The association between adrenal adenoma size, autonomous cortisol secretion and metabolic derangements.

OBJECTIVE: Autonomous cortisol secretion (ACS) is common in patients with adrenal incidentalomas (AI). ACS is associated with increased cardiovascular morbidity and mortality. Data regarding the association between radiological characteristics of adrenal adenomas, their hormonal functionality and metabolic outcomes, are scarce and inconclusive. In this study, we aim to delineate the association between radiological characteristics of AI, ACS and metabolic status. METHODS: A cross-sectional study of 77 patients with AI who underwent a comprehensive hormonal evaluation. Radiological assessments were performed by an independent radiologist blinded to the clinical and hormonal phenotype of each case. Linear regression models were used to evaluate the association between post dexamethasone suppression test (DST) cortisol levels, metabolic indices and radiological measurements. RESULTS: Mean maximal adenoma diameter was greater in patients with versus without ACS (20.35 ± 6 vs. 27.09 ± 9.3 mm, respectively, p < .01). Maximal adenoma diameter was found to be positively and linearly correlated with post-DST morning cortisol levels across their entire range (R = .474, p < .01). Linear correlations between maximal adenoma diameter and indices of glycemic control showed a correlation coefficient (R) of .481 and .463 for fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c), respectively, p < .01. When analysis included only patients with ACS, an R = .584 and R = .565 was observed for FPG and HbA1c, respectively (p < .01 for both). The association between maximal adenoma diameter and both FPG and post-DST morning cortisol intensified in patients with metabolic syndrome. CONCLUSION: There is a quantitative positive mild correlation between AI size and both cortisol autonomy and metabolic parameters.

Association between early change in neutrophil-to-lymphocyte ratio after radical cystectomy and treatment outcomes.

OBJECTIVES: To evaluate the associations of peri-operative neutrophil-to-lymphocyte ratio (NLR) and change in NLR with survival after radical cystectomy. PATIENTS AND METHODS: We retrospectively reviewed a multicentre cohort of patients with bladder cancer who underwent radical cystectomy between 2010 and 2020. Preoperative NLR, postoperative NLR, delta-NLR (postoperative minus preoperative NLR) and NLR change (postoperative divided by preoperative NLR) were calculated. Patients were stratified based on elevation of preoperative and/ or postoperative NLR above the median values. Multivariable Cox regression models were used to evaluate the associations of peri-operative NLR and NLR change with survival. RESULTS: The study cohort included 346 patients with a median age of 69 years. The median (interquartile range) preoperative NLR, postoperative NLR, delta-NLR and NLR change were 2.55 (1.83, 3.90), 3.33 (2.21, 5.20), 0.43 (-0.50, 2.08) and 1.2 (0.82, 1.96), respectively. Both preoperative and postoperative NLR were elevated in 110 patients (32%), 126 patients (36%) had an elevated preoperative or postoperative NLR, and 110 patients (32%) did not have an elevated NLR. On multivariable analysis, increased preoperative and postoperative NLR were significantly associated with decreased survival. While delta-NLR and NLR change were not associated with outcome, patients with elevations in both preoperative and postoperative NLR had the worst overall (hazard ratio [HR] 2.97, 95% confidence interval [CI] 1.78, 4.95; P < 0.001) and cancer-specific survival rates (HR 2.41, 95% CI 1.3, 4.4; P = 0.004). CONCLUSIONS: Preoperative and postoperative NLR are significant predictors of survival after radical cystectomy; patients in whom both NLR measures were elevated had the worst outcomes. Future studies should evaluate whether an increase in NLR during long-term follow-up may precede disease recurrence.

Quality of life with tandem ureteral stents compared to percutaneous nephrostomy for malignant ureteral obstruction.

PURPOSE: Malignant ureteral obstruction (MUO) is treated with kidney decompression by a percutaneous nephrostomy (PCN) or internal ureteral stents. The objective of this study was to compare quality of life (QoL) with a PCN compared to tandem ureteral stents (TUS) in cases of MUO. METHODS: We reviewed the medical records of patients with MUO who were treated by PCN/TUS in our institution between June 2019 and May 2020. Patients were asked to fill out a QoL questionnaire, a tube-symptoms questionnaire, report a general health scale, and asked for a drain preference if they had experience with both drains. Scores of both groups were compared and predictors of all QoL and tube-symptoms measures were searched using multivariate analysis. RESULTS: Seventy-four patients with a PCN and 30 with TUS were included in the study. No statistically significant difference was found in all QoL and tube-symptoms measurements between the two drains. Type of drain was not found to be a predictor of QoL or tube-related symptoms. Eighty-four percent of patients (11/13) who have experience with both types of drains preferred TUS. CONCLUSION: TUS and PCN for relief of MUO have a negative and similar effect on various areas of QoL and urinary symptoms. Most patients who had experience with both types of drains preferred TUS over PCN. In this patient population with a grim prognosis, this negative effect must be communicated to patients, and calculated against the potential benefits of drainage.

