Patients Undergoing Radical Nephrectomy Research Articles

Perioperative Morbidity of Lymph Node Dissection for Renal Cell Carcinoma: A Propensity Score–based Analysis

BackgroundThere are little data regarding the morbidity of lymph node dissection (LND) for renal cell carcinoma (RCC) to assess its risk–benefit ratio. ObjectiveTo evaluate the association of LND with 30-d complications among patients undergoing radical nephrectomy (RN) for RCC. Design, setting, and participantsA total of 2066 patients underwent RN for M0 or M1 RCC between 1990 and 2010, of whom 774 (37%) underwent LND. InterventionRN with or without LND. Outcome measurements and statistical analysisAssociations of LND with 30-d complications were examined using logistic regression with several propensity score techniques. Extended LND, defined as removal of ≥13 lymph nodes, was examined in a sensitivity analysis. Results and limitationsA total of 184 (9%) patients were pN1 and 302 (15%) were M1. Thirty-day complications occurred in 194 (9%) patients, including Clavien grade ≥3 complications in 81 (4%) patients. Clinicopathologic features were well balanced after propensity score adjustment. In the overall cohort, LND was not statistically significantly associated with Clavien grade ≥3 complications, although there was an approximately 40% increased risk of any Clavien grade complication that did not reach statistical significance. Likewise, LND was not significantly associated with any Clavien grade or Clavien grade ≥3 complications when separately evaluated among M0 or M1 patients. Extended LND was not significantly associated with any Clavien grade or Clavien grade ≥3 complications. LND was not associated with length of stay or estimated blood loss. Limitations include a retrospective design. ConclusionsLND is not significantly associated with an increased risk of Clavien grade ≥3 complications, although it may be associated with a modestly increased risk of minor complications. In the absence of increased morbidity, LND may be justified in a predominantly staging role in the management of RCC. Patient summaryLymph node dissection for renal cell carcinoma is not associated with increased rates of major complications.

Platelet to white blood cell ratio predicts 30-day postoperative infectious complications in patients undergoing radical nephrectomy for renal malignancy.

We sought to examine the relationship between preoperative platelet to white blood cell ratio (PLT/WBC), a hematological marker of the systemic inflammatory response, and postoperative infectious complications following radical nephrectomy for localized renal cell carcinoma. We performed a retrospective cohort study of patients treated with radical nephrectomy for localized kidney cancer between January 1, 2005 and December 31, 2014 (n=6235) using the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database. Univariate and multivariate analyses were used to assess the association between PLT/WBC ratio and 30-day infectious complications, including surgical site infection, urinary tract infection (UTI), pneumonia, and sepsis. Secondarily, we examined major complications and bleeding requiring transfusion. A lower PLT/WBC ratio was associated with an increased risk of sepsis, pneumonia, and UTI rates (p<0.05 for all). Furthermore, there was a significant trend of decreasing rates of sepsis and pneumonia with increasing PLT/WBC ratio across quintiles (p<0.05 for all). On multivariate analysis, patients with the lowest PLT/WBC ratios (Quintile 1) had a two-fold risk of having a postoperative infectious complication compared to patients in the highest quintile (odds ratio [OR] 2.01; 95% confidence interval [CI] 1.42-2.86; p<0.0001). Patients in Quintile 5 had a higher risk of requiring blood transfusion than those in Quintiles 2-4 (p<0.05 for all). The PLT/WBC ratio represents a widely available and novel index to predict risk of infectious and bleeding complications in patients undergoing radical nephrectomy. External validation is required and the biological underpinning of this phenomenon requires further study.

Association of Robotic-Assisted vs Laparoscopic Radical Nephrectomy With Perioperative Outcomes and Health Care Costs, 2003 to 2015

