Narrative review-focal therapy: are we ready to change the prostate cancer treatment paradigm?

Background and Objective: Prostate cancer (PCa) has seen improved detection methods with a subsequent rise in disease prevalence, making novel prostate cancer treatment options an exciting yet controversial topic. Current treatment modalities encompass traditional approaches, namely surgery (radical prostatectomy) and radiation therapy. While heralded as a standard of care, these modalities may come with significant risk profiles, primarily sexual (erectile dysfunction) and urinary incontinence. Advances in technology and imaging, specifically multi-parametric MRI, have afforded great leaps in targeted focal therapy as a primary treatment option for localized PCa. This review identifies and highlights published data for novel and emerging PCa focal therapy (FT) modalities. Methods: Our study identified and reviewed the current literature for relevant investigations related to primary FT modalities as they apply to the treatment of prostate cancer. After an internal review, relevant studies (published in English, between 2000-April 2022) were included for analysis and summarization. Key Content and Findings: We provide a concise review of several novel focal therapy modalities that offer realistic potential for primary treatment of localized prostate cancer. Our narrative includes studies that primarily include their respective results, specifically focusing on those that reported both oncologic and quality-of-life outcomes after focal therapy. While still in its cumulative infancy, we discuss the current limitations, future directions, and advancements that hopefully push focal therapy into the limelight. Conclusions: While many of the mentioned focal therapies for PCa have shown promising pathologic and quality of life outcomes, further clinical evidence is required to change overall management guidelines and recommendations. The advantages of FT in avoiding sexual and urinary side-effects of radical surgery or radiation are apparent; however, it is necessary to recognize the need for further long-term evidence that is durable over time and comparable to current gold-standard treatment options.

Alternatives to whole gland treatment for localized prostate cancer: a review of novel focal therapies.

PURPOSE OF REVIEW: The mainstays of the management of clinically localized prostate cancer have historically rested upon active surveillance, radiation therapy, or radical prostatectomy. Although both radiation and surgical treatment of localized prostate cancer can achieve excellent oncologic outcomes, the subsequent potential adverse effects of urinary stress incontinence and erectile dysfunction are unappealing to patients. This has led to investigational studies centered upon focal treatment of the cancerous lesion, with the aim to improve quality-of-life outcomes. In this review, we describe numerous novel modalities, including nanoparticle ablation and irreversible electroporation, which are being utilized for the focal treatment of clinically localized prostate cancer. RECENT FINDINGS: Although many of these novel therapies are in their investigational infancy, several have revealed very promising results both in their post-treatment pathologic outcomes as well as objective quality-of-life measures. SUMMARY: Initial data regarding novel focal therapy for prostate cancer treatment show promising short-term outcomes in regards to oncologic and quality-of-life assessments. Further investigational studies are needed to determine inclusion criteria for the selection of optimal candidates.

Novel Automated Three-Dimensional Surgical Planning Tool and Magnetic Resonance Imaging/Ultrasound Fusion Technology to Perform Nanoparticle Ablation and Cryoablation of the Prostate for Focal Therapy.

Purpose: Although MRI/ultrasound fusion has been primarily used to assist in the diagnosis of prostate cancer, this technology can also be used to focally treat localized prostate cancer. We present one case of nanoparticle-directed ablation and two cases of cryoablation to focally treat prostate tumors. Patients and Methods: Three patients underwent MRI/ultrasound fusion transperineal prostate biopsies to confirm low- to intermediate-risk prostate cancer. The MRI lesions correlated with the biopsy-proven disease. Pelvic MRI segmentation was performed with DynaCAD 5.0 workstation. The MRI lesion including a 6 to 10 mm margin, prostate, bladder, urethra, urethral sphincter, rectum, and pubic bone were segmented. MRI/ultrasound fusion was performed with the novel Philips UroNav 4.0 system. Lesions were treated with focal nanoparticle ablation or focal cryoablation. Results: A 69-year-old man with a right posterior medial peripheral zone lesion positive for Gleason grade group (GG)3 cancer was treated with focal nanoparticle ablation. The UroNav 4.0 system reported 100% ablation of the segmented tumor and 94% of the 6 to 10 mm margin at the end of the case. A 68-year-old man with a left anterior fibromuscular stroma lesion positive for Gleason GG2 cancer and a 71-year-old man with a right peripheral zone posterior lateral lesion positive for Gleason GG1 cancer were treated with focal cryoablation. The UroNav 4.0 system reported 100% ablation of the segmented tumor and 82% of the 6 to 10 mm margin at the end of the case. Conclusion: Observation of the prostate tumor(s), surrounding critical structures, and pelvis in three dimensions (3D), along with the anticipated ablation zone, is one of the challenges of pelvic surgery and percutaneous ablation. The DynaCAD 5.0 Urology system can create an auto-segmented 3D rendering of critical structures and the tumor(s), as well as observation and quantification of the anticipated ablation coverage, to facilitate preoperative planning of needle placement. ClinicalTrials.gov nos.: NCT02680535 and NCT04656678.

