Population pharmacokinetics of everolimus in renal transplant recipients receiving long-term multiple immunosuppressive therapy.

Everolimus is used for immunosuppression after renal transplantation. This study aimed to develop a population pharmacokinetic (PopPK) model of everolimus using therapeutic drug monitoring (TDM) data of patients under long-term multiple immunosuppressive therapy, including tacrolimus. To develop the model, 185 renal transplant recipients with 3358 everolimus blood concentrations during a median postoperative period of 35.3 months were included. The PopPK model is described as a one-compartment model with first-order absorption. The population mean of apparent clearance is 8.92 L/h (relative standard error = 3.6%), and this negatively correlated with the dose-normalized concentration (C/D) of tacrolimus and hematocrit value, and positively correlated with a daily dose of everolimus (i.e. TDM effect). The usefulness of dose adjustment using the final popPK model was assessed by a simulation study. The ratio of the first trough measurement within the therapeutic range of 3-8 ng/mL increased from 69.8% in the original dose to 87.9% in the individual dose calculated by the final PopPK model. The tacrolimus C/D ratio before initiating everolimus therapy and the hematocrit value were useful to estimate the initial dose of everolimus and can improve the safety and effectiveness of immunosuppressive therapy involving everolimus.

Myosteatosis as a novel predictor of new-onset diabetes mellitus after kidney transplantation.

OBJECTIVES: We evaluate the effect of myosteatosis on new-onset diabetes mellitus after kidney transplantation. METHODS: Consecutive patients who had renal transplant between 2006 and 2021 were reviewed, and 219 patients were finally included. Psoas muscle index was used to evaluate sarcopenia and average total psoas density (calculated by computed tomography before surgery) for myosteatosis. We used Cox proportional regression analyses in investigation of whether skeletal muscle depletion before surgery inclusive of sarcopenia and myosteatosis is a new additional predictor of new-onset diabetes mellitus. RESULTS: Median recipient age and body mass index were 45 years and 21.1 kg/m2 , respectively, and 123 patients (56%) were male. Preoperative impaired glucose tolerance was present in 58 patients (27%) and new-onset diabetes mellitus in 30 patients (14%), with median psoas muscle index of 6 cm2 /m2 and average total psoas density of 41 Hounsfield Unit. In multivariate analysis, significant risk factors were body mass index ≥25 kg/m2 (p < 0.01), impaired glucose tolerance (p < 0.01), and average total psoas density < 41.9 Hounsfield Unit (p = 0.03). New-onset diabetes mellitus had incidence rates of 3.7% without risk factors, 10% with a single risk factor, 33% with two, and 60% with three. Patients with new-onset diabetes mellitus were effectively stratified by the number of risk factors (p < 0.01). CONCLUSIONS: Myosteatosis could be a new risk factor used to predict new-onset diabetes mellitus.

Association of Alpha-Actinin-3 Polymorphism With Sarcopenia in Kidney Transplant Recipients.

BACKGROUND: Sarcopenia is defined as the loss of skeletal muscle mass and function and is associated with increased mortality. Certain genetic polymorphisms represent risk factors used to assess the incidence of sarcopenia; however, few studies have evaluated the association between genetic polymorphisms and sarcopenia after kidney transplantation (KTx). We examined single-nucleotide polymorphisms (SNPs) in the genes involved in sarcopenia after KTx. METHODS: Sixty-five patients who underwent KTx were enrolled in this study. We used the psoas mass index (PMI; the cross-sectional area of the bilateral psoas muscle/height) as a surrogate marker for assessing the extent of sarcopenia. We determined the PMI before KTx and 1 year after KTx, and we identified 5 SNPs in 5 genes associated with sarcopenia in the general population. Finally, the link between the changes in PMI 1 year after KTx and each SNP was examined. RESULTS: The median PMI before KTx and 1 year after KTx was 7.4 (4.6-13.2) and 7.0 (3.6-13.6), respectively. The PMI decreased in 43 patients (66.2%). The alpha-actinin-3 rs1815739 genotype was associated with changes in PMI; the distribution of CT+TT genotypes in the PMI decrease group was significantly higher than that of the CC genotype (odds ratio, 4.23; 95% CI 0.05-0.97; P = 0.025). Moreover, the T allele frequency was significantly higher in the PMI decrease group than in the PMI increase group (odds ratio, 2.34; 95% CI 0.18-0.950; P = 0.025). CONCLUSION: The alpha-actinin-3 rs1815739 genotype may represent a genetic risk factor for sarcopenia after KTx.

