Effects of alendronate on bone mineral density in men with prostate cancer treated with androgen deprivation therapy.

Bone mineral density (BMD) is low in men with prostate cancer treated with androgen deprivation therapy (ADT). Intravenous bisphosphonates have been shown to prevent the bone loss, however, the effectiveness of oral bisphosphonates have not been studied in this population. In this retrospective cohort study, we examine the effect of alendronate on BMD in men with prostate cancer receiving ADT. We reviewed the charts of patients receiving ADT referred from the VA Urology Clinic for BMD measurements. Forty seven patients had follow up BMD measurements (17.6+8.3 months). Twenty-two men (47%) were also receiving alendronate 70 mg every week. There was a statistically significant difference (p<0.05) in the percent change of BMD per year at the spine (-1.29+/-0.7% vs. +1.41+/-0.7%), total hip (-0.94+/-0.6% vs. +0.97+/-0.5%), femoral neck (-2.17+/-0.7% vs. +0.32+/-0.6%) and trochanter (-2.01+/-0.7% vs. +0.79+/-0.8%) in the patients not treated compared to those treated with alendronate. In the four other measured sites at the radius (proximal, mid, ultra distal and total), there were no statistically significant differences (p>0.05). These findings confirm that bone loss occurs in men receiving ADT at all sites measured. The use of alendronate prevents bone loss at the spine and hip, but does not seem to have the same protective effect at the radius.

Genitourinary trauma.

Injuries to the GU system commonly occur in patients with high-energy lower abdominal or pelvic trauma. The emergency physician should be well versed in the diagnosis and management of GU trauma, although these injuries are not usually life threatening because of the potential for loss of urinary or sexual function. In the setting of hemodynamic instability, diagnosis and treatment of GU injuries is often accomplished in the operative setting. In the stable patient, diagnostic testing is directed by the type of suspected injury and must proceed in a reverse manner, i.e., external injury then urethral injury then bladder, and finally urethral and renal damage. Treatment focuses on a team approach between the emergency physician, general, orthopedic, and urologic surgeon. The decision for operative repair is often dictated more by other associated injuries than urologic injuries, and the urologic surgeon often provides temporizing measures with definitive repair at a later time. Prompt diagnosis and treatment of injuries to the external genitals results in excellent long-term outcome, minimizing the devastating consequences of impotence, urinary incontinence, and sexual disfiguration.

Does urethral-sparing prostatectomy risk residual prostate cancer?

OBJECTIVES: Urethral length after radical prostatectomy has correlated positively with postoperative urinary continence. Because sparing the prostatic urethra may improve continence after prostatectomy, we evaluated anatomic and pathologic consequences of urethral-sparing surgery. METHODS: From February to October 1999, 12 patients with clinically localized prostate cancer received a bladder neck-sparing radical retropubic prostatectomy by one surgeon. At the time of operation, the prostatic urethra was anatomically dissected from the prostatectomy specimen and sent separately to pathology to evaluate for the presence of adenoma or prostate cancer. RESULTS: All patients had clinically localized prostate cancer with routine preoperative evaluations, including negative bone scans for prostate-specific antigen (PSA) greater than 10 or Gleason score higher than 7. Pathologic specimens confirmed localized prostate cancer in 7 of 12 specimens. Positive margins were identified in 5, including 2 patients with locally advanced disease. All 12 urethral specimens showed residual prostate adenoma but no prostate cancer. Follow-up ranged from 8 to 16 months with a zero PSA for all evaluated. CONCLUSIONS: Residual prostate adenoma is found on dissected urethral specimens during radical retropubic prostatectomy. Although urethral-sparing prostatectomy may improve continence after radical prostatectomy, residual adenoma may confound follow-up PSA results. Furthermore, the malignant potential of the benign periurethral adenoma is unknown. The patient and clinician must understand the implications of residual prostatic tissue when performing urethral-sparing radical retropubic prostatectomy.

Renal medullary carcinoma.

PURPOSE: Renal medullary carcinoma is a rare and extremely aggressive neoplasm that almost always develops in young patients with sickle cell trait. To our knowledge all cases to date have been metastatic at surgical resection. Pathological examination reveals an aggressive tumor mainly involving the renal medulla with a varied morphology. The prognosis is dismal. Mean survival from the time of resection is 15 weeks (range 2 to 52). The disease course has not been altered by surgery, radiotherapy or various regimens of chemotherapeutic agents. MATERIALS AND METHODS: We add to the literature our experience treating renal medullary carcinoma in 2 cases and review the existing literature on this disease. RESULTS: Both patients whom we treated died of the disease, as have the other 35 patients described in the literature. CONCLUSIONS: A high index of suspicion may lead to earlier diagnosis and treatment, and survival of patients with renal medullary carcinoma.