Feasibility and Utility of Mobile Applications for the Evaluation of Urology Residents' Surgical Competence.

OBJECTIVE: To provide real-time assessment and feedback on the competency of urology residents' surgical skill via mobile applications and examine their feasibility and utility. MATERIALS AND METHODS: Two mobile application-based systems (SIMPL and myTIPreport) were sequentially implemented for the case-by-case assessment of residents' performance of surgical skills at a single institution. Data was collected regarding residents' perception of their feedback pre- and post-implementation of the applications. Faculty were surveyed after their implementation to determine their feasibility and utility. RESULTS: 297 individual evaluations were completed with SIMPL and 822 with myTIPreport over four and eleven months respectively. Post-implementation, residents showed significantly improved perceptions regarding the quantity and personalization of surgical skill feedback (P = .043 and .005 respectively). A majority (75%) of the faculty found the mobile applications feasible to use, an improvement compared to prior methods of resident evaluation, and would recommend continued use. CONCLUSION: This study represents the first documented use of real-time surgical competency assessment in urology. The use of mobile applications to evaluate urology residents' surgical competency in clinical practice is both feasible and useful. Their use may allow for more individualized surgical skill teaching during training and for the verification of the surgical skills necessary to practice autonomously.

Extracapsular extension on multiparametric magnetic resonance imaging better predicts pT3 disease at radical prostatectomy compared to perineural invasion on biopsy.

INTRODUCTION: Risk assessment for non-organ-confined prostate cancer (PCa) is important in the surgical planning for radical prostatectomy (RP). Perineural invasion (PNI) on prostate biopsy has been associated with adverse pathological outcomes at prostatectomy. Similarly, the identification of suspected extracapsular extension (ECE) on multiparametric magnetic resonance imaging (mpMRI) has been shown to predict non-organ-confined disease. However, no prior study has compared these factors in predicting adverse pathology at prostatectomy. We evaluated mpMRI ECE and prostate biopsy PNI on multivariable analysis to determine their ability to predict pathological stage at time of RP. METHODS: We retrospectively investigated the prostatectomy database at our institution to identify men who underwent prostate biopsy with pre-biopsy mpMRI and subsequent RP from 2013-2017. Multivariable regression analysis was performed to compare the association of mpMRI ECE (mECE) and PNI on prostate biopsy on the likelihood of finding pT3 disease on pathology post-prostatectomy. RESULTS: Of a total 454 RP between 2013 and 2017, 191 patients met our inclusion criteria. Stage pT2 and pT3+ were found in 120 (62.8%) and 71 (37.2%) patients, respectively. Patients with mECE had 4.84 cumulative odds of worse pathological stage on RP (p=0.045) compared to PNI on biopsy, which showed cumulative odds of 2.25 (p=0.048). When controlling only for those patients without PNI, mECE was still found to be a significant predictor of pT3 disease at RP (p=0.030); however, in patients without mECE, PNI was not significant (p=0.062). CONCLUSIONS: While mECE and biopsy PNI were both associated with worse pathological stage on RP, mECE had significantly higher cumulative odds compared to PNI. The significant predictive ability of mECE adds further clinical value to the use of mpMRI in PCa management. While validation in a larger cohort is required, these factors have important clinical implications with regards to early diagnosis of advanced disease and surgical planning.

