Cox Proportional Hazards Model Analysis Research Articles

Hepatitis B virus core antigen mutations predict post-operative prognosis of patients with primary hepatocellular carcinoma.

The aim of this study was to explore the relationship between hepatitis B virus (HBV) core antigen (HBc) mutations and the post-operative prognosis of HBV-related hepatocellular carcinoma (HCC). In total, 98 patients suffering from HBV-related HCC and treated with surgery were enrolled, with a 48 month follow-up. The preCore/Core region of the HBV genome from tumour tissue (TT) and paired adjacent non-tumour tissue (ANTT) of these patients was sequenced, and a phylogenetic tree was reconstructed. The correlations between the viral features and evolutionary divergence of preCore/Core amino acid sequences from 67 paired TTs and ANTTs were analysed. Cox proportional hazard model analysis was applied for post-operative hazard risk evaluation. Phylogenetic analysis revealed that all of the sequences were ascribed to genotype C. The evolutionary divergence of amino acid sequences from matched TTs and ANTTs was significantly negatively correlated with serum and intrahepatic HBV DNA levels. Multivariate analysis showed that the HBc E77 mutation was associated with shorter overall survival, and HBc S87 and P156 mutations were independent risk factors for relapse. Furthermore, in contrast to with patients without the S87 mutation, no correlation was observed between serum HBV DNA and intrahepatic HBV DNA in HCC patients with the S87 mutation. Analysis of the intrahepatic sequence may advance our understanding of viral status; thus, it is useful for prognosis prediction for HBV-related HCC.

The incidence, risk factors and in-hospital mortality of acute kidney injury in patients after abdominal aortic aneurysm repair surgery

BackgroundAcute kidney injury (AKI) is a severe complication associated with abdominal aortic aneurysm (AAA) repair. In this study, we evaluated the incidence, risk factors and in-hospital mortality of AKI in patients after the AAA repair surgery.MethodsA total of 314 Chinese AAA patients who underwent endovascular aneurysm repair (EVAR) or open aneurysm repair (OPEN) were enrolled in this study. AKI was diagnosed according to the 2012 KDIGO criteria. Logistic regression modeling was used to explore risk factors of AKI, while risk factors associated with in-hospital mortality in AKI patients were investigated using Cox proportional hazards model and Kaplan-Meier analysis, respectively. Multicollinearity analysis was performed to identify the collinearity between the variables before logistic regression analysis and Cox proportional hazards analysis.ResultsAmong 314 patients, 94 (29.9%) developed AKI after AAA repair surgery. Severity of AKI and ruptured AAA were independently associated with an increase in in-hospital mortality in AKI patients after AAA repair. Kaplan-Meier analysis identified severity of AKI as being negatively associated with hospital survival in AKI patients. Risk factors associated with AKI included cardiovascular disease (OR 3.169, 95% confidence interval (CI) 1.538 to 6.527, P = 0.002), decreased eGFR (OR 0.965, 95%CI 0.954 to 0.977, P < 0.001), ruptured AAA (OR 2.717, 95%CI 1.320 to 5.592, P = 0.007), renal artery involvement (OR 2.903, 95%CI 1.219 to 6.912, P = 0.016) and OPEN (OR 2.094, 95%CI 1.048 to 4.183, P = 0.036). Further subgroup analysis identified OPEN as an important risk factor of AKI in ruptured AAA patients but not in ruptured AAA patients. The incidence of AKI was significantly lower in EVAR than in OPEN (27.1% vs. 42.8%) and, similarly lower in nonruptured AAA than in ruptured AAA (26.2% vs. 48.1%).ConclusionOne-third of AAA patients developed AKI after repair surgery. Severity of AKI was associated with reduced survival rate in AAA patients who developed postoperative AKI. Decreased preoperative creatinine clearance, cardiovascular disease, ruptured AAA and OPEN were independent risk factors for postoperative AKI in all 314 AAA patients. Although a lower rate of incident AKI was observed in EVAR compared with OPEN, subgroup analysis of ruptured AAA versus nonruptured AAA showed that EVAR was an independent protective factor for AKI only in ruptured AAA patients but not in nonruptured AAA patients.

