Multivariate Cox Hazard Regression Analysis Research Articles

Overexpression of EWSR1 (Ewing sarcoma breakpoint region 1/EWS RNA binding protein 1) predicts poor survival in patients with hepatocellular carcinoma

ABSTRACT Hepatocellular carcinoma (HCC) is one of the most prevalent malignant neoplasms with high relapse and mortality rate. It is of great importance to identify novel and effective molecular markers to predict prognosis for the treatment of HCC. The Ewing sarcoma breakpoint region 1 (EWSR1) gene is well known to fuse with various partner genes and involved in promoting the development of multiple sarcomas, especially the Ewing sarcoma family of tumors. Nevertheless, seldom studies have focused on the role of EWSR1 in cancers of epithelial origin, let alone in HCC. In the current study, the transcriptional and clinical data of EWSR1 in HCC patients were obtained from TCGA and GEO databases, as well as 124 cases from the department of Pathology of Sichuan Jianyang People’s Hospital. Kaplan-Meier and Cox regression analysis were used to assess patient prognosis. EWSR1 mRNA levels were significantly upregulated in HCC tissues than in normal liver tissues (P < 0.001). The TCGA database analysis showed upregulation of EWSR1 was associated with histological grade, pathologic T stage and death, in addition to that, the T staging, N staging, TNM staging, Ki67, AFP expression were extremely higher in the EWSR1 over-expression group in our cohort. Univariate and multivariate Cox hazard regression analysis results revealed that EWSR1 was an independent prognostic factor for OS in HCC, and bioinformatics analysis showed RNA splicing process represented the major function and pathway. In conclusion, our data showed EWSR1 could serve as a novel promising prognostic biomarker for HCC patients. Abbreviations: AFP, Alpha-fetoprotein; CCL14, C-C motif chemokine ligand 14; CK19, Cytokeratin 19; CI, coefficient interval; COL1A1, Collagen 1A1; DFS, Disease-free Survival; EWSR1, Ewing Sarcoma breakpoint region 1/EWS RNA binding protein 1; FLI1, Friend leukemia virus integration 1; GEO, Gene Expression Omnibus; GO, Gene Ontology; HCC, Hepatocellular carcinoma; HR, Hazard ratio; KEGG, Kyoto Encyclopedia of Genes and Genomes; mRNA, messenger Ribonucleic Acid; N, nodule; OS, Overall survival; PPI, Protein-Protein Interaction analysis; RNA, Ribonucleic Acid; SD, Standard Deviation; TCGA, The Cancer Genome Atlas; T, tumor; TNM, tumor-nodule-metastasis.

Genetic variants in long non-coding RNAs UCA1 and NEAT1 were associated with the prognosis of oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) is known for its high incidence, death rate, and relatively low 5-year survival. Long non-coding RNAs (lncRNAs) have been shown to play a significant role in cancerization and cancer progression. However, research on the association of polymorphisms in these lncRNAs with the prognosis of OSCC is lacking. Fifteen functional single-nucleotide polymorphisms (SNPs) in seven lncRNAs were selected to explore the relationship between these lncRNA SNPs and the prognosis among 209 OSCC patients. Kaplan–Meier analysis and Cox proportional hazards regression models were used to examine the associations. Further functional exploration of significant SNPs was done by eQTL analysis. Using multivariate Cox hazards regression analysis, a predictive role of NEAT1 rs3741384 GG and UCA1 rs7255437 TC+TT in a worse prognosis of OSCC was identified. In addition, a marked increased risk of death was observed with an increasing number of unfavourable genotypes (NUG). The NUG was then incorporated with clinical variables in the receiver operating characteristic curve, and the results indicated a potential role of the NUG in predicting OSCC patient risk of death (area under the curve increase from 0.616 to 0.703). In conclusion, the study findings indicate that genetic variants rs3741384 in NEAT and rs7255437 in UCA1 may influence the survival of OSCC patients.

Negative first follow-up prostate biopsy on active surveillance is associated with decreased risk of upgrading, suspicion of progression and converting to active treatment.

