Radially expanding single-step nephrostomy tract dilator.

OBJECTIVES: To compare the radial and axial forces produced by balloon, Amplatz, and radially expanding single-step nephrostomy (RESN) systems and report our initial clinical results using the new RESN device. Balloon, Amplatz, and Alken dilators are commonly used to establish nephrostomy tracts in percutaneous surgery. They require multiple steps, with the potential for kinking and displacement of the working guidewire. In contrast, the new RESN tract dilator expands a unique sleeve conduit and places an Amplatz-like sheath in a single step with less dependence on a guidewire for dilation. METHODS: An experimental model was designed using a perforated silicon disc with a 10F central opening to measure the axial force transmission as 30F balloon, Amplatz, and RESN systems were inserted through the silicon discs. We also report our first 9 patients who underwent percutaneous dilation with the RESN system. RESULTS: Thirty French expansion was achieved with each dilator tested. Substantially lower axial forces were transmitted with the RESN device compared with the balloon and Amplatz dilators (5.2 versus 13.1 and 19.2 lb, respectively, P <0.001). Intraoperatively, all 9 patients were successfully dilated, and the kidney was relatively stationary as imaged with fluoroscopy. One patient with multiple prior renal procedures was successfully dilated with RESN system after failed attempts with balloon dilation. CONCLUSIONS: The RESN dilator is a rapid, single-step access system successfully used in our first 9 patients. Intraluminal sleeve dilation eliminates guidewire dependence for maintaining access, limits renal displacement, and facilitates appropriate vector force for percutaneous dilation.

Treatment of refractory kidney transplant ureteral strictures using balloon cautery endoureterotomy.

OBJECTIVES: To report our long-term clinical results with the use of endoureterotomy in patients undergoing renal transplant with a minimum follow-up of 23 months. METHODS: Six renal transplant patients developed persistent ureteral obstruction demonstrated by elevated serum creatinine levels, renal ultrasound, and antegrade pyelography. Stent placement and balloon dilation were performed as the initial therapy in all patients. Persistent ureteral obstruction was managed with balloon cautery endoureterotomy. Ureteral stents were removed cystoscopically 6 weeks after the procedure. RESULTS: Four men and 2 women, mean age 45 years (range 38 to 54), underwent eight procedures: six by way of an antegrade percutaneous approach and two in an endoscopic retrograde fashion. The sites of ureteral stricture were ureterovesical junction (n = 4), ureteropelvic junction (n = 1), and midureteroureteral (n = 1). Two patients required a second endoureterotomy 3 months after the first attempt. Patients were followed up for a mean of 27 months (range 23 to 34). The mean serum creatinine level for all patients at follow-up was 2.6 mg/dL (range 1.6 to 3.9), including a mean serum creatinine level of 1.8 mg/dL (range 1.6 to 1.9) for nonrejected kidneys and a mean of 3.4 mg/dL (range 2.5 to 3.9) in those found to have concurrent rejection. Overall, five (63%) of eight procedures were successful in 5 (83%) of 6 patients. No intraoperative complications occurred and no blood transfusions were required. CONCLUSIONS: Balloon cautery endoureterotomy was successful in this select group of renal transplant patients with persistent ureteral strictures after initial balloon dilation and stenting failed. This modality proved durable to 27 months of follow-up without significant complications.

Frequently deleted loci on chromosome 9 may harbor several tumor suppressor genes in human renal cell carcinoma.

