An In Vitro Study for the Role of Schizophrenia-Related Potential miRNAs in the Regulation of COMT Gene.

This study aimed to analyze the possible association of miR-30a-5p, miR-30e-5p, and miR-34a-5p identified as potential candidate miRNAs in schizophrenia, with the COMT gene. Candidate miRNAs were obtained from the TargetScan database. The SH-SY5Y human neuroblastoma cell line was used as a cellular model for schizophrenia. miR-30a-5p, miR-30e-5p, and miR-34a-5p mimics were transfected into the SH-SY5Y cell line. Total RNA was isolated from transfected cells and RNA-IP samples and reverse transcripted for miRNA and mRNA analysis. RT-qPCR and western blot were performed to observe changes in expression levels of COMT. RNA-immunoprecipitation was performed to determine RNA-protein interactions after mimic transfection. In the study, it was observed that COMT gene expression levels decreased significantly after miR-30a-5p and miR-34a-5p expressions, whereas increased significantly as a result of miR-30e-5p transfection. RNA-IP data have shown that the amount of COMT pulled down by Ago2 was increased after miR-30a-5p and miR-34a-5p transfections. RNA-IP results revealed that miR-30a-5p and miR-34a-5p are direct targets for the COMT gene.

Exosome inhibition improves response to first-line therapy in small cell lung cancer.

Exosomes are recognized as important mediators of cell-to-cell communication, facilitating carcinogenesis. Although there have been significant advancements in exosome research in recent decades, no drugs that target the inhibition of sEV secretion have been approved for human use. For this study, we employed GW4869 and Nexinhib20 as inhibitors of exosome synthesis and trafficking combined. First, we found that Nexinhib20 and GW4869 effectively inhibited RAB27A and neutral sphingomyelinase 2 (nSMase2) nsMase2. Interestingly, the inhibition of nsMase2 and RAB27A decreased expression of CD9, CD63 and Tsg101, both at RNA and protein levels. We used a combination treatment strategy of cisplatin/etoposide plus GW4869 or Nexinhib20 on small cell lung cancer (SCLC) cell lines. The combination treatment of GW4869 or Nexinhib20 effectively enhanced the inhibitory effects of first-line chemotherapy on the SCLC cells. Furthermore, we demonstrated that reducing exosome release through GW4869 and Nexinhib20 treatment effectively reduced cellular proliferation and significantly induced apoptosis in SCLC cells. Also, we showed that combining exosome inhibition with chemotherapy has a significant synergistic effect on cellular proliferation. We also found increased p53 and p21 expressions with western blot and significantly changing Bax, BCL2, caspase-3 and caspase-9 expressions. Inhibiting the exosome pathway offers opportunities for developing novel, effective treatment strategies for SCLC.

The effects of MYC on exosomes derived from cancer cells in the context of breast cancer.

MYC amplification and overexpression in breast cancer occur 16% and 22%, respectively, and MYC has a linchpin role in breast carcinogenesis. Emerging evidence has started to shed light on central role of MYC in breast cancer progression. On the contrary, tumor-derived exosomes and their cargo molecules are required for the modulation of the tumor environment and to promote carcinogenesis. Still, how MYC regulates tumor-derived exosomes is still a matter of investigation in the context of breast cancer. Here, we investigated for the first time how MYC affects the biological functions of normal breast cells cocultured with exosomes derived from MYC-expression manipulated breast cancer cells. Accordingly, exosomes were isolated from MCF-7 and MDA-MB-231 cells that MYC expression was manipulated through siRNAs or lentiviral vectors by using exosome isolation reagent. Then, normal breast epithelial MCF-10A cells were treated with breast cancer cell-derived exosomes. The cellular activity of MCF-10A was investigated by cell growth assay, wound healing assay, and transwell assay. Our results suggested that MCF-10A cells treated with exosomes derived from MYC-overexpressing breast cancer cells demonstrated higher proliferation and migration capability compared with nontreated cells. Likewise, MCF-10A cells treated with exosomes derived from MYC-silenced cancer cells did not show high proliferation and invasive capacity. Overall, MYC can drive the functions of exosomes secreted from breast cancer cells. This may allow exploring a new mechanism how tumor cells regulate cancer progression and modulate tumor environment. The present study clears the way for further researches as in vivo studies and multi-omics that clarify exosomal content in an MYC-dependent manner.