To determine the risk of disease progression and conversion to active treatment following a negative biopsy while on active surveillance (AS) for prostate cancer (PCa). Men on an AS programme at a single tertiary hospital (London, UK) between 2003 and 2018 with confirmed low-intermediate-risk PCa, Gleason Grade Group <3, clinical stage <T3 and a diagnostic prostate-specific antigen (PSA) level of <20ng/mL. This cohort included men diagnosed by transrectal ultrasonography guided (12-14 cores) or transperineal (median 32 cores) biopsy. Multivariate Cox hazards regression analysis was undertaken to determine (i) risk of upgrading, (ii) clinical or radiological suspicion of disease progression, and (iii) transitioning to active treatment. Suspicion of disease progression was defined as any biopsy upgrading, >30% positive cores, magnetic resonance imaging (MRI) Likert score >3/T3 or PSA level of >20ng/mL. Conversion to treatment included radical or hormonal treatment. Among the 460 eligible patients, 23% had negative follow-up biopsy findings. The median follow-up was 62months, with one to two repeat biopsies and two MRIs per patient during that period. Negative biopsy findings at first repeat biopsy were associated with decreased risk of converting to active treatment (hazard ration [HR] 0.18, 95% confidence interval [CI] 0.09-0.37; P<0.001), suspicion of disease progression (HR 0.56, 95% CI: 0.34-0.94; P=0.029), and upgrading (HR 0.48, 95% CI 0.23-0.99; P=0.047). Data are limited by fewer men with multiple follow-up biopsies. A negative biopsy finding at the first scheduled follow-up biopsy among men on AS for PCa was strongly associated with decreased risk of subsequent upgrading, clinical or radiological suspicion of disease progression, and conversion to active treatment. A less intense surveillance protocol should be considered for this cohort of patients.

Prognostic Threshold for Circulating Tumor Cells in Patients With Pancreatic and Midgut Neuroendocrine Tumors.

Circulating tumor cells (CTCs) are detectable in patients with neuroendocrine tumors (NETs) and are accurate prognostic markers although the optimum threshold has not been defined. This work aims to define optimal prognostic CTC thresholds in PanNET and midgut NETs. CellSearch was used to enumerate CTCs in 199 patients with metastatic pancreatic (PanNET) (90) or midgut NETs (109). Patients were followed for progression-free survival (PFS) and overall survival (OS) for a minimum of 3 years or until death. The area under the receiver operating characteristic curve (AUROC) for progression at 12 months in PanNETs and midgut NETs identified the optimal CTC threshold as 1 or greater and 2 or greater, respectively. In multivariate logistic regression analysis, these thresholds were predictive for 12-month progression with an odds ratio (OR) of 6.69 (P < .01) for PanNETs and 5.88 (P < .003) for midgut NETs. The same thresholds were found to be optimal for predicting death at 36 months, with an OR of 2.87 (P < .03) and 5.09 (P < .005) for PanNETs and midgut NETs, respectively. In multivariate Cox hazard regression analysis for PFS in PanNETs, 1 or greater CTC had a hazard ratio (HR) of 2.6 (P < .01), whereas 2 or greater CTCs had an HR of 2.25 (P < .01) in midgut NETs. In multivariate analysis OS in PanNETs, 1 or greater CTCs had an HR of 3.16 (P < .01) and in midgut NETs, 2 or greater CTCs had an HR of 1.73 (P < .06). The optimal CTC threshold to predict PFS and OS in metastatic PanNETs and midgut NETs is 1 and 2, respectively. These thresholds can be used to stratify patients in clinical practice and clinical trials.

Prognostic impact of right ventricular overload in patients with acute coronary syndrome

Abstract Background Right ventricular (RV) overload is associated with adverse outcome in patients with chronic heart failure. However, its prognostic value in acute coronary syndrome (ACS) patients remains unknown. Purpose The purpose of this study was to investigate the prevalence and prognostic impact of right ventricular overload in ACS patients. Methods We studied 2797 ACS patients from Mie ACS registry, a prospective and multicenter registry in Japan. They were divided into 4 subgroups according to the severity of RV overload and the extent of Left Ventricle Ejection Fraction (LVEF) assessed by echocardiography before hospital discharge. High RV overload was defined as trans-tricuspid pressure gradient (TRPG) ≥40mmHg and preserved LVEF was defined as ≥50%. The primary outcome was defined as 2-year all-cause mortality. Median follow up duration was 730 days (1–2215 days). Results High RV overload was detected in 76 patients (2.7%). In basic patients characteristics, high RV overload patients were significantly older and higher killip classification than low RV overload patients (P&amp;lt;0.01, respectively). Laboratory data in high RV overload patients showed lower hemoglobin level and higher serum creatinine level than those in low RV overload patients (P&amp;lt;0.01, respectively). Echocardiographic findings in high RV overload represented lower LVEF, higher rate of moderate or severe mitral regurgitation and left atrial enlargement than those in low RV overload patients (P&amp;lt;0.01, respectively). During the follow-up periods (median 730 days), 260 (9.3%) patients experienced all-cause death. Multivariate cox hazard regression analysis for all-cause mortality demonstrated that high RV overload was an independent poor prognostic factor in the entire study population. Among patients with preserved LVEF, high RV overload resulted in an increased risk of all-cause mortality compared to low RV overload (P&amp;lt;0.0001). Conclusion In ACS patients, high RV overload strongly contributes to worsening of prognosis regardless of the extent of LVEF. Kaplan-Meier survival curve Funding Acknowledgement Type of funding source: None

Integrated Analysis of a Risk Score System Predicting Prognosis and a ceRNA Network for Differentially Expressed lncRNAs in Multiple Myeloma.

