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BMC Urol [journal]
- Percutaneous cryoablation for tuberous sclerosis-associated renal angiomyolipoma with neoadjuvant mTOR inhibition. [JOURNAL ARTICLE]
- BMC Urol 2014 Sep 25; 14(1):77.
Renal angiomyolipomas (AMLs) are frequent in tuberous sclerosis and are responsible for a significant proportion of the morbidity in adulthood, mainly from bleeding complications, which are correlated to the size of the AMLs. We describe the case of a 19-year-old female with multiple bilateral renal angiomyolipomas.The renal AMLs measured up to 6 cm in size. She was first treated with a low dose of the mammalian target of rapamycin (mTOR) inhibitor sirolimus (up to 3 mg/day over a 12-month period) and following significant AML size reduction, percutaneous cryoablation was performed. No side-effects of either treatment were reported. At 12 months post-cryoablation, no recurrence of the AML was noted.This is the first report of this treatment strategy and the case study reveals that combining a low dose of an mTOR inhibitor with percutaneous cryoablation to treat small tumors mitigates the side-effects while providing a good clinical outcome. This therapeutic approach is a novel tool for the clinician involved in the management of patients with tuberous sclerosis.
- Dutasteride plus Tamsulosin fixed-dose combination first-line therapy versus Tamsulosin Monotherapy in the treatment of benign prostatic hyperplasia: a budget impact analysis in the Greek healthcare setting. [JOURNAL ARTICLE]
- BMC Urol 2014 Sep 26; 14(1):78.
The purpose of this study was to explore the budget impact of dutasteride plus tamsulosin fixed-dose combination (DUT + TAM FDC) versus tamsulosin monotherapy, in the treatment of patients with benign prostatic hyperplasia (BPH) from the perspective of the Greek healthcare insurance system.A Microsoft Excel-based model was developed to estimate the financial consequences of adopting DUT + TAM FDC within the Greek healthcare setting. The model, compared six mutually exclusive health states in two alternative treatment options: current standard of care and the introduction of DUT + TAM FDC in the market. The model used clinical inputs from the CombAT study; data on resource use associated with the management of BPH in Greece were derived from expert panel, and unit cost data were derived from official reimbursement tariffs. A payer perspective was taken into account. As patient distribution data between public and private sectors are not available in Greece two scenarios were investigated, considering the whole eligible population in each scenario. A 4 year time horizon was taken into account and included treatment costs, number of transurethral resections of the prostate (TURPs) and acute urinary retention (AUR) episodes avoided.The clinical benefit from the market adoption of DUT + TAM FDC in Greece was 1,758 TURPs and 972 episodes of AUR avoided cumulatively in a four year period. The increase in total costs from the gradual introduction of DUT + TAM FDC to the Greek healthcare system ranges from [euro sign]1.3 million in the first year to [euro sign]5.8 million in the fourth year, for the public sector, and [euro sign]1.2 million to [euro sign]4.0 million, for the private sector. This represents an increase of 1.91% to 7.94% for the public sector and 1.10% 3.29% in the private sector, during the 4-year time horizon.Budget impact analysis (BIA) results indicated that the gradual introduction of DUT + TAM FDC, would increase the overall budget of the disease, however providing better clinical outcomes. DUT + TAM FDC drug acquisition cost is partly offset by the reduction in the costs associated with the treatment of the disease.
- Preoperative lymphocyte-to-monocyte ratio predicts clinical outcome in patients undergoing radical cystectomy for transitional cell carcinoma of the bladder: a retrospective analysis. [Journal Article]
- BMC Urol 2014.:76.
Inflammation is a critical component of tumorigenesis, and many cancers arise from sites of infection, chronic irritation, and inflammation. Inflammatory cytokines triggered by tumors alter hematologic components, including neutrophil, lymphocyte, and monocyte counts. The neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios have been shown to be valuable prognostic markers in various types of cancers, including bladder cancer. Risk stratification based on clinicopathologic data is insufficient to support treatment-related choices in patients with bladder cancer. Novel prognostic markers are therefore needed. An elevated pretreatment lymphocyte-to-monocyte ratio (LMR) is reportedly associated with improved overall survival (OS) and a longer time to treatment recurrence (TTR) in some types of cancers. However, these data are lacking in patients with bladder cancer. The aim of the present study was to investigate the effect of the preoperative LMR on OS and TTR in a cohort of patients with bladder cancer.Sixty-eight patients with transitional cell carcinoma of the bladder were included in this retrospective analysis. The associations between a high and low LMR with OS and TTR were analyzed using Kaplan-Meier curves and compared by the log-rank test.In our study cohort, an elevated preoperative LMR was significantly associated with an increased TTR (P = 0.001) and OS (P = 0.020). Patients with an LMR of ≤2.87 showed a median TTR of 2.0 years (95% CI, 0.27-3.73), whereas patients with an LMR of >2.87 had a median TTR of 11.1 years (95% CI, 2.31-19.88) (P = 0.001). Patients with an LMR of ≤2.81 showed a median OS of 2.7 years (95% CI, 0.63-4.70), whereas patients with an LMR of >2.81 had a median OS of 6.0 years (95% CI, 3.60-8.40) (P = 0.020). The clinical stage at diagnosis was the only clinicopathologic feature associated with the LMR, while tumor invasion depth showed borderline significance.The LMR is an easily measured and inexpensive prognostic marker that was significantly correlated with OS and TTR in the present retrospective analysis. However, because of the small sample size in this study, larger multicenter, prospective studies are needed.
