Intracorporeal Double-J stent placement during robot-assisted urinary tract reconstruction: technical considerations.

BACKGROUND AND PURPOSE: An integral component of many urologic reconstructive surgical procedures is the positioning of a Double-J stent to span the anastomosis. Some surgeons prefer to place a retrograde stent during cystoscopy, either during or after the reconstruction. In this communication, we describe our straightforward and effective approach of performing this critical step intracorporeally using robotic assistance in a variety of upper tract urologic reconstructive procedures. PATIENTS AND METHODS: We examined our Institutional Review Board-approved database of robotic surgeries to identify reconstructive operations that included the intracorporeal placement of a Double-J stent since 2008. Our step-by-step method for stent placement during various robotic urologic reconstructions is detailed, including procedures involving the proximal, mid, and distal ureter. With the aid of a bedside assistant-surgeon, we delineate how the console surgeon is able to perform this step of the procedure completely intracorporeally, without the need for repositioning or cystoscopy. RESULTS: Since the inception of our robotic surgical program in 2008, we have used these robotic stent placement techniques in 150 patients. The average time of robotic intracorporeal stent placement across the anastomosis was 3.5 minutes. Three patients did experience proximal stent migration, as documented on postoperative radiographs, but all were treated with conservative measures, because their anastomosis was not affected and severe symptoms did not develop. No patient needed stent replacement, and each stent was subsequently removed ureteroscopically without sequelae. CONCLUSIONS: Our robotic intracorporeal Double-J stent placement approach is simple and effective, avoids the need for cystoscopy and fluoroscopy, and can be used in any type of upper urinary tract urologic reconstruction.

Does nephrometry scoring of renal tumors predict outcomes in patients selected for robot-assisted partial nephrectomy?

BACKGROUND AND PURPOSE: Robot-assisted partial nephrectomy has emerged as a viable surgical treatment for patients with certain renal tumors. We hypothesized that extirpation of more complex tumors, as graded with the nephrometry score, would result in worse operative and postoperative outcomes when compared with tumors with lower nephrometry scores. We report whether nephrometry-graded tumor complexity impacted operative or postoperative outcomes. PATIENTS AND METHODS: A single experienced surgeon at our tertiary-care institution performed more than 100 robot-assisted partial nephrectomies. Istitutional Review Board-approved data collection was available for 95 patients, and nephrometry scores were available for 92 patients. Cases were divided into tertiles, based on their nephrometry score of low, medium, or high. We compared preoperative, operative, and postoperative data to evaluate any differences between the three tertiles. Statistical analysis was performed using JMP 8 software. RESULTS: There were 66, 22, and 4 patients in the low, medium, and high nephrometry score tertiles, respectively. There were no statistically significant differences between the tertiles regarding warm ischemia time, estimated blood loss, operative time, length of stay, change in glomerular filtration rate, Clavien-graded complication rates, or any other metric. Mean follow-up for each tertile was also similar. CONCLUSIONS: We have routinely been using the nephrometry scoring system to anatomically describe renal masses before robot-assisted partial nephrectomy. Our findings demonstrate that nephrometry-graded tumor complexity was not related to any differences in outcomes for patients with renal tumors who were selected at our institution to undergo robot-assisted partial nephrectomy. The nephrometry system remains a reproducible standardized classification of renal tumor anatomy, but it remains to be seen if this can be used to predict surgical outcomes.

Growth inhibition of androgen-responsive prostate cancer cells with brefeldin A targeting cell cycle and androgen receptor.