Psychosocial and Ethical Behaviors and Attitudes of Health Care Professionals in the Clinical Setting of Living Kidney Donors: A Qualitative Study.

BACKGROUND: There are several psychosocial and ethical issues surrounding the decision making of living kidney transplant donors. This study aimed to determine what health care professionals (HPs) consider in their clinical practice and their attitudes toward donors' decision-making processes. METHODS: Face-to-face semistructured interviews were conducted with 15 HPs. A thematic analysis was performed to categorize the thematic elements of the transcripts. All procedures were approved by the relevant review board and conducted in accordance with the Declaration of Helsinki. RESULTS: Six main categories-maintaining family relationships, improving donor understanding, supporting voluntary decision making, setting the environment for the examination, having different attitudes toward the donor's intentions, and resisting confirmation of intent-were identified. The HPs provided diverse considerations to respect the donors' autonomy. CONCLUSION: In clinical practice, there is a lack of practical methods to confirm living donors' levels of understanding and spontaneity, suggesting that these methods need to be established. Factors related to family functioning may reflect the unique culture of Japan, and this may be indicative of the need to consider treatment based on cultural values.

No Influence of Everolimus on Mycophenolic Acid Area Under the Concentration-Time Curve: Limited Sampling Strategy for Mycophenolic Acid in Japanese Kidney Transplant Recipients Treated With Tacrolimus, Mycophenolate Mofetil, Steroid, and Everolimus.

BACKGROUND: Despite a growing need for everolimus (EVR) to reduce calcineurin inhibitor toxicity in kidney transplantation (KTx), the influence of EVR on the pharmacokinetics of mycophenolic acid (MPA), a mycophenolate mofetil (MMF) active metabolite, is obscure, and no suitable limited sampling strategy (LSS) for MPA when EVR is concomitantly present exists. We aimed to investigate the influence of EVR on MPA pharmacokinetics in KTx. MATERIALS AND METHODS: This study complied with all principles of the Declaration of Helsinki. Twenty patients were initially administered tacrolimus, MMF, and methylprednisolone and then received EVR 4 months after KTx. Approximately 4 weeks before and after EVR administration, the estimated value of the area under the concentration-time curve for MPA from 0 to 12 hours (MPA-AUC0-12) was calculated using MPA blood concentration just before and 1, 2, 4, and 6 hours after MMF administration. We compared several MPA pharmacokinetics parameters before and after EVR addition and determined the best estimation equation for LSS of MPA-AUC0-12. RESULTS: Although MPA-C6 per dose (MPA-C6/D) significantly decreased after EVR addition (from 3.4 [±2.2] ng/mL/g to 2.5 [±0.9] ng/mL/g), MPA-C0/D, -C1/D, -C2/D, -C4/D, and MPA-AUC0-12/D showed no significant change. MPA-AUC0-12/D did not correlate with EVR-AUC0-12/D. The best estimation equation for LSS of MPA-AUC0-12 by 2 time points was [(2.94 × C2) + (5.09 × C4) + 5.32] (R2 = 0.73) and [(5.70 × C0) + (1.39 × C1) + 22.45] (R2 = 0.72) before and after EVR addition, respectively. CONCLUSIONS: EVR can be safely combined with MMF after KTx once our results have been reevaluated.

Suppression of Allograft Fibrosis by Regulation of Mammalian Target of Rapamycin-Related Protein Expression in Kidney-Transplanted Recipients Treated with Everolimus and Reduced Tacrolimus.