- Robotic radical nephrectomy for renal cell carcinoma: a systematic review. [Journal Article]
- BMC Urol 2014.:75.
Laparoscopic radical nephrectomy (LRN) is the actual gold-standard for the treatment of clinically localized renal cell carcinoma (RCC) (cT1-2 with no indications for nephron-sparing surgery). Limited evidence is currently available on the role of robotics in the field of radical nephrectomy. The aim of the current study was to provide a systematic review of the current evidence on the role of robotic radical nephrectomy (RRN) and to analyze the comparative studies between RRN and open nephrectomy (ON)/LRN.A Medline search was performed between 2000-2013 with the terms "robotic radical nephrectomy", "robot-assisted laparoscopic nephrectomy", "radical nephrectomy". Six RRN case-series and four comparative studies between RRN and (ON)/pure or hand-assisted LRN were identified.Current literature produces a low level of evidence for RRN in the treatment of RCC, with only one prospective study available. Mean operative time (OT) ranges between 127.8-345 min, mean estimated blood loss (EBL) ranges between 100-273.6 ml, and mean hospital stay (HS) ranges between 1.2-4.3 days. The comparison between RRN and LRN showed no differences in the evaluated outcomes except for a longer OT for RRN as evidenced in two studies. Significantly higher direct costs and costs of the disposable instruments were also observed for RRN. The comparison between RRN and ON showed that ON is characterized by shorter OT but higher EBL, higher need of postoperative analgesics and longer HS.No advantage of robotics over standard laparoscopy for the treatment of clinically localized RCC was evidenced. Promising preliminary results on oncologic efficacy of RRN have been published on the T3a-b disease. Fields of wider application of robotics should be researched where indications for open surgery still persist.
- Renal surgery for kidney cancer in Germany 2005-2006: length of stay, risk of postoperative complications and in-hospital death. [JOURNAL ARTICLE]
- BMC Urol 2014 Sep 12; 14(1):74.
Representative statistics of surgical care among patients with kidney cancer are scant. With the introduction of the diagnosis related group system in Germany, it is now possible to provide nationwide statistics on surgical care. We studied in-hospital mortality risk in relation to comorbidity and complications, length of hospital stay in relation to surgical approach and comorbidity, and risk of complications in relation to surgical approach among kidney cancer patients undergoing nephrectomy.We analyzed the nationwide hospitalization file of the years 2005 and 2006 including 23,753 hospitalizations with a diagnosis of renal cancer and partial or complete nephrectomy and classified comorbidity (Charlson comorbidity index) and complications. Length of stay, risk of in-hospital complications and in-hospital death were analyzed by linear regression and log-linear regression (relative risks (RR) and 95% confidence intervals (95%CI)).The overall in-hospital mortality was 1.4%. Per one unit increase of the Charlson comorbidity index, the adjusted risk of in-hospital mortality increased by 53% (95%CI 47-59%). The risks of bleeding or acute posthaemorrhagic anemia, respiratory, urological and gastrointestinal complications and infections ranged between 1.1% and 2.7% with the exception of bleeding or acute posthaemorrhagic anemia with 18.4%. Complications were associated with an increased adjusted in-hospital mortality risk. Highest adjusted mortality risk ratios were observed for gastrointestinal (RR = 3.61, 95%CI 2.32-5.63) and urological complications (RR = 3.62, 95%CI 2.62-5.00). The risk of haemorrhage or acute posthaemorrhagic anemia was lower for total laparoscopic nephrectomies than total open nephrectomies. The adjusted risk of gastrointestinal complications was lower for partial open compared to total open nephrectomy (adjusted RR = 0.66, 95%CI 0.45-0.97). Total laparoscopic nephrectomy was associated with shorter length of stay (-3.3 days; 95%CI 2.9-3.7 days) compared to total open nephrectomy. The estimated age-adjusted increase of length of stay per one unit increase of the Charlson comorbidity index was 1.3 days (95%CI 1.2-1.4 days).In this representative population-based analysis, we found that the surgical approach is associated with the risk of complications and length of hospital stay. Furthermore, in the era of ageing populations, renal cancer patients with comorbidities should be counseled about their increased in-hospital mortality risk.