Glyoxalase 1 expression is associated with an unfavorable prognosis of oropharyngeal squamous cell carcinoma

BackgroundGlyoxalase 1 is a key enzyme in the detoxification of reactive metabolites such as methylglyoxal and induced Glyoxalase 1 expression has been demonstrated for several human malignancies. However, the regulation and clinical relevance of Glyoxalase 1 in the context of head and neck squamous cell carcinoma has not been addressed so far.MethodsArgpyrimidine modification as a surrogate for methylglyoxal accumulation and Glyoxalase 1 expression in tumor cells was assessed by immunohistochemical staining of tissue microarrays with specimens from oropharyngeal squamous cell carcinoma patients (n = 154). Prognostic values of distinct Glyoxalase 1 staining patterns were demonstrated by Kaplan-Meier, univariate and multivariate Cox proportional hazard model analysis. The impact of exogenous methylglyoxal or a Glyoxalase 1 inhibitor on the viability of two established tumor cell lines was monitored by a colony-forming assay in vitro.ResultsGlyoxalase 1 expression in tumor cells of oropharyngeal squamous cell carcinoma patients was positively correlated with the presence of Argpyrimidine modification and administration of exogenous methylglyoxal induced Glyoxalase 1 protein levels in FaDu and Cal27 cells in vitro. Cal27 cells with lower basal and methylglyoxal-induced Glyoxalase 1 expression were more sensitive to the cytotoxic effect at high methylgyoxal concentrations and both cell lines showed a decrease in colony formation with increasing amounts of a Glyoxalase 1 inhibitor. A high and nuclear Glyoxalase 1 staining was significantly correlated with shorter progression-free and disease-specific survival, and served as an independent risk factor for an unfavorable prognosis of oropharyngeal squamous cell carcinoma patients.ConclusionsInduced Glyoxalase 1 expression is a common feature in the pathogenesis of oropharyngeal squamous cell carcinoma and most likely represents an adaptive response to the accumulation of cytotoxic metabolites. Oropharyngeal squamous cell carcinoma patients with a high and nuclear Glyoxalase 1 staining pattern have a high risk for treatment failure, but might benefit from pharmacological targeting Glyoxalase 1 activity.

Incidence and Predictors of Pericardial Effusion After Chemoradiation Therapy for Locally Advanced Non-Small Cell Lung Cancer

Findings from Radiation Therapy Oncology Group (RTOG) 0617 suggested that collateral radiation to the heart may contribute to early death in patients receiving chemoradiation therapy for non-small cell lung cancer (NSCLC); however, reports of cardiac toxicity after thoracic radiation therapy (RT) remain limited. Because pericardial disease is the most common cardiac complication of thoracic RT, we investigated the incidence of and risk factors for pericardial effusion (PCE) in patients enrolled in a phase 2 prospective randomized study of intensity modulated RT versus proton therapy for locally advanced NSCLC. From July 2009 through April 2014, 201 patients were prospectively treated with proton beam therapy or intensity modulated RT to 60 to 74Gy with concurrent chemotherapy. The primary endpoint (grade ≥2 PCE) was diagnosed on review of follow-up images. Clinical characteristics and cardiac dose-volume parameters associated with PCE were identified via Cox proportional hazards modeling and recursive partitioning analysis of null Martingale residuals. Reproducibility was evaluated in a separate retrospective cohort of 301 patients. The cumulative incidence rates of PCE among patients in the trial were 31.4% at 1year and 45.4% at 2years, with a median time to PCE of 8.9months. Several cardiac dose-volume parameters (eg, V20 [volume receiving ≥20Gy] to V65 [volume receiving ≥65Gy]) predicted PCE, but heart volume receiving ≥35Gy (HV35) was the most strongly associated, with a cutoff volume of 10%.On multivariate analysis, HV35>10% independently predicted PCE (hazard ratio [HR], 2.14; P=.002), a finding that maintained reproducibility in the retrospective validation cohort. Other factors associated with PCE included receipt of adjuvant chemotherapy (HR, 2.82; P<.001) and prior cardiac disease (HR, 1.68; P=.020). PCE was common after RT for NSCLC, occurring in nearly half of patients even after moderate radiation doses to the heart. Adjuvant chemotherapy may increase the risk of PCE, and HV35>10% may identify patients at risk of development of this cardiac toxicity.

No improvement in metastatic bladder cancer health disparity over the last two decades.

e18076 Background: Bladder cancer (BCa) is one of the top ten most common cancers in the world. However, very few studies have reported on health disparities involving advanced BCa. Methods: Patients with metastatic BCa diagnosed between 1991 and 2014 were identified through the California Cancer Registry. Included in the analysis were age at diagnosis, sex, race/ethnicity, area-based socioeconomic status (SES), first course of treatment, and survival time. Predictors of treatment were identified using logistic regression, and cause-specific survival was analyzed using Cox regression. Results: A total of 3,073 cases of metastatic BCa were identified. Among these cases, 67.39% were male, and 32.61% were female. The race distribution was 74.78% non-Hispanic white (NHW), 6.25% non-Hispanic black (NHB), 12.46% Hispanic and 5.96% NH Asian/Pacific Islander (Asian/PI). A Cox proportional hazards model analysis showed that NHB were more likely to die from BCa. After adjustment for sex, age, and SES quintile, the hazard ratio of overall survival for NHB over NHW was 1.18 (p=0.214) during 1991-2002, but it increased to 1.24 (p=0.041) during 2003-2014. A smaller proportion of NH black patients survived two years after diagnosis (6.5% versus 14.4% NH white, 18.3% Hispanic, and 15.4% Asian/PI). Patients over age 65, female patients and those residing in all but the wealthiest census tracts were less likely to receive chemotherapy with or without local treatment. Patients diagnosed between 2003 and 2014 were 32% more likely to receive chemotherapy than those diagnosed between 1991 and 2002 (p&lt;.001). There was no improvement of overall survival in the most recent time period. Conclusions: There had been no improvement in this heath disparity or in overall survival over the last two decades. Non-Hispanic blacks and patients who were not treated with chemotherapy experienced poorer survival than other groups. [Table: see text]

Optimal thoracic radiation dose in limited stage small cell lung cancer.

