Interaction Between Prediabetes and the ABO Blood Types in Predicting Postsurgical Esophageal Squamous Cell Carcinoma-Specific Mortality: The FIESTA Study.

Background: We aimed to investigate the interaction between prediabetes and the ABO blood types in predicting esophageal squamous cell carcinoma (ESCC)-specific mortality by analysing data from the FIESTA study on normal/prediabetic patients with ESCC. Methods: Total 1,857 normal/prediabetic patients with ESCC who underwent three-field lymphadenectomy between January 2000 and December 2010 and survived hospitalization were analyzable, with follow-up beginning in 2000 and ending in 2015. Results: At the end of the follow-up, there were 1,161 survivors and 696 non-survivors. The follow-up time ranged from 0.5 to 180 months. The cumulative survival rates in normal patients were obviously better than in prediabetic patients. The cumulative survival rates were significantly higher in normal patients than in prediabetic patients for the blood types O and A (Log-rank test P < 0.05), while no significance was detected for the blood types B and AB. Adjusted risk estimates for ESCC-specific mortality for prediabetic patients relative to normal patients were statistically significant in the blood type B- group (hazard ratio [HR]: 1.71; 95% confidence interval [CI]: 1.33-2.20; P < 0.001), but not in the blood type B+ group (HR: 1.12; 95% CI: 0.77-1.64; P = 0.5544). Conclusions: Our findings indicate that prediabetes can predict the significant risk of ESCC-specific mortality in Chinese Han patients with the blood types O and A.

Different Risk Profiles for the Postsurgical Prognosis of Gastric Cancer Patients with Different Blood Types: The FIESTA Study.

Objectives: We here attempted to evaluate the prediction of different "ABO" blood groups for postsurgical gastric cancer-specific mortality by using data from the ongoing Fujian prospective investigation of cancer (FIESTA) study. Methods: Initially, a total of 3413 patients with gastric cancer were consecutively enrolled between January 2000 and December 2010 to receive radical gastrectomy, and they were followed up until December 2015. Study patients were divided into the "O+" group and the blood type "O-" group. Results: Of 2781 eligible patients, 1116 (40.1%) were in the "O+" group and 1665 (59.9%) in the "O-" group, with mortality rate of being 45.0% (n = 502) and 45.3% (n = 755), respectively. A 1:1 propensity score match between the "O+" and the "O-" groups was used. After adjustment, neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), high total cholesterol and high low-density lipoprotein cholesterol, had non-overlapping 95% confidence intervals between the "O+" and the "O-" groups and simultaneously had detectable statistical significance in either group only. A forward method in the multivariate-adjusted COX model was employed and there were five shared risk factors between both groups, including diabetes mellitus, low high-density lipoprotein cholesterol, regional lymph node metastasis, tumor size and TNM stage. Further nomogram plot revealed that presurgical risk factors selected can better predict the risk of early gastric cancer-specific mortality (C-index: 0.737 for the "O-" group and 0.751 for the "O+" group). Conclusions: Our findings indicated that the prognostic factors differed between postsurgical gastric cancer patients with "O+" and "O-" blood types.

Prediction of three lipid derivatives for postoperative gastric cancer mortality: the Fujian prospective investigation of cancer (FIESTA) study.

BACKGROUND: As we previously reported, the presence of preoperative metabolic syndrome can predict the significant risk of gastric cancer mortality. As a further extension, we evaluated the prediction of three lipid derivatives generated from triglycerides (TG), total cholesterol (TC), high- and low-density lipoprotein cholesterol (HDLC and LDLC) at baseline for postoperative gastric cancer mortality by prospectively analysing 3012 patients. The three lipid derivatives included the ratio of TC minus HDLC to HDLC known as atherogenic index (AI), the ratio of TG to HDLC abbreviated as THR and the ratio of LDLC to HDLC abbreviated as LHR. METHODS: Gastric cancer patients who received gastrectomy between January 2000 and December 2010 were consecutively recruited from Fujian Cancer Hospital. Follow-up assessment was implemented annually before December 2015. RESULTS: Finally, there were 1331 deaths from gastric cancer and 1681 survivors, with a median follow-up time of 44.05 months. 3012 patients were evenly randomized into the derivation group and the validation group, and both groups were well balanced at baseline. Overall adjusted estimates in the derivation group were statistically significant for three lipid derivatives (hazard ratio [HR]: 1.20, 1.17 and 1.19 for AI, THR and LHR, respectively, all P < 0.001), and were reproducible in the validation group. The risk prediction of three lipid derivatives was more obvious in males than females, in patients with tumor-node-metastasis stage I-II than stage III-IV, in patients with intestinal-type than diffuse-type gastric cancer, in patients with normal weight than obesity, and in patients without hypertension than with hypertension, especially for AI and LHR, and all results were reproducible. Calibration and discrimination statistics showed good reclassification performance and predictive accuracy when separately adding three lipid derivatives to baseline risk model. A prognostic nomogram was accordingly built based on significant attributes to facilitate risk assessment, with a good prediction capability. CONCLUSIONS: Our results indicate that preoperative lipid derivatives, especially AI and LHR, are powerful predictors of postoperative gastric cancer mortality, with more obvious prediction in patients of male gender or with tumor-node-metastasis stage I-II or intestinal-type gastric cancer, and in the absence of obesity or hypertension before gastrectomy.

