Vaporization phosphorization-mediated synthesis of phosphorus-doped TiO2 nanocomposites for combined photodynamic and photothermal therapy of renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a disease with high incidence and poor prognosis. The conventional treatment involves radiotherapy and chemotherapy, but chemotherapeutic agents are often associated with side effects, i.e., cytotoxicity to nontumor cells. Therefore, there is an urgent need for the development of novel therapeutic strategies for ccRCC. We synthesized spherical P/TiO2 nanoparticles (P/TiO2 NPs) by vaporization phosphorization (VP). X-ray photoelectron spectroscopy (XPS) and ultraviolet-visible diffuse reflectance spectroscopy (UV-Vis DRS) analyses confirmed that the anatase TiO2 surface was successfully doped with phosphorus and produced a large number of oxygen vacancies (OV). Serving as a photosensitizer, P/TiO2 NPs not only extended the photoresponse range to the near-infrared II region (NIR II) but also introduced a donor energy level lower than the TiO2 conduction band, narrowing the band gap, which could facilitate the migration of photogenerated charges and trigger the synergistic treatment of photodynamic therapy (PDT) and photothermal therapy (PTT). During NIR irradiation in vitro, the P/TiO2 NPs generated local heat and various oxygen radicals, including 1O2, ˙O2-, H2O2, and ˙OH, which damaged the ccRCC cells. In vivo, administration of the P/TiO2 NPs + NIR reduced the tumor volume by 80%, and had the potential to inhibit tumor metastasis by suppressing intratumor neoangiogenesis. The P/TiO2 NPs showed superior safety and efficacy relative to the conventional chemotherapeutic agent used in ccRCC treatment. This study introduced an innovative paradigm for renal cancer treatment, highlighting the potential of P/TiO2 NPs as safe and effective nanomaterials and presenting a compelling new option for clinical applications in anticancer therapy.

Inflammatory response-based prognostication and personalized therapy decisions in clear cell renal cell cancer to aid precision oncology.

OBJECTIVE: The impact of inflammatory response on tumor development and therapeutic response is of significant importance in clear cell renal cell carcinoma (ccRCC). The customization of specialized prognostication approaches and the exploration of supplementary treatment options hold critical clinical implications in relation to the inflammatory response. METHODS: In the present study, unsupervised clustering was implemented on TCGA-KIRC tumors using transcriptome profiles of inflammatory response genes, which was then validated in two ccRCC datasets (E-MATB-1980 and ICGC) and two immunotherapy datasets (IMvigor210 and Liu et al.) via SubMap and NTP algorithms. Combining co-expression and LASSO analyses, inflammatory response-based scoring system was defined, which was evaluated in pan-cancer. RESULTS: Three reproducible inflammatory response subtypes (named IR1, IR2 and IR3) were determined and independently verified, each exhibiting distinct molecular, clinical, and immunological characteristics. Among these subtypes, IR2 had the best OS outcomes, followed by IR3 and IR1. In terms of anti-angiogenic agents, sunitinib may be appropriate for IR1 patients, while axitinib and pazopanib may be suitable for IR2 patients, and sorafenib for IR3 patients. Additionally, IR1 patients might benefit from anti-CTLA4 therapy. A scoring system called IRscore was defined for individual ccRCC patients. Patients with high IRscore presented a lower response rate to anti-PD-L1 therapy and worse prognostic outcomes. Pan-cancer analysis demonstrated the immunological features and prognostic relevance of the IRscore. CONCLUSION: Altogether, characterization of inflammatory response subtypes and IRscore provides a roadmap for patient risk stratification and personalized treatment decisions, not only in ccRCC, but also in pan-cancer.

Targeting Alpha-Ketoglutarate Disruption Overcomes Immunoevasion and Improves PD-1 Blockade Immunotherapy in Renal Cell Carcinoma.

