Psoas hitch ureteral reimplantation in adults--analysis of a modified technique and timing of repair.

OBJECTIVES: The psoas hitch ureteral reimplantation technique has been used with great success to bridge defects in ureteral length due to injury or planned resection. Several surgical principles have been historically stressed when performing this procedure, including adequate mobilization of the bladder, fixation of the bladder to the psoas tendon before reimplantation, the use of a submucosal nonrefluxing-type ureteral anastomosis, and a 6-week delay before attempting repair after a surgical injury. We retrospectively reviewed patients who underwent ureteroneocystostomy with a psoas hitch, evaluated the relevance of these principles, and describe a modification of the technique. METHODS: All patients undergoing psoas hitch ureteral reimplantation were reviewed. The indications, complications, and long-term outcomes were assessed. RESULTS: Between 1989 and 1999, 24 patients underwent psoas hitch reimplantation at our institution. The indications were operative injury in 11, planned surgical resection during nonurologic pelvic surgery in 4, cancer in 4, stricture in 4, and trauma in 1. Refluxing-type ureteral anastomoses were performed in 17 cases. One case of postoperative urosepsis occurred. A delayed repair after operative injury did not improve the operative time or overall morbidity. No cases of chronic flank pain, recurrent pyelonephritis, persistent severe hydronephrosis, or compromised renal function, as measured by a change in baseline serum creatinine level, occurred. No patient required reoperation for either early or delayed complications or failure of the repair at a follow-up of 1 to 122 months (mean 32.75). CONCLUSIONS: Psoas hitch ureteral reimplantation is an effective means of treating defects in ureteral length. Immediate repair may be safely undertaken as soon as the ureteral injury is recognized. Long-term sequelae are unusual in adults, even when using refluxing-type ureteral anastomoses.

The use of hydrogen peroxide to enhance the efficacy of doxorubicin hydrochloride in a murine bladder tumor cell line.

PURPOSE: We determined whether the cytotoxicity of doxorubicin hydrochloride would be enhanced by adding hydrogen peroxide as a source of oxygen free radicals. MATERIALS AND METHODS: Mouse bladder tumor cells (MBT-2) were grown in RPMI 1640 medium and treated with various concentrations of doxorubicin hydrochloride for 2 hours. Protein content was assayed as a measure of cell growth. A similar set of experiments was done with cells exposed to hydrogen peroxide only and combined doxorubicin and hydrogen peroxide. Protein content was again assayed as a measure of cell growth. Cells were also assayed for glutathione peroxidase and malonyl dialdehyde, a product of lipid peroxidation, to determine the mechanism of cell damage. Furthermore, MBT-2 cells were incubated with 100 M. alpha-tocopherol, a free radical scavenger, before exposure to hydrogen peroxide to determine whether the effects of hydrogen peroxide could be reversed. RESULTS: We observed a dose dependent inhibition of MBT-2 cell growth after exposure to doxorubicin hydrochloride. Exposure to doxorubicin and hydrogen peroxide resulted in greater cell growth inhibition than exposure to either agent alone. The effects of hydrogen peroxide on cell proliferation were reversed by pre-incubation with alpha-tocopherol. CONCLUSIONS: As a source of oxygen free radicals, hydrogen peroxide enhances the antiproliferative effect of doxorubicin hydrochloride on a mouse bladder tumor cell line. Thus, hydrogen peroxide may be a relatively inexpensive, nontoxic method of augmenting the cytotoxicity of doxorubicin hydrochloride. Further studies are warranted to determine whether these observations may have clinical application.

DAZ family proteins exist throughout male germ cell development and transit from nucleus to cytoplasm at meiosis in humans and mice.

The human DAZ gene family is expressed in germ cells and consists of a cluster of nearly identical DAZ (deleted in azoospermia) genes on the Y chromosome and an autosomal homolog, DAZL (DAZ-like). Only the autosomal gene is found in mice. Y-chromosome deletions that encompass the DAZ genes are a common cause of spermatogenic failure in men, and autosomal homologs of DAZ are essential for testicular germ cell development in mice and Drosophila. Previous studies have reported that mouse DAZL protein is strictly cytoplasmic and that human DAZ protein is restricted to postmeiotic cells. By contrast, we report here that human DAZ and human and mouse DAZL proteins are present in both the nuclei and cytoplasm of fetal gonocytes and in spermatogonial nuclei. The proteins relocate to the cytoplasm during male meiosis. Further observations using human tissues indicate that, unlike DAZ, human DAZL protein persists in spermatids and even spermatozoa. These results, combined with findings in diverse species, suggest that DAZ family proteins function in multiple cellular compartments at multiple points in male germ cell development. They may act during meiosis and much earlier, when spermatogonial stem cell populations are established.

