Adenomyosis and obstetric complications: A retrospective case-control study.

OBJECTIVE: Adenomyosis is a uterine pathology affecting an increasing number of women of childbearing age. Its diagnosis is based upon histology or imaging [ultrasound or magnetic resonance imaging (MRI)]. Several studies have investigated the impact of adenomyosis on obstetric complications, with its diagnosis based on clinical symptoms, ultrasound or composite criteria. The aim of this study was to identify potential obstetric complications related to adenomyosis in women with an MRI-confirmed diagnosis. METHODS: A single centre retrospective case-control study was undertaken in pregnant patients with an MRI-confirmed diagnosis of adenomyosis between January 2013 and December 2017 at the University Hospitals of Strasbourg. Controls were matched in a 4:1 ratio for age, parity and body mass index. Multivariate analysis was performed to identify obstetric complications. RESULTS: In total, 291 women with an MRI-confirmed diagnosis of adenomyosis were identified during the study period. Of these, 89 patients achieved pregnancy after 24 weeks of gestation. The mean age of patients was 30.8 years. The adenomyosis group and the control group were comparable for matching criteria. Adenomyosis was found to be associated with increased risk of caesarean section [odds ratio (OR) 1.1, 95 % confidence interval (CI) 1.0-1.2; p = 0.03], intrauterine growth restriction (OR 1.3, 95 % CI 1.1-1.4; p < 0.001), postpartum haemorrhage (OR 1.2, 95 % CI 1.1- 1.4; p < 0.01), pre-eclampsia (OR 1.3, 95 % CI 1.0-1.6; p = 0.004) and previous spontaneous miscarriage (OR 2.09, 95 % CI 1.36-3.33; p < 0.001). Premature rupture of membranes, preterm delivery, severe intrauterine growth restriction and the risk of placenta praevia were not significantly higher in the adenomyosis group compared with the control group on multivariate analysis. CONCLUSION: This study demonstrates increased risk of several obstetric complications (caesarean section, intrauterine growth restriction, postpartum haemorrhage, pre-eclampsia, history of spontaneous miscarriage) in women with adenomyosis. To the authors' knowledge, this is the first study to use MRI as the sole criterion for diagnosis. These results could be complemented by larger-scale prospective studies in order to manage these patients more effectively during pregnancy.

Tumor and immune remodeling following radiotherapy in human renal cell carcinoma.

BACKGROUND: Studies evaluating peripheral patient samples show radiation can modulate immune responses, yet the biological changes in human tumors particularly at the cellular level remain largely unknown. Here, we address how radiation treatment shapes the immune compartment and interactions with cancer cells within renal cell carcinoma (RCC) patient tumors. METHODS: To identify how radiation shaped the immune compartment and potential immune interactions with tumor cells we evaluated RCC tumors from patients treated only with nephrectomy or with radiation followed by nephrectomy. Spectral flow cytometry using a 35-marker panel was performed on cell suspensions to evaluate protein expression within immune subsets. To reveal how radiation alters programming of immune populations and interactions with tumor cells, we examined transcriptional changes by single-cell RNA sequencing (scRNAseq). RESULTS: Spectral flow cytometry analysis revealed increased levels of early-activated as well as effector programmed cell death protein-1 (PD-1)+ CD8 T-cell subsets within irradiated tumors. Following quality control, scRNAseq of tumor samples from nephrectomy-only or radiation followed by nephrectomy-treated patients generated an atlas containing 34,626 total cells. Transcriptional analysis revealed increased transition from stem-like T-cell populations to effector T cells in irradiated tumors. Interferon (IFN) pathways, that are central to radiation-induced immunogenicity, were enriched in irradiated lymphoid, myeloid, and cancer cell populations. Focused cancer cell analysis showed enhanced antigen presentation and increased predicted TRAIL-mediated and IFN-mediated interactions between tumor cells and the same effector T-cell subsets increased by radiation. TRAIL and IFN pathways enriched in irradiated tumors were associated with survival in patients treated with immunotherapy. CONCLUSIONS: These findings identify the source of IFN enrichment within irradiated RCC and reveal heightened levels of PD-1+ CD8+ T-cell subsets and increased probability of interactions with tumor cells following standalone radiation treatment. This study provides a window into the irradiated tumor-immune microenvironment of patients and rationale for treatment combinations.

Bowel resection performed by gynecologists - Outcomes and learning curves. Activity profile in a Gynecology Department: 7-year observational cohort.

