The urologist's learning curve of "in-bore" magnetic resonance-guided prostate biopsy.

BACKGROUND: The combination of multi-parametric MRI to locate and define suspected lesions together with their being targeted by an MRI-guided prostate biopsy has succeeded in increasing the detection rate of clinically significant disease and lowering the detection rate of non-significant prostate cancer. In this work we investigate the urologist's learning curve of in-bore MRI-guided prostate biopsy which is considered to be a superior biopsy technique. MATERIALS AND METHODS: Following Helsinki approval by The Chaim Sheba Medical Center ethics committee in accordance with The Sheba Medical Center institutional guidelines (5366-28-SMC) we retrospectively reviewed 110 IB-MRGpBs performed from 6/2016 to 1/2019 in a single tertiary center. All patients had a prostate multi-parametric MRI finding of at least 1 target lesion (prostate imaging reporting and data system [PI-RADS] score ≥ 3). We analyzed biopsy duration and clinically significant prostate cancer detection of targeted sampling in 2 groups of 55 patients each, once by a urologist highly trained in IB-MRGpBs and again by a urologist untrained in IB-MRGpBs. These two parameters were compared according to operating urologist and chronologic order. RESULTS: The patients' median age was 68 years (interquartile range 62-72). The mean prostate-specific antigen level and prostate size were 8.6 ± 9.1 ng/d and 53 ± 27 cc, respectively. The mean number of target lesions was 1.47 ± 0.6. Baseline parameters did not differ significantly between the 2 urologists' cohorts. Overall detection rates of clinically significant prostate cancer were 19%, 55%, and 69% for PI-RADS 3, 4 and 5, respectively. Clinically significant cancer detection rates did not differ significantly along the timeline or between the 2 urologists. The average duration of IB-MRGpB targeted sampling was 28 ± 15.8 min, correlating with the number of target lesions (p < 0.0001), and independent of the urologist's expertise. Eighteen cases defined the cutoff for the procedure duration learning curve (p < 0.05). CONCLUSIONS: Our data suggest a very short learning curve for IB-MRGpB-targeted sampling duration, and that clinically significant cancer detection rates are not influenced by the learning curve of this technique.

Associations between T cell infiltration, T cell receptor clonality, histology and recurrence in renal cell carcinoma.

Renal cell carcinoma (RCC) is comprised of clear-cell (ccRCC) and non-clear-cell (nccRCC) tumors. Despite definitive surgical resection in localized disease, recurrence often occurs. A commercial method based on a multiplex polymerase chain reaction (PCR) assay exclusively targets rearranged T cell receptor (TCR) genes to generate high-throughput sequencing-based data, allowing characterization of the immune repertoire within tumors. In this study we performed a retrospective analysis on archived tumor samples from patients with recurring versus non-recurring T3 ccRCC and on samples from early nccRCC versus ccRCC. Following genomic DNA extraction and multiplex PCR, the fraction of T cells within tumors, the number of unique receptors ('richness') and their relative abundances ('clonality') were calculated. Statistical significance and correlations were calculated using Student's t-test and Spearman's rho, respectively. Average fraction and clonality of T cells in tumors from non-recurring patients was 2.5- and 4.3-fold higher than in recurring patients (P = 0.025 and P = 0.043, respectively). A significant positive correlation was found between T cell fraction and clonality (Spearman's rho = 0.78, P = 0.008). The average fraction of T cells in ccRCC tumors was 2.8-fold higher than in nccRCC tumors (P = 0.015). Clonality and estimated richness were similar between ccRCC and nccRCC tumors. In summary, recurrence of ccRCC is associated with a lower fraction and clonality of T cells within tumors; nccRCC tumors are more 'deserted' than ccRCC, but similar in their ability to generate a clonal T cell repertoire. Our work suggests associations between the characteristics of T cell infiltrate, histology and tumor recurrence.

Cannabis-Derived Compounds Cannabichromene and Δ9-Tetrahydrocannabinol Interact and Exhibit Cytotoxic Activity against Urothelial Cell Carcinoma Correlated with Inhibition of Cell Migration and Cytoskeleton Organization.