BACKGROUND: Androgen ablation is one of the viable therapeutic options for patients with primary hormone (androgen)-dependent prostate cancer. However, an antibiotic brefeldin A (BFA) has been shown to exhibit the growth inhibitory effect on human cancer cells. We thus investigated if BFA might inhibit proliferation of androgen-responsive prostate cancer LNCaP cells and also explored how it would be carried out, focusing on cell cycle and androgen receptor (AR). METHODS: Androgen-mediated cellular events in LNCaP cells were induced using 5alpha-dihydrotestosterone (DHT) as an androgenic mediator. Effects of BFA on non-DHT-stimulated or DHT-stimulated cell growth were assessed. Its growth inhibitory mechanism(s) was further explored; performing cell cycle analysis on a flow cytometer, assessing AR activity by AR binding assay, and analyzing AR protein expression using Western blot analysis. RESULTS: DHT (1 nM) was capable of stimulating LNCaP cell growth by ~40% greater than non-stimulated controls, whereas BFA (30 ng/ml) completely inhibited such DHT-stimulated proliferation. Cell cycle analysis showed that this BFA-induced growth inhibition was associated with a ~75% reduction in the cell number in the S phase and a concomitant increase in the G1 cell number, indicating a G1 cell cycle arrest. This was further confirmed by the modulations of specific cell cycle regulators (CDK2, CDK4, cyclin D1, and p21WAF1), revealed by Western blots. In addition, the growth inhibition induced by BFA was accompanied by a profound (~90%) loss in AR activity, which would be presumably attributed to the significantly reduced cellular AR protein level. CONCLUSIONS: This study demonstrates that BFA has a potent growth inhibitory activity, capable of completely inhibiting DHT (androgen)-stimulated LNCaP proliferation. Such inhibitory action of BFA appears to target cell cycle and AR: BFA led to a G1 cell cycle arrest and the down-regulation of AR activity/expression, possibly accounting for its primary growth inhibitory mechanism. Thus, it is conceivable that BFA may provide a more effective therapeutic modality for patients with hormone-dependent prostate cancer.

Synergistic potentiation of interferon activity with maitake mushroom d-fraction on bladder cancer cells.

OBJECTIVE: To examine whether the combination of interferon (IFN)-alpha and maitake mushroom D-fraction (PDF), a bioactive mushroom extract, might potentiate the anticancer activity of IFN-alpha in bladder cancer T24 cells in vitro. MATERIALS AND METHODS: Effects of recombinant IFN-alpha(2b) (0-50 000 IU/mL), PDF (0-700 microg/mL), or their combinations were assessed on T24 cell growth at 72 h. Cell cycle analysis and assays for double-stranded DNA-dependent protein kinase (DNA-PK) were performed to explore possible antiproliferative mechanism of these agents. RESULTS: IFN-alpha(2b) was able to induce a significant ( approximately 50%) growth reduction at 20 000 IU/mL, which further declined to approximately 66% at 50 000 IU/mL. PDF had no effects up to 200 microg/mL, but there was an approximately 20% and approximately 53% growth reduction at 400 and 700 microg/mL, respectively. When the varying concentrations of IFN-alpha(2b) and PDF were combined, 10 000 IU/mL of IFN-alpha(2b) combined with 200 microg/mL of PDF resulted in an approximately 75% growth reduction. This was accompanied by a G(1) cell cycle arrest, shown by cell cycle analysis. Concurrently, DNA-PK activity in IFN-alpha(2b)/PDF-treated cells was almost three-fold higher than controls. CONCLUSIONS: The combination of IFN-alpha(2b) (10 000 IU/mL) and PDF (200 microg/mL) reduced growth by approximately 75% in T24 cells. This appears to be due to a synergistic potentiation of these two agents, inducing a G(1) arrest with DNA-PK activation. Therefore, the IFN-alpha(2b)/PDF combination could trigger DNA-PK activation that may act on the cell cycle to cease cancer cell growth.

Mode of cytotoxic action of nephrotoxic agents: oxidative stress and glutathione-dependent enzyme.

OBJECTIVE: To investigate the cytotoxic action of nephrotoxic agents using an in vitro renal cell model, focusing on the cellular oxidative status and a specific glutathione (GSH)-dependent enzyme, glyoxalase I (Gly-I). MATERIALS AND METHODS: Renal proximal tubular LLC-PK(1) cells were exposed to mercuric chloride, glycerol, cisplatin, gentamicin and cyclosporin A, and cell number/viability were determined. Oxidative stress was assessed by lipid peroxidation (LPO) assay, and Gly-I activity was measured by enzymatic method on a spectrophotometer. RESULTS: Both mercuric chloride (30 microm) and glycerol (2.5%) were highly toxic to LLC-PK(1) cells, inducing >90% cell death within 24 h. The remaining agents led to slightly >50% growth inhibition at 72 h. The LPO levels at 3 h in cells exposed to mercuric chloride or glycerol were approximately 2.5 times higher than that in controls. N-acetylcysteine (NAC), a potent antioxidant and precursor for GSH, almost completely (>95%) prevented renal cell death from mercuric chloride or glycerol. Gly-I activity was dependent on NAC and closely associated with cell viability. A approximately 65% loss in Gly-I activity by mercuric chloride/glycerol led to >90% cell death, while restoring a basal activity of Gly-I with NAC was accompanied by complete cell viability. CONCLUSIONS: The cytotoxic action of nephrotoxic agents appears to be triggered by oxidative stress, leading to Gly-I inactivation. As Gly-I plays a key role in cellular detoxification, its inactivation under oxidative stress probably becomes fatal to cells. However, cytoprotection provided with NAC is significant and might have implications in preventing renal cell injury mediated through nephrotoxic agents.