Evaluation of cyclin expression in testicular germ cell tumors: cyclin E correlates with tumor type, advanced clinical stage, and pulmonary metastasis.

The measurement of proliferative index has yielded promising yet conflicting results in the evaluation of testicular tumors. We have examined the role of Ki-67, along with the cyclins A and E in testicular tumorigenesis. We compared the immunoreactivity of 20 pure seminomas with 20 mixed germ cell tumors composed predominantly of embryonal carcinoma with a variety of proliferation markers, including Ki-67, cyclin A, and cyclin E. All 40 tumors stained for Ki-67, and 19 of 20 (95%) seminomas and 18 of 20 (90%) embryonal carcinomas stained positively for cyclin A. Cyclin E stained 14 of 19 (74%) of the embryonal carcinomas and only 4 of 20 (20%) of the seminomas (Fisher's exact two-tailed test, P = .0012). There was a trend toward larger tumor size for cyclin E-positive seminomas (median, 5.92 cm versus 3.96 cm; P = .08), although the same correlation was not significant in embryonal carcinomas. For both seminomas and embryonal carcinomas, staining with cyclin E did not correlate with the presence of lymphovascular invasion or capsular invasion. However, patients who had cyclin E-positive tumors presented with higher clinical stage (P = .0015). In addition, pulmonary spread in embryonal carcinomas (four patients) and seminomas (one patient) occurred only in patients whose tumors were cyclin E positive (P = .014). Although Ki-67 and cyclin A offer little prognostic information in testicular germ cell tumors, cyclin E immunoreactivity correlates with tumor type and is strongly predictive of distant tumor spread.

Virtual CT cystoscopy: color mapping of bladder wall thickness.

RATIONALE AND OBJECTIVES: To improve the conspicuity of bladder tumors in a virtual environment, we developed an algorithm for color mapping the thickness of the bladder wall. The purpose of this study was to demonstrate the feasibility of this algorithm as a component of virtual CT cystoscopy. METHODS: Five subjects with a history of superficial transitional-cell carcinoma of the bladder underwent helical CT scanning after insufflation of the bladder with air. Source images were transformed into three-dimensional models, and the thickness of the bladder wall was demarcated by using a new computer algorithm and a fixed color scale. Results were compared with those obtained by conventional cystoscopy. RESULTS: Three tumors, one site of benign wall thickening, and normal wall thickness were correctly identified by using axial source images and virtual cystoscopy with color mapping. CONCLUSIONS: Color mapping of bladder wall thickness is feasible and demonstrates both normal and thickened urothelium. Its value in identification of small or sessile tumors will require further trials.

Telomerase in human bladder cancer.

Biomarkers for human bladder cancer are currently available and more are being developed. However, the ultimate goal of diagnosing bladder cancer consistently in a noninvasive fashion has not yet been achieved. Telomerase is an enzyme that may play a role in maintaining telomere sequences in the ends of chromosomes and its activity may reflect the presence of immortal or cancer cells. In this article, we reviewed the potential applications of telomerase in the diagnosis, monitoring, and treatment of human bladder cancer.

An overview of the treatment of superficial bladder cancer. Intravesical chemotherapy.

Superficial bladder cancer accounts for approximately 70% to 80% of all newly diagnosed bladder cancers. The vast majority of these cancers are transitional bladder tumors of various histologic grades (I to III). Superficial tumors include carcinoma in situ (CIS), tumors confined to the epithelium (Ta), and superficial tumors that invade the lamina propria (T1) but do not involve superficial muscle layers. The primary treatment for eradication of stage Ta and T1 bladder cancers is transurethral resection of the tumor. Many patients with superficial bladder tumors treated with endoscopic surgery alone have recurrence or tumor progression at some point in their follow-up, and, in these patients, the need for adjuvant treatment becomes a major concern.

Appropriateness of prostate-specific antigen testing.

We established criteria for appropriate use of the prostate-specific antigen (PSA) assay and used them to evaluate PSA test utilization at 1 tertiary care institution. During a 6-month period, 2,330 PSA results were reported for outpatients and 95 for inpatients. We reviewed medical records for a random sample of 338 outpatient results (14.51%) and all 95 inpatient results, of which 21% (71/338) of outpatient and 17% (16/95) of inpatient results were inappropriate according to our test utilization criteria. Among outpatients, 52% of tests were done for screening and 19% for monitoring for cancer recurrence. For inpatients, workup for cancer (53/95 [56%]) was the most frequent indication for testing and screening the second (24/95 [25%]). Of tests failing the criteria, 66 (76%) of 87 resulted from excessively frequent and age-inappropriate screening. We assessed the potential effect on clinical outcome if these tests were not performed. Of the 87 tests considered inappropriate, only 1 test result influenced clinical management for patients younger than 75 years. By instituting simple limits on age and frequency, we estimate that 74% (64/87) of the inappropriate tests could have been eliminated.