8562 Background: Several studies have demonstrated improved overall survival in limited stage small cell lung cancer (LS-SCLC) patients (pts) with the addition of thoracic radiation therapy (RT) to chemotherapy. However, the optimal dose of thoracic RT when given daily, which is the most common practice pattern in the US, is yet to be firmly established. We analyzed outcomes associated with once-daily low dose (LD) RT relative to once-daily high dose (HD) RT for LS-SCLC in the National Cancer Data Base (NCDB). Methods: The NCDB was queried to capture pts with LS-SCLC treated with thoracic RT from 2004-2013. The cohort of pts that received 60 Gy (LD) was compared with the cohort that received RT ≥70 Gy (HD). The univariate (UV) association of overall survival (OS) was assessed using Cox proportional hazards models and log-rank tests. A multivariable (MV) Cox proportional hazard model and Kaplan-Meier (KM) analyses were performed to compare the LD vs. HD cohorts. Propensity score matching method was also implemented to reduce treatment selection bias. All analyses were performed using SAS Version 9.4. Results: A total of 5,159 pts (LD-3441; HD- 1718) were included in the analysis. Pt characteristics (LD/HD): median age 65/64 yrs; males 44/46%; whites 89/88%, academic centers 28/31%, Charlson-Deyo comorbidity score 0- 61%/64%; government insured 61/57%. 96% of pts in LD and 95% in HD cohorts had received chemotherapy. On MV analysis, no differences were found in OS between HD and LD RT(HR 0.98, p = 0.5), which was confirmed by KM analysis with 5-yr survival of 21% in LD vs 21.5% in HD (p = 0.8). On MV analysis of OS stratified by comorbidity score, LD was associated with significantly better survival compared to HD in pts with a comorbidity score of 1 and above (HR 0.87, p = 0.02). The LD group also had a better 5-yr survival than HD group in pts with higher comorbidity score (19% vs 14%, p = 0.01). No difference in survival was noted between the two cohorts for pts with no recorded comorbidities (HR 1.03, p = 0.6). Conclusions: In LS SCLC pts, survival was similar in pts who received daily RT of 60 Gy compared to those that received 70 Gy and above. In pts with worse performance status, those who received LD RT of 60 Gy had better survival.

Survival outcomes in extensive stage small cell lung cancer patients treated with thoracic radiation.

8565 Background: The benefit of consolidation thoracic radiation in extensive stage small cell lung cancer (E-SCLC) remains unclear. This study utilized the National Cancer Database (NCDB) to evaluate overall survival outcome (OS) for patients receiving chemotherapy (CT) alone for E-SCLC versus CT + thoracic radiation (TRT). Methods: The NCDB was queried to capture patients (pts) with stage E-SCLC from 2010-2013. Patients with brain metastases at diagnosis were excluded, as were patients receiving radiation prior to initiation of chemotherapy. Univariate association of OS was assessed using Cox proportional hazards models and log-rank tests. A multivariable Cox proportional hazard model and Kaplan-Meier analyses were performed to compare treatment with CT only to CT + TRT. Propensity score matching method was also implemented to reduce treatment selection bias. All analyses were performed using SAS Version 9.4. Results: A total of 14,367 (12,019 received CT, 2,348 received CT + TRT) pts were included in the analysis. Patient characteristics included a median age of 66 years; 66 years for pts receiving CT, and 63 for pts receiving CT + TRT (p &lt; 0.001). Male gender comprised 51% of pts; 52% in CT group versus 49% in CT + TRT (p &lt; 0.001). Charlson-Deyo comorbidity score was zero in 53% of all patients; 52% in the CT group versus 57% of CT + TRT group (p &lt; 0.001). In the CT + TRT group, the median total thoracic radiation dose was 45 Gy. On multivariate analysis, CT only was associated with an increased risk of death relative to CT+ TRT (HR 1.74 [1.65 – 1.84], p &lt; 0.001). 5 year OS was 7% vs. 2% for CT + TRT versus CT alone (p &lt; 0.001). On propensity matched analysis, CT + TRT was associated with better 5-year OS compared to CT alone (8% vs. 2%; p &lt; 0.001). On multivariate analysis of propensity matched samples, chemotherapy alone continued to be associated with worse survival (HR 1.76 [1.62 – 1.91], p &lt; 0.001). Conclusions: For E-SCLC, CT alone as standard of care is associated with worse survival relative to CT + TRT.