The Warburg effect-related metabolic dysfunction of the tricarboxylic acid (TCA) cycle has emerged as a hallmark of various solid tumors, particularly renal cell carcinoma (RCC). RCC is characterized by high immune infiltration and thus recommended for immunotherapeutic interventions at an advanced stage in clinical guidelines. Nevertheless, limited benefits of immunotherapy have prompted investigations into underlying mechanisms, leading to the proposal of metabolic dysregulation-induced immunoevasion as a crucial contributor. In this study, a significant decrease is found in the abundance of alpha-ketoglutarate (αKG), a crucial intermediate metabolite in the TCA cycle, which is correlated with higher grades and a worse prognosis in clinical RCC samples. Elevated levels of αKG promote major histocompatibility complex-I (MHC-I) antigen processing and presentation, as well as the expression of ß2-microglobulin (B2M). While αKG modulates broad-spectrum demethylation activities of histone, the transcriptional upregulation of B2M is dependent on the demethylation of H3K4me1 in its promoter region. Furthermore, the combination of αKG supplementation and PD-1 blockade leads to improved therapeutic efficacy and prolongs survival in murine models when compared to monotherapy. Overall, the findings elucidate the mechanisms of immune evasion in anti-tumor immunotherapies and suggest a potential combinatorial treatment strategy in RCC.

SEOM SOGUG clinical guideline for treatment of kidney cancer (2022).

Renal cancer is the seventh most common cancer in men and the tenth in women. The aim of this article is to review the diagnosis, treatment, and follow-up of renal carcinoma accompanied by recommendations with new evidence and treatment algorithms. A new pathologic classification of RCC by the World Health Organization (WHO) was published in 2022 and this classification would be considered a "bridge" to a future molecular classification. For patients with localized disease, surgery is the treatment of choice with nephron-sparing surgery recommended when feasible. Adjuvant treatment with pembrolizumab is an option for intermediate-or high-risk cases, as well as patients after complete resection of metastatic disease. More data are needed in the future, including positive overall survival data. Clinical prognostic classification, preferably IMDC, should be used for treatment decision making in mRCC. Cytoreductive nephrectomy should not be deemed mandatory in individuals with intermediate-poor IMDC/MSKCC risk who require systemic therapy. Metastasectomy can be contemplated in selected subjects with a limited number of metastases or long metachronous disease-free interval. For the population of patients with metastatic ccRCC as a whole, the combination of pembrolizumab-axitinib, nivolumab-cabozantinib, or pembrolizumab-lenvatinib can be considered as the first option based on the benefit obtained in OS versus sunitinib. In cases that have an intermediate IMDC and poor prognosis, the combination of ipilimumab and nivolumab has demonstrated superior OS compared to sunitinib. As for individuals with advanced RCC previously treated with one or two antiangiogenic tyrosine-kinase inhibitors, nivolumab and cabozantinib are the options of choice. When there is progression following initial immunotherapy-based treatment, we recommend treatment with an antiangiogenic tyrosine-kinase inhibitor. While no clear sequence can be advocated, medical oncologists and patients should be aware of the recent advances and new strategies that improve survival and quality of life in the setting of metastatic RC.

Contemporary care patterns in the management of small renal masses.

OBJECTIVES: Incidental small renal masses (SRMs) now account for the majority of new diagnoses of renal cancers. Although there are established management guidelines, referral and management patterns can vary. We aimed to explore identification, practice patterns, and management of identified SRMs in an integrated health system. STUDY DESIGN: Retrospective analysis. METHODS: We identified patients with a newly diagnosed SRM measuring 3 cm or less from January 1, 2013, to December 31, 2017, at Kaiser Permanente Southern California. These patients were flagged at the time of radiographic identification to ensure adequate notification of findings. Diagnostic modality, referral, and treatment patterns were analyzed. RESULTS: Of 519 patients with SRMs, 65% were found on abdominal CT and 22% on renal/abdominal ultrasounds. Within 6 months, 70% of patients consulted with a urologist. Initial management patterns were as follows: active surveillance (60%), partial/radical nephrectomy (18%), and ablation (4%). Among 312 patients on surveillance, 14% eventually received treatment. The majority of patients (69.4%) did not receive guideline-recommended chest imaging for initial staging. Urologist visit within 6 months of SRM diagnosis was associated with increased adherence to staging (P = .003) and subsequent surveillance imaging (P < .001). CONCLUSIONS: In this contemporary analysis of an integrated health system's experience, referral to a urologist was associated with guideline-concordant staging and surveillance imaging. Frequent utilization of active surveillance with a low rate of progression to active treatment was noted in both groups. These findings shed light on care patterns upstream of urologic evaluation and support the need for clinical pathways to be implemented at the time of radiologic diagnosis.