Cannabis sativa contains more than 500 constituents, yet the anticancer properties of the vast majority of cannabis compounds remains unknown. We aimed to identify cannabis compounds and their combinations presenting cytotoxicity against bladder urothelial carcinoma (UC), the most common urinary system cancer. An XTT assay was used to determine cytotoxic activity of C. sativa extracts on T24 and HBT-9 cell lines. Extract chemical content was identified by high-performance liquid chromatography (HPLC). Fluorescence-activated cell sorting (FACS) was used to determine apoptosis and cell cycle, using stained F-actin and nuclei. Scratch and transwell assays were used to determine cell migration and invasion, respectively. Gene expression was determined by quantitative Polymerase chain reaction (PCR). The most active decarboxylated extract fraction (F7) of high-cannabidiol (CBD) C. sativa was found to contain cannabichromene (CBC) and Δ9-tetrahydrocannabinol (THC). Synergistic interaction was demonstrated between CBC + THC whereas cannabinoid receptor (CB) type 1 and type 2 inverse agonists reduced cytotoxic activity. Treatments with CBC + THC or CBD led to cell cycle arrest and cell apoptosis. CBC + THC or CBD treatments inhibited cell migration and affected F-actin integrity. Identification of active plant ingredients (API) from cannabis that induce apoptosis and affect cell migration in UC cell lines forms a basis for pre-clinical trials for UC treatment.

Histology results of systematic prostate biopsies by in-bore magnetic resonance imaging vs. transrectal ultrasound.

INTRODUCTION: We aimed to compare systematic biopsies (SBs) of in-bore magnetic resonance-guided prostate biopsy (MRGpB) with those performed under transrectal ultrasound (TRUS) guidance in the clinical setting. METHODS: Data on all 161 consecutive patients undergoing prostate biopsy at our institution between November 2017 and July 2019 were retrospectively collected. The patients were referred to biopsy due to elevated prostate-specific antigen (PSA) and/or abnormal digital rectal examination (DRE) and/or at least one Prostate Imaging Reporting and Data System (PI-RADS) lesion score of ≥3 on multiparametric magnetic resonance imaging (mpMRI). We included patients with PSA levels ≤20 ng/ml and those with 8-12 core biopsies. Histology results of SBs performed by in-bore MRGpB were compared to TRUS SBs. Chi-squared, Fischer's exact, and multivariate Pearson regression tests were used for statistical analysis (SPSS, IBM Corporation). RESULTS: In total, 128 patients were eligible for analysis. Their median age was 68 years (interquartile range [IQR] 61.5-72), mean prostate size 55±29 cc, and mean PSA and PSA density levels 7.6±3.5 ng/ml and 0.18±0.13 ng/ml/cc, respectively. Thirty-five patients (27.3%) had suspicious DRE findings. Both biopsy groups were similar for these parameters. Thirty-eight (62.3%) MRGpB patients had a previous biopsy vs. five (7.1%) TRUS-SB patients (p<0.0001). The number of patients diagnosed with clinically significant and non-significant disease was similar for both groups. High-risk disease was more prevalent in the TRUS-SB group (22.4% vs. 4.9%, p<0.01). CONCLUSIONS: Our data suggest that in-bore MRGpB is no better than TRUS for guiding SBs for the detection of clinically significant prostate cancer.

Trends in urologic oncology clinical practice and medical education under COVID-19 pandemic: An international survey of senior clinical and academic urologists.

