Comparison of nocturia response to desmopressin treatment between patients with normal and high nocturnal bladder capacity index.

OBJECTIVE: To compare efficacy of desmopressin for treatment of nocturia between patients with normal and high nocturnal bladder capacity index (NBCi). METHODS: Retrospective analysis of adult patients treated with desmopressin for nocturia. Patients were analyzed according to high or normal NBCi value before treatment. RESULTS: 55 patients were identified, aged 49-84, 47 males, 8 females, who started desmopressin 0.2 mg nocte between 2009 and 2011. Two groups (N: normal and H: high NBCi) were similar regarding number, gender, age, 24 h urine volume, and nocturnal urine volume. On treatment, nocturnal volume decreased by mean of 364 mL. Number of nightly voids decreased in N group from 3.11 to 1.50, in H from 3.96 to 1.44. Nocturnal polyuria and nocturia indices also decreased significantly. NBCi remained the same in N group (0.56 on therapy) and in H group decreased to mean 0.63. All on-treatment values were statistically similar in N and H groups. Pretreatment differences were abolished with treatment. NBCi was significantly correlated to nocturia reduction-larger reduction was observed in patients with higher NBCi. In 8/55 patients, hyponatremia was detected, but without clinical consequences. CONCLUSIONS: The results indicate that the effectiveness of desmopressin on nocturia is not dependent upon the patient's pretreatment NBCi.

Evaluation of safety and analgesic consumption in patients with advanced cancer treated with zoledronic acid.

BACKGROUND: The aim of the study was evaluation of zoledronic acid with regard to safety, effect on analgesic consumption and impact on occurrence of skeletal related events in patients with bone lesions from solid tumors and multiple myeloma. METHODS: We conducted an observational, 12-month, phase IV and multi-center study. One hundred and twenty-five symptomatic (pain) bone-metastatic patients were included between 2007 and 2009: 92 prostate cancers, 28 multiple myelomas, 5 others. They were prescribed monthly infusions of zoledronic acid in accordance to each disease's treatment guidelines. Analgesics consumption, pain and laboratory values were evaluated. RESULTS: Zoledronic acid was prescribed concurrent to initial therapy for myeloma and only in late stage of prostate cancer. With treatment, percentage of patients on analgesics decreased in myeloma group (from 57% to 24%) and increased in prostate cancer group (from 70% to 88%). In patients with any analgesics, the use of opiates' prescription dropped from 72.9% to 64%, percentages of non-steroidal analgesics and other mild analgesics increased slightly. Pain score (Visual Analog Scale, VAS) decreased non significantly (by 22%) in prostate cancer but significantly in myeloma (by 97%). Hypocalcaemia grade 3 or 4 was observed in 4% of patients. Deviations in creatinine remained stable throughout. A total of 31 skeletal related events were reported for 10 patients (8%). CONCLUSIONS: Zoledronic acid was safe medication. Different response of pain was seen between prostate cancer and myeloma patients, which might be due to different stages of disease where it was prescribed according to present guidelines. Possibility of earlier start of treatment should be explored in prostate cancer.

Polymorphism L26V in the cathepsin B gene may be associated with a risk of prostate cancer and differentiation.

Cathepsin B is a lysosomal enzyme thought to be involved in tumour cell invasion and metastasis. This study was designed to investigate the presence of a known leucine to valine mutation at position 26 (L26V) single nucleotide polymorphism (SNP) in the cathepsin B (CTSB) gene in a Slovenian Caucasian population, and to evaluate the association with risk of prostate adenocarcinoma (PCa). A total of 168 PCa patients were compared with 168 controls. There was a significant difference between the frequency of alleles in control subjects and PCa patients: the VV genotype was found in 35.7% of the controls versus 48.8% of the PCa patients. The relative risk for the VV genotype in PCa patients was 1.71. When evaluating the frequency of alleles of the CTSB gene according to tumour grade, increased frequency of the VV genotype was associated with less differentiated tumours. The VV genotype of the CTSB L26V SNP may indicate an increased risk for PCa and less differentiated cancer (higher Gleason score).