OBJECTIVE: Bowel resection is frequently used when performing oncological surgery to obtain complete cytoreduction or to remove endometriosis in case of intestinal invasion. Acquiring the surgical skills to perform this kind of procedure is crucial to offer to our patients an optimal management. The aim of this study is to describe a 7-years surgical experience in bowel resections of a gynecologic surgeon and to determine his learning curves. STUDY DESIGN: This is a monocentric retrospective cohort study reporting digestive resection performed between January 2013 and April 2020 in the Gynecology Department of Strasbourg University Hospital. Ninety-one consecutive patients were assigned in two groups: gynecological cancer (n = 44) and deep infiltrating endometriosis (DIE) (n = 47). The main outcome measure was the postoperative complications rate at 30 days, based on the modified Clavien-Dindo severity system. Learning curves were evaluated using cumulative sum (CUSUM) analysis of operative time and risk-adjusted cumulative sum (RA-CUSUM) analysis of severe perioperative complications. Identification of predictive factors for operation duration and severe perioperative complication occurrence was conducted using multivariate analysis. RESULTS: Minor complications were found in 25% of cases. Major complication rate (Clavien-Dindo ≥ IIIa) was 14% in total and only involved patients operated for cancer. The CUSUM curve for operative time peaked at the 35th case and showed a downward slope after the 45th case. Significant predictive factors of operating time were cytoreductive tumoral surgery, size of the bowel resection and laparoscopic surgery, while learning phase 3 significantly decreased it. The RA-CUSUM curve for severe perioperative complications (Clavien-Dindo ≥ IIIa) showed a progressive decrease in the complication rate as the number of interventions increases without showing clear inflection points. Only cardiopulmonary pathologies were found as significant predictive factor of severe complications. CONCLUSION: Proficiency in performing highly complex surgery was achieved after approximately 45 cases, cancer and DIE all together. Acceptable rates of severe perioperative complications were observed even during the initial learning period and are comparable with those found in the literature concerning bowel resection performed by gynecologic oncologists but also by general and digestive surgeons.

Surgical Video Tutorial: Treatment of Congenital Vaginal Agenesis: Laparoscopic Modified Davydov in 8 Steps.

OBJECTIVE: To describe the different steps of the Davydov surgical technique for creating a neovagina, emphasizing visualization of the rectovesical cleavage and peritoneal-vaginal anastomosis by laparoscopic and vaginal approaches. DESIGN: Production of a step-by-step surgical video tutorial with narrative video footage. SETTING: Uterovaginal agenesis is a rare congenital defect, observed in 1 case per 4000 to 5000 newborn female infants [1]. Vaginal agenesis treatment can be performed by different nonsurgical and surgical techniques that are based on neocavity creation. The Davydov intervention uses the pelvic peritoneum as "covering" tissue for a neocavity and avoids the use of allogenic or autologous transplants, traction devices, or specialized surgical equipment. It is a minimally invasive technique that provides long-term functionality and anatomically satisfying results [2]. INTERVENTIONS: We treated an 18-year-old patient with Mayer-Rokitansky-Küster-Hauser syndrome who underwent the Davydov procedure after dissatisfaction with the Franck self-expansion method. We created a neovagina using peritoneal flaps that were obtained after rectovesical cleavage by laparoscopic approach and were then fastened to the introitus by vaginal approach. Finally, the vaginal vault was reconstructed laparoscopically, and an intravaginal dilator was left in place. The result after 1 year showed the transition from a narrow vaginal dimple 2 cm in length to a neovagina 10 cm in length, permeable, well epithelialized, and correctly healed without associated stenosis. Sexual intercourse is satisfying for both partners. CONCLUSION: The Davydov technique is less invasive than other surgical techniques and allows good outcomes [3,4] without the invasive use of sigmoidal grafts, cutaneous flaps, or prostheses. It should be proposed to patients experiencing failure with the Franck nonsurgical method.

Radiation induces dynamic changes to the T cell repertoire in renal cell carcinoma patients.