Use of robotic surgery has increased in urological practice over the last decade. However, the use, outcomes, and costs of robotic nephrectomy are unknown. To examine the trend in use of robotic-assisted operations for radical nephrectomy in the United States and to compare the perioperative outcomes and costs with laparoscopic radical nephrectomy. This retrospective cohort study used the Premier Healthcare database to evaluate outcomes of patients who had undergone robotic-assisted or laparoscopic radical nephrectomy for renal mass at 416 US hospitals between January 2003 and September 2015. Multivariable regression modeling was used to assess outcomes. Robotic-assisted vs laparoscopic radical nephrectomy. The primary outcome of the study was the trend in use of robotic-assisted radical nephrectomy. The secondary outcomes were perioperative complications, based on the Clavien classification system, and defined as any complication (Clavien grades 1-5) or major complications (Clavien grades 3-5, for which grade 5 results in death); resource use (operating time, blood transfusion, length of hospital stay); and direct hospital cost. Among 23 753 patients included in the study (mean age, 61.4 years; men, 13 792 [58.1%]), 18 573 underwent laparoscopic radical nephrectomy and 5180 underwent robotic-assisted radical nephrectomy. Use of robotic-assisted surgery increased from 1.5% (39 of 2676 radical nephrectomy procedures in 2003) to 27.0% (862 of 3194 radical nephrectomy procedures) in 2015 (P for trend <.001). In the weighted-adjusted analysis, there were no significant differences between robotic-assisted and laparoscopic radical nephrectomy in the incidence of any (Clavien grades 1-5) postoperative complications (adjusted rates, 22.2% vs 23.4%, difference, -1.2%; 95% CI, -5.4 to 3.0%) or major (Clavien grades 3-5) complications (adjusted rates, 3.5% vs 3.8%, difference, -0.3%; 95% CI, -1.0% to 0.5%). The rate of prolonged operating time (>4 hours) for patients undergoing the robotic-assisted procedure was higher than for patients receiving the laparoscopic procedure in the adjusted analysis (46.3% vs 25.8%; risk difference, 20.5%; 95% CI, 14.2% to 26.8%). Robotic-assisted radical nephrectomy was associated with higher mean 90-day direct hospital costs ($19 530 vs $16 851; difference, $2678; 95% CI, $838 to $4519), mainly accounted for operating room ($7217 vs $5378; difference, $1839; 95% CI, $1050 to $2628) and supply costs ($4876 vs $3891; difference, $985; 95% CI, $473 to $1498). Among patients undergoing radical nephrectomy for renal mass between 2003 and 2015, the use of robotic-assisted surgery increased substantially. The use of robotic-assistance was not associated with increased risk of any or major complications but was associated with prolonged operating time and higher hospital costs compared with laparoscopic surgery.

Psychological distress in patients undergoing surgery for urological cancer: A single centre cross-sectional study

PurposeInterest in the disease-specific psychological well-being of patients with cancer has increased, and it has been estimated that less than half of all patients with cancer are properly identified and subsequently treated for anxiety or depression. The aim of this study is to evaluate psychological distress in uro-oncological patients undergoing different surgeries: radical cystectomy, radical prostatectomy, radical nephrectomy, or transurethral resection (TUR) before the surgery. Materials and methodsWe performed a cross-sectional study in consecutively enrolled patients with bladder, kidney, or prostate cancer, scheduled for surgery. Demographic data, socioeconomic status, education level, and diagnoses were recorded. Patients with a previous diagnosis of depression or anxiety were excluded.We evaluated the level of clinically meaningful depression and anxiety assessed by 2 tools: the Hospital Anxiety and Depression Scale (HADS; score ≥8 presence of anxiety and depression; score ≥11 clinical anxiety and depression) and the State-Trait Anxiety Inventory (STAI). To determine variables related to depression and anxiety among the demographic variables, logistic regression analyses were conducted, with P<0.05 considered as statistically significant. ResultsA total of 207 patients were recruited, completed the questionnaires and were included in the study. Patients presented a mean age of 70.8 (±10.8) years, 89% were males (n = 184) and 19% of patients presented previous cancer. The majority of patients underwent surgery for bladder tumors (60.4%) and the most common type of surgery was TUR. The most frequent procedures were performed for bladder tumors (60.4%), being TUR the most common type of surgery (52.7%) followed by radical prostatectomy (24.6%). Mean STAI-State score was 19.3 (±10.3), and mean STAI-Trait score was 18.4 (±11.9) points. Clinical levels of anxiety and depression (HADS ≥ 11 points) were found in 19 (9.8%) and 7 (3.6%) cases. And HADS anxiety 8 to 10 points was present in 14.5% (n = 28) and HADS depression 8 to 10 points in 5.7% (n = 11) of the sample, representing presence of psychological distress. Female patients showed a higher level of anxiety and STAI-Trait compared to males. ConclusionThe present results show that our patients had lower levels of anxiety and depression than those described in the literature. Sex, tumor type, and surgical approach were significantly related to psychological distress in patients undergoing surgery for urological cancer. Females and patients with kidney tumor and patients undergoing radical nephrectomy presented higher levels of anxiety. Patients with radical cystectomy showed a higher level of STAI-State compared with other surgeries.

