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The incidence of ectopic kidney is 1 in 2100–3000 autopsies. Renal cell cancer (RCC) in pelvic kidney is a rare entity with limited case reports available in the literature. Symptoms can vary from abdominal pain to haematuria, or RCC can be detected incidentally. Contrast imaging with computed tomography (CT) angiography is recommended to determine the location of the renal mass and the anatomy of surrounding organs and major vessels feeding it. Treatment of choice is radical nephrectomy. We report a case of RCC in ectopic pelvic kidney managed with radical nephrectomy that was deemed unresectable on CT imaging.

The purpose of the study was the analysis of the structure of the pathology of the ipsilateral adrenal gland after radical nephrectomy or partial nephrectomy in patients with renal cell cancer. Materials and methods. To study the structure of adrenal pathology in a sample of 2,084 patients who were treated for renal cell cancer, a retrospective study of the pathological findings and case reports of 108 patients, in whom surgical treatment included adrenalectomy or adrenal resection, was performed. Results and discussion. In 10 (83.3%) of 12 patients with adrenal gland resection, mass lesions of this organ served as an indication for adrenal surgery, while in 2 (16.7%) patients intraoperative adrenal trauma was noted. In this group, there were no situations of preservation of the adrenal gland with a direct generalization of the renal tumor to it. Among 98 patients who underwent adrenalectomy, the main indications for removal of the adrenal gland were its mass lesions in 65 (66.3%) cases, while direct tumor generalization to the ipsilateral adrenal gland took place in 8 (8.2%) cases. In other 7 (7.1%) situations, a tumor thrombus penetrated through the lumen of the renal or inferior vena cava into the lumen of the adrenal vein. In 16 (16.7%) patients, adrenalectomy was performed due to massive trauma to the adrenal gland during the removal of massive renal tumors localized in the upper pole of the kidney. Among all 75 patients with mass ipsilateral lesions of the adrenal glands, metastases of renal cell cancer were detected in 12 (16%) cases. In 59 (78.7%) cases benign adrenal adenomas were found, in 2 (2.7%) cases – myelolipomas, in 1 (1.3%) – adrenal hyperplasia, in another 1 (1.3%) – pheochromocytoma. The proportion of synchronous malignant pathology of the ipsilateral adrenal gland in patients with renal cell cancer and with indications for adrenalectomy was 25% (27 out of 108 observations). In relation to all 2,084 operated patients, this indicator did not exceed 1.3%. In the group of organ-preserving surgery, it was significantly lower – 0.2% (2 out of 968 patients), while in the group of radical or cytoreductive nephrectomy it reached 2.2% (25 out of 1116 cases). The total amount of cases of the ipsilateral adrenal gland lesions with renal cell cancer was also studied: 12 (0.6%) – metastases, 8 (0.4%) – direct tumor generalization and 7 (0.3%) – tumor invasion into the adrenal vein, which was determined in 27 (1.3%) patients. Conclusion. The need for ipsilateral adrenalectomy or adrenal resection is extremely rare in the large modern cohort of patients. At the same time, a significant part of the synchronous formations of the ipsilateral adrenal glands is benign tumors. In this regard, further study of the feasibility and safety of adrenal organ-preserving surgeries is necessary

KIM-1 (kidney injury molecule 1), a marker of acute kidney injury, is produced by epithelial cells of renal proximal tubules. Elevated KIM-1 levels in urine and plasma are associated with renal cell carcinoma (RCC). The aim of this study was to compare the significance of non-normalized uKIM-1 values and those normalized to urine creatinine, as urinary biomarkers in RCC. The uKIM-1, urine creatinine and their ratio (uKIM-1/Cre) were studied in 118 RCC patients and 58 apparently healthy subjects. The median of uKIM-1 in the healthy group was 0.71 ng/ml (1st and 3rd quartiles were 0.35 and 1.23, respectively) and in RCC patients it was 2.36 (1.43; 5.93) ng/ml. The medians of uKIM-1/Cre were 0.77 (0.49; 1.18) and 2.42 (1.41; 4.61) ng/mgCre, respectively. Stage I RCC is statistically significantly different from stages II-III and stage IV using uKIM-1/Cre values (p = 0.0056 and p = 0.0012, respectively); using uKIM-1 values significant differences occur only when comparing stages I and IV (p = 0.015). In both healthy individuals and RCC patients, uKIM-1/Cre levels were slightly lower in subgroups younger than 50 years than in subgroups older than 50 years, whereas a similar trend was observed for uKIM-1 only in patients. In healthy men and male patients, uKIM-1 levels were higher than in the corresponding groups of women (the differences were not statistically significant), but the use of uKIM-1/Cre values eliminated the gender differences. A high correlation was found between the concentrations of uKIM-1 and urine creatinine in three healthy subjects followed up for 3 weeks (Spearman’s correlation coefficients were 0.758, 0.825 and 0.933, respectively). The data obtained are clear evidence of the need for normalization uKIM-1 to urine creatinine in RCC patients.

