Outcome Of Renal Cell Carcinoma Research Articles

Predictive factors for recurrence and outcomes in T1a renal cell carcinoma: Analysis of the INMARC (International Marker Consortium for Renal Cancer) database.

728 Background: Stage migration in renal cell carcinoma (RCC) has led to an increasing proportion of diagnoses at earlier clinical tumor stage and has rendered the phenomenon of the ‘small renal mass’ as a dominant presenting clinical paradigm. While thought of as being low risk, emerging knowledge about heterogeneity of RCC histologies and consequent impact on prognosis, in addition to awareness of impact of functional decline and demographic drivers on outcomes led us to further explore outcomes and predictive factors in T1a RCC patients treated with surgical resection. Methods: The INMARC database was queried for patients with small renal masses (≤ 4 cm) who underwent surgery via partial or radical nephrectomy and who presented without nodal or distant metastases. Patients were stratified into two groups based on having recurrence (distant or loco-regional) or not. Primary outcome was overall survival (OS). Multivariable analyses (MVA) were performed to analyze clinicopathological variables associated with recurrence and identify predictors of recurrence, cancer-specific mortality (CSM), and all-cause mortality (ACM). Kaplan-Meier analyses (KMA) were performed to compare recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) between histology types clear cell, chromophobe, papillary, and “other.” Results: We analyzed 1,878 cT1aN0M0 RCC patients; 101 (5.4%) developed recurrence (median follow up 53.6 months; median time to recurrence 19.3 months); 51.1% developed distant recurrence, 35.6% had loco-regional recurrence, and 13.9% experienced distant and loco-regional recurrence. MVA demonstrated age (HR=1.02, p=0.02), sex (HR=1.71, p=0.045), diabetes (HR=1.94, p=0.006), high/unclassified grade (HR=2.82-4.40, p<0.001-0.007), papillary (HR=0.37, p=0.013) and other (HR=2.51, p=0.019) RCC as predictive factors for recurrence. MVA identified high/unclassified grade (HR=3.17-6.22, p=0.002-0.003) and papillary RCC (HR=0.12, p=0.036) as predictive factors for CSM. MVA for ACM demonstrated age (HR=1.03, p<0.001), non-Caucasian race (HR=0.85, p<0.001), high grade (HR=1.42, p=0.024), recurrence (HR=1.86, p=0.003), and GFR<45 (HR=2.89, p<0.001) to be independent risk factors. KMA comparing Clear Cell, Papillary, Chromophobe and Other RCC revealed significant differences for 5-year CSS (97.8% vs. 99.3% vs. 98.5% vs. 87.0%, p=0.018) and 5-year RFS (92.4% vs. 96.0% vs. 97.8% vs. 81.7%, p<0.001), but not 5-year OS (89.4% vs. 85.2% vs. 93.2% vs. 73.7%, p=0.34). Conclusions: We noted differential outcomes in T1a RCC based on histology and grade for recurrence and CSM, while renal functional decline in addition to pathological factors and recurrence were predictive for ACM. These findings suggest consideration to refine management and post treatment surveillance strategies in T1a RCC.

A New Treatment Landscape for RCC: Association of the Human Microbiome with Improved Outcomes in RCC.

Microbes play different roles in metabolism, local or systemic inflammation, and immunity, and the human microbiome in tumor microenvironment (TME) is important for modulating the response to immunotherapy in cancer patients. Renal cell carcinoma (RCC) is an immunogenic tumor, and immunotherapy is the backbone of its treatment. Correlations between the microbiome and responsiveness to immune checkpoint inhibitors have been reported. This review summarizes the recent therapeutic strategies for RCC and the effects of TME on the systemic therapy of RCC. The current understanding and advances in microbiome research and the relationship between the microbiome and the response to immunotherapy for RCC are also discussed. Improving our understanding of the role of the microbiome in RCC treatment will facilitate the development of microbiome targeting therapies to modify the tumor microbiome and improve treatment outcomes.

Patient Factors Impacting Perioperative Outcomes for T1b-T2 Localized Renal Cell Carcinoma May Guide Decision for Partial versus Radical Nephrectomy.