Obesity and its implications on oncological urological surgery.

To review and summarize the contemporary knowledge of the implications of obesity on perioperative outcomes in oncological urologic surgeries. In men undergoing radical prostatectomy, obesity seems to confer a higher risk of intraoperative bleeding, biochemical recurrence, urinary incontinence, and postoperative erectile dysfunction. The literature was not consistent regarding the benefits of a minimally invasive approach in overweight and obese patients. Similarly, available data suggest a higher risk of complications in obese patients undergoing radical cystectomy. Obesity does not seem to confer a higher risk of morbidity in patients undergoing radical nephrectomy and nephroureterectomy. However, studies reported conflicting surgical outcomes in obese patients treated with partial nephrectomy. Overweight and obesity status are associated with higher morbidity in patients treated with inguinal lymph node dissection for penile cancer. No data are available regarding the impact of obesity in obese patients treated with retroperitoneal lymph node dissection for testicular cancer. Although randomized clinical data are lacking and the results of many studies are inconsistent, evidence supports the feasibility and safety of different oncological urological surgeries in obese patients. Nevertheless, obesity is an important comorbidity associated with a higher morbidity rate in most oncological urological surgeries.

Influence of hospital volume on nephrectomy mortality and complications: a systematic review and meta-analysis stratified by surgical type

ObjectivesThe provision of complex surgery is increasingly centralised to high-volume (HV) specialist hospitals. Evidence to support nephrectomy centralisation however has been inconsistent. We conducted a systematic review and meta-analysis to...

Effect of median household income on surgical approach and survival in renal cell carcinoma

PurposeWe sought to determine whether median household income (MHI) independently predicts surgical approach (partial vs. radical nephrectomy) and survival in patients with renal cell carcinoma. MethodsThe U.S. Surveillance Epidemiology and End Results Database (1988–2011) was queried to examine kidney cancer cases and linked to the Area Health Resources File. We correlated surgical approach and survival, both overall and cancer-specific, with tumor stage, age, race, sex, and income data. ResultsOf 152,589 patients diagnosed with renal cell carcinoma, 24,221 (16%) patients underwent partial nephrectomy, 102,771 (67%) patients underwent radical nephrectomy, and 25,597 (17%) patients had no surgery. There was no significant difference in stage of presentation between the wealthiest and poorest MHI quartiles, with approximately 35% of patients in each quartile presenting with T1aN0M0 disease and 17% of patients presenting with metastatic disease. Despite this, 18% of patients in the wealthiest quartile underwent partial nephrectomy compared to 14% of patients in the poorest quartile. Although the percentage of patients undergoing partial nephrectomy rose over the timeframe studied in both the wealthiest and poorest quartiles, the rate of rise was highest in the wealthier group. Those in the poorest quartile were 0.10 times more likely to die of all causes (95% CI: 1.09–1.11, P<0.001) and 0.09 times more likely to die of kidney cancer (95% CI: 1.05–1.10, P<0.001) than those in the wealthiest quartile over the timeframe studied. ConclusionsDespite presenting with similar stage, patients with lower MHI less commonly undergo partial nephrectomy and are more likely to die of kidney cancer than those in the highest MHIs.

Renal Functional Outcomes after Surgery, Ablation, and Active Surveillance of Localized Renal Tumors: A Systematic Review and Meta-Analysis.

Management strategies for localized renal masses suspicious for renal cell carcinoma include radical nephrectomy, partial nephrectomy, thermal ablation, and active surveillance. Given favorable survival outcomes across strategies, renal preservation is often of paramount concern. To inform clinical decision making, we performed a systematic review and meta-analysis of studies comparing renal functional outcomes for radical nephrectomy, partial nephrectomy, thermal ablation, and active surveillance. We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from January 1, 1997 to May 1, 2015 to identify comparative studies reporting renal functional outcomes. Meta-analyses were performed for change in eGFR, incidence of CKD, and AKI. We found 58 articles reporting on relevant renal functional outcomes. Meta-analyses showed that final eGFR fell 10.5 ml/min per 1.73 m2 lower for radical nephrectomy compared with partial nephrectomy and indicated higher risk of CKD stage 3 or worse (relative risk, 2.56; 95% confidence interval, 1.97 to 3.32) and ESRD for radical nephrectomy compared with partial nephrectomy. Overall risk of AKI was similar for radical nephrectomy and partial nephrectomy, but studies suggested higher risk for radical nephrectomy among T1a tumors (relative risk, 1.37; 95% confidence interval, 1.13 to 1.66). In general, similar findings of worse renal function for radical nephrectomy compared with thermal ablation and active surveillance were observed. No differences in renal functional outcomes were observed for partial nephrectomy versus thermal ablation. The overall rate of ESRD was low among all management strategies (0.4%-2.8%). Renal functional implications varied across management strategies for localized renal masses, with worse postoperative renal function for patients undergoing radical nephrectomy compared with other strategies and similar outcomes for partial nephrectomy and thermal ablation. Further attention is needed to quantify the changes in renal function associated with active surveillance and nephron-sparing approaches for patients with preexisting CKD.