Biological variation of total, free and percent free serum prostate specific antigen levels in screening volunteers.

PURPOSE: We determined the biological variation of the total, free and percent free serum prostate specific antigen (PSA) in men 50 years old or older. MATERIALS AND METHODS: Between July 1995 and February 1996 we studied 84 healthy men from our PSA screening study to determine biological variation by calculating the coefficients of variation of 3 PSA measurements on blood samples drawn from each subject 2 weeks apart. RESULTS: The mean coefficients of variation for total, free and percent free serum PSA were 15, 17 and 14%, respectively. Age, total PSA and ejaculation were not confounding factors in this analysis (that is multivariate R2 less than 5% for all indexes). CONCLUSIONS: There is a mean variation of approximately 15% in measurements of total, free and percent free PSA that does not appear to be significantly affected by age and total PSA level.

Effect of digital rectal examination and needle biopsy on serum total and percentage of free prostate specific antigen levels.

PURPOSE: We determined the effect of digital rectal examination and prostatic biopsy on serum total and free prostate specific antigen (PSA) concentrations in men undergoing screening for prostate cancer. MATERIALS AND METHODS: In 93 men recruited from our PSA screening program we measured the serum concentrations of total and free PSA on 3 occasions during a 30-day interval before performing digital rectal examination. Total and free PSA measurements were repeated 1 and 24 hours after the rectal examination. Serum total and free PSA also was measured immediately before, and 1 hour, 24 hours and 1 week after prostatic biopsy in 30 men. RESULTS: Biological variation for total and free PSA was 14.7 and 14.0%, respectively. At 1 hour after rectal examination total and free PSA increased by more than the biological variation in 31 and 48% of the men, respectively. Increases were significantly greater in men whose initial PSA concentrations were less than 4.0 ng./ml. There was a dramatic increase in total and percentage of free PSA in all men 1 hour after prostatic biopsy. Increases in percentage of free PSA were greater in men whose biopsies revealed cancer. Total PSA remained elevated for at least 1 week in most men, while percentage of free PSA returned to within or less than the biological variation of the baseline level in 90% of the men by 24 hours. CONCLUSIONS: Digital rectal examination causes a modest increase in total and percentage of free PSA. Prostate needle biopsy causes more dramatic increases in both forms of PSA. Free PSA is preferentially released into the serum after prostatic manipulation and appears to be cleared more rapidly than complexed PSA. The differential return of the different PSA forms to baseline levels after biopsy could affect the use of measurements of the percentage of free PSA in clinical practice.

Delayed infection of a pelvic lymphocele following pelvic lymphadenectomy.

Pelvic lymphocele is an infrequent complication of pelvic surgery, usually presenting shortly after surgery. We report a case of an infected pelvic lymphocele presenting more than 1 year after a staging pelvic lymphadenectomy for adenocarcinoma of the prostate. This case illustrates that late infection of pelvic lymphoceles can occur following a pelvic lymphadenectomy and radical prostatectomy.

Prostatic nerve growth factor inducible A gene binds a novel element in the retinoblastoma gene promoter.

We are investigating the role of the early response transcription factor, nerve growth factor inducible A gene (NGFI-A), as a modulator of retinoblastoma (RB) gene transcription in prostate cells. Examination of the RB promoter reveals a novel element GCGGGGGAG located at nucleotides 152-144 upstream of the methionine initiation codon. This sequence shares strong homology with the consensus NGFI-A binding element GCGGGGGCG varying by a single nucleotide. In DNA binding assays, an NGFI-A fusion protein and the native protein product of the NGFI-A gene purified from prostate cancer cells bound specifically to an oligonucleotide containing the RB promoter element. Gene expression studies in rat ventral prostate demonstrated a 1.9-fold increase in RB mRNA following castration that parallels a 2.7-fold induction of NGFI-A mRNA. In summary, the in vitro DNA binding data and the transient coregulation of rat NGFI-A and RB following castration suggests that the RB gene may be transcriptionally regulated by NGFI-A in prostate cells.

Return of erections and urinary continence following nerve sparing radical retropubic prostatectomy.

We evaluated recovery of erections and urinary continence following anatomical radical retropubic prostatectomy in a series of 784 consecutive patients with clinical stage A or B prostate cancer. Nerve sparing radical prostatectomy was performed in men deemed appropriate candidates. Recovery of erections sufficient for intercourse and urinary continence were analyzed controlling for patient age, pathological tumor stage and the performance of unilateral or bilateral nerve sparing surgery in men followed for a minimum of 18 months. Erections were regained in 149 of 236 preoperatively potent men (63%) treated with bilateral and 24 of 59 (41%) treated with unilateral nerve sparing surgery. Recovery of erections correlated with patient age and pathological tumor stage in patients treated with bilateral nerve sparing surgery. Continence was regained in 409 of 435 patients (94%) and did not correlate with patient age, tumor stage or nerve sparing surgery. Anatomical radical retropubic prostatectomy can be performed with favorable results in preserving potency and urinary continence. Better results are achieved in younger men with organ confined cancer.