Long non-coding RNAs (lncRNAs) are non-protein-coding RNAs longer than 200 nucleotides. Accumulating evidence demonstrates that lncRNA is a potential biomarker for cancer diagnosis and prognosis. However, there are no prognostic biomarkers and lncRNA models for multiple myeloma (MM). Hence, it is necessary to screen novel lncRNA that can potentially participate in the initiation and progression of MM and consequently construct a risk score system for the disease. Raw microarray datasets were obtained from the Gene Expression Omnibus website. Weighted gene co-expression network analysis and principal component analysis identified 12 lncRNAs of interest. Then, univariate, least absolute shrinkage and selection operator Cox regression and multivariate Cox hazard regression analysis identified two lncRNAs (LINC00996 and LINC00525) that were formulated to construct a risk score system to predict survival. Receiver operating characteristic analysis certificated the superior performance in predicting 3-year overall survival (area under the curve = 0.829). The similar prognostic values of the two-lncRNA signature were also observed in the tested The Cancer Genome Atlas dataset. Furthermore, two other lncRNAs (LINC00324 and LINC01128) were differentially expressed between CD138+ plasma cells from normal donors and MM patients and were verified to be associated with cancer stage in the Gene Expression Omnibus dataset. A lncRNA-mediated competing endogenous RNA network, including 2 lncRNAs, 12 mitochondrial RNAs, and 103 target messenger RNAs, was constructed. In conclusion, we developed a two-lncRNA expression signature to predict the prognosis of MM and constructed a key lncRNA-based competing endogenous RNA network in MM. These lncRNAs were associated with survival and are probably involved in the occurrence and progression of MM.

Triglyceride-glucose index predicts adverse cardiovascular events in patients with diabetes and acute coronary syndrome

BackgroundThe triglyceride-glucose index (TyG index) has been regarded as a reliable alternative marker of insulin resistance and an independent predictor of cardiovascular outcomes. Whether the TyG index predicts adverse cardiovascular events in patients with diabetes and acute coronary syndrome (ACS) remains uncertain. The aim of this study was to investigate the prognostic value of the TyG index in patients with diabetes and ACS.MethodsA total of 2531 consecutive patients with diabetes who underwent coronary angiography for ACS were enrolled in this study. Patients were divided into tertiles according to their TyG index. The primary outcomes included the occurrence of major adverse cardiovascular events (MACEs), defined as all-cause death, non-fatal myocardial infarction and non-fatal stroke. The TyG index was calculated as the ln (fasting triglyceride level [mg/dL] × fasting glucose level [mg/dL]/2).ResultsThe incidence of MACE increased with TyG index tertiles at a 3-year follow-up. The Kaplan–Meier curves showed significant differences in event-free survival rates among TyG index tertiles (P = 0.005). Multivariate Cox hazards regression analysis revealed that the TyG index was an independent predictor of MACE (95% CI 1.201–1.746; P < 0.001). The optimal TyG index cut-off for predicting MACE was 9.323 (sensitivity 46.0%; specificity 63.6%; area under the curve 0.560; P = 0.001). Furthermore, adding the TyG index to the prognostic model for MACE improved the C-statistic value (P = 0.010), the integrated discrimination improvement value (P = 0.001) and the net reclassification improvement value (P = 0.019).ConclusionsThe TyG index predicts future MACE in patients with diabetes and ACS independently of known cardiovascular risk factors, suggesting that the TyG index may be a useful marker for risk stratification and prognosis in patients with diabetes and ACS.

Clinicopathologic Features and Survival Outcomes of Signet Ring Cell Carcinoma of the Appendix: An Analysis of the Surveillance, Epidemiology, and End Results Database.

Background and objectiveSignet ring cell carcinoma of the appendix (SRCCA) is an exceedingly rare tumor, and very limited data are available regarding its characteristics and survival probabilities. Our objective in this study was to utilize the Surveillance, Epidemiology, and End Results (SEER) database to explore the patient and tumor characteristics and to characterize the three- and five-year cancer-specific survival (CSS) probabilities of SRCCA.MethodsPatients with SRCCA diagnosed between 2000 and 2015 were analyzed using the SEER database. The three- and five-year CSS probabilities were estimated by the Kaplan-Meier method, and the groups were compared using log-rank comparisons and multivariable Cox hazard regression analysis.Results A total of 527 patients were identified. The median age of the participants at diagnosis was 56 years, with a majority of them being female and white. Histologically, 60% of the tumors were high grade, and 61.3 % of the tumors were found to be metastatic on presentation. Three- and five-year CSS probabilities were 39% and 18.4%, respectively, and median survival was 26 months. Best survival outcomes were noted in males (five-year CSS: 25.4%, p=0.027), unmarried patients (five-year CSS: 19.1%, p=0.042), tumors <2 cm in size (five-year CSS: 50.5%, p<0.001), and low-grade tumors (five-year CSS: 44.8%, p<0.001). Subtotal colectomy yielded better three- and five-year CSS probabilities compared to no surgery and partial colectomy (48.5% and 26.5%, respectively, p<0.001). On the multivariate analysis, it was found that age and stages T4, N1, and M1 were associated with an increased risk of mortality, while surgery, regardless of the extent, was a protective factor.Conclusion SRCCA is a rare tumor with a high prevalence among old-aged white females. This tumor is usually diagnosed in an advanced stage and has a dismal prognosis. Surgical intervention, regardless of the extent, showed better survival probabilities compared to no surgery.