In vitro simulation of stent fracture mechanisms in ureteric nitinol wire stents.

The ZebraStent is a new-concept lumen-less teflon-coated nitinol double-J wire-stent, designed to facilitate the passage of residual fragments after extracorporeal shock wave lithotripsy. In clinical practice we observed a small number of stent fractures. Hence, an experimental model was designed to simulate the physical forces that may lead to material fatigue of the stent. Flexion force was simulated by "half circular kidney mimicking structures" (HCKMS) into which the upper part of the stent was placed. All experiments were done for a minimum of 5 million cycles representing a stent indwelling time of 9 months, or until stent fracture, and simulating respiratory kidney movement. It was demonstrated that as the diameter of the HCKMS decreases, thus leading to an increased bending of the stent, the likelihood of stent fracture increased proportionally and occurred earlier. From our results it appears that stent fractures can be avoided by observing a maximum indwelling time of 6-8 weeks (which should suffice for the duration of a average SWL treatment), by choosing the correct (and shortest possible) stent length, and perhaps by manufacturer's modifications decreasing the stent's resistance to flexion. The ZebraStent concept remains appealing if it is considered as a short-term stent for post-SWL residual fragments.

UroVysion FISH test for detecting urothelial cancers: meta-analysis of diagnostic accuracy and comparison with urinary cytology testing.

OBJECTIVES: Since the introduction of the UroVysion test for detecting urothelial cancers in urine, its reported performance has varied. This article systematically analyzed reported results. METHODS: Articles in English conforming to the Oxford EBM criteria were included, with the evaluation focused on cancers that were histologically confirmed at the time of testing rather than on any cancers that might develop later. Where applicable, samples with no cells were reclassified as negative so as to further improve the actual estimation of test performance. Where available, cytology data were also analyzed. Meta-DiSc software was used for the statistical analyses. RESULTS: We identified 14 studies involving 2477 FISH tests. The overall prevalence of urothelial cancers was 35%. The pooled sensitivity and specificity of all studies were 72% (69%-75%) and 83% (82%-85%), respectively. Cytology data were available from 12 studies, with the overall sensitivity and specificity being 42% (38%-45%) and 96% (95%-97%). Excluding Ta tumors, the sensitivity was 86% (82%-89%) for UroVysion and 61% (56%-66%) for cytology. The overall performance was higher for UroVysion than for cytology: diagnostic odds ratio, 16.8 and 14.1; AUC, 0.867 (SE 0.021) and 0.626 (SE 0.091). These differences in overall test performance measures almost disappeared when superficial cancer cases were excluded from the analysis. CONCLUSIONS: The published trials suggest that for a general mix of cases, cytology results are highly specific. However, a negative cytology result does not meaningfully change the post-test probability of the presence of urothelial cancer. UroVysion FISH test results should not be considered to provide conclusive evidence for the presence or absence of urothelial cancer, but both positive and negative results do moderately influence the post-test probability of disease.

Use of optical dilating trocar for initial access during extraperitoneal laparoscopic radical prostatectomy.

BACKGROUND AND PURPOSE: For fully extraperitoneal laparoscopic radical prostatectomy, open port placement is standard. This takes quite some time, so with the availability of trocars that combine optical control and radial dilation, an easier and faster technique was tested. PATIENTS AND METHODS: In 70 consecutive cases, preperitoneal space creation was attempted with only a 1-cm skin incision, developing further access using an optical dilating trocar with a laparoscope. Open preparation of the subcutaneous fat and incision of the anterior rectus fascia was not necessary. RESULTS: Access was successful on the first attempt in 67 cases. The time from the first skin incision to an established preperitoneal space was <10 minutes. CONCLUSIONS: We believe this technique offers an easier, faster, and safe way to introduce the first port for extraperitoneal laparoscopic radical prostatectomy.

