Biomedical subjects
Publications and source records attributed to J E Oesterling.
Between 1981 and 1985, 6 patients with transitional cell carcinoma in bladder diverticula had preoperative computerized tomography (CT). CT suggested no invasion through the wall of the diverticulum in all 5 patients who had pathologic confirmation. CT is a useful staging procedure and is helpful in determining the management of patients with transitional cell carcinoma.
Erosion of a penile prosthesis into the urethra is an uncommon complication of implantation. However, such conditions as too large a prosthesis, iatrogenic injury to the urethra at operation, postoperative prosthetic infection and subsequent urethritis may result in this untoward effect. A simple technique for removal of an eroded malleable or self-contained, inflatable or mechanical prosthesis is reported. This procedure is performed without an incision and may be conducted at the bedside with intravenous sedation only.
Ureteral fibroepithelial polyps are rare benign mesodermal tumors that occur predominantly in the upper ureter. We report on a patient with a fibroepithelial polyp in the distal ureter that resulted in entrapment of a calculus and partial obstruction of the collecting system. Preoperatively, diagnosis by standard radiographic methods, such as excretory urogram, retrograde pyelogram and conventional computerized tomography with and without contrast enhancement, was not possible because of the close proximity of the fibroepithelial polyp, the ureteral calculus and calcifications in the adjacent internal iliac artery. The new diagnostic modality of real-time, multiplanar computerized tomography imaging using the Sun/Pixar computer system and the 2D/3D Orthotool software was used to make the correct preoperative assessment. Subsequently, the patient underwent ureteroscopic resection of the polyp and extraction of the calculus. A year later she was free of symptoms and there was no evidence of regrowth of the polyp. To our knowledge this is the first report to describe the use of real-time, multiplanar computerized tomography imaging as an effective diagnostic modality in the genitourinary tract. In addition, this is the first ureteral fibroepithelial polyp reported in the literature to be associated with a ureteral calculus and to be excised endoscopically with no recurrence on long-term followup.
This study was designed to investigate the relationship of serum prostate-specific antigen to prostatic size and hormonal stimulation. Seven patients with benign prostatic hyperplasia were treated for six months with nafarelin acetate and then followed for an additional six months. Nafarelin acetate is a potent luteinizing-hormone-releasing hormone agonist which causes reversible testosterone deprivation resulting in involution of the prostate. During therapy and follow up, serum prostate-specific antigen correlated with: 1) serum testosterone (p less than 0.001); 2) quantity of prostatic epithelium (p less than 0.001); and 3) prostatic size (p less than 0.05). Before therapy, serum prostate-specific antigen (mean +/- SD) was 0.43 +/- 0.2 ng./ml. per gram of epithelium. This did not change significantly after six months of androgen deprivation (0.48 +/- 0.36), although the ratios of prostate-specific antigen to testosterone and to prostatic size each changed significantly. Despite testosterone levels in the castrate range at six months, five of seven patients had serum prostate-specific antigen concentrations above the female range and three of seven patients had prostatic biopsies containing columnar epithelium which stained positively for prostate-specific antigen. These results demonstrate that serum prostate-specific antigen is related to prostatic size, prostatic epithelial weight, and testosterone stimulation. However, prostatic size is not a good predictor of serum prostate-specific antigen because there is tremendous variation in the relative amount of epithelium in a prostate; in this study the ratio of prostatic size to epithelial weight varied threefold. Furthermore, although testosterone determines prostatic size and amount of prostatic epithelium, it may not totally control prostate-specific antigen production.
A new technique of using the in situ appendix to construct a continent catheterizable stoma is described in a patient who underwent continent urinary diversion, and the technical aspects of this procedure are illustrated in detail. The appendix is remodeled by invaginating its base into the cecum for 1 cm., cecoplicating the middle portion for 2 cm. and bringing the distal end to the skin as a cutaneous stoma. This new technique demonstrates that the in situ appendix can be constructed successfully to provide continence without the need for isolating it from the cecum and implanting the distal end into the urinary reservoir as described in the Mitrofanoff technique.
A pure seminal vesicle abscess is a rare condition. We report case 7 in the literature and to our knowledge the first patient who has been managed successfully by noninvasive, conservative antibiotic treatment alone. All previously reported cases of seminal vesicle abscesses have been managed with invasive therapy. In 5 cases the seminal vesicle abscess was incised and drained surgically, while in 1 the abscess was drained percutaneously. We describe a patient with a seminal vesicle abscess, review the literature and recommend a more conservative method of management.