BACKGROUND Although renoprotective effects of everolimus (EVR) in kidney transplantation (KTx) have been widely reported, its pathophysiological mechanism remains unclear. MATERIAL AND METHODS We compared changes in eGFR (ΔGFR, ml/min/1.73 m²) and the ratio of the fibrotic area in biopsy specimens (ΔFI,%) from 3 months to 3 years after KTx between the EVR+ group (EVR addition and Tac reduction early after KTx, n=32), and the EVR- group (normal Tac without EVR, n=28). We also immunohistochemically evaluated mTOR-related protein expression. RESULTS ΔGFR and ΔFI in the EVR+ vs. EVR- groups were -0.27±6.8 vs. -9.8±12.8 (p<0.001) and 2.4±4.9 vs. 9.5±10.5 (p<0.001), respectively. Phosphorylated mTOR and phosphorylated 4EBP1 expression at 3 years in the EVR+ group was significantly lower than that in the EVR- group. Moreover, in the subgroup analysis comparing ΔGFR and ΔFI among groups stratified by immunosuppressive regimen and mTOR signal enhancement, the ΔFI in patients with EVR+ with decreased mTOR signal enhancement was significantly milder than that in other patients. In addition, in the multivariate analysis, EVR addition was the only independent predictor for allograft fibrosis, whereas the Tac C0 concentration at neither 1 nor 3 years proved to be a risk factor. CONCLUSIONS These results suggested that EVR addition and Tac reduction may attenuate kidney allograft fibrosis, and that the suppression of mTOR signaling process may be involved in the anti-fibrotic effect of this immunosuppressive regimen. These results provide suggestions of how to utilize EVR for patients with KTx and improve graft function.

One-Year Impact of Kidney Transplantation on Cardiac Abnormalities and Blood Pressure in Hemodialysis Patients.

Cardiac abnormalities, including left ventricular hypertrophy and systolic dysfunction, are frequently observed among patients with CKD, including kidney transplant recipients; they are closely linked to cardiovascular disease and mortality. Although several studies have been performed for elucidating changes and mechanisms of cardiac abnormalities after kidney transplantation, details remain unclear. This study included 43 consecutive patients who underwent HD and received kidney transplantation between 2008 and 2012 at our institution. All subjects underwent echocardiography before and 1 year after kidney transplantation. One year after kidney transplantation, left ventricular mass index, cardiac chamber sizes, BP, and the number of antihypertensive agents were reduced. Although the percentage of patients with concentric hypertrophy did not change, the percentage of those with eccentric hypertrophy significantly decreased after kidney transplantation. Volume reduction due to the recovery of kidney function may be primarily attributed to the improvement of cardiac abnormalities, including left ventricular hypertrophy.

Application of hyaluronic acid/carboxymethyl cellulose membrane for early continence after nerve-sparing robot-assisted radical prostatectomy.

BACKGROUND: To assess whether application of a hyaluronic acid-carboxymethyl cellulose membrane (HA/CMC) to the prostate bed and neurovascular plate facilitated early return of continence after nerve-sparing robot-assisted radical prostatectomy (RARP). METHODS: The subjects were 183 consecutive patients with organ-confined prostate cancer who underwent unilateral or bilateral nerve-sparing RARP. After vesicourethral anastomosis, HA/CMC was placed to cover Denonvilliers' fascia (behind the anastomotic suture) and the preserved neurovascular plate. The time until complete continence after RARP and perioperative complications were compared between patients with or without HA/CMC. RESULTS: HA/CMC was applied in 13/46 patients (28.3%) receiving bilateral nerve-sparing surgery and 40/137 patients (29.2%) receiving unilateral nerve-sparing surgery. After bilateral nerve-sparing RARP, the median time until continence was significantly shorter in patients with HA/CMC than in those without HA/CMC (3.2 vs. 9.3 months, respectively, p < 0.01). After unilateral nerve-sparing RARP, the median time until continence was also significantly shorter in patients with HA/CMC than in those without HA/CMC (3.2 vs. 12.0 months, respectively, p < 0.01). Multivariate Cox proportional hazards regression analysis showed that an age < 70 years (hazard ratio [HR]: 1.74, 95% confidence interval [CI]: 1.12-2.80), institutional caseload > 200, (HR: 1.64, 95%CI: 1.10-2.47), and use of HA/CMC (HR: 1.84, 95%CI: 1.22-2.76) were independent predictors of early postoperative continence. Complication rates, including urinary leakage, did not differ significantly between patients with or without HA/CMC. CONCLUSION: Application of HA/CMC to the prostate bed and neurovascular plate resulted in significantly faster postoperative return of continence after both unilateral and bilateral nerve-sparing RARP.

