We evaluated the efficacy of the α1-adrenergic antagonist tamsulosin for conservative expulsive therapy in patients with ureteral colic due to juxtavesical stones.
A total of 60 consecutive ...symptomatic patients with stones located in the juxtavesical tract of the ureter were randomly divided into group 1—30 who received oral floroglucine-trimetossibenzene 3 times daily and group 2—30 who received 0.4 mg tamsulosin daily. The 2 groups received 30 mg deflazacort daily for 10 days plus cotrimoxazole 2 times daily for 8 days and 75 mg diclofenac injected intramuscularly on demand. Ultrasound followup and medical visits were performed weekly for 4 weeks. Stone passage rate and time, analgesic use, hospitalization and endoscopical intervention were evaluated. Statistical analysis was performed using the Student t test.
The stone expulsion rate was 70% for group 1 and 100% for group 2. Mean stone size was 5.8 and 6.7 mm, respectively (p = 0.001). Mean expulsion time was 111.1 hours for group 1 and 65.7 hours for group 2 (p = 0.020). The mean number of diclofenac injections was 2.83 for group 1 and 0.13 for group 2 (p <0.0001). Ten group 1 patients were hospitalized, of whom 9 underwent ureteroscopy, compared with none in group 2 (p <0.0001 and 0.001, respectively).
Tamsulosin used as a spasmolytic drug during renal colic due to juxtavesical calculi increased the stone expulsion rate and decreased expulsion time, the need for hospitalization and endoscopic procedures, and provided particularly good control of colic pain.
Everolimus is a mammalian target of rapamycin inhibitor approved for the treatment of metastatic renal cell carcinoma (mRCC). We aimed to assess the association between pre-treatment ...neutrophil-to-lymphocyte ratio (NLR) and the outcome of patients treated with everolimus for mRCC.
Ninety-seven patients with mRCC were treated with everolimus till April 2013 in our institutions. Patients were stratified in two groups with NLR >3 (Group A) vs <3 (Group B). Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier method. Gender, age, Motzer prognostic group, PFS on first-line therapy, neutrophilia and NLR were included in the Cox analysis to investigate their prognostic relevance.
Median OS and PFS were 10.6 and 5.3 months, respectively. Median OS was 12.2 months in Group A and 24.4 months in Group B (P=0.001). Median PFS was 3.4 months in Group A and 9.9 months in Group B (P<0.001). At multivariate analysis, only Motzer prognostic group and NLR were independent prognostic factors for OS and PFS.
Pre-treatment NLR is an independent prognostic factor for patients with mRCC treated with second- or third-line everolimus. This should be investigated and validated in prospective studies.
Currently, sunitinib represents one of the therapeutic strongholds for renal cell carcinoma, but the criteria for treatment selection are lacking. We assessed the role of vascular endothelial growth ...factor (VEGF) and VEGF receptor (VEGFR) polymorphisms in the prediction of the clinical outcome in metastatic renal cell carcinoma (mRCC) patients.
A total of 84 tumour samples from mRCC patients receiving first-line sunitinib were tested for VEGF and VEGFR single-nucleotide polymorphisms (SNPs). The SNP results were correlated with progression-free survival (PFS) and overall survival (OS).
Median PFS was 8.22 months, although whereas median OS was 32.13 months. The VEGF A rs833061 resulted significant in PFS (17 vs 4 months; P<0.0001) and OS (38 vs 10 months; P<0.0001). The VEGF A rs699947 was significant for PFS (18 vs 4 months; P=0.0001) and OS (37 vs 16 months; P<0.0001). The VEGF A rs2010963 was significant in PFS (18 vs 8 vs 2 months; P=0.0001) and OS (31 vs 36 vs 9 months; P=0.0045). The VEGR3 rs6877011 was significant in PFS (12 vs 4 months; P=0.0075) and OS (36 vs 17 months; P=0.0001). At multivariate analysis, rs833061, rs2010963 and rs68877011 were significant in PFS, and rs833061 and rs68877011 were independent factors in OS.
In our analysis, patients with TT polymorphism of rs833061, CC polymorphism of rs699947, CC polymorphism of rs2010963 and CG polymorphism of rs6877011 seem to have a worse PFS and OS when receiving first-line sunitinib.
To assess the clinical efficacy of the addition of a corticosteroid drug to tamsulosin in the medical-expulsive therapy of distal ureterolithiasis.
Sixty consecutive patients with a symptomatic ...distal ureteral stone were included in our study and randomized to one of two home treatment groups. Group 1 patients (n = 30) received tamsulosin (0.4 mg daily), and group 2 patients (n = 30) were treated with a corticosteroid drug (deflazacort, 30 mg daily) plus tamsulosin. The treatment duration was until stone expulsion or 28 days, whichever came first. The primary endpoint of the study was the stone expulsion rate. The secondary endpoints were the expulsion time; use of analgesics; number of emergency room admissions, hospitalizations, and workdays lost; drug side effects; and quality of life of the patients (EuroQol questionnaire, EQ-5D) during treatment.