Clinical studies combining radiation and immunotherapy have shown promising response rates, strengthening efforts to sensitize tumors to immune-mediated attack. Thus, there is an ongoing surge in trials using preconditioning regimens with immunotherapy. Yet, due to the scarcity of resected tumors treated in situ with radiotherapy, there has been little investigation of radiation's sole contributions to local and systemic antitumor immunity in patients. Without this access, translational studies have been limited to evaluating circulating immune subsets and systemic remodeling of peripheral T cell receptor repertoires. This constraint has left gaps in how radiation impacts intratumoral responses and whether tumor-resident T cell clones are amplified following treatment. Therefore, to interrogate the immune impact of radiation on the tumor microenvironment and test the hypothesis that radiation initiates local and systemic expansion of tumor-resident clones, we analyzed renal cell carcinomas from patients treated with stereotactic body radiation therapy. Transcriptomic comparisons were evaluated by bulk RNA sequencing. T cell receptor sequencing monitored repertoires during treatment. Pathway analysis showed radiation-specific enrichment of immune-related processes, and T cell receptor sequencing revealed increased clonality in radiation-treated tumors. The frequency of identified, tumor-enriched clonotypes was tracked across serial blood samples. We observed increased abundance of tumor-enriched clonotypes at 2 wk postradiation compared with pretreatment levels; however, this expansion was not sustained, and levels contracted toward baseline by 4 wk posttreatment. Taken together, these results indicate robust intratumoral immune remodeling and a window of tumor-resident T cell expansion following radiation that may be leveraged for the rational design of combinatorial strategies.

Tumor-associated macrophage expression of interferon regulatory Factor-8 (IRF8) is a predictor of progression and patient survival in renal cell carcinoma.

Tumor-associated macrophages have been well-characterized in solid malignancies, including renal cell carcinoma and generally correlate with poor prognosis. However, the molecular mechanisms which govern intratumoral macrophage behavior and patient outcome are unclear. Here, we investigated whether alterations in macrophage expression of the transcriptional regulator for myeloid commitment and function, interferon regulatory factor-8 (IRF8), could predict survival of clear cell renal cell carcinoma patients. Transcriptional analysis of publicly available data revealed elevated IRF8 expression was associated with prolonged disease-free survival. Evaluation of protein expression within histologic sections of primary clear cell renal cell carcinoma patient samples showed intensity of IRF8 by CD68+ macrophages correlated inversely with stage. Survival outcomes of patients with primary or metastatic disease could be stratified on the basis of IRF8 levels by macrophages. Patients with high levels of IRF8 expression within metastatic sites had prolonged overall survival (log-rank P < 0.01, HR = 0.44, 95% C.I.: 0.23-0.84) compared to patients with low levels of IRF8 expression. When patient cohorts were further separated based on macrophage infiltration within metastatic lesions, patients with a macrophagelo IRF8hi profile had a more than 10 year increase in median overall survival compared to patients with a macrophagelo IRF8lo profile (log-rank, P < 0.001). In summary, we report that macrophage expression of IRF8 is inversely correlated with tumor mass and directly related to survival outcome. These findings support the utilization of IRF8 expression by macrophages to predict patient outcome, which may have important implications for guiding treatment decisions for renal cell carcinoma patients with metastatic disease.

Identification and Validation of Radiographic Enhancement for Reliable Differentiation of CD117(+) Benign Renal Oncocytoma and Chromophobe Renal Cell Carcinoma.

Purpose: The diagnostic differential for CD117/KIT(+) oncocytic renal tumor biopsies is limited to benign renal oncocytoma versus chromophobe renal cell carcinoma (ChRCC); however, further differentiation is often challenging and requires surgical resection. We investigated clinical variables that might improve preoperative differentiation of CD117(+) renal oncocytoma versus ChRCC to avoid the need for benign tumor resection.Experimental Design: A total of 124 nephrectomy patients from a single institute with 133 renal oncocytoma or ChRCC tumors were studied. Patients from 2003 to 2012 comprised a retrospective cohort to identify clinical/radiographic variables associated with renal oncocytoma versus ChRCC. Prospective validation was performed among consecutive renal oncocytoma/ChRCC tumors resected from 2013 to 2017.Results: Tumor size and younger age were associated with ChRCC, and multifocality with renal oncocytoma; however, the most reliable variable for ChRCC versus renal oncocytoma differentiation was the tumor:cortex peak early-phase enhancement ratio (PEER) using multiphase CT. Among 54 PEER-evaluable tumors in the retrospective cohort [19 CD117(+), 13 CD117(-), 22 CD117-untested], PEER classified each correctly as renal oncocytoma (PEER >0.50) or ChRCC (PEER ≤0.50), except for four misclassified CD117(-) ChRCC variants. Prospective study of PEER confirmed 100% accuracy of renal oncocytoma/ChRCC classification among 22/22 additional CD117(+) tumors. Prospective interobserver reproducibility was excellent for PEER scoring (intraclass correlation coefficient, ICC = 0.97) and perfect for renal oncocytoma/ChRCC assignment (ICC = 1.0).Conclusions: In the largest clinical comparison of renal oncocytoma versus ChRCC to our knowledge, we identified and prospectively validated a reproducible radiographic measure that differentiates CD117(+) renal oncocytoma from ChRCC with potentially 100% accuracy. PEER may allow reliable biopsy-based diagnosis of CD117(+) renal oncocytoma, avoiding the need for diagnostic nephrectomy. Clin Cancer Res; 24(16); 3898-907. ©2018 AACR.

