Nephrectomy For Renal Cell Carcinoma Research Articles

The impact of visceral adipose tissue on postoperative renal function after radical nephrectomy for renal cell carcinoma.

The objective of this study was to evaluate the usefulness of pre-operative visceral (VAT) and subcutaneous adipose tissue (SAT) evaluation in the prediction of acute kidney injury (AKI) and decrease of eGFR at 12 months after radical nephrectomy (RN). We relied on 112 patients who underwent RN between January 2010 and March 2017 at a single institution. Images from the pre-operatory CT scan were analyzed and both SAT and VAT assessments were carried out on a cross-sectional plane. eGFR was measured before surgery, at 7 days, and 12 months after surgery. ROC analysis was used to compare the diagnostic value of BMI, VAT ratio, and abdominal circumference in predicting AKI. Logistic regression models were fitted to predict the new onset of AKI, and the progression from chronic kidney disease (CKD) stage 1-3a to CKD stage 3b or from 3b to 4 at 12 months follow-up. Two logistic regression models were also performed to assess the predictors for AKI and CKD stage progression. The predictive accuracy was quantified using the receiver operating characteristic-derived area under the curve. Sixty-six patients (58.9%) had AKI after RN. Thirty-five (31.3%) patients were upgraded to CKD IIIb or from CKD stage IIIb to CKD IV. In the ROC analysis, VAT% performed better than the BMI and abdominal circumference (AUC=0.66 vs. 0.49 and 0.54, respectively). At multivariable analyses, VAT reached an independent predictor status for AKI (OR: 1.03) and for CKD stage at 12-month follow-up (OR: 1.05). Inclusion of VAT% into the multivariable models was associated with the highest accuracy both for AKI (AUC=0.700 vs. 0.570) and CKD stage progression (AUC=0.848 vs. 0.800). In patients undergoing RN, preoperative visceral adipose tissue ratio significantly predicts AKI incidence and is significantly predictive of 12-month CKD stage worsening.

Analysis of plasma KIM-1 as a biomarker for recurrence risk after resection for localized renal cell carcinoma.

342 Background: Recurrence is common after nephrectomy for renal cell carcinoma (RCC), but no circulating biomarkers are available to identify patients at highest risk of recurrence who may benefit from adjuvant therapy. Kidney injury molecule-1 (KIM-1) is overexpressed in RCC and its ectodomain circulates in plasma. We investigated whether plasma KIM-1 is a prognostic biomarker in patients with localized RCC after nephrectomy. Methods: Banked plasma samples were analyzed from the ECOG-ACRIN 2805 (ASSURE) trial evaluating adjuvant sunitinib, sorafenib, and placebo in resected high-risk RCC. KIM-1 levels were measured at trial enrollment 4-12 weeks post-nephrectomy (baseline) and on cycle 2 day 1 (C2D1) using a previously validated microbead assay. A lognormal accelerated failure time model was used to test for association between circulating KIM-1 and disease-free survival (DFS). Results: Plasma samples from 418 patients were analyzed. In univariable and multivariable analyses, higher post-nephrectomy KIM-1 was associated with worse DFS across all study arms. This association remained independently significant after adjustment for Fuhrman grade, T-stage, N-stage, and tumor histology (survival time ratio 0.56 for 75th vs 25th percentile of KIM-1, 95% CI 0.42-0.73, p < 0.001). The association between KIM-1 and DFS was stronger among patients with pathologic nodal involvement. The addition of baseline KIM-1 improved the concordance of both the SSIGN and UISS prognostic models (SSIGN concordance 0.57 vs 0.43, p = 0.05; UISS concordance 0.60 vs 0.40, p = 0.0005). C2D1 KIM-1 was not an independent predictor for DFS after adjusting for baseline KIM-1. Conclusions: Elevated plasma KIM-1 level at post-nephrectomy baseline is associated with worse DFS in RCC. This is consistent with the hypothesis that post-nephrectomy plasma KIM-1 may be a biomarker for microscopic residual disease. The model was additionally adjusted for papillary and chromophobe histology, sex, and ECOG performance status. [Table: see text]

Pre-treatment Delta Neutrophil Index as a Predictive Factor in Renal Cell Carcinoma.