Automated renal cortical volume measurement for assessment of renal function in patients undergoing radical nephrectomy.

Renal volume change greatly affects renal function after nephrectomy. Although various measuring techniques were reported, no standard measuring method is available. In this study, we examined the computational automated volumetric method, and evaluated the volumetric change to assess the functional outcome in patients undergoing radical nephrectomy. We developed the predictive equation for postoperative renal function from volume alternation and validated the performance. Thirty-two patients undergoing radical nephrectomy participated in this study. Renal volume was calculated using three different methods [ellipsoid method, conventional manual voxel count method for renal parenchyma (manual RPV), and automated voxel count method for renal cortex (automated RCV)] through newly developed imaging software. Statistical analysis was performed to evaluate the correlation between renal functional alternation 7days after the nephrectomy and renal volumetric change. A simple predictive equation for the postoperative renal function by renal volume loss was developed and externally validated through another 12 cases. The automated RCV method had the strongest correlation between renal function alternation and RCV change (R = 0.82), than manual RPV (R = 0.69) and ellipsoid method (R = 0.50). Subsequently, a simple equation for postoperative renal function by renal volume alternation was developed: predicted postoperative estimated glomerular filtration rate (eGFR) from renal volume change = preoperative eGFR×(postoperative renal volume / preoperative renal volume). In the external validation cohort, automated RCV demonstrated the predictive performance of the constructed equations for renal function (R = 0.77). The computational automated RCV measurements is a simple estimation of renal functional outcome for patients undergoing radical nephrectomy.

780 - Lymph node dissection is not associated with increased 30-day complications among patients undergoing radical nephrectomy for renal cell carcinoma: A propensity-score based analysis

780 - Lymph node dissection is not associated with increased 30-day complications among patients undergoing radical nephrectomy for renal cell carcinoma: A propensity-score based analysis

Clinicopathologic characterization and outcomes for patients with renal medullary carcinoma: Results from the National Cancer Database.

456 Background: Renal medullary carcinoma (RMC) is a rare, aggressive malignancy for which relatively limited characterization exists to date. We evaluated clinicopathologic features, treatment patterns, and variables associated with outcomes for patients with RMC. Methods: We reviewed the National Cancer Database to identify patients diagnosed with RMC between 1998-2012. Overall survival (OS) was estimated using the Kaplan-Meier method. Clinicopathologic features associated with all-cause mortality (ACM) were assessed using Cox regression analysis. Results: We identified 153 patients with RMC, comprising approximately 0.04% of renal malignancies during this time period. Median age at diagnosis for RMC was 24 years (IQR 20, 31). The majority of RMC patients were black (135; 88%), male (108; 71%), and presented with unilateral, right-sided tumors (101; 66%). Notably, nearly half (72; 48.9%) presented with metastatic disease. A total of 92 (64.3%) patients underwent radical nephrectomy (RN), and 2 (1.3%) were treated with partial nephrectomy. Pathologic stage at nephrectomy was ≤pT2 in 30 patients (32.6%), pT3 in 43 (46.7%), pT4 in 7 (7.6%), and N+ in 50 (55.6%). Of the patients who underwent RN, 60 (65.2%) received multimodal therapy (MMT), including radiation (3; 3.3%), systemic therapy (49; 53.3%), and radiation + systemic therapy (8; 8.7%). Of the 59 patients who did not undergo surgical resection, the majority (46; 77.8%) presented with M1 disease. Median OS was 7.8 months for the entire RMC cohort, with 1- and 3-year OS of 34% and 11%, respectively. Notably, median OS for patients presenting with M1 and M0 disease was 5.2 months versus 11.2 months, respectively (p&lt; 0.01). On multivariable analysis, treatment with RN (HR 0.40; p=0.003) or RN+MMT (HR 0.44; p&lt;0.001) were associated with decreased ACM, whereas the presence of metastatic disease at diagnosis remained associated with an increased risk of ACM (HR 1.74; p=0.02). Conclusions: The prognosis for patients with RMC is dismal, with a median OS under 8 months. Further studies, including the development of novel therapies, are needed to establish the optimal multimodal management approach for these patients.

