Association of comorbid disease burden at diagnosis with higher tumor grade in men with non-metastatic prostate cancer.

BACKGROUND: While older age is associated with higher tumor grade, it is unknown whether comorbid disease burden has a similar, independent association. We sought to evaluate the impact of comorbid disease burden on tumor grade at diagnosis as indicated by biopsy Gleason score. METHODS: We conducted an observational cohort study of 1260 men newly diagnosed with non-metastatic prostate cancer from 1998 to 2004 at two Veterans Affairs Medical Centers. Multivariable ordinal and multinomial logistic regression were used to evaluate the association between Charlson Comorbidity Index score and biopsy Gleason score. RESULTS: Men with Charlson scores of 2 (odds ratio (OR) 1.8, P<0.001) and 3+ (OR 1.8, P<0.001) had significantly greater odds of higher Gleason scores, compared with men with Charlson scores of 0. In a multinomial logistic regression model predicting Gleason 7 vs ⩾6, only men with Charlson scores of 2 (OR 1.6, P=0.01) had greater odds of having a Gleason 7 tumor, compared with those with Charlson scores of 0. In a multinomial logistic regression model predicting Gleason 8-10 vs ⩽6, those with Charlson scores of 1 (OR 1.6, P=0.047), 2 (OR 2.8, P=0.01) and 3+ (OR 2.9, P=0.001) had higher odds of having a Gleason 8-10 tumor. CONCLUSIONS: Moderate-to-heavy comorbid disease burden at diagnosis may be associated with high tumor grade, independent of age, and is a stronger predictor of Gleason 8-10 than Gleason 7 disease.

Long-term outcome of detectable PSA levels after radical prostatectomy.

Detectable prostate-specific antigen levels (PSA) following radical prostatectomy (RP) are believed to represent treatment failure. In this retrospective review, we characterize long-term PSA outcomes following RP (n = 204) in a non-referral hospital performed between 1984 and 1994. With an average follow-up of 10 y, 90 (44%) patients developed a PSA recurrence: 15 (17%) died of prostate cancer despite hormonal intervention, 39 (43%) responded to hormonal therapy with stable remission and 36 (40%) were observed without intervention. Following RP many patients may have a detectable PSA that does not require treatment. PSA doubling time (< 12 months) was the best predictor of disease progression.

Laparoscopic radical prostatectomy: review and assessment of an emerging technique.

BACKGROUND: Several recent reports have affirmed the feasibility of the laparoscopic approach for radical prostatectomy. In this review, we discuss the morbidities associated with this technique and compare outcomes and convalescence with standard open radical prostatectomy. METHODS: We reviewed all currently published data on laparoscopic radical prostatectomy and our series of 45 robotic-assisted radical prostatectomies and compared them to several landmark series of open retropubic and perineal radical prostatectomies. RESULTS: Although the initial series reported long operating times, these times have been significantly reduced in more recent series. Data on blood loss, convalescence, impotence, and incontinence rates have also been promising. CONCLUSIONS: Although follow-up has been short thus far, laparoscopic radical prostatectomy has been shown to be similar to open radical prostatectomy in several areas.

Prostate needle biopsy infection after four or six dose ciprofloxacin.

OBJECTIVE: This retrospective analysis is to determine rates of clinical infection after prostate needle biopsy with four versus six doses of ciprofloxacin to previous literature. MATERIALS AND METHODS: Two groups were treated with pre and post biopsy 500 mg of ciprofloxacin twice daily by either six doses (n=337) or four doses (n=288) with the first dose given 24 or 12 hours prior to the procedure respectively. RESULTS: Six (0.96%) of the 625 patients had symptomatic urinary tract infections with a positive urinalysis and/or culture. One (0.3%) infection occurred among patients receiving six doses of ciprofloxacin, and five infections (1.7%), were identified among four dose patients. Two febrile episodes occurred in the four dose group, one requiring hospitalization. CONCLUSION: A low infection rate associated with prophylactic regimens. Six doses of ciprofloxacin appears more effective than four doses in reducing the clinical and febrile infection rate following ultrasound guided biopsy of the prostate. No obvious financial benefit was observed.

Simplified technique with short and long-term followup of conversion of an ileal conduit to an Indiana pouch.