Prostate-specific antigen has proven to be a new useful marker for the evaluation of men with prostatic cancer. In addition to its proven value for immunohistochemical staining and for the followup evaluation of men treated with hormonal therapy, the monoclonal immunoradiometric assay for PSA has proven to be a unique, sensitive, and specific marker for the followup evaluation of men who have undergone radical prostatectomy.
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Spontaneous rupture of the kidney or collecting system during pregnancy is an unusual condition. We report the sixteenth such case and, to our knowledge, the first case managed successfully with temporary insertion of a ureteral catheter. Based on our experience in this case, we recommend a modified approach to therapy for this condition.
The usefulness of prostate specific antigen to predict final pathological stage was studied in 178 consecutive patients. Prostate specific antigen was determined preoperatively in all patients by a monoclonal immunoradiometric assay. All pathological specimens were examined for capsular penetration, seminal vesicle involvement and lymph node involvement. Prostate specific antigen correlated directly with capsular penetration (p less than 0.002), seminal vesicle involvement (p less than 0.02) and lymph node involvement (p less than 0.05). However the diagnostic accuracy of an elevated serum antigen level on an individual basis was only 55 per cent for capsular penetration and 50 per cent for seminal vesicle involvement and lymph node involvement. With a log-linear regression model, the half-life of prostate specific antigen was calculated to be 3.15 +/- 0.09 days. From the equation PSA (t) equals PSA (2) e[-0.2197(t-2)], prostate specific antigen can be used to detect residual cancer on day t in the immediate postoperative period. With respect to long-term followup, 127 patients have been monitored for longer than 2 months postoperatively with prostate specific antigen (mean followup 2 years, range 2 months to 8.6 years). Of the 101 patients who had favorable pathological findings at operation (organ-confined cancer or capsular penetration only) 92 (91 per cent) had a followup antigen concentration in the female range (0.0 to 0.2 ng. per ml.), whereas only 5 of 26 men (19 per cent) with either seminal vesicle involvement or lymph node involvement had an antigen value that was less than 0.2 ng. per ml. All patients with a documented clinical recurrence (8 of 127, 6 per cent) had an elevated followup serum prostate specific antigen concentration. These findings suggest that preoperative levels of prostate specific antigen are not sufficiently reliable to predict final pathological stage on an individual basis in patients with early prostatic cancer, and that the antigen is a sensitive tumor marker for the detection of residual disease after radical prostatectomy and subsequent recurrence of tumor on long-term followup.
Chronic treatment of intact male beagles with an orally active nonsteroidal aromatase inhibitor (4-(5,6,7,8-tetrahydroimidazo [1,5a] pyridin-5-yl) benzonitrile hydrochloride; CGS 16949; CIBA-GEIGY) at a dosage of 2.5 mg./kg. per day for six months resulted in increased (p less than 0.01) serum LH and testosterone concentrations compared to placebo-fed controls. The increases in serum LH and testosterone concentrations occurred by one week of treatment and were maintained over the six month period. Testes of CGS 16949A fed dogs obtained at termination of the experiment when perfused in vitro in the presence of a maximally stimulating concentration of LH secreted nondetectable amounts of estradiol and estrone and higher (p less than 0.01) amounts of testosterone, androstenedione and dihydrotestosterone than testes of control dogs. Despite these changes in androgen secretion there was no evidence on any effect of aromatase inhibition upon spermatogenesis. These data support the hypothesis that in the dog, estrogens play a major role in negative feedback of the hypothalamic-pituitary-testicular axis.