Myc manipulates the miRNA content and biologic functions of small cell lung cancer cell-derived small extracellular vesicles.

BACKGROUND: MYC genes are amplified/overexpressed in 20% of SCLCs, showing that Myc and Myc-dependent cellular mechanisms are strong candidates as therapeutic targets in SCLC. Small extracellular vesicles support the carcinogenesis process by acting as messengers delivering nucleic acids and proteins-moreover, no reports associate Myc and the functional effect of small extracellular vesicles in small cell lung cancer. METHODS AND RESULTS: After the effects of small extracellular vesicles (sEVs) obtained from H82 and H209 cells on HUVEC and MRC-5 cells were observed, the Myc-dependent effect of the sEVs on oncogenic potentials was further evaluated by manipulating Myc expression via lentiviral vectors in H82 and H209 cells. Then, small extracellular vesicles of Myc-manipulated SCLC cells were isolated using sEVs isolation reagents. Finally, HUVEC and MRC5 cells were treated with SCLC-derived small extracellular vesicles. Cellular activity of recipient normal lung cells was investigated by cell growth assay, wound healing assay, and transwell assay. miRNA composition changes in small extracellular vesicles and SCLC cells were investigated using miRNA microarray and QRT-PCR assay. Our results indicated that normal lung cells treated with SCLC-derived small extracellular vesicles had higher proliferation, migration capability than non-treated counterparts. Additionally, after investigating the potential effects of small extracellular vesicles derived from Myc-dysregulated SCLC cell lines, we further evaluated the Myc-dependent miRNA composition in the small extracellular vesicles. The present study revealed that Myc regulates hsa-miR-7, hsa-miR-9, hsa-miR-125b, hsa-miR-181a_2, hsa-miR-455, hsa-miR-642, and hsa-miR-4417 expressions in SCLC cell lines, not only in cellular but also in exosomal content. CONCLUSIONS: Small extracellular vesicles and MYC are essential targets for therapeutic strategy in SCLC. Our study revealed that the expression level of MYC can affect the function of sEVs and encapsulate the miRNA composition in SCLC. Besides, small extracellular vesicles derived from SCLC cells can modulate normal lung cells.

Therapeutic Effect of Teneligliptin in Drug-Induced Nephrotoxicity: An In-Vitro Study.

Background Drug-induced nephrotoxicity is an important side effect of many commonly used drugs. In this study, we planned to evaluate the effects of teneligliptin (TG), which is a dipeptidyl peptidase-4 (DPP-4) inhibitor, on cell healing by creating nephrotoxicity models in human renal proximal tubule cell and human embryonic kidney epithelial cells cell lines in-vitro with cisplatin, vancomycin, and gentamicin. Methodology First, we determined the 50% inhibitory concentration doses of nephrotoxic drugs and the nephroprotective dose of TG. Then, we analyzed the difference in cell viability, apoptosis, and oxidative stress (reactive oxygen and nitrogen species (ROS/RNS) production) between TG-treated and untreated cells after nephrotoxicity occurred. Moreover, we evaluated the expression of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) in cells. Results We found that when cell lines were treated after toxicity was induced with TG, cell viability increased, apoptosis and ROS/RNS production were significantly decreased, and expressions of KIM-1 and NGAL were significantly reduced. Conclusions This study showed that TG has positive effects on the recovery of drug-induced nephrotoxicity in an in-vitro setting.

Bryonia multiflora Extract Induces Autophagy via Regulating Long Non-coding RNAs in Breast Cancer Cells.

Bryonia multiflora, one of the species of Bryonia L. (Cucurbitaceae) genus, is a perennial, dioecious, herbaceous plant with rhizome-shaped roots. Bryonia species have anti-inflammatory, antimicrobial, cytotoxic, antioxidant, etc., activities and their components consume antitumoral effects. Purpose of the study to investigate the effect of Bryonia Multiflora extract (BMST) on breast cancer cells. Our results revealed that MCF-7 and MDA-MB-231 cells underwent significant morphological changes leading to cell rounding. No significant changes were observed in the cell viability by MTT. Acridine orange staining of our cells gave rise to think that BMST might lead our cells to autophagy. Therefore, possible molecular mechanisms underlying morphological changes such as autophagy (LC-3B, Beclin, AMBRA1) and apoptosis (Bcl-2) were evaluated on mRNA and protein levels. BMST treated MCF-7 and MDA-MB-231 cells had increased levels of autophagy markers whereas decreased levels of Bcl-2. p21 levels were also found to be increased in both cells. Analysis of lncRNA expressions has shown that BMST treatment led to changes in the expression levels of several lncRNAs playing roles in autophagy. The current study has shown that BMST induces autophagy in MCF-7 and MDA-MB-231 cells via regulating the lncRNAs revealing that BMST could be a promising therapeutic agent.