There remains debate surrounding partial (PN) versus radical nephrectomy (RN) for T1b-T2 renal cell carcinoma (RCC). PN offers nephron-sparing benefits but involves increased perioperative complications. RN putatively maximizes oncologic benefit with complex tumors. We analyzed newly available nephrectomy-specific NSQIP data to elucidate predictors of perioperative outcomes in localized T1b-T2 RCC. We identified 2094 patients undergoing nephrectomy between 2019-2020. Captured variables include surgical procedure and approach, staging, comorbidities, prophylaxis, peri-operative complications, reoperations, and readmissions. 816 patients received PN while 1278 received RN. Reoperation rates were comparable; however, PN patients more commonly experienced 30-day readmissions (7.0% vs. 4.7%, p = 0.026), bleeds (9.19% vs. 5.56%, p = 0.001), renal failure requiring dialysis (1.23% vs. 0.31%, p = 0.013) and urine leak or fistulae (1.10% vs. 0.31%, p = 0.025). Infectious, pulmonary, cardiac, and venothromboembolic event rates were comparable. Robotic surgery reduced occurrence of various complications, readmissions, and reoperations. PN remained predictive of all four complications upon multivariable adjustment. Several comorbidities were predictive of complications including bleeds and readmissions. This population-based cohort explicates perioperative outcomes following nephrectomy for pT1b-T2 RCC. Significant associations between PN, patient-specific factors, and complications were identified. Risk stratification may inform management to improve post-operative quality of life (QOL) and RCC outcomes.

Kidney Cancer Screening and Epidemiology

The incidence of renal cell carcinoma (RCC) has risen worldwide over the past few decades, and this has been associated with a stage shift. Survival outcomes of RCC depend largely on the stage at diagnosis. Although overall mortality has stabilized or declined in most countries, survival remains poor in late-stage disease, suggesting early detection may improve overall survival outcomes. A number of potential candidate screening tools have been considered (including urinary dipstick, blood- and urine-based biomarkers, ultrasound, and computed tomography [CT]), though it may be that a combination of these approaches may be optimal. Ultimately, the sensitivity and specificity of the chosen screening tool will determine the rate of false positives and false negatives, which must be minimized. One of the key challenges is the relatively low prevalence of the disease, which might be overcome by performing risk-stratified screening or screening for more than one condition (such as combined lung and kidney cancer screening). Both approaches have been shown to be acceptable to the general public, and they may maximize the efficiency of screening while reducing harms. Indeed, quantifying benefits and harms of screening is key (including the impact on overdiagnosis and quality of life). Whether screening for RCC will lead to a stage shift and the impact on survival are the decisive missing pieces of information that will determine whether the screening program might be adopted into clinical practice (along with feasibility, acceptability, and cost-effectiveness).

Clinicopathological characteristics and outcomes of synchronous renal cell carcinoma and urothelial carcinoma: A population-based analysis.

To better understand the characteristics, and survival outcomes of synchronous renal cell carcinoma (RCC) and urothelial carcinoma (UC), we described and analyzed the clinical features, factors, and prognosis of patients with synchronous RCC and UC using a large population-based database. Within the Surveillance, Epidemiology, and End Results (SEER) database (2004-2016), we identified patient with concurrent RCC and UC at initial diagnosis. Their clinicopathological features and prognosis were evaluated. A logistic regression model was used to examine risk factors for the occurrence of concomitant RCC and UC, and Kaplan-Meier survival curves were used to estimate overall survival. A total of 61,454 RCC patients were identified from the SEER database, 704 (1.1%) patients presented with synchronous RCC and UC. Among these patients, concurrent bladder tumors (566/704) are more common. Subsequently, subgroup analysis based on the location of UC indicated that patients with concurrent RCC and upper tract urothelial carcinoma (UTUC) had unfavorable UC characteristics (higher tumor stage and grade), compared with patients with concomitant bladder cancer. An increased risk of concurrent UC was observed among older age, male sex, and white race. Meanwhile, papillary RCC histology [odds ratio (OR) 3.23; 95% confidence interval (CI) 2.13-4.90], and smaller tumor (OR 6.63; 95% CI 4.46-9.87) were independent risk factors for concomitant UTUC. In addition, we found that synchronous RCC and UTUC was associated with worse survival by using Kaplan-Meier and multivariable analysis [hazard ratio (HR) 2.36, 95% CI 1.89-2.95]. However, concomitant bladder cancer did not affect survival outcomes of patients with RCC (HR 1.00, 95% CI 0.86-1.17). We found that synchronous concurrent RCC and UC is relatively uncommon and mostly located in the bladder. Older age, male sex, and white race increase the risk of synchronous RCC and UC. Meanwhile, patients with papillary RCC histology, and smaller tumors are more likely to have concomitant RCC and UTUC. Furthermore, our findings suggest that synchronous RCC and UTUC has a worse prognosis, while, concomitant bladder tumor did not affect the oncological outcomes of RCC.

Impact of Bone Metastases on Patients with Renal Cell Carcinoma or Melanoma Treated with Combotherapy Ipilimumab Plus Nivolumab.