Factors Associated With Palliative Intervention Utilization for Metastatic Renal Cell Carcinoma.

INTRODUCTION: Several guidelines have adopted early integration of palliative intervention (PI) into oncologic care to improve quality of life among patients with advanced malignancies. However, PI utilization patterns and factors associated with its use in metastatic renal cell carcinoma are poorly understood. PATIENTS AND METHODS: Using the National Cancer Database (NCDB), we abstracted patients diagnosed with Stage IV RCC from 2004 to 2014 and evaluated the utilization of PI within this cohort. Socioeconomic and clinical factors were compared for patients receiving and not receiving PI for metastatic RCC. Multivariable logistic regression (MLR) models identified factors that were associated with receipt of PI within overall cohort and treatment-based cohorts. RESULTS: We identified 42,014 patients with Stage IV RCC, of which 7,912 patients received PI. From 2004 to 2014, the use of PI minimally increased from 17% to 20% for Stage IV RCC. MLR analysis demonstrated that increased comorbidities, insurance status, higher education status, facility location, care at a comprehensive cancer program or integrated network, sarcomatoid histology, and treatment type significantly increased the likelihood of PI use. Various socioeconomic, clinical, and geographical factors that are associated with use of PI-based on the treatment received for Stage IV RCC. CONCLUSIONS: While PI utilization has minimally increased for Stage IV RCC, there are several geographic, socioeconomic, and clinical factors that predict its use among patients with Stage IV RCC in a treatment-specific manner. Taken together, this suggests the need for earlier initiation of PI in a more equitable and systematic fashion among patients with metastatic RCC.

Supportive therapy and complementary medicine in renal cell carcinoma.

PURPOSE: As part of the German interdisciplinary S3-guideline "Diagnosis, Treatment and Followup of Renal Cell Carcinoma", this article aimes to provide guidance regarding the use of supportive therapy and complementary medicine in patients with advanced or metastatic renal cell carcinoma. METHODS: The German interdisciplinary S3-guidelines are national clinical practice guidelines that implement the highest methodological quality of evidence-based medicine. Recommendations and evidence-based statements are provided according to available evidence. RESULTS: Supportive and palliative care are important areas of tumor treatment and require knowledge on the management of a variety of issues. This article outlines the management of tumor-related symptoms such as pain, undesired treatment-related effects, palliative care and end-of-life care in patients with renal cell carcinoma. CONCLUSION: Patients with advanced or metastatic renal cell carcinoma should have access to supportive and palliative care according to their individual needs. There is very limited evidence regarding the impact of complementary medicine for the treatment of patients with renal cell carcinoma.

Astragalus-mediated stimulation on antigen-presenting cells could result in higher IL-21 production from CXCR5+ Tfh-like cells and better IL-21-mediated effector functions.

T cells in renal cell carcinoma (RCC) patients display multiple features of impairment and exhaustion. Here, we hypothesize that Astragalus membranaceus, a herbal medicine commonly used to accompany chemotherapy, might have adjuvating effects on T cells from RCC patients. To investigate this, circulating T cells from healthy individuals and RCC patients were cocultured ex vivo with aqueous extract from Astragalus. Functional characteristics of T cells in the absence and presence of Astragalus extract were then compared. We first identified a downregulation of IL-21 expression in RCC patients in association with a functional dysregulation of CXCR5+ Tfh-like cells. Astragalus extract could significantly increase IL-21 expression in a dose-dependent manner. This Astragalus-mediated effect depended on the presence of antigen-presenting cells (APCs), as purified CXCR5+ Tfh-like cells presented little IL-21 upregulation following Astragalus stimulation. APCs primed by Astragalus extract also promoted IL-21 expression from Tfh-like cells. Interestingly, Astragalus-stimulated Tfh-like cells presented enhanced helper function and resulted in higher humoral responses and better CD8 T cell survival. This effect was dependent on the presence of IL-21. Overall, these data indicated that Astragalus could enhance IL-21 production and effector function from CXCR5+ Tfh-like cells in a manner that depended on the presence of APCs.