OBJECTIVE: Ad-hoc guidelines for managing the COVID-19 pandemic are published worldwide. We investigated international applications of such policies in the urologic-oncology community. METHODS: A 20-item survey was e-mailed via SurveyMonkey to 100 international senior urologic-oncology surgeons. Leaders' policies regarding clinical/surgical management and medical education were surveyed probing demographics, affiliations, urologic-oncologic areas of interest, and current transportation restrictions. Data on COVID-19 burden were retrieved from the ECDC. Statistical analyses employed non-parametric tests (SPSS v.25.0, IBM). RESULTS: Of 100 leaders from 17 countries, 63 responded to our survey, with 58 (92%) reporting university and/or cancer-center affiliations. Policies on new-patient visits remained mostly unchanged, while follow-up visits for low-risk diseases were mostly postponed, for example, 83.3% for small renal mass (SRM). Radical prostatectomy was delayed in 76.2% of cases, while maintaining scheduled timing for radical cystectomy (71.7%). Delays were longer in Europe than in the Americas for kidney cancer (SRM follow-up, P = 0.014), prostate cancer (new visits, P = 0.003), and intravesical therapy for intermediate-risk bladder cancer (P = 0.043). In Europe, COVID-19 burden correlated with policy adaptation, for example, nephrectomy delays for T2 disease (r = 0.5, P =0.005). Regarding education policies, trainees' medical education was mainly unchanged, whereas senior urologists' planned attendance at professional meetings dropped from 6 (IQR 1-11) to 2 (IQR 0-5) (P < 0.0001). CONCLUSION: Under COVID-19, senior urologic-oncology surgeons worldwide apply risk-stratified approaches to timing of clinical and surgical schedules. Policies regarding trainee education were not significantly affected. We suggest establishment of an international consortium to create a directive for coping with such future challenges to global healthcare.

Outreach and Influence of Surgical Societies' Recommendations on Minimally Invasive Surgery During the COVID-19 Pandemic-An Anonymized International Urologic Expert Inquiry.

OBJECTIVE: To assess the outreach and influence of the main recommendations of surgical governing bodies on adaptation of minimally invasive laparoscopic surgery (MIS) procedures during the coronavirus disease 2019 (COVID-19) pandemic in an anonymized multi-institutional survey. MATERIALS AND METHODS: International experts performing MIS were selected on the basis of the contact database of the speakers of the Friends of Israel Urology Symposium. A 24-item questionnaire was built using main recommendations of surgical societies. Total cases/1 Mio residents as well as absolute number of total cases were utilized as surrogates for the national disease burden. Statistics and plots were performed using RStudio v0.98.953. RESULTS: Sixty-two complete questionnaires from individual centers performing MIS were received. The study demonstrated that most centers were aware of and adapted their MIS management to the COVID-19 pandemic in accordance to surgical bodies' recommendations. Hospitals from the countries with a high disease burden put these adoptions more often into practice than the others particularly regarding swabs as well as CO2 insufflation and specimen extraction procedures. Twelve respondents reported on presumed severe acute respiratory syndrome coronavirus 2 transmission during MIS generating hypothesis for further research. CONCLUSION: Guidelines of surgical governing bodies on adaptation of MIS during the COVID-19 pandemic demonstrate significant outreach and implementation, whereas centers from the countries with a high disease burden are more often poised to modify their practice. Rapid publication and distribution of such recommendation is crucial during future epidemic threats.

Management of Pancreatic Injuries Following Nephrectomy.

BACKGROUND: Pancreatic injuries during nephrectomy are rare, despite the relatively close anatomic relation between the kidneys and the pancreas. The data regarding the incidence and outcome of pancreatic injuries are scarce. OBJECTIVES: To assess the frequency and the clinical significance of pancreatic injuries during nephrectomy. METHODS: A retrospective analysis was conducted of all patients who underwent nephrectomy over a period of 30 years (1987-2016) in a large tertiary medical center. Demographic, clinical, and surgical data were collected and analyzed. RESULTS: A total of 1674 patients underwent nephrectomy during the study period. Of those, 553 (33%) and 294 patients (17.5%) underwent left nephrectomy and radical left nephrectomy, respectively. Among those, four patients (0.2% of the total group, 0.7% of the left nephrectomy group, and 1.36% of the radical left nephrectomy) experienced iatrogenic injuries to the pancreas. None of the injuries were recognized intraoperatively. All patients were treated with drains in an attempt to control the pancreatic leak and one patient required additional surgical interventions. Average length of stay was 65 days (range 15-190 days). Mean follow-up was 23.3 months (range 7.7-115 months). CONCLUSIONS: Pancreatic injuries during nephrectomy are rare and carry a significant risk for postoperative morbidity.