Development of a Patient-Based Model for Estimating Operative Times for Robot-Assisted Radical Prostatectomy.

OBJECTIVES: To develop a methodology for predicting operative times for robot-assisted radical prostatectomy (RARP) using preoperative patient, disease, procedural, and surgeon variables to facilitate operating room (OR) scheduling. METHODS: The model included preoperative metrics: body mass index (BMI), American Society of Anesthesiologists score, clinical stage, National Comprehensive Cancer Network risk, prostate weight, nerve-sparing status, extent and laterality of lymph node dissection, and operating surgeon (six surgeons were included in the study). A binary decision tree was fit using a conditional inference tree method to predict operative times. The variables most associated with operative time were determined using permutation tests. Data were split at the value of the variable that results in the largest difference in mean for surgical time across the split. This process was repeated recursively on the resultant data. RESULTS: A total of 1709 RARPs were included. The variable most strongly associated with operative time was the surgeon (surgeons 2 and 4-102 minutes shorter than surgeons 1, 3, 5, and 6, p < 0.001). Among surgeons 2 and 4, BMI had the strongest association with surgical time (p < 0.001). Among patients operated by surgeons 1, 3, 5, and 6, RARP time was again most strongly associated with the surgeon performing RARP. Surgeons 1, 3, and 6 were on average 76 minutes faster than surgeon 5 (p < 0.001). The regression tree output in the form of box plots showed operative time median and ranges according to patient, disease, procedural, and surgeon metrics. CONCLUSION: We developed a methodology that can predict operative times for RARP based on patient, disease and surgeon variables. This methodology can be utilized for quality control, facilitate OR scheduling, and maximize OR efficiency.

A Pilot Study of Stereotactic Body Radiation Therapy Combined with Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma.

Purpose: While stereotactic body radiotherapy (SBRT) can reduce tumor volumes in patients with metastatic renal cell carcinoma (mRCC), little is known regarding the immunomodulatory effects of high-dose radiation in the tumor microenvironment. The main objectives of this pilot study were to assess the safety and feasibility of nephrectomy following SBRT treatment of patients with mRCC and analyze the immunological impact of high-dose radiation.Experimental Design: Human RCC cell lines were irradiated and evaluated for immunomodulation. In a single-arm feasibility study, patients with mRCC were treated with 15 Gray SBRT at the primary lesion in a single fraction followed 4 weeks later by cytoreductive nephrectomy. RCC specimens were analyzed for tumor-associated antigen (TAA) expression and T-cell infiltration. The trial has reached accrual (ClinicalTrials.gov identifier: NCT01892930).Results: RCC cells treated in vitro with radiation had increased TAA expression compared with untreated tumor cells. Fourteen patients received SBRT followed by surgery, and treatment was well-tolerated. SBRT-treated tumors had increased expression of the immunomodulatory molecule calreticulin and TAA (CA9, 5T4, NY-ESO-1, and MUC-1). Ki67+ -proliferating CD8+ T cells and FOXP3+ cells were increased in SBRT-treated patient specimens in tumors and at the tumor-stromal interface compared with archived patient specimens.Conclusions: It is feasible to perform nephrectomy following SBRT with acceptable toxicity. Following SBRT, patient RCC tumors have increased expression of calreticulin, TAA, as well as a higher percentage of proliferating T cells compared with archived RCC tumors. Collectively, these studies provide evidence of immunomodulation following SBRT in mRCC. Clin Cancer Res; 23(17); 5055-65. ©2017 AACR.

Outcomes of Minimal Invasive vs Open Radical Nephrectomy for the Treatment of Locally Advanced Renal-Cell Carcinoma.