Complementary Role of 68Ga-Prostate-Specific Membrane Antigen and 18F-FDG PET/CT for Evaluation of Metastases and Treatment Response in Renal Cell Carcinoma.

ABSTRACT: We present a case of clear cell renal cell carcinoma, which demonstrates complementary FDG and prostate-specific membrane antigen (PSMA) uptake on metastases in PET/CT, as an example of tumor heterogeneity. The patient had non-FDG-avid lung and bone metastases with PSMA uptake, whereas metastatic cervical and axillary lymph nodes showed vice versa, and skeletal muscle metastasis to vastus lateralis, which is an unusual region for metastasis, showed both PSMA and FDG positivity. In response assessment, mix response was detected. It seems that 68Ga-PSMA and 18F-FDG may have a complementary role in demonstration of metastasis accurately and assessment of treatment response in clear cell renal cell carcinoma.

The Influence of the Extremely Low Frequency Electromagnetic Field on Clear Cell Renal Carcinoma.

The development of new technologies and industry is conducive to the increase in the number and variety of electromagnetic field (EMF) sources in our environment. The main sources of EMF are high-voltage lines, household appliances, audio/video devices, mobile phones, radio stations, and radar devices. In the growing use of electronic devices, scientists are increasingly interested in the effects of EMF on human health. Even though many studies on the effects of EMF have already been carried out, none of them has shown a significant effect on mammals, including humans. Moreover, it is not entirely clear how EMF influences cell behavior. The International Agency for Research on Cancer on 31 May 2011, classified PEM as a possible carcinogenic factor. This study aimed to investigate the effect of the electromagnetic field on morphological and functional changes in clear cell renal carcinoma. The research was carried out on in vitro cultures of four cell lines: HEK293, 786-O 769-P, and Caki1. The results of the research showed that the EMF of low frequency had a slight effect on the viability of cells. EMF, which induced cell arrest in the G1 phase, increased the number of early apoptotic cells and decreased the number of viable cells in the 786-O line. EMF did not affect the proliferation and viability of HEK293 cells. Extreme low-frequency EMF (ELF-EMF) also showed an inhibitory effect on the migration and metastatic properties of clear cell kidney cancer cells. Moreover, shortly after the end of ELF-EMF exposure, significant increases in ROS levels were observed in all tested cell lines. As part of the work, it was shown that low-frequency EMF shows an inhibitory effect on the proliferation of primary cancer cells, diminishing their migratory, invasive, and metastatic abilities. It also increases the apoptosis of cancer cells and the amount of reactive oxygen species. Based on the results of our research, we want to point up that the effect of ELF-EMF depends on a specific metabolic state or at a specific stage in the cell cycle of the cells under study.

PD-L1 and VEGFR-2 expression in synchronous metastatic renal cell carcinoma treated with targeted therapy following cytoreductive nephrectomy.