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.

Endoscopic Treatment for Large Multifocal Upper Tract Urothelial Carcinoma.

PURPOSE: We reviewed the oncologic and surgical outcomes of endoscopic treatments for low grade upper tract urothelial carcinoma, and assessed the prognostic significance of tumor size, location and multifocality. MATERIALS AND METHODS: We retrospectively reviewed all patients who underwent endoscopic treatment for low grade upper tract urothelial carcinoma at our institution between 2014 and 2019. Tumors were treated with a dual laser generator, which alternately produces holmium and neodymium lasers. A stringent ureteroscopic followup protocol was conducted. We looked for an association between outcome and tumor size, location or multifocality, and for predictive factors for time to local recurrence and progression. RESULTS: The cohort included 59 patients (62 renal units), 27% of tumors were multifocal and 40% were >2 cm. The median followup time was 22 months (IQR 11-41), and the median number of ureteroscopies was 5.5 (4-9). Local recurrence was observed in 46 renal units (74.1%) at a median of 6.5 months after initial surgery. Four patients (6.4%) developed disease progression and were referred for radical surgery: 2 had pathological progression and 2 had a rapid and high volume local recurrence, and 1 later developed metastatic disease. The progression-free rate was 93.2%. Tumor location in kidney (p=0.03, HR 1.95) and multifocality (p=0.005, HR 3.25) significantly predicted time to local recurrence. No factor predicted time to progression. CONCLUSIONS: Ureteroscopic treatment of large, multifocal, low grade upper tract urothelial carcinoma is feasible, does not involve significant complications and has good short-term oncologic outcomes, with a 93.2% progression-free survival rate. Tumors located in the kidney and multifocality yielded shorter time to local recurrence but not progression.

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.

Successful Introduction of Human Renovascular Units into the Mammalian Kidney.

BACKGROUND: Cell-based therapies aimed at replenishing renal parenchyma have been proposed as an approach for treating CKD. However, pathogenic mechanisms involved in CKD such as renal hypoxia result in loss of kidney function and limit engraftment and therapeutic effects of renal epithelial progenitors. Jointly administering vessel-forming cells (human mesenchymal stromal cells [MSCs] and endothelial colony-forming cells [ECFCs]) may potentially result in in vivo formation of vascular networks. METHODS: We administered renal tubule-forming cells derived from human adult and fetal kidneys (previously shown to exert a functional effect in CKD mice) into mice, alongside MSCs and ECFCs. We then assessed whether this would result in generation of "renovascular units" comprising both vessels and tubules with potential interaction. RESULTS: Directly injecting vessel-forming cells and renal tubule-forming cells into the subcutaneous and subrenal capsular space resulted in self-organization of donor-derived vascular networks that connected to host vasculature, alongside renal tubules comprising tubular epithelia of different nephron segments. Vessels derived from MSCs and ECFCs augmented in vivo tubulogenesis by the renal tubule-forming cells. In vitro coculture experiments showed that MSCs and ECFCs induced self-renewal and genes associated with mesenchymal-epithelial transition in renal tubule-forming cells, indicating paracrine effects. Notably, after renal injury, renal tubule-forming cells and vessel-forming cells infused into the renal artery did not penetrate the renal vascular network to generate vessels; only administering them into the kidney parenchyma resulted in similar generation of human renovascular units in vivo. CONCLUSIONS: Combined cell therapy of vessel-forming cells and renal tubule-forming cells aimed at alleviating renal hypoxia and enhancing tubulogenesis holds promise as the basis for new renal regenerative therapies.

Oncologic Outcomes Following Robot-Assisted Radical Prostatectomy for Clinical T3 Prostate Disease.

