Metabolomic profile of glycolysis and the pentose phosphate pathway identifies the central role of glucose-6-phosphate dehydrogenase in clear cell-renal cell carcinoma.

The analysis of cancer metabolome has shown that proliferating tumor cells require a large quantities of different nutrients in order to support their high rate of proliferation. In this study we analyzed the metabolic profile of glycolysis and the pentose phosphate pathway (PPP) in human clear cell-renal cell carcinoma (ccRCC) and evaluate the role of these pathways in sustaining cell proliferation, maintenance of NADPH levels, and production of reactive oxygen species (ROS). Metabolomic analysis showed a clear signature of increased glucose uptake and utilization in ccRCC tumor samples. Elevated levels of glucose-6-phosphate dehydrogenase (G6PDH) in association with higher levels of PPP-derived metabolites, suggested a prominent role of this pathway in RCC-associated metabolic alterations. G6PDH inhibition, caused a significant decrease in cancer cell survival, a decrease in NADPH levels, and an increased production of ROS, suggesting that the PPP plays an important role in the regulation of ccRCC redox homeostasis. Patients with high levels of glycolytic enzymes had reduced progression-free and cancer-specific survivals as compared to subjects with low levels. Our data suggest that oncogenic signaling pathways may promote ccRCC through rerouting the sugar metabolism. Blocking the flux through this pathway may serve as a novel therapeutic target.

Pre-existing type 2 diabetes mellitus is an independent risk factor for mortality and progression in patients with renal cell carcinoma.

Malignancies are one of the main causes of mortality in diabetic patients; however, to date, very limited data have been reported on the specific influence of type 2 diabetes mellitus (T2DM) on the survival of patients with renal cell carcinoma (RCC). In the present long-term retrospective study, we investigated whether T2DM may influence the overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) in patients with surgically treated RCC. Medical records of 924 patients treated by radical or partial nephrectomy for sporadic, unilateral RCC were reviewed. Patients with type-1 DM and with T2 DM receiving insulin treatment were excluded. Survival estimates were calculated according to the Kaplan-Meier method and compared with the log-rank test. Univariate and multivariate analyses were performed using the Cox regression model.Of the 924 RCC patients, 152 (16.5%) had T2DM. Mean follow-up was 68.5 months. Mean OS was 41.3 and 96.3 months in T2DM and non-T2DM patients, respectively (P < 0.0001).The estimated CSS rates at 1, 3, and 5 years in T2DM versus non-T2DM patients were 63.4% versus 76.7%, 30.4% versus 56.6%, and 16.3% versus 48.6%, respectively (P = 0.001). Mean PFS was significantly lower (31.5 vs 96.3 months; P < 0.0001) in the T2DM group. At multivariate analysis, T2DM was an independent adverse prognostic factor for OS (hazard ratio [HR]  = 3.44; 95% confidence interval [CI]:2.40-4.92), CSS (HR = 6.39; 95% CI: 3.78-10.79), and PFS (HR = 4.71; 95% CI: 3.11-7.15). In conclusion, our findings suggest that patients with RCC and pre-existing T2DM have a shorter OS, increased risk of recurrence, and higher risk for kidney cancer mortality than those without diabetes.

CTR2 identifies a population of cancer cells with stem cell-like features in patients with clear cell renal cell carcinoma.