Multi-institutional Evaluation of Producing and Testing a Novel 3D-Printed Laparoscopic Trainer.

OBJECTIVE: To create, distribute, and evaluate the efficacy of a portable, cost-effective 3D-printed laparoscopic trainer for surgical skills development. METHODS: The UCI Trainer (UCiT) laparoscopic simulator was developed via computer-aided designs (CAD), which were used to 3D-print the UCiT. Once assembled, a tablet computer with a rear-facing camera was attached for video and optics. Four institutions were sent the UCiT CAD files with a 3D-printer and instructions for UCiT assembly. For a comparison of the UCiT to a standard trainer, peg transfer and intracorporeal knot tying skills were accessed. These tasks were scored, and participants were asked to rate their experience with the trainers. Lastly, a questionnaire was given to individuals who 3D-printed and assembled the UCiT. RESULTS: We recruited 25 urologists; none had any 3D-printing experience. The cost of printing each trainer was $26.50 USD. Each institution used the Apple iPad for optics. Six of eight participants assembled the UCiT in < 45 minutes, and rated assembly as somewhat easy. On objective scoring, participants performed tasks equally well on the UCiT vs the conventional trainer. On subjective scoring, the conventional trainer provided a significantly better experience vs the UCiT; however, all reported that the UCiT was useful for surgical education. CONCLUSION: The UCiT is a low cost, portable training tool that is easy to assemble and use. UCiT provided a platform whereby participants performed laparoscopic tasks equal to performing the same tasks on the more expensive, nonportable standard trainer.

A Hospital Is Not Just a Factory, but a Complex Adaptive System-Implications for Perioperative Care.

Many methods used to improve hospital and perioperative services productivity and quality of care have assumed that the hospital is essentially a factory, and therefore, that industrial engineering and manufacturing-derived redesign approaches such as Six Sigma and Lean can be applied to hospitals and perioperative services just as they have been applied in factories. However, a hospital is not merely a factory but also a complex adaptive system (CAS). The hospital CAS has many subsystems, with perioperative care being an important one for which concepts of factory redesign are frequently advocated. In this article, we argue that applying only factory approaches such as lean methodologies or process standardization to complex systems such as perioperative care could account for difficulties and/or failures in improving performance in care delivery. Within perioperative services, only noncomplex/low-variance surgical episodes are amenable to manufacturing-based redesign. On the other hand, complex surgery/high-variance cases and preoperative segmentation (the process of distinguishing between normal and complex cases) can be viewed as CAS-like. These systems tend to self-organize, often resist or react unpredictably to attempts at control, and therefore require application of CAS principles to modify system behavior. We describe 2 examples of perioperative redesign to illustrate the concepts outlined above. These examples present complementary and contrasting cases from 2 leading delivery systems. The Mayo Clinic example illustrates the application of manufacturing-based redesign principles to a factory-like (high-volume, low-risk, and mature practice) clinical program, while the Kaiser Permanente example illustrates the application of both manufacturing-based and self-organization-based approaches to programs and processes that are not factory-like but CAS-like. In this article, we describe how factory-like processes and CAS can coexist within a hospital and how self-organization-based approaches can be used to improve care delivery in many situations where manufacturing-based approaches may not be appropriate.

Partial Nephrectomy is Associated with Higher Risk of Relapse Compared with Radical Nephrectomy for Clinical Stage T1 Renal Cell Carcinoma Pathologically Up Staged to T3a.