BACKGROUND: Little is known about oncologic outcomes following robot-assisted-radical-prostatectomy (RALP) for clinical T3 (cT3) prostate cancer. OBJECTIVES: To investigate oncologic outcomes of patients with cT3 prostate cancer treated by RALP. METHODS: Medical records of patients who underwent RALP from 2010 to 2018 were retrieved. cT3 cases were reviewed. Demographic and pre/postoperative pathology data were analyzed. Patients were followed in 3-6 month intervals with repeat PSA analyses. Adjuvant/salvage treatments were monitored. Biochemical recurrence (BCR) meant PSA levels of ≥ 0.2 ng/ml. RESULTS: Seventy-nine patients met inclusion criteria. Median age at surgery was 64 years. Preoperative PSA level was 7.14 ng/dl, median prostate weight was 54 grams, and 23 cases (29.1%) were down-staged to pathological stage T2. Positive surgical margin rate was 42%. Five patients were lost to follow-up. Median follow-up time for the remaining 74 patients was 24 months. Postoperative relapse in PSA levels occurred in 31 patients (42%), and BCR in 28 (38%). Median time to BCR was 9 months. The overall 5-year BCR-free survival rate was 61%. Predicting factors for BCR were age (hazard-ratio [HR] 0.85, 95% confidence interval [95%CI] 0.74-0.97, P = 0.017) and prostate weight (HR 1.04, 95%CI 1.01-1.08, P = 0.021). Twenty-six patients (35%) received adjuvant/salvage treatments. Three patients died from metastatic prostate cancer 31, 52, and 78 months post-surgery. Another patient died 6 months post-surgery of unknown reasons. The 5-year cancer-specific survival rate was 92. CONCLUSIONS: RALP is an oncologic effective procedure for cT3 prostate cancer. Adjuvant/salvage treatment is needed to achieve optimal disease-control.

[ROBOT ASSISTED PYELOPLASTY IN ADULTS WITH URETERO-PELVIC JUNCTION OBSTRUCTION (UPJO)].

BACKGROUND: Robotic-pyeloplasty (RP) for uretero-pelvic-junction-obstruction (UPJO) has been performed in our institution since 2013. OBJECTIVES: To summarize the outcomes of RP in adults over 18 years of age. METHODS: Adult RP cases have been prospectively documented. Analysis included demographic data such as age, sex, American Association of Anesthesiology-ASA Score, surgical-side, pre-operative imaging. Operative time (OT), estimated blood loss (EBL), length of stay (LOS) and short-term complications were also recorded. In all cases a JJ-stent has been left in place and subsequently taken out. Complications were classified in accordance with the Clavien-Dindo classification criteria. Patients were seen periodically with repeat imaging. The renal scan was performed at least once during the post-operative follow-up. Results are given as median (inter-quartile range) or numeric values (%). RESULTS: A total of 32 patients aged 33.5 years (21-45.2) had RP between the years 2013-2020, among which 53% were females and 59% right sided. An ASA score of 1-2 has been observed in 87.5% of all cases. Skin-to-skin OT was 163 min (136-185), and EBL was 5 ml (0-30). Short-term post-operative complications were hematuria (3.1%), urinary leak/urinoma (12.5%), body temperature>38.30C (12.5%). In 2 cases (6.2%) the JJ-stent had been re-positioned in the operating-theater (Clavien-Dindo 3b). LOS was 3 days (2-4) and JJ-stent had been taken out 39 days (31.7-45.2) post-operatively. Median length of follow-up was 19.5 months (9.5-26.7). In 92.3% of cases an improvement in hydronephrosis has been observed in post-operative imaging. The renal scan did not demonstrate renal function deterioration. CONCLUSIONS: Adult robotic pyeloplasty for UPJO is safe and effective. Low complication rates and over 90% success rates have been observed. These findings are in line with those found in previous studies.

[FACTORS PREDICTING FULL URINARY CONTINENCE FOLLOWING ROBOT-ASSISTED LAPAROSCOPIC RADICAL PROSTATECTOMY (RALP)].