Hereditary leiomyomatosis is a genetic disorder that follows an autosomal dominant pattern of inheritance. Along with a variety of leiomyomas, affected individuals are predisposed to developing an aggressive form of type 2 papillary renal malignancy known as Hereditary Leiomyomatosis Associated Renal Cell Carcinoma (HLRCC) that can occur in both the tubulo-papillary and collecting-duct systems. We present a rare case of HLRCC with components of urothelial carcinoma. The patient was treated with cisplatin-based neoadjuvant chemotherapy followed by left radical nephroureterectomy to achieve complete remission of disease.

We report two cases of women with metastatic cancers to ampulla of Vater. The first was 91 years old and presented with severe anemia, due to upper gastrointestinal bleeding. She had history of renal cell cancer treated with nephrectomy 8 years ago and diagnosis confirmed to be metastasis of renal cell cancer to ampulla of Vater. The second patient was 54 years old with breast cancer, metastasis and developed obstructive jaundice; diagnosis confirmed to be breast metastasis in the ampulla of Vater. Secondary tumors of the ampulla of Vater due to breast cancer and renal cell cancer are rare findings and prognosis can be poor.

Objective:Estimating surgical complications is crucial to assess the benefit-harm balance of partial nephrectomy (PN), a complex surgical option compared to radical nephrectomy. This study aimed to assess the factors affecting the occurrence of modified Clavien-Dindo grade 2 or higher complications after PN.Materials and Methods:Data of patients who underwent PN due to renal cancer from January 2015 to June 2018 were prospectively collected. Database was analysed retrospectively by dividing into two groups with Clavien-Dindo grade 0-1 complications (group 1) and with grade 2 or higher complications (group 2). The resection technique was classified by the surgeon as enucleation, enucleo-resection or resection according to the Surface-Intermediate-Base (SIB) margin scores of 0, 1 and 2, respectively. Factors affecting the occurrence of grade 2 or higher complications were evaluated by univariate and multivariate regression analysis.Results:A total of 161 patients were included in the study. The overall rate of perioperative complications was 18.6%. Twenty-four patients (14.9%) had grade 2 or higher complications and 11 patients (6.8%) had serious complications (grade 3 or higher). SIB-score was 0 in 103 (63.9%) patients, 1 in 36 (22.4%) patients and 2 in 22 (13.7%) patients. Multivariate binary logistic regression analysis revealed that the C-index [odds ratio (OR): 0.224, 95% confidence interval (CI): 0.092-0.493, p=0.001], laparoscopic surgical technique (OR: 12.668, 95% CI: 2.825-59.326, p=0.001), and SIB-score 1-2 (OR: 2.852, 95% CI: 1.416-9.826, p=0.002) are independent factors in predicting complications of Clavien-Dindo grade 2 or higher.Conclusion:C-index, laparoscopic approach and resection techniques (SIB-score 1-2) are independent factors in predicting perioperative complications of Clavien- Dindo grade 2 or higher following PN.

The development and review of combination drug regimens in oncology may present unique challenges to investigators and regulators. For regulatory approval of combination regimens, it is necessary to demonstrate the contribution of effect of each monotherapy to the overall combination. Alternative approaches to traditional designs may be needed to accelerate oncology drug development, for example, when combinations are substantially superior to available therapy, to reduce exposure to less effective therapies, and for drugs that are inactive as single agents and that in combination potentiate activity of another drug. These approaches include demonstration of activity in smaller randomized trials and/or monotherapy trials conducted in a similar disease setting. This article will discuss alternative approaches used in the development of approved drugs in combination, based on examples of recent approvals of combination regimens in renal cell carcinoma.

Aim: Percutaneous tumor ablation is the most important alternative to surgery in early stage renal cell cancers (RCC). Although many studies are conducted with radiofrequency ablation and cryoablation therapy in RCC, the data regarding microwave ablation (MWA) is more limited. In this study, we aimed to evaluate the efficacy of percutaneous MWA in the treatment of RCC, its safety in terms of residual renal function and other complications, and its clinical results. Methods: In T1b patients, the suitability for MWA was evaluated with a urologist based on characteristics such as size, and location of the mass (intestinal proximity, proximity to the main renal vascular structures and renal pelvis). Fourteen T1a, five T1b and one T2 RCC patients treated with MWA were included in this retrospective study. MWA was preferred when partial nephrectomy was highly risky or contraindicated due to medical comorbidities or the patients refused to undergo surgical treatment. The patients were ablated with uncooled MWA device with 30W energy under sedation or general anesthesia under ultrasound guidance for an average of 13 minutes. Multiple antennas were used for masses larger than 4 cm. Hydrodissection with saline was performed in cases where there was a non-target organ adjacent to the lesion. Lesion size, location of the lesion, ablation time, complications, Charlson comorbidity index, Hb, and creatinine values were recorded. Patients were followed by CT. Results: The mean age of the patients was 68.9 years, and the median lesion size was 2.8 cm. While the tumor was exophytic in 12 patients, it was intraparenchymal or endophytic in 8 patients. The average Charlson comorbidity index score of the patients was 6.9. Technical success was achieved in all patients. Average ablation time was 13 minutes. Minor complications occurred in 3 patients. The median follow-up period of the patients was 13.5 months. In Kaplan Meier analysis, progression-free survival was 12 months. During follow up, distant organ metastasis was not observed in any of the patients, recurrence was observed in 2, and no patients died. Conclusion: MWA can be applied in early stage RCCs with very high technical success. The results of our study show that MWA is effective and highly reliable in RCCs. It can be safely applied, especially in patients who are not suitable for surgery and in residual RCCs.