To evaluate the role of aromatase inhibitors in the treatment of benign prostatic hyperplasia (BPH), the effects of a potent, oral, nonsteroidal aromatase inhibitor [4-(5,6,7,8-tetrahydroimidazo[1,5a]pyridin-5yl)benzonitrile; CGS-16949A, CIBA-GEIGY] on canine BPH have been studied. Twelve mature beagles with enlarged prostates were divided into two groups of similar age, prostatic size, and prostatic histology. Dogs were given either CGS-16949A at a dosage of 2.5 mg./kg./day p.o. (n = 6) or an oral placebo (n = 6) for 25 weeks. Treatment with aromatase inhibitor had no significant effect on prostatic weight nor on total DNA content when compared to controls (p greater than 0.1). Semen volume did not change with treatment, and prostatic tissue concentrations of testosterone, dihydrotestosterone (DHT), and 5 alpha-androstan-3 alpha,17 beta-diol (3 alpha-diol) were similar for the treated and control beagles (p greater than 0.1). Protein concentration in the ejaculate, however, was significantly greater for the dogs receiving CGS-16949A (p less than 0.01). Histologically, there was no difference in the incidence or type of BPH between the two treatment groups. Beagles treated with aromatase inhibitor, however, did have a more severe inflammatory infiltrate of the prostatic parenchyma than the control dogs (p less than 0.01). The mean serum testosterone concentration for the beagles treated with aromatase inhibitor was 10 times greater than that for the control animals (p less than 0.01). The endocrine effect of this aromatase inhibitor in the male canine is presented in the preceding paper. Taken together, these results suggest that inhibition of endogenous aromatase activity is not an effective treatment for spontaneous BPH in the intact canine.
A detailed histological analysis of 21 prostatectomy specimens for stage A1 disease was performed. Three cases (14 per cent) demonstrated no tumor, although all had foci of severe dysplasia. Of the prostates 18 (86 per cent) contained residual tumor: 13 (62 per cent) had minimal residual tumor and 5 (24 per cent) had substantial tumor. The residual carcinoma in the prostates with minimal tumor was predominantly in the apex of the gland or peripherally adjacent to the capsule such that complete removal by repeat transurethral resection would have been unlikely. Of the 5 specimens with substantial tumor, although some would have been upstaged by repeat transurethral resection, others would have remained stage A1 because of the peripheral location of the residual tumor. Within the definition of stage A1, using either the percentage of tumor involvement, weight of tumor or number of tumor foci in the transurethral resection specimen, one could not predict whether the prostatectomy specimen would have no, minimal or substantial residual tumor. Postoperatively, all patients are continent and 93 per cent are potent. Because some men with stage A1 carcinoma of the prostate will have substantial residual tumor not necessarily detected by repeat transurethral resection and the majority will have minimal residual tumor, which also appears to have an increased long-term risk of progression, radical prostatectomy should remain an option in the management of relatively young men with stage A1 disease.
Previous studies from this institution have shown that in untreated stage A prostate cancer when 5 per cent of the specimen or less was involved by tumor (stage A1) only 2 per cent of the patients had progression at 4 years. Of the specimens with greater than 5 per cent cancer (stage A2) 33 per cent had progression at 4 years. More recently, we have shown that 16 per cent of the men with stage A1 disease who remained at risk for 8 years or longer after diagnosis had progression of disease despite a small percentage of the specimen involved by tumor. To address whether the actual volume of tumor resected may be a better predictor of progression than the percentage of the specimen involved by tumor the data from these studies were re-evaluated. We demonstrated that at 4 and 8 years of followup the percentage of the specimen and resected tumor volume were strongly associated with tumor progression, with the percentage of the specimen showing a stronger association especially at 4 years. Our study reaffirms the use of the percentage of resected tissue involved by tumor as a means to distinguish between stages A1 and A2 prostate cancer. Although at 8 years the distinction between stages A1 and A2 disease is blurred, this staging classification still is useful to identify those tumors with a relatively indolent course and a minimal short-term risk of progression from those that are more aggressive.
We have shown previously that administration of an orally active competitive aromatase inhibitor 4-(5,6,7,8-tetrahydroimidazo [1,5a] pyridin-5-yl) benzonitrile monohydrochloride to adult male beagles increases peripheral blood LH and testosterone concentrations, and that testes from treated dogs produce more testosterone when perfused in vitro than age-matched controls. In the present study we posed the question of whether the increased testosterone secretion by testes from these same aromatase-treated dogs was due to Leydig cell hypertrophy or hyperplasia, and if the latter, whether cytoplasmic organelles are increased. Beagles were treated with the inhibitor at a dosage of 2.5 mg/kg.day for 25 weeks and were euthanized by an overdose of iv sodium pentobarbital; testes were perfusion-fixed, embedded, and sectioned for stereological analysis. There were no significant differences in testis volume and absolute volumes of seminiferous tubules, blood vessels, lymphatic space, macrophage cells, and mesenchymal cells between the control and treated dogs. In contrast absolute interstitium volume and the absolute volume of Leydig cells per testis were significantly increased (P less than 0.05) in treated dogs. This increased Leydig cell volume per testis was due to increased volume of individual Leydig cells rather than to increases in Leydig cell number per testis. Additional studies showed that the surface area per Leydig cell of smooth endoplasmic reticulum, outer and inner mitochondrial membranes, and membranes of lipid droplets per testis were significantly higher (P less than 0.05) in the treated dogs as compared to the controls. In summary, the results of this study lead us to conclude that aromatase inhibition in the mature dog causes Leydig cell hypertrophy rather than hyperplasia and increased surface area per Leydig cell of subcellular organelles that contain enzymes involved in steroid biosynthesis.