PURPOSE: In clear cell renal cell carcinoma tissue samples we identified and characterized a population of renal cell carcinoma derived CD133+/CD24+ cancer cells. We studied differences between these cells and their nonneoplastic counterpart, tubular adult renal progenitor cells. MATERIALS AND METHODS: CD133+/CD24+ renal cell carcinoma derived cells were isolated from 40 patients. The mesenchymal phenotype and stemness proteomic profile of these renal cell carcinoma derived cells were characterized. Colony forming efficiency and self-renewal ability were tested by limiting dilution. Tumorigenic properties were evaluated in vitro by soft agar assay. The angiogenic response was evaluated in vivo by the chorioallantoic membrane angiogenic assay. Microarray analysis was performed on 6 tubular adult renal progenitor cell and 6 renal cell carcinoma derived cell clones. Membrane protein expression was evaluated by flow cytometry and immunofluorescence staining. RESULTS: CD133+/CD24+ cells were isolated from normal and tumor kidney tissue. Fluorescence activated cell sorting revealed that renal cell carcinoma derived cells did not express mesenchymal stem cell markers. CD133+/CD24+ tumor cells were more undifferentiated than tubular adult renal progenitor cells. Renal cell carcinoma derived cells were clonigenic and could differentiate into adipocytes, epithelial and osteogenic cells. They could also regenerate tumor cells in vitro and induce angiogenesis in vivo. Gene expression profile identified CTR2 as a membrane marker for this neoplastic population. CTR2 was involved in renal cell carcinoma derived cell cisplatin resistance. CONCLUSIONS: Our results indicate the presence of a CD133+/CD24+/CTR2+ cancer cell population in clear cell renal cell carcinoma. These cells have some stem cell-like features, including in vitro self-maintenance and differentiating capabilities, and they can induce an angiogenic response in vivo.

Diagnostic and prognostic role of preoperative circulating CA 15-3, CA 125, and beta-2 microglobulin in renal cell carcinoma.

CA 15-3, CA 125 and ß-2 microglobulin are three common tumor markers currently used for diagnosis, prognosis, assessment of therapeutic response, and/or to evaluate recurrence in breast and ovarian cancer and malignant lymphoproliferative disorders, respectively. In the present prospective study we assessed the role of these three serum proteins as biomarkers for renal cell carcinoma (RCC), as well as any association between tumor marker levels and clinical-pathological parameters. CA 15-3, CA 125, and ß-2 microglobulin were preoperatively measured in 332 patients who underwent nephrectomy for RCC. Estimates of cancer-specific survival (CSS) was calculated according to the Kaplan-Meier method. Multivariate analysis was performed to identify the most significant variables for predicting CSS. Preoperatively, 35.2% (n = 117), 9.6% (n = 32) and 30.4% (n = 101) of the patients had abnormal levels of CA 15-3, CA 125 and ß-2 microglobulin, respectively. Statistically significant differences resulted between CA 15-3, CA 125 and ß-2 microglobulin values and tumor size, Fuhrman grade, presence of lymph node, and visceral metastases. CSS was significantly decreased for patients with high levels of CA 15-3, CA 125, and ß-2 microglobulin (P < 0.0001, P < 0.0001, and P = 0.001, resp.). At multivariate analysis only age, the presence of visceral metastases, and high levels of CA 15-3 were independent adverse prognostic factors for CSS.

Impact of donor-recipient gender on kidney graft and patient survival: short- and long-term outcomes.

PURPOSE: Donor and recipient gender influence on post-transplant kidney and patient survival is still controversial, and the literature data do not present unanimous conclusions. The aim of this study was to evaluate the effect of gender disparities between donor and recipient in 963 kidney transplants performed at our center from January 2000 to December 2010. METHODS: The patients were subdivided into four groups according to recipient and donor gender: male donor-to-male recipient (MDMR; n = 305), male donor-to-female recipient (MDFR; n = 203), female donor-to-female recipient (FDFR; n = 206), and female donor-to-male recipient (FDMR; n = 249). Independent sample's t test and one-way ANOVA were used for statistical analyses. Graft and patient survival were calculated by the Kaplan-Meier method and compared using the log rank test. RESULTS: There were no statistically significant differences between the groups with regard to age, cold ischemia time, delayed graft function, primary non-function, and episodes of acute and chronic rejection. Moreover, no difference in either graft (p = 0.92) or patient (p = 0.41) survival at 1, 3, and 5 years was observed. However, female recipients had significantly lower serum creatinine values and higher estimated GFR, particularly if they received a male donor kidney, and these findings were stable up to 3-year post-transplantation. CONCLUSIONS: No impact of gender on short- or long-term graft and patient survival was observed in deceased kidney transplantation. However, we report a lower creatinine level in the male donors to female recipients group as compared with other recipient-donor gender combinations, although this difference loses statistical significance after the third-year post-transplantation.

Predictive value of resistive index in graft survival after kidney transplant.

