bluuebunny/crossref_metadata_2025_split huggingface dataset:
The usefulness of serum X-linked inhibitor of apoptosis protein (XIAP) for predicting recurrence of renal cell carcinoma.
Authors: Hongo Fumiya , Toiyama Daisuke , Ueda Takashi , Kimura Yasunori , Nakamura Terukazu , Mikami Kazuya , Takaha Natsuki , Miki Tsuneharu 
Published: March 2020

e15055 Background: The X-linked Inhibitor of Apoptosis protein (XIAP) is associated with cell survival by blocking caspase-mediated apoptosis. We have reported the expression and prognostic value of XIAP in human prostate cancer using prostate tissue microarrays (Clin Cancer Res 2007). The expression and prognostic significance of XIAP in renal cell cancer (RCC) has been rarely studied. To our knowledge, no report on the serum XIAP levels from RCC patients has been published. In this study, we examined serum XIAP levels of RCC patients and normal individuals and evaluated its utility as biomarker. Methods: Peripheral blood samples were obtained from 99 patients (68 men and 31 women, median age; 60.7 years [36-85]) with RCC before surgery. All the patients underwent radical or partial nephrectomy. Blood samples were also collected from 52 healthy controls. The histological grade was as follows: grade 1; n= 5, grade 2; n=72, grade 3; n= 22. The serum XIAP levels were measured by a sandwich enzyme-linked immunosorbent assay. Cut off value was calculated by ROC analysis. Results: The serum XIAP levels in patients with RCC were higher than those of normal control individuals (328.3 pg/ml vs 156.2 pg/ml, p<0.001). At a median follow up of 33 months (1-105M), tumor with low serum XIAP showed significantly longer progression free survival (PFS) than those with high serum XIAP in grade 1-2 group (p<0.001). Conclusions: Serum XIAP level is associated with recurrence and prognosis. These results suggest that it may be used as a novel prognosticator and a potential target for renal cell cancer diagnosis and therapy.
Prognostic factors for metastatic renal cell carcinoma patients with removed metastases: A multicenter study of 559 patients.
Authors: Naito Sei , Kinoshita Hidefumi , Kondo Tsunenori , Shinohara Nobuo , Kasahara Takashi , Saito Kazutaka , Takayama Tatsuya , Masumori Naoya , Terachi Toshiro , Ozono Seiichiro , Naito Seiji , Tomita Yoshihiko 
Published: March 2020

e15071 Background: Metastasectomy considered to prolong survival in patients with metastatic renal cell carcinoma (mRCC). However, data on the indications for metastasectomy are limited. We aimed to examine the prognosis and the prognostic factors of mRCC patients who underwent metastasectomy. Methods: We sent questionnaires to Japanese hospitals and collected the data of patients who were diagnosed with mRCC between January 1988 and December 2009 and who had their metastatic lesions removed. We calculated the overall survival between metastasectomy and death or until the last follow-up. We also analyzed the relationship between survival and clinical features and identified adverse prognostic factors by multivariate analysis. Furthermore, we identified the group with a poor prognosis on the basis of the number of prognostic factors for which the patients were positive. These findings were internally validated using bootstrap procedures and the c-index. Results: We collected the data of 559 patients from 48 institutions. The median overall survival period was 80 months (95% CI, 69.7-90.6 months). We detected 5 adverse prognostic factors: incomplete resection by metastasectomy (hazard ratio, 1.75; p = 0.0169); brain metastasis (hazard ratio, 3.26; p = 0.0002); C-reactive protein levels of >1.0 mg/dl (hazard ratio, 2.84; p < 0.0001); Eastern Cooperative Oncology Group performance status of >1 (hazard ratio, 1.65; p = 0.0274); and the worst nuclear grade, i.e., the nuclei of tumor cells are larger than those of normal tubular cells (hazard ratio, 1.59; p = 0.0348). Patients positive for 3 or more of theseadverse prognostic factors had a worse prognosis (median overall survival, 24 months) than those positive for less than 3 factors (median overall survival, 105 months). The c-index for this model was 0.65 at 2 years. Conclusions: We identified 5 adverse prognostic factors for predicting the survival of patients who underwent metastasectomy.
Sunitinb in advanced renal cell carcinoma (RCC): Is effectiveness good enough in real life practice?
Authors: Trojniak Marta Paulina , Imbevaro Silvia , Palozzo Angelo Claudio , Jirillo Antonio 
Published: March 2020