OBJECTIVES: Few studies have independently investigated the population of patients with synchronous metastatic renal cell carcinoma (smRCC). In this study, we evaluated programmed death protein-ligand 1 (PD-L1) and vascular endothelial growth factor receptor 2 (VEGFR-2) expression in primary tumor tissue of smRCC. METHODS: A total of 96 patients with smRCC who were treated with cytoreductive nephrectomy followed by targeted therapy from January 2006 to January 2013 were identified. PD-L1 and VEGFR-2 expression were evaluated by immunohistochemistry. Kaplan-Meier and Cox methods were used for analysis. RESULTS: PD-L1 and VEGFR-2 protein immunopositivity were observed in 39.6% (38 of 96) and 58.3% (56 of 96) of patients, respectively. A significant correlation was detected between VEGFR-2 and PD-L1 expression (P = 0.030). Based on PD-L1 and VEGFR-2 expression, patients with intermediate-risk disease (n = 63) were divided into 4 subgroups including patients who were PD-L1 (+) VEGFR-2 (+) (n = 21), PD-L1 (+) VEGFR-2 (-) (n = 11), PD-L1 (-) VEGFR-2 (+) (n = 15) and PD-L1 (-) VEGFR-2 (-) (n = 16). Compared to the PD-L1 (-) VEGFR-2 (+), PD-L1 (+) VEGFR-2 (+) and PD-L1 (-) VEGFR-2 (-) groups, patients in the PD-L1 (+) VEGFR-2 (-) group had shorter progression-free survival (median, 9.0 vs. 20.0, 16.0 and 15.5 months, P < 0.05) and overall survival (median, 14.0 vs. 33.0, 24.0 and 26.5 months, P < 0.05). CONCLUSIONS: Intermediate-risk smRCC patients with PD-L1-positive and VEGFR-2-negative expression who were treated with targeted therapy following cytoreductive nephrectomy had poor prognoses. We suggest that other treatments beyond sunitinib or sorafenib may be explored in this subgroup.

Association between tyrosine-kinase inhibitor induced hypertension and treatment outcomes in metastatic renal cancer.

BACKGROUND: Tyrosine-kinase inhibitor (TKI) drugs have been considered first line treatment for metastatic renal cell cancer (RCC) for over a decade. TKI-induced hypertension is a common adverse-event in patients treated for metastatic RCC. AIM: This study was aimed at investigating an association between TKI-induced hypertension and treatment outcomes for metastatic RCC patients. METHODS AND RESULTS: Retrospective data pertaining to patients with histologically or radiologically confirmed metastatic RCC treated with sunitinib, pazopanib, sorafenib, axitinib or cabozantinib between June 2012 and May 2019 were evaluated. Clinical information and serial blood pressure measurements were extracted from medical records for each patient. We compared objective response rate, progression-free survival (PFS), and 12-month survival between TKI-induced hypertension (TIH) and non-TIH groups using χ2 and Mann-Whitney tests. Out of 72 patients screened, 52 met study eligibility criteria. The median age at diagnosis was 61 years (range: 42-85 years) with a clear male predominance. The majority of patients had a history of nephrectomy with clear cell pathology. Almost all patients were on first-line TKI therapy with sunitinib or pazopanib. Median follow-up was 11 months. About half of patients developed TKI-induced hypertension (grade 2-3). In the TIH group 82% were commenced on an antihypertensive agent. Median PFS measured 30.5 weeks for TIH group compared to 22.2 weeks for non-TIH (P = .05). The 6 month and 12 month survival rates for TIH were 82% and 56%, respectively, as compared to 76% and 44% for non-TIH. CONCLUSION: The occurrence of TKI-induced hypertension was found to be a positive prognostic factor for progression in patients with metastatic RCC.

The impact of cytoreductive nephrectomy on survival outcomes in patients treated with tyrosine kinase inhibitors for metastatic renal cell carcinoma in a real-world cohort.

BACKGROUND: Tyrosine kinase inhibitor therapy (TKI) has changed the treatment paradigm of metastatic renal cell carcinoma (mRCC). The recent CARMENA and SURTIME trials challenged the role of the cytoreductive nephrectomy (CN). OBJECTIVE: To assess the impact of CN prior to TKI therapy in patients with mRCC in a real-world setting. METHODS: Overall, 262 consecutive patients with mRCC were treated with CN plus TKI or TKI only at our institution between 2000 and 2016. Patients with prior immunotherapy or metastasectomy were excluded. Multiple imputation and inverse probability of treatment weighting (IPTW) were performed to account for missing values and imbalances between the treatment groups, respectively. Unadjusted and adjusted Kaplan-Meier estimates were used to determine differences in progression-free (PFS), overall (OS), and cancer-specific survival (CSS). RESULTS: Overall, 104 (40%) patients received CN before TKI treatment. Most frequent first line therapy was Sunitinib (66%), followed by Sorafenib (20%) and Pazopanib (10%). After adjustment with IPTW, there was no difference in PFS, CSS, and OS (all P > 0.05) between the treatment groups. In subgroup analyses, CSS was improved when CN was performed in patients with sarcomatoid features and clear cell histology (P = 0.04 and P = 0.03) and PFS was improved in patients with clear cell histology when CN was performed [0.04]). CN did not improve OS in any subgroup analysis. CONCLUSION: The role of CN remains controversial. We found no difference in survival outcomes between patients treated with and without CN before TKI therapy. However, CN was associated with improved survival in specific patient subgroups. Tailored, individualized treatment is key to further improve oncological outcomes for mRCC.