Abstract B126: The Will Rogers phenomenon in breast cancer: The AJCC 8th Ed. and the importance of caution in the interpretation of outcomes differences for overall population and race-specific cohorts

Abstract Purpose: To assess whether the Will Roger’s phenomenon [WRP] exists with the move from the AJCC 7th to AJCC 8th edition in Breast Cancer staging and if racial differences are manifested in the expression of the WRP. Methods: A retrospective analysis of 300 women diagnosed with breast cancer between 2007 and 2017 at an academic medical center was performed. Pearson’s square test was used to compare the proportional differences between the anatomic staging system represented by the 7th edition and the prognostic staging of the 8th edition among Caucasian [C] and African-American [AA] women. Kaplan- Meier analysis was used to estimate overall survival [OS] and disease-free survival [DFS] between the races and compared using the log-rank test. Bi and multi-variate Cox hazard regression analyses were used to identify any racial factors associated with outcomes. The SPSS v.24.0 was used for all statistical analyses. Results: Our patient cohort included 30.3% C and 69.7% AA (median age, 62 y; range 34- 92 y). Stages I, II, III, and IV accounted for 46.2%, 26.3%, 23.1%, and 4.4% of C and 28.7%, 43.1%, 24.4%, and 3.8% of AA respectively, in anatomic staging (p= 0.043). In prognostic staging, 52.8%, 18.7%, 23%, and 5.5% were C while 35%, 17.2%, 43.5%, and 4.3 % were AA, respectively (p=0.011). A total number of 41 C (45.05 %) were upstaged compared to 100 AA (47.85 %) patients. Fifteen C patients (16.49 %) and 30 AA patients (14.35 %) were down-staged. Of the remainder, 35 C (38.46 %) and 79 AA (37.79 %) patients had their stages unchanged (P=0.859). The median follow-up duration for this cohort was 58 months (range 4- 235 months). The AA patients showed better stage -by- stage 5- year OS rates using 8th edition compared to the 7th edition, suggesting a manifestation of the WRP. Among the C patients, those who were stage IIIA in the 7th edition but became stage IB in the 8th had a better prognosis than stages IIA and IIB in the 8th edition (p=0.000). For AA patients, stage IIIA, IIIB, IIIC, and IV all demonstrated better prognoses in the 8th edition when compared to the 7th edition (p=0.000). In terms of DFS, the 8th edition’s clinical staging showed complex results (p=0.176) compared to DFS estimated using the 7th’s anatomic staging system (p=0.004). For C patients, stages IA, IB, IIB, and IIIC all recorded better DFS when using the 8th edition while for AA patients, only those with stages IB and IIIC showed better DFS in the 8th edition compared to the 7th. Conclusion: Our analyses suggest that the WRP exists in the move from the AJCC 7thto the 8th edition in breast cancer staging in both C and AA patients. However, there was significant variability between the races in the extent of its manifestation. We suggest that caution needs to be exercised when results are compared across staging systems to account for the WRP in the interpretation of the data. Citation Format: Mary R Nittala, Eswar K Mundra, SatyaSeelan Packianathan, Divyang Mehta, William C Woods, Shawn Mckinney, Barbara S Craft, Srinivasan Vijayakumar. The Will Rogers phenomenon in breast cancer: The AJCC 8th Ed. and the importance of caution in the interpretation of outcomes differences for overall population and race-specific cohorts [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr B126.

Perioperative Continuous Femoral Nerve Block Reduces Postoperative Cognitive Dysfunction of High-Risk Patients with Femoral Neck Fracture: Evidence from a Retrospective Propensity-Matched Study.