(1) Background: Ipilimumab plus nivolumab (combo-ICI) improves overall survival (OS) in patients with advanced renal cell carcinoma (RCC) or melanoma. The impact of bone metastases (BM) on survival outcomes of combo-ICI-treated patients is unknown. (2) Methods: This single-center retrospective observational study involved 36 combo-ICI-treated patients with advanced RCC and 35 with melanoma. Clinical and laboratory data preceding the initiation of combo-ICI were collected. Univariate and multivariate Cox proportional hazard models were used to assess the effect of BM on overall survival (OS) and progression-free survival (PFS). (3) Results: zNine RCC and 11 melanoma patients had baseline BM. In unadjusted analysis, baseline BM was associated with a poorer OS in the RCC cohort. Baseline BM did not have any impact on survival outcomes in melanoma patients. After adjustment on baseline performance status and on neutrophil-to-lymphocyte ratio (NLR), the impact of BM was no longer significant, but a NLR ≥ 3 was significantly associated with a poorer OS in the RCC cohort. (4) Conclusions: The presence of baseline BM seems to be associated with worse outcomes in RCC combo-ICI-treated patients, while its effect might not be independent from the inflammatory state (approximated by the NLR). BM seems to have no impact on the outcomes of melanoma combo-ICI-treated patients.

Recent Advances in the First-Line Management of Advanced Renal Cell Carcinoma: Focus on the Role of Lenvatinib Plus Pembrolizumab Combination Treatment

As part of the 37th Annual European Association of Urology (EAU) Congress, this symposium presented key data from the CLEAR study: a Phase III randomised controlled trial evaluating lenvatinib plus pembrolizumab versus sunitinib in patients with advanced renal cell carcinoma (RCC) in the first-line (1L) setting.1 Leading experts discussed strategies for optimising treatment outcomes in RCC using lenvatinib plus pembrolizumab and considered how to identify the right patients for this combination therapy in clinical practice.

Exosomal microRNA-1 and MYO15A as a target for therapy and diagnosis in renal cell carcinoma

Exosomes are 40–100 nm nano-sized extracellular vesicles and are receiving increasing attention as novel structures that participate in intracellular communication. We previously found that miRNA-1 (miR-1) functions as a tumor suppressor in renal cell carcinoma (RCC). In this study, we investigated the function of exosomal miR-1 and the possibility that the exosome constitutes a tumor maker in RCC. First, we established the method to collect exosomes from cell lysates and human serum by a spin column-based method. Next, we assessed exosomes using Nanosight nanoparticle tracking analysis and Western blot analysis with exosome marker CD63. We confirmed that exosomes labeled with PKH26 fused with recipient cells. Moreover, miR-1 expression was elevated in RCC cells treated with exosomes derived from miR-1-transfected cells. Functional analyses showed that exosomal miR-1 significantly inhibited cell proliferation, migration and invasion compared to control treatment. Our analyses with TCGA database of RCCs showed that miR-1 expression was significantly downregulated in clinical RCC samples compared to that in normal kidney samples, and patients with low miR-1 expression had poorer overall survival in comparison to patients with high expression. Furthermore, RNA sequence analyses showed that expression levels of several genes were altered by exposure to exosomal miR-1. The analyses with TCGA database indicated that high expression of MYO15A was associated with a poorer outcome in RCC. In addition, RT-qPCR analysis of exosomes from clinical patients’ sera showed that MYO15A was significantly upregulated in RCC patients compared to that in healthy controls. This study showed that treatment with exosomal miR-1 might be an effective approach to treating RCCs. In addition, exosomal MYO15A could be a diagnostic tumor marker in RCCs.

Abstract 95: In vitro, in vivo and molecular effects of triptolide and minnelide in renal cell carcinoma

Abstract Background: The worldwide incidence of Renal Cell Carcinoma (RCC) is increasing. Although new therapies have improved outcomes in advanced RCC, most patients eventually fail treatment and succumb to this devastating disease. Systemic therapy strategies have focused on TKI and immunotherapy, alone or in combination. Triptolide, a diterpenoid epoxide extracted from Tripterygium wilfordii Hook f (TWHf), has potent antitumor activity in multiple cancer models. Few studies have focused on the potential of triptolide as a novel therapeutic option in RCC. Objective: the objectives of this study are to characterize the in vitro and in vivo effects of Triptolide (T) and its water-soluble form, Minnelide (M), in models of renal cell carcinoma. Methods: The in vitro effects of triptolide (T) on human and murine RCC (786-0, A498, Caki-1, ACHN, and RENCA) cell proliferation was assessed using cell count and xCelligence assays at 24, 48, 72 and 96h. Molecular and mechanistic characterization of triptolide’s effects in 786-0 cells were analyzed by the (Reverse Phase Protein Array) and validated by western blot analysis. The in vivo effects (tumor progression and survival) of M were assessed in nude mice bearing 786-0 tumors (8x106 cells per mouse). M was administered to tumor-bearing mice at two different doses (0.21mg/kg and 0.42mg/kg daily), intraperitoneally, for 21 days. Correlative studies to explain the in vivo effect of M and the correlation with the molecular changes in vitro seen are being performed and will be shown in the poster. Results: T significantly inhibited, in a dose-response manner, cell proliferation in all human and murine renal cancer cell lines, with IC50 ranging between 12.5 and 25 nM). T was associated with significant negative modulation of proliferation, cell cycle, survival, increased apoptosis, and ER stress pathways in 786-0 cells, as demonstrated by RPPA analysis and validated by western Blot of selected pathway proteins, such as apoptosis (PARP cleavage and Caspase 3 activation), ER stress induction (pEIF2a, CHOP), and down-regulation of survival and proliferation pathways (pAKT). In vivo, M was associated with significant antitumor effects in 786-0 xenografts, with complete responses in the majority of mice while on treatment. These effects were associated with significant prolongation in overall survival in M treated vs. control mice. No significant toxicity or treatment-related deaths were observed. Conclusion: Our results have shown for the first time the potent in vitro and in vivo antitumor effects of T in RCC and the molecular changes associated with these effects. The profound antitumor effects in the aggressive 786-0 RCC xenograft model are highly encouraging and warrant further preclinical studies and potential clinical trials of M this devastating disease. Correlative tumor studies to understand the mechanisms of M in vivo antitumor effects are underway and will be presented at the meeting. Citation Format: Valery A. Chavez, Floritza Bustamante, Abner Murray, Ashok Saluja, Jaime Merchan. In vitro, in vivo and molecular effects of triptolide and minnelide in renal cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 95.