Detection of organ-confined prostate cancer is increased through prostate-specific antigen-based screening.

OBJECTIVE: To determine whether prostate-specific antigen (PSA)-based screening alters the proportion of organ-confined prostate cancers detected. DESIGN: A prospective, nonrandomized, serial PSA-based screening trial (follow-up from 6 to 37 months), and a concurrent comparison group. SETTING: General community outpatient screening program based at a university center. PATIENTS: The study group consisted of 10,251 men aged 50 years and older (mean and median age, 63 years; mean and median age of patients who underwent biopsies, 66 years) who presented to a prostate cancer screening program and consented to phlebotomy. The comparison group consisted of 266 concurrently studied private patients in the same age range (mean and median age, 68 years) who were referred for prostatic ultrasonography and biopsy because of an abnormal digital rectal examination (DRE). MAIN OUTCOME MEASURE: Proportion detected with clinically or pathologically advanced prostate cancer. RESULTS: The men were divided into three groups: the comparison group, the initial PSA-based screening group, and the serial PSA-based screening group. The proportions of prostate cancers detected that were clinically or pathologically advanced were as follows: comparison group, 57% (27/47); initial PSA-based screening group, 37% (91/244); and serial PSA-based screening group, 29% (37/129). Screened patients had a lower proportion of advanced cancers than the comparison group (chi 2 [2] = 12.3; P = .002); this advantage was observed principally in patients younger than 70 years. Surgical staging revealed that the cancer was microscopically focal and well differentiated (possibly latent cancer) in 2.5% (1/40) of the nonscreened group, 2.9% (7/244) of the initially screened group, and 7.8% (10/129) of the serially screened group (generalized Fisher's Exact Test, P = .08). CONCLUSION: Screening based on PSA identifies some men with prostate cancer who have a significantly increased proportion of organ-confined tumors compared with those detected through evaluation for an abnormal DRE alone.

Modification of Mitrofanoff principle for continent urinary diversion.

In 1980, Mitrofanoff described a method of achieving continent urinary diversion by surgically closing the bladder neck and creating a continent catheterizable stoma from the appendix, which had been implanted in a non-refluxing manner into the bladder, or from a non-refluxing distal ureter. We describe a modification of the Mitrofanoff procedure for continent urinary diversion in 7 children in whom a standard Mitrofanoff procedure was not possible due to either body habitus or appendiceal anatomy. All 7 patients are continent both day and night. Four have required stomal revisions. Renal function has remained stable or improved in all patients. Although the revision rate was high, this modification of the Mitrofanoff principle has provided good long-term results in these patients and may be useful when patient's anatomy does not allow the creation of a standard appendicovesicostomy.

Percutaneous management of urolithiasis during pregnancy.

A total of 6 pregnant women with obstructing urinary calculi was managed by percutaneous nephrostomy drainage placed under ultrasound guidance with the patient under local anesthesia. All patients initially had relief of acute obstruction. However, occlusion of the percutaneous nephrostomy tubes with debris necessitated tube changes in 5 of 6 patients. In 2 patients recurrent nephrostomy tube obstruction, fever and pain led to percutaneous stone removal during pregnancy. In the remaining 4 patients the nephrostomy tubes were left indwelling through delivery. During the postpartum period 3 patients successfully underwent ureteroscopic stone extraction and 1 passed the stone spontaneously. Bacteriuria developed in each patient despite the use of preventive antibiotics. All 6 women had uncomplicated vaginal deliveries of healthy newborns and are currently asymptomatic with no evidence of obstruction. Percutaneous drainage of an acutely obstructed kidney in a pregnant woman is an effective temporizing alternative to ureteral stent placement until definitive treatment can be performed.

Mediation of skin allograft rejection in scid mice by CD4+ and CD8+ T cells.