BackgroundElderly patients often suffer from postoperative cognitive impairment which increases mortality, morbidity, and the economic burden. However, how continuous femoral nerve block (cFNB) influence the incidence of postoperative cognitive dysfunction (POCD) has never been reported. This study tried to explore how cFNB affects the incidence of POCD among low-risk and high-risk patients with femoral neck fractures.Material/MethodsWe conducted a retrospective propensity score-matched study and allocated matched patients (n=172) with femoral neck fractures into the cFNB group (n=86) and the control group (n=86). Demographical and clinical data were collected and compared, including the visual analog scale (VAS) score, the morphine consumption, and the POCD incidence. Subgroup analysis of high-risk patients (Mini-Cog score ≤2) and low-risk patients (Mini-Cog score ≥3) was also carried out.ResultsAfter matching, baseline characteristics of 2 groups were comparable between the 2 groups (all P>0.05). Compared with the control group, the cFNB group had significantly lower visual analog scale (VAS) score and morphine consumption in the postoperative 3 days (P<0.05). For high-risk patients, the Kaplan-Meier survival curve suggested that the incidence of POCD the cFNB group was significantly lower than the control group (P=0.005), without statistical difference for total or low-risk patients (P>0.05). Multivariate Cox hazard regression analysis showed that the adoption of cFNB conferred a protective effect on POCD (HR=0.556, 95% CI 0.316–0.981, P=0.043).ConclusionsFor patients undergoing femoral neck fracture surgery, perioperative cFNB administration is useful in decreasing the incidence of POCD, especially for high-risk patients with a Mini-Cog score equal to or less than 2 points.

Diffuse mesothelin expression leads to worse prognosis through enhanced cellular proliferation in colorectal cancer.

Mesothelin (MSLN) is a glycophosphatidylinositol (GPI)-linked cell surface protein that is highly expressed in several types of malignant tumor, including malignant pleural mesothelioma, ovarian cancer and pancreatic adenocarcinoma. Recently, a comprehensive immunohistochemical study using MN-1 monoclonal antibody identified a significant number of colorectal tumors in which MSLN was expressed. However, the clinicopathological profiles and survival of patients with MSLN-positive colorectal cancer have not been fully analyzed. In the current study, the expression of MSLN in 270 primary and 44 metastatic colorectal tumors was immunohistochemically analyzed to determine the clinical usefulness of MSLN immunohistochemistry and to identify potential candidates for future anti-MSLN therapy. In vitro experiments using colon cancer cell lines were performed to investigate the biological significance of MSLN expression in tumors. The results of univariate analyses identified a significant correlation between MSLN expression and females (P=0.0042). Furthermore, an inverse correlation between MSLN expression and solid/sheet-like proliferation (P=0.014) was also revealed. Additionally, overall survival was significantly shorter in patients with diffuse luminal/membranous expression of MSLN (P=0.018). Multivariable Cox hazards regression analysis revealed diffuse MSLN expression (hazard ratio, 2.26; 95% confidence interval, 1.04–4.91; P=0.039) as a potential risk factor. When comparing primary CRCs and the metastasis of each, a weakly positive correlation was identified for MSLN positivity (% positive cells; R=0.484; P<0.0001). The in vitro experiments revealed a positive role for MSLN in colon cancer cell proliferation. Thus, MSLN immunohistochemistry may be useful in the prognostication of patients with CRC. The results demonstrated that significant numbers of patients with MSLN-positive CRC exhibiting metastasis could be targeted by anti-MSLN therapies.

Impact of Baseline LDL-C and Lp(a) Elevation on Coronary Revascularization in Patients with Acute Coronary Syndrome One-Year after First Percutaneous Coronary Intervention

Objective: The aim of this study was to investigate the effect of Lipoprotein-a [Lp(a)] on Coronary Revascularizaton (CR) on one year follow up in patients with Acute Coronary Syndrome (ACS) after the first Percutaneous Coronary Intervention (PCI). Method: A retrospective study was designed. A total of 475 patients that underwent their first PCI treatment due to ACS between January 2016 and December 2017 were recruited and followed for one year at the Zhongda Hospital, China. The clinical end point after first PCI was prevalence of Major Adverse Cardiovascular Events (MACE) including nonfatal Myocardial Infarction (MI), cardiovascular death, ischemic stroke and Coronary Revascularization (CR). According to the cut point of Lp(a), participants were divided into low Lp(a) subgroup (Lp(a) mg/L) and high Lp(a) subgroup (Lp(a) ≥ 300 mg/L). Furthermore, based on baseline Low Density Lipoprotein Cholesterol (LDL-C) level, participants were divided into low LDL-C (LDL-C mmol/L) and high LDL-C (LDL-C ≥ 1.8 mmol/L) subgroups. Results: The number of prevalence of CR was higher with elevated serum Lp(a) in both low LDL-C subgroup and high LDL-C subgroup, and was significantly different in both the low LDL-C subgroup and high LDL-C subgroup (p = 0.009 and p = 0.006, respectively). Multivariate Cox-hazard regression analysis for CR showed increase in serum LDL-C and Lp(a) increased prevalence of CR by 1.514 and 1.002 folds respectively. Furthermore, Kaplan-Meier cumulative survival curves showed that increased prevalence of CR within one year after first PCI in patients with high Lp(a) [log rank p = 0.000]. Conclusion: Baseline increase of serum LDL-C and Lp(a) significantly increases the prevalence of CR after first PCI within one year. It indicates that after PCI treatment, in patient with serum LDL-C and Lp(a) elevation, treatment with high-dose statin therapy or PCSK9 inhibitors may alleviate the adverse effects imposed by Lp(a) elevation.