To determine the diagnostic value of the pre-treatment delta neutrophil index (DNI) before treatment in patients with renal cell carcinoma (RCC) and to compare this marker with other routine inflammation markers, such as neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR). Descriptive study. Department of Urology, Kahramanmaras Sutcu Imam University, Turkey, from February 2017 to January 2020. Data of patients who underwent radical nephrectomy for RCC, were evaluated. For comparison, healthy individuals were included in the study as a control group. Demographic data, such as age, gender, routine laboratory tests, DNI, NLR, and PLR levels of the groups were recorded and compared. There were 73 patients in the RCC group and 71 healthy individuals in the control group. DNI, NLR and PLR levels were significantly higher in the RCC group (p <0.001, each). DNI and NLR were significantly higher in patients with advanced stage (T3-T4) and high grade (G3-G4). In univariate logistic regression analysis hemoglobin (p=0.023), neutrophil (p<0.001), lymphocyte (p=0.009), platelet (p<0.001), DNI (p<0.001), NLR (p<0.001) and PLR (p<0.001) were identified as predictors for RCC. In multivariate logistic regression analysis, DNI and NLR (p<0.001, each) were found to be the predictors of RCC. Cut-off values were 0.45% for DNI, 1.80 for NLR, and 130.09 for PLR. DNI is a new inflammatory marker, which is included in complete blood count parameters; and does not require any additional calculation, unlike NLR and PLR. It can be used in the prediction of RCC. Key Words: Renal cell carcinoma, Delta neutrophil index, Neutrophil-lymphocyte ratio, Platelet-lymphocyte ratio.

Change in renal function post-nephrectomy for renal cell carcinoma in patients with and without hypertension and/or diabetes

The standard of care for surgically resectable disease renal cell carcinoma (RCC) is a nephrectomy. Post-nephrectomy, these patients are at risk for the development of new onset chronic kidney disease or the progression of pre-existing chronic kidney disease. We aimed to report the changes in renal function in patients who had a nephrectomy for RCC. This retrospective, descriptive, cross-sectional study identified 137 patients who had a nephrectomy for RCC from 1 January 2009 to 31 December 2017. The pre-nephrectomy and post-nephrectomy estimated glomerular filtration rate (eGFR) and the histological subtype of RCC on histopathological analysis of the resected specimen were recorded from the National Health Laboratory Services online results platform. All analyses were conducted using SPSS (Version 25) and the significance level was set at p < 0.05. After a mean follow-up period of 26.5 ± 22 months (median = 19 months), the patients' eGFR dropped by a mean of 4.82 ± 8.67 ml/min/1.73 m2 (95% CI 3.23-6.41) post-nephrectomy. The mean eGFR fall in patients' who had hypertension and/or diabetes (n = 63) was significantly larger compared to patients who had neither of these comorbidities (n = 54; p < .001; mean = 7.30 ± 8.40 ml/min/1.73 m2 (95% CI 5.19-9.42) and 1.93 ± 8.14 ml/min/1.73 m2 (95% CI 0.30-4.15) respectively. The decline in renal function in patients with hypertension and/or diabetes mellitus is more pronounced than in patients with neither of these comorbidities. In these high-risk patients, measures must be taken to prevent the development and limit the progression of chronic kidney disease.

Recommandations françaises du Comité de transplantation de l’association française d’urologie (CTAFU) : carcinome rénal sur reins natifs chez le patient transplanté rénal ou en attente de transplantation