Overexpression of NIMA-related kinase 2 is associated with poor prognoses in malignant glioma.

Eleated expression of NIMA-related kinase 2 (NEK2) was frequently observed in a variety of malignant cancers, and it appears to be involved in the initiation, maintenance, progression, metastasis of cancer and is positively associated with poor prognosis. We sought to investigate NEK2 expression and its predictive roles in malignant gliomas, and study the correlation of NEK2 protein expression with proliferation, clinical parameters, overall survival and some other parameters. We investigate NEK2 protein expression in 99 samples of malignant gliomas, including 35 WHO grade II, 22 grade III, and 42 grade IV gliomas, by immunohistochemistry and western blot (n = 50). We then made correlative analysis of protein overexpression using the Kaplan-Meier method, Log rank test, and Cox proportional-hazards model analysis. NEK2 protein was overexpressed in malignant gliomas, but not in normal brain tissues. Overexpression of NEK2 correlated with malignancy, proliferation and adverse overall survival in gliomas. Moreover, chemotherapy, resection extent and WHO grade also correlate with overall survival in gliomas. However, within WHO grade II glioma subgroup, NEK2 overexpression showed no impact on overall survival. The present study firstly reveals that NEK2 protein is widely overexpressed in gliomas. NEK2 overexpression correlates significantly with malignancy (WHO grades), proliferation (Ki-67) and prognosis in malignant gliomas. NEK2 is a potential gene therapy target and prognostic indicator.

Risk of acute myocardial infarction in patients with gastroesophageal reflux disease: A nationwide population-based study.

ObjectiveGastroesophageal reflux disease (GERD) is a common disease which can cause troublesome symptoms and affect quality of life. In addition to esophageal complications, GERD may also be a risk factor for extra-esophageal complications. Both GERD and coronary artery disease (CAD) can cause chest pain and frequently co-exist. However, the association between GERD and acute myocardial infarction (AMI) remain unclear. The purpose of the study was to compare the incidence of acute myocardial infarction in GERD patients with an age-, gender-, and comorbidity matched population free of GERD. We also examine the association of the risk of AMI and the use of acid suppressing agents in GERD patients.MethodsWe identified patients with GERD from the Taiwan National Health Insurance Research Database. The study cohort comprised 54,422 newly diagnosed GERD patients; 269,572 randomly selected age-, gender-, comorbidity-matched subjects comprised the comparison cohort. Patients with any prior CAD, AMI or peripheral arterial disease were excluded. Incidence of new AMI was studied in both groups.ResultsA total 1,236 (0.5%) of the patients from the control group and 371 (0.7%) patients from the GERD group experienced AMI during a mean follow-up period of 3.3 years. Based on Cox proportional-hazard model analysis, GERD was independently associated with increased risk of developing AMI (hazard ratio (HR) = 1.48; 95% confidence interval (CI): 1.31–1.66, P < 0.001). Within the GERD group, patients who were prescribed proton pump inhibitors (PPIs) for more than one year had slightly decreased the risk of developing AMI, compared with those without taking PPIs (HR = 0.57; 95% CI: 0.31–1.04, P = 0.066).ConclusionsThis large population-based study demonstrates an association between GERD and future development of AMI, however, PPIs use only achieved marginal significance in reducing the occurrence of AMI in GERD patients. Further prospective studies are needed to evaluate whether anti-reflux medication may reduce the occurrence of acute ischemic event in GERD patients.

The impact of esophagogastric varices on the prognosis of patients with hepatocellular carcinoma

Whether or not esophagogastric varices (EGV) could determine the outcomes of patients with hepatocellular carcinoma (HCC) is still unclear. A total of 990 treatment-naive HCC patients who received an esophagogastroduodenoscopy at the time of HCC diagnosis were retrospectively enrolled. The factors in terms of prognosis were analyzed by Cox proportional hazards model and propensity score matching analysis. Among the enrolled patients, 480 (48.5%) patients had EGV. Patients with EGV had a significantly lower cumulative 5-year survival rate than those without EGV (24.9% versus 46.4%, p < 0.001). It was confirmed by a multivariate analysis and propensity score matching analysis. Stratified by tumor stage, the patients with EGV had lower survival rates than the patients without EGVs in all Barcelona Clinic Liver Cancer stages except stage D. Moreover, the patients with EGV had lower survival rates than those without EGV, both by curative or non-curative treatment modalities. In conclusion, EGV was an independent risk factor predicting poor prognosis for the patients with HCC by multivariate analysis, propensity score matching analysis, and subgroup analysis.

Increased Eps15 homology domain 1 and RAB11FIP3 expression regulate breast cancer progression via promoting epithelial growth factor receptor recycling.