Comparison of mid-term outcomes of endovascular repair and medical management in patients with acute uncomplicated type B aortic dissection

ObjectivesTo further assess the early and mid-term outcomes of thoracic endovascular aortic repair (TEVAR) in patients with acute uncomplicated type B aortic dissection (TBAD) compared with those receiving best medical treatment (BMT). MethodsBetween February 2008 and March 2018, 357 consecutive patients with acute uncomplicated TBAD were retrospectively analyzed. Among them, 191 patients underwent TEVAR, and 166 received BMT. After propensity score matching, we obtained 145 matched pairs for analysis. ResultsIn the matched population, the 30-day mortality between the TEVAR group and the BMT group showed no statistically significant difference, whereas the early adverse events rates in the TEVAR group were significantly greater than that of the BMT group (P = .003). Freedom from all-cause mortality in the TEVAR group was significantly greater than that of the BMT group (TEVAR: 91.9% at 5 years, BMT: 82.2% at 5 years, P = .028). Freedom from aortic-related mortality in the TEVAR group was significantly greater than that of the BMT group (TEVAR: 94.1% at 5 years, BMT: 86.1% at 5 years, P = .044). Multivariable Cox-hazard regression analysis demonstrated that the older age (hazard ratio [HR], 1.04; 95% confidence interval [CI], 1.01-1.08, P = .013), BMT (HR, 2.33; 95% CI, 1.08-5.05, P = .032), and the distance between the primary entry tear and the left subclavian artery <2.0 cm (HR, 2.30; 95% CI, 1.06-4.99, P = .035) were the significant risk factors for all-cause death. Given death as a competing factor, the cumulative incidence of rupture in the BMT group was significantly greater than that of the TEVAR group (BMT: 13.7% at 5 years, TEVAR: 5.1% at 5 years, P = .024). ConclusionsDespite more complications in the early stage, TEVAR was associated with decreased risk of late death and had fewer late aortic ruptures compared with BMT in patients with acute uncomplicated TBAD. Therefore, TEVAR may be considered as the first option to improve the late outcomes in these patients.

Eliminating microscopic lymph node metastasis by performing pelvic lymph node dissection during radical prostatectomy for prostate cancer.

The oncological benefit of pelvic lymph node dissection (PLND) for prostate cancer (PCa) remains unclear. The therapeutic effect of PLND on the elimination of microscopic metastases during radical prostatectomy (RP) for PCa was examined in the current study. A total of 348 Japanese patients with high- or intermediate-risk PCa without lymph node metastasis, who underwent antegrade RP at the Kyushu Cancer Center (Fukuoka, Japan) between August 1998 and May 2013 were retrospectively analyzed. The patients were divided into the standard (obturator + internal iliac nodes) group and the expanded (standard + additional nodes) group according to the extent of PLND. Preoperative and postoperative characteristics were also analyzed to determine the factors associated with prostate-specific antigen (PSA) failure. Standard and expanded PLND were performed in 70.9% (247/348) and 29.1% (101/348) of cases, respectively. The results revealed that preoperative PSA levels were the only marked difference between the two groups. No differences were observed in the other preoperative and postoperative characteristics. Furthermore, the rate of PSA recurrence in each group did not differ to a statistically significant extent (P=0.3622). Reducing the area of dissection from expanded PLND to standard PLND significantly reduced the number of dissected lymph nodes (P<0.0001). Additionally, the PSA level, clinical tumor stage, Gleason score of the biopsy specimen, pathological tumor stage and extent of PLND were all associated with PSA recurrence, as determined via multivariate Cox hazards regression analysis (P=0.0177, P=0.0023, P=0.0027, P<0.0001 and P=0.0164, respectively). In high- and intermediate-risk patients without lymph node metastasis, a greater number of lymph nodes were dissected when the extent of dissection was greater. Furthermore, the extent of PLND was a significantly associated with PSA failure. The results indicated that PLND exerted a therapeutic effect by eliminating microscopic pelvic lymph node metastases that were not detected by routine pathological examinations.