PURPOSE: We studied recurrence-free survival after partial vs radical nephrectomy for clinical stage T1 renal cell carcinoma in all patients and in those up staged to pathological stage T3a. MATERIALS AND METHODS: We retrospectively reviewed the records of 1,250 patients who underwent partial or radical nephrectomy for clinically localized T1 renal cell carcinoma between 2006 and 2014. Recurrence-free survival was estimated using the Kaplan-Meier method and evaluated as a function of nephrectomy type with the log rank test and Cox models, adjusting for clinical, radiological and pathological characteristics. RESULTS: A total of 86 recurrences (7%) were observed during a median followup of 37 months. No difference in recurrence-free survival between partial and radical nephrectomy was found among all clinical stage T1 renal cell carcinomas. T3a up staging was noted in 140 patients (11%) and recurrent disease was observed in 44 (31.4%) during a median followup of 38 months. Among up staged T3a cases partial nephrectomy was associated with shorter recurrence-free survival compared to radical nephrectomy on univariable analysis (recurrence HR 2.04, 95% CI 1.12-3.68, p = 0.019) and multivariable analysis (recurrence HR 5.39, 95% CI 1.94-14.9, p = 0.001). CONCLUSIONS: In a subgroup of patients clinically staged T1 renal cell carcinoma will be pathologically up staged to T3a. Among these patients those who undergo partial nephrectomy appear to have inferior recurrence-free survival relative to those who undergo radical nephrectomy.

Reanalysis comparisons of upper tropospheric/lower stratospheric jets and multiple tropopauses.

The representation of upper tropospheric/lower stratospheric (UTLS) jet and tropopause characteristics is compared in five modern high-resolution reanalyses for 1980 through 2014. Climatologies of upper tropospheric jet, subvortex jet (the lowermost part of the stratospheric vortex), and multiple tropopause frequency distributions in MERRA (Modern Era Retrospective Analysis for Research and Applications), ERA-I (the ECMWF interim reanalysis), JRA-55 (the Japanese 55-year Reanalysis), and CFSR (the Climate Forecast System Reanalysis) are compared with those in MERRA-2. Differences between alternate products from individual reanalysis systems are assessed; in particular, a comparison of CFSR data on model and pressure levels highlights the importance of vertical grid spacing. Most of the differences in distributions of UTLS jets and multiple tropopauses are consistent with the differences in assimilation model grids and resolution: For example, ERA-I (with coarsest native horizontal resolution) typically shows a significant low bias in upper tropospheric jets with respect to MERRA-2, and JRA-55 a more modest one, while CFSR (with finest native horizontal resolution) shows a high bias with respect to MERRA-2 in both upper tropospheric jets and multiple tropopauses. Vertical temperature structure and grid spacing are especially important for multiple tropopause characterization. Substantial differences between MERRA and MERRA-2 are seen in mid- to high-latitude southern hemisphere winter upper tropospheric jets and multiple tropopauses, and in the upper tropospheric jets associated with tropical circulations during the solstice seasons; some of the largest differences from the other reanalyses are seen in the same times and places. Very good qualitative agreement among the reanalyses is seen between the large scale climatological features in UTLS jet and multiple tropopause distributions. Quantitative differences may, however, have important consequences for transport and variability studies. Our results highlight the importance of considering reanalyses differences in UTLS studies, especially in relation to resolution and model grids; this is particularly critical when using high-resolution reanalyses as an observational reference for evaluating global chemistry climate models.

Active surveillance for incidental renal mass in the octogenarian.

OBJECTIVE: To evaluate the oncologic outcomes among a large cohort of octogenarian patients placed on active surveillance for a localized renal mass. METHODS: We retrospectively reviewed patients ≥80 years of age presenting for asymptomatic, incidentally detected clinically localized stage T1 renal mass between 2006 and 2013 who were followed by active surveillance (AS). The primary endpoint was development of metastatic renal cell carcinoma. Secondary outcomes included intervention-free survival, cancer-specific survival, and overall survival. RESULTS: Eighty-nine octogenarians (median age = 83.4 years) were placed on AS for a median 29.9 months. Median Charlson Comorbidity Index and Katz Index of Independence in Activities of Daily Living scores were 2 and 5, respectively. For all comers, median initial tumor size was 2.4 cm with median growth rate of 0.20 cm/year. Eight (9.0%) patients failed AS due to delayed intervention and three (1.1%) due to systemic progression after median follow-up of 27.8 and 39.9 months, respectively. Two (2.2%) patients in the delayed intervention cohort developed metastasis after treatment. Tumor growth rate was significantly higher among those undergoing intervention versus no intervention (0.60 vs. 0.15 cm/year, P = 0.05) and among patients with systemic progression versus no metastasis (1.28 vs. 0.18 cm/year, P = 0.001). Five-year intervention-free, metastasis-free, cancer-specific, and overall survivals were 90.6, 95.6, 95.6, and 85.7%, respectively. CONCLUSION: AS represents an effective management strategy in octogenarians given low overall risk of metastasis. Tumor growth kinetics may identify patients at risk of systemic progression in whom treatment should be considered.