[EFFICACY AND SAFETY OF PAZOPANIB FOR ADVANCED OR METASTATIC RENAL CELL CARCINOMA: A SINGLE-INSTITUTION STUDY].

To investigate the efficacy and safety of first-line Pazopanib advanced or metastatic renal cell carcinoma (RCC): a single-institution study. (Patients and methods) We gathered 23 RCC patients treated between April 2014 and February 2018 in our institution and examined the treatments outcome and adverse events (AEs). (Results) Their risk criteria were categorized as follows: Favorable (n=2), Intermediate (n=12) and Poor (n=9) by International mRCC Database Consortion (IMDC). Median progression free survival (PFS) was 8.6 months and median overall survival (OS) was unreached. Best response (BR) of Pazopanib was partial response (PR): n=10, 50.0%, stable disease (SD): n=8, 40.0% and progression disease (PD): n=2, 10.0% (Three patients had no evaluable data,). AEs of Grade3 had liver dysfunction (n=3), thrombocytopenia (n=2), hand-foot syndrome (n=1), vomiting (n=1) and bowel bleeding (n=1). (Conclusion) The fist-line pazopanib demonstrated good clinical benefit with well-tolerance.

Low-Grade Myxofibrosarcoma of the Rectus Abdominus Muscle Infiltrating into Abdominal Cavity: A Case Report.

Objective: Myxofibrosarcoma (MFS) is a relatively rare tumor that is histologically characterized by myxoid stroma and spindle cell proliferation. This tumor most commonly arises as a slow growing, enlarging painless mass in the extremities of elderly patients. Methods: We report a case of a primary, low-grade MFS in the rectus abdominis muscle infiltrating the abdominal cavity of a 75-year-old man. Results: The patient underwent a wide excision of the right abdominal wall mass with a 3-cm surgical margin from the scar due to a biopsy. The tumor infiltrated the urinary bladder, peritoneum, and external iliac vessels. Twenty-six months after the initial operation, he had recurrences in his abdominal wall, urinary bladder, and right iliac vessels. Conclusions: To our knowledge, primary MFS of the muscle in the abdomen has not been documented previously. Although this case was histopathologically classified as a low-grade tumor, it infiltrated the abdominal cavity. The tumor is suspected to have penetrated the abdominal cavity below the linea arcuata, which lacks the posterior sheath of the rectus abdominis muscle; from there, it could easily spread without being blocked by any biological barriers.

Expression profile of mammalian target of rapamycin-related proteins in graft biopsy specimens: Significance for predicting interstitial fibrosis after kidney transplantation.

OBJECTIVE: To investigate the influence of the expression profile of mammalian target of rapamycin-related proteins on the development of interstitial fibrosis after kidney transplantation. METHODS: Immunohistochemical staining was carried out to evaluate the expression of five mammalian target of rapamycin-related proteins (phosphorylated-Akt, Ras homolog enriched in brain, phosphorylated-mammalian target of rapamycin, phosphorylated-p70 ribosomal S6 kinase and phosphorylated-4E binding protein 1) in graft biopsy specimens obtained from 77 patients at 3 months after kidney transplantation. The change of the estimated glomerular filtration rate and the change of the fibrosis index (defined as the change in the percent area of fibrosis on Masson's trichrome-stained sections of biopsy specimens) from 3 months to 3 years after kidney transplantation were determined. RESULTS: There was a significant correlation between change of the estimated glomerular filtration and change of the fibrosis index in the 77 patients. Univariate analysis identified expression of phosphorylated-Akt, phosphorylated-mammalian target of rapamycin and phosphorylated-p70 ribosomal S6 kinase, as well as donor type and pre-transplant dialysis duration, as significant predictors of a change of the fibrosis index >10%. However, only phosphorylated-mammalian target of rapamycin expression, phosphorylated-p70 ribosomal S6 kinase expression and donor type were independently associated with a change of the fibrosis index >10% according to multivariate analysis. CONCLUSIONS: These findings suggest that mammalian target of rapamycin-related proteins are involved in the development of interstitial fibrosis after kidney transplantation.

Granular swollen epithelial cells in the kidney allograft: A clinicopathological study with special emphasis on possible marker for kidney allograft aging.