A 1-year-old male infant developed a classic Wilms' tumor of the left kidney. Treatment consisted of a left nephrectomy, chemotherapy, and irradiation to the left flank and associated abdomen. Two years later, a mass in the right kidney was discovered; open renal biopsy demonstrated a mature Wilms' tumor consisting entirely of rhabdomyomatous elements in the biopsy specimen. The patient was given a second course of chemotherapy and 2000 rad to the right flank. Over the next 8 years, the mass continued to grow without evidence of metastatic spread. Renal function deteriorated secondary to compression of the surrounding normal renal parenchyma by the enlarging tumor; creatinine clearance from the solitary kidney decreased from 120 ml/min to 40 ml/min during the 12 months prior to removal of the lesion. Via a nephron-sparing procedure, the 3400 g tumor measuring 19 cm X 16 cm X 9 cm was enucleated from the right kidney without compromise to the remaining normal tissue. Pathologic examination of the surgical specimen revealed a mature Wilms' tumor with a malignant anaplastic sarcoma arising in the central portion. Postoperatively, the patient received a third course of chemotherapy with no irradiation to the tumor bed. Currently, he is disease-free with normal renal function more than 20 years after diagnosis of the metachronous bilateral Wilms' tumor. This is the first reported case of an anaplastic sarcoma arising within a Wilms' tumor; this individual also is the longest surviving patient with metachronous Wilms' tumor. The various possibilities regarding the development of the anaplastic sarcoma within the Wilms' tumor of the right kidney are discussed, including the possible role of chemotherapy and irradiation in the development of a second malignancy.
To determine which form of urinary diversion is most effective for each type of hypospadias, we polled all full-time practicing pediatric urologists in the United States and Canada. Each was asked to complete a questionnaire, specifying the method of urinary diversion used, based on the severity of the hypospadias. Ninety-eight per cent (84 of 86) of the urologists contacted replied to the survey. Our findings suggest that: Urinary diversion is usually not necessary for very mild types of hypospadias. Intraurethral drainage is the preferred form of diversion for moderate types of hypospadias. Suprapubic drainage with an intraurethral stent is the favored means of diversion for severe types of hypospadias. Perineal urethrostomy is rarely used today in hypospadias surgery.
In reviewing the Johns Hopkins Hospital records of over 1,000 radical prostatectomies performed since 1904, only 10 men have had a subsequent autopsy. All were managed by radical perineal prostatectomy without adjunctive therapy; 4 individuals had pathologic Stage B disease, and 6 men had pathologic Stage C cancer. The mean time interval between surgery and death was 8.9 years and 8.8 years for pathologic Stages B and C patients, respectively. Four patients (2 pathologic Stage B and 2 pathologic Stage C) had no evidence of disease, either local or distant, at autopsy. Two men (1 pathologic Stage B and 1 pathologic Stage C) had only microscopic foci of local recurrence without distant metastases. Four other patients (1 pathologic Stage B and 3 pathologic Stage C) had bulky distant metastases; of these, 1 had no local disease, and 3 patients had only microscopic recurrence in the pelvis. No patient had gross pelvic recurrence, and no individual with microscopic local disease had symptoms secondary to that recurrence. Four patients (1 pathologic Stage B and 3 pathologic Stage C) died of prostatic cancer secondary to distant metastases. These data suggest: radical prostatectomy alone provides excellent local control of the primary tumor, irrespective of the pathologic stage; in patients where bulky metastatic disease was responsible for death, distant dissemination may have occurred prior to radical prostatectomy since all patients had either no pelvic disease or only microscopic local recurrence.