Positive Surgical Margins Increase Risk of Recurrence after Partial Nephrectomy for High Risk Renal Tumors.

PURPOSE: The clinical significance of a positive surgical margin after partial nephrectomy remains controversial. The association between positive margin and risk of disease recurrence in patients with clinically localized renal neoplasms undergoing partial nephrectomy was evaluated. MATERIALS AND METHODS: A retrospective multi-institutional review of 1,240 patients undergoing partial nephrectomy for clinically localized renal cell carcinoma between 2006 and 2013 was performed. Recurrence-free survival was estimated using the Kaplan-Meier method and evaluated as a function of positive surgical margin with the log rank test and Cox models adjusting for tumor size, grade, histology, pathological stage, focality and laterality. The relationship between positive margin and risk of relapse was evaluated independently for pathological high risk (pT2-3a or Fuhrman grades III-IV) and low risk (pT1 and Fuhrman grades I-II) groups. RESULTS: A positive surgical margin was encountered in 97 (7.8%) patients. Recurrence developed in 69 (5.6%) patients during a median followup of 33 months, including 37 (10.3%) with high risk disease (eg pT2-pT3a or Fuhrman grade III-IV). A positive margin was associated with an increased risk of relapse on multivariable analysis (HR 2.08, 95% CI 1.09-3.97, p=0.03) but not with site of recurrence. In a stratified analysis based on pathological features, a positive surgical margin was significantly associated with a higher risk of recurrence in cases considered high risk (HR 7.48, 95% CI 2.75-20.34, p <0.001) but not low risk (HR 0.62, 95% CI 0.08-4.75, p=0.647). CONCLUSIONS: Positive surgical margins after partial nephrectomy increase the risk of disease recurrence, primarily in patients with adverse pathological features.

To clamp or not to clamp? Long-term functional outcomes for elective off-clamp laparoscopic partial nephrectomy.

OBJECTIVE: To evaluate whether elective off-clamp laparoscopic partial nephrectomy (LPN) affords long-term renal functional benefit compared with the on-clamp approach. PATIENTS AND METHODS: This is a retrospective review of patients who underwent elective LPN between 2006 and 2011. Patients were followed longitudinally for up to 5 years. In all, 315 patients with radiographic evidence of a solitary renal mass and normal-appearing contralateral kidney underwent elective LPN; 209 were performed on-clamp vs 106 off-clamp. One patient who required conversion from LPN to open PN was excluded from the study. Additionally, four patients in the on-clamp cohort who underwent subsequent radical nephrectomy for local-regional recurrence were excluded from longitudinal functional evaluation after their procedure. The primary objective was to evaluate differences in postoperative estimated glomerular filtration rate (eGFR) between hilar clamping groups. Subgroup analyses were performed for patients with clamp times >30 min and those with baseline renal insufficiency (eGFR <60 mL/min/1.73m(2) ). Risk of developing worsened or new-onset renal insufficiency was also compared. RESULTS: The mean preoperative eGFR was similar between the on-clamp and off-clamp cohorts (80.7 vs 84.1 mL/min/1.73m(2) , P > 0.05). Univariable and multivariable analyses did not show significant differences in postoperative eGFR between both groups among all-comers, those with clamp times >30 min, and patients with baseline renal insufficiency. Risk of chronic kidney disease was not diminished by the off-clamp approach with up to 5 years of follow-up. CONCLUSIONS: Progressive recovery of renal function after hilar clamping in the elective setting eclipses short-term functional benefit achieved with off-clamp LPN by 6 months; there was no significant difference in eGFR or the percentage incidence of chronic kidney disease between the on-clamp and off-clamp cohorts with up to 5 years follow-up. As such, eliminating transient ischaemia during elective LPN does not confer clinical benefit.