lncRNAs as Potential Targets in Small Cell Lung Cancer: MYC -dependent Regulation.

BACKGROUND: Small Cell Lung Cancer (SCLC) is a highly aggressive malignancy. MYC family oncogenes are amplified and overexpressed in 20% of SCLCs, showing that MYC oncogenes and MYC regulated genes are strong candidates as therapeutic targets for SCLC. c-MYC plays a fundamental role in cancer stem cell properties and malignant transformation. Several targets have been identified by the activation/repression of MYC. Deregulated expression levels of lncRNAs have also been observed in many cancers. OBJECTIVE: The aim of the present study is to investigate the lncRNA profiles which depend on MYC expression levels in SCLC. METHODS: Firstly, we constructed lentiviral vectors for MYC overexpression/inhibition. MYC expression is suppressed by lentiviral shRNA vector in MYC amplified H82 and N417 cells, and overexpressed by lentiviral inducible overexpression vector in MYC non-amplified H345 cells. LncRNA cDNA is transcribed from total RNA samples, and 91 lncRNAs are evaluated by qRT-PCR. RESULTS: We observed that N417, H82 and H345 cells require MYC for their growth. Besides, MYC is not only found to regulate the expressions of genes related to invasion, stem cell properties, apoptosis and cell cycle (p21, Bcl2, cyclinD1, Sox2, Aldh1a1, and N-Cadherin), but also found to regulate lncRNAs. With this respect, expressions of AK23948, ANRIL, E2F4AS, GAS5, MEG3, H19, L1PA16, SFMBT2, ZEB2NAT, HOTAIR, Sox2OT, PVT1, and BC200 were observed to be in parallel with MYC expression, whereas expressions of Malat1, PTENP1, Neat1, UCA1, SNHG3, and SNHG6 were inversely correlated. CONCLUSION: Targeting MYC-regulated genes as a therapeutic strategy can be important for SCLC therapy. This study indicated the importance of identifying MYC-regulated lncRNAs and that these can be utilized to develop a therapeutic strategy for SCLC.

The Early Histological Effects of Intravesical Instillation of Platelet-Rich Plasma in Cystitis Models.

PURPOSE: To evaluate the early histological effects of the intravesical instillation of platelet-rich plasma (PRP) in rabbit models of interstitial and hemorrhagic cystitis. METHODS: Thirty-six rabbits were classified into 6 groups: saline (S), S+PRP, hydrochloric acid (HCl), HCl+PRP, cyclophosphamide (CyP), and CyP+PRP. At 48 hours after induction, PRP was prepared and intravesically administered to the S+PRP, HCl+PRP, and CyP+PRP groups. Bladder sections were stained with toluidine blue for mast cell counting and with hematoxylin and eosin for histopathology and mitotic index determination. The proliferation index was determined by proliferating cell nuclear antigen (PCNA) immunolabeling. The nonparametric Mann-Whitney U-test was used for statistical analysis. RESULTS: No abnormalities were observed in the S group, whereas increased interstitial edema and increased average mitotic and proliferation indices were observed in the S+PRP group (P=0.023, P=0.004, and P=0.009, respectively). Intense epithelial loss, hemorrhage, and leukocyte infiltration were detected in the HCl and HCl+PRP groups, whereas a significantly increased average mitotic index was observed in the HCl+PRP group (P=0.002). When compared with its CyP counterpart, a significant reduction in hemorrhage and an increase in leukocyte infiltration and mitotic index were observed in the CyP+PRP group (P=0.006, P=0.038, and P=0.002, respectively). In addition, PCNA staining revealed a significantly increased proliferation index in the HCl+PRP and CyP+PRP groups (P=0.032 and P=0.015, respectively). CONCLUSIONS: The intravesical instillation of PRP increased the mitotic index in the saline and cyclophosphamide groups while decreasing macroscopic bleeding.

