David M. Quinlan

Sexual Function following Radical Prostatectomy: Influence of Preservation of Neurovascular Bundles

The influence of preservation or excision of the neurovascular bundles on return of sexual function is analyzed. Between 1982 and 1988, 600 men 34 to 72 years old underwent radical retropubic prostatectomy for prostate cancer. Of the 503 patients who were potent preoperatively and followed for a minimum of 18 months 342 (68%) are potent postoperatively. Three factors were identified that correlated with the return of sexual function: 1) age, 2) clinical and pathological stage, and 3) surgical technique (preservation or excision of the neurovascular bundle). In men less than 50 years old potency was similar in patients who had both neurovascular bundles preserved (90%) and patients who had 1 neurovascular bundle widely excised (91%). With advancing age of more than 50 years sexual function was better in patients in whom both neurovascular bundles were preserved than in patients in whom 1 neurovascular bundle was excised (p less than 0.05). When the relative risk of postoperative impotence was adjusted for age the risk of postoperative impotence was 2-fold greater if there was capsular penetration or seminal vesicle invasion, or if 1 neurovascular bundle was excised (p less than 0.05). These data indicate that the return of sexual function postoperatively in men more than 50 years old is quantitatively related to preservation of autonomic innervation. In these men when it is necessary to excise the neurovascular bundle on 1 side, consideration in the future should be given to approaches that may restore autonomic function through nerve regeneration, for example partial excision of the bundle or cavernous nerve grafts.

The rat as a model for the study of penile erection

A model has been developed for the study of penile erection in the Sprague-Dawley rat. Anatomical dissections demonstrate a bilateral ganglion lateral to the prostate called the major pelvic ganglion. This ganglion receives input from the pelvic and hypogastric nerves and innervates the pelvic viscera. A large fiber from the major pelvic ganglion courses along the urethra and innervates the corpus cavernosum, the cavernous nerve. In 40 animals, electrical stimulation of either the cavernous nerve or the pelvic nerve resulted in reproducible repetitive tumescence of the corpora cavernosum. Following ablation of the cavernous nerve, electrical stimulation failed to produce erections. Standard mating behavior tests of mounting, intromission and ejaculation in 38 rats showed that surgical ablation of the cavernous nerve resulted in a decrease in the rate of intromissions and ejaculations compared with sham operated controls. Present models for the study of erection have been limited to the dog, monkey and cat. The rat model presented here offers several advantages over these existing models: 1) the cavernous nerve is easily identified, 2) electrical stimulation is easily accomplished and reproducible, 3) behavioral and neurophysiological studies are possible, and 4) animal purchase, housing, and maintenance costs are low. These advantages make this model a uniquely useful tool in the further study of penile erection.

Cavernous nerve grafts restore erectile function in denervated rats

Although potency can be preserved in most men following radical prostatectomy, in some patients one or both cavernous nerves must be sacrificed in order to excise all tumor. For these patients we have considered nerve reconstruction at the time of surgery using an interposition nerve graft. This possibility has been tested in a rat model. Animals were divided into three groups. In the sham control group, a pelvic exploration was conducted without division of the cavernous nerves. In the nerve ablation group, a five mm. segment of cavernous nerve was excised. In the graft group, five mm. of cavernous nerve was excised bilaterally and replaced with an interposition graft of genito-femoral nerve. At one month intervals postoperatively animals from each group underwent mating tests to determine potency; the ratio of vaginal intromission to unsuccessful mounts (I/M ratio) was determined. Following the mating tests the animals were re-explored and attempts were made to stimulate erections electrically via the pelvic nerve. Results at two months show the I/M ratio of the rats with grafts (0.05) and the nerve ablations (0.14) are low compared with the sham operated animals (1.0). By month four the graft group (0.89) has approached the sham group (0.91) while the ablation group (0.18) remains unchanged (p less than .05). Electrical stimulation at month two produced no erections in the nerve ablated or the grafted rats and 100% erections in the sham-operated animals. At month four, 50% of the rats with grafts, 10% of the nerve ablated animals, and 100% of the intact animals produced erections upon electrical stimulation (p less than .05). These results suggest that cavernous nerve grafting in rats can be successful in restoring potency after surgical injury. Application of these techniques to man may be indicated.

Nerve growth factor, nerve grafts and amniotic membrane grafts restore erectile function in rats.

In an effort to reduce complications arising from radical pelvic surgery, an improved technique for restoration of autonomic innervation has been developed. The ability of nerve growth factor (NGF) alone or in combination with interposition nerve grafts, as well as the use of fetal amniotic membrane as an alternative growth matrix to enhance regeneration of ablated cavernous nerves were investigated in rats. Rats with ablated cavernous nerve displayed little or no penile erection, either in response to direct electrical stimulation or to an estrous female rat. A step wise improvement in electrically induced erections was observed by NGF alone, nerve graft alone, and the combination of NGF and nerve graft. Restoration of sexual behavior followed the same pattern obtained with electrical stimulation. Furthermore, the use of neonatal amniotic membrane as an alternative nerve growth matrix enhanced both electrically stimulated erection and mating behavior. These results suggest that the use of NGF and appropriate grafting materials can facilitate autonomic nerve regrowth and potentially reduce the morbidity of surgically induced nerve injuries.

Do Alpha-Blockers Have a Role in Lower Urinary Tract Dysfunction in Multiple Sclerosis?