Outcomes of Laparoscopic Partial Nephrectomy in Patients Continuing Aspirin Therapy.

PURPOSE: A clinical dilemma surrounds the use of aspirin therapy during laparoscopic partial nephrectomy. Despite reduced cardiac morbidity with perioperative aspirin use, fear of bleeding related complications often prompts discontinuation of therapy before surgery. We evaluate perioperative outcomes among patients continuing aspirin and those in whom treatment is stopped preoperatively. MATERIALS AND METHODS: A total of 430 consecutive cases of laparoscopic partial nephrectomy performed between January 2012 and October 2014 were reviewed. Patients on chronic aspirin therapy were stratified into on aspirin and off aspirin groups based on perioperative status of aspirin use. Primary end points evaluated included estimated intraoperative blood loss and incidence of bleeding related complications, major postoperative complications, and thromboembolic events. Secondary outcomes included operative time, transfusion rate, length of hospital stay, rehospitalization rate and surgical margin status. RESULTS: Among 101 (23.4%) patients on chronic aspirin therapy, antiplatelet treatment was continued in 17 (16.8%). Bleeding developed in 1 patient in the on aspirin group postoperatively and required angioembolization. Conversely 1 myocardial infarction was observed in the off aspirin cohort. There was no significant difference in the incidence of major postoperative complications, intraoperative blood loss, transfusion rate, length of hospital stay and rehospitalization rate. Operative time was increased with continued aspirin use (181 vs 136 minutes, p=0.01). CONCLUSIONS: Laparoscopic partial nephrectomy is safe and effective in patients on chronic antiplatelet therapy who require perioperative aspirin for cardioprotection. Larger, prospective studies are necessary to discern the true cardiovascular benefit derived from continued aspirin therapy as well as better characterize associated bleeding risk.

Pfannenstiel laparoendoscopic single-site (LESS) vs conventional multiport laparoscopic live donor nephrectomy: a prospective randomized controlled trial.

OBJECTIVE: To present outcomes of a randomized, patient-blinded controlled trial on Pfannenstiel laparoendoscopic single-site (LESS) vs conventional multiport laparoscopic live donor nephrectomy. PATIENTS AND METHODS: Patients presenting as left kidney donors between January 2009 and November 2011 were randomized to LESS donor nephrectomy (LESS-DN: n = 15) or conventional laparoscopic donor nephrectomy (LDN: n = 14). Patients were blinded to the surgical approach preoperatively and attempts to continue patient blinding postoperatively were made by applying dressings consistent with multiple conventional laparoscopic incisions for all patients. De-identified data related to the operation, peri-operative course and postoperative follow-up were prospectively collected and compared between the two groups with an intention-to-treat analysis. RESULTS: There were no significant differences between the groups when comparing operating time, estimated blood loss (EBL), i.v. fluid administration, renal allograft warm ischaemia time (WIT), length of hospital stay (LOS) and total inpatient analgesic requirements. Quantitative pain assessment was not significantly different on postoperative day (POD) #0, however, it was significantly lower in the LESS-DN group, beginning on POD #1 (P < 0.05). The changes in haematocrit and serum creatinine in the two groups were not significantly different, and there were no blood transfusions in either group, nor was there a decline in estimated glomerular filtration rate to <60 mL/min per 1.73 m² of body surface area in any patients. Two patients in the LESS-DN group were converted to conventional LDN, both because of failure to progress effectively. All allografts were functional at the time of transplantation and revascularization, with no cases of hyperacute rejection. CONCLUSIONS: Peri-operative variables including EBL, WIT and LOS were equivalent when comparing Pfannenstiel LESS-DN with conventional LDN. Patient-reported visual analogue pain scale scores were significantly lower in the LESS-DN group beginning on the first postoperative day.

Perioperative outcomes of off-clamp vs complete hilar control laparoscopic partial nephrectomy.