PURPOSE: Loss of various loci on chromosome 9 has been reported in various cancers. To determine the frequency of deletions at different loci of chromosome 9 in renal cell carcinoma microdissected samples of normal renal epithelium and carcinoma from the same patients were analyzed. MATERIALS AND METHODS: DNA was isolated from microdissected sections of normal and tumor cells of 60 renal specimens, amplified by polymerase chain reaction and analyzed for loss of heterozygosity on chromosome 9 using the 16 microsatellite markers D9S178, D9S157, D9S274, D9S168, D9S285, D9S156, D9S1839, D9S162, IFNA, D9S736, D9S171, D9S1749, D9S273D9S270, D9S153 and D9S170. Loss of heterozygosity was analyzed by a polymerase chain reaction based technique developed at our laboratory. RESULTS: This study showed a high incidence of loss of heterozygosity on chromosome 9 in renal cell carcinoma. Of 60 cases 44 (73%), 24 (40%) and 14 (23%) showed loss of heterozygosity at a minimum of 1, at a minimum of 3 and at 4 or more loci, respectively. The main deletion was found on the 9p21 region at loci DS171 in 38% of cases, D9S1749 in 42% and DS270 in 14%. Overall deletion on chromosome 9p21 was noted in 57% of renal cancer cases. Other deleted regions were on chromosome 9p'0022 to 23 at loci D9S157 in 37% of cases, D9S274 in 20%, D9S168 in 27%, D9S285 in 20%, D9S156 in 12%, D9S1839 in 17% and D9S162 in 24%. Overall deletion at chromosome 9q32 to 33 was noted in 46% of renal cell carcinoma cases. Chromosome 9q32 to 33 also showed deletion at locus D9S170 in 22% of renal cell carcinoma cases. When we compared the incidence of deletion at various loci on chromosome 9 according to renal cell carcinoma grade, we found a higher rate of deletion in advanced grades of renal cell carcinoma. A candidate target tumor suppressor gene, p16 (MTS-1/CDKN2), has been identified within the 9p21 deleted region in various cancers. In our study the expression of p16 protein was absent or low in renal cell cancer samples, suggesting that loss of the p16 gene may be involved in renal cell carcinogenesis. CONCLUSIONS: Our study demonstrates a high incidence of loss of heterozygosity on chromosome 9, mainly 9p21 and 9p22 to 23, in renal cell carcinoma, suggesting several putative tumor suppressor genes on these regions. The identification of other tumor suppressor genes on the 9p21 and 9p22 to 23 regions warrants further studies.

Expression analysis of Y chromosome genes in human prostate cancer.

PURPOSE: We hypothesized that alterations in Y chromosome gene expression may be associated with prostate cancer. To test this hypothesis we analyzed the expression of 19 Y chromosome genes in benign and malignant prostate tissue. MATERIALS AND METHODS: To study the expression of Y chromosome genes RNA was extracted from prostate cancer and benign prostatic hyperplasia (BPH) tissue as well as from prostate cancer cell lines. RNA was reverse transcribed and polymerase chain reaction amplified using specific primers. These primers were designed for each gene sequence obtained from the gene data bank. We analyzed 19 Y chromosome genes using 6 cell lines, 7 BPH and 7 prostate cancer tissues. Normal testis RNA served as a positive control. RESULTS: Of the 19 genes analyzed in cell lines BPH-1 cells expressed the RPS4Y, USP9Y, TMSB4Y and DBY genes; DUPro expressed RPS4Y, USP9Y, TMSB4Y, DBY and UTY; DU145 expressed DAZ, RPS4Y, USP9Y, TMSB4Y, DBY, EIAFIY, PRKY and SMCY; LNCaP expressed TSPY, SRY, BPY1, PRY, DAZ, RBMIH, RPS4Y, DBY, EIAFIY, PRKY and SMCY; ND1 expressed DAZ, RPS4Y, USP9Y, TMSB4Y, DBY, EIAFIY, PRKY and SMCY; and PC3 expressed RPS4Y, USP9Y and DBY. BPH tissue expressed the SRY, PRY, DBY, PRKY, RPS4Y, TMSB4Y, USP9Y and ZFY genes. Prostate cancer tissue expressed the PRY, TSPY, USP9Y, UTY, DBY, SMCY, ZFY, EIAFIY, TMSB4Y and RPS4Y genes. CONCLUSIONS: The differential expression of Y chromosome genes in prostate cancer, BPH tissue and prostate cancer cell lines indicates that they may have a role in prostate cancer.

Additional treatments and reimbursement rates associated with prostate cancer treatment for patients undergoing radical prostatectomy, interstitial brachytherapy, and external beam radiotherapy.