- Renal cell carcinoma with intramyocardial metastases. [JOURNAL ARTICLE]
- BMC Urol 2014 Sep 6; 14(1):73.
Cardiac metastases from renal cell carcinoma without vena caval involvement are extremely rare with a limited number of cases reported in the worldwide literature until now. Nevertheless, this rare location of metastasis may significantly influence patient treatment and prognosis. Cooperation between oncology, cardiology, and urology teams are indispensable in cases of patients suffering from intramyocardial tumors. For these individuals, treatment guidelines based on large-scale studies are unavailable and only case/case series analysis may provide clinicians with decision assistance.In this paper, we report a case of a 50-year-old Caucasian male diagnosed with a 10.2 x 10.3 x 10.0 cm lower pole left renal mass in January 2002. He was subsequently treated with immunochemotherapy, tyrosine kinase inhibitors (TKIs), and mTOR inhibitors (mTORIs) - that is sunitinib, everolimus, and sorafenib. In March 2012, contrast-enhancing tumors in the left myocardium ([empty set]22 mm) and in the interventricular septum ([empty set]26 mm) were seen on CT. Cardiology testing was conducted and the patient was treated with pazopanib with a profound response. Overall survival since the clear cell renal cell carcinoma (ccRCC) diagnosis was 11 years 2 months and since diagnosis of multiple heart metastases was 1 year.Cardiac metastases present a unique disease course in renal cell carcinoma. Cardiac metastases may remain asymptomatic, as in the case of this patient at the time of diagnosis. The most common cardiac presentation of renal cell carcinoma is hypertension, but other cardiac presentations include shortness of breath, cough, and arrhythmias. Targeted systemic therapy with tyrosine kinase inhibitors may be useful for this group of patients, but necrosis in the myocardium can result in tamponade and death. Regular cardiac magnetic resonance imaging scans are required for treatment monitoring.
- Panobinostat synergizes with bortezomib to induce endoplasmic reticulum stress and ubiquitinated protein accumulation in renal cancer cells. [JOURNAL ARTICLE]
- BMC Urol 2014 Aug 30; 14(1):71.
Inducing endoplasmic reticulum (ER) stress is a novel strategy used to treat malignancies. Inhibition of histone deacetylase (HDAC) 6 by the HDAC inhibitor panobinostat hinders the refolding of unfolded proteins by increasing the acetylation of heat shock protein 90. We investigated whether combining panobinostat with the proteasome inhibitor bortezomib would kill cancer cells effectively by inhibiting the degradation of these unfolded proteins, thereby causing ubiquitinated proteins to accumulate and induce ER stress.Caki-1, ACHN, and 769-P cells were treated with panobinostat and/or bortezomib. Cell viability, clonogenicity, and induction of apoptosis were evaluated. The in vivo efficacy of the combination was evaluated using a murine subcutaneous xenograft model. The combination-induced ER stress and ubiquitinated protein accumulation were assessed.The combination of panobinostat and bortezomib induced apoptosis and inhibited renal cancer growth synergistically (combination indexes <1). It also suppressed colony formation significantly (p <0.05). In a murine subcutaneous tumor model, a 10-day treatment was well tolerated and inhibited tumor growth significantly (p <0.05). Enhanced acetylation of the HDAC6 substrate alpha-tubulin was consistent with the suppression of HDAC6 activity by panobinostat, and the combination was shown to induce ER stress and ubiquitinated protein accumulation synergistically.Panobinostat inhibits renal cancer growth by synergizing with bortezomib to induce ER stress and ubiquitinated protein accumulation. The current study provides a basis for testing the combination in patients with advanced renal cancer.
- The impact of tumour size on the probability of synchronous metastasis and survival in renal cell carcinoma patients: a population-based study. [Journal Article]
- BMC Urol 2014; 14(1):72.