Factors affecting complication rates of percutaneous nephrolithotomy in children: results of a multi-institutional retrospective analysis by the Turkish pediatric urology society.

PURPOSE: We assessed factors affecting complication rates of percutaneous nephrolithotomy in children. MATERIALS AND METHODS: We retrospectively evaluated data on 1,205 renal units in 1,157 children treated with percutaneous nephrolithotomy at 16 Turkish centers between 1991 and 2012. Of the patients 28.3% had a history of urolithiasis. Complications were evaluated according to the Satava classification system and modified Clavien grading system. Univariate and multivariate analyses were done to determine predictive factors affecting complication rates. RESULTS: A total of 515 females and 642 males were studied. Mean ± SD patient age was 8.8 ± 4.7 years (range 4 months to 17 years). Mean ± SD stone size, operative time and postoperative hospital stay were 4.09 ± 4.06 cm(2), 93.5 ± 48.6 minutes and 5.1 ± 3.3 days, respectively. Postoperative stone-free rate was 81.6%. A total of 359 complications occurred in 334 renal units (27.7%). Complications were intraoperative in 118 cases and postoperative in 241. While univariate analysis revealed that stone history, positive urine culture, operative time, length of hospitalization, treatment success, punctured calyx and location of the stone significantly affected the complication rates (p <0.05), operative time, sheath size, mid calyceal puncture and partial staghorn formation were the statistically significant parameters affecting complication rates on multivariate logistic regression analysis. CONCLUSIONS: Percutaneous nephrolithotomy is the treatment of choice for most renal calculi in children. The technique is effective and safe in children, with a high success rate and a low rate of major complications. The significant factors identified should be considered by clinicians to decrease associated complication rates.

Autologous blood-clot embolisation of cavernosal artery pseudoaneurysm causing delayed high-flow priapism.

BACKGROUND: High-flow priapism is a rare condition characterized by a prolonged and painless erection. Since it may permanently impair erectile function, it must be managed and treated as soon as possible, in order to restore potency. The case we are presenting here was successfully treated by embolizing the penile artery using an autologous clot. CASE REPORT: A case of delayed painless high-flow priapism that occured after blunt straddle-type perineal trauma, that was persistent for more than 30 days is being presented. Doppler ultrasonographic examination of the cavernosal artery revealed a 1.5 cm-diameter pseudoaneurysm at the right cavernosal artery, together with a high-velocity shunt between the two cavernous arteries. Extravasation from the proximal sites of both of the cavernous arteries and a right cavernosal artery pseudoaneurysm was detected on angiography. The patient was successfully treated by embolization of the penile artery with an autologous clot in two sessions with a 3-day interval. CONCLUSIONS: This experience along with a survey of the literature made us conclude that embolization of cavernous artery by means of an autologous clot is a very effective procedure and a method of choice for treatment of high-flow priapism and for restoration of penile erectile function. What makes our case even more interesting and important, is the fact that priapism of one month's duration could well be treated by means of this method.

The role of varicocele treatment in the management of non-obstructive azoospermia.

The literature on male reproductive medicine is continually expanding, especially regarding the diagnosis and treatment of infertility due to non-obstructive azoospermia. The advent of in vitro fertilization with intracytoplasmic sperm injection has dramatically improved the treatment of male infertility due to nonobstructive azoospermia. Assisted reproduction using testicular spermatozoa has become a treatment of hope for men previously thought to be incapable of fathering a child due to testicular failure. In addition, numerous studies on non-obstructive azoospermia have reported that varicocelectomy not only can induce spermatogenesis but can also increase the sperm retrieval rate; however, the value of varicocelectomy in patients with non-obstructive azoospermia still remains controversial. The purpose of this review is to present an overview of the current status of varicocele repair in men with non-obstructive azoospermia.

Upper urinary tract transitional cell carcinoma: is there a best?