Active surveillance is superior to radical nephrectomy and equivalent to partial nephrectomy for preserving renal function in patients with small renal masses: Results from the DISSRM registry

PurposeWe compared renal function outcomes among patients in the surveillance and intervention arms of the DISSRM registry. Materials and methodsPatients were grouped into chronic kidney disease stages by estimated glomerular filtration rate range. Cases were considered up staged if a more advanced chronic kidney disease stage was entered during followup. Chronic kidney disease up staging-free survival was compared among groups using Kaplan-Meier analysis and paired comparisons log rank tests. Multivariate Cox regression identified independent predictors of chronic kidney disease up staging-free survival. ResultsA total of 162 patients met the study inclusion criteria, with 68 in the surveillance arm, 65 undergoing partial nephrectomy, 15 undergoing radical nephrectomy, and 14 undergoing cryoablation. Median tumor size was 2.2cm. Mean estimated glomerular filtration rate change was significantly larger for radical nephrectomy vs. surveillance (−9.2 vs. −0.5ml/min/1.73m2) and for radical vs. partial nephrectomy (−9.2 vs. −1.9ml/min/1.73m2) (P = 0.001). No other groups differed significantly. On Kaplan-Meier analysis, patients undergoing radical nephrectomy had significantly worse chronic kidney disease up staging-free survival vs. those treated with partial nephrectomy (P = 0.029), surveillance (P = 0.007), and cryoablation (P = 0.019). No other groups differed significantly. On multivariate analysis, radical nephrectomy independently predicted poor chronic kidney disease up staging-free survival (odds ratio vs. surveillance 30.6, P = 0.001). Neither partial nephrectomy (P = 0.985) nor cryoablation (P = 0.976) predicted poor chronic kidney disease up staging-free survival relative to surveillance. ConclusionsPatients in the surveillance arm had superior estimated glomerular filtration rate preservation compared to those in the radical nephrectomy but not the partial nephrectomy arm. In certain patients with small renal masses, surveillance and partial nephrectomy may offer comparable renal functional outcomes. This could be partly attributable to a modest estimated glomerular filtration rate decrease associated with surveillance itself. A thorough understanding of the renal functional impacts of treatment modalities is critical in the management of small renal masses.

Transitional cell carcinoma with extension of the renal vein and IVC tumor thrombus: report of three cases and literature review

BackgroundTransitional cell carcinoma (TCC) originating from the renal pelvis with a venous tumor thrombus is a rare entity. However, clinicians should be aware of it because of its high malignancy and poor prognosis.Case presentationHere, we report three cases of pathologically confirmed TCC originating from the renal pelvis with extension into the renal vein or inferior vena cava (IVC). Of these patients, two are males and one is female (58~73 years old). Their main symptom is flank pain; besides, gross hematuria and weight loss is observed in one of the patients. Computed tomography (CT) scan of the first patient revealed multiple space-occupying lesions in the left renal pelvis and left medium and lower ureter with a tumor thrombus in the left renal vein. CT scan of the second patient revealed a right renal mass and extension into the IVC. Abdominal magnetic resonance imaging (MRI) of the third patient showed a soft tissue mass in the region of the left renal sinus, and the signal of the soft tissue was observed in the left renal vein. The preoperative diagnoses of the first and third patient were TCC, while the second patient was renal cell carcinoma (RCC). Two patients with the preoperative diagnosis of TCC underwent laparoscopic radical nephroureterectomy with thrombectomy, and the other patient underwent radical nephrectomy with thrombectomy. The surgeries were successful. Although two of our patients underwent chemotherapy and radiotherapy, they died 2 and 19 months after the surgery, respectively. The other patient refused any adjuvant therapy and died 3 months after the operation.ConclusionsCompared to the extension of RCC to the renal vein or IVC, extension of TCC to the renal vein or IVC is rare. TCC with a venous tumor thrombus is often misdiagnosed as RCC. However, a correct preoperative or intraoperative diagnosis is of great importance to decide surgical strategy. Laparoscopic radical nephroureterectomy with thrombectomy may be a safe and feasible operative method in treatment of TCC with a renal vein thrombus. The prognosis of such cases is poor even if chemotherapy and radiotherapy are scheduled.