A clinical case of the successful surgical treatment of patient with multiple primary cancers, including locally-advanced right renal cell cancer, transitional-cell cancer bladder cancer and metachronous transitional-cell cancer of the left kidney with one of the longest follow-up and survival time described in the literature.

Objectives: To evaluate outcomes in our patients undergoing inferior vena cava (IVC) resection without reconstruction, as part of an adrenal/renal cell cancer (RCC) operation. Methods: British Association of Urological Surgeons (BAUS) Data and Audit System records were obtained for two operating surgeons, each at geographically separate urological cancer centres. Retrospectively reviewed case notes of patients who had undergone IVC resection without reconstruction as part of an adrenal/RCC operation, assessing operative parameters, length of stay, complications and follow-up status. Results: A total of Twenty-eight patients (20 right-sided tumours, 8 left sided) underwent IVC resection without reconstruction in May 2013–February 2017. No perioperative or early deaths occurred. Fourteen patients (50%) had complications: sepsis; pneumonia; congestive cardiac failure; acute kidney injury; symptomatic peripheral deep venous thrombosis; splenectomy; and significant chyle leak. At a median follow-up of 21 months (range 1–55 months) six patients (21.4%) have died and two patients (7.1%) progressed to metastatic disease, giving a 71.4% progression-free survival in this series. Conclusions: This case series illustrates our experience of IVC resection without reconstruction as an acceptably safe procedure. This should be considered as an alternative to graft reconstruction, particularly as minimal invasive approaches are being adopted. Level of Evidence: 3

The European Association of Urology (EAU) Renal Cell Carcinoma (RCC) Guideline Panel performed a protocol-driven systematic review (SR) on thermal ablation (TA) compared with partial nephrectomy (PN) for T1N0M0 renal masses, in order to provide evidence to support its recommendations. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed, and only comparative studies published between 2000 and 2019 were included. Twenty-six nonrandomised comparative studies were included, recruiting a total of 167 80 patients. Risk of bias (RoB) assessment revealed high or uncertain RoB across all studies, with the vast majority being retrospective, observational studies with poorly matched controls and short follow-up. Limited data showed TA to be safe, but its long-term oncological effectiveness compared with PN remains uncertain. A quality assessment of pre-existing SRs (n=11) on the topic, using AMSTAR, revealed that all SRs had low confidence rating, with all but two SRs being rated critically low. In conclusion, the current data are inadequate to make any strong and clear conclusions regarding the clinical effectiveness of TA for treating T1N0M0 renal masses compared with PN. Therefore, TA may be cautiously considered an alternative to PN for T1N0M0 renal masses, but patients must be counselled carefully regarding the prevailing uncertainties. We recommend specific steps to improve the evidence base based on robust primary and secondary studies. PATIENT SUMMARY: In this report, we looked at the literature to determine the effectiveness of thermoablation (TA) in the treatment of small kidney tumours compared with surgical removal. We found that TA could cautiously be offered as an option due to many remaining uncertainties regarding its effectiveness.

There are many inherited renal cell cancer syndromes that increase an individual's risk of developing renal cell cancer. The age of onset for these renal cell cancer syndromes ranges from infancy to age 65 years. Clinical manifestations vary widely, and multiple body systems can be involved and present unique challenges to the healthcare team. With the advancement of genetic panels, clinicians can screen individuals with known hereditary syndromes for genetic mutations. This article offers clinically relevant information specific to various major renal cell cancer syndromes.