The observed low metastatic potential and favorable survival of small incidentally detected renal cell carcinomas (RCCs) have been a part of the rationale for recommending partial nephrectomy as a first treatment option and active surveillance in selected patients. We examined the relationship between tumor size and the odds of synchronous metastases (SMs) (primary outcome) and disease specific survival (secondary outcome) in a nationwide RCC registry.Retrospective study of the 794 RCC patients diagnosed in Iceland between 1971 and 2005. Histological material and TNM staging were reviewed centrally. The presence of SM and survival were recorded. Cubic spline analysis was used to assess relationship between tumor size and probability of SM. Univariate and multivariate statistics were used to estimate prognostic factors for SM and survival.The probability of SM increased in a non-linear fashion with increasing tumor size (11, 25, 35, and 50%) for patients with tumors of ≤4, 4.1-7.0, 7.1-10.0, and >10 cm, respectively. On multivariate analysis, tumor size was an independent prognostic factor for disease-specific survival (HR = 1.05, 95% CI 1.02-1.09, p < 0.001), but not for SM.Tumor size affected the probability of disease-specific mortality but not SM, after correcting for TNM staging in multivariate analysis. This confirms the prognostic ability of the 2010 TNM staging system for renal cell cancer in the Icelandic population.
- Clinical , molecular and cytogenetic analysis of 46, XX testicular disorder of sex development with SRY-positive. [JOURNAL ARTICLE]
- BMC Urol 2014 Aug 28; 14(1):70.
To review the possible mechanisms proposed to explain the etiology of 46, XX sex reversal by investigating the clinical characteristics and their relationships with chromosomal karyotype and the SRY(sex-determining region Y)gene.Five untreated 46, XX patients with SRY-positive were referred for infertility. Clinical data were collected, and Karyotype analysis of G-banding in lymphocytes and Fluorescence in situ hybridization (FISH) were performed. Genomic DNA from peripheral blood of the patients using QIAamp DNA Blood Kits was extracted. The three discrete regions, AZFa, AZFb and AZFc, located on the long arm of the Y chromosome, were performed by multiplex PCRs(Polymerase Chain Reaction) amplification. The set of PCR primers for the diagnosis of microdeletion of the AZFa, AZFb and AZFc region included: sY84, sY86, sY127, sY134, sY254, sY255, SRY and ZFX/ZFY.Our five patients had a lower body height. Physical examination revealed that their testes were small in volume, soft in texture and normal penis. Semen analyses showed azoospermia. All patients had a higher follicle-stimulating hormone(FSH), Luteinizing Hormone(LH) level, lower free testosterone, testosterone level and normal Estradiol, Prolactin level. Karyotype analysis of all patients confirmed 46, XX karyotype, and FISH analysis showed that SRY gene were positive and translocated to Xp. Molecular analysis revealed that the SRY gene were present, and the AZFa, AZFb and AZFc region were absent.This study adds cases on the five new 46, XX male individuals with SRY-positive and further verifies the view that the presence of SRY gene and the absence of major regions in Y chromosome should lead to the expectance of a completely masculinised phenotype, abnormal hormone levels and infertility.
- Histologic and functional outcomes of small intestine submucosa-regenerated bladder tissue. [Journal Article]
- BMC Urol 2014; 14(1):69.
Intestinal bladder augmentation has more disadvantages. One of the most promising alternative methods is tissue engineering in combination with surgical construction. Small intestine submucosa (SIS) is commonly used materials in tissue engineer. The aim of this study is determine the histologic and functional characteristics of SIS as bladder wall replacement in a rabbit augmentation model.18 New Zealand adult male rabbits, weight 2.5 ± 0.5Kg, were used in this study. The rabbits were divided into 3 groups of 6 based on the number of days post-operative (A, 4 weeks; B, 12 weeks; C, 24 weeks). All of the animals underwent urodynamic testing under anesthesia before cystoplasty with SIS patch. The cystometrograms were repeated 4, 12, and 24 weeks after surgery with the same method. SIS-regenerated bladder strips (10 × 3 × 3 mm) and normal bladder strips (10 × 3 × 3 mm) from the same bladder were obtained at 4, 12, and 24 weeks for in vitro detrusor strip study. The frequency and amplitude of the strip over 15 min was recorded. The regenerated tissue and normal tissue underwent histologic and immunocytochemical analysis. The results were quantified as optical density (OD) values.Histologically, the SIS-regenerated bladders of group C (24 weeks post-operation) resembled normal bladder in that all 3 layers (mucosa with submucosa, smooth muscle, and serosa) were present. In the in vitro detrusor strip study, there were no significant differences in autorhythmicity and contractility between regenerated and normal tissues in group C (p > 0.05). Immunohistochemical analysis indicated that the quantity of A-actin grew to a normal level. Urodynamic testing showed that compliance remained stable in all groups post-operatively, and the volume increased 24 weeks post-operatively.Regenerated tissue has similar histologic and functional characteristics. SIS seems to be a viable material in the reconstruction of the rabbit urinary bladder.