Prognostic Significance of the Controlling Nutritional Status (CONUT) Score in Patients with Advanced Renal Cell Carcinoma Treated with Nivolumab after Failure of Prior Tyrosine Kinase Inhibitors.

PURPOSE: The controlling nutritional status (CONUT) score, consisting of albumin, lymphocytes and total cholesterol, is a validated, objective tool for nutritional assessment. Patients with advanced cancer frequently have malnutrition in association with cachexia and chronic inflammation. We explored the prognostic significance of the CONUT score in patients with advanced renal cell carcinoma receiving nivolumab. MATERIALS AND METHODS: This retrospective study included 60 patients with stage IV renal cell carcinoma treated with nivolumab after failure of prior tyrosine kinase inhibitors at 2 cancer centers between 2016 and 2019. Associations of the CONUT score with progression-free survival, cancer specific survival and tumor shrinkage rate were assessed. RESULTS: The median (range) CONUT score was 2 (0-10). During followup periods 29 and 14 patients exhibited disease progression and died of cancer, respectively. Both progression-free survival and cancer specific survival were significantly stratified by CONUT scores of 0 to 1, 2 to 4 and 5 or more (p=0.002). A CONUT score of 5 or more (versus score 0 to 1) was independently associated with unfavorable progression-free survival (HR 5.18, p=0.003) and cancer specific survival (HR 15.34, p=0.014), as was the absence of prior nephrectomy (HR 4.23, p=0.004 and HR 6.57, p=0.001, respectively). C-indices of the CONUT score for predicting progression-free survival and cancer specific survival were 0.694 and 0.737, respectively. The CONUT score was significantly associated with the best response to nivolumab with the median tumor shrinkage rate of -23%, +8% and +24% for CONUT scores of 0 to 1, 2 to 4 and 5 or more, respectively (p=0.021). CONCLUSIONS: The CONUT score may be useful to predict the clinical outcomes and therapeutic response in patients with advanced renal cell carcinoma receiving nivolumab.

Religious Coping in Cancer: A Quantitative Analysis of Expressive Writing Samples From Patients With Renal Cell Carcinoma.

CONTEXT: Past religiosity/spirituality (R/S) research has mainly relied on self-report instruments, which may result in self-presentation and defensive biases. OBJECTIVES: To address these limitations, we reviewed the writing samples that were generated as part of an expressive writing (EW) trial, coded the samples for R/S content, and examined cross-sectional and prospective associations between R/S content and symptom and psychosocial outcomes. METHODS: Participants diagnosed with renal cell carcinoma who were randomized to the EW arm completed a standard writing protocol. Before randomization, they completed validated measures of R/S, depressive symptoms, social support, fatigue, and sleep disturbances and one, four, and 10 months after completing the intervention. Writing samples were coded for positive and negative religious coping (RC), and personal (e.g., private prayer) and collective (e.g., church attendance) religious engagement (RE). RESULTS: Of the 138 patients, 117 provided at least one writing sample, and 89% of participants made at least one R/S reference with 70% including at least one positive RC statement, and 45.3% revealed personal and 42.3% collective RE. Negative RC was rare (8%). Although positive RC and RE were significantly associated with the R/S Index (P < 0.01), negative RC was not. In prospective analyses, RE was associated with reduced cancer-related symptoms over time (P = 0.04), and negative RC was associated with increased psychological distress over time (P = 0.004). CONCLUSION: Behavioral coding of EW samples supported the literature suggesting that positive RC is common among patients with cancer. Although negative RC may be relatively rare, it may be associated with psychological distress.