Head-to-head comparison of all the prognostic models recommended by the European Association of Urology Guidelines to predict oncologic outcomes in patients with renal cell carcinoma

European Urology Association guidelines suggest the use of integrated prognostic systems to assess oncologic outcomes after surgery in patients with localized renal cell carcinoma (RCC). We performed a head-to-head comparison among all the EAU guidelines recommended prognostic models in RCC. The study included 2,014 patients treated with surgery for clinically localized RCC. Patients were classified into prognostic risk groups, based on each of the five EAU guidelines recommended prognostic model definition, namely UISS, Leibovich 2003, VENUSS, GRANT, and Leibovich 2018 score. Prognostic accuracy of each prognostic model to predict clinical progression or cancer-specific mortality (CSM) was assessed, and ROC curves were calculated, according to histological subtype, namely clear-cell, papillary, and chromophobe RCC. Of 2,014 patients, 1,575 (78%) harboured clear-cell, 312 (16%) papillary, and 127 (6%) chromophobe RCC. Median follow-up was 66 months [Interquartile range (IQR): 29-120]. In clear-cell RCC, low-risk patients rates ranged from 21% to 64%, according prognostic model. The same phenomenon was observed for papillary and chromophobe RCC. In clear-cell RCC, Leibovich 2018 resulted the most accurate model in predicting clinical progression (88.1%) and CSM (86.8%). Conversely, VENUSS or UISS prognostic models predicting oncologic outcomes represented the most accurate in papillary (88.7% and 84.8%) or chromophobe (87.8% and 89.1%) RCC, respectively. A non-negligible difference in terms of performance accuracy exists among the EAU guidelines recommended prognostic models. Thus, their adoption in RCC should be histology-specific and follow-up strategies based on prognostic risk class appear justified only if the appropriate model is used to stratify patients into prognostic risk groups.

MP47-16 DECLINE TO "SEVERE" CKD-S IS A PREDICTIVE MARKER FOR ALL-CAUSE AND NON-CANCER MORTALITY IN RENAL CELL CARCINOMA: ANALYSIS OF THE INTERNATIONAL MARKER CONSORTIUM FOR RENAL CANCER (INMARC)