BACKGROUND: Urinary Incontinence (UI) following Robot-Assisted Laparoscopic-Radical Prostatectomy (RALP) adversely affects patients' quality of life. OBJECTIVES: To find parameters that predict full urinary continence (FUC) following RALP. METHODS: Out of an established prospective RALP database, we retrieved and analyzed parameters that potentially predict FUC: age, Body Mass Index, American Anesthesiology Association (ASA) score, previous abdominal surgeries, pre-operative IPSS (International Prostate-Symptom Score), operative time (OT), estimated blood loss (EBL), peritoneum closure and prostate weight. FUC has been defined as 0 pads/day. Univariate analysis has been executed for comparison between patient groups, whereas multivariate analysis has been implemented for the detection of predicting factors for FUC. Data are presented as median (interquartile range) or numeric value (%). RESULTS: A total of 431 RALP cases were recorded between the years 2010-2019. Final analysis included 364 patients with full medical records; 81% gained FUC within 15 weeks (8-28); 96% gained FUC or used 1 pad/day within 17.5 weeks (8-36). Among those who gained FUC, smaller prostates (p=0.028) and low EBL (p=0.025) have been observed. On multivariate analysis EBL has been associated with UI (OR=0.9). CONCLUSIONS: Most patients gained FUC following RALP. EBL was found as risk factor for UI.

[CLINICAL OUTCOMES FOLLOWING ROBOT-ASSISTED PARTIAL NEPHRECTOMY (RAPN)].

BACKGROUND: Partial nephrectomy is the gold standard treatment for renal tumors less than 7 cm. OBJECTIVES: To describe surgical techniques and trends of treating renal tumors less than 7 cm at our department and present the clinical outcomes of our experience with Robot-Assisted Partial Nephrectomy (RAPN). METHODS: Out of an established prospective RAPN database, we retrieved demographic, clinical, surgical and pathological parameters. Operation length was defined as the time between the first surgical incision and the last suture (skin to skin). Warm ischemia time (WIT) was defined as the time between the renal artery clamping and clamp releasing. Data is presented as mean (range, standard deviation) or numeric value (%). RESULTS: Overall, 250 RAPN cases were recorded between the years 2013-2020. Mean tumor size was 32 mm. Mean operation length was 153 minutes. Mean warm ischemia time was 17.5 minutes. Intra-operative complication rates, including converting the surgery to an open approach or to radical nephrectomy, was low. Mean estimated blood loss was 359 cc. An increase in the utilization of the robotic approach has been recorded throughout the years, with a concurrent decrease in the open and laparoscopic approaches. CONCLUSIONS: RAPN is associated with lower complication rates and superior perioperative outcomes, therefore considered a good alternative to the open and laparoscopic approaches. Thus, RAPN is the gold standard treatment for renal tumors less than 7 cm at our institute.

[FOCAL TREATMENT OF PROSTATE CANCER - LEADING AND FUTURE TECHNIQUES, OUTCOMES AND COMPLICATIONS].

INTRODUCTION: Focal treatment for prostate cancer has been proposed as an innovative strategy that aims to achieve oncological benefit while reducing treatment-related morbidity. This treatment is suitable for patients with low and intermediate risk, organ-confined disease. Focal therapy can be categorized as follows: unifocal index lesion ablation, multifocal ablation, hemi-gland ablation or subtotal gland ablation. Different types of energies are applied in focal therapy including high intensity focal ultrasound (HIFU), cryotherapy, focal laser ablation (FLA), irreversible electroporation (IRE) and Photodynamic therapy (PDT). In this review we will briefly present a summary of leading techniques and the available data regarding their oncological outcomes and adverse events. Whole-gland therapies were excluded from this review.

[UPPER TRACT UROTHELIAL CARCINOMA].

INTRODUCTION: Upper tract urothelial carcinoma is a relatively rare malignancy, but with an increasing prevalence. The main risk factor for the disease is smoking. The most common presentation is hematuria or flank pain. Workup is made by imaging of the upper tract - CTU/MRU (Computed Tomography-Urography/Magnetic resonance (MR) urography) and diagnostic uretero-nephroscopy with biopsy. In the past several years there is major advancement in our understanding of the disease and how to treat it, mainly in nephron-sparing treatments. A risk-stratification is usually conducted according to parameters such as tumor size, distribution, and pathologic diagnosis. The low-risk group is usually offered nephron-sparing treatments such as segmental ureterectomy, endoscopic treatments, and lately - local chemotherapy. The high-risk group is usually offered radical resection of the kidney and ureter, with the possible addition of new-adjuvant and adjuvant treatments. In this article we will review the epidemiology, risk factors, diagnosis, and treatment of this malignancy, with a distinction between the risk groups.

The Quantitative Relationship Between Autonomous Cortisol Secretion, Dysglycemia and the Metabolic Syndrome.

