoscopic evaluation and possible treatment (punch procedure) is the second step in management of these children and can be very effective in carefully selected patients.

 

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!