Clinicopathological and immunohistochemical markers after radical gastrectomy for gastric cancer.

BACKGROUND/AIMS: The aim of the study was to verify the classic clinicopathological prognostic factors of the expected survival, to determine the frequency of immunohistochemical factors (C-erB-2, p53) and to verify these immunohistochemical factors in their function as prognostic factors in gastric cancer patients after a potentially curative gastric resection. METHODOLOGY: In 78 gastric cancer patients after a potentially curative resection the clinicopathological factors (age, general performance of the patient, tumor diameter, TNM stage, stage according to UICC, type of operation and the extent of lymphadenectomy) and immunohistochemical factors (p53 and C-erB-2) were analyzed. RESULTS: In univariate analysis ASA stage of general performance, size of tumor, TNM stage and stage according to UICC exert significant influence on the median survival. Median survival is higher in patients with C-erB-2 negative reaction and in those with p53 positive reaction, although not significant. In patients with tumor located in proximal two thirds, patients with negative reaction to C-erB-2 have a significantly higher median survival than patients with positive reaction to C-erB-2. The Cox regression model reveals ASA stage and UICC classification to be significant factors whereas immunohistochemical parameters C-erB-2 and p53 do not reveal any significance in the multivariate survival analysis. CONCLUSIONS: According to the results of our study the ASA stage and UICC classification influence the expected survival of potentially radically resected gastric cancer patients significantly, while immunohistochemical parameters C-erB-2 and p53 do not.

Relation between intracavernosal dose of prostaglandin Pge 1 and mean duration of erection in men with different underlying causes of erectile dysfunction.

AIM: To analyze differences in effect of intracavernosally applied alprostadil (prostaglandin PGE 1) on men with different underlying causes of erectile dysfunction. METHODS: Forty eight men with erectile dysfunction lasting for at least six months were stratified according to the etiology of erectile dysfunction into one of 4 groups comprising 12 patients. The groups were the following: psychogenic, arteriogenic, veno-occlusive, and neurological erectile dysfunction group. All men filled out International Index of Erectile Function (IIEF)-5 questionnaire, which is a 5-question version of International Index of Erectile Function Questionnaire, underwent clinical examination including neurological assessment, were tested for nocturnal penile tumescence, and had Doppler color sonography of penile arteries. Intracavernosal alprostadil was then applied to the patients, starting with a 5 mug dose and then increased in 5 microg increments until the final dose of 20 microg was reached. We measured the time from the moment of application until the start of erection and time of erection duration. For statistical analysis, non-parametric Friedman test for significant differences between repeated measurements in small groups and Wilcoxon test for differences between doses were used. RESULTS: Significant relation was found between the applied dose of intracavernosal alprostadil and the duration of erection in all 4 groups of men with erectile dysfunction. In patients with arteriogenic erectile dysfunction, mean (+/-standard deviation) duration of erection for consecutive doses of alprostadil 5 microg, 10 microg, 15 microg, and 20 microg were 40.0+/-20.6, 54.6+/-23.6, 65.0+/-29.6, and 82.1+/-35.4 minutes, respectively, with significant increase for each dose. In patients with veno-occlusive dysfunction, mean durations of erection significantly increased from 8.2+/-7.8 minutes at 10 microg to 17.3+/-9.5 minutes at 20 microg. In patients with neurogenic erectile dysfunction, mean durations of erection were 40.4+/-16.6, 61.7+/-24.7, 82.5+/-34.4, and 101.0+/-28.5 minutes respectively, with significant increase for each dose. In patients with psychogenic erectile dysfunction, mean durations of erection were 32.4+/-15.4, 45.8+/-15.1, 69.9+/-23.5, and 98.3+/-37.9 minutes respectively, with a significant increase for each dose. CONCLUSION: Men with different underlying cause of erectile dysfunction show different response to the intracavernosally applied alprostadil. In order to achieve the optimal result, the treatment should be started with the smallest doses which are gradually increased until the maximum effect is reached.