e15072 Background: The sunitnib approval trials have established this multi-targeted TKI as a standard treatment in patients with metastatic RCC. However, even RCTs may fail to show relevant clinical benefit in wider population, as certain patient subtypes are under-represented, notably those with poorer prognostic factors and pretreated. The purpose of the study was to evaluate effectiveness of sunitinb in unselected RCC patients in real life practice in Italy. Methods: The data were collected through national registry on oncology drugs as part of mandatory surveillance program, which allows prospective investigations of effectiveness. RCC patients receiving sunitinb once daily, on schedule 4/2, between 2007 and 2011, had been included. All patients were checked prospectively for toxicity, clinical outcomes and length of treatment using registry inputs. Retrospective analysis of previous and following treatments and mortality data was performed based on clinical records and hospital databases. Results: A total of 106 patients (median age 64 years, M 70/F 36) were reviewed, 77% had prior nephrectomy and 74% were treatment-naïve. At first evaluation we found 28% partial responses, 25% stable diseases, 46% progressions and one discontinuation due to toxicity. The median TTP and OS were 7 and 11.3 months, respectively. Among 102 RCC patients (pts) with metastases (mets) at first diagnosis, 65% had lung mets, 19% pts had liver mets, 25% had bone mets and 8% had brain mets. The Cox regression model showed in subgroups analysis significantly worse survival prognosis in males, brain and liver mets, ECOG PS>1, non-clear cell histology and non prior nephrectomy. Sorafenib treatment after progression on sunitinib (33% pts) did not improved OS. Grade 3 thrombocytopenia, neutropenia, mucositis and HFS caused dosage reductions. Conclusions: The results on examined RCC study population show that sunitinib clinical benefit was gained in selected responders, but in overall the effectiveness was nearly half of that reported in the approval RCTs. Post-marketing studies in real life practice are required in order to verify both effectiveness and safety in general population, testing for external validity of randomized trials.
Expression of Notch family members in stage IV renal cell carcinoma tumors: Notch1 as medium-risk prognosis factor.
Authors: Antón Aparicio Luis M. , Medina Villaamil Vanessa , Aparicio Gallego Guadalupe , Quindós Varela Maria , Vazquez-Estevez Sergio , Leon Mateos Luis , Afonso Afonso Francisco J. , Firvida Perez Jose Luis , Ramos Vazquez Manuel , Calvo Ovidio Fernández , Santomé Lucía , Lázaro Quintela Martin , Santamarina Cainzos Isabel , Anido Urbano 
Published: March 2020

e15076 Background: The characterization of factors involved in the etiology of renal cell carcinoma (RCC) may lead to the identification of new targets for therapy and prognostic markers. Recent data indicate that Notch family members can be expressed by malignant RCC cells and this expression may have potential use as a strong prognostic factor. The aim of this study was to investigate the potential of Notch family members as prognostic markers for stage IV patients. Methods: We analyzed, by means of immunohistochemistry and quantitative polymerase chain reaction, protein and mRNA levels of 4 Notch family members in tumor specimens obtained from 48 patients with stage IV RCC. Clinicopathological data for these patients were evaluated. A 34% of the population had hypertension, 7.3% had hypothyroidism, 19.5% were diabetic, 7.7% prediabetic, and 22% showed hyperlipidemia. RCC specimens included clear cell RCC: 34; papillary: 3; mixed: 1; undifferentiated: 1; hypernephroma: 1.The association among biomarkers and clinicopathological factors were explored using One-Way ANOVA test and non-parametric statistics, Mann-Whitney U and Kruskal-Wallis tests. Results: Relative expression of Nocth3 and Notch4 transcript levels were elevated 25-fold in clear cell RCC tumors when compared with normal kidney tissues. Notch1 and Notch2 were overexpressed at protein level in clear cell RCC (p>0.05). Those renal tumors with right localization showed highest levels of Notch4 protein (p=0.096). Notch2 overexpression was associated with patients who had undergone nefrectomy (p=0.038). Finally, Bonferroni post-hoc statistic test showed us a statistically significant association (p = 0.020) between Nocth1 protein expression levels and patients with medium risk prognosis. Conclusions: These results show a deregulated expression of Notch receptors in RCC and suggest a role for this pathway in the progression of this tumoral pathology.
Analysis of the expression of Wnt signaling ligands in metastatic renal cell carcinomas tissue samples.
Authors: Anido Urbano , Medina Villaamil Vanessa , Aparicio Gallego Guadalupe , Quindós Varela Maria , Vazquez-Estevez Sergio , Leon Mateos Luis , Afonso Afonso Francisco J. , Ramos Vazquez Manuel , Firvida Perez Jose Luis , Santomé Lucía , Calvo Ovidio Fernández , Lázaro Quintela Martin , Santamarina Cainzos Isabel , Antón Aparicio Luis M. 
Published: March 2020