To define guidelines for the management of renal cell carcinoma of the native kidney (NKRCC) in kidney transplant (KTx) recipients and renal cell carcinoma (RCC) in end-stage renal disease (ESRD) patients candidates for renal transplantation. A review of the literature following a systematic approach (Medline) was conducted by the CTAFU to report renal cell carcinoma epidemiology, screening, diagnosis and management in KTx candidates and recipients. References were assessed according to a predefined process to propose recommendations with the corresponding levels of evidence. ESRD patients are at higher risk of RCC with a standardized incidence ratio of approximately 4,5as compared with general population. NKRCC tumors occur in 1to 3% of KTx recipients with a 10to 15-fold increased risk as compared with general population, especially in patients with acquired multicystic kidney disease. Most authors suggest yearly monitoring of the native kidneys using ultrasound imaging. Radical nephrectomy (either open or laparoscopic approach) is the preferred treatment of NKRCC in KTx recipients and RCC in ESRD. Surveillance in a valid option in small or cystic renal masses. In the localized setting, change in immunosuppressive therapy is not recommended besides perioperative avoidance of mTOR inhibitor to limit morbidity. CTAFU does not recommend a mandatory waiting time after nephrectomy for RCC in ESRD patients candidates for renal tranplantation when tumor stage<T3and low ISUP grade. Follow-up modalities should follow recommendations in general population. The French recommendations should contribute to improve management of NKRCC in KTx recipients and RCC in ESRD candidates for KTx, integrating oncological objectives in the context of kidney transplantation.

A rare complication following partial nephrectomy for renal cell carcinoma

A rare complication following partial nephrectomy for renal cell carcinoma

SGLT2 Inhibition in Patients With Type 2 Diabetes Mellitus Post-Nephrectomy: A Single-Center Case Series

Background:Nephrectomy is the mainstay of treatment for many kidney cancers, but has been correlated with increased incidence of acute kidney injury (AKI) and chronic kidney disease (CKD). Recently, sodium-glucose cotransporter-2 (SGLT2) inhibition has been shown to decrease the incidence of end-stage kidney disease and death in people with type 2 diabetes mellitus (T2D). However, at present, there has been no description of the use of SGLT2 inhibition in patients with T2D and solitary kidney despite the high risk of CKD progression.Objective:To characterize the use of SGLT2 inhibition and kidney function in a series of patients with T2D with prior nephrectomy for renal cell carcinoma (RCC).Design:Retrospective case series.Setting:University hospital outpatient onco-nephrology clinic.Patients:Patients post-nephrectomy for RCC with T2D who were prescribed an SGLT2 inhibitor.Measurements:Serum creatinine, albumin to creatinine ratio (ACR), HgA1c, and blood pressure measurements.Methods:Patients post-nephrectomy with incident use of SGLT2 inhibitor were identified from an existing registry of patients followed in the Onco-Nephrology Clinic at our institution from May 2019 to March 2021. Demographics, medication use, time since nephrectomy, cancer diagnosis, serum creatinine, ACR measurements, and blood pressure measurements were extracted from electronic medical records.Results:Five patients were identified who had initiated SGLT2 inhibition post-nephrectomy. All patients were male, had T2D, and a prior history of hypertension. Renal cell carcinoma was the clinical indication for nephrectomy in all patients. None of patients were prescribed diuretics, and all were receiving renin-angiotensin system (RAS) inhibition therapies. The time from nephrectomy to SGLT2 inhibitor initiation ranged from 5 to 74 months. Baseline mean estimated glomerular filtration rate (eGFR) values were 49 mL/min/1.73 m2 (95% confidence interval [CI]: 31.5-66.5), and mean ACRs were 8.7 mg/mmol (95% CI: 0.6-16.9). After 6 months of SGLT2 inhibition, the mean eGFR and ACR values were 58 mL/min/1.73 m2 (95% CI: 29.7-86.2) and 23.8 mg/mmol (95% CI: 0-60), respectively. After 16 to 18 months of follow-up (4 patients), the mean eGFR was 56 mL/min/1.73 m2 (95% CI: 37.3-74.7), and mean ACR was 10.5 (95% CI: 0-30.5), similar to baseline values before SGTL2i therapy initiation. At baseline, mean systolic blood pressure was 128 mm Hg (95% CI: 118.3-140.9) and remained similar after 12 months of treatment (mean 131 mm Hg [95% CI: 112.3-149.7]). There were no adverse events related to AKI, electrolyte disturbances, ketoacidosis, or genitourinary infections during the 18-month follow-up period.Limitations:Small sample size, lack of a comparison group, and the variable timing of clinical data collection, including eGFR levels following initiation of SGLT2 inhibition.Conclusions:SGLT2 inhibition is becoming a standard component of nephrology care to reduce kidney function decline, cardiovascular risk, and mortality. To our knowledge, our report is the first to provide longitudinal data on SGLT2 inhibitor usage in patients with T2D and solitary kidneys post-nephrectomy. Larger prospective studies are needed to determine the efficacy and safety of SGLT2 inhibition strategies for kidney protection in patients post-nephrectomy.