PURPOSE: We compare oncologic outcomes of minimally invasive and open nephrectomy for locally advanced kidney cancer. MATERIALS AND METHODS: A retrospective review of a single-institutional, prospectively maintained database from a National Comprehensive Cancer Network-designated center was conducted. All patients who underwent radical nephrectomy at Roswell Park Cancer Institute with diagnosis of pT3 and pT4 renal-cell carcinoma (RCC) between years 1998 and 2015 were reviewed. Patients who underwent partial nephrectomy and nephroureterectomy were excluded. RESULTS: We identified 172 patients with pT3 or pT4 tumors resected by minimally invasive (laparoscopic and robotic) or open radical nephrectomy. Demographic characteristics were similar between the two groups. Patients in the minimally invasive group had a higher mean body mass index (31.9 vs 28.1, p = 0.002), radiologically smaller tumors (7.7 cm vs 9.1 cm, p = 0.008), lower mean estimated blood loss (277 vs 1429, p < 0.001), lower rate of blood transfusion (4.7% vs 45.5%, p < 0.001), and a shorter mean length of stay (3.5 days vs 5.7 days, p < 0.001) compared with patients who underwent open surgery. At a median follow-up of 32.8 months, there was no significant difference in overall survival (p = 0.8) between the two groups. CONCLUSION: Minimal invasive nephrectomy is a safe approach with similar oncologic outcomes to open nephrectomy for select patients with locally advanced RCC.

Minimally invasive cytoreductive nephrectomy: a multi-institutional experience.

PURPOSE: To analyze the functional and oncologic outcomes of minimally invasive cytoreductive nephrectomy (CN) in three high-volume cancer centers. PATIENTS AND METHODS: Three prospectively maintained, IRB-approved kidney surgery databases were queried from three high-volume cancer centers. All patients who underwent minimally invasive surgery (laparoscopic, hand-assisted laparoscopic, or robotic) partial or radical CN with existing measurable extra-renal metastatic disease between May 2001 and May of 2013 were included in this analysis. RESULTS: We identified 120 patients who underwent minimally invasive CN for metastatic renal cell carcinoma. Most of the surgeries were radical (93.3 %) and performed laparoscopically (96.6 %). Median operative time was 210 min, with a median estimated blood loss of 150 cc, and 11 (9.2 %) patients received blood transfusions. Four (3.3 %) patients were converted to open surgery due to locally advanced disease and/or bleeding. Postoperative complications were seen in 28 (23.3 %) patients, of which 20 (71.4 %) were classified as minor (Clavien-Dindo I-II). The median survival of the entire cohort was 25.7 months, with a 3-year survival rate of 35 %. Multivariate analysis indicated that only hypertension, brain metastasis, and pT stage were independently associated with worse overall survival (HR > 1). CONCLUSIONS: Minimally invasive cytoreductive nephrectomy is feasible and safe in experienced hands with acceptable morbidity and oncological outcomes.

Oncological control associated with surgical resection of isolated retroperitoneal lymph node recurrence of renal cell carcinoma.

OBJECTIVE: To evaluate the outcome of patients after surgical resection of isolated retroperitoneal lymph node (RPLN) recurrence of renal cell carcinoma (RCC) using a multicentre international cohort. PATIENTS AND METHODS: In all, 50 patients were identified who underwent resection of isolated RPLN recurrence of RCC at four institutions after nephrectomy for pTany Nany M0 disease. Progression-free (PFS) and cancer-specific survival (CSS) were estimated using the Kaplan-Meier method. Cox proportional hazards regression models were used to assess the association of clinicopathological characteristics with disease progression. RESULTS: The median (interquartile range, IQR) age at resection was 57.0 (50.0-62.5) years. The median (IQR) time to RPLN recurrence after nephrectomy was 12.6 (6.9-39.5) months, with no significant difference in median time to RPLN recurrence between patients with N+ disease at nephrectomy (10.7 [6.5-24.6] months) and those with Nx/pN0 disease at nephrectomy (13.7 [8.7-44.2] months) (P = 0.66). The median (IQR) size of the RPLN recurrence before resection was 2.6 (1.9-5) cm. The most common site for RPLN recurrence was within the interaortocaval region (34%). The median (IQR) follow-up after RPLN resection for patients alive at last follow-up was 28.0 (13.7-51.2) months. During follow-up, 26 patients developed RCC recurrence, at a median (IQR) of 9.9 (4.0-18.5) months after RPLN resection. Of those who developed a secondary recurrence, disease was again isolated to the retroperitoneum in seven patients. In all, 11 patients subsequently died, including 10 who died from disease. The median PFS after RPLN resection was 19.5 months, with a 3- and 5-year PFS of 40.5% and 35.4%, respectively. We also found that RPLN recurrence at ≤12 months after nephrectomy was associated with a significantly inferior median PFS (12.3 months) compared with RPLN recurrence at >12 months after nephrectomy (47.6 months; P = 0.003). Moreover, on multivariate analysis, a shorter time to recurrence remained associated with a significantly increased risk for subsequent disease progression (hazard ratio 3.51; P = 0.005). CONCLUSION: Surgical resection of isolated RPLN recurrence from RCC may result in durable cancer control in appropriately selected patients. Recurrence at ≤12 months after nephrectomy was associated with a significantly increased risk of progression after resection, underscoring the importance of this variable for risk stratification. Thus, we recommend that, in the setting of isolated RPLN recurrence of RCC (in patients without precluding comorbidities), careful consideration with the patients and medical oncology colleagues be undertaken about the relative and individualised benefits of surgical resection, systemic therapy, and surveillance.