e15077 Background: Renal cell carcinomas (RCC) constitute a morphologically and genetically heterogeneous tumor.Wnt proteins are a large family of secreted glycoproteins that activate intracellular signal transduction pathways to control a wide variety of cellular processes such as determination of cell fate, proliferation, migration, and polarity.Wnt signalling may be playing a central role during RCC development. Methods: To characterize Wnt signalling activity in RCC, we gathered 48 tumor samples from patients diagnosed with metastatic RCC between years 2006 and 2011. Expression levels of Wnt family members (Wnt1, Wnt2, Wnt3a, Wnt4, Wnt5a, Wnt7a, and Wnt9a) were examined by real-time PCR and immunohistochemistry in tumor and normal tissue from removed kidneys. Results: Wnt1 and Wnt5a were up-regulated in clear cell RCC being their relative expression 2.4.103 (Wnt1) and 4.102 (Wnt5a) times higher in renal tumor tissue than in normal tissue. One-way ANOVA test showed Wnt3a and Wnt4 as the best protein markers to distinguish clear cell RCC (F=3.95, p=0.010 and F=3.05, p=0.029, respectively). Wnt1 and Wnt7a were over-expressed in those cases which had undergone nefrectomy (Mann-Whitney U test p=0.065 and p=0.056 respectively). Finally, Wnt2 protein level was associated with those patients with high risk prognosis (Kruskal-Wallis test p=0.001). Conclusions: Our results indicate that Wnt3a and Wnt4 are potentially useful immunohistochemical markers for the differential diagnosis between clear cell RCC and other subtypes of RCC and also suggest a role for Wnt2 as a high risk prognosis marker.
Molecular expression profiling and pathway analysis in human renal cell carcinoma.
Authors: Medina Villaamil Vanessa , Anido Urbano , Aparicio Gallego Guadalupe , Quindós Varela Maria , Santamarina Cainzos Isabel , Valladares Ayerbes Manuel , Antón Aparicio Luis M. 
Published: March 2020

e15079 Background: Many studies have demonstrated genetic and environmental factors lead to renal cell carcinoma (RCC) occurring during a protracted period of tumorigenesis. It seemed suitable identify and characterize potential molecular markers appearing during of tumorigenesis which might provide rapid and effective possibilities for early detection of RCC. Methods: We assessed using quantitative real-time PCR (qPCR) the profile of 32 markers involved in the cascade of events leading to the formation and progression of RCC: invasiveness, angiogenesis and antiapoptotic mechanisms. RNA of quality was obtained in 90% of samples (N=80, 64/80 clear RCC, 8/80 papillary RCC and 8/80 chromophobe RCC) to carry out the study of gene expression. Nonparametric tests (Pearson's correlation coefficient test and Spearman's rho test, Kruskal — Wallis and Mann — Whitney) and Bonferroni post-hoc test were applied for statistical data analysis. Additionally, a knowledgebase of biological pathways, Reactome, was used to superimpose our quantitative expression data. Results: Statistical analysis comparing medians and means showed the following candidates as the best gene predictors related to different pathological variables (histological type, number of involved nodes, renal pelvis invasion, lymphatic vessels invasion and rupture of the renal capsule): Hif1-α (p<.001), Hif1-β (p=.035), DLL1 (p=0.012), DLL3 (p<.001), c-Kit (p=.002), PDGFR-β (p=.002), PDGFR-α (p=0.026), Bax-β (p=.005), Survivin (p=.028), Notch1 (p=.006), Notch2 (p=.007), Notch3 (p=.016), Notch4 (p=.005), EGFR (p=.029), Glut3 (p=.026), Glut5 (p=.036) and FH (p=.018). Analysis of these genes expression profiles in Reactome tool revealed those cellular pathways over-represented in our RCC cohort, among others, Extrinsic Pathway for Apoptosis and Double-Strand Break Repair (100 and 95% matching in our data, respectively). Conclusions: Our study highlights the reasons to deepen in the knowledge of pathways components and their associations with the underlying pathology characteristics in order to understand the molecular pathology of a tumor and how that influences its biologic behavior. More detailed studies of these pathways are in progress.
Effect of combination of systemic therapy and local therapy with cryoablation on outcome in metastatic renal cell cancer (mRCC): An extended follow-up report.
Authors: Vankayala Hema M. , Litrup Peter , Heilbrun Lance K. , Dickow Brenda , Bang Hyun J , Smith Daryn W. , Adam Barbara , Vaishampayan Ulka N. 
Published: March 2020