INTRODUCTION: The intrarenal resistance index (RI) is a calculated parameter for the assessment of the status of the graft during the follow-up ultrasound of the transplanted kidney. Currently it is still unclear the predictive value of RI, also in function of the time. MATERIALS AND METHODS: We retrospectively investigated the correlation between the RI and the graft survival (GS) and the overall survival (OS) after transplantation. We evaluated 268 patients transplanted between 2003 and 2011, the mean followup was 73 months (12-136). The RI was evaluated at 8 days, 6 months, 1 year and 3 years. The ROC analysis was used to calculate the predictive value of RI and the Kaplan Mayer curves was used to evaluated the OS and PS. RESULTS: The ROC analysis, correlated to the GS, identified a value of RI equal to 0.75 as a cut-off. All patients was stratified according to the RI at 8 days (RI ≤ 0,75: 212 vs RI > 0.75: 56), at 6 months (RI ≤ 0.75: 237 vs RI > 0.75: 31), at 1 year (RI ≤ 0.75: 229 vs RI > 0.75: 39) and at 3 years (RI ≤ 0.75: 224 vs RI > 0.75: 44). The RI showed statistically significant differences between the two groups in favor of those who had an RI ≤ 0.75 only at 8 days and at 6 moths (p = 0.0078 and p = 0.02 to 8 days to 6 months) on the GS. On the contrary, we observed that the RI estimated at 1 year and 3 years has not correlated with the GS. The same RI cut-off was correlate with PS after transplantation. We observed that there are no correlations between the RI and OS. CONCLUSIONS: The RI proved to be a good prognostic factor on survival organ when it was evaluated in the first months of follow- up after transplantation. This parameter does not appear, however, correlate with OS of the transplanted subject.

Capillary hemangioma of the scrotum mimicking an epididymal tumor: case report.

We report a case of capillary hemangioma of the scrotum. A 52-year-old male presented with a left scrotum swelling that had arisen suddenly two months before. Scrotal ultrasound revealed a dishomogeneous mass in the left scrotum. The mass demonstrated blood flow in the color Doppler mode. Scrotal mass excision was performed. Pathological evaluation revealed a capillary hemangioma.

Spondin-2, a secreted extracellular matrix protein, is a novel diagnostic biomarker for prostate cancer.

PURPOSE: SPON2 belongs to the F-spondin family of secreted extracellular matrix proteins. It is deregulated in some tumors, including prostate cancer. In this prospective study we assessed the role of serum SPON2 as a biomarker for prostate cancer diagnosis as well as any association between SPON2 levels and clinicopathological features. We also compared the diagnostic performance of this biomarker to that of serum sarcosine, and percent free-to-total and total prostate specific antigen. MATERIALS AND METHODS: SPON2 was measured using a sandwich enzyme linked immunosorbent assay in serum samples from 286 patients with prostate cancer and 68 with no evidence of malignancy, as confirmed by 10 to 12-core ultrasound guided prostate biopsy. Nonparametric statistical tests and ROC analysis were done to assess the diagnostic performance of SPON2 vs the other biomarkers. RESULTS: Median serum SPON2 was significantly higher in patients with prostate cancer than in those with no evidence of malignancy (77.5 vs 23.6 ng/ml, p<0.0001). ROC analysis showed a higher predictive value of SPON2 (AUC 0.952) than of serum sarcosine (AUC 0.674), percent free-to-total prostate specific antigen (AUC 0.806) and total prostate specific antigen (AUC 0.561). Moreover, patients with low grade prostate cancer had higher median SPON2 levels (p=0.001). Spearman rank correlation confirmed a negative association with Gleason score (rs=-0.29, p=0.0005). CONCLUSIONS: We found evidence that SPON2 levels were significantly higher in patients with prostate cancer than in healthy individuals. Moreover, this biomarker had better diagnostic performance than serum sarcosine, and percent free-to-total and total prostate specific antigen. This greater accuracy was also present in a subset of patients with normal prostate specific antigen.

Serum sarcosine is a risk factor for progression and survival in patients with metastatic castration-resistant prostate cancer.