Background: Evaluation and search for new molecular markers of renal cell cancer, first of all, associated with angiogenic and invasive activity, continue to be highly relevant. In our previous publications, we have assessed the potential diagnostic value of matrix metalloproteinases (MMP) 2, 7, 8, and 9, their tissue inhibitor type 1 (TIMP1) and components of the VEGF signaling system in renal cell cancer. Aim: To assess the role of serum VEGF, VEGFR1, VEGFR2, MMP2, 7, 8, 9, and TIMP1 levels in renal cell patients as diagnostic and prognostic markers of overall survival. Materials and methods: 99 renal cell cancer patients (94 primary and 5 at progression) were recruited into the study. The control group included 97 healthy control blood donors. Ninety three (93) primary patients with renal cell cancer were followed for 1 to 45 (median, 26) months for assessment of their overall survival. Serum concentrations of the study proteins were measured by direct immunoenzyme analysis (Quantikine® ELISA kits, R&D Systems, США). Results: Serum VEGF, VEGFR1, VEGFR2, MMP7, MMP8, and TIMP1 levels in renal cell cancer patients are significantly higher than those in the control group. The diagnostic characteristics of the markers are considerably different, the most reliable marker with 84% sensitivity at 87.5% specificity being MMP7. VEGFR1, MMP7, MMP8, and TIMP1 were positively associated with disease stage and TNM indices. MMP7 and TIMP1 levels also increased with a higher tumor grade. MMP7 was found to be a significant unfavorable prognostic factor for overall survival: the 3-years survival in those with low (< 6.3 ng/ml) marker level amounted to 93%, whereas with high, 51% (p < 0.001). MMP7 prognostic value remained significant also in stage I renal cancer: after 3-years' follow-up, all patients with low MMP7 were alive, while survival of those with high marker levels was 72% (p=0.02). Increased serum MMP8 level (> 51 ng/ml) also had an unfavorable prognostic value in the whole renal cell cancer patient group, with 3-years' survival being 78 and 58% for low and high levels, respectively (p < 0.01). The components of VEGF signaling system, MMP2, MMP9, and TIMP1 had no significant prognostic values. Conclusion: MMP7 should be viewed as the most promising diagnostic and prognostic renal cell cancer marker. VEGF and its soluble receptors could be useful for monitoring of patients receiving anti-angiogenic treatments and prediction of their sensitivity to these agents.

Objective:In order to make the most appropriate treatment decision for kidney masses, accurate radiological evaluation is vital. In this study, we aimed to discuss how would be the concordance between a multidisciplinary approach to renal masses and the histopathological outcome.Materials and Methods:Between June 2017 and July 2019, 75 patients who were evaluated for complex renal tumors at the Council of Uroradiology and treated at our clinic were included in the study and their clinical-pathological data were examined. After radiological reporting, all patients were re-evaluated in this council consisting of 4 urologists and 2 radiologists.Results:Forty-three patients underwent partial nephrectomy and 32 patients underwent radical nephrectomy. Malignant histopathology was present in 85.3% of patients. The mass was solid in 35 patients and was of cystic nature in 40 patients. Cystic and solid component assessments were similar in both groups. There was no difference between the two groups in terms of tumor node metastasis staging. Subgroup analysis showed that the correlation between radiological T3 and pathological T3 was not significant in radiology reports. However, this correlation was significant in the council assessment (p

The therapeutic landscape of renal cell cancer has evolved rapidly over the past 2 years with nivolumab and ipilimumab for patients with metastatic disease and an intermediate or poor prognosis, in the first line setting. More recently, data from trials combining antiangiogenic agents and immune checkpoint inhibitors demonstrated a major benefit of this treatment approach for all patients.One of three recent trials evaluated the combination of atezolizumab, an anti-programmed death ligand 1 antibody, with bevacizumab, an anti-vascular endothelial growth factor monoclonal antibody. In this manuscript, we summarize the preclinical, clinical, and safety data on atezolizumab for treatment of renal cell carcinoma and describe ongoing trials.Atezolizumab was evaluated in combination with an antiangiogenic agent. These trials were designed based on the hypothesis that selecting patients according to the expression of programmed death ligand 1 would increase the benefit of the treatment combination. Despite positive effects on the primary endpoints progression-free survival and response rate in this selected population, overall survival in the global population did not meet the criteria for significance at the time of the intermediate analysis. The major information was a proposed tumor gene expression signature. The signature was predictive of the sensitivity to anti-angiogenic and/or immune checkpoint inhibitor therapy.

Immune checkpoint inhibitor&ndash, based therapies that target ctla-4, PD-1, or the PD-1 ligand PD-L1 have received approval in Canada and many parts of the world for the treatment of melanoma, renal cell cancer, urothelial cancer, classical Hodgkin lymphoma, and non-small-cell lung cancer. However only a small proportion of patients derive long-term clinical benefit. Here, we describe the biomarkers associated with the complex relationship between tumour-related immune stimulus, T cell&ndash, mediated immune response, and immune modulation of the microenvironment that can help to predict improved patient outcomes.

The immune system plays an important role in the development and treatment of many cancer types. This fact determined the emergence of numerous immunotherapeutic approaches, including that of adoptive cell therapy (ACT). In this article, we set out to describe the basic methods of adoptive cell cancer therapy, their application and development prospects. The first part of the article deals with the significance of immunotherapeutic methods for cancer treatment and describes the current state of the problem. The main part of the article provides information on the mechanisms of adoptive T cell (unmodified and genetically modified) transfer, the creation of dendritic cell vaccines and cytokine-induced killers (CIK). In addition, a review of recent achievements in the introduction of the aforementioned methods into the clinical practice is carried out. The conclusion is made that adoptive cell therapy can be considered as one of the most promising methods of cancer immunotherapy, which should be optimized for more effective use in the treatment of cancer.