e15081 Background: Resection of metastasis in renal cancer (mRCC) yields 5-year survival rates of 20% to 30%. Yet most patients (pts) poor surgical candidates or have unresectable disease. Percutaneous cryoablation is a minimally invasive procedure employed for local therapy of metastatic foci, but its role in inducing long term remissions in combination with systemic therapy is unknown. Methods: Following IRB approval and HIPAA compliance, a retrospective review of records for pts receiving cryotherapy and systemic targeted therapy from 2004-2007 at Karmanos Cancer Institute was performed to enable a minimum follow up of 3 years. OS was estimated using the Kaplan-Meier methodology. Results: Of the 27 patients identified 85% were male, 88% Caucasian, and 77% had clear cell histology. 2 pts had sarcomatoid mRCC. All patients had prior nephrectomy. 24 patients had multiple metastatic sites: 9 with 2 sites, 8 with 3 sites and 7 with ≥ 4 sites. 15%, 52%, 11%, and 22% had favorable, intermediate, poor, and indeterminate MSKCC risk score, respectively. Systemic therapy was interrupted for at least 1 week prior to and after cryotherapy and resumed after complete healing. One major complication of nerve paresis was noted from lumbar paravertebral mass cryotherapy. Median number of ablations was 2 (range 1-4). Of the 60 total ablations 13%, 28%, 27%, 17%, and 15% were renal bed, visceral, soft tissue, bone, and lymph nodes respectively. The median OS from diagnosis of metastatic disease was 49.6 months (95% confidence interval: 21.2- 54.9 months).The 2 yr OS rate is 90% (95% CI: 78-100%) and 5 yr OS rate is 68% (49-87%). 8 patients (30%) are alive to date. Conclusions: The strategy of combining systemic therapy and local control of metastasis with cryoablation had favorable impact on OS in mRCC even after longer follow up. Cryoabalation is a minimally invasive, well tolerated technique, applicable to the majority of mRCC patients. Prospective investigation or case-control studies to evaluate the incorporation of cryoabalation with targeted systemic therapy in advanced RCC is warranted.
The association between the treatment-induced hypertension (Htn) and response to neoadjuvant sunitinib in renal cell carcinoma (RCC).
Authors: Maiti Baidehi , Wood Laura S. , Elson Paul , Garcia Jorge A. , Dreicer Robert , Campbell Steven C. , Rini Brian I. 
Published: March 2020

e15095 Background: Prior studies have shown that development of htn, which is an on-target side effect of VEGF inhibition, is a potential biomarker for response to sunitinib in patients with metastatic RCC. The association of htn with response to neoadjuvant sunitinib was evaluated from a completed phase II trial. Methods: Patients with initially unresectable RCC were treated with sunitinib 50 mg daily until surgical eligibility or disease progression / toxicity. Htn was defined as SBP >=140mm and/or DBP >= 90mm while on sunitinib. Fisher’s exact test was used to assess associations between htn and clinical outcome. Results: Twenty-nine patients with unresectable RCC (72% male; 76% clear cell histology; median age 61 years (range 37-80)) were enrolled. One patient withdrew consent and was excluded from subsequent analysis. Overall, 78% of patients had primary tumor shrinkage, 57% became eligible for surgery based on primary tumor change in the opinion of the treating urologic surgeon, 50% underwent surgery and 57% developed htn. Patients who had primary tumor shrinkage had a non-significantly higher incidence of htn compared to patients who did not have primary tumor shrinkage (77% vs. 50%; p=0.31). Patients who became surgically resectable after sunitinib, however, had significantly more htn than patients who did not attain eligibility for surgery (88% vs. 45% p=0.03). Similar results were seen when the analysis was restricted to patients with clear cell histology tumors (n=20, p=1.0 and 0.06 respectively). Conclusions: There is a significant positive association between the incidence of htn and the ability of neoadjuvant sunitinib to affect surgical eligibility in patients with unresectable RCC.
Real-world treatment profile for patients with tuberous sclerosis complex related angiomyolipoma: A U.S. Healthcare Claims Database study.
Authors: Sun Peter , Liu Zhimei , Kohrman Michael , Bissler John 
Published: March 2020