Impact of long-term antihypertensive and antidiabetic medications on the prognosis of post-surgical colorectal cancer: the Fujian prospective investigation of cancer (FIESTA) study.

Hypertension and diabetes mellitus are common comorbidities of colorectal cancer. We designed a prospective cohort study aiming to investigate the impact of long-term antihypertensive and antidiabetic medications on colorectal cancer-specific survival and recurrence among 713 post-surgical patients. All participants received radical resection for colorectal cancer during 2000-08, and they were followed up until July 2017. Colorectal cancer patients without hypertension had better survival than those with hypertension (median survival time [MST]: 190.3 months versus 99.0 months, p <0.001). The impact of antidiabetic medications on prolonging colorectal cancer survival was statistically significant, that is, patients receiving antidiabetic medications had longer survival time than untreated diabetic patients (MST: 135.8 months versus 80.2 months, p: 0.007), whereas the prognosis was greatly improved in colorectal cancer patients without diabetes mellitus (p <0.001). Medical treatment for hypertension and diabetes mellitus was associated with 28% (hazard ratio [HR]: 0.72; 95% confidence interval [CI]: 0.47-1.10; p: 0.131) and 57% (HR: 0.43; 95% CI: 0.22-0.82; p: 0.010) reduced risk of dying from colorectal cancer relative to those without medications, respectively. Our data indicate that long-term antidiabetic medications can significantly prolong the survival and improve the prognosis of post-surgical colorectal cancer.

Baseline Metabolic Risk Score and Postsurgical Esophageal Cancer-Specific Mortality: The Fujian Prospective Investigation of Cancer (FIESTA) Study.

Backgrounds: Compelling evidence has emerged to support a close relationship between metabolic syndrome and esophageal cancer (EC). Aims: Using five baseline metabolism-related markers, we constructed a metabolic risk score (MRS), aiming to test whether MRS can improve the prediction of postsurgical EC-specific mortality over traditional demographic and clinicopathologic characteristics. Methods: Total 2535 EC patients who received three-field lymphadenectomy were enrolled from January 2000 to December 2010, and they were followed up until December 2015. Results: All EC patients were randomly split into derivation group (n=1512, 60%) and validation group (n=1014, 40%). MRS was generated in derivation group by adopting the Framingham 'points' system and shrinkage method, and it ranged from -9 to 17. EC-specific mortality risk increased with the increase of MRS, and adjusted estimates were more obvious in patients with upper tertile (MRS>6) than patients with lower MRS (≤2) in either derivation (hazard ratio [HR]=2.28, 95% confidence interval [CI]: 1.90-2.73, P<0.001) or validation group (HR=2.11, 95% CI: 1.66-2.67, P<0.001) or both groups (HR=2.37, 95% CI: 1.95-2.88, P<0.001). In Kaplan-Meier curve, cumulative survival rates differed significantly across tertiles of MRS. Further analysis indicated that MRS can improve classification accuracy and discriminatory ability over clinicopathologic parameters. Conclusions: Our findings supported the usefulness of baseline MRS in predicting the prognosis of postsurgical EC-specific mortality.

An in-depth prognostic analysis of baseline blood lipids in predicting postoperative colorectal cancer mortality: The FIESTA study.

BACKGROUND: Dyslipidaemia is key to colorectal carcinogenesis, and the prediction of baseline triglycerides (TG), total cholesterol (TC), high- and low-density lipoprotein cholesterol (HDLC and LDLC) for postsurgical colorectal cancer mortality has not been researched. OBJECTIVES: We attempted to re-analyse the FIESTA database to assess the prognostic value of three informative lipid derivatives - AI (atherogenic index: (TC - HDLC)/HDLC), THR (TG/HDLC) and LHR (LDLC/HDLC) in predicting colorectal cancer mortality. METHODS: Based on the FIESTA database, 1318 patients received radical resection from 2000 to 2008, with the latest follow-up completed in December 2015. Median follow-up time was 58.6 months. RESULTS: Total 1318 patients were randomly evenly divided into the derivation and validation groups. Overall, baseline AI and LHR were associated with the significantly increased risk of colorectal cancer mortality in both derivation (hazard ratio (HR): 1.41 and 1.35, respectively) and validation (HR: 1.37 and 1.32, respectively) groups (all P < 0.001). The predictive performance of AI and LHR was remarkably enhanced in patients with female gender, former/current smoking, colon cancer, early stage, positive vein tumor embolus, normal weight, preoperative hypertension or diabetes comorbidities. Calibration/discrimination analyses revealed that adding AI or LHR to the traditional model had a better fit in both groups. A prognostic nomogram was finally constructed with good predictive accuracy and discriminative capability (C-index = 0.814, P < 0.001). CONCLUSION: We consolidated the prognostic superiority of AI and LHR in predicting colorectal cancer mortality over TNM stage.