AIM: Sarcosine has been identified as a differential metabolite that is greatly increased during progression from normal tissue to prostate cancer and metastatic disease. In this study we assessed the role of serum sarcosine in metastatic castration-resistant prostate cancer (mCRPC) patients. PATIENTS & METHODS: Data from 52 mCRPC patients treated with docetaxel-based chemotherapy were retrospectively analyzed. Receiver operating characteristic curves, and Kaplan-Meier and Cox multivariate analyses were performed. RESULTS: Median sarcosine values were significantly higher in mCRPC versus non-mCRPC patients (0.81 vs 0.52 nmol/µl; p < 0.0001). A significant correlation resulted between serum sarcosine levels and the duration of hormone sensitivity (Spearman's correlation coefficient: -0.51; p = 0.001). At multivariate analysis sarcosine was an independent prognostic factor of outcome in terms of overall and progression-free survival. CONCLUSION: Serum sarcosine values were significantly increased in patients with metastatic disease. Moreover, this biomarker is a risk factor for progression and survival in chemotherapy-treated mCRPC patients.

Impact of transplant nephrectomy on retransplantation: a single-center retrospective study.

PURPOSE: Kidney retransplantation is the best treatment option for transplanted patients returning to dialysis. The aim of this study was to explore the effect of removal of a failed graft on the outcome of a subsequent transplant. METHODS: We identified 140 patients who underwent retransplantation at our institution. Retrospective comparison was performed between patients undergoing kidney retransplantation with (group A, n = 28) and without (group B, n = 112) preliminary nephrectomy. Graft and patient survival were calculated by the Kaplan-Meier method. RESULTS: After a mean follow-up of 64.5 months, patients survival was comparable between the two groups (group A = 68.6 vs. group B = 63.5 months; p = 0.6). Mean graft survival was 65.5 versus 56.0 months in group A and B, respectively (p = 0.14). Surgical complications after retransplantation were significantly higher in group A compared to group B (57.1 vs. 19.6 %; p = 0.0002). There was no significant difference between the two groups in the panel reactive antibody level at the time of retransplantation (group A = 20 % vs. group B = 32 %; p = 0.22). The acute rejection rate was 35.7 % in group A and 25 % in group B (p = 0.36). The risk of delayed graft function was not significantly increased in group A (p = 0.63). Finally, 2 years after retransplantation, patients who had not undergone nephrectomy had lower serum creatinine concentrations (1.3 vs. 1.7 mg/dl; p = 0.01) and higher estimated GFR (77.9 vs. 59.3 ml/min/1.73 m(2); p = 0.02). CONCLUSION: Our experience shows that there is no advantage in performing allograft nephrectomy before retransplantation, and that this procedure does not seem to significantly influence the survival of a subsequent graft.

Delayed relief of ureteral obstruction is implicated in the long-term development of renal damage and arterial hypertension in patients with unilateral ureteral injury.

PURPOSE: A delay in the diagnosis and treatment of iatrogenic obstructive ureteral injury is the most important prognostic factor for worse results in terms of lesion repair and renal function recovery. The role of the time of relief in determining the onset of renal failure and arterial hypertension in patients with obstructive ureteral injury was evaluated. In addition, we analyzed the prognostic value of the ratio of urinary epidermal growth factor-to-monocyte chemotactic peptide-1 in predicting long-term renal function deterioration. MATERIALS AND METHODS: A total of 76 patients with obstructive ureteral injury and treated with reconstructive procedures were prospectively enrolled in the study. The ratio of epidermal growth factor-to-monocyte chemotactic peptide-1 was evaluated 4 weeks after the relief of obstruction. After a median followup of 60.8 months, estimated creatinine clearance and (99m)technetium-mercaptoacetyltriglycine scan were evaluated. RESULTS: Within 2 weeks of the obstructive ureteral injury 36 patients underwent surgery for relief of obstruction while in the remaining 40 patients the surgery was performed after more than 2 weeks. Significant differences between the 2 groups were observed regarding mean mercaptoacetyltriglycine clearance of the obstructed kidney (p <0.0001), estimated creatinine clearance (p <0.001) and ratio of epidermal growth factor-to-monocyte chemotactic peptide-1 (p <0.0001). There was a direct correlation between mercaptoacetyltriglycine clearance and epidermal growth factor-to-monocyte chemotactic peptide-1 (rs = 0.78, p <0.0001). Patients with a time of relief greater than 2 weeks had a higher incidence of postoperative hypertension. On logistic regression the time of relief was the only significant variable predicting renal function deterioration (OR 1.49, p = 0.01). CONCLUSIONS: Patients who experience delayed relief of obstructive ureteral injury have decreased long-term renal function as suggested by the lower values of estimated creatinine clearance and mercaptoacetyltriglycine clearance, and are at risk for hypertension or exacerbation of preexisting hypertension.