e15096 Background: Angiomyolipoma (AML) is a common benign neoplasm associated with tuberous sclerosis complex (TSC). The objective of this study is to examine the treatment profile for patients with TSC related AML in a real world setting. Methods: A retrospective cohort study was performed using a large US commercial healthcare claims database. Patients with a TSC claim (ICD-9CM: 759.5X) and an AML claim (ICD-9CM: 223.0X) between 2000 and 2009 and with continuous 12-month health plan enrollment after their first AML claim were included into the study. The utilization rates of thirty two medication groups, eight procedure categories, five service places and fifteen provider types were assessed and ranked respectively for the year before first AML claim and the year after the first AML claim. Repeated measures analysis was used to compare these utilization rates between the last pre-AML year and the first post-AML year. Results: The study included 180 patients with a mean age of 28.2 years on their first AML claims, and 67.8% were females. During the first post-AML year, the top five medication groups were central nervous system medications (59.4%), anti-infective agents (50.6%), hormones & synthetic substance (22.8%), cardiovascular agents (18.9%), and autonomic drugs (17.8%); the most commonly used outpatient procedures were evaluation & management procedures (99.4%), anesthesia procedures (99.4%), surgical procedures (72.8%), radiology procedures (96.1%), and medicine procedures (100.0%). More patients consume the following care in the first post-AML year than in the last pre-AML year: anti-infective agents (50.6% vs. 35.0%, p<0.05), surgical procedures (72.8% vs. 60.6%, p<0.05), emergency rooms care (31.1% vs. 18.3%, p<0.05), urologists’ care (38.9% vs. 16.1%, p<0.05), nephrologists’ care (22.3% vs. 11.7%, p<0.05). Conclusions: In a real world setting and among TSC patients with AML, treatment profile changed after the first observed AML diagnosis. Further research is needed to examine the impact of these changes on economic and clinical outcomes of healthcare for patients with TSC related AML.
Post-prostatectomy PSA slope (ProsVue) in Gleason score ≥7 disease
Authors: Moul Judd W. , Lilja Hans , Semmes Oliver John , Vessella Robert , McDermed Jonathan E. , Sarno Mark J. , Klem Robert E. 
Published: March 2020

e15113 Background: A case-cohort designed multicenter clinical study addressed the prognostic value of the linear slope of PSA in 304 men after radical prostatectomy (RP) – 64 with clinical recurrence and 240 with stable disease. PSA was measured with Nucleic Acid Detection Immunoassay (NADiA) technology having a limit of quantification of 0.00065 ng (0.65 pg) per mL. Least-squares linear PSA slope (ProsVue) was calculated using 3 serum samples drawn 1.5-20 months (mo) post-RP. Multivariate Cox proportional hazards regression analysis showed that a ProsVue cutpoint of ≤2.0 pg/mL/mo was an independent prognostic factor for identifying men at reduced risk for recurrence along with clinical evaluation (HR=9.824). Of traditional risk factors – pre-RP PSA, Gleason score (GS) and pathologic stage, only GS was an independent prognostic factor (HR=5.3). This study tested the prognostic performance of ProsVue in a 164-man subset with pathologic GS ≥7. Methods: Recurrence was documented by positive imaging, positive biopsy or prostate cancer death. The same ProsVue cutpoint dichotomized men “at reduced” or “not at reduced” recurrence risk compared to clinically recurrent or stable disease status. Uni- and multivariate Cox proportional hazards regression were employed. Results: Median age, pre-RP PSA and percent tumor volume in the subset were 62.6, 7.2 ng/mL, and 20%. Distributions of GS 7, 8, 9 were 76.8%, 14.6% and 8.5%, respectively. Pathologic stages were T0-T2, T3a, T3b and T4 in 41%, 57%, 29% and 7% of men, respectively. Median follow-up in stable and recurrent groups was 10.8 and 4.8 yr. The table compares results in the full cohort and the GS ≥7 subgroup. Conclusions: ProsVue prognostic performance is maintained with GS ≥7. Performance parameters, especially the multivariate hazard ratio (HR) are minimally attenuated vs. the full case-cohort. [Table: see text]