Lower urinary tract dysfunction is a major cause of morbidity in patients with multiple sclerosis. alpha 1-Adrenergic receptors are present at the bladder neck, where increased tone may be responsible for urinary retention and diminished flow rates. A randomized placebo controlled study was designed to test the hypothesis that blockade of these receptors using the selective alpha 1-adrenergic receptor antagonist indoramin would improve bladder emptying in patients with multiple sclerosis. Peak and mean urinary flow rates, residual volume and symptom score were evaluated at trial entry and again after 4 weeks in 18 men with multiple sclerosis. There was a mean 41% improvement in peak flow rate in the actively treated group compared with a 7.4% deterioration in the placebo group (p < 0.05). Residual volume improved in both groups. Patients taking indoramin reported a greater improvement in urinary symptoms. Modulation of the alpha 1-receptor may have a role in the management of lower urinary tract dysfunction in multiple sclerosis.

Application of argon beam coagulation in urological surgery

Argon beam coagulation is a new form of electrocautery that has proved useful to control diffuse bleeding in other surgical specialties. We report its application to urology. Three cases are presented in which argon beam coagulation provided excellent hemostasis in situations that are often difficult to control, such as partial nephrectomy for penetrating trauma, hemorrhagic cystitis refractory to other forms of treatment and after anterior exenteration for bladder cancer. The basis, technique and advantages of argon beam coagulation are discussed, as well as other instances in urological surgery in which it may have application. Argon beam coagulation is an alternative to conventional methods of hemostasis whenever there is a diffusely bleeding operative site.

Can we avoid surgery in elderly patients with renal masses by using the Charlson comorbidity index

To determine the safety of surveillance for localized contrast‐enhancing renal masses in elderly patients whose comorbidities precluded invasive management; to provide an insight into the natural history of small enhancing renal masses; and to aid the clinician in identifying those patients who are most suitable for a non‐interventional approach.

A Quantitative Histological Analysis of the Dilated Ureter of Childhood

A quantitative histological study of the dilated ureter of childhood was performed on 26 ureters. The specimens were from 15 male and 11 female patients 10 days to 12 years old (mean age 2.0 years). A color image analysis system was used to examine and compare collagen and smooth muscle components of the muscularis layers to normal control ureters of similar age. In comparing primary obstructed (12) to primary refluxing (14) megaureters and control ureters (6), there was a statistically different collagen-to-smooth muscle ratio (p < 0.001) between the primary obstructed and primary refluxing megaureter groups. For patients with primary refluxing megaureter there was a 2-fold increase in the tissue matrix ratio of collagen-to-smooth muscle when compared to patients with primary obstructed megaureter. In the primary obstructed megaureters the amount of collagen and smooth muscle was not statistically different from controls (p > 0.01). The increased tissue matrix ratio of 2.0 +/- 0.35 (collagen-to-smooth muscle) in the refluxing megaureter group compared to 0.78 +/- 0.22 in the obstructed megaureter group and 0.52 +/- 0.12 in controls was found to be due not only to a marked increase in collagen but also a significant decrease in the smooth muscle component of the tissue. Primary obstructed and normal control ureters had similar quantitative amounts of smooth muscle with 60 +/- 5% and 61 +/- 6%, respectively, while refluxing megaureters had only 40 +/- 5% smooth muscle. The percentage collagen was 36 +/- 5 in the obstructed megaureter group and 30 +/- 5 in controls, with refluxing megaureters having 58 +/- 5% collagen on analysis. Our findings emphasize the significant differences in the structural components (collagen and smooth muscle) of the dilated ureter of childhood, and provide us with further insight into the pathological nature of these dilated ureters and their surgical repair.

Late Massive Hematuria as a Complication of Conservative Management of Blunt Renal Trauma in Children

The conservative management of blunt renal trauma in children is well accepted and well documented in the medical literature. The majority of children who sustain blunt renal trauma do well with such an approach. However, the complications of conservative management are also well documented. We present 2 patients with blunt renal trauma who were treated conservatively and suffered massive life threatening hemorrhage several weeks after the initial injury. Angiography was not performed until late and in both cases it identified the cause of bleeding. Percutaneous transcatheter embolization provided immediate definitive treatment in both patients.

Can aggressive prostatic carcinomas be identified and can their natural history be altered by treatment

The factors that determine tumor aggressiveness are multifactorial: age, stage, and grade. Even a well differentiated tumor in a young patient may be aggressive someday because of genetic drift and tumor heterogeneity. In a recent review of 826 favorably selected cases managed with conservative therapy, metastatic disease had developed in 19% with grade I tumors, 42% with grade II, and 74% with grade III at 10 years. Recognizing that < 20% of men present with grade I disease, most prostate cancers are a threat to life in men who are going to live longer than 10 years. On the other hand, some tumors at presentation are too far advanced to cure. To improve the accuracy of preoperative staging in identifying these cases, we have developed nomograms based upon clinical stage, grade, and serum prostate-specific antigen (PSA). Traditionally, patients with high-grade tumors (Gleason 8-10) were never considered candidates for radical prostatectomy because of their poor expectancy for long-term survival. However, with improvements in the staging of prostate cancer and with a reduction in the morbidity of radical prostatectomy, a subset of these patients are potential candidates for curative therapy. We have recently studied the clinical outcome of 72 men with Gleason scores of 8-10 on needle biopsies who presented with clinically localized disease (9 T1c, 22 T2a, 17 T2b, 13 T2c, and 11 T3a). Of the 63 men who underwent radical prostatectomy, 46 (68%) had negative lymph nodes; nine did not undergo surgery because of positive lymph nodes identified from frozen section. The actuarial likelihood of an undetectable serum PSA at 5 years was 43% for men with negative lymph nodes and 45% for men with organ-confined disease. Thus, with proper evaluation, some men with even the most aggressive tumors can be cured by surgery if their pelvic lymph nodes are negative.