Comparative analysis of histopathological subtypes of renal cell carcinoma in the Middle East compared to other world regions.

Introduction:Renal cell carcinoma (RCC) has various histopathological tumor subtypes which have a significant implication on the oncological outcome of these patients. We aimed to evaluate the distribution of RCC subtypes presenting at a tertiary care center in the Middle East, in comparison to the distribution reported in different geographic areas worldwide.Methods:A retrospective chart review was conducted on all patients who underwent partial or radical nephrectomy for RCC at the American University of Beirut Medical Center between January 2012 and January 2018. Data on histologic subtypes were compiled and compared to representative series from different continents.Results:One hundred and seventy-nine patients with RCC were identified, of whom 122 (68.2%) were classified as clear cell, 30 (16.8%) as papillary, 17 (9.5%) as chromophobe, and 10 (5.6%) as unclassified. When compared to other regions of the world, this Middle Eastern series demonstrated a higher prevalence of the chromophobe subtype compared to Western populations (9.5% in the Middle East vs. 5.3% in the US and 3.1% in Europe) and a lower prevalence of clear cell subtype (68.2% in the Middle East vs. 78.7% in the US and 85.8% in Europe). Conversely, there was a higher prevalence of papillary RCC in the Middle East (16.8%) compared to North America (13.1%, 95% confidence interval [CI]: 12.7–13.6), Europe (11.1%, 95% CI: 10.0–12.1), and Australia (10.2%). The prevalence of chromophobe and clear cell RCC in the Middle East was similar to that reported in South America.Conclusions:The distribution of RCC subtypes in this Middle Eastern cohort was significantly different from that reported in the Western hemisphere (Europe and the US) but similar to that reported in South America and Australia. These findings may point to a possible genetic predisposition underlying the global variation in distribution.

Prognostic Evaluation of the Site of Invasion in Pathological Stage T3a Renal Cell Carcinoma.

To investigate the prognostic values of fat invasion (FI) and renal vein invasion (RVI) in pT3a renal cell carcinoma (RCC), as single factors or concomitant presence. We retrospectively reviewed the data of 173 patients who underwent radical or partial nephrectomy for RCC in our Institution. At a median follow-up time of 48 months, patients with RVI showed significantly increased risk of disease recurrence and worse cancer-specific survival (CSS) when compared to those with FI (p=0.007, p=0.022, respectively). Having combined RVI and FI did not show inferior prognosis compared to those with RVI only. In multivariable analysis, RVI was an independent factor for disease recurrence (HR=2.06, 95% CI=1.10-3.87, p=0.024) and CSS (HR=2.46, 95% CI=1.01-6.0, p=0.048). For patients with T3a renal tumors, RVI was associated with inferior prognosis compared to those with FI.

Preoperative Assessment of Renal Sinus Invasion by Renal Cell Carcinoma according to Tumor Complexity and Imaging Features in Patients Undergoing Radical Nephrectomy.