PURPOSE: We report a simplified technique for converting an existing conduit to an Indiana pouch as well as short and long-term results. MATERIALS AND METHODS: From May 1988 to February 1998 we evaluated short and long-term outcome and complications in 23 patients 14 to 82 years old (average age 51.8) who underwent conversion of a conduit to an Indiana pouch. When no obstruction of the existing ureteroileal anastomoses was identified, the conduit was freed from the abdominal wall and surrounding bowel. The proximal conduit and ureteral anastomoses were not dissected. The conduit was opened along the antimesenteric wall proximal to the ureteral anastomoses and attached to 25 to 28 cm. of detubularized right colon as a refluxing Studer limb. The pouch was completed in the usual fashion and the stoma was matured at a virgin site. RESULTS: Surgical indications included stomal complications in 10 patients, an infected nonfunctioning kidney in 2 and patient preference in 11. There were no perioperative deaths although 3 patients died of cancer progression. Average operative time was 6.6 hours, estimated blood loss 518 cc and length of stay 7.8 days. Average followup after conversion was 4.7 years (range 0.2 to 11.0). Six late complications developed in 4 cases, including pyelonephritis in 2, severe pouchitis in 1, dehydration in 1 and stomal revision in 2. Renal function was well preserved with an average preoperative and postoperative creatinine of 0.91 and 1.14 mg./dl., respectively. CONCLUSIONS: This technique simplifies conversion and decreases bowel requirements. The low complication rate and stable serum creatinine support the finding that conversion of a conduit to an Indiana pouch is a safe, viable procedure.

Vena caval resection for bulky metastatic germ cell tumors: an 18-year experience.

PURPOSE: The operative management and followup of vena caval resection for bulky metastatic germ cell tumors have been previously described in 3 series. In 1989 Ahlering and Skinner described their experience with 12 patients. We now update this experience with the most recent followup on 19 patients. MATERIALS AND METHODS: From April 1978 to May 1995, 19 men underwent retroperitoneal lymph node dissection for stage B3 (N3) or C (N3, M+) germ cell tumor after induction chemotherapy. In all cases the inferior vena cava was resected because of extensive thrombosis or direct involvement of the vessel wall by a tumor. The inferior vena cava was resected from just below the renal veins to beyond the level of disease involvement. Complete resection of retroperitoneal disease was accomplished in all patients. Morbidity and mortality were examined. RESULTS: The mean hospital stay was 10 days (range 7 to 13) for uncomplicated recoveries (9 patients) versus 19 days (range 6 to 32) for complicated recoveries (10 patients). Followup ranged from 1 month to 16 years. Complications included prolonged ileus, small bowel obstruction, fascial dehiscence and pneumonia with pleural effusion. Chronic edema persisted in 3 of 11 patients with followup of greater than 6 months. Of the 6 patients who died of disease recurrence 4 did not have normalization of tumor markers before surgery, and all 4 had persistence of cancer in the resected specimen. Seven patients are without disease at followup of 24 months to 16 years. All survivors had normalized tumor markers before surgery. Only 1 patient (5%) had retroperitoneal recurrence. CONCLUSIONS: En bloc vena caval resection for tumor involvement or extensive thrombosis can be associated with short and long-term morbidity, is feasible, and may contribute to a prolonged tumor-free interval and a chance for cure.

Retrospective analysis of urologic complications in male patients with spinal cord injury managed with and without indwelling urinary catheters.

OBJECTIVES: To compare, in a retrospective fashion, the long-term urologic complications in male patients with spinal cord injury managed with and without indwelling urinary catheters. METHODS: The records of 142 consecutive male patients with traumatic spinal cord injuries sustained between 1975 and 1985 (inclusive) were reviewed. Fifty-six patients were managed with indwelling urinary catheters, and 86 were managed without an indwelling catheter. Urinary complications were recorded for each patient under the following general subheadings: renal, urinary tract infection, stones, urethral, and other. RESULTS: In all, there were 95 complications in the noncatheterized group versus 202 in the catheterized group (P = 0.007). The catheterized group experienced significantly more problems with renal damage, recurrent urinary tract infection, stones, and urethral complications. CONCLUSIONS: Our study shows that elimination of indwelling urinary catheters in patients with spinal cord injury will significantly reduce the incidence of urinary tract complications and lead to better preservation of renal function.

Screening cystoscopy and survival of spinal cord injured patients with squamous cell cancer of the bladder.