The study compared the levels of MMP-2,7,8,9, and TIMP-1 in blood serum of healthy people (N=97) and patients with primary renal cell carcinoma (N=93) to assess relevance of these markers to prognosis of overall survival of these patients, which were followed-up over 1 to 45 months (median 26 months). To evaluate the survival with the Kaplan-Meier estimator, the median values of examined markers in the total group of patients were taken as the threshold levels. This estimator showed that the high levels of serum MMP-7 and MMP-8 were indicative for unfavorable prognosis in the total group of patients with renal cell cancer. Of them, the most significant marker was the level of MMP-7: at its low level (

ObjectivesPrevious studies have reported that cases with clinical T1 renal cell cancer upstaging to pathological T3 are a risk factor to predicting postoperative recurrence after partial nephrectomy. The aim of our study was to investigate the impact of the radiological morphology of the enhanced CT scan of clinical T1 renal cell cancer on predicting upstaging to pathological T3.MethodsThree hundred sixty-seven cases with clinical T1 renal cell cancer diagnosed from enhanced CT scans were enrolled in this study. Based on the findings from the enhanced CT scan, the cases were classified into ‘round’, the margins of which were smooth and round; ‘lobular’, one or more findings of smooth dent and no spiky dent were identified on the margin of the tumor; and ‘irregular’, one or more spiky dent were identified on the margin of the tumor. The association of postoperative upstaging with these radiological morphology and other clinical characteristics of each case was analyzed.ResultsEighteen cases (4.9%) pathologically upstaged to T3a. Two round case (0.7%), 3 lobular cases (10.0%) and 13 irregular cases (22.0%) pathologically upstaged (P ConclusionsEvaluation of the radiological morphology of clinical T1 renal cell cancer based on enhanced CT scans is useful for predicting pathological upstaging.

Primary paratesticular adenocarcinoma is an extremely rare form of non-germ cell cancer. There are very few reports documented in the medical literature. It is notoriously challenging to diagnose and no treatment guidelines currently exist. Herein we present a case of a 45-year old male presenting with a chronic cough resulting from an underlying primary paratesticular adenocarcinoma. The patient was enrolled in a clinical trial for rare genitourinary cancers, known as the Iconic Trial. The following case report explores the immunopathologic characterization of this malignancy and describes the outcome from treatment for a single patient. In addition, a detailed review of the current medical literature is included.

Summary ADAPTeR is a prospective, phase II study of nivolumab (anti-PD-1) in 15 treatment-naive patients (115 multiregion tumor samples) with metastatic clear cell renal cell carcinoma (ccRCC) aiming to understand the mechanism underpinning therapeutic response. Genomic analyses show no correlation between tumor molecular features and response, whereas ccRCC-specific human endogenous retrovirus expression indirectly correlates with clinical response. T cell receptor (TCR) analysis reveals a significantly higher number of expanded TCR clones pre-treatment in responders suggesting pre-existing immunity. Maintenance of highly similar clusters of TCRs post-treatment predict response, suggesting ongoing antigen engagement and survival of families of T cells likely recognizing the same antigens. In responders, nivolumab-bound CD8+ T cells are expanded and express GZMK/B. Our data suggest nivolumab drives both maintenance and replacement of previously expanded T cell clones, but only maintenance correlates with response. We hypothesize that maintenance and boosting of a pre-existing response is a key element of anti-PD-1 mode of action., Graphical abstract, Highlights • 115 pre- and post-nivolumab multiregion tumor samples in a prospective phase II study • Maintenance of pre-treatment expanded TCR clones associates with response • Expanded CD8+ T cells upregulate GZMB/K in responders • HERV expression reflects tumor purity and indirectly correlates with response, ADAPTeR is a phase II study of nivolumab (anti-PD-1) in treatment-naive patients with metastatic clear cell renal cell carcinoma. Through multi-omic analysis of multiregion tumor biopsies taken pre- and post-treatment, Au et al. evaluate genomic and tumor immune microenvironment features underpinning anti-PD-1 response and resistance using bulk and single-cell approaches.

Introduction: Partial nephrectomy (PN) is the treatment of choice in localized renal cell cancer. It depends largely on the anatomy and location of the tumor, as well as the surgeon's expe...

BackroundSeveral hematological markers of systemic inflammation were reported as prognostic in renal cell carcinoma (RCC). We aimed to re-evaluate the prognostic significance of clinicopathologic features and compare the predictive value of different inflammatory markers in RCC.MethodsFour hundred ninety-five patients treated with nephrectomy for primary localized or locally advanced RCC were included in the retrospective analysis. The median follow-up was 48 months.ResultsPatients with higher neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), systemic inflammatory response index (SIRI), systemic immune-inflammation index (SII), neutrophil/erythrocyte ratio (NER), derived neutrophil/lymphocyte ratio (dNLR), and lower lymphocyte/monocyte ratio (LMR) and hemoglobin/platelet ratio (HPR) had worse cancer-specific survival (CSS). In the multivariate analysis tumour stage, grade, age and high SIRI constituted independent factors predicting CSS. The model including SIRI values achieved C-index 0.903. Alternative multivariate models that included SII and NLR were characterized by comparable C-indexes i.e. 0.902 and 0.890, respectively. Different inflammatory markers could not be utilized in a single model, as they show a strong correlation with one other (SII, SIRI and NLR), and seem to provide similar prognostic information. Tumour grade and diameter were independent predictors for recurrence-free survival, whereas age, tumour grade and high NER (or high SIRI/ SII in alternative models) were prognostic for overall survival.ConclusionsMarkers of systemic inflammation might provide additional prognostic information (especially SIRI, SII, NLR and NER) and further increase the predictive accuracy of already available models in localized and locally advanced renal cell carcinoma. Clinicopathological features (stage, grade and age) remain the most important prognostic factors for oncological outcomes in RCC patients treated with nephrectomy. For the first time, we show the prognostic value of neutrophil-to-erythrocyte ratio, which constitutes an independent risk factor of overall survival.Trial registrationnot applicable