AIM: To elucidate the clinicopathological significance of granular swollen epithelial cells (GSECs), which provides histological evidence in the diagnosis of mitochondrial nephropathy, but incidentally observed in renal allografts, we evaluated GSECs as a surrogate histological marker for kidney allograft aging, as previously reported for p16, p21, and ß-galactosidase. METHODS: We retrospectively reviewed 426 kidney allograft biopsy specimens diagnosed at our university from January 2009 to April 2015. The prevalence and density of GSECs were compared with an age-matched control group of 508 native kidney biopsies. GSECs were defined as swollen (>2 times larger than normal renal tubular cells) epithelial cells best observed using Masson trichrome staining. Morphometric analyses were performed using digital microscopy software. RESULTS: The prevalence of GSECs was 7.7% in allograft kidneys and 8.1% in native kidneys. GSECs in kidney allografts were predominantly detected in medullary renal tubules, but not in the Bowman's capsular epithelium or podocytes. GSECs were observed in the following cases; no remarkable changes, n = 11; interstitial fibrosis and tubular atrophy, n = 7; chronic calcineurin inhibitor toxicity, n = 5; antibody-mediated rejection, n = 3; T cell-mediated rejection grade IA, n = 1; and others, n = 6. Compared with control specimens, medullary density of GSECs in kidney allografts was significantly increased. The prevalence of GSECs slightly increased with post-transplant duration; however, this trend was not statistically significant. CONCLUSIONS: The present study does not provide pathological significance of GSEC in kidney allografts in terms of allograft aging, and warrant the further research with molecular approach.

A suspected case of plasma cell-rich acute renal transplant rejection associated with de novo donor-specific antibody.

A kidney transplant case with de novo donor-specific antibody showed monoclonal plasma cell infiltration into the graft with ABO incompatibility. Three years after transplantation, the patient's graft function suddenly deteriorated. Interstitial edema and the predominant infiltration of inflammatory plasma cells with kappa chain monoclonality were observed in biopsy specimens. The in situ hybridization of Epstein-Barr virus was negative and post-transplant lymphoproliferative disorder was not evident from radiological examinations. On laboratory examination, the patient had de novo donor-specific antibody for HLA-DQ. We suspected plasma cell-rich acute rejection for which methylprednisolone pulse therapy, plasma exchange, rituximab, and 15-deoxyspergualin were given. In the ensuing biopsy, the degree of plasma cell infiltration was similar to the first biopsy; however, kappa chain monoclonality relatively weakened. Owing to resistance to these treatments, intravenous immunoglobulin (IVIG) (0.5 g/kg/day) was added. The serum creatinine level gradually declined to 3.1 mg/dL; however, it increased up to 3.6 mg/dL again. In the final biopsy, the infiltrated plasma cells disappeared but severe interstitial fibrosis developed. This case showed difficulty in the diagnosis and treatment of plasma cell-rich acute rejection. A detailed consideration of this case may be helpful in understanding the clinical features and pathogenesis of this condition.

Effect of cinacalcet cessation on hyperparathyroidism in kidney transcaplant patients after long-term dialysis therapy.

BACKGROUND: Cinacalcet is a promising therapy widely used in dialysis patients with hyperparathyroidism resistant to conventional therapy. However, reports regarding the influence of cinacalcet cessation after long-term use on kidney transplantation patients are few. METHODS: This retrospective observational study included 40 dialysis patients who underwent kidney transplantation. Creatinine, corrected calcium, phosphorus, alkaline phosphatase, and intact parathyroid hormone levels were assessed before and after kidney transplantation according to pretransplant treatment of chronic kidney disease-mineral and bone disorder. RESULTS: Ultrasonography revealed enlargement of the parathyroid in all patients treated with cinacalcet. Although the data at the time of kidney transplantation were comparable, the serum levels of calcium, alkaline phosphatase, and intact parathyroid hormone after kidney transplantation were higher in patients treated with cinacalcet than in those treated without. However, serum phosphate levels in the cinacalcet group were slightly higher at the time of kidney transplantation and significantly lower 3 months later. CONCLUSIONS: Mineral abnormalities persisted in kidney transplant patients with enlarged parathyroid glands after discontinuation of cinacalcet treatment. Parathyroidectomy should be considered in kidney transplant candidates with the risk of developing refractory hyperparathyroidism after transplantation.