Incidence of Clear Cell Papillary Renal Cell Carcinoma in Low-Grade Renal Cell Carcinoma Cases: A 12-Year Retrospective Clinicopathologic Study From a Single Cancer Center.

Clear cell papillary renal cell carcinoma (CCPRCC) is a recently recognized subtype of renal cell carcinoma entity after 2004 World Health Organization classification of renal tumors. CCPRCC has unique histomorphological and immunohistochemical characteristics. The distinction of CCPRCC from renal cell carcinoma (RCC) with clear cell morphology is crucial because the former is considered to have a favorable clinical outcome. CCPRCC may be interpreted in the past as other renal cell carcinomas, particularly low-grade clear cell RCC. In this study, the frequency of CCPRCC in previously diagnosed low-grade RCC and its clinicopathologic features were examined. A total of 126 cases of stage T1a with low nuclear grade RCC were identified from 625 consecutive RCCs removed by radical/partial nephrectomy over 12-year period (2000-2011). Archival tissue sections were retrospectively reviewed along with patient medical charts. Eight cases (1.3% of all RCC, 6.3% of pT1a low grade RCC) with characteristic histologic features of CCPRCC were confirmed by immunohistochemical studies. Seven cases were previously diagnosed as clear cell RCC and one as multilocular cystic RCC. Radiographically, CCPRCC favored a mid-pole location in the kidneys. At a median follow-up period of 52 months (range 20-114.5 months), there were no cases of local or distant recurrence. In conclusion, CCPRCC is not uncommon among small low-grade RCC tumors. CCPRCC can be correctly recognized by its unique histomorphological features and confirmed by immunohistochemistry studies, which is important due to the excellent clinical outcome following resection.

Early identification of asymptomatic brain metastases from renal cell carcinoma.

Current guidelines for metastatic renal cell carcinoma (mRCC) do not recommend routine brain imaging as part of the surveillance protocol unless central nervous system (CNS) symptoms or abnormal laboratory values suggest brain involvement. We hypothesized that strict adherence to these guidelines will delay diagnosis and management of RCC brain metastases. Retrospective review of our IRB-approved kidney cancer database examined a consecutive series of subjects from 1995 to 2012. We identified all mRCC patients with radiographic evidence of renal cell brain metastasis (RCCBM). RCCBM patients were divided into two cohorts: CNS symptoms present at RCCBM diagnosis and those without symptoms present at diagnosis. Fifty-two patients within our database met criteria; CNS symptoms were present at RCCBM diagnosis in 73 % (36) of patients. Median size of RCCBM on presentation was smaller in the asymptomatic verses the symptomatic cohort (0.83 vs. 1.7 cm, p = 0.003). Multivariate analysis demonstrated presence of CNS symptoms and female gender as a survival advantage (p < 0.05) while poor performance status, history of tobacco abuse and coexistence of lung metastasis were poor indicators for survival (p < 0.05). Patients with pulmonary metastases and a history of tobacco abuse are more likely to harbor RCCBM and perhaps in the absence of CNS symptoms these subjects should have routine brain surveillance incorporated into the RCC follow up. Overall, the current urologic guidelines may be missing a subset of metastatic RCC patients who could potentially benefit from early radiation or neurosurgical intervention. This may result in improved overall survival.

Comparative Analysis of Smoking as a Risk Factor among Renal Cell Carcinoma Histological Subtypes.