Recent research indicates that the C-terminal Eps15 homology domain 1 is associated with epithelial growth factor receptor-mediated endocytosis recycling in non-small-cell lung cancer. The aim of this study was to determine the clinical significance of Eps15 homology domain 1 gene expression in relation to phosphorylation of epithelial growth factor receptor expression in patients with breast cancer. Primary breast cancer samples from 306 patients were analyzed for Eps15 homology domain 1, RAB11FIP3, and phosphorylation of epithelial growth factor receptor expression via immunohistochemistry. The clinical significance was assessed via a multivariate Cox regression analysis, Kaplan-Meier curves, and the log-rank test. Eps15 homology domain 1 and phosphorylation of epithelial growth factor receptor were upregulated in 60.46% (185/306) and 53.92% (165/306) of tumor tissues, respectively, as assessed by immunohistochemistry. The statistical correlation analysis indicated that Eps15 homology domain 1 overexpression was positively correlated with the increases in phosphorylation of epithelial growth factor receptor ( r = 0.242, p < 0.001) and RAB11FIP3 ( r = 0.165, p = 0.005) expression. The multivariate Cox proportional hazard model analysis demonstrated that the expression of Eps15 homology domain 1 alone is a significant prognostic marker of breast cancer for the overall survival in the total, chemotherapy, and human epidermal growth factor receptor 2 (-) groups. However, the use of combined expression of Eps15 homology domain 1 and phosphorylation of epithelial growth factor receptor markers is more effective for the disease-free survival in the overall population, chemotherapy, and human epidermal growth factor receptor 2 (-) groups. Moreover, the combined markers are also significant prognostic markers of breast cancer in the human epidermal growth factor receptor 2 (+), estrogen receptor (+), and estrogen receptor (-) groups. Eps15 homology domain 1 has a tumor suppressor function, and the combined marker of Eps15 homology domain 1/phosphorylation of epithelial growth factor receptor expression was identified as a better prognostic marker in breast cancer diagnosis. Furthermore, RAB11FIP3 combines with Eps15 homology domain 1 to promote the endocytosis recycling of phosphorylation of epithelial growth factor receptor.

Significant upstaging of patients with stage I pancreatic cancer from clinical to pathologic staging.

349 Background: Clinical staging of patients with pancreatic cancer is essential to determine if neo-adjuvant treatment, surgery or palliative treatment is required. Patients with early stage disease often receive upfront surgery, where as patients with more advanced disease often receive neo-adjuvant therapy. Therefore the accuracy of clinical staging significantly influences management decisions. This study investigates the correlation between clinical and pathologic staging for patients with stage I pancreatic cancer. Methods: A retrospective review of patients with pancreatic cancer in National Cancer Data Base from 1998-2006 was preformed. The clinical stage of patients with presumed stage I disease was compared to the postoperative pathologic stage. Cox proportional hazard ratio model and regression analysis were used to determine factors associated with mortality and upstaging, respectively. Results: 1697 patients with clinical stage I pancreatic cancer were divided into two groups. Group 1 was comprised of patients who were stage I postoperatively and Group 2 was comprised of patients that were upstaged to either stage II, III or IV postoperatively. There were 704 (41%) in group 1 and 993 (59%) in group 2. Within group 2, 595 (60%) were stage II, 321 (32%) were stage III and 77 (8%) were stage IV. Patients that were upstaged after surgery had an increased risk of mortality (HR 1.414, p &lt; 0.001), whereas patients that received adjuvant chemotherapy had a decreased risk of mortality (HR 0.799, p &lt; 0.001). Compared to Grade 1 tumors, Grade 2 and 3 tumors on biopsy were most likely to be upstaged on final pathology (p &lt; 0.001). Conclusions: Patients with stage I pancreatic cancer are often candidates for upfront surgery, however this study demonstrates that a large number are upstaged on postoperative staging. Recognizing this may lead clinicians to administer neo-adjuvant treatment in a greater number of patients with early stage disease in order to optimize survival.

Defining the Ideal Time Interval Between Planned Induction Therapy and Surgery for Stage IIIA Non-Small Cell Lung Cancer