INTRODUCTION AND OBJECTIVE:Hereditary Leiomyomatosis and Renal Cell Carcinoma (HLRCC) is a hereditary condition in which affected individuals are at risk for the development of renal cysts, renal t...

INTRODUCTION AND OBJECTIVE:Venous tumor thrombus (VTT) extension occurs in 4-15% cases of renal cell cancer (RCC). Although surgery is performed with curative intent, mortality is high (5-15%). The...

INTRODUCTION AND OBJECTIVE:Hereditary Leiomyomatosis and Renal Cell Carcinoma (HLRCC) is a hereditary condition characterized by an increased risk for a clinically aggressive papillary renal cell c...

Vertebral epithelioid hemangioma is a rare vascular tumor composed of the many vessels lined by distinct epithelioid endothelial cells. We present the case of a patient with renal cell cancer (RCC) and suspicious vertebral metastasis presenting with back pain, who was later found to have epithelioid hemangioma. FDG PET/CT demonstrated uptake of FDG not only in RCC, but also in the sixth thoracic vertebral body. The SUVmax of the vertebra was more than twice as high as RCC. This report indicates importance of quantitative assessment of FDG uptake, as well as combined use of MRI.

Renal cell cancer (RCC) metastasizes predominantly by haematogenous route. Metastasis may occur synchronously with the primary tumour or in various organs many years after the treatment of the primary RCC. Involvement of ipsilateral adrenal gland is now considered T4 disease, and contralateral adrenal gland involvement suggests metastatic disease according to latest TNM classification. However, isolated synchronous adrenal metastasis in case of RCC is rare. Solitary metastatic lesion should be considered for metastatectomy whenever feasible as it prolongs survival. We discuss a unique case of solitary synchronous contralateral adrenal metastasis in a case of RCC and discuss the feasibility of metastatectomy and preservation of ipsilateral adrenal gland to prevent adrenal insufficiency.

Background The existence of renal cell cancer (RCC) in a donated kidney may cause some confusion for clinicians. We aim to present our clinical experiences with 2 recipients who received an RCC-containing kidney from their living related donors. Methods Two male patients received a kidney containing resectable size RCC from their living related donors. The recipients were discharged with well-functioning kidneys and currently are being monitored on standard follow-up protocols, and there is no evidence of RCC in their grafts. Results The kidneys with resectable sizes of renal cell carcinoma were transplanted to the recipients after nephron-sparing surgery, with no sign of recurrent RCC in the 12-month follow-up period. Conclusions In the era of transplantation, the shortage of organ sources is the major barrier for the provision of organs to recipients. To enhance the graft donation pool, kidneys with resectable size RCC might be used in providing grafts to patients with end-stage kidney disease.

Background: Xanthogranulomatous pyelonephritis (XGP) is a rare chronic bacterial inflammation of the renal parenchyma and is often a diagnostic dilemma.Case Presentation: We present a challenging case of a patient with XGP. Initially thought to have had renal cell cancer she was treated accordingly with a partial nephrectomy. However, on the final pathology, she was found to have XGP and required further antibiotic therapy and referral to the infectious disease service.Discussion: Management of XGP and diagnostic pitfalls are discussed.Conclusion: XGP is a diagnostic and therapeutic dilemma. Partial Nephrectomy may be appropriate in management of XGP in select cases.

Cystic renal neoplasms can be classified as benign and malignant, consisting of multilocular cystic renal cell cancer, cystic renal cell cancer, multilocular cystic nephroma and benign multilocular cysts. The objective of this article is to summarize the clinical aspects of multilocular cystic nephroma and discuss the major similarities that provoke difficulties in proper diagnosis and treatment.

Fumarate hydratase (FH) is a metabolic enzyme that is part of the Krebs-cycle, and reversibly catalyzes the hydration of fumarate to malate. Mutations of the FH gene have been associated with fumarate hydratase deficiency (FHD), hereditary leiomyomatosis, renal cell cancer (HLRCC), and other diseases. Currently there are no high-quality small molecule probes for studying human fumarate hydratase. To address this, we developed a quantitative high throughput screening (qHTS) FH assay and screened a total of 57,037 compounds from in-house libraries in dose-response. While no inhibitors of FH were confirmed, a series of phenyl-pyrrolo-pyrimidine-diones were identified as activators of human fumarate hydratase. These compounds were not substrates of fumarate hydratase, were inactive in a malate dehydrogenase counter screen, and showed no detectable reduction–oxidation activity. The binding of two compounds from the series to human fumarate hydratase was confirmed by microscale thermophoresis. The low hit rate in this screening campaign confirmed that FH is a ‘tough target’ to modulate, and the small molecule activators of human fumarate hydratase reported here may serve as a starting point for further optimization and development into cellular probes of human FH and potential drug candidates.