OBJECTIVE: To evaluate perioperative and 6-month renal functional outcomes of patients undergoing off-clamp vs complete hilar control laparoscopic partial nephrectomy (LPN). PATIENTS AND METHODS: A retrospective review of 489 patients undergoing LPN was completed. Preoperative imaging assessed tumour characteristics. Patient demographics, perioperative parameters, and postoperative outcomes were documented. Multivariable regression analysis was used to assess factors contributing to changes in postoperative renal function between off-clamp and clamped LPN. RESULTS: In all, 289 LPNs were performed on-clamp and 150 were performed off-clamp. Tumours in the on-clamp group were larger than those in the off-clamp group (mean [range] 3.3 [0.5-13.5] vs 2.7 [0.4-9] cm, P = 0.003). Univariable analysis comparing off-clamp to on-clamp cohorts showed that estimated glomerular filtration rate (eGFR) was better preserved in the off-clamp cohort at 6 months (-5.8% vs -11.4%, P = 0.046). Multivariable analysis of the groups showed that estimate blood loss (P = 0.015) and warm ischaemia time (WIT, P < 0.001) were the only significant predictors of decreased eGFR in the postoperative period. Difference in eGFR at 6 months was not significant when WIT was limited to 30 min. The complication rate was greater in the clamped cohort (10% vs 20%, P = 0.012). There was no difference in transfusion rate or positive margin status. CONCLUSIONS: LPN without hilar clamping is feasible, safe and associated with less renal injury as assessed by postoperative GFR in select patients. With experience, it can be applied to complex renal lesions.

Toll-like receptor 7 agonist therapy with imidazoquinoline enhances cancer cell death and increases lymphocytic infiltration and proinflammatory cytokine production in established tumors of a renal cell carcinoma mouse model.

Imidazoquinolines are synthetic toll-like receptor 7 and 8 agonists and potent dendritic cell activators with established anticancer activity. Here we test the hypothesis that imidazoquinoline has in vivo efficacy within established renal cell carcinoma (RCC) tumors. Immunocompetent mice bearing syngeneic RCC xenografts were treated with imidazoquinoline or placebo at two separate time points. Harvested tumors were assayed by TUNEL/caspase-3/Ki67 immunostains to evaluate cell death/apoptosis/proliferation, and CD3/B220/CD45 immunostains to evaluate T-cell lymphocyte/B-cell lymphocyte/pan-leukocyte tumor infiltration. ELISA measurement of tumor and serum levels of proinflammatory cytokines, IL-6 and MCP-1, was performed. A single imidazoquinoline dose significantly decreased RCC tumor growth by 50% and repeat dosing compounded the effect, without observed weight loss or other toxicity. Tumor immunostaining revealed significant increases in cell death and apoptosis without changes in cell proliferation, supporting induction of apoptosis as the primary mechanism of tumor growth suppression. Imidazoquinoline treatment also significantly enhanced peritumoral aggregation and intratumoral infiltration by T-cell lymphocytes, while increasing intratumoral (but not serum) levels of proinflammatory cytokines. In conclusion, imidazoquinoline treatment enhances T-cell lymphocyte infiltration and proinflammatory cytokine production within established mouse RCC tumors, while suppressing tumor growth via induction of cancer cell apoptosis. These findings support a therapeutic role for imidazoquinoline in RCC.

Controversial technology: the Chunnel and the laparoscopic retroperitoneal lymph node dissection (RPLND).

• Laparoscopic retroperitoneal lymph node dissection (L-RPLND) was first introduced in 1992, initially as a staging procedure. • With advances in instrumentation and laparoscopic techniques, as well as improved understanding of laparoscopic anatomy, L-RPLND has developed to duplicate open RPLND. • Unlike the relatively rapid adoption of laparoscopy for other applications including nephrectomy and prostatectomy, L-RPLND has been slow to be universally accepted. • The limited numbers of patients requiring RPLND and technical challenges in performing the dissection have undoubtedly contributed to its delayed reception. • This review will present available data on this technique and discuss issues potentially inhibiting acceptance by traditional surgeons.