The two groups had a similar expulsion rate (90% for group 1 and 96.7% for group 2;
P = 0.612), but the expulsion time was significantly reduced in group 2 patients (
P = 0.036). During the treatment period, we did not observe significant differences between the two groups in the number of emergency room visits or hospitalizations, analgesic use, number of workdays lost, or incidence of drug side effects. The quality of life of the patients during therapy, as determined using the EQ-5D, was similar in both groups.
The use of a corticosteroid drug in association with tamsulosin seemed to induce more rapid stone expulsion. In addition, tamsulosin alone as medical-expulsive therapy for distal ureteral calculi had excellent expulsive effectiveness.
Conventional renal cell carcinoma (RCC) is characterized by rich neovascularization and shows a fine vascular network around tumor cells. Nephron sparing surgery has been established as a method of ...choice or necessity for localized tumors. We investigated the importance of microvessel density (MVD), vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (Flk-1) immunohistochemical expression in a large series of small conventional clear cell renal carcinomas treated with partial nephrectomy and assessed the prognostic value of their expression in terms of patients survival at long-term followup.
A total of 48 patients with a mean age ± SD of 58.2 ± 9.5 years who had conventional single RCC were considered. Median tumor diameter was 2.92 ± 0.82 cm (range 1.3 to 5). Disease was grades 1 to 4 in 15, 29, 2 and 2 patients, respectively. Median followup was 92.9 months (range 17 to 186).
Four patients (3.9%) had died of metastatic renal cancer at a median followup of 23.5 months, of whom 1 had a grade 2, 1 had a grade 3 and 2 had grade 4 RCC. Patients with MVD expression higher than the median (44.4 vessels per mm
2) did not show a significant difference in survival compared to patients with MVD expression lower than the median. Patients with VEGF expression higher than 25% in the histological specimen showed worse survival than patients with VEGF expression lower than 25%. Different Flk-1 expression did not determine a significant difference in survival. On univariate analysis of patient survival in relation to the different considered factors Fuhrman grading was the most important factor for survival.
Our study shows that recurrence and death are possible even in patients with small renal tumors. MVD, VEGF and Flk-1 expression do not depend on tumor size in pT1a RCC. Therefore, to date Fuhrman grading appears to be the only factor predictive of survival even in small RCC. Thus, Fuhrman grading is predictive of mortality. While VEGF is not predictive of survival as a single parameter, based on its percent of expression (lower or higher than 25%) it can determine 2 groups that are different from the prognostic point of view.
Purpose
Evidences have shown that neutrophil-to-lymphocyte ratio (NLR) has a prognostic value in patients with cancer. We wanted to test the prognostic significance of NLR in prostatic cancer of ...patients who are candidate to radical prostatectomy.
Methods
We have considered 731 patients. Complete demographic data including age, tumor stage, Gleason score, complete blood count and serum biochemical profile were collected. Pre-treatment percentage of neutrophils and NLR were considered, and correlated with patients data and recurrence free survival.
Results
389 patients were evaluated, mean age 65 years, mean follow-up 51.5 months, mean recurrence free survival 51.3 months. Total neutrophil count does not correlate with biochemical recurrence and disease free survival. Patients with a value higher of 60% of neutrophils are more likely to have a recurrence. Patients with a total lymphocyte count <1,500 have a higher rate of relapse. NLR was not correlated with baseline total PSA, with Gleason score and with pathological stage; patients with a NLR >3 has a higher incidence of recurrence. In multivariate analysis including age, total PSA and NLR, NLR is the most important factor able to predict recurrence. There are some limitations to this study; first, this is a retrospective study, and the total number of patients analyzed is relatively small.
Conclusions
Our study suggests that pre-treatment NLR may be associated with disease free survival in patients with prostate cancer, and could be introduced in clinical practice. NLR has the advantage of low economic cost and wide availability.
Cardiovascular peptides such as angiotensin II (Ang II) and atrial natriuretic peptide (ANP) have metabolic effects on adipose cells. These peptides might also regulate adipocyte proliferation and ...visceral adipose tissue (VAT) expansion. Well-differentiated and stabilized primary cultures of human visceral mature adipocytes (MA) and in vitro-differentiated preadipocytes (DPA) were used as a model to study regulation of VAT expansion.
Adipocyte differentiation was evaluated by Oil Red O staining and antiperilipin antibodies. MA and DPA from intra- and retro-peritoneal depots were treated with increasing Ang II (with or without valsartan, a highly selective, competitive, 'surmountable' AT1 antagonist devoid of peroxisome proliferator-activated receptor gamma agonistic activity) or ANP concentrations. Cell counts and bromodeoxyuridine incorporation were used to evaluate proliferation. Apoptosis was evaluated by Hoechst 33342 staining. 8-Bromo cyclic guanosine monophosphate (8Br-cGMP) was used to investigate ANP effects, and real-time PCR to evaluate Ang II and ANP receptors' expression.