Here we explore the recent and relevant trials for treatment of renal cell cancer (RCC) in the adjuvant and neoadjuvant settings as well as recent updates to the guidelines for RCC management.Most phase III studies of tyrosine kinase inhibitors in the adjuvant setting have been negative. Notably, sunitinib received regulatory approval by the FDA after showing improved disease-free survival in high risk populations. Recent improvements in the genetic classification and understanding of RCC molecular and genetic disorder will hopefully improve patient selection. Meanwhile, recent advances in metastatic RCC treatment, particularly with the combination of tyrosine kinase inhibitors and immune checkpoint inhibitors, have given rise to hope that advances can be made by moving these treatment strategies forward to the adjuvant or neoadjuvant settings.In the absence of a clinical trial, observation remains the standard of care. Based on the S-TRAC data, sunitinib is approved for use in the adjuvant setting, and can be considered under select circumstances. Although there is optimism for checkpoint monotherapy and combination therapy in the adjuvant or neoadjuvant setting, ongoing studies will determine clinical benefit and tolerability in this setting. Therefore, for patients with high risk of recurrent disease clinical trials of checkpoint inhibitor therapy are viable options.

Introduction Although horseshoe kidney (HSK) is the most common congenital anomaly of the upper urinary tract, renal cell cancer (RCC) in HSK develops extremely rarely. Until 2012 y. there were less than 200 cases of RCC in HSK published in PubMed. Only five cases of laparoscopic partial nephrectomies and some cases of heminephrectomies have been described in PubMed. Aim To conduct a multicenter retrospective analysis of laparoscopic surgery for tumors in HSK. Material and methods From January 2013 to December 2018 a total of 19 conventional laparoscopic interventions were performed in patients with RCC in HSK, including 1 isthmusectomy, 5 partial nephrectomies and 13 heminefrectomies. In addition, 16 divisions of isthmus were done in 15 patients. The video describing our operation technique is available on: http://youtu.be/nk-WlbjNtIs . Results There were no conversions to open surgery and mortality as well as intra- and postoperative complications of Clavien grade 3 or higher. Warm ischemia time during partial nephrectomy didnt exceed 19 minutes. Operative time ranged from 110 to 270 min, while max estimated blood loss was 400 ml. All patients were followed for 6 month and no case of disease recurrence or progression was noted. Conclusions The small number of laparoscopic interventions in patients with RCC in HSK doesnt allow to carry out a proper statistical analysis and draw certain conclusions. We presented the largest experience available in the literature and our results demonstrate the efficacy and safety of conventional laparoscopic technologies in the treatment of RCC in HSK.

Renal cell carcinoma (RCC) exhibits multidrug resistance protein P-glycoprotein expression due to the proximal tubular origin and in this regard, it is resistant to a large number of cytotoxic chemotherapy. The identification of the molecular pathogenesis, genetics, and epigenetics of RCC has led to new target points such as vascular endothelial growth factor. Tyrosine kinase inhibitors have been used mainly for treatment, but recently, immune checkpoint inhibitors have also been used in the treatment of RCC. Despite these treatments, response rates are not sufficient in the majority of patients. Primary resistance or acquired resistance to the treatment might be seen. Defining these resistance mechanisms will contribute to the management of the treatment and will help in to identify new treatment targets. In this review, we focus on the molecular mechanisms and resistance mechanisms of targeted-therapy.

PURPOSE OF REVIEW In addition to the provision of nutrients and growth factors that facilitate tumor cell proliferation and metastasis, the tumor microenvironment (MEV) restricts immune surveillance of tumor-associated antigens and limits the efficacy of immune checkpoint inhibitors, tumor vaccines, and other immune therapies. This review will focus on the immunosuppressive mechanisms operative within the tumor MVE of renal cell carcinoma. RECENT FINDINGS Several of the immunosuppressive mechanisms within the tumor MEV have been identified and are potentially druggable. Clinical trials with agents that target several of these inhibitory pathways are currently underway. SUMMARY Although renal cell carcinoma is one of several tumor types responsive to immune checkpoint inhibitors, the effectiveness of these agents is likely to be limited by the various tumor-infiltrating bone marrow-derived myeloid cells that comprise the MEV. Several strategies to combat the recruitment of these cells into tumor tissue or to neutralize their immunosuppressive function have shown encouraging results in animal tumor models and clinical trials.