The fate of aortic root and aortic regurgitation after supracoronary ascending aortic replacement for acute type A aortic dissection

BackgroundThe aim of this study was to evaluate the fate of the preserved aortic root after supracoronary aortic replacement for acute type A aortic dissection. MethodsBetween October 1999 and March 2018, 339 patients underwent supracoronary aortic replacement for acute type A aortic dissection at our institution. Late outcomes were evaluated, including overall survival, aortic-related death, and aortic root–related reoperation. The median follow-up was 3.7 years (1.4-8.4 years). ResultsOperative mortality was 46 patients (13.6%). The cumulative incidences at 5 years for aortic root–related reoperation, aortic-related death, and non–aortic related death were 2.5%, 14.5% and 12.4%, respectively. Multivariable Cox hazard regression analysis demonstrated greater sinus of Valsalva diameter and number of commissural detachments to be significant risk factors for a composite outcome consisting of aortic-related death or aortic root–related reoperation. Mixed-effects regression demonstrated that sinus of Valsalva diameter significantly increased with time (P < .001), and aortic regurgitation significantly worsened (P < .001). ConclusionsSinus of Valsalva diameter and commissural detachment were independent predictors of unfavorable outcomes after supracoronary aortic replacement. Close follow-up is particularly necessary for these patients, and aortic root replacement at the time of initial operation may lead to more favorable late outcomes.

P.482 Olfactory neurons as surrogate tissue to investigate disorders of the brain

To evaluate the association between impaired heart rate variability (HRV) and cardiovascular disease (CVD) in patients with type 2 diabetes (T2DM).A total of 655 patients with T2DM who underwent cardiovascular autonomic function testing were consecutively recruited and followed up prospectively. Time- and frequency-domain HRV were assessed for 5 min by beat-to-beat heart rate recording. We estimated the development of CVD events during a follow-up period.During a median follow-up of 7.8 years, 9.6% (n = 49) of patients developed CVD (10.6 per 1000 patient-years). The mean age and diabetes duration were 54.9 ± 8.6 years and 9.4 ± 7.3 years, respectively. Patients who had cardiovascular autonomic neuropathy (CAN) had decreased HRV compared with those with normal autonomic function. Multivariable cox hazard regression analysis revealed the lowest 10th percentile of the SD of the normal-to-normal interval (HR 2.62; 95% CI 1.30–5.31), total power (HR 2.81; 95% CI 1.37–5.79), low-frequency power (HR 2.68; 95% CI 1.28–5.59), and high-frequency power (HR 2.24; 95% CI 1.09–4.59) were significant predictors for developing CVD in patients with T2DM.Time- and frequency-domain measures of HRV independently predicted cardiovascular outcome in patients with T2DM.

Worse characteristics can predict survival effectively in bilateral primary breast cancer: A competing risk nomogram using the SEER database.

ObjectiveThere is limited information from population‐based cancer registries regarding prognostic features of bilateral primary breast cancer (BPBC).MethodsFemale patients diagnosed with BPBC between 2004 and 2014 were randomly divided into training (n = 7740) and validation (n = 2579) cohorts from the Surveillance, Epidemiology, and End Results Database. We proposed five various models. Multivariate Cox hazard regression and competing risk analysis were to explore prognosis factors in training cohort. Competing risk nomograms were constructed to combine significant prognostic factors to predict the 3‐year and the 5‐year survival of patients with BPBC. At last, in the validation cohort, the new score performance was evaluated with respect to the area under curve, concordance index, net reclassification index and calibration curve.ResultsWe found out that age, interval time, lymph nodes invasion, tumor size, tumor grade and estrogen receptor status were independent prognostic factors in both multivariate Cox hazard regression analysis and competing risk analysis. Concordance index in the model of the worse characteristics was 0.816 (95% CI: 0.791‐0.840), of the bilateral tumors was 0.819 (95% CI: 0.793‐0.844), of the worse tumor was 0.807 (0.782‐0.832), of the first tumor was 0.744 (0.728‐0.763) and of the second tumor was 0.778 (0.762‐0.794). Net reclassification index of the 3‐year and the 5‐year between them was 2.7% and −1.0%. The calibration curves showed high concordance between the nomogram prediction and actual observation.ConclusionThe prognosis of BPBC depended on bilateral tumors. The competing risk nomogram of the model of the worse characteristics may help clinicians predict survival simply and effectively. Metachronous bilateral breast cancer presented poorer survival than synchronous bilateral breast cancer.

Primary renal lymphoma: a population-based study in the United States, 1980\u20132013

Primary renal lymphoma (PRL) is a rare lymphoid malignancy with only a few cases reported in the literature. We performed a population-based study of PRL to determine its incidence, clinical characteristics and factors associated with survival using the Surveillance, Epidemiology, and End Results (SEER) database. We identified 723 patients with PRL. The most common histological subtype of PRL was diffuse large B-cell lymphoma (56.3%). The incidence and mortality rate of PRL was 0.053/100,000 person-years and 0.036/100,000 person-years, respectively. The incidence rate of PRL was increasing significantly with an annual percentage change (APC) of 3.45% (p < 0.001). The 1-year and 5-year relative survival (RS) rates of patients with PRL were 78% and 64%. The RS of patients diagnosed between 2000 to 2013 was better than that of patients diagnosed between 1980–1999. A multivariate Cox hazards regression analysis revealed that older age, male gender, diagnosis before 2000, advanced stage, not receiving surgical treatment, and DLBCL or T/NK cell lymphoma type were independent predictors of unfavorable survival.