PURPOSE: Yearly cystoscopy has been advocated in spinal cord injured patients with chronic or recurrent urinary tract infections secondary to the increased risk of squamous cell cancer of the bladder. We examined the effectiveness of this protocol in our patients. MATERIALS AND METHODS: The medical records of all spinal cord injured patients with squamous cell cancer of the bladder between 1980 and 1996 were reviewed for the method of detection of the lesion. Screened patients (those presenting with chronic or recurrent urinary infections) were considered asymptomatic and were compared to symptomatic patients (those presenting with overt signs or symptoms of the bladder lesion) with respect to age, latency since spinal cord injury, treatment of neurogenic bladder, therapy, pathological stage and survival. RESULTS: Of 14 patients (9 symptomatic at presentation) 13 underwent cystoprostatectomy, while 1 presented with metastatic disease and was treated with supportive care only. Three symptomatic patients received adjuvant radiation therapy for positive lymph nodes or margins. Pathological stage was more advanced in the symptomatic group, including 7 patients (78%) with stage pT3a or pT3b (4 had positive lymph nodes), 1 with stage pT1N0M0 and 1 with stage pT2N0M0 cancer. In the asymptomatic group 3 patients had stage pT2N0M0, 1 had stage pT3aN0M0 and 1 had pT3bN0M0 disease. Overall and cancer specific survival rates for symptomatic patients were 44 and 50%, respectively, with a median of 40 months to death. In the asymptomatic group there was 1 noncancer related death, while the remaining patients were alive at a mean followup of 8.2 years. CONCLUSIONS: Cystoscopy to screen for squamous cell cancer of the bladder in spinal cord injured patients with chronic or recurrent urinary tract infection results in an earlier stage at diagnosis and appears to convey a survival advantage. Such a protocol should be strictly followed and careful prospective studies must be performed to ascertain if this will become significant.

Use of an anti-ras ribozyme to alter the malignant phenotype of a human bladder cancer cell line.

PURPOSE: In this study, we evaluated the ability of a ribozyme (catalytic RNA), which site specifically cleaves the mRNA of the activated H-ras gene, to alter the malignant phenotype of an invasive human bladder cancer cell line. MATERIALS AND METHODS: The human bladder cancer cell line EJ which contains the activated H-ras gene was used in these studies. Cell lines with and without the anti-ras ribozyme were examined for their malignant potential in athymic (nude) mice by using an orthotopic model of bladder cancer. Endpoints evaluated included tumor take and animal survival. RESULTS: EJ tumors containing the anti-ras ribozyme showed a reduction in tumor take (35% versus 45%) and prolonged survival (74 days versus 65 days) compared with standard EJ cells. This survival advantage was not as pronounced as anticipated. To evaluate this finding, we examined the tumor from mice originally inoculated with the ribozyme-containing cell line to determine if the ribozyme was still present. Approximately 60% of the animals had lost ribozyme expression. Animals that maintained ribozyme expression had a mean survival of 81 +/- 4 days which was significantly prolonged compared with control mice (65 +/- 5 days). CONCLUSION: This study suggests that the invasive phenotype is blunted with the anti-ras ribozyme, delaying but not abolishing the metastatic phenotype. These results further delineate the roles of ras genes in malignancy and demonstrate that ribozymes may be a powerful tool for exploring the role of individual oncogenes and may be used as anticancer agents.

The pathogenesis and management of urothelial malignancies.

Urothelial malignancies are frequently encountered among elderly persons. Host susceptibility and the presence of urothelial carcinogens are of primary importance in the development of these cancers. The natural history of these cancers produces a spectrum of disease processes with varying tendencies regarding invasion, spread, and multicentric origin. Consequently, a multitude of treatment options exist for the clinician and patient dealing with urothelial tumors. Essential to the reduction of morbidity and mortality attributable to these malignancies is the elimination of known risk factors, coupled with prompt diagnosis and treatment. Finally, the high propensity for these tumors to recur necessitates an aggressive cancer surveillance program in the patient population at risk.

A comparative study of postoperative complications associated with the modified Indiana pouch in elderly versus younger patients.

PURPOSE: We defined the nature and risk of complications associated with the modified Indiana pouch in patients older than 75 years. MATERIALS AND METHODS: We analyzed the clinical course of 25 elderly patients and a control group of 25 selected randomly from the cohort of those younger than 75 years. All patients underwent the modified Indiana pouch procedure. Charts were reviewed for type of operation, mean patient age, length of hospital stay, medical conditions, and early and late morbidity and mortality. Comparisons were made between the 2 groups. RESULTS: Simultaneous cystectomy or anterior exenteration was performed in 84% and 95% of patients in the elderly and younger groups, respectively. Mean age was 78.5 years in the elderly and 59.3 years in the younger group. Medical illnesses and early postoperative complication rates did not differ significantly between the 2 groups. Mean hospital stay was increased but not significantly in the elderly group (12.4 versus 11.1 days). There were 2 perioperative deaths in the elderly group (8%) and 1 in the control group (4%). Mean followup was 24.5 months (range 4 to 64) in the elderly versus 29.5 months (range 6 to 69) in the younger group. Late complications with the pouch were also similar (16% in the elderly and 12% in the control group). Of the elderly patients 9 died (intercurrent medical disease in 1 and cancer progression in 8) compared to 4 in the younger group (intercurrent medical disease in 1 and cancer progression in 3). Of the elderly patients 13 are alive (mean age 81 years) with a well functioning continent diversion. CONCLUSIONS: The modified Indiana pouch can be created with acceptable postoperative morbidity and mortality in elderly patients, and it provides an excellent functional result.