OBJECTIVES: To define patterns of treatment among contemporary patients undergoing radical prostatectomy, interstitial radiation, and external beam radiation for prostate cancer. METHODS: We analyzed 291 consecutive patients (Stage T1-T3NXM0) who underwent definitive local treatment for prostate cancer with radical prostatectomy, interstitial seed implantation, or external beam radiation. Patients were stratified into three risk groups based on clinical T stage, serum prostate-specific antigen level at diagnosis, and biopsy Gleason score. The frequency of additional treatments, including androgen deprivation and external beam radiation, given within 3 months of initial local therapy was assessed. Patterns of care were compared and adjusted for risk. RESULTS: Of the 291 patients, 107 (36. 8%) underwent radical prostatectomy, 94 (32.3%) underwent interstitial seed implantation, and 90 (30.9%) underwent external beam radiation. Use of combination therapy differed significantly according to the type of initial local treatment and risk category. No patient in the low-risk group received combination therapy. For patients in the intermediate and high-risk groups, the frequency of combination therapy was significantly lower in the radical prostatectomy group when compared with either the interstitial seed implantation (P <0.001 and P <0.02, respectively) or external beam radiation group (P <0.001 and P <0.001, respectively). CONCLUSIONS: There are significant differences in resource utilization for contemporary patients undergoing definitive local therapy for prostate cancer. These differences may have a significant effect on treatment cost and morbidity, and they will likely make short-term comparisons between different treatment modalities difficult because of the high use of androgen deprivation in men treated with radiation therapy.

Microsatellite instability of dinucleotide tandem repeat sequences is higher than trinucleotide, tetranucleotide and pentanucleotide repeat sequences in prostate cancer.

In order to investigate whether the change in length of simple repetitive genomic sequences (microsatellite instability) is associated with prostate cancer, we analyzed 40 prostate cancer samples with 44 microsatellite loci markers on chromosomes 1, 3, 5, 6, 8, 9, 11, 13, 16, 17 and X. DNA was extracted from normal and tumor cells of 40 microdissected cancer samples, amplified by PCR and analyzed for microsatellite instability using 44 primers for dinucleotide, trinucleotide, tetranucleotide and pentanucleotide repeat sequences. The results of this study demonstrate that 45% of the prostate cancer specimens (18 out of 40) showed microsatellite instability (MSI) at a minimum of one locus using dinucleotide repeat sequences. Two out of 40 samples (5%) showed MSI at a minimum of one locus using three different trinucleotide repeat primers (AR, SR and TBP). Ten out of 40 (25%) samples showed MSI at a minimum of one locus using five different tetranucleotide repeat primers (HPRT1, HPRTII, MYCL1, RB, REN). There were no MSI observed in samples using pentanucleotide repeat sequences. There were no MSI in benign prostatic hyperplasia samples (25 samples). These experiments suggest that the microsatellite instability of dinucleotide tandem repeat sequences is much higher than trinucleotide, tetranucleotide and pentanucleotide repeat sequences in prostate cancer. The MSI with different lengths of nucleotide repeat sequences did not correlate with the stage and grades of prostate cancer.

Differential effects of pinacidil and cromakalim on vascular relaxation and sympathetic neurotransmission.

We tested the hypothesis that pinacidil and cromakalim acted at different sites to relax vascular smooth muscle, in vitro. We compared the effects of pinacidil and cromakalim on tension development in isolated canine and bovine pulmonary artery and vein and canine mesenteric artery and dorsal metatarsal vein, and on the pre- and post-synaptic responses of the canine blood vessels to transmural nerve stimulation. Both pinacidil and cromakalim relaxed bovine and canine blood vessels precontracted to 50% of maximal tension with U46619, prostaglandin F2 alpha, or norepinephrine. Pinacidil- and cromaklim-mediated relaxations of the blood vessels were not mediated by endothelium-derived factors, prostanoids, muscarinic receptors, beta-adrenoceptors, or Ca(2+)-activated or voltage-dependent K+ channels, since they were unaffected by endothelium-rubbing, indomethacin, L-NG-monomethyl-L-arginine, atropine, propranolol, and charybdotoxin. Glibenchlamide, an inhibitor of ATP-activated K+ channels (K+ATP), and KCl (25-60 mM) sufficient to minimize the role of K+ channels almost abolished cromakalim- but not pinacidil-induced relaxation of the blood vessels. Pinacidil inhibited the contractions of the dorsal metatarsal vein and mesenteric artery to norepinephrine and transmural nerve stimulation and the efflux of 2-[14C]norepinephrine during transmural nerve stimulation. In contrast, 1 and 10 nM cromakalim enhanced while 0.1 and 1 microM cromakalim inhibited the contractions of, and 2-[14C]norepinephrine efflux from, the mesenteric artery and dorsal metatarsal vein during transmural nerve stimulation. Thus, pinacidil and cromakalim relax smooth muscle by stimulation of K+ATP channels. Pinacidil also relaxes the blood vessels by a K+ channel independent mechanism. Pinacidil-induced relaxation may also result from presynaptic inhibition of norepinephrine release from the sympathetic neuron.