Induction therapy leads to significant improvement in survival for selected patients with stage IIIA non-small cell lung cancer. The ideal time interval between induction therapy and surgery remains unknown. Clinical stage IIIA non-small cell lung cancer patients receiving induction therapy and surgery were identified in the National Cancer Database. Delayed surgery was defined as greater than or equal to 3 months after starting induction therapy. A logistic regression model identified variables associated with delayed surgery. Cox proportional hazards modeling and Kaplan-Meier analysis were performed to evaluate variables independently associated with overall survival. From 2006 to 2010, 1,529 of 2,380 (64.2%) received delayed surgery. Delayed surgery patients were older (61.2 ± 10.0 years versus 60.3 ± 9.2; p= 0.03), more likely to be non-white (12.4% versus 9.7%; p=0.046), andless likely to have private insurance (50% versus 58.2%; p= 0.002). Delayed surgery patients were also more likely to have a sublobar resection (6.3% versus 2.9%). On multivariate analysis, age greater than 68 years (odds ratio [OR], 1.37; 95% confidence interval [CI], 1.1 to 1.7) was associated with delayed surgery, whereas whiterace (OR, 0.75; 95% CI, 0.57 to 0.99) and private insurance status (OR, 0.82; 95% CI, 0.68 to 0.99) were associated with early surgery. Delayed surgery was associated with higher risk of long-term mortality (hazard ratio, 1.25; 95% CI, 1.07 to 1.47). Delayed surgery after induction therapy for stage IIIA lung cancer is associated with shorter survival, and is influenced by both social and physiologic factors. Prospective work is needed to further characterize the relationship between patient comorbidities and functional status with receipt of timely surgery.

The combination of PD-L1 expression and decreased tumor-infiltrating lymphocytes is associated with a poor prognosis in triple-negative breast cancer.

This study included patients with primary triple-negative breast cancer (TNBC) who underwent resection without neoadjuvant chemotherapy between January 2004 and December 2014. Among the 248 TNBCs studied, programmed cell death ligand-1 (PD-L1) expression was detected in 103 (41.5%) tumors, and high levels of tumor-infiltrating lymphocytes (TILs) were present in 118 (47.6%) tumors. PD-L1 expression correlated with high levels of TILs, but was not a prognostic factor. Patients with TILs-high tumors had better overall survival than those with TILs-low tumors (P = 0.016). There was a strong interaction between PD-L1 expression and TILs that was associated with both recurrence-free survival (P = 0.0018) and overall survival (P = 0.015). Multivariate Cox proportional hazards model analysis showed that PD-L1-positive/TILs-low was an independent negative prognostic factor for both recurrence-free survival and overall survival. Our findings suggest that PD-L1-positive/TILs-low tumors are associated with a poor prognosis in patients with TNBC, and that it is important to focus on the combination of PD-L1 expression on tumor cells and TILs present in the tumor microenvironment. These biomarkers may be useful for stratification of TNBCs and for predicting prognosis and developing novel cancer immunotherapies.

Liver imaging reporting and data system category 4 observations in MRI: Risk factors predicting upgrade to category 5.

To identify demographic and imaging features in magnetic resonance imaging (MRI) that are associated with upgrade of Liver Imaging Reporting and Data System (LI-RADS) category 4 (LR-4) observations to category 5 (LR-5), and to assess their effects on risk of upgrade and time to upgrade. Institutional Review Board approval was obtained for this retrospective, dual-institution Health Insurance Portability and Accountability Act (HIPAA)-compliant study. Radiologists reviewed 1.5T and 3T MRI examinations for 181 LR-4 observations in 139 patients, as well as follow-up computed tomography (CT) and MRI examinations and treatment. A stepwise multivariate Cox proportional hazards model analysis was performed to identify predictive risk factors for upgrade to LR-5, including patient demographics and LI-RADS imaging features. Overall cumulative risk of upgrade was calculated by using the Kaplan-Meier method. The cumulative risks were compared in the presence/absence of significant predictive risk factors using the log-rank test. The independent significant predictive risk factors in the 56 LR-4 observations that upgraded to LR-5 were mild-moderate T2 hyperintensity (P < 0.001; hazard ratio = 1.84), growth (P < 0.001; hazard ratio = 3.71), and hepatitis C infection (P = 0.02; hazard ratio = 1.69). The overall 6-month cumulative risk of upgrade was 32.7%. The 6-month cumulative risk rate was significantly higher in the presence of T2 hyperintensity (P = 0.03; 48.1% vs. 25.4%). For LR-4 observations, mild-moderate T2 hyperintensity, threshold growth, and hepatitis C infection are associated with significantly higher risk of upgrade to LR-5. Although mild-moderate T2 hyperintensity was the most useful risk factor for predicting upgrade, actual risk level was only mildly elevated, and the risk of upgrade associated with LR-4 observations is similar across subtypes. 3 Technical Efficacy: Stage 5 J. MAGN. RESON. IMAGING 2017;46:783-792.

Pancreaticoduodenectomy for duodenal papilla carcinoma: A single-centre 9-year retrospective study of 112 patients with long-term follow-up.