Smoking and alcohol use may be risk factors for poorer outcome in patients with clear cell renal carcinoma.

OBJECTIVES: To correlate the clinical outcomes of 148 patients with clear cell renal carcinoma treated at a single institution with a variety of other factors. METHODS: Cases were derived from a consecutive series of nephrectomy specimens obtained from 1980 to 1994. A retrospective review of clinical records was performed, with tobacco use, alcohol use, recurrence, and survival noted. RESULTS: The median age of the patients was 62 years. The median follow-up was 4.4 years. Of 148 patients, 82% had localized disease (MO), and 18% had suspected metastases (M1) at the time of nephrectomy. Of 121 patients without metastases at diagnosis, T classification was assessed for 117: 48 (41%) had T1 disease, 18 (15%) T2, 46 (39%) T3, and 5 (4%) T4. The Fuhrman grade was 1 or 2 in 51% of patients and 3 or 4 in 45%. Both clinical stage and grade were significantly associated with overall survival (P <0.0001 and P = 0.0028, respectively) and recurrence-free survival (P = 0.0002 and P = 0.0011, respectively). Smoking and alcohol use history was determined in 70% and 63% of patients, respectively. In patients with Stage M0, smokers had a significantly worse overall survival rate compared with nonsmokers (P = 0.039). Also, in patients with Stage M0, a trend toward a worse recurrence-free survival rate was noted in alcohol users compared with those who never used alcohol regularly (P = 0.06). CONCLUSIONS: The prognosis of clear cell renal carcinoma depends on the pathologic stage at diagnosis and the Fuhrman grade. Smoking is a known risk factor for developing renal cancer and may be associated with increased mortality from clear cell carcinoma in patients with Stage M0. Also, regular alcohol use may decrease the recurrence-free survival rate.

The thimble: a useful adjunct to needle suspension procedures for female stress incontinence.

All needle suspension procedures carry the risk of inadvertent puncture of the surgeon's finger. The thimble provides simple, inexpensive protection for the surgeon while maintaining tactile feedback during surgery.

Amphiregulin is coordinately expressed with heparin-binding epidermal growth factor-like growth factor in the interstitial smooth muscle of the human prostate.

Peptide growth factors have been proposed as mediators of smooth muscle-epithelial cell interactions in the human prostate; however, the identity of these molecules has not been established. In this study, we compared expression levels of messenger RNAs (mRNAs) encoding the epidermal growth factor (EGF) receptor-related receptor tyrosine kinases (ErbB1 through 4), the six EGF receptor ligands, EGF, transforming growth factor (TGF)-alpha, amphiregulin (ARG), HB-EGF, betacellulin, and epiregulin, and the related molecule heregulin-alpha, in a series of 10 prostate tissue specimens. Only EGF showed a disease-specific association, with increased mRNA levels in four of five PCa specimens in comparison to matched normal tissue from the same subject. In contrast, ARG and HB-EGF mRNAs showed a coordinate pattern of expression in 7/10 specimens that was distinct from all other growth factor or receptor genes examined and from mRNAs for prostate specific antigen, the androgen receptor and GAPDH, a house-keeping enzyme. Analysis of an additional series of benign prostatic hyperplasia and prostate cancer specimens from 60 individuals confirmed that ARG and HB-EGF mRNA levels varied in a highly coordinate manner (r = 0.93; P < 0.0001) but showed no association with disease. ARG was immunolocalized largely to interstitial smooth muscle cells (SMC), previously identified as the site of synthesis of HB-EGF in the prostate, while the cognate ARG and HB-EGF receptor, ErbB1, was localized exclusively to ductal epithelial cells and carcinoma cells. Although ARG was a relatively poor mitogen for Balb/c3T3 cells in comparison to HB-EGF, it was similar in potency to HB-EGF in stimulating human prostate epithelial cell growth, suggesting that prostate epithelia may be a physiologic target for ARG in vivo. Expression of both ARG and HB-EGF mRNAs was induced in cultured prostate SMC by fibroblast growth factor-2, a human prostate SMC mitogen linked to prostate disease. These findings indicate that ARG and HB-EGF are likely to be key mediators of directional signaling between SMC and epithelial cells in the human prostate and appear to be coordinately regulated.

Short and long-term morbidity of thoracoabdominal incision for nephrectomy: a comparison with the flank approach.