ObjectiveTo identify the association between renal tumor complexity and pathologic renal sinus invasion (RSI) and evaluate the usefulness of computed tomography tumor features for predicting RSI in patients with renal cell carcinoma (RCC).Materials and MethodsThis retrospective study included 276 consecutive patients who underwent radical nephrectomy for RCC with a size of ≤ 7 cm between January 2014 and October 2017. Tumor complexity and anatomical renal sinus involvement were evaluated using two standardized scoring systems: the radius (R), exophytic or endophytic (E), nearness to collecting system or sinus (N), anterior or posterior (A), and location relative to polar lines (RENAL) nephrometry and preoperative aspects and dimensions used for anatomical classification (PADUA) system. CT-based tumor features, including shape, enhancement pattern, margin at the interface of the renal sinus (smooth vs. non-smooth), and finger-like projection of the mass, were also assessed by two independent radiologists. Univariable and multivariable logistic regression analyses were performed to identify significant predictors of RSI. The positive predictive value, negative predictive value (NPV), accuracy of anatomical renal sinus involvement, and tumor features were evaluated.ResultsEighty-one of 276 patients (29.3%) demonstrated RSI. Among highly complex tumors (RENAL or PADUA score ≥ 10), the frequencies of RSI were 42.4% (39/92) and 38.0% (71/187) using RENAL and PADUA scores, respectively. Multivariable analysis showed that a non-smooth margin and the presence of a finger-like projection were significant predictors of RSI. Anatomical renal sinus involvement showed high NPVs (91.7% and 95.2%) but low accuracy (40.2% and 43.1%) for RSI, whereas the presence of a non-smooth margin or finger-like projection demonstrated comparably high NPVs (90.0% and 91.3% for both readers) and improved accuracy (67.0% and 73.9%, respectively).ConclusionA non-smooth margin or the presence of a finger-like projection can be used as a preoperative CT-based tumor feature for predicting RSI in patients with RCC.

Individualised Predictions of the Survival Benefit Due to Adjuvant Therapy in a Randomised Trial of Sorafenib after Nephrectomy for Localised Renal Cell Carcinoma

BACKGROUND: Little has been published regarding how doctors think and talk about prognosis and the potential benefits of adjuvant therapy. OBJECTIVE: We sought predictions of survival rates and survival times, for patients with and without adjuvant therapy, from the clinicians of patients participating in a randomised trial of adjuvant sorafenib after nephrectomy for renal cell carcinoma. METHODS: A subset of medical oncologists and urologists in the SORCE trial completed questionnaires eliciting their predictions of survival rates and survival times, with and without adjuvant sorafenib, for each of their participating patients. To compare predictions elicited as survival times versus survival rates, we transformed survival times to survival rates. To compare predicted benefits elicited as absolute improvements in rates and times, we transformed them into hazard ratios (HR), a measure of relative benefit.We postulated that a plausible benefit in overall survival (OS) should be smaller than that hypothesized for disease–free survival (DFS) in the trials original sample size justification (i.e. HR for OS should be ≥ 0.75). RESULTS: Sixty–one medical oncologists and 17 urologists completed questionnaires on 216 patients between 2007 and 2013. Predictions of survival without adjuvant sorafenib were similar whether elicited as survival rates or survival times (median 5–year survival rate of 61% vs 60%, p = 0.6). Predicted benefits of sorafenib were larger when elicited as improvements in survival rates than survival times (median HR 0.76 vs 0.83, p &lt; 0.0001). The proportion of HR for predicted OS with sorafenib that reflected a plausible benefit (smaller effect of sorafenib on OS than hypothesized on DFS, i.e. HR ≥ 0.75) was 51% for survival rates, and 65% for survival times. CONCLUSIONS: The predicted benefits of adjuvant sorafenib were larger when elicited as improvements in survival rates than as survival times, and were often larger than the sample size justification for the trial. These potential biases should be considered when thinking and talking about individual patients in clinical practice, and when designing clinical trials.

New Baseline Renal Function after Radical or Partial Nephrectomy: A Simple and Accurate Predictive Model.