Cell proliferation was progressively stimulated by increasing Ang II concentrations (starting at 10-11 M) and inhibited by ANP (already at 10-13 M) in both MA and DPA. Co-incubation with increasing Ang II concentrations and valsartan indicated that Ang II effects were AT1-mediated. Indeed, AT2 receptors were not expressed. Valsartan alone slightly inhibited basal proliferation indicating an autocrine/paracrine growth factor-like effect of endogenous, adipocyte-derived Ang II. 8Br-cGMP experiments indicated that the effects of ANP were mediated by the guanylyl cyclase type A receptor.
A cell-culture model to study VAT growth showed stimulation by Ang II and inhibition by ANP at physiological concentrations. Because similar effects are likely to occur in vivo, Ang II and ANP might be important modulators of VAT expansion and associated metabolic and cardiovascular consequences.
To evaluate the outcome of the long-term follow-up in patients who underwent corporoplasty-straightening treatment for Peyronie's disease. Between 1990 and 2012, a total of 89 patients underwent ...corporoplasty-straightening surgery using penile plication for Peyronie's disease. We followed up on all the patients for the following: (a) the correction of the curvature; (b) any penile shortening; (c) sexual function; and (d) complications. The mean follow-up period was 103 months. Complete correction of the curvature was obtained in 81 patients (91%). Shortening of the penis (1.5 to <3 cm) occurred in 20 patients (22.5%) and 79 patients (88.7%) had good erectile function (International Index of Erectile Function (IIEF) 5> 21). The most frequent complication was the sensitivity reduction of the glans in eight patients (8.9%), which was resolved within about a year after surgery (mean 11 months) and the shortening of the penis in 20 patients (22.5%), which, however, did not result in problems during sexual intercourse. Corporoplasty using penile straightening plication is a safe procedure whose results are maintained for even many years after surgery. It is a procedure that can be applied to any type of curvature. Any reduction in the length of the penis, as a result of the surgery procedure, does not lead to difficulties in sexual intercourse.
Surgery is the main treatment for renal cell carcinoma (RCC); nephron sparing surgery can be performed as a treatment of choice for small peripheral lesions. Epigenetics configures a new entity that ...regulates gene expression throughout methylation, acetylation and chromatin remodelling. In addition to silencing as a result of mutations, loss of heterozygosity, or classic genetic events, epigenetic modification symbolizes essential events during carcinogenesis and tumour development. We investigated global methylation and histone acetylation expression in a series of small conventional clear cell renal carcinomas (i.e. less than 5 cm) (pT1a) treated with partial nephrectomy, to assess their possible role as diagnostic biomarkers. A total of 54 patients with conventional single RCC were selected and treated with partial nephrectomy; they were followed up to 186 months. Immunohistochemistry was performed on paraffin‐embedded sections, using anti‐5‐methylcytosine (5mc) and anti‐Acetyl‐Histone H3 (Lys 9). Our results confirm that the mean percentage of global cellular methylation in tumoural tissue was significantly higher compared to healthy peritumoural tissue, whereas the mean percentage of histone cellular acetylation in tumoural tissue was significantly lower. The percentage of methylation was significantly higher in grades 3 and 4 (P= 0.033), whereas the percentage of histone acetylation was significantly lower (P= 0.023), suggesting therefore that these markers could correlate with tumour aggressiveness in pT1a RCC. On univariate analysis of patient survival in relation to the different considered factors, Fuhrman grade was the most important survival factor. These epigenetic markers can give us interesting information about chromatin remodelling in RCCs; the percentage of global methylation increases with increasing Fuhrman grade, whereas histone acetylation decreases with increasing grade in small RCC; our results suggest that global hypermethylation and histone hypoacetylation can be assumed to be an early event in RCC and to correlate with tumour aggressiveness.
Basic Fibroblast Growth Factor (bFGF) is a heparin-binding cationic protein involved in a variety of pathological conditions including angiogenesis and solid tumour growth. The basic Fibroblast ...Growth Factor Receptor (FGFR) family comprises at least 4 high affinity tyrosine kinase receptors that require syndecans for their function. Mounting evidence indicates that syndecans, that bind both bFGF and their FGFRs, will act as stimulators, whereas syndecans that only bind bFGF will act as inhibitors of signaling by sequestering the growth factor. Recent findings have highlighted the importance of syndecans in urological cancers. The aim of this study is to investigate the expression of bFGF, its receptors (R1 and R2) and syndecans (1-4) in invasive urothelial carcinoma and normal-looking urothelium by Western blotting, RT-PCR, and immunohistochemistry analyses. Interestingly, bFGF, FGFR1 and FGFR2 protein levels statistically increased in bladder cancer tissues. mRNA of FGFR1 and syndecans (1-4), showed a statistically significant increase while an mRNA increase in the other molecules analysed was not significant. bFGF, its receptors and syndecan immunostaining were mainly present in the urothelium both in normal-looking tissues and urothelial neoplastic cells. In conclusion, our data report that the bFGF, FGFR and syndecan expressions are altered in bladder tumours.
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