Interventional oncology at the time of COVID-19 pandemic: Problems and solutions.

The COVID-19 pandemic has deeply impacted the activity of interventional oncology in hospitals and cancer centers. In this review based on official recommendations of different international societies, but also on local solutions found in different expert large-volume centers, we discuss the changes that need to be done for the organization, safety, and patient management in interventional oncology. A literature review of potential solutions in a context of scarce anesthesiologic resources, limited staff and limited access to hospital beds are proposed and discussed based on the literature data.

[Why have tyrosine kinase inhibitors failed in the adjuvant situation and do checkpoint inhibitors make more sense?] / Warum haben Tyrosinkinaseinhibitoren in der adjuvanten Situation versagt bzw. können Checkpoint-Inhibitoren eher Sinn machen?

In view of a considerable risk of recurrence especially in patients with a high-risk profile after organ-sparing surgery or nephrectomy, adjuvant treatment seems to make sense in renal cell carcinoma. After the failed attempts using older immunotherapeutics or vaccination therapies, new hope was put in the panel of targeted VEGF/R inhibitors. But the results from these studies published so far are also disappointing. In this context the instruments for selecting the best suitable patients for adjuvant trials have to be discussed. It remains to be seen whether using the same selection criteria as in ongoing trials with checkpoint inhibitors will show better results.

Blue Dye Embolization of Renal Tumor: A New Technique to Improve Tumor Localization During Laparoscopic Partial Nephrectomy.

Purpose: To improve the tumor localization during laparoscopic surgery, we describe an innovative technique involving superselective intra-arterial injection of blue dye in tumoral vessels to color the tumor before surgical enucleation. Materials and Methods: The dye injection was performed at the same time as superselective embolization, immediately before laparoscopic surgery in a hybrid operating room. We used this new treatment sequence on 50 consecutive patients. Results: The selective intra-arterial injection of an emulsion of blue dye and lipiodol was feasible in 46 (92%) cases and well tolerated, followed by superselective embolization of the tumor vessels with glue or coils. The tumor was easily localized during surgery due to the blue coloration. Tumor coloration was not associated with postoperative complication, especially allergic reaction or renal failure. Pathologic analysis of the tumor was not modified by the coloration and all tumors had negative surgical margins. Conclusions: The preoperative dye localization is a feasible, safe, and accurate procedure. This combined approach reduces the difficulty of surgery and increases patient safety.

The relationship between prognostic nutritional index and treatment response in patients with metastatic renal cell cancer.

INTRODUCTION AND AIM: To investigate the effect of the prognostic nutritional index on treatment response and survival in patients with metastatic renal cell cancer. METHODS: We retrospectively analyzed the treatment modalities; the demographic, clinical and pathological features of 396 patients with RCC and prognostic nutritional index. Based on the median value, patients were grouped as having low and high prognostic nutritional index values. Kaplan-Meier method was used for survival analysis, and Cox-regression analysis was used for multivariate analysis. RESULTS: The median overall survival was 39 months (95% CI 26.1-51.8), 28 months (95% CI 17.9-38) and 7 months (95% CI 4.7-9.2) in patients with favorable, intermediate and poor International Metastatic Renal Cell Carcinoma Database Consortium risk group, respectively. The difference between the groups was statistically significant (p < 0001). Overall survival was 11 months (95% CI 7.5-14.5) in the low-prognostic nutritional index (prognostic nutritional index ≤38.5) group, and 41 months (95% CI 30.5-51.4) in the high prognostic nutritional index (prognostic nutritional index >38.5) group (p < 0.001). In Cox regression analysis, Eastern Cooperative Oncology Group performance score (HR: 2.5), time to systemic treatment (HR: 1.7) and prognostic nutritional index (HR: 1.8) were associated with overall survival. CONCLUSION: In patients with renal cell cancer, prognostic nutritional index is closely related to survival and has prognostic significance.