Preoperative estimation of new baseline glomerular filtration rate after partial nephrectomy or radical nephrectomy for renal cell carcinoma has important clinical implications. However, current predictive models are either complex or lack external validity. We aimed to develop and validate a simple equation to estimate postoperative new baseline glomerular filtration rate. For development and internal validation of the equation, a cohort of 7,860 patients with renal cell carcinoma undergoing partial nephrectomy/radical nephrectomy (2005-2015) at the Veterans Affairs National Health System was analyzed. Based on preliminary analysis of 94,327 first-year postoperative glomerular filtration rate measurements, new baseline glomerular filtration rate was defined as the final glomerular filtration rate within 3 to 12 months after surgery. Multivariable linear regression analyses were applied to develop the equation using two-thirds of the renal cell carcinoma Veterans Administration cohort. The simplest model with the highest coefficient of determination (R2) was selected and tested. This model was then internally validated in the remaining third of the renal cell carcinoma Veterans Administration cohort. Correlation/bias/accuracy/precision of equation were examined. For external validation, a similar cohort of 3,012 patients with renal cell carcinoma from an outside tertiary care center (renal cell carcinoma-Cleveland Clinic) was independently analyzed. New baseline glomerular filtration rate (in ml/minute/1.73 m2) can be estimated with the following simplified equation: new baseline glomerular filtration rate = 35 + preoperative glomerular filtration rate (× 0.65) - 18 (if radical nephrectomy) - age (× 0.25) + 3 (if tumor size >7 cm) - 2 (if diabetes). Correlation/bias/accuracy/precision were 0.82/0.00/83/-7.5-8.4 and 0.82/-0.52/82/-8.6-8.0 in the internal/external validation cohorts, respectively. Additionally, the area under the curve (95% confidence interval) to discriminate postoperative new baseline glomerular filtration rate ≥45 ml/minute/1.73 m2 from receiver operating characteristic analyses were 0.90 (0.88, 0.91) and 0.90 (0.89, 0.91) in the internal/external validation cohorts, respectively. Our study provides a validated equation to accurately predict postoperative new baseline glomerular filtration rate in patients being considered for radical nephrectomy or partial nephrectomy that can be easily implemented in daily clinical practice.

Can kidney parenchyma metabolites serve as prognostic biomarkers for long-term kidney function after nephrectomy for renal cell carcinoma? A preliminary study.

ObjectiveNephrectomy, the standard of care for localized renal cell carcinoma (RCC), may lead to kidney function loss. Our goal was to identify prognostic biomarkers of postoperative renal function using metabolomics.MethodsMetabolomics data from benign kidney parenchyma were collected prospectively from 138 patients with RCC who underwent nephrectomy at a single institution. The primary endpoint was the difference between the postoperative and preoperative estimated glomerular filtration (eGFR) rate divided by the elapsed time (eGFR slope). eGFR slope was calculated ∼2 years post-nephrectomy (GFR1), and at last follow-up (GFR2). A multivariate regularized regression model identified clinical characteristics and abundance of metabolites in baseline benign kidney parenchyma that were significantly associated with eGFR slope. Findings were validated by associating gene expression data with eGFR slope in an independent cohort (n = 58).ResultsData were compiled on 78 patients (median age 62.6 years, 65.4% males). The mean follow-up was 25 ± 3.4 months for GFR1 and 69.5 ± 23.5 months for GFR2 and 17 (22%) and 32 (41%) patients showed eGFR recovery, respectively. Nephrectomy type, blood lipids, gender and 23 metabolites from benign parenchyma were significantly associated with eGFR slope. Some metabolites associated with eGFR slope overlapped with previously reported chronic kidney disease-related processes. Subgroup analysis identified unique ‘metabolite signatures’ by older age, nephrectomy type and preoperative eGFR.ConclusionsNephrectomy type, gender, blood lipids and benign parenchyma metabolites at nephrectomy were associated with long-term kidney function. On further study, these metabolites may be useful as potential biomarkers and to identify novel therapeutic targets for malignancy-associated renal disease.

Re: Editorial Comment from Dr Bertolo etal. to Partial nephrectomy preserves renal function without increasing the risk of complications compared with radical nephrectomy for renal cell carcinomas of stages pT2-3a.

None declared.

Transplant Radical Nephrectomy and Transplant Radical Nephroureterectomy for Renal Cancer: Postoperative and Survival Outcomes.