Surgery-related outcomes and postoperative split renal function by scintigraphy evaluation in robot-assisted partial nephrectomy in complex renal tumors: an initial case series.

PURPOSE: To assess surgery-related outcomes and split renal function evaluated by renal scintigraphy in robot-assisted partial nephrectomy (RPN) through the comparison between low and intermediate or highly complex renal tumors. METHODS: In the initial 39 consecutive RPNs performed for solid renal tumors in our hospital, tumors were categorized for their complexity (low, intermediate, and high risk for partial nephrectomy) by R.E.N.A.L. (radius; exophytic/endophytic; nearness; anterior/posterior; location) nephrometry and P.A.D.U.A. (preoperative aspects and dimensions used for an anatomic) scores. The comparison between low, intermediate, and highly complex tumors according to these scoring systems were performed regarding preoperative factors, surgery-related factors, and postoperative renal function factors (split renal function at 3 months and serum creatinine level and estimated glomerular filtration rate (eGFR) at 1 week, 1, 3, 6, and 12 months postoperatively,). RESULTS: There was no significant difference between low and intermediate or highly complex tumors for all the categories tested in preoperative data. Especially in split renal function, the changes in mercaptoacetyltriglycine (MAG3) effective renal plasma flow (ERPF) from preoperative data were -7.00±20.2 mL/min in low complexity in R.E.N.A.L. nephrometry and -14.1±22.7 mL/min in intermediate or highly complex tumors in R.E.N.A.L. nephrometry (p=0.477), -8.21±21.3 mL/min for low complexity in P.A.D.U.A. and -13.4±22.4 in intermediate or highly complex tumors in P.A.D.U.A. (P=0.607). There was either no significant difference in the decrease of renal function (serum creatinine level and eGFR), operative time, estimated blood loss, or warm ischemia time between low and intermediate or highly complex tumors as measured by both R.E.N.A.L. nephrometry and P.A.D.U.A. scores (P>0.05). CONCLUSIONS: Our data showed that RPN can be performed without compromising the outcome in surgery-related factors and postoperative split renal function even in intermediate or highly complex tumors. Further studies with a larger number of cases need to be performed to confirm these findings.

Novel telementoring system for robot-assisted radical prostatectomy: impact on the learning curve.

OBJECTIVE: To develop a Web-based audiovisual telementoring system for robot-assisted radical prostatectomy (RARP) and to assess the utility of this system. METHODS: A telementoring system for RARP, consisting of a 3-dimensional high-definition view of the operating field, overview of the operating room, annotation function, and 2-channel audio feed with bidirectional connectivity between 2 institutions, was developed. The outcome of RARP performed for the initial 30 patients by 2 surgeons with telementoring was compared with that for 2 surgeons who received direct mentoring. RESULTS: This system was shown to function properly with an acceptable latency. There were no significant differences in several parameters reflecting surgical outcomes, including the operating time, complication rate, early continence status, and positive margin rate between the telementoring and direct mentoring groups. CONCLUSION: These findings suggest the usefulness of the telementoring system for promoting the spread of precise surgical techniques associated with RARP. To our knowledge, this is the first report concerning telementoring for robot-assisted surgery.

Evaluation of a 3D system based on a high-quality flat screen and polarized glasses for use by surgical assistants during robotic surgery.

INTRODUCTION: One of the main benefits of robotic surgery is the surgeon's three-dimensional (3D) vision system. The purpose of this study is to evaluate the efficacy of 3D vision using a flat screen and polarized glasses for surgical skills during robotic surgeries. MATERIALS AND METHODS: In an experimental model, six surgeons performed three surgical tasks with laparoscopic devices using a standard 2D and a flat-screen 3D model with polarized glasses. Performance times were compared between two-dimensional (2D) and 3D vision for each task. The surgeons also graded the efficiency of the 3D system, on a subjective scale of 0-100. RESULTS: Performance times for task 1 (seven holes) and 2 (elastic bands) were significantly reduced by 84% and 56% using 3D compared with a 2D system and experienced surgeons performed all three tasks faster in 3D than 2D. The surgeons reported the polarized glasses were comfortable to wear and direct vision was seldom affected. CONCLUSIONS: The use of 3D visualization seems to improve the efficiency of surgical skills during robotic surgery and reduce performance time for characteristic surgical procedure tasks.