BACKGROUND: This study aimed to determine the prognostic and risk factors for bladder and systemic recurrence after nephroureterectomy (NU) in patients with upper urinary tract (UUT) transitional cell carcinoma (TCC). PATIENTS AND METHODS: Data from 101 patients with nonmetastatic UUT TCC who underwent NU between 1987 and 2009 were retrospectively evaluated. Kaplan-Meier curves for sex, age, anemia, smoking, stone disease, or history of bladder tumor, primary tumor localization, multiplicity, and disease stage and grade were constructed to predict 5-year recurrence-free survival (RFS). Multivariate Cox regression analysis was used to identify independent risk factors for recurrence. RESULTS: Bladder, distant, and local recurrence rates at a mean of 56.19 ± 5.30 months after NU were 38.5%, 19.8%, and 7.9%, respectively. Univariate analysis showed that among the patients with bladder recurrence, female patients had significantly lower 5-year RFS than did male patients (34.7% ± 0.13% vs. 62.4% ± 0.06%, P = .038); however multivariate analysis showed that both female sex and a history of smoking were independent risk factors for bladder recurrence (odds ratio [OR], 4.22; 95% confidence interval [CI], 1.56-11.4; P = 0.005 and OR, 2.84; 95% CI, 1.1-7.4; P = .032, respectively). Univariate analysis showed that among the patients with local and distant recurrence, anemia, a positive history of bladder tumor, localization of the primary tumor, multiplicity, disease stage, and tumor grade significantly affected RFS, whereas primary tumor stage and grade were the only independent risk factors for 5-year RFS (OR, 4.48; 95% CI, 1.45-13.79; P = .009 and OR, 5.82; 95% CI, 2.08-16.26; P = .001, respectively). CONCLUSION: Female sex and a history of smoking were independent risk factors for bladder recurrence after NU. Such patients should be monitored closely using cystoscopy and urine cytologic examination. Invasive and higher grade UUT TCC was associated with worse local or systemic RFS.

The role of varicocele treatment in the management of non-obstructive azoospermia

The literature on male reproductive medicine is continually expanding, especially regarding the diagnosis and treatment of infertility due to non-obstructive azoospermia. The advent of in vitro fertilization with intracytoplasmic sperm injection has dramatically improved the treatment of male infertility due to nonobstructive azoospermia. Assisted reproduction using testicular spermatozoa has become a treatment of hope for men previously thought to be incapable of fathering a child due to testicular failure. In addition, numerous studies on non-obstructive azoospermia have reported that varicocelectomy not only can induce spermatogenesis but can also increase the sperm retrieval rate; however, the value of varicocelectomy in patients with non-obstructive azoospermia still remains controversial. The purpose of this review is to present an overview of the current status of varicocele repair in men with non-obstructive azoospermia.

Prevalence and predictors of benign lesions in renal masses smaller than 7 cm presumed to be renal cell carcinoma.

UNLABELLED: The present study was designed to determine the incidence and predictive factors of benign renal lesions in 450 patients who underwent surgical removal of solitary renal masses <7 cm in diameter. Of the 450 renal masses, 88 (19.9%) were benign lesions. Female sex, nephron-sparing surgery, surgery between 1990 and 1996, cystic components on imaging, and small tumors (<4 cm) were independently associated with benign pathology. PURPOSE: To determine the association between preoperative parameters with final benign pathology in patients who underwent surgical removal of solitary renal masses <7 cm in diameter. MATERIALS AND METHODS: A database of 450 patients without metastatic disease who underwent radical nephrectomy or nephron-sparing surgery (NSS) for removal of renal masses <7 cm between January 1990 and December 2009 was reviewed. Age, sex, symptoms, year and type of surgery, solid or cystic appearance, and tumor size were analyzed as presumed predictors of benign pathology. Multivariate analysis was performed to identify parameters associated with benign pathology. RESULTS: In all, 88 (19.9%) of the tumors were benign, including 39 (8.7%) oncocytomas and 22 (4.9%) angiomyolipomas. The benign lesion rate for tumors ≤2, 2.1-4, and 4.1-7 cm was 30.3%, 27.1%, and 12.5%, respectively (2P < .001). For the periods of 1990-1996, 1997-2003, and 2004-2009, the frequency of benign tumors was 25%, 17.3%, and 18.4% (2P = .271), the incidental tumor rate was 48.1%, 60.4%, and 63.8% (2P = .027), mean tumor size was 5, 4.6, and 4.1 cm (2P < .001), and the NSS rate was 28.8%, 43.2%, and 52.7% (2P < .001), respectively. Logistic regression analysis revealed that female sex, NSS, surgery between 1990 and 1996, cystic components on imaging, and small tumors (<4 cm) based on radiologic examination were independently associated with benign pathology (odds ratio [OR] = 3.26, 2.56, 2.43, 2.41, and 1.96, respectively). CONCLUSIONS: The incidence of incidental and small tumors amenable to NSS increased over time. Female sex was the strongest predictor of benign pathology.