Effects of "real life" prostate MRI inter-observer variability on total needle samples and indication for biopsy.

PURPOSE: Prostate multiparametric magnetic resonance imaging (mpMRI) improves diagnosis of clinically significant cancer and reduces over-detection of nonsignificant cancer. Disagreement in the interpretation of mpMRI readings is well-known, with a reported discrepancy rate of 10% to 42%. We report the clinical repercussions of this variability on prostate biopsy candidates. MATERIALS AND METHODS: Medical records of patients referred from 11 medical centers for MR-guided prostate biopsy (MRGpB) between October, 2017 and January, 2019 were retrospectively analyzed. Patients with at least one prostate imaging reporting and data system (PI-RADS) 3 or greater prostate lesion were selected, and the mpMRI studies (all read by others) were reviewed by our prostate mpMRI reader. Outcomes included changes in PI-RADS score and the subsequent effect on total needle samples and indication for biopsy. RESULTS: Eighty-two patients with 128 lesions were suitable for analysis (mean age 66.5 ± 7.1 years, mean PSA 6.8 ± 8.5 ng/ml). Nine (11%) patients had suspicious rectal exams (T2a). Following our prostate mpMRI reader's imaging revisions, the PI-RADS score was downgraded in 66 (52%) lesions, upgraded in 15 (12%), and unchanged in 47 (37%), leaving a total of 84 suspected lesions (kappa = 0.17). Biopsy was deferred in 22 (27%) patients, and an estimated 136.4 (34.4%) samples were avoided (P = 0.0001 for both). There was a trend toward prostate size to correlate with imaging revision and abortion of biopsy (P = 0.06) while enrollment in active surveillance correlated with proof from such outcome (P = 0.007). CONCLUSION: These data suggest that high interobserver disagreement in prostate mpMRIs from diverse institutes significantly affects prostate biopsy practice. The clinical consequences of this discord are significant.

[THE EFFICACY OF ENDOSCOPIC DUAL LASER TREATMENT FOR LOW GRADE UPPER TRACT UROTHELIAL CARCINOMA].

INTRODUCTION: Until recently, radical nephroureterectomy was considered the gold standard treatment for upper tract urothelial carcinoma (UTUC). Post-operative complications, long-term adverse effects of nephrectomy as well as the risk of contralateral recurrence have led to the development of nephron-sparing techniques. OBJECTIVES: To evaluate the safety, complication rate, and oncologic outcomes of ureteroscopic nephron-sparing treatment for low-grade UTUC utilizing a hybrid laser system that incorporates two types of lasers: Nd:YAG and Ho:YAG. METHODS: We reviewed the files of patients who underwent ureteroscopic treatment for UTUC with the hybrid laser system between the years 2014-2018. Only cases of low-grade UTUC and follow-up time of at least 6 months were included in the present study. The following were analyzed: demographic data, tumor histologic characteristics, peri-operative complications, histologic upgrade, oncologic outcomes (i.e: local recurrence, local spread, metastatic progression). RESULTS: A total of 38 patients, who underwent 74 ureteroscopies, met inclusion criteria. Mean tumor size was 16.2 mm. No intra-operative complications were recorded. Two post-operative complications were recorded in one patient - hematuria and retroperitoneal bleeding - both had been treated conservatively. Mean follow-up time was 21.8 months. Local recurrence rate was 73%. Histologic upgrade has been observed in two patients. Four patients (10.5%) were referred to radical nephroureterectomy. There were no cases of local spread, distant metastases or death during the follow-up period. DISCUSSION: Endoscopic dual-laser treatment for low-grade UTUC is safe, surgically feasible and associated with good short-term oncologic outcome. Patient selection and strict follow-up are mandatory.