Aim: To investigate the prognostic significance of clinical and pathological factors of non-metastatic renal cell cancer after surgery. Patients and methods: We conducted a retrospective cohort study based on the records of patients with non-metastatic renal cancer submitted to radical or partial nephrectomy between 2000 and 2015 in Salah-Azaiez Institute. Results: Median follow-up was 38 months (interquartile range: 20–64). Five-year overall and disease-free survival were 53.8% and 43.1%. In the multivariate setting, lymph node invasion (p = 0.01), clear cell renal carcinoma subtype (p = 0.014), and tumor necrosis (p = 0.009) were the only independent statistically significant predictors of disease-free survival, while Fuhrman grade (p = 0.025), clear cell renal carcinoma subtype (p = 0.044), and TNM stage (0.041) were the only factors correlated with overall survival. Conclusion: For patients with non-metastatic renal cell carcinoma, independent predictors of disease-free survival and overall survival were clear cell renal cell carcinoma, Fuhrman grade, TNM stage, lymph node invasion, and tumor necrosis. Such information could be used to guide the intensity of follow-up and identify high-risk patients who can be targeted for adjuvant therapy trials.

Purpose:Numerous studies have suggested that dyslipidemia is closely related to various cancers and the high-density lipoprotein cholesterol (HDL-C) levels are associated with the outcome of cancer patients. However, the predictive value of HDL-C in patients with renal cell carcinoma remains unclear. Our study aims to explore the relationship between the levels of serum HDL-C and the prognosis of renal cell carcinoma.Methods:A total of 308 patients diagnosed with clear cell renal cell carcinoma (CCRCC) who received surgical treatment were retrospectively enrolled in our study. The necessary clinical data of each enrolled patient were collected and the Kaplan–Meier method and the Cox proportional hazards regression model were used to calculate the overall survival and cancer-specific survival.Results:Kaplan–Meier and univariate analysis showed that a lower preoperative serum HDL-C level was a risk factor of CCRCC patients. Multivariate analyses demonstrated that a higher serum HDL-C level was closely associated with better overall survival (hazard ratio = 0.32; 95% confidence interval (0.13, 0.78); P=0.013) and cancer-specific survival (hazard ratio =0.42; 95% confidence interval (0.15, 0.99); P=0.048).Conclusion:Our findings suggest that an increased serum level of HDL-C might predict better overall survival and cancer-specific survival in patients with CCRCC.

Although anticancer systemic therapy agents clearly lead to improved survival in patients with cancer, these can come at the cost of serious complications including cardiotoxicity. Two types of targeted systemic therapies currently in use for colorectal cancer (CRC) and renal cell cancer (RCC), respectively, include the vascular endothelial growth factor inhibitor bevacizumab (BVZ) and the tyrosine kinase inhibitor sunitinib (SNT). Despite the beneficial effects of BVZ and SNT in improving clinical outcomes in the settings of CRC and RCC, there is an increased risk of cardiac dysfunction. The aim of the present study was to determine whether prophylactic administration of renin-angiotensin system (RAS) inhibitors would attenuate the cardiotoxic side effects of BVZ or SNT in a chronic in vivo murine model. A total of 194 wild-type C57Bl/6 male mice received: 1) 0.9% saline, 2) BVZ (10 mg·kg−1·wk−1), or 3) SNT (40 mg·kg−1·day−1) for 4 wk. Within each arm, mice received daily prophylactic treatment with hydralazine (0.05 mg/ml), aliskiren (50 mg/kg), perindopril (4 mg/kg), or valsartan (2 mg/kg). Although hydralazine effectively lowered blood pressure in BVZ- or SNT-treated mice, it did not prevent left ventricular systolic dysfunction. Prophylactic administration of aliskiren, perindopril, or valsartan prevented adverse cardiovascular remodeling in mice treated with either BVZ or SNT. The addition of RAS antagonists also downregulated expression of phosphorylated p38 and Bcl-2-like 19-kDa interacting protein 3 in SNT-treated mice. In our chronic in vivo murine model, RAS antagonists partially attenuated the development of BVZ- or SNT-mediated cardiac dysfunction. Future clinical studies are warranted to investigate the cardioprotective effects of prophylactic treatment with RAS inhibitors in the settings of CRC and RCC. NEW & NOTEWORTHY In the evolving field of cardio-oncology, bevacizumab and sunitinib improve clinical outcomes in the settings of metastatic colorectal cancer and renal cell cancer, respectively. These anticancer drugs, however, are associated with an increased risk of cardiotoxicity. The prophylactic administration of renin-angiotensin system antagonists is partially cardioprotective against bevacizumab- and sunitinib-mediated cardiac dysfunction.

Lymph node metastasis in renal cell cancer (RCC) portends an extremely poor prognosis. Despite proven staging benefit, the therapeutic value of lymph node dissection in RCC remains questionable. The only prospective randomized trial examining its role failed to show any benefit. However, subsequent retrospective publications have attempted to identify high-risk cohorts and clinical scenarios where removal of nodes may improve survival. The aim of this article is to provide a comprehensive review looking at the role of lymph node dissection in RCC if any, the ideal extent of dissection, and also tools a clinician could employ to identify those who would most likely benefit from this exercise.