OBJECTIVE: Autonomous cortisol secretion (ACS) is the most common endocrine abnormality in the evaluation of adrenal incidentalomas. The categorization of ACS is derived from a 1 mg dexamethasone suppression test (DST). Impaired DST is associated with several metabolic derangements. In this study we analyzed the association between post-DST cortisol level, analyzed as a continuous parameter, and indices of glycemic metabolism. METHODS: We prospectively collected data of 1,976 patients evaluated for adrenal incidentalomas in a large tertiary medical center between December 1, 2017, and August 31, 2019. Seventy-three patients completed the evaluation process. Post-DST cortisol levels were analyzed for correlation with various metabolic parameters, including fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) among the general cohort and for subgroups stratified by the number of metabolic syndrome (MS) criteria. RESULTS: Post-DST cortisol demonstrated a linear association with FPG and HbA1c across its entire cortisol range (R = 0.51 and 0.41, respectively; P≤.01). The association between post-DST cortisol and FPG was strengthened with an increased number of metabolic syndrome criteria. Patients with 4 MS criteria show a stronger association (R = 0.92) compared to patients with only a single criterion (R = 0.509). Furthermore, mean post-DST cortisol levels increased as the number of MS criteria accumulated. CONCLUSION: Post-DST cortisol should be viewed as a continuous parameter in risk stratification algorithms for the development of MS and particularly dysglycemia.

Kidney Cancer Following Heart Transplantation, a Common Presentation of an Uncommon Malignancy: A Unique Case Series.

BACKGROUND: Heart transplantation (HT) success rate is limited by a high incidence of cancer post-HT. Data on kidney cancer following solid organ transplantation, especially HT, are limited, and only a few cases have been reported. OBJECTIVES: To report a unique case series of detected kidney cancer following HT. METHODS: Between 1997 and 2018, 265 patients who underwent HT were enrolled and prospectively followed in the HT registry of the Sheba Medical Center. RESULTS: The series included 5 patients, 4 men and a woman (age range 35-50 years at HT). The patients were diagnosed with kidney tumors 6-11 years after HT (age range at diagnosis 40-72 years). Two of the men were identical twin brothers. At HT four patients received induction therapy with anti-thymocyte globulin and all received an initial immunosuppressive regimen based on cyclosporine. All male HT recipients had a history of heavy smoking. Two male patients developed allograft vasculopathy, but all had preserved heart function. The 72-year-old woman developed a kidney tumor of the native kidney 5 years after re-HT and kidney transplantation. Two patients had features of multifocal papillary renal cell carcinoma (RCC) and eventually underwent bilateral nephrectomy, while another patient underwent left partial nephrectomy with preserved renal function. CONCLUSIONS: To the best of our knowledge, this is the first case series study describing kidney tumors following HT. With the improving outcomes and life expectancy of HT patients, a better understanding of the factors that determine cancer risk is of the utmost importance and may have a major impact on the non-cardiac surveillance.

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.

[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.

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.

Predictive factors for perioperative blood transfusions in partial nephrectomy for renal masses.

BACKGROUND: Allogeneic perioperative blood transfusions (PBT) have been associated with higher rates of postoperative complications and tumour recurrence in a number of malignancies. This study evaluates the risk factors for PBT in patients undergoing partial nephrectomy (PN), in order to identify patients who could benefit from alternatives to allogenic blood. METHODS: Data on 822 patients who underwent elective PN between 1988 and 2013 were analysed. Patient demographics and clinicopathologic variables were collected retrospectively. PBT was defined as transfusion of allogeneic red blood cells during PN (in the operating-room) or postoperative hospitalization. RESULTS: Of the 822 patients, 122 (14.8%) received PBT. Of these, 45.9% were transfused intraoperatively and 47.5% in the postoperative period. Only 14.3% of the patients who were transfused intraoperatively required additional postoperative transfusions. On multivariable analysis, age ≥65 (P < 0.01), lower preoperative haemoglobin levels (P < 0.001), larger renal masses (P < 0.001), central lesions (P < 0.01) and cumulative surgical experience (P < 0.001) were found to be associated with higher rate of PBT. CONCLUSIONS: Age, low preoperative haemoglobin level, lesion size, surgeons' experience and central renal lesions are independent pre-operative risk factors for PBT in patients undergoing PN. Evaluation of these risk factors prior to surgery may be helpful in constituting guidelines for a more responsible use of allogeneic blood and its alternatives.