Serum sarcosine increases the accuracy of prostate cancer detection in patients with total serum PSA less than 4.0 ng/ml.

BACKGROUND: Sarcosine is reported to be a differential metabolite that is greatly increased during prostate cancer (PCa) progression. In this study, we assessed the role of serum sarcosine as a biomarker for PCa, as well as any association between sarcosine levels and clinical-pathological parameters. METHODS: Sarcosine was measured by fluorometric assay in serum samples from 290 PCa patients and 312 patients with no evidence of malignancy (NEM), confirmed by 8-12 core prostate biopsies. Nonparametric statistical tests and receiver operating characteristics (ROC) analyses were performed to assess the diagnostic performance of sarcosine in different (prostate-specific antigen) PSA ranges. RESULTS: ROC analyses in subjects with PSA < 4 ng/ml showed a higher predictive value of sarcosine (AUC = 0.668) versus total PSA (AUC = 0.535) (P = 0.03), whereas for the other two PSA ranges (4-10 ng/ml and >10 ng/ml), percent ratio of free to total PSA (%fPSA) showed a predictive superiority over sarcosine. Moreover, in patients with a PSA < 4 ng/ml, the percentage of low/intermediate-grade cancers was positively associated with sarcosine levels (P = 0.005). The specificities for serum sarcosine, %fPSA, PSA, and the logistic regression model at 95% sensitivity were 24.4, 3.41, 2.22, and 28.4%, respectively. CONCLUSIONS: We provide evidence that serum sarcosine has a higher predictive value than tPSA and %fPSA in patients with PSA < 4 ng/ml. Moreover, sarcosine levels were significantly different in low grade versus high grade cancers in this subset of patients, suggesting that this marker may be a further tool not only for diagnosing PCa in normal PSA and abnormal DRE/TRUS patients but also for selecting candidates for non-aggressive therapies and active surveillance.

Ultrasonographic findings in dual kidney transplantation.

INTRODUCTION: Organ shortage has led to using grafts from expanded criteria donors (ECD). Double kidney transplantation is an accepted strategy to increase the donor pool, using organs from an ECD which are not acceptable for single kidney transplantation (SKT). Aim of this retrospective study was to analyse the role of colour Doppler ultrasound (CDUS) in the diagnosis of major surgical complications in DKT, performed with unilateral or bilateral placement. MATERIALS AND METHODS: From 2000 to 2011 we performed 54 DKT. Unilateral placement of both kidneys was done in 26 patients and bilateral DKT in 28, through two separate Gibson incisions (18) or one midline incision (10). Each patient underwent at least 3 CDUS before hospital discharge. The main surgical complications, discovered initially thanks to ultrasound (US), were hydronephrosis from ureteral obstruction, lymphocele and deep venous thrombosis (DVT). RESULTS: Mean follow-up was 42.7 months. Good postoperative renalfunction was demonstrated in 25 patients (46.3%), while delayed graft function occurred in 29 (53.7%). US showed ureteral obstruction requiring surgery in 5 unilateral DKT while no patient subjected to bilateral DKT developed severe hydronephrosis. Lymphoocele, surgically drained, was demonstrated in 6 bilateral DKT with a midline incision, 2 bilateral DKT with two separate incisions and 3 unilateral DKT. CDUS also enabled diagnosis of 2 cases of DVT in ipsilateral DKTs. CONCLUSIONS: CDUS provides useful information in patients with DKT, allowing the detection of clinically unsuspected unilateral diseases. US study of our patients demonstrated that unilateral DKTs are more susceptible to the development of DVT and ureteral stricture, while the incidence of voluminous lymphocele is more frequent in bilateral DKT through a single midline incision. In this scenario, all patients undergoing DKT should be carefully monitored by US after surgery.