Selective Arterial Embolization for Large or Symptomatic Renal Angiomyolipoma: 10 Years of Follow-up.

OBJECTIVE: To assess long-term outcome after selective arterial embolization (SAE) as first-line treatment for large or symptomatic AML. DESIGN, SETTING, AND PARTICIPANTS: Data from a prospectively maintained database on 71 patients who underwent SAE for large or symptomatic AML were reviewed. Patients with sporadic and tuberous-sclerosis-complex (TSC) were included. OUTCOME MEASUREMENTS: The main endpoints were re-embolization rates, occurrence of clinical events related to AML, size of AML, and renal function. RESULTS: Thirteen (19.1%) patients reported at least 1 major clinical event. Major complications affected 2 patients (2.9%), both ending in complete loss of renal unit function. Four renal units (5.9%) were eventually treated surgically. The re-embolization rate was 41.1%, with an average time from the initial to a repeat SAE of 2.18 years (range 0.31-10.65 years). The size of the tumor prior to SAE and after 5 and 10 years of follow-up were 8.9 cm (7-12), 6.5 cm (4-7.5), 7 cm (4-7.8), respectively [median (IQR)]. These results are translated to a size reduction of 27% in 10 years follow-up. Patients with TSC had larger tumors on long-term follow-up (77.8 vs 41.3 mm, P = .045). The long-term follow-up estimated average glomerular filtration rate was 81.97 (range 26-196). No patient needed renal replacement therapy, and disease-specific survival was 100%. CONCLUSIONS: SAE is a safe treatment option for patients with symptomatic or large AML. It represents a minimally invasive intervention with good long-term outcome. SAE may be offered as first-line treatment in most cases, though, it is associated with high retreatment rates.

Tandem Ureteral Stents for Malignant Ureteral Obstruction.

Objectives: Malignant ureteral obstruction (MUO) is a devastating complication of cancer, and it is commonly treated by drainage via percutaneous nephrostomy (PCN). The objective of this study was to determine the efficacy, safety, and functional outcome of tandem ureteral stents (TUS) in the management of MUO. Materials and Methods: The medical records of all patients with MUO who underwent balloon dilation and TUS insertion in Sheba Medical Center between 2014 and 2018 were retrospectively analyzed. Safety was measured by intra- and postoperative complications, efficacy by time to event analysis, and failure by the requirement of PCN attributable to renal failure or infection. Independent risk predictors of TUS failure were determined by a multivariable Cox regression analysis. Results: A total of 103 procedures were performed on 81 patients during the study period. The median follow-up was 32 weeks (interquartile range [IQR] 24-67). Fifty-nine (72.9%) patients remained with TUS while 22 patients required PCNs. The median time to procedural failure was 4 months (IQR 2-8). Complications developed after 18 (22.2%) procedures. Two patients requested stent removal due to lower urinary tract symptoms. Independent predictors for TUS failure were metastasis (hazard ratio [HR] 3.03, 95% confidence interval [CI] 1.27, 7.23, p = 0.013) and prior PCN (HR 3.38, 95% CI 1.40, 8.13, p = 0.007). Conclusions: TUS is an efficient and safe management option for patients with MUO. It can alleviate renal failure without the need for an external PCN. Metastasis and prior PCN are associated with TUS failure.

Impact of perioperative blood transfusions on clinical outcomes in patients undergoing surgery for major urologic malignancies.

The association between allogeneic perioperative blood transfusion (PBT) and decreased survival among patients undergoing various oncological surgeries has been established in various malignant diseases, including colorectal, thoracic and hepatocellular cancer. However, when focusing on urologic tumors, the significance of PBT and its adverse effect remains debatable, mainly due to inconsistency between studies. Nevertheless, the rate of PBT remains high and may reach up to 62% in patients undergoing major urologic surgeries. Hence, the relatively high rate of PBT among related operations, along with the increasing prevalence of several urologic tumors, give this topic great significance in clinical practice. Indeed, recent retrospective studies, followed by systematic reviews in both prostate and bladder cancer surgery have supported the association that has been demonstrated in several malignancies, while other major urologic malignancies, including renal cell carcinoma and upper tract urothelial carcinoma, have also been addressed retrospectively. It is only a matter of time before the data will be sufficient for qualitative systematic review/qualitative evidence synthesis. In the current study, we performed a literature review to define the association between PBT and the oncological outcomes in patients who undergo surgery for major urologic malignancies. We believe that the current review of the literature will increase awareness of the importance and relevance of this issue, as well as highlight the need for evidence-based standards for blood transfusion as well as more controlled transfusion thresholds.