AIMTo retrospectively evaluate the factors that influence long-term outcomes of duodenal papilla carcinoma (DPC) after standard pancreaticoduodenectomy (SPD).METHODSThis is a single-centre, retrospective study including 112 DPC patients who had a SPD between 2006 and 2015. Associations between serum levels of CA19-9 and CEA and various clinical characteristics of 112 patients with DPC were evaluated by the χ2 test and Fisher’s exact test. The patients were followed-up every 3 mo in the first two years and at least every 6 mo afterwards, with a median follow-up of 60 mo (ranging from 4 mo to 168 mo). Survival analysis was conducted using the Kaplan-Meier survival and Cox proportional hazards model analysis. The difference in survival curves was evaluated with a log-rank test.RESULTSIn 112 patients undergoing SPD, serum levels of CA19-9 was associated with serum levels of CEA and drainage mode (the P values were 0.000 and 0.033, respectively); While serum levels of CEA was associated with serum levels of CA19-9 and differentiation of the tumour (the P values were 0.000 and 0.033, respectively). The serum levels of CA19-9 and CEA were closely correlated (χ² = 13.277, r = 0.344, P = 0.000). The overall 5-year survival was 50.00% for 112 patients undergoing SPD. The Kaplan-Meier survival analysis showed that increased serum levels of CA19-9, CEA, and total bilirubin were correlated with a poor prognosis, as well as a senior grade of infiltration depth, lymph node metastases, and TNM stage(the P values were 0.033, 0.018, 0.015, 0.000, 0.000 and 0.000, respectively). Only the senior grade of infiltration depth and TNM stage retained their significance when adjustments were made for other known prognostic factors in Cox multivariate analysis (RR = 2.211, P = 0.022 and RR = 2.109, P = 0.047).CONCLUSIONFor patients with DPC, the serum levels of CA19-9 and CEA were closely correlated, and play an important role in poor survival. Increased serum levels of total bilirubin and lymph node metastases were also correlated with a poor prognosis. The senior grade of infiltration depth and TNM stage can serve as independent prognosis indexes in the evaluation of patients with DPC after SPD.

Impact of High Altitude on Clinicopathological Features and Prognosis after R0 Resection for Gastric Cancer: A Population-Based Multicenter Study.

Geographic variation has an important role in both carcinogenesis and prognosis of gastric cancer (GC). High altitude is a special hypoxic environment that is also correlated with the occurrence of GC. Different onset features and prognoses of GC in high altitude with respect to plains are rarely reported and remain unknown. This multicenter study compared different clinicopathological characteristics and prognoses of patients with resected GC who were from locations of both high altitudes and plains in China. From December 2009 to December 2011, patients with resected GC were retrospectively recruited at four centers located at high altitudes and the plains. Clinicopathological data were analyzed to explore the differences between the two groups. The Cox proportional-hazards model was used to investigate the prognostic factors for GC and estimate the independent impact of altitude on long-term survival after adjusting for covariates. Noncardia GC, from a moderate to well tumor grade, was more common in patients from high altitudes. Moreover, a higher proportion of moderate to well and moderate tumor grade and younger age of onset was found in patients with noncardia GC coming from high altitudes. Different overall survival (OS) presented in noncardia GC rather than cardia GC, with 69.94% GC-related 3-yr OS in high altitude versus 75.23% in the plains. High altitude was confirmed as a significant prognostic factor for noncardia GC (the hazard ratio for high altitude vs. plains was 1:50, with a 95% confidence interval; 1.06-1.82, p = 0.018) through a multivariate Cox proportional-hazards model analysis. This prognostic value was independent of all other factors. High altitude has an important role in clinicopathological features and prognosis of GC. Improvements in GC diagnosis and management at high altitudes are urgently needed.

PUB063 PD-L1 Expression Level Could Predict the Survival of Patients with Resectable Small Cell Lung Cancer

Several studies indicated PD-L1 expression on tumor cells is the potential predictive biomarker. However, the prevalence of PD-L1 expression in small cell lung cancer (SCLC) is unclear. This retrospective study aims to detect PD-L1 expression in patients with resectable SCLC and investigate the correlation between PD-L1 expression and the survival of patients. Formalin-fixed, paraffin-embedded samples were stained with PD-L1 antibody by immunohistochemical (IHC) analysis (M4424 antibody). IHC score was calculated according to staining intensity and the percentages of staining tumor cells. Kaplan-Meier method and Cox proportional hazards model analyses were used to evaluate the role of PD-L1 expression on the prognosis of patients with SCLC. From 2011 - 2013, totally 61 patients (43 males/18 females) who underwent complete resection were collected with median age 56 years (range, 30-74) at the time of diagnosis. For the whole group, 32.8% (20/61), 27.9% (17/61) and 39.3% (24/61) patients were diagnosed as pathological stage I, II and III. Until the end of follow-up, 60.7% (37/61) patients are alive. For entire group, the median survival time (MST) was not reached (NR) (range, 6-133.2+ months); 3- and 5-year survival rates were 57.3% and 54.2%, respectively. For the whole cohort, 57.4% (35/61), 37.7% (23/61) and 21.3% (13/61) patients expressed PD-L1 ≥ 1%, 5% and 10%, respectively; and 3-year survival rate was 60.0%, 72.3% and 74.0%, respectively. When the positivity threshold of PD-L1 expression was defined as PD-L1 expression ≥ 5%, the MST in patients with PD-L1 (+) tumors was significantly longer than that with PD-L1 (-) tumors (NR vs. 34 months, p = 0.0321). No significantly survival differences were observed when PD-L1 positivity threshold was defined as 1% or 10%. For patients with stage I SCLC, the MST in patients with PD-L1 expression ≥ 5%, was significantly longer than that in patients with PD-L1 expression < 5% (NR vs. 56 moths, p = 0.03). Regardless of the positivity threshold of PD-L1 expression with 1%, 5% or 10%, for patients with stage II or III SCLC, no significant survival differences were observed. Multivariate analysis indicated postoperative chemotherapy (hazard ratio [HR] = 0.322, p = 0.023), PCI (HR = 0.105, p = 0.029) and PD-L1 expression (HR = 0.253, p = 0.008) were independent prognostic factors for OS. PD-L1 highly expressed in patients with resectable SCLC. The level of PD-L1 expression could predict the survival of patients in this setting.