Value of the resistive index in patient and graft survival after kidney transplant.

INTRODUCTION: The resistive index (RI) obtained by performing doppler sonography is a hemodynamic index commonly used to measure flow resistance within an organ to assess if there is a vascular disease associated with that organ. It is a well-known predictor of kidney transplant outcome. The purpose of this study was to analyze the impact of RI values on patient and graft survival, as well as kidney graft function during 5-year follow-up. MATERIALS AND METHODS: We retrospectively investigated 761 kidney transplant recipients from cadaveric donors performed between 1998 to 2011. RI was measured at hospital discharge after the kidney transplant. All the patients were divided into tertiles, according to the baseline RI value (group 1: RI < 0.70, group 2: RI between 0.70 and 0.79 and group 3: RI > 0.80). RESULTS: Patients with a low RI (<0.70) showed the lowest incidence of delayed graft function (DGF) compared to the other two groups (20.2% vs. 32.2% vs. 33%). Recipients with low RI values displayed significantly better creatinine clearance (70 vs. 55 vs 35 ml/min, respectively) than those with medium or high RI values at 5-year follow-up. Kaplan-Meier estimates of cumulative graft survival were significantly worse in patients who had a RI of 0.70 or more than in patients with a RI of less than 0.70 (p = 0.02). Cumulative patient survival showed the same behavior (0.01) CONCLUSIONS: Low RI values measured in segmental arteries in the very early post-transplant period predict better kidney graft function and reduce the risk of all-cause graft loss, including patient death in a 5-year follow-up period.

The European Union Interreg Program: Italian-Albanian experience with kidney transplants.

INTRODUCTION: A collaboration between the Regional Health Agency of Puglia (ARES), the Italian Ministry of Health and the Albanian Ministry of Health, was realized in 2008. One of the areas of interest was to promote the performance of kidney transplants in Albania by Albanian medical staff, funded with nearly 2 million euros. The program included two major goals: to transmit the required know-how to health care staff and to upgrade the Albanian facilities and equipment to the standards necessary for successful transplantation. MATERIALS AND METHODS: During the year 2008, two couples of Albanian patients were transplanted at the Department of Emergency and Organ Transplantation-Urology Unit in Bari, Italy. The surgical procedures were performed by mixed surgical teams, with the active participation of Albanian medical staff under the guidance of the Italian colleagues. The first kidney transplant was performed at the end of January 2008 and the second in June 2008. Both surgical procedures and post-transplant periods were clinically uneventful. RESULTS: After returning to Albania the trained team started to carry out team-work, preparing the patients for the first kidney transplantation. The first donor-patient couple was prepared for kidney transplantation at the end of 2008. On the 26th March 2009 the first kidney transplant was performed by the Albanian medical team, with the active participation of 2 Italian urologists from the University of Bari. CONCLUSIONS: Appropriate training, equipment, and infrastructure are necessary to build a rational, functional national system for organ transplantation. Continuous exchange of ideas and data on kidney transplantation between Albania and Italy will probably contribute to extend such forms of cooperation to the western Balkans in the near future.

High energy microwave thermotherapy for symptomatic benign prostatic enlargment: predictive parameters of long term outcome.