MicroRNA 193b-3p as a predictive biomarker of chronic kidney disease in patients undergoing radical nephrectomy for renal cell carcinoma.

Background:A significant proportion of patients undergoing radical nephrectomy (RN) for clear-cell renal cell carcinoma (RCC) develop chronic kidney disease (CKD) within a few years following surgery. Chronic kidney disease has important health, social and economic impact and no predictive biomarkers are currently available. MicroRNAs (miRs) are small non-coding RNAs implicated in several pathological processes.Methods:Primary objective of our study was to define miRs whose deregulation is predictive of CKD in patients treated with RN. Ribonucleic acid from formalin-fixed paraffin embedded renal parenchyma (cortex and medulla isolated separately) situated >3 cm from the matching RCC was tested for miR expression using nCounter NanoString technology in 71 consecutive patients treated with RN for RCC. Validation was performed by RT–PCR and in situ hybridisation. End point was post-RN CKD measured 12 months post-operatively. Multivariable logistic regression and decision curve analysis were used to test the statistical and clinical impact of predictors of CKD.Results:The overexpression of miR-193b-3p was associated with high risk of developing CKD in patients undergoing RN for RCC and emerged as an independent predictor of CKD. The addition of miR-193b-3p to a predictive model based on clinical variables (including sex and estimated glomerular filtration rate) increased the sensitivity of the predictive model from 81 to 88%. In situ hybridisation showed that miR-193b-3p overexpression was associated with tubule-interstitial inflammation and fibrosis in patients with no clinical or biochemical evidence of pre-RN nephropathy.Conclusions:miR-193b-3p might represent a useful biomarker to tailor and implement surveillance strategies for patients at high risk of developing CKD following RN.

Neuropeptide Levels as well as Neprilysin Activity Decrease in Renal Cell Carcinoma.

Calcitonin Gene-related Peptide (CGRP), Vasoactive Intestinal Peptide (VIP) and Substance P (SP) are sensory neuropeptides which may alter cancer growth through modulation of chronic inflammation. We recently reported that SP suppresses breast cancer growth and metastasis through neuroimmune modulation. These neuropeptides are hydrolyzed by Neprilysin (NEP) to bioactive fragments. Decreased activity of NEP was reported in clear cell and chromophobe type renal cell carcinoma (RCC). It is however not known how the levels of neuropeptides hydrolyzed with NEP changes in RCC. Decrease activity of SP and CGRP containing sensory nerve endings was previously reported to increase cancer metastasis in animal models. It is however not known how peptidergic nerve endings are altered in RCC. Hence we here evaluated the levels of neuronal and non-neuronal neuropeptides and NEP activity in RCC including papillary type as well as neighboring uninvolved kidney. A cross-sectional study was conducted in 57 patients undergoing radical nephrectomy and diagnosed with RCC. NEP activity, levels and expression were determined using flourogenic substrate, western blot and qPCR respectively in freshly-frozen tissues. Immunohistochemical analyses were also performed. Neuronal and non-neuronal levels of CGRP, SP and VIP levels were determined using two-step acetic acid extraction. Levels and activity of NEP were markedly decreased in RCC regardless of subtype. Similar levels of VIP were detected in first and second extractions. VIP levels were higher in clear cell and papillary RCC compared to nearby kidney tissue. VIP levels of neighboring kidney tissue of papillary type RCC was significantly lower compared to kidney samples from clear cell RCC. CGRP levels were higher in second extraction. Similar to VIP levels, CGRP levels of neighboring kidney tissue from clear cell and chromophobe type RCC was significantly lower compared to corresponding tumor samples, an effect observed in the second extraction. VIP and CGRP levels of nearby kidney tissue varied subtype dependently demonstrating that different subtypes of RCC alter their local environment differently. Furthermore NEP-induce hydrolysis of VIP creates selective VPAC-1 receptor agonist which has anti-proliferative and anti-inflammatory effects. Hence loss of NEP activity may prevent anti-tumoral effects of VIP on RCC.