Abnormally expressed circular RNAs as novel non-invasive biomarkers for hepatocellular carcinoma: A meta-analysis.

BACKGROUNDCircular RNAs (circRNAs) are a newly discovered class of endogenous non-coding RNAs that may have roles in cancer genesis and development. In the recent literature, dysregulated circRNAs have been extensively investigated in hepatocellular carcinoma (HCC). Whether or not circRNAs are of clinical value for the management of HCC has not been characterized.AIMTo meta-analyze the diagnostic and prognostic value of abnormally expressed circRNAs in HCC.METHODSEligible studies were sourced from PubMed, EMBASE, and CNKI online databases. Data on patients’ clinical characteristics, including diagnostic efficacy and overall survival, were extracted. The diagnostic and prognostic parameters were respectively synthesized using the bivariate meta-analysis model and multivariate Cox hazard regression analysis based on Stata 12.0. The trim and fill method was adopted to assess the possible effects from publication bias.RESULTSA total of 21 eligible studies were included. The pooled sensitivity, specificity, and area under the curve of abnormally expressed circRNAs in distinguishing HCC from non-cancer controls were 0.78 (95%CI: 0.69–0.85), 0.80 (95%CI: 0.74–0.86), and 0.86, respectively. Survival analyses showed that the down-regulated circRNA expression signature correlated perfectly with HCC survival [hazard ratio (HR) = 0.42, 95%CI: 0.19–0.91, P = 0.028; I2 = 92.7%, P = 0.000], whereas the HCC cases with high circRNA levels had significantly poorer prognoses than those of patients with low circRNA levels (HR = 2.22, 95%CI: 1.50–3.30, P = 0.000; I2 = 91%, P = 0.000). Moreover, abnormally expressed circRNAs were intimately associated with tumor size, differentiation grade, microvascular invasion, metastasis, TNM stage, and serum alpha fetal protein level in patients with HCC. Stratified analysis based on sample type, control source, and expression status also yielded robust results.CONCLUSIONAbnormally expressed circRNA signatures show immense potential as novel non-invasive biomarker(s) for HCC diagnosis and prognosis.

Current trend of worsening prognosis of prostate small cell carcinoma: A population-based study.

ObjectiveTo determine the accurate age‐adjusted incidence of prostate small cell carcinoma (SCC), update the clinical and pathological characteristics, as well as survival data of prostate SCC from Surveillance, Epidemiology, and End Results (SEER) datasets.MethodsA total of 260 patients with prostate SCC were selected from the SEER database of the National Cancer Institute between 2004 and 2015. Age‐adjusted incidence (AAI) rates, the observed and relative survival rates were evaluated over time by the SEER*Stat Software version 8.3.5. Overall survival (OS) rates that stratified by summary stage and treatment effects were evaluated by Kaplan‐Meier method. The significant differences were assessed in a log‐rank test. Univariate and multivariate cox hazard regression analysis were performed to determine independent predictors of OS.ResultsThe incidence of prostate SCC has increased over time. The average age of prostate SCC patients was 70.25 years. More than 90% of tumors were poorly differentiated or undifferentiated. The majority of prostate SCC (77.7%) was at stage IV. 49% of patients had lymph node metastases and 68% of patients presented distant metastases (Compared with 60.5% of patients with distant metastases between 1973‐2003). Interestingly only 23.5% patients had high level PSA (>10 ng/mL). 58.8% of patients underwent chemotherapy, 25.4% of patients were treated by surgery, and 31.9% of patients were treated by radiotherapy. The observed survival rates of 1‐year, 2‐year, and 5‐year were 42.1%, 22.1%, and 12.5%, respectively (Compared with 47.9%, 27.5%, and 14.3%, respectively, between 1973 and 2003). Chemotherapy prolonged the OS of patients with regional (distant) metastases from 3 months (2 months) to 12 months (9 months). Multivariate cox regression analysis showed age, race, and stage were independent prognostic factors for prostate SCC patients.ConclusionProstate SCC is a highly malignant cancer and our analysis of recent data has shown its incidence is increasing. Incidence rate of metastatic prostate SCC has increased and the survival rates have worsened in recent years. However, chemotherapy shows some survival benefit for prostate SCC patients with regional and distant metastasis over other treatment methods. Further work is needed to understand the reason prognosis of this type prostate cancer is worsening.