OBJECTIVES: High-energy transurethral microwave thermotherapy (HE-TUMT) has become one of the most preferred minimally invasive procedure for the treatment of benign prostatic enlargement (BPE). In this study we report the long term results in a subset of patients treated with the 30-minute high energy protocol. PATIENTS AND METHODS: A total of 135 patients were treated with TUMT Prostasoft 3.5. The International Prostate Symptom Score (IPSS), Madsen Symptom Score (MSS), Quality of Life (QoL) score, peak urinary flow rate (Qmax) and post-voiding residual urine volume (PVR) were assessed at baseline and at 12, 24, 36, 48 and 60 months after treatment. RESULTS: The mean follow-up period was 46.1 months. The mean IPSS at baseline was 17.8 and decreased to 5.6 at 60 months (p < 0.001). The MSS decreased from 12.6 at baseline to 4.3 at 5 years (p < 0.0001). The QoL score improved from 4.1 to 2.2 at 5 years (p < 0.001). The mean Qmax value at baseline was 9.4 ml/sec and it improved to 15.7 ml/sec at 60 months (p = 0.001), whereas PVR decreased from 97 to 24 ml at 5 years (p = 0.001). Retreatment was required for 47 patients (34.8%). Univariate and multivariate analysis showed that the only baseline parameters able to predict the long-term efficacy were a IPSS <18 and a Qm, > 10 ml/sec (p = 0.04). CONCLUSIONS: These data shows a high response rate obtained with 30-minute TUMT protocol and a durability of response up to 5 years after treatment, making this procedure a safe and effective alternative to TURP in selected patients.

Transperitoneal deviceless hand-assisted laparoscopic living donor nephrectomy: an alternative technique for kidney recovery.

PURPOSE: Deviceless hand-assisted laparoscopic living donor nephrectomy is an alternative surgical technique that relies on the classic laparoscopic approach, supported by insertion of the surgeon's hand during kidney recovery without the need to use any device because of the sealing effect of the particular wall incision. PATIENTS AND METHODS: From 2006 to 2008, deviceless hand-assisted laparoscopic living donor nephrectomy was performed in 25 patients (M/F = 7/18; mean age = 53 years; range = 30-68). One right nephrectomy was performed. We made a lateral paramedian incision. No sealing device is required in our technique because the pneumoperitoneum is maintained by the sealing effect of two complexes: the peritoneum/deep rectus abdominis muscle fascia and muscle itself/lateral edge of the double fascial incision. These structures clench around the surgeon's wrist, preventing leakage of CO2. After dissection, the kidney is removed through the hand port without an endobag. RESULTS: Mean surgical time was 105 minutes (range = 60-150), estimated blood loss was 50 to 200 mL, and mean warm ischemia time was 3.5 minutes (range = 2-11). Mean hospital stay was 4 days (range = 3-6). One uncontrollable hemorrhage due to a renal vein lesion required conversion to open surgery. As to graft function, recipient serum creatinine on day 7 ranged from 0.8 to 2.6 mg/dL. CONCLUSIONS: The ability to better control bleeding by manual compression, as well as the advantages related to decreased donor morbidity, shorter hospital stay, cost saving, and excellent graft function, make this deviceless technique a good option for kidney recovery.

Surgery for renal cell carcinoma in two European urologic clinics: to compare or compete?

OBJECTIVES: To evaluate and compare the incidence, TNM staging and the current strate- gy for the surgical treatment of renal cell carcinoma (RCC) in two European urologic institutions, situated in Varna, Bulgaria and in Bari, Italy. Both clinics have sound experience of RCC surgery, and modern laparoscopic equipment. A retrospective chart review of all patients with RCC diagnosed and treated in the last year was conducted at the two sites. MATERIALS AND METHODS: In total, 88 patients (66 males and 22 females, mean age 58 years, range 24-81 years) were enrolled in the study. Comparisons were made between some clinical and pathologic parameters with an established prognostic and therapeutic impact. The type of surgery perormed at both sites was analyzed as well. All these comparative studies were performed in relation to the 2008 EAU guidelines on the current management of RCC. Commercially available statistical software was used for the purpose. RESULTS: The results showed no difference between the two sites regarding the RCC incidence and the patients' age and gender. Significant differences (p value < 0.0001) emerged in terms of: the median size of the tumors at surgery (8.5 cm in Varna, SD + 4.04 vs. 4.4 cm in Bari, SD _ 2.02); T-stage of the tumor (Varna T T2-30%, T3-22%, T4-15% vs. Bari T1-64%, T2-12%, T3-24%, T4-0%); N-positive disese (24% vs. 2%); distant metastases (20% vs. 2%) and presence of necrosis in the renal masses (37% vs. 19%). Thus, 85% of Varna patients underwent open radical nephrectomy, 11% nephron-sparing surgery and 4% explorative laparotomy, due to inoperability of the renal mass. Only 29% of Bari patients were treated by open radical nephrectomy, 12% underwent laparoscopic nephrectomy, 57% open partial nephrectomy and 2% laparoscopic partial tumor resection. CONCLUSIONS: These numbers demonstrate more advantageous tumour features at the Italian clinic in terms of organ-sparing surgical options (open and laparoscopic), whereas in the Bulgarian clinic the tumour features pose certain limitations to the application of modern surgical techniques. This difference is due to early diagnosis of RCC in Italy, allowing treatment of smaller volume tumors.