Measurement of Spleen Stiffness With Acoustic Radiation Force Impulse Imaging Predicts Mortality and Hepatic Decompensation in Patients With Liver Cirrhosis

Hepatic venous pressure gradient can predict mortality and hepatic decompensation in patients with cirrhosis. Measurement of hepatic venous pressure gradient requires an invasive procedure; therefore, prognostic markers are needed that do not require invasive procedures. We investigated whether measurements of spleen stiffness, made by acoustic radiation force impulse (ARFI) imaging, associated with mortality and decompensation in patients with cirrhosis, compared with liver stiffness and other markers. We measured spleen stiffness in 393 patients diagnosed with cirrhosis (based on histologic or physical, laboratory, and radiologic findings) at a hospital in Japan from September 2010 through August 2013 (280 patients with compensated and 113 patients with decompensated cirrhosis). Patients underwent biochemical, ARFI, ultrasonography, and endoscopy evaluations every 3 or 6 months to screen for liver-related complications until their death, liver transplantation, or the end of the study period (October 2015). The primary outcome was the accuracy of spleen stiffness in predicting mortality and decompensation, measured by Cox proportional hazards model analysis. We compared spleen stiffness with other noninvasive parameters using the Harrell's C-index analysis. During a median follow-up period of 44.6 months, 67 patients died and 35 patients developed hepatic decompensation. In the multivariate analysis, spleen stiffness was an independent parameter associated with mortality, after adjustment for levels of alanine aminotransferase and serum sodium, and the model for end-stage liver disease score (P < .001). Spleen stiffness was associated independently with decompensation after adjustment for Child-Pugh score and model for end-stage liver disease score (P < .001). Spleen stiffness predicted mortality and decompensation with greater accuracy than other parameters (C-indexes for predicting mortality and decompensation were 0.824 and 0.843, respectively). A spleen stiffness cut-off value of 3.43 m/s identified the death of patients with a 95.3% negative predictive value and 75.8% accuracy. A spleen stiffness cut-off value of 3.25 m/s identified patients with decompensation with a 98.8% negative predictive value and 68.9% accuracy. Spleen stiffness, measured by ARFI imaging, can predict death of patients with cirrhosis withalmost 76% accuracy and hepatic decompensation with almost 70% accuracy. It might beauseful noninvasive test to predict patient outcome. UMIN Clinical Trials Registry no.UMIN000004363.

Prospective Cohort Study to Elucidate the Correlation between Occupational Stress and Hypertension Risk in Oil Workers from Kelamayi City in the Xinjiang Uygur Autonomous Region of China.

The purpose of this study was to assess the major risk factors for hypertension in oil workers, and investigate the effect of occupational stress on the incidence of hypertension after controlling for other risk factors. A prospective cohort approach was used following enrollment of 1354 oil workers. The occupational stress experienced by oil workers was higher than for the general population in China. By the end of the cohort study, 231 new cases of hypertension among the oil workers had been diagnosed. The cumulative incidence of hypertension was 17.06%. There were 44, 112, and 75 workers who developed hypertension in the low, intermediate, and high occupational stress groups, which represented a 12.0%, 15.6%, and 20.3% cumulative incidence, respectively (chi-square value = 9.812, p < 0.01). Multivariate Cox proportional hazard model analysis showed that type of work, cigarette smoking, excess body weight, and obesity were risk factors for hypertension (p < 0.05). After risk factors such as type of work, cigarette smoking, alcohol consumption, and body mass index (BMI) were controlled, the hypertension risk (hazard ratio, HR) in the high occupational stress group was 1.549 (1.072–2.236) compared to the low exposure group, and 2.337 (1.191–4.585) in female subjects. Our study indicated that an increase in occupational stress was associated with an increased risk of hypertension after other factors were adjusted.