You have accessJournal of UrologyCME1 May 2022MP47-16 DECLINE TO "SEVERE" CKD-S IS A PREDICTIVE MARKER FOR ALL-CAUSE AND NON-CANCER MORTALITY IN RENAL CELL CARCINOMA: ANALYSIS OF THE INTERNATIONAL MARKER CONSORTIUM FOR RENAL CANCER (INMARC) Mimi Nguyen, Arman Walia, Rekha Narasimhan, Ava Saidian, John Matthew Perry, Hajime Tanaka, Kevin Hakimi, Margaret Meagher, Dattatraya Patil, Yosuke Yasuda, Kazutaka Saito, Yasuhisa Fujii, Viraj Master, and Ithaar Derweesh Mimi NguyenMimi Nguyen More articles by this author , Arman WaliaArman Walia More articles by this author , Rekha NarasimhanRekha Narasimhan More articles by this author , Ava SaidianAva Saidian More articles by this author , John Matthew PerryJohn Matthew Perry More articles by this author , Hajime TanakaHajime Tanaka More articles by this author , Kevin HakimiKevin Hakimi More articles by this author , Margaret MeagherMargaret Meagher More articles by this author , Dattatraya PatilDattatraya Patil More articles by this author , Yosuke YasudaYosuke Yasuda More articles by this author , Kazutaka SaitoKazutaka Saito More articles by this author , Yasuhisa FujiiYasuhisa Fujii More articles by this author , Viraj MasterViraj Master More articles by this author , and Ithaar DerweeshIthaar Derweesh More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002618.16AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Impact of surgically induced Chronic Kidney Disease (CKD-S) on outcomes in renal cell carcinoma (RCC) is controversial. We evaluated effects of worsening CKD-S on oncologic and non-oncologic survival outcomes in RCC. METHODS: We performed a retrospective multicenter analysis of patients who underwent Partial (PN) or Radical Nephrectomy (RN). Primary outcome was all-cause mortality (ACM). Secondary outcomes were non-cancer mortality (NCM), cancer specific mortality (CSM), and de novo CKD-S Stage 4 [estimated glomerular filtration rate <30 mL/min/1.73m2). Patients were stratified by CKD stage: no CKD-S (eGFR≥60), de novo “moderate” CKD-S 3a (eGFR 59-45), de novo “moderate-severe” CKD-S 3b (eGFR 44-30) and de novo “severe” CKD-S 4 (eGFR 29-15). Multivariable analysis (MVA) was utilized to identify risk factors associated with development of CKD-S Stage 4 and mortality outcomes. Kaplan-Meier analysis (KMA) was utilized to evaluate for overall survival (OS), non-cancer survival (NCS), and cancer-specific survival (CSS) with respect to CKD-S categories. RESULTS: We analyzed 3239 patients [no CKD-S (n=1876), de novo CKD-S 3a (n=606), de novo CKD-S 3b (n=489) and de novo CKD-S 4 (n=268)]. On MVA, de novo CKD-S 4 was independently associated with ACM (HR 2.1, p <0.001) and NCM (OR 2.8, p <0.001), but not CSM (p=0.219); de novo CKD-S 3b was independently associated with ACM (HR 1.3, p=0.033) and NCM (OR 1.5, p=0.021), but not CSM (p=0.909); de novo CKD-S 3a was not predictive for any mortality outcomes (p=0.81-0.102). RN was independently associated with de novo CKD-S 4 (HR 1.4, p=0.047). Comparing no CKD, CKD-S 3a, CKD-S 3b and CKD-S 4, KMA demonstrated worsening outcomes with progressive CKD-S stage: 5 year OS 84% vs. 78% vs. 71% vs. 60%, p <0.001; 5 year NCS 93% vs. 87% vs. 83% vs. 72%, p <0.001; 5 year CSS, 91% vs. 92% vs. 86% vs. 83%, p <0.001 (Figure). CONCLUSIONS: Development of CKD-S Stage 3b and 4, but not Stage 3a, was associated with worsened ACM and NCM. Worsening CKD-S was not associated with increased oncological risk. While RN was predictive of “severe” CKD-S, decision to proceed with nephron preservation via PN should be individualized based on oncological risk and risk of functional decline to CKD-S 3b or 4, and not CKD-S 3. Source of Funding: Stephen Weissman Kidney Cancer Research Fund © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e816 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mimi Nguyen More articles by this author Arman Walia More articles by this author Rekha Narasimhan More articles by this author Ava Saidian More articles by this author John Matthew Perry More articles by this author Hajime Tanaka More articles by this author Kevin Hakimi More articles by this author Margaret Meagher More articles by this author Dattatraya Patil More articles by this author Yosuke Yasuda More articles by this author Kazutaka Saito More articles by this author Yasuhisa Fujii More articles by this author Viraj Master More articles by this author Ithaar Derweesh More articles by this author Expand All Advertisement PDF DownloadLoading ...

Does presence of diabetes mellitus impact patient oncological outcomes in renal cell carcinoma: A multicenter analysis.

325 Background: Diabetes mellitus (DM) has been hypothesized to be a risk factor for development of renal cell carcinoma (RCC). We evaluated impact of DM on survival outcomes in RCC. Methods: We performed a retrospective analysis of the International Marker Consortium for Renal Cancer (INMARC). The cohort was divided into three subgroups (patients with stage I vs. stage II vs. stage III RCC) for descriptive, survival and multivariable analysis of outcomes. Kaplan Meier Analysis (KMA) was used to compare diabetic and non-diabetic patients in the different stage subgroups to evaluate overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS). Cox Regression multivariable analysis (MVA) was used to elucidate independent risk factors for all-cause mortality (ACM). Results: 2,927 patients with stage I RCC (709-DM/ 2218 non-DM), 2,513 with stage II RCC (688 DM/1825 non-DM) and 460 with stage 3 RCC (355 DM/ 105 non-DM) were analyzed. MVA revealed DMII having no impact on CSM (p=0.118) or PFS (p=0.316) across all stages. MVA for ACM revealed age (HR 1.026, p&lt;0.001), male sex (HR=1.425, p&lt;0.001), hypertension (HR=1.693, p &lt;0.001) and tumor size (HR=1.064, p&lt;0.001) as independent risk factors. KMA identified increased ACM in stage I (p&lt;0.001) and stage III (p&lt;0.001) RCC patients with non-DM compared to diabetic patients. Conclusions: Our findings suggest that DM may have impact on survival of in RCC, but this impact is mostly driven by non-oncologic, as opposed to oncologic effects. Further investigation is requisite.