Laparoscopic pyeloplasty in adults: stented versus stentless.

INTRODUCTION: In this study, we aimed to investigate the efficacy and feasibility of stentless laparoscopic pyeloplasty (LP), compared with the stented counterpart. MATERIALS AND METHODS: We compared the results of stented and stentless LP procedures performed at two centers. The indications included symptoms such as loin pain or urinary tract infection with documented obstruction on renal scintigraphy. Transperitoneal approach was standard for both techniques. The stented and stentless patient groups were compared with regard to surgical duration, length of hospital stay, postoperative symptomatology, complications, and radiologic and scintigraphic findings. RESULTS: Twenty-seven patients with stentless pyeloplasty with at least 6 months of follow-up were included in the study and compared with a matched group of 21 stented LP patients. All had Anderson-Hynes dismembered pyeloplasty. Mean operative time was 151.9 minutes and 144.6 minutes in the stented and stentless groups, respectively (p > 0.05). Mean drain removal time and hospital stay were 1.9 days (range: 1-9 days) and 3.4 days (range: 2-9 days) in the stented group, respectively, and 2 days (range: 1-10 days) and 3.1 days (range: 1-10 days) in the stentless group, respectively (p > 0.05). Renal scintigraphy studies improved in 14 patients in the stented group and in 22 patients in the stentless group during the 6-month follow-up. Symptoms completely resolved in 19 of the stented and in 24 of the stentless cases. CONCLUSION: Stentless LP is a feasible technique as its stented counterpart. Although it has a relatively high prolonged leakage risk, it could be performed without compromising the success rate by experienced surgeons.

Presence of teratoma in orchiectomy specimen increases the need for postchemotherapy RPLND.

OBJECTIVES: This study was carried out to evaluate the impact of the presence of teratomatous component in orchiectomy specimen on complete response rates to primary chemotherapy in a large series of patients with stage II nonseminomatous germ cell tumors (NSGCT). MATERIALS AND METHODS: Chemotherapy was administered to 113 patients with stage II testicular NSGCT. Resection of retroperitoneal residual tumor masses was performed in all patients with partial response to chemotherapy. Patients were categorized into 2 groups according to presence or absence of teratomatous component in the primary orchiectomy specimen. RESULTS: Of patients with teratomatous component in the orchiectomy specimen, 32.1% (17/53) had complete response to primary chemotherapy and of those without teratomatous component 55% (33/60) had complete response (P = 0.022). Stage IIC patients had lower response rate 28.8% (23/80) compared with IIA and IIB patients (P = 0.0001). Teratomatous elements were found in retroperitoneal mass in 70.6% of patients with teratomatous component in orchiectomy specimens compared to 36.8% of patients without teratomatous component (P = 0.022). After retroperitoneal surgery and additional treatments, complete response rate increased to 92.4% and 89.5% in patients with and without teratomatous component in primary pathology, respectively, (P > 0.05). CONCLUSIONS: Since teratomatous component in orchiectomy specimen is a predictor of teratoma in the residual retroperitoneal mass, it decreases the response rate to primary chemotherapy and increases the need for postchemotherapy retroperitoneal lymph node dissection (RPLND) in metastatic NSGCT patients.

Tubeless mini percutaneous nephrolithotomy in infants and preschool children: a preliminary report.