Comparison of the transperitoneal and retroperitoneal approach in robot-assisted partial nephrectomy in an initial case series in Japan.

PURPOSE: To compare the results from the transperitoneal and retroperitoneal approaches in our initial case series of robot-assisted partial nephrectomy (RAPN) in terms of surgical time, renal artery clamping time, postoperative renal function, adverse events, and surgical margin status. PATIENTS AND METHODS: The initial 26 consecutive RAPNs performed for solid renal tumors in our hospital were categorized by the approach used, transperitoneal or retroperitoneal, and compared for body mass index, tumor size, R.E.N.A.L. nephrometry score, PADUA score, tumor location, surgical time, renal artery clamping time, renal function change after surgery, operative blood loss, surgical margin status, and adverse events (AEs). RESULTS: The median tumor size was 25 mm (range 15-50). A transperitoneal approach was used in 16 patients and a retroperitoneal approach was used in 10 patients. There was no significant difference in renal tumor and patient characteristics between the two groups except tumor location (anterior tumor was significantly more in the transperitoneal approach and posterior tumor was significantly more in retroperitoneal approach (P=0.0144 and P=0.0100, respectively)). Operative time (239 ± 63.0 minutes in the transperitoneal group vs. 193 ± 40.6 minutes in the retroperitoneal group), warm ischemic time (24.3 ± 9.07 minutes in the transperitoneal group vs. 24.7 ± 8.35 minutes in the retroperitoneal group) and AEs (1/16 in the transperitoneal group vs. 1/10 in the retroperitoneal group; both cases were Clavien-Dindo grade I) did not show any significant difference between the two approaches (P=0.0792, 0.5485, and 0.7270, respectively). CONCLUSIONS: The retroperitoneal approach in RAPN appears to be a safe and technically feasible minimally invasive option for nephron-sparing surgery, based on our initial case series, and showed equivalent outcomes to those of the transperitoneal approach even though it was an initial robotic renal surgery series. Future studies, including a larger number of cases, are planned to draw more definitive conclusions.

Increased testicular 8-hydroxy-2'-deoxyguanosine in patients with varicocele.

OBJECTIVES: To assess immunohistochemically 8-hydroxy-2'-deoxyguanosine (8-OHdG, a sensitive biological marker of oxidative damage and stress) in testicular tissue from patients with varicocele, to determine whether 8-OHdG is related to spermatogenesis, as oxidative stress in testicular DNA is associated with poor semen quality and reduced fertility. PATIENTS, SUBJECTS AND METHODS: Testicular tissue samples were collected from the testes of 36 patients with varicocele and five normal volunteers. The mean (sd) age of the patients was 35.3 (5.4) years. The prevalence of immunostained germ cells among all the germ cells in >20 seminiferous tubules was calculated. RESULTS: The mean (sd) sperm concentration and Johnsen's score in the varicocele group was lower than in the normal group, at 27.6 (11.8) vs 80.4 (21.7) million/mL (P < 0.001) and 7.6 (1.1) vs 9.0 (0.7), respectively (P < 0.05). In all patients, 8-OHdG was mainly expressed in the spermatogonia and spermatocytes in the seminiferous tubule. Immunostained germ cells correlated negatively with sperm concentration (r = -0.48, P = 0.01) and Johnsen's score (r = -0.46, P = 0.02), but not with follicle-stimulating hormone, luteinizing hormone or testosterone level. Immunostained germ cells were significantly more prevalent in the varicocele group, at 53.6 (5.7)%, than that in the normal group, at 14.3 (2.3)% (P < 0.001). The prevalence of immunostained germ cells and clinical grades were positively related; the ratio recorded for varicocele grades I, II and III was 38.0 (10.0)%, 41.0 (9.1)%, and 57.0 (9.3)%, respectively (grade I vs grade III, P < 0.05). CONCLUSIONS: Increased 8-OHdG expression in the testis was associated with deficient spermatogenesis in infertile men with varicocele.