Clinicopathologic characteristics of thyroid-like follicular carcinoma of the kidney: an analysis of five cases and review of literature

Objective: To study the clinicopathologic features of thyroid-like follicular renal cell carcinoma. Methods: Clinical data were collected in 5 cases of thyroid-like follicular renal cell carcinoma. HE staining and immunohistochemistry were carried out in surgically-removed specimen to analyze the clinical and pathological features with review of the literatures. Results: The patients aged 20-55 years, with one male and four females; the tumor occurred in the left kidney in three cases and right kidney in two cases. One case had a history of thyroid papillary carcinoma 3 years ago, and the patient had left flank pain, macroscopic haematuria for 2 weeks. The rest four cases had no consciousness of clinical symptoms and signs, without history of thyroid gland surgery; the physical examination found a mass in the kidney and normal thyroid glands. Three patients underwent radical nephrectomy, and the other two patients underwent tumor partial nephrectomy. The tumors were 2-4 cm in size. They showed a solitary nodular mass of well circumscribed with taupe and gray on cut surface. Microscopically, most of tumor cells arranged in thyroid follicular pattern in different sizes, with papillary configuration in a small portion, in four cases; the follicular structure was intermixed with the papillary each half in one case. A large amount of thyroid colloid was deposited within follicule-like structure or papillary axis, lined by simple columnar cells or cubic cells, with obvious atypia, ground-glass nuclei, nuclear groove and rare mitosis. Immunohistochemical staining showed tumor cells were positive for PAX8, and negative for thyroid transcription factor 1 (TTF1) and thyroglobulin (Tg). One of five patients presented with lymph node metastases (4/4) of renal hilum the same time in the diagnosis. Five cases were followed up for 5-84 months after operation, and no tumor progression was found. Conclusions: Thyroid-like follicular renal cell carcinoma is primary renal epithelial malignant tumor. The diagnosis mainly depends on its characteristics of histological appearance, namely similar to the histological morphology of well-differentiated thyroid follicular carcinoma and papillary carcinoma, and the metastasis from the thyroid papillary or follicular carcinoma must be excluded. On the premise of clinical history, immunohistochemical markers TTF1 and Tg have certain value in the differential diagnosis.

Changes in expressions of ADAM9, 10, and 17 as well as α-secretase activity in renal cell carcinoma

BackgroundADAM9, 10, and 17 are a class of disintegrins and metallproteinases with α-secretase activity. There are conflicting results regarding the role(s) of ADAM9, 10, and 17 in carcinogenesis, and only a few studies have examined their levels and cellular localization in renal cell carcinoma (RCC). Studies examining changes in α-secretase activity in RCC compared to enzymatic activity of the uninvolved kidney are lacking. MethodA cross-sectional study was conducted in 56 patients undergoing radical nephrectomy after the diagnosis of RCC. α-Secretase activity was determined using flourogenic substrate in freshly frozen tumor tissues as well as similarly treated tissues from the neighboring kidney. Immunohistochemical analyses of ADAM9, 10, and 17 were also performed. Resultsα-Secretase activity decreased markedly in all types of RCC as compared to neighboring uninvolved kidney tissue having 5 to 10 times higher levels of α-secretase activity. Although type-dependent variations were observed, tumoral expressions of ADAMs, except for ADAM17, were lower in the tumors compared to that of neighboring tissues, but the changes in α-secretase activity were greater. In RCC tissue, ADAM9 expressions were localized in nuclear and cytoplasmic compartments, whereas ADAM10 and 17 were present predominately in the cytoplasm potentially explaining the markedly decreased enzyme activity. Membranous localization of ADAMs was noted in uninvolved kidney tissue. ConclusionsThe loss of α-secretase activity observed here in conjunction with previous findings argue against tumorigenic effects of ADAM9, 10, and 17 supporting that increased nuclear and cytoplasmic expression may be an attempt to compensate for loss of function.

Radical Nephrectomy With or Without Lymph Node Dissection for Nonmetastatic Renal Cell Carcinoma: A Propensity Score-based Analysis