What have we learned from surgical treatment of gastric adenocarcinoma? A comparison of two periods.

In January 1992, a standardized and more radical surgical approach in gastric cancer treatment and a standardized pathohistological workup of specimens was introduced at our institution. The aim of our retrospectively designed study was to compare the results of two consecutive groups of altogether 348 patients who underwent a total or subtotal gastrectomy for gastric cancer (period A: 162 patients operated between 1992 and 1996; period B: 186 patients operated between 1997 and 2000). The two groups of patients were comparable in age, sex, their general condition, and the proportion of potentially curable (R0) resections. There was a significant difference between the groups with regard to tumor site (fewer distal and more proximal stomach tumors in period B), type of operation (more total gastrectomies in period B), extent of lymphadenectomy (more D2 and D3 in period B), average number of affected lymph nodes (higher in period B), average number of examined nodes (higher in period B), and in UICC stage (less stage II in period B). UICC classification was impossible in 19 patients overall, but there were fewer non-classified patients in period B. The incidence of surgical complications (15.6% vs. 18.7%) and average hospital stay (14.72 days vs. 14.70 days) was not significantly different in the two groups. The drop in overall mortality rate (potentially curable and non-curable resections) in period B almost reached statistical significance (period A: 8%, period B: 6.5%; p = 0.57). The 5-year survival for all R0 resected patients (279) in 9 years was 31%. The median survival was significantly longer in period B (941 days) than in period A (570 days) for R0 and non-curable (R2) resections together (p=0.0132) as well as for R0 resections alone (period A: 844 days, period B: 1176 days; p = 0.0127). Comparison of the two consecutive groups of patients shows that after a defined period of systematic surgical work our results improved, reflected in the higher number of extracted lymph nodes, the higher number of total gastrectomies, and the longer median survival in the second period.

Prostate cancer and polymorphism D85Y in gene for dihydrotestosterone degrading enzyme UGT2B15: Frequency of DD homozygotes increases with Gleason Score.

BACKGROUND: Although, a functional rationale for influence of polymorphism D85Y in gene UGT2B15 on prostate cancer (PCa) exists (different V(max) of enzyme), conflicting results have been reported. METHODS: DNA from 178 controls and 206 PCa patients with known Gleason score were genotyped using a newly developed RFLP assay, which allowed the detection of both alleles in an individual after single PCR amplification. CONTROLS: 16% DD, 52% DY; PCa patients: 23% DD, 49% DY. Subgroups of PCa: well differentiated: 11% DD, 37% DY; moderately differentiated: 22% DD, 50% DY; poorly differentiated: 34% DD, 50% DY. Correlation was confirmed between Gleason score and number of D alleles (P = 0.018) and persisted after age adjustment. When comparing controls to patients with a Gleason score of 7 or more, difference for the frequency of homozygosity DD was significant between the groups (P = 0.032, OR = 2.04). CONCLUSIONS: Polymorphism D85Y in gene UGT2B15 correlates with differentiation of PCa.

In vitro functional tests for evaluation of stimulating capacity of cultured human dendritic cells.

Basic functional test for evaluation of in vitro cultured human dendritic cells (DC) is primary allogeneic one-way mixed lymphocyte reaction (MLR). In this way, one can evaluate stimulating capacity, which is a basic characteristic of DC. The proliferation of cells is measured through incorporation of 3H-thymidine. Normally proliferation is measured at days 5-7. We studied kinetics of proliferative responses initiated with different stimulating cell suspensions to evaluate differences and possibly reduce time needed to perform this test.Gradual increase in response from days 1 to 7 and a significant difference from controls (peripheral blood mononuclear cells) seen from day 4 was noted if macrophages were used as stimulators. A consistently higher proliferation, compared to controls, was always found already on day 2 when mature DC were used as stimulators. The reaction peaked 2 to 3 days earlier and was also more than two times more intense.This maximal and significantly higher response, consistently seen already after 48 hours, allows us to confirm the presence of mature DC in stimulating suspensions much earlier than previously.