Tumor-Infiltrating Myeloid Cells Co-Express TREM1 and TREM2 and Elevated TREM-1 Associates With Disease Progression in Renal Cell Carcinoma

Myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAM) contribute to cancer-related inflammation and tumor progression. While several myeloid molecules have been ascribed a regulatory function in these processes, the triggering receptors expressed on myeloid cells (TREMs) have emerged as potent modulators of the innate immune response. While various TREMs amplify inflammation, others dampen it and are emerging as important players in modulating tumor progression—for instance, soluble TREM-1 (sTREM-1), which is detected during inflammation, associates with disease progression, while TREM-2 expression is associated with tumor-promoting macrophages. We hypothesized that TREM-1 and TREM-2 might be co-expressed on tumor-infiltrating myeloid cells and that elevated sTREM-1 associates with disease outcomes, thus representing a possibility for mutual modulation in cancer. Using the 4T1 breast cancer model, we found TREM-1 and TREM-2 expression on MDSC and TAM and that sTREM-1 was elevated in tumor-bearing mice in multiple models and correlated with tumor volume. While TREM-1 engagement enhanced TNF, a TREM-2 ligand was detected on MDSC and TAM, suggesting that both TREM could be functional in the tumor setting. Similarly, we detected TREM-1 and Trem2 expression in myeloid cells in the RENCA model of renal cell carcinoma (RCC). We confirmed these findings in human disease by demonstrating the expression of TREM-1 on tumor-infiltrating myeloid cells from patients with RCC and finding that sTREM-1 was increased in patients with RCC. Finally, The Cancer Genome Atlas analysis shows that TREM1 expression in tumors correlates with poor outcomes in RCC. Taken together, our data suggest that manipulation of the TREM-1/TREM-2 balance in tumors may be a novel means to modulate tumor-infiltrating myeloid cell phenotype and function.

CLINICOPATHOLOGICAL PROFILE OF RENAL TUMOURS IN EASTERN INDIA: A STUDY FROM TERTIARY CARE ARMED FORCES HOSPITAL

Aprimary renal tumor comprises a wide spectrum of neoplastic lesions of the kidney with patterns, which are relatively distinct among children and adults. Primary renal tumors may be benign or malignant. A wide variety of both benign and malignant renal tumors may arise from the different components of the renal parenchyma, mostly from the tubular epithelium (1,2). With the widespread use of cross sectional imaging modalities the incidence of renal tumors has been increased throughout the world during the last few decades. Until now, the gold standard treatment for most of the renal tumors is their surgical removal, either by radical nephrectomy or partial nephrectomy (3). Incidence of renal cell carcinoma (RCC) is 2-3% of all malignancy. Seventh most common tumour in western world. Country to country the incidence varies and most common in the western part of the world. Incidence of RCC is less in Asian country, particularly in India (4,5). The prole of these patients has not been studied enough in our country as yet and the data regarding RCC in India is scarce. The data available in our country either retrospective or inadequately collected. This study will help to understand characteristics of renal tumor in this geographical area and can be used as source for future reference. The study was conducted among 38 patients of renal mass from the eastern India. In the absence of robust Indian data on Renal tumours, this study provides baseline information on epidemiology, stage at presentation, and outcomes of RCC at Indian population compared with the Western population. Though symptomatic tumour still more common in India, asymptomatic tumour detection rate has been increased due to more health care facility and available imaging modalities.

Clinical- pathological features and surgical outcome of renal cell carcinoma: Experience from a zonal referral hospital-northern of Tanzania

Background: Renal cell carcinoma (RCC) is the most common primary malignant tumour of kidney in adults. Recent studies from developed countries have shown that most renal tumour are currently diagnosed incidentally during screening for other disease which leads to better prognosis while few studies done in Africa still shows significant proportion of patients present with classic triad ( &gt;10%) which is a sign of advanced disease. Objectives: This study aimed at determining clinical pathological feature and outcome of RCC in Northern zone of Tanzania. Patients and Methods: This was a hospital based descriptive retrospective cohort study conducted at Kilimanjaro Christian Medical (KCMC) from January 2002 to December 2017. Data were analysed using statistical package for social science (SPSS) version 16. 0 and summarized in tables and figures. Results: Forty three patients (43) underwent radical nephrectomy for RCC during the study period. Male to female ratio was1. 7: 1 with mean age of 53+/- 12 years. Flank pain (84%), abdominal mass (76%) and hematuria (44%) were the most common clinical presentation while classical triad was found in 40%. The most common clinical tumor stage was T3(72. 1%) whilst clear cell carcinoma was the commonest histological pattern. Five years survival length for T1, T2, T3 and T4 were 100%, 62. 5%, 32. 3% and 0% respectively. Conclusion: The most common presenting symptom of RCC in our centre is flank pain, and abdominal mass. Majority of the patients presented with advanced disease with less than five year survival rate. Clear cell type was the predominant histological type.