We analyzed the role of CD4+ and CD8+ T cells in H-2-disparate skin allograft rejection in the mutant mouse strain C.B-17/Icr scid with severe combined immunodeficiency. On the day of skin allografting, scid mice were adoptively transferred with negatively selected CD4+ or CD8+ splenocytes from normal unsensitized C.B-17/Icr mice. These populations were obtained using a double-mAb--plus--complement elimination protocol using anti-CD4 or anti-CD8 mAb that resulted in no detectable CD4+ or CD8+ cells by FACS and negligible numbers of cytolytic T lymphocytes by limiting dilution analysis in anti-CD8 treated populations. Spleen cells were removed from grafted mice at the time of rejection and were tested in vitro for antidonor reactivity in several assays: mixed lymphocyte culture, cell-mediated lympholysis, and LDA for CTL and for IL-2-producing HTL. The presence of Thy 1.2+, CD4+, or CD8+ cells was determined by FACS. All control C.B-17 mice and scid mice adoptively transferred with nondepleted CD4+, and CD8+ cells rejected skin allografts with similar mean survival times (15.6 +/- 1.5, 18.8 +/- 3.4, 18.0 +/- 5.4, respectively), whereas control scid mice retain skin allografts indefinitely (all greater than 100 days). C.B-17 syngeneic grafts survived indefinitely in all groups. At the time of rejection, splenocytes from scid mice receiving CD4+ cells had negligible donor-specific cytotoxicity in CML and negligible numbers of CTL by LDA, but demonstrated a good proliferative response in MLC and IL-2-producing cells by LDA (frequency = 1/1764). There were no detectable CD8+ cells present by FACS analysis. Conversely, splenocytes from scid mice adoptively transferred with CD8+ cells had strong donor-specific cytotoxicity in CML (58.8% +/- 16.1%) and CTL by LDA (frequency = 1/3448), but no significant proliferation was detected in MLC. There were no detectable CD4+ cells by FACS, but there were small numbers of IL-2-producing cells by LDA (frequency = 1/10,204). These data demonstrate that CD4+ cells adoptively transferred into scid mice are capable of mediating skin allograft rejection in the absence of any detectable CD8+ cells or significant functional cytolytic activity. The adoptive transfer of CD8+ cells also results in skin allograft rejection in the absence of detectable CD4+ cells. The detection of small numbers of IL-2 secreting cells in these mice may indicate that CD(8+)-mediated allograft rejection in this model is dependent on IL-2-secreting CD8+ cells.

Inflammatory central nervous system disease in lupus-prone MRL/lpr mice: comparative histologic and immunohistochemical findings.

The brains of pathogen-free autoimmune MRL/lpr, NZBWF1 and NZB mice were examined for central nervous system (CNS) inflammation in premoribund 8-week-old animals and at ages when active systemic lupus erythematosus (SLE) was present. CNS inflammation was observed only in MRL/lpr mice. Immunohistochemical studies of brains from young MRL/lpr mice found that infiltrates were composed primarily of CD4+ cells. Older MRL/lpr mice (22 and 26 weeks of age) had CD4+ cells predominantly, but CD8+ and B220+ cells were also present. Perivascular leakage of IgG was a prominent and unexpected finding in the MRL/lpr model. Congenic MRL/+ mice with late-onset autoimmunity had no inflammatory cells in brain tissue, and there was no perivascular staining with IgG or albumin. Our findings suggest that MRL/lpr mice are a useful model for studies of lupus-associated CNS inflammatory disease, and perivascular leakage may be a primary mechanism for entry of IgG into the brain.

Ureteronephroscopic endopyelotomy.

The percutaneous nephrostomy tract has provided urologists with antegrade access to the upper urinary tract. Via this approach ureteropelvic junction obstruction has been treated with an endoscopically controlled incision with a cold knife. While less invasive than an open operation, we have noted significant discomfort from the 24 to 32F percutaneous tract. Accordingly, we sought to achieve the same results by using a less invasive approach, that is retrograde ureteronephroscopic endopyelotomy. A total of 10 patients (9 women and 1 man) with 5 primary and 5 secondary ureteropelvic junction obstructions underwent ureteroscopic endopyelotomy with a 3 or 5F Greenwald cutting electrode passed through a 12F rigid, 10.8F flexible or 9.8F flexible deflectable ureteronephroscope. Preoperatively, ureteropelvic junction obstruction was documented by a furosemide washout renal scan and/or a Whitaker test in 8 of 10 patients. In 2 patients an excretory urogram or retrograde pyelography was diagnostic. Duration of the procedure averaged 180 minutes (245 minutes with a concurrent Whitaker test). At the conclusion of the procedure a 7/14F indwelling ureteral stent was placed. The nephrostomy tube was removed after 3 days and average hospital stay was 5 days. The ureteral stents were routinely left in place for 6 weeks. Followup in 10 patients averaged 12 months. Flank pain was largely resolved in all patients. A followup Whitaker test, excretory urogram or renal scan ultimately has demonstrated decreased or no obstruction in 9 of 10 patients. In summary, early results with retrograde ureteronephroscopic endopyelotomy, specifically in female patients, appear to be promising. Morbidity is minimal and efficacy is satisfactory given the favorable objective response noted in 90% of the patients.