PURPOSE: Smoking is the best established modifiable risk factor for renal cell carcinoma. However, the risks of individual renal cell carcinoma histological subtypes are unknown. Therefore, we investigated the relationship between smoking and renal cell carcinoma subtype. MATERIALS AND METHODS: Cigarette smoking data were prospectively collected from 816 consecutive patients with nonfamilial renal cell carcinoma (705) or benign pathology (111) undergoing nephrectomy at a single National Comprehensive Cancer Network® cancer center, and were retrospectively tested for an association with histological diagnosis on univariable and propensity adjusted analyses. RESULTS: Smoking was reported by 51% of patients, including 21% active smokers and 30% former smokers. Active smoking was more common with clear cell (23%) or papillary (26%) renal cell carcinoma than benign histology (14%, p <0.05 each), yet strikingly less common with chromophobe renal cell carcinoma (6%, p <0.05 vs clear cell or papillary). Any smoking history (active or former) was also relatively uncommon with chromophobe (26%) vs clear cell (53%, p = 0.003) or papillary (58%, p = 0.001) histology. Smoking extent based on mean pack-years was significantly greater with clear cell (15.3 mean pack-years) or papillary (15.2 mean pack-years) renal cell carcinoma but not chromophobe renal cell carcinoma (9.4 mean pack-years) compared to benign histology (9.4 mean pack-years, p ≤0.05, p <0.05, p = 1.0, respectively). On propensity analyses adjusting for multiple variables, clear cell (OR 2.2, p <0.05) and papillary (OR 2.4, p <0.05) histologies but not chromophobe histology remained independently associated with active smoking. CONCLUSIONS: Traditional understanding of smoking as a renal cell carcinoma risk factor applies to clear cell and papillary renal cell carcinoma but not the chromophobe subtype. These findings underscore distinct carcinogenic mechanisms underlying the various renal cell carcinoma subtypes.

Cancer control of partial nephrectomy for high-risk localized renal cell carcinoma: population-based and single-institutional analysis.

PURPOSE: Cancer control of partial nephrectomy for high-risk localized renal cell carcinoma is unclear. To assess whether PN provides adequate cancer control in high-risk disease (HRD), survival outcomes were compared in both a population-based cohort and an institutional cohort. METHODS: Surveillance, Epidemiology, and End Results database and a prospectively maintained institutional database were queried for patients with RCC who underwent PN or RN for a localized tumor ≤7 cm and were found to have high-grade and/or high-stage disease (HRD). Cancer-specific (CSS) or recurrence-free survival (RFS) and overall survival (OS) were primary outcomes measured and were compared between those who underwent PN and RN using multivariable Cox proportional hazards and propensity analysis. RESULTS: The population cohort consisted of 12,757 (24.9 %) patients with HRD, 85.2 and 14.8 % of which underwent RN and PN, respectively. RN was not associated with CSS (HR 1.23, p = 0.08) but was independently associated with poor OS (HR 1.16, p = 0.031). Propensity analysis showed that RN resulted in a 20 % increased risk of death from all causes (p = 0.008). In the institutional cohort, of 317 patients, 35.9 % had HRD, 56 and 52 of which underwent RN and PN, respectively. Adjusting for age-adjusted Charlson index, RN was a predictor of poor OS (OR 6.20, p = 0.041). Propensity analysis showed that RFS and OS were not related to nephrectomy type (RN HR 0.65, p = 0.627 and RN HR 1.70, p = 0.484). CONCLUSIONS: In patients with pathologic high-risk RCC, partial excision is associated with similar cancer control as compared to radical excision.

Learning curves for robot-assisted and laparoscopic partial nephrectomy.

OBJECTIVES: To evaluate the learning curve of robot-assisted partial nephrectomy (RAPN) and laparoscopic partial nephrectomy (LPN) between two surgeons at a single institution. METHODS: A prospectively maintained, Institutional Review Board (IRB)-approved kidney surgery database was reviewed retrospectively and the first 116 consecutive LPNs performed by one surgeon (Hyung Kim) and 116 consecutive RPNs performed by a second surgeon (Thomas Schwaab) were identified. The learning curve was evaluated by examining the operative times, warm ischemia times (WITs), estimated blood loss, the postoperative estimated glomerular filtration rate (eGFR), and intra- and postoperative complications in the quartiles of 29 patients. The LPNs performed by Hyung Kim were done following completion of a minimally invasive fellowship. Thomas Schwaab had minimal experience with LPN and no fellowship training before starting RAPN. RESULTS: The RAPN and LPN groups had similar patient and tumor characteristics. The RAPN group had a higher preoperative eGFR (74.1±22.04 vs. 80.95±21.25 mL/minutes, p=0.015) and a worse Eastern Cooperative Oncology Group (ECOG) performance status (ECOG 1+ in 12% vs. 2.6%, p<0.001) compared with the LPN group. Rates of intraoperative (p=0.203) and postoperative (p=0.193) complications were similar. In the RAPN group, operating room (OR) time (161±51 vs. 203±55 minutes, p<0.001) and WIT (17.7±14.8 vs. 21.8±9.1 minutes, p<0.001) were shorter. Postoperative stay was longer in the RAPN group (2.4±2.2 vs. 1.67±1.1 days, p<0.001). The percentage decrease in postoperative eGFR was lower in the RAPN group versus the LPN (9.6% vs. 10%). The learning curves differed for log tumor size, log WIT, and postoperative complications. CONCLUSIONS: The variables of the learning curve for RAPN can be obtained earlier than the same variables for LPN. RAPN had a shorter OR time and WITs. The shorter WITs, earlier in the series, led to consistently lower fluctuations in GFR and preservation of the renal function. The learning curves for each procedure need to be re-evaluated at longer intervals to ensure their accuracy.