THSD7A expression: a novel immunohistochemical determinant in predicting overall survival of metastatic renal cell carcinoma treated with targeted therapy.

The association of thrombospondin type 1 domain-containing 7A (THSD7A) expression, a novel angiogenesis-related marker, with survival outcomes of tumors including renal cell carcinoma (RCC) remains to be clarified. Therefore, we investigated the impact of THSD7A on outcomes of metastatic RCC (mRCC) patients treated with targeted therapy. A total of 86 mRCC patients were included. The expression of THSD7A in nephrectomy material of the patients was assessed by immunohistochemistry and expression patterns were categorized into two groups: negative (no staining) and positive. Univariable and multivariable Cox regression models evaluated the impact of THSD7A expression on progression free survival (PFS) and overall survival (OS) of the patients. THSD7A expression was determined in 77.9% of the patients. Kaplan-Meier analyses showed that while the patients with THSD7A expression had significantly inferior OS times than those with negative THSD7A expression (19.9months vs. 52.2months, P = 0.024, respectively), there was no association between THSD7A expression and PFS. The univariate analyses demonstrated that the significant variables in predicting OS were presence of bone metastasis (P = 0.030), THSD7A expression (P = 0.028), and International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) scoring system (P < 0.001). However, applying multivariate analyses, the independent variables in predicting OS were THSD7A expression (HR: 2.639, P = 0.037) and IMDC scoring system (P < 0.001). We revealed that THSD7A expression was associated with OS of mRCC patients treated with targeted therapy. There might be an important link between THSD7A expression and resistance to targeted therapy.

No Detection of Pseudocapsule of Tumor-Parenchyma Interface on Multidetector Computed Tomography (MDCT) Images: Clinical Significance and Histological Reflections in Renal Cell Carcinoma

ObjectivePseudocapsule (PS) of tumor-parenchyma interface (TPI) can be detected by MDCT (ctPS) in renal cell carcinoma (RCC) with exceptions. We aim to study the prognostic implications and histological reflections of no detection of ctPS in RCC.Patients and MethodsA total of 210 RCC patients who had MDCT examination and received nephrectomy in our institution were included in the analysis. Absence or presence of ctPS was recognized, and its associations with overall survival (OS) and progression-free survival (PFS), pathological PS (pPS) and vasculature were studied.ResultsA total of 172 (81.9%) patients were recognized to have a ctPS and 38 (18.1%) had no detection of it. They had comparable histology, stage, grade, and necrosis. Patients without a ctPS had significantly shortened overall survival (OS, p = 0.001) and progression-free survival (PFS, p <0.001), the significance of which persisted in multivariable analysis (OS, HR 3.104, p = 0.003; PFS, HR 3.313, p = 0.001). Nearly all tumors (34/38, 89.4%) without a ctPS actually had a pPS being detected and incompleteness of pPS was also irrelevant (p = 0.739). Compared with ctPS presence, those without a ctPS had significantly thinned pPS (0.36 vs 0.43 mm, p = 0.005). In clear-cell histology, those without a ctPS also contained increased vascular density and cross-sectional area of vessels with long diameter ≥200 um in the pPS layer (p = 0.005 and 0.011) and increased vascular density in the 500 um layer outside pPS (p = 0.017).ConclusionAbsence of ctPS on MDCT significantly increases the risk of adverse clinical outcome in RCC. It is the reflection of a thinner pPS and enriched vasculature of TPI rather than absence of pPS itself.

A histopathological study of renal cell carcinoma at a tertiary care hospital

Background: Renal cell carcinoma (RCC) accounts for 80-85% of malignant kidney tumors. However incidence of RCC is less in Asian Countries including India and data available from Indian studies is scarce. Outcome of RCC depends on the morphological type and hence accurate classification is essential. Aims and Objectives: The objective of the present study was to assess the profile of patients of RCC in respect to age distribution, Sex distribution, laterality of the tumor, location within the kidney and Pathological tumor stage and compare our results with available literature from India and other countries. Material and Methods: The study is a retrospective study, which was conducted over a three and half year period from January 2016 to June 2019 at Goa Medical College, Bambolim Goa. A total of 60 cases of RCC diagnosed over this period were included in the study. Patient details were obtained from the Histopathology requisition forms from the records of Pathology department. The data was collected, analysed and compared with other similar studies. Histopathological examination of the specimens was conducted using standard processing technique and taking 5 micron sections and staining by Hematoxylin and Eosin technique. Results: A total of 60 cases of RCC were diagnosed over 3and 12 year period with Clear Cell Carcinoma 38(63.3%) cases being the commonest histopathological type. The tumor was more commonly seen in males with a M:F ratio of 3.6:1. The age ranged from 25 to 78 years with a median of 56.5 years which is decade earlier as compared to Western data. The tumor size(Pathological stage pT) in this study was lower with 24 cases(40%) being diagnosed in pTa stage and 22cases(36.7%) treated with nephron sparing surgery which is a much higher figure as compared to other Indian studies. Keywords: Renal cell carcinoma, Clear cell, Chromophobe, Multilocular cystic, Papillary.