PURPOSE: We retrospectively analyzed the outcomes of tubeless mini percutaneous nephrolithotomy in infants and preschool children, and compared them with age matched controls who underwent nephrostomy drainage. MATERIALS AND METHODS: A total of 28 renal units in 26 children were operated on for stone disease using the mini percutaneous nephrolithotomy technique. Holmium laser and pneumatic lithotriptor were used for stone fragmentation. Children who underwent complete stone removal and had a clear nephrostomy tract only had a ureteral catheter placed. Those with residual stones or bleeding from the nephrostomy tract underwent nephrostomy drainage. We compared both groups with regard to patient and stone characteristics, and postoperative findings. RESULTS: A total of 12 renal units had only a ureteral catheter for diversion, while 16 had nephrostomy drainage. Mean respective ages of the stentless and nephrostomy groups were 3 (range 0.58 to 6) and 3.3 years (1.5 to 6). Mean respective stone burdens were 192 (range 100 to 400) and 416 (775 to 1,380) mm2. Surgery and fluoroscopy times were shorter in the tubeless group. Complication rates were higher (6 of 14 vs 0 of 12) and duration of hospitalization was longer (4.9 [range 3 to 14] vs 3.1 days [2 to 6]) in the nephrostomy group. Stone-free rates were 91.6% in the tubeless and 78.5% in the nephrostomy groups. CONCLUSIONS: Tubeless percutaneous nephrolithotomy was observed to be a safe option for selected children with stone disease. The success and safety of tubeless percutaneous nephrolithotomy depends on patient selection criteria, including low volume and infection-free stones that are removed completely without any bleeding from the access tract.

Sildenafil attenuates renal ischemia reperfusion injury by decreasing leukocyte infiltration.

The aim of the study was to investigate the effects of sildenafil citrate (SC) on renal ischemia reperfusion (I/R) injury in a rat model. Forty eight male Wistar albino rats were randomly assigned into six groups: sham, ischemia, I/R, SC+sham, SC+ischemia and SC+I/R. In the I/R groups, the right kidney was removed and the artery and vein of the left kidney were clamped for 45 min followed by reperfusion for 1 h. In the SC-treated groups, SC dissolved in saline solution was given as a single dose (1 mg/kg) 60 min before the operation. Renal histology was analyzed by scoring the tubular damage and neutrophil infiltration. Tissue myeloperoxidase activity and lipid peroxidation were analyzed. The histological damage and the neutrophil infiltration induced by I/R were significantly less in the SC+I/R group (p = 0.004 and p = 0.003, respectively). Pretreatment with SC significantly diminished the tissue myeloperoxidase activity, indicating the prevention of the neutrophil sequestration into the kidney in the SC+I/R group (p = 0.004); however, it did not result in any changes in lipid peroxidation. Our results in a rat model of ischemia-reperfusion indicate that pre-ischemic treatment with sildenafil citrate can significantly attenuate ischemia/reperfusion-induced renal injury by decreasing leukocyte infiltration.

Renal cell carcinoma with inferior vena cava thrombus: the Hacettepe experience.

OBJECTIVES: We evaluated the clinical outcome and factors affecting survival in patients with renal cell carcinoma (RCC) and tumor thrombus involving inferior vena cava (IVC). METHODS: Between 1990 and 2007, 28 patients with RCC and tumor thrombus extending into IVC underwent radical nephrectomy and thrombectomy. Patient data were reviewed retrospectively to evaluate the demographics, clinical presentation, surgical approach, pathological features, clinical outcomes, and survival. RESULTS: Twenty-eight patients with a mean age of 52.7 years were operated. Thrombus level was infrahepatic in 15 patients (54%), intrahepatic in 3 patients (10%), suprahepatic in 3 patients (10%), supradiaphragmatic in 2 patients (8%), and intracardiac in 5 patients (18%). All patients with intracardiac thrombi underwent cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA). The mean tumor size was 98.21 mm. Four patients had distant metastases and 3 patients had lymph node involvement. Pathological examination revealed RCC of clear cell type in 26 patients, papillary in 1 and chromophobe in 1 patient. At a mean follow-up of 36.4 months, 16 patients were still alive while 8 patients died due to disease progression and 2 patients died of other causes. Two patients died of pulmonary emboli in the early postoperative period. Lymph node involvement, distant metastases, hypercalcemia, and sarcomatoid component were found to be factors affecting overall survival significantly. Level of tumor thrombus and Fuhrman grade did not affect survival. CONCLUSIONS: Radical nephrectomy and tumor thrombectomy is currently known to be the most effective method in patients with RCC and tumor thrombus extending into IVC. Factors affecting survival are the ones related to tumor biology. Tumor thrombus level does not affect the prognosis.