High-dose interleukin-2 therapy for metastatic renal cell carcinoma: a contemporary experience.

OBJECTIVE: To present our experience of high-dose interleukin-2 (HDIL-2) in a high-volume National Cancer Institute-designated center for patients with metastatic renal cell carcinoma (mRCC). METHODS: Patients with mRCC who received HDIL-2 monotherapy as a first- or second-line therapy during 2004-2011 were identified. Demographics, pathologic variables, renal function, time until the start of HDIL-2 therapy, number of cycles (1-3), responses (complete response, partial response, stable disease, and progressive disease), and primary renal cell carcinoma treatment were analyzed. Progression-free survival and overall survival (OS) were determined. RESULTS: Of 906 patients in the kidney cancer database, 91 patients with mRCC were treated with HDIL-2 and 18 patients (20.5%) underwent prior cytoreductive nephrectomy. Median age was 51 years, and 73.9% were men. Median follow-up was 45 months. Pretreatment renal function impairment led to more treatment cycles (2-3) than in those with adequate initial kidney function (92.3% vs 50.6%, respectively; P = .002). Lower tumor stage correlated with a better response (P = .023) and with longer time from diagnosis to initiation of HDIL-2 (P = .011). Complications included hypotension (67.4%), renal impairment (63%), impaired liver function (42.4%), and thrombocytopenia (31.5%). Four patients (4.5%) had a complete response, 10 (11.4%) had a partial response, and 28 (31.8%) had a stable disease. Median progression-free survival and OS were 8.6 and 35.5 months, respectively. The estimated 2-year OS rate was 60.6%. CONCLUSION: Incorporating HDIL-2 therapy in the treatment strategies for mRCC added to the patients' survival in this series. HDIL-2 therapy is well tolerated in patients with pre-existing renal impairment with no long-term renal toxicity.

Surgical outcomes in the management of isolated nodal recurrences: a multicenter, international retrospective cohort.

PURPOSE: We report a multicenter international cohort representing what is to our knowledge the largest surgical experience with managing isolated retroperitoneal nodal recurrence of renal cell carcinoma, a unique subset of locoregional disease, yet to be described in detail. MATERIALS AND METHODS: Patients with isolated nodal recurrence of pTanyN+M0 disease after nephrectomy were identified by retrospective chart review at 3 independent institutions. Progression-free survival was estimated by the Kaplan-Meier method and used to compare survival outcomes between primary T(1-2)N(any)M0 and T3N(any)M0 tumors as well as clear cell and nonclear cell histology renal cell carcinoma. RESULTS: A total of 22 patients met study inclusion criteria. Median time to local postoperative recurrence was 31.5 months (IQR 12.9-43.3). After resection of isolated nodal recurrence 10 patients (46%) had a secondary recurrence at a median of 11.2 months (IQR 8.1-18.4), of whom 2 (9%) died of the disease. Overall median progression-free survival was 12.7 months, including 24.8 months for T(1-2)N(any)M0 tumors, 9.9 months for T3N(any)M0 tumors, and 13.4 and 17.6 months for clear and nonclear cell renal cell carcinoma, respectively. CONCLUSIONS: Surgical resection represents the best curative option for patients who present with isolated retroperitoneal lymph node recurrence of renal cell carcinoma. Durable postoperative progression-free survival is attainable in many patients regardless of histology or clinical TNM stage. In addition, our cohort showed a lower renal cell carcinoma related mortality rate than in previous series of local metastasis. As such, all patients free of precluding comorbidities should be considered candidates for complete surgical resection performed by an experienced genitourinary surgeon.