BackgroundThe treatment of complex tumors in non-functioning renal transplants requiring surgical extirpation is challenging. Here, we report the largest series of patients who underwent transplant radical nephrectomy for renal cell carcinoma (RCC) and transplant radical nephroureterectomy for urothelial cell carcinoma (UCC) in their transplanted kidneys.Material/MethodsFrom 2004 to 2018, 10 patients underwent transplant radical nephrectomy (7 patients) and nephroureterectomy (3 patients). Retrospective analyses, in terms of complications, oncological recurrence, and survival, of peri-operative and long-term outcomes, were performed.ResultsOut of the 10 patients, 7 had RCC and 3 had UCC. No intraoperative mortality occurred. Three patients presented with Clavien-Dindo grade IIIa or greater within 30 days of surgery. Two patients died within 60 days of surgery, both due to vascular events: one due to myocardial infarction and one due to stroke. Two other patients died: one after 2.9 years, due to myocardial infarction, and the other after 6 years, due to unknown reasons. At the 7-year follow-up, there was a 60% overall survival rate. For all patients, average survival post-nephrectomy was approximately 4.5 years, including the 6 living patients and 4 deceased patients. Importantly, there was no observed cancer recurrence.ConclusionsThis study reports outcomes of the largest series of transplant radical nephrectomy and nephroureterectomy for malignancies of renal allografts. In the optimized setting, extirpative surgeries appear safe, with favorable long-term oncological and survival outcomes.

Single Fraction Stereotactic Body Radiation Therapy Induces Dynamic Changes to the Peripheral Blood 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 scarcity of resected tumors treated in situ with radiotherapy, there has been little investigation of radiation’s sole contributions towards local and systemic anti-tumor 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 carcinoma from patients treated with stereotactic body radiation therapy. Blood and tumor samples were collected from patients prior to nephrectomy for renal cell carcinoma. These samples were compared to samples from patients treated on a 15 patient clinical trial of single fraction stereotactic body radiation therapy delivered 4 weeks prior to nephrectomy. Transcriptomic comparisons were evaluated by bulk RNA sequencing. T cell receptor sequencing monitored repertoires during the 4-week period between SBRT and nephrectomy. Pathway analysis from tumor transcriptomic data showed radiation-specific enrichment of immune-related processes. T cell receptor sequencing revealed increased clonality in radiation-treated tumors. The frequency of identified, tumor-enriched clonotypes was tracked across serial blood samples. Compared to pre-treatment, we observed increased abundance of tumor-enriched clonotypes 2 weeks post-radiation. However, this expansion was not sustained and contracted towards baseline levels 4 weeks after treatment. Altogether, these results indicate robust intratumoral immune remodeling and a window of tumor-resident T cell expansion following radiation that may be leveraged for rational design of combinatorial strategies. Samples from renal cell carcinoma (RCC) patients underwent high-throughput analysis to reveal transcriptional immune activation and increased clonality in irradiated tumors. Analysis across longitudinal blood samples showed tumor-enriched clonotypes undergo phases of peripheral expansion and contraction following radiation. Collectively, these findings demonstrate radiotherapy remodels intratumoral T cell responses and have significant implications for refined sequencing of combination strategies in RCC.

A spurious decline in kidney function: A reality check.

A man aged 70 years was referred to a renal clinic by his general practitioner for evaluation of a decline in his renal function. He had a history of hypertension, for which he was taking perindopril and amlodipine in combination, and left nephrectomy for renal cell carcinoma in 2013. A drop in his estimated glomerular filtration rate (eGFR) from a baseline of approximately 70 mL/min in February 2019 to 51 mL/min in May 2019 was noted with no obvious cause. His perindopril was withheld in view of this decline. However, by the time he was reviewed in the clinic, his renal function had recovered and he had recommenced perindopril. On perusing his blood tests, it was noted that he had significantly different eGFR reported for the same serum creatinine value (eGFR of 51 mL/min and 68 mL/min for a serum creatinine value of 98 mumol/L). Between May and August 2019, when a lower eGFR was reported, the serum creatinine reference range for females (45-85 mumol/L) had been used instead of that for males (60 -115 mumol/L). The patient's results are shown in Table 1. The patient had a unisex first name, likely resulting in an inadvertent biological sex misassignment and a spuriously low eGFR. This was subsequently corrected, resulting in an improvement in his eGFR. On contacting the reporting laboratory, it was established that the correct biological sex had been ascribed to the patient on the request form, but the error had occurred at the level of the laboratory, likely from an error of manual transcription.