PURPOSE: A thoracoabdominal incision provides optimal exposure for radical nephrectomy, especially for large tumors. Intuitively it is perceived that the morbidity of a thoracoabdominal incision far exceeds that of a flank incision. We compare the morbidity of thoracoabdominal and flank incisions, which to our knowledge has not been reported previously. MATERIALS AND METHODS: A questionnaire assessing postoperative pain, use of pain medications and return to activities was sent to the last 100 renal donors who underwent nephrectomy at our institution through the 11th rib (flank incision, group 1) and the last 100 patients who underwent radical nephrectomy through the 8th to 10th rib (thoracoabdominal incision, group 2). A total of 52 group 1 and 42 group 2 questionnaires were returned. Pain was assessed at 4 periods using a visual analog scale. RESULTS: Length of stay was the same in both groups. There were no differences between groups in terms of pain severity on postoperative day 1, on day of discharge home, 1 month postoperatively and at the time of study (p >0.05). There were no significant differences between groups in times following surgery when pain completely disappeared, when pain medications were discontinued, and when the patient returned to daily activities and work (p >0.05). CONCLUSIONS: Morbidity was comparable for thoracoabdominal and flank incisions in terms of incisional pain, analgesic requirements after discharge home and return to normal activities.

Morbidity of flank incision for renal donors.

OBJECTIVES: To analyze the short and long-term morbidity of flank incision in renal donors. The flank incision has been widely used by urologists for decades, and its morbidity has always been an issue. METHODS: A questionnaire assessing the morbidity and quality of life was sent to the last 100 living donors at our institution. All operations had been performed through the flank approach. Fifty-two questionnaires were returned. The mean age was 45 years. The mean follow-up was 29.5 months (range 7 to 58). The questionnaire was composed of questions regarding pain, cosmesis of the incision, and quality-of-life issues after surgery. RESULTS: No patients had any major postoperative complications. Pain was described in the first postoperative day as severe, moderate, or mild by 36 (69.3%), 6 (11.5%), and 10 (19.2%) patients, respectively. On the day of discharge (mean 4 days), 17 patients (32.7%) reported severe pain. Pain was completely or somewhat controlled with analgesics after surgery in all but 3 patients. Most (81%) discontinued pain medication by the end of fourth postoperative week (54% by the end of second week). Only 3 patients (5.8%) related being very bothered by the incision at the time of the questionnaire. Bother relates to pain, location, length, and unsightliness of scar. In 43 patients (83%), the incision did not impact negatively on their self-esteem and quality of life, and 93% of patients in retrospect would undergo the same procedure without any reservation. CONCLUSIONS: The short and long-term morbidity of the flank incision for living donor nephrectomy is acceptable. Most patients are content after the kidney donation, and all would undergo the same procedure all over again, the vast majority without any reservation.

A phase II trial of methotrexate, cisplatin, 5-fluorouracil, and leucovorin in the treatment of invasive and metastatic urothelial carcinoma.

BACKGROUND: The current treatment of advanced urothelial carcinoma generates high response rates but is associated with poor overall survival. The current study evaluated the efficacy and toxicity of a new combination of active drugs in the treatment of urothelial carcinoma. METHODS: Twenty-four patients with muscle invasive or metastatic urothelial carcinoma were enrolled. Fifteen patients (63%) had metastatic disease whereas 9 patients had T2-T4 disease. Three patients were unevaluable for response because of significant toxicity. Patients were treated every 28 days with methotrexate, 60 mg/m(2), intravenously (i.v.) on Day 1; cisplatin, 25 mg/m(2)/day, by continuous i.v. infusion on Days 2-6; 5-flurouracil (5-FU) 800 mg/m(2)/day by continuous i.v. infusion on Days 3-6; and leucovorin, 500 mg/m(2)/day, by continuous i.v. infusion on Days 2-6. Dosage in subsequent cycles was adjusted according to toxicity. RESULTS: The median follow-up was 81 months (range, 53-97+ months). The overall response rate (complete response + partial response) for all 24 patients was 63% (95% confidence interval, 41-81%). The median survival was 65 months in the patients with muscle invasive disease and 17 months in the patients with metastatic disease. The duration of response in patients with metastatic disease was 6 months (range, 4-19 months). Toxicity was significant, with 82% of patients experiencing Common Toxicity Criteria Grade 3 or 4 neutropenia and 63% experiencing Grade 3 or 4 thrombocytopenia. However, only three patients developed febrile neutropenia and gastrointestinal and neurologic toxicity was moderate. CONCLUSIONS: The combination of methotrexate, cisplatin, 5-fluorouracil, and leucovorin represents an active regimen in the treatment of urothelial carcinoma with a moderate toxicity profile. As new drugs are found to treat urothelial carcinoma, further studies will be needed to evaluate the role of traditional agents such as 5-fluorouracil and methotrexate in new combination chemotherapeutic regimens.