Possible disease remission in patient with invasive bladder cancer with D-fraction regimen.

Superficial bladder tumors are the most prevalent form of bladder cancers and transurethral resection is the primary surgical modality for those tumors. However, nearly 65% of patients will have tumor recurrence in five years while about 15% will have progression to muscle invasion. Thus, the primary therapeutic aim is to prevent multiple recurrences and progression to a more advanced, invasive disease. We here report an 87-year-old white male patient with invasive bladder cancer who received an unconventional oral regimen of D-fraction, the bioactive extract of Maitake mushroom (Grifola frondosa), following endoscopic transurethral resection of bladder tumor. Despite a high risk for disease recurrence, follow-up yet indicated no clinical evidence of progression of residual disease or recurrence of invasive cancer. It has been nearly two years but the patient remains remarkably well and appears to be in remission. To our knowledge, this is the first and only case report of possible disease remission in a bladder cancer patient after the two-year follow-up of D-fraction regimen, so that further studies with long terms are required for drawing a relevant conclusion. Nevertheless, it is conceivable that D-fraction is a natural agent that may have clinical implications in patients with superficial bladder tumors.

Possible immunotherapeutic potentiation with D-fraction in prostate cancer cells.

BACKGROUND: Prostate cancer remains the most common malignancy among elderly men and the second leading cause of cancer death in the United States. Although several conventional therapies are currently available, they have a low efficacy and the more effective treatment modalities need to be established. Interferons (IFNs) are one of such options known as immunotherapy and demonstrated their antitumor effects on certain cancer types. Yet such antitumor activity should be improved or potentiated to have the satisfactory outcomes. In fact, combination therapy has been proposed as an alternative approach and is being underway in human and animal studies. Accordingly, we studied whether the combination of IFN-alpha and D-fraction (PDF), a bioactive mushroom extract, might potentiate anticancer activity of IFN-alpha in prostate cancer PC-3 cells in vitro. RESULTS: Potential effects of recombinant IFN-alpha(2b) (0-100,000 IU/ml), PDF (0-1,000 microg/ml), or their combinations were assessed on the growth of PC-3 cells at 72 h. Cell cycle analysis using a flow cytometer and Western blot analysis were performed to explore antiproliferative mechanism of these agents. The dose-dependent study showed that IFN-alpha(2b) up to 20,000 (20 K) IU/ml had no significant effects, but >60% growth reduction was attained 60%) down-regulated in IFN/PDF-treated cells. CONCLUSION: The combination of IFN-alpha(2b) (10 K IU/ml) and PDF (250 microg/ml) is capable of inducing a approximately 65% reduction in PC-3 cell growth. This appears to be due to a synergistic potentiation of two agents, leading to a G1 cell cycle arrest. Thus, it is conceivable that PDF may potentiate IFN-alpha(2b) activity, improving immunotherapy for prostate cancer.

Flexible ureteroscopy update: indications, instrumentation and technical advances.

Retrograde ureteroscopy has recently gained a broadened indication for use from diagnostic to a variety of complex minimally invasive therapies. This review aims to look at the recent advances in the instrumentation and accessories, the widened indications of its use, surgical techniques and complications. With minimization of ureteroscopic instruments manufacturers are challenged to develop new, smaller and sturdier instruments that all will also survive the rigors of surgical therapy.

Accuracy of three-dimensional CT angiography for preoperative vascular evaluation of laparoscopic living renal donors.

PURPOSE: A retrospective review of preoperative three-dimensional (3D) CT and the operative findings during laparoscopic donor nephrectomy. PATIENTS AND METHODS: Fifty-four consecutive patients underwent laparoscopic donor nephrectomy. Of these patients, 51 had preoperative 3D reconstructed CT scans. Each radiologic report was compared with the operative report. RESULTS: The 3D CT correctly identified the arteries in 98% of the patients and the veins in 96%. CONCLUSIONS: Preoperative CT angiography can accurately identify the renal vasculature.