Intraoperative but not postoperative blood transfusion adversely affect cancer recurrence and survival following nephrectomy for renal cell carcinoma.

The association between perioperative blood transfusion (PBT) with adverse oncological outcomes have been previously reported in multiple malignancies including RCC. Nevertheless, the importance of transfusion timing is still unclear. The primary purpose of this study is to appraise whether the receipt of intraoperative blood transfusion (BT) differ from postoperative BT in regards to cancer outcomes in renal cell carcinoma (RCC) patients treated with nephrectomy. Data on 1168 patients with RCC, who underwent radical or partial nephrectomy as primary therapy between 1988-2013 were analyzed. PBT was defined as transfusion of allogeneic red blood cells (RBC) during surgery or the postsurgical period. Survival was analyzed and compared using the Kaplan-Meier method with the log-rank test. Of 1168 patients, 198 patients (16.9%) received a PBT. Including 117 intraoperative BT and 81 postoperative BT. Only 21 (10.6%) patients required both intraoperative and postoperative BT. On multivariate analyses, receipt of PBT was associated with significantly worse local disease recurrence (HR: 2.4; P = 0.017), metastatic progression (HR: 2.7; P = 0.005), cancer-specific mortality (HR: 3.5; P = 0.002) and all-cause mortality (HR: 2.1; P = 0.005). Nevertheless, postoperative BT was not independently associated with increased risk of local recurrence (p = 0.1), metastatic progression (P = 0.16) or kidney cancer death (P = 0.63), yet did significantly increase the risk of overall mortality (HR: 2.6; P = 0.004). In the current study, intraoperative transfusion of allogeneic RBC is associated with increased risks of cancer recurrence and mortality following nephrectomy.

Retzius space reconstruction following transperitoneal laparoscopic robot-assisted radical prostatectomy: does it have any added value?

Retzius space sparing (RSS) during laparoscopic robot-assisted radical prostatectomy (RALP) has been offered as an approach that reduces perioperative complications and enables faster gaining of full urinary continence due to bladder anatomy preservation. Retro and transperitoneal techniques have been proposed, whereby RSS has been implemented. We sought to explore whether Retzius space reconstruction (RSR) following transperitoneal RALP will be an advantageous step as well. A prospective registry database of 102 consecutive transperitoneal RALP cases performed by a single surgeon was reviewed. The Retzius space had been opened by dissecting the bladder away from the anterior abdominal wall to the level of both internal rings. In the last 51 cases (RSR group), the peritoneal layer had been sutured back, thus repositioning the bladder back to the anterior abdominal wall and reconstructing the Retzius space. Perioperative factors were analyzed and compared between the two groups. Demographic and perioperative data did not differ between the two groups. RSR group demonstrated shorter length of stay (LOS) compared with the control group (p = 0.01), as well as faster urinary continence recovery (i.e., 0 pads) (p = 0.01). Moreover, lower numbers of Clavien-Dindo class 3 complications and 12 mm port-site hernias (p = 0.03) were seen in the RSR group compared with the control group. RSR following transperitoneal RALP is a simple and efficient step that potentially reduces early and late post-operative complications, shortens LOS and accelerates full urinary continence.

Perioperative blood transfusion adversely affects prognosis after nephrectomy for renal cell carcinoma.