Depth of penetration of the neodymium: yttrium-aluminum-garnet laser in the human prostate and clinical results of high-dose laser energy in 50 patients.

We evaluated the treatment of the human prostate with the Nd:YAG laser using a Cytocare Prolase II fiber. We utilized this first in 12 patients prior to radical prostatectomy and then appropriately serially sectioned the prostate to measure the depth of penetration. The studies clearly revealed that 60 W of power and 60 s of pulse duration gave the most consistent depth of penetration in the human prostate model. This depth of penetration averaged 2 cm in the glands that were removed. At the same time there was absolutely no evidence of damage to the neurovascular bundle or to the capsule of the prostate using the above-mentioned dosimetry regime. This study was then transferred to our initial experience in treating 50 patients with benign prostatic hypertrophy and obstructive voiding symptoms. The first 25 patients were also treated with so-called spot radiation of the prostate, whereas the second 25 patients were treated by total photoirradiation of all visible endoscopic tissue. The results reveal that both groups of patients had a fairly highly satisfactory result as measured objectively with American Urological Association (AUA) symptom scores and uroflow studies. In the latter group (photoirradiation of all visible endoscopic tissue) a significantly higher dose of laser energy was utilized and a smaller failure rate was noted on a long-term basis in patients who subsequently came to transurethral resection of the prostate (TURP) because of failure of the laser procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Continent urinary diversion using a Modified Indiana Pouch in elderly patients.

A total of 25 patients at least 75 years old underwent continent urinary diversion via a modified Indiana Pouch during a 68-month period, 21 of these with simultaneous radical cystectomy or anterior exenteration. The preoperative medical conditions as well as the early and late operative morbidity and mortality are reviewed with a mean follow up of 27 months. Average age of patients was 78.5 years, and the mean age of survivors is 81 years. There were two early mortalities attributed to ileal gangrene with secondary sepsis and aspiration pneumonia. Postoperative complications (superficial wound infection, middle colic vein bleed, right ureteral leak, ileus) occurred in five patients, two of whom required re-operation. Mean hospital stay was 12.4 days and ranged from 9-20. There were only six late complications [ureteral stricture (3), small bowel obstruction (1), incontinence (1)] necessitating re-hospitalization and surgical intervention. Late infectious complications included recurrent urinary tract infections (3), pyelonephritis (2), and C. Difficile enterocolitis (2) all managed medically. In addition, 10 other patients have died, 9 from metastatic disease and 1 from intercurrent medical problems. Of the 13 remaining patients, 11 are disease free and all are continent with a mean follow-up time of 33 months. We conclude that continent urinary diversion via a modified Indiana pouch with radical cystectomy or anterior exenteration can be performed with minimal morbidity or mortality, even in an elderly population.

Metastatic renal cell carcinoma to the contralateral ureter.

Renal cell carcinoma uncommonly metastasizes to the ureter, with only rare reports of metastatic lesions developing in the contralateral side. Recently at our institution, two patients presented with contralateral ureteral metastases from a primary renal adenocarcinoma; one was synchronous and the second metachronous. Following extensive metastatic evaluations, both lesions were believed to be solitary metastases. The involved ureters were managed with total ureterectomy and construction of an ileal ureter. We report these two cases and review the literature.

Depth of penetration of the neodymium:yttrium-aluminum-garnet laser in the human prostate at various dosimetry.

OBJECTIVE: To determine depth of thermal penetration by the neodymium:yttrium-aluminum-garnet (Nd:YAG) laser at various dosimetry in the human prostate and to compare results of two techniques of laser application, single spot versus whole tissue photoirradiation. METHODS: Twelve men with Stage T2 (B) cancer of the prostate consented to laser prostatectomy immediately prior to a planned radical prostatectomy. In the first 3 patients (group I) the prostate was treated with the Nd:YAG laser in one spot area of each lobe. The next 9 patients underwent photoirradiation of all endoscopically visible tissues on one side of the prostate at different dosimetries: 60 W at sixty seconds (group II), 50 W at sixty seconds (group III), and 40 W at ninety seconds (group IV). Depth of laser penetration was measured from both histologic and gross evaluations of removed specimens within twenty-four hours. RESULTS: Thermal necrosis in group I showed an inconsistent depth of penetration even with the same amount of laser energy. Groups II, III, and IV all demonstrated clearly demarcated areas of thermal necrosis. Group II showed the greatest depth of laser effect among all groups, with a mean depth of 1.75 cm. No laser effect is detected near the true capsule of the prostate on any specimen. CONCLUSIONS: High dosage laser energy application at 60 W and sixty seconds of pulse duration with the whole tissue treatment provide the greatest depth of penetration in the human prostate while maintaining safety for the capsular area.