BackgroundIt is uncertain whether lymph node dissection (LND) provides a therapeutic benefit in renal cell carcinoma (RCC). ObjectiveTo evaluate the association of LND with oncologic outcomes among patients undergoing radical nephrectomy (RN) for nonmetastatic RCC. Design, setting, and participantsA retrospective cohort study of 1797 patients treated with RN for M0 RCC between 1990 and 2010, including 606 (34%) who underwent LND. InterventionRN with or without LND. Outcome measurements and statistical analysisThe associations of LND with the development of distant metastases, cancer-specific mortality (CSM), and all-cause mortality (ACM) were evaluated using 1:1 propensity score (PS) matching, adjustment for/stratification by PS quintile, and inverse probability weighting. Cox models were used to evaluate the association of the number of lymph nodes removed with oncologic outcomes. Results and limitationsA total of 111 (6.2%) patients were pN1. The median follow-up after surgery was 10.6 yr. Following PS adjustment, there were no significant differences in clinicopathologic features between patients with and without LND. In the overall cohort, LND was not significantly associated with a reduced risk of distant metastases, CSM, or ACM. Moreover, LND was not associated with improved oncologic outcomes even among patients at increased risk of pN1 disease, including those with preoperative radiographic lymphadenopathy, or across increasing threshold probabilities for pN1 disease from 0.05 to 0.50. Among patients who underwent LND, the extent of LND was not significantly associated with the development of distant metastases, CSM, or ACM. Limitations include the retrospective design. ConclusionsWe did not identify an oncologic benefit to LND in the overall cohort or among patients at increased risk of nodal disease. These findings do not support a therapeutic benefit to LND in patients with M0 RCC. Patient summaryLymph node dissection does not appear to provide a therapeutic benefit in patients with nonmetastatic renal cell carcinoma.

Renal cell carcinoma with inferior vena cava involvement: Prognostic effect of tumor thrombus consistency on cancer specific survival.

Renal cell carcinoma forming a venous tumor thrombus (VTT) in the inferior vena cava (IVC) has a poor prognosis. Recent investigations have been focused on prognostic markers of survival. Thrombus consistency (TC) has been proposed to be of significant value but yet there are conflicting data. The aim of this study is to test the effect of IVC VTT consistency on cancer specific survival (CSS) in a multi-institutional cohort. The records of 413 patients collected by the International Renal Cell Carcinoma-Venous Thrombus Consortium were retrospectively analyzed. All patients underwent radical nephrectomy and tumor thrombectomy. Kaplan-Meier estimate and Cox regression analyses investigated the impact of TC on CSS in addition to established clinicopathological predictors. VTT was solid in 225 patients and friable in 188 patients. Median CSS was 50 months in solid and 45 months in friable VTT. TC showed no significant association with metastatic spread, pT stage, perinephric fat invasion, and higher Fuhrman grade. Survival analysis and Cox regression rejected TC as prognostic marker for CSS. In the largest cohort published so far, TC seems not to be independently associated with survival in RCC patients and should therefore not be included in risk stratification models. J. Surg. Oncol. 2016;114:764-768. © 2016 Wiley Periodicals, Inc.

The natural history of renal function after surgical management of renal cell carcinoma: Results from the Canadian Kidney Cancer Information System

Introduction and objectivePatients who undergo surgical management of renal cell carcinoma (RCC) are at risk for chronic kidney disease and its sequelae. This study describes the natural history of renal function after radical and partial nephrectomy and explores factors associated with postoperative decline in renal function. MethodsThis is a multi-institutional cohort study of patients in the Canadian Kidney Cancer Information System who underwent partial or radical nephrectomy for RCC. Estimated glomerular filtration rate (eGFR) and stage of chronic kidney disease were determined preoperatively and at 3, 12, and 24 months postoperatively. Linear regression was used to determine the association between postoperative eGFR and type of surgery (radical vs. partial), duration of ischemia, ischemia type (warm vs. cold), and tumor size. Results and limitationsWith a median follow-up of 26 months, 1,379 patients were identified from the Canadian Kidney Cancer Information System database including 665 and 714 who underwent partial and radical nephrectomy, respectively. Patients undergoing radical nephrectomy had a lower eGFR (mean = 19ml/min/1.73m2 lower) at 3, 12, and 24 months postoperatively (P<0.001). Decline in renal function occurred early and remained stable throughout follow-up. A lower preoperative eGFR and increasing age were also associated with a lower postoperative eGFR (P<0.01). Ischemia type and duration were not predictive of postoperative decline in eGFR (P>0.05). Severe renal failure (eGFR<30ml/min/1.73m2) developed postoperatively in 12.5% and 4.1% of radical and partial nephrectomy patients, respectively (P<0.001). ConclusionsAfter the initial postoperative decline, renal function remains stable in patients undergoing surgery for RCC. Patients undergoing radical nephrectomy have a greater long-term reduction in renal function compared with those undergoing partial nephrectomy. Ischemia duration and type are not predictive of postoperative renal function when adhering to generally short ischemia durations.