BACKGROUND: It has been previously suggested that perioperative blood transfusion (PBT) may induce adverse oncological outcomes following cancer surgery. The aim of the current study is to evaluate the effect of PBT on the prognosis of patients who underwent nephrectomy due to renal cell carcinoma (RCC). METHODS: Study included 1,159 patients who underwent radical nephrectomy or partial nephrectomy (PN) between the years 1987 and 2013. Univariate and multivariate models were used to evaluate the association of PBT with cancer-specific survival (CSS), disease-free survival, and overall survival (OS). RESULTS: Of 1,159 patients undergoing nephrectomy, 198 patients (17.1%) received a PBT. The median follow-up was 63.2 months. Risk factors for PBT included: lower preoperative hemoglobin (P<0.01), size of the renal mass (P<0.05), open surgical approach (P<0.01), and capsular invasion. Receipt of a PBT was associated with significantly adverse disease-free survival (hazard ratio [HR] = 2.1, P = 0.02), metastatic progression (HR = 2.4, P= 0.007), CSS (HR = 2.5, P = 0.02), and OS (HR = 2.2, P = 0.001). In the current study, 582 patients underwent PN; of these, 87 (14.9%) required PBT. The association of PBT with outcome remained significant in this subgroup after controlling for patient and tumor-related variables with respect to metastatic progression (HR = 5.9, P = 0.006), CSS (HR = 5.8, P = 0.007) and OS (HR = 2.1, P = 0.05). CONCLUSION: PBT is associated with reduced recurrence-free survival, CSS, and OS in patients undergoing nephrectomy for RCC. Worse oncological outcomes are also found in a separate analysis for patients undergoing PN.

Oncologic Outcomes of Partial Nephrectomy for Stage T3a Renal Cell Cancer.

BACKGROUND: Partial nephrectomy (PN) for clinical stage T3 tumors is controversial. Radical nephrectomy (RN) has been associated with a greater rate of chronic kidney disease, an increased risk of cardiovascular disease, and increased mortality compared with PN. We present our long-term 2-center experience with PN for stage pT3a tumors and compare the oncologic outcomes with those of similar patients treated with RN. MATERIALS AND METHODS: We reviewed the data from all patients who had undergone nephrectomy for renal cell carcinoma from 1987 to 2015 in 2 medical centers. The study included 134 patients with pathologic stage T3a tumors, of whom 48 and 86 underwent PN and RN, respectively. We compared the 2 groups (PN and RN) using univariate and multivariate analyses. RESULTS: The tumors of all patients with pathologic stage T3a who had undergone PN had been pathologically upstaged from clinical stage T1 or T2. Univariate and multivariate analyses revealed tumor size was significantly different statistically between the study groups (median, 7.0 cm in RN group vs. 4.0 cm in PN group; P < .001). Surgery type was not a predictor of local recurrence (P = .978), metastatic progression (P = .972), death from renal cancer (P = .626), or death from all causes (P = .974) at the 5-year follow-up point. CONCLUSION: The results of the present study have shown similar oncologic outcomes between 48 patients with stage pT3a renal cancer who underwent PN and 86 patients who underwent RN. Although PN was not performed on clinical T3a tumors, our findings suggest that PN can also be considered for these tumors and, thus, avoid the long-term complications of RN. However, strict follow-up protocols are mandatory.

Nephrectomy in children with wilms' tumor: 15 years of experience with "Tumor Delivery Technique".

BACKGROUND: The contemporary surgical approach to Wilms' tumors follows that used in adults with renal cell carcinomas, namely, early occlusion of the renal vessels and then removal of the kidney as an intact mass. For years, the surgical approach at our institution has been different, starting with blunt separation of the kidney from the surrounding tissues, followed by its delivery outside the abdominal cavity while it is only attached to the major blood vessels which are subsequently ligated. We aimed to present this "tumor delivery technique" and evaluate its outcomes. MATERIALS AND METHODS: We retrospectively reviewed medical records of children who underwent nephrectomy for Wilms' tumor using "tumor delivery technique." All procedures were performed by the same team, according to the same surgical principles. RESULTS: Between 2000 and 2015, 36 children were operated. Median age was 31 months (interquartile range [IQR]: 6-45 mo), and median maximal tumor diameter was 10 cm (IQR: 8-13.9 cm). Tumors were located to the right side in 47%, left side in 42%, and bilateral in 11%. Twelve children have received preoperative neoadjuvant chemotherapy. Capsular disruption and tumor spillage were documented in 4 cases (11%). CONCLUSIONS: "Tumor delivery technique" is an easy and safe approach which might reduce the overall complication rates and the incidence of intraoperative tumor spillage.