Therapeutic targeting of classical and lectin pathways of complement protects from ischemia-reperfusion-induced renal damage.

Ischemia-reperfusion injury is the major cause of delayed graft function in transplanted kidneys, an early event significantly affecting long-term graft function and survival. Several studies in rodents suggest that the alternative pathway of the complement system plays a pivotal role in renal ischemia-reperfusion injury. However, limited information is currently available from humans and larger animals. Here we demonstrated that 30 minutes of ischemia resulted in the induction of C4d/C1q, C4d/MLB, and MBL/MASP-2 deposits in a swine model of ischemia-reperfusion injury. The infusion of C1-inhibitor led to a significant reduction in peritubular capillary and glomerular C4d and C5b-9 deposition. Moreover, complement-inhibiting treatment significantly reduced the numbers of infiltrating CD163(+), SWC3a(+), CD4a(+), and CD8a(+) cells. C1-inhibitor administration led to significant inhibition of tubular damage and tubular epithelial cells apoptosis. Interestingly, we report that focal C4d-deposition colocalizes with C1q and MBL at the peritubular and glomerular capillary levels also in patients with delayed graft function. In conclusion, we demonstrated the activation and a pathogenic role of classical and lectin pathways of complement in a swine model of ischemia-reperfusion-induced renal damage. Therefore, inhibition of these two pathways might represent a novel therapeutic approach in the prevention of delayed graft function in kidney transplant recipients.

Transrectal ultrasound approach for identification and radioguided biopsy of sentinel node in lymph node staging of localized prostate cancer.

INTRODUCTION: The limited pelvic lymphadenectomy (LPL) is currently considered the referred method of identification of nodal micrometastases in localized prostate cancer. Lymphoscintigraphy (LS) and radioguided sentinel node biopsy (RSNB) could be an alternative method of nodal staging. MATERIALS AND METHODS: Between June 2003 and February 2007 19 patients with prostate cancer without metastases were included in the study. Mean age was 66 years, mean PSA 15.51 ng/ml, Gleason score > 6. A transrectal ultrasound was performed with intraprostatic administration of 0.2 ml/190 MBq 99 mTc bound to nanocolloid particles, prepared the day before surgery. Dynamic and static scans of the pelvis were obtained at 30', 60' and 120' after injection. Hot spots outside the site of administration were considered as sentinel nodes (SLNs). Prior to prostatectomy, LPL was performed. The presence of a labeled node after LPL, identified by a gamma probe slided slowly down the chain of lymphatic drainage, was indication for an LPE. RESULTS: A sentinel node was identified in 17/19 patients with preoperative lymphoscintigraphy (identification rate 89%) and in 16/19 patients during surgery (84%) with a negative predictive value of 97%. The most frequent site was identified at the level of hypogastric lymph nodes (56%), outside the standard of limited pelvic lymphadenectomy, followed by external iliac (33%), obturator (7%) and common iliac (4%) lymph nodes. Lymph node metastases were detected by histological examination in 2 patients (13%); total metastatic nodes found were 9: one in the first, and 8 in the second patient. Two metastatic nodes (22%) not removed by the limited pelvic lymphadenectomy were found with the sentinel lymph node dissection. CONCLUSIONS: Ultrasound approach for lymphoscintigraphy and sentinel node identification, is a valuable tool in the staging of localized prostate cancer.