Prognostic Value of Positive Lymph Nodes in Patients with Renal Cell Carcinoma and Tumor Thrombus Undergoing Nephrectomy and Thrombectomy

Introductions: The objective of this study was to determine the prognostic value of positive lymph nodes (LNs) in patients with renal cell carcinoma (RCC) and tumor thrombus (TT) and to explore risk factors predicting LNs metastasis. Methods: We retrospectively analyzed 216 patients with RCC and TT treated at a single institution from January 2015 to December 2019. Overall survival (OS) and progression-free survival (PFS) was estimated using the Kaplan-Meier curves divided by pathological LN status. Associations between clinicopathological features and survival outcomes were evaluated using Cox regression models. Logistic regression model was performed to determine risk factors associated with LN metastasis. Results: We identified 216 patients with RCC and TT including 85 (39.4%) who did and 131 (60.6%) who did not undergo lymph node dissection. Pathologically positive LNs were found in 18 (8.3%) cases. pN1 had significant worse OS (median: 21 vs. 41 and 56 months, p < 0.001) and PFS (median:14 vs. 29 and 33 months, p < 0.001) than pN0 and pNx respectively. However, survival outcomes of OS and PFS were similar between pNx-0/M1 and pN1/M0 group and between 1- and ≥2-node-positive group. Non-CCRCC (p = 0.001), sarcomatoid differentiation (p < 0.001), and pathologically positive LNs (p = 0.025) were independent prognostic predictors predicting worse OS while distance metastasis (p = 0.009), non-CCRCC (p = 0.023), necrosis (p = 0.014), sarcomatoid differentiation (p = 0.003), and pathologically positive LNs (p = 0.007) were independent prognostic indicators predicting worse PFS. Clinically positive LNs (p = 0.014) and sarcomatoid differentiation (p = 0.009) were predictors of positive LNs. Conclusions: LNs metastasis independently associated with worse survival outcomes in RCC and TT populations, with similar survival outcomes compared to distance metastasis. Therefore, more accurate risk stratification is warranted for guiding postoperative surveillance and adjuvant therapy.

The Diagnostic and Immunotherapeutic Value of CD248 in Renal Cell Carcinoma

Background: Renal cell carcinoma (RCC) is the most common malignancy in the urinary system. Despite substantial improvements in available treatment options, the survival outcome of advanced RCC is unsatisfactory. Identifying novel biomarkers to assist in early diagnosis and to screen patients who are sensitive to immunotherapy would be beneficial. CD248 is a promising candidate that deserves to be investigated.Methods: The Cancer Genome Atlas (TCGA) data set and clinical specimens were adopted to analyze the expression of CD248 between normal and tumor tissues. Univariate and multivariate Cox regression analyses were employed to identify independent prognostic factors and construct a CD248-based prognostic signature. The correlation among the present signature, tumor-infiltrating immune cells (TIICs), the tumor mutation burden (TMB), and immunomodulatory molecules was evaluated. The weighted gene co-expression network analysis (WGCNA), the enrichment analysis, and the miRNA correlation analysis were performed to explore the underlying mechanism of CD248 in the progression of RCC.Results: The overexpression of CD248 in RCC was related to a poor prognosis, and a CD248-based prognostic signature could precisely stratify patients with RCC with different survival outcomes regardless of the training or testing cohort. The present signature could reflect the immunosuppressive landscape of RCC (i.e., increased infiltration of regulatory T cells and upregulated immune checkpoints), accompanied by deteriorated clinicopathologic indexes. The TMB and immunostimulatory molecules expression also increased with the risk score generated from the present signature. CD248 co-expressed gene sets were identified through the WGCNA algorithm, and several immunosuppressive Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were significantly enriched. The result of CD248-correlated miRNA further emphasized the importance of CD248 in RCC.Conclusion: CD248 is a valuable biomarker to improve the diagnostic and therapeutic efficiency of RCC. The immunosuppressive effect of CD248 co-expressed genes may provide insight for the present study, and miRNA would help to reveal the mechanism of the expressive regulation of CD248.