Positive surgical margin following radical nephrectomy is an independent predictor of local recurrence and disease-specific survival.

BACKGROUND: Positive surgical margins (PSM) are recognized as an adverse prognostic sign and are often associated with higher rates of local and systemic disease recurrence. The data regarding the oncological outcome for PSM following radical nephrectomy (RN) is limited. We examined the predictive factors for PSM and its influence on survival and site of recurrence in patients treated with RN for renal cell carcinoma (RCC). METHODS: Clinical, pathologic and follow-up data on 714 patients undergoing RN for kidney cancer were analyzed. Secondary analysis included 44 patients with metastatic RCC upon diagnosis who underwent cytoreductive nephrectomy (CRN). Univariate and multivariable logistic regression models were fit to determine clinicopathologic features associated with PSM. A Cox proportional-hazards regression model was used to test the independent effects of clinical and pathologic variables on survival. RESULTS: PSM was documented in 17 cases (2.4%). PSM were associated with tumour size, advanced pathologic stage (pT3 vs. ≤ pT2) and presence of necrosis. On multivariate analysis, cancer-specific survival (CSS) was associated with tumour stage, size, presence of necrosis and PSM. PSM was also associated with local recurrence but not distant metastasis or overall survival (OS). CSS and OS were comparable between the PSM and metastatic RCC groups, but significantly lower than the negative margin group. CONCLUSIONS: The prevalence of PSM following RN is rare. Pathological data, including advanced stage (> pT2), tumour necrosis and tumour size, are associated with the presence of PSM. PSM is associated with tumour recurrence and CSS. Patients with PSM are a potential group for adjuvant therapy or for more careful and thorough follow-up following surgery.

Salvage Radiation Therapy for Biochemical Failure Following Radical Prostatectomy.

BACKGROUND: Radiotherapy to the prostate bed is used to eradicate residual microscopic disease following radical prostatectomy for prostate cancer. Recommendations are based on historical series. OBJECTIVES: To determine outcomes and toxicity of contemporary salvage radiation therapy (SRT) to the prostate bed. METHODS: We reviewed a prospective ethics committee-approved database of 229 patients referred for SRT. Median pre-radiation prostate-specific antigen (PSA) was 0.5 ng/ml and median follow-up was 50.4 months (range 13.7-128). Treatment was planned and delivered using modern three-dimensional radiation techniques. Mean bioequivalent dose was 71 Gy (range 64-83 Gy). Progression was defined as two consecutive increases in PSA level > 0.2 ng/ml, metastases on follow-up imaging, commencement of anti-androgen treatment for any reason, or death from prostate cancer. Kaplan-Meier survival estimates and multivariate analysis was performed using STATA. RESULTS: Five year progression-free survival was 68% (95%CI 59.8-74.8%), and stratified by PSA was 87%, 70% and 47% for PSA < 0.3, 0.3-0.7, and > 0.7 ng/ml (P < 0.001). Metastasis-free survival was 92.5%, prostate cancer-specific survival 96.4%, and overall survival 94.9%. Low pre-radiation PSA value was the most important predictor of progression-free survival (HR 2.76, P < 0.001). Daily image guidance was associated with reduced risk of gastrointestinal and genitourinary toxicity (P < 0.005). CONCLUSIONS: Contemporary SRT is associated with favorable outcomes. Early initiation of SRT at PSA < 0.3 ng/ml improves progression-free survival. Daily image guidance with online correction is associated with a decreased incidence of late toxicity.