Transnasal Endoscopic Resection of the Intraconal Metastases From Renal Cell Carcinoma: a Case Report and Review of Literature.

Renal cell carcinoma (RCC) is the most common malignancy to cause metastasis to sinonasal cavity. These metastases can occasional cause invasion into the orbit. Isolated intraconal intraorbital metastasis from RCC is very rare. We hereby describe a case of 72-year-old female, who underwent right nephrectomy for RCC, 8 years back, and now presenting with a space occupying lesion in the right intraorbital intraconal compartment with no involvement of the paranasal sinuses. En bloc resection of the tumor was achieved via transnasal endoscopic approach. This is a rare case where minimally invasive surgery was done for metastatic lesion, with minimal postoperative morbidity.

PUK4 Cost-Effectiveness of Robotic-Assisted Partial Nephrectomy

To evaluate the cost-effectiveness of robotic-assisted partial nephrectomy (RAPN) compared to laparoscopic PN (LPN) and open procedure (OPN). A model combined decision tree and Markov model with a 10-year time horizon was developed to evaluate outcomes and costs for a hypothetical cohort of patients underwent partial nephrectomy for renal cell carcinoma. The decision tree was used to characterize the intraoperative infection, and the Markov model comprised four health states was used to estimate the expected survival duration and costs. Parameter estimates were derived from literature and claims data of the National Health Insurance in Taiwan. Univariate and probabilistic sensitivity analyses were conducted. The expected quality-adjusted life years (QALYs)/total costs for RAPN, LPN and OPN were 7.38/$12,548, 7.33/$8,587 and 6.60/$11,087, respectively. OPN was a dominated strategy as it provided fewer QALYs at increased cost compared with LPN. The incremental cost-effectiveness ratio for RAPN compared with LPN was $81,521 per QALY gained. Probabilistic sensitivity analysis indicated a 45% probability of RAPN being cost-effective at a hypothetical threshold of $75,000/QALY (3 times Taiwan‘s GDP per capita). This study shows that RAPN and LPN have similar outcomes, but RAPN has higher costs. There needs to be a decrease in costs of RAPN for the robot surgery to be cost effective.

Feasibility and Safety of Robotic Excision of Ipsilateral Retroperitoneal Recurrence After Nephrectomy for Renal Cell Carcinoma

To determine feasibility and safety of robotic excision of local ipsilateral recurrences after nephrectomy for renal cell carcinoma (RCC). Surgical resection is an option for treatment of low burden locally recurrent RCC, potentially delaying the use of systemic therapy. This has historically been performed by open technique, which can impart significant morbidity. We present our experience with robotic excision. We reviewed our institutional experience of patients with surgically excised RCC who underwent robotic excision of ipsilateral retroperitoneal recurrence in 2015-2018. Demographics and clinicopathological variables, including operative and postoperative outcomes, were examined. Twelve robotic excisions of ipsilateral local recurrences were performed in our hospital in 2015-2018. Mean age was 65.48 years (± standard deviation, SD: 9.51), 10 patients were male, and mean BMI 34.75 kg/m2 (± 6.71). Nine patients recurred after radical nephrectomy, and 3 after partial nephrectomy. Mean size of recurrence was 2.97 cm (±1.69). Mean anesthesia time, EBL, and LOS were 213 minutes (± 38.92), 152 mL (± 130.75), and 43 hours (± 12.64), respectively. All surgical margins were negative. No surgical complications were reported. Median follow-up was 19.0 months [interquartile range, IQR 12.7-30.0]. Five patients out of 12 recurred following robotic excision, these were treated with either systemic therapy, radiation, or palliative surgeries. Mean time for subsequent recurrence was 26.5 months. In this small case series, robotic excision of ipsilateral RCC retroperitoneal recurrence appears safe, technically feasible, and oncologically sound in expert hands and carefully selected patients.