Elevated preoperative neutrophil-to-lymphocyte ratio can predict poor survival in early stage gastric cancer patients receiving radical gastrectomy: The Fujian prospective investigation of cancer (FIESTA) study.

Aims: This cohort study was conducted to evaluate the prognostic impact of blood-routine parameters before radical gastrectomy on gastric cancer mortality. Methods: Total 3012 patients with gastric cancer were consecutively enrolled from a mono-center between 2000 and 2010, and the latest follow-up was completed in 2015. Results: The median follow-up time was 44.05 months. Finally, 1331 out of 3012 gastric cancer patients died from gastric cancer. Per standard deviation increment in neutrophil (hazard ratio or HR=1.08, P<0.001), white blood cell count (HR=1.07, P=0.001), neutrophil-to-lymphocyte ratio or NLR (HR=1.08, P<0.001) and platelet-to-lymphocyte ratio (HR=1.08, P<0.001) was significantly associated with an increased risk of gastric cancer mortality, while that in lymphocyte (HR=0.69, P<0.001), hemoglobin (HR=0.82, P<0.001) and lymphocyte-to-monocyte ratio (HR=0.68, P<0.001) was associated with a reduced risk. Survival tree analysis indicated that in patients with TNM stage I/II, the contrasts of NLR>2.61 with ≤2.61 and NLR>1.87 with ≤1.87 were respectively associated with a 5.21-fold (P=0.004) and 2.36-fold (P=0.001) increased risk of gastric cancer mortality. The effect-size magnitude of NLR was further potentiated in patients with invasion depth T1/T2 (HR=1.73, P=0.001), regional lymph node metastasis N0 (HR=1.60, P<0.001), TNM stage I/II (HR=1.36, P=0.009) and tumor size ≤ 4.5 cm (HR=1.17, P<0.001). Conclusions: Our findings consolidated the prognostic impact of preoperative NLR on gastric mortality, and demonstrated that elevated preoperative NLR was a robust indicator of poor survival in patients at early stage.

The monocyte to red blood cell count ratio is a strong predictor of postoperative survival in colorectal cancer patients: The Fujian prospective investigation of cancer (FIESTA) study.

Background and Aims: We sought to evaluate the prognosis of preoperative blood routine parameters for the mortality of colorectal cancer patients after surgery by eliciting a subset of data from the ongoing Fujian prospective investigation of cancer (FIESTA) study. Methods: 1318 colorectal cancer patients with completed survival data were enrolled between 2000 and 2008. Effect-size estimates are expressed as hazard ratio (HR) and 95% confidence interval (CI). Results: The median follow-up time was 58.6 months. Elevated levels of neutrophil (adjusted HR, 95% CI, P: 1.22, 1.06-1.41, 0.006) and monocyte (1.32, 1.06-1.65, 0.013) were significantly associated with an increased risk of colorectal cancer mortality, whereas that of lymphocyte (0.60, 0.44-0.82, 0.001) and red blood cell count (0.20, 0.09-0.43, <0.001) were significantly associated with a reduced risk. Additionally, remarkable significance was reached for the neutrophil-to-lymphocyte ratio (1.12, 1.06-1.19, <0.001) and lymphocyte-to-monocyte ratio (0.60, 0.46-0.79, <0.001). Based on individual effect-estimates, a new derivate, monocyte to red blood cell count ratio namely MRR was created, and its association with colorectal cancer mortality was strikingly significant (1.48, 1.18-1.85, 0.001). Notably, elevated MRR was significantly associated with the mortality of early stage colorectal cancer, especially in patients with stage I-II (1.63, 1.04-2.56, 0.034), invasion depth T1-T2 (2.85, 1.45-5.61, 0.002), regional lymph node metastasis N0 (1.89, 1.29-2.77, 0.001) and tumor size ≤ 4.5 cm (1.84, 1.25-2.70, 0.002). Conclusions: We created a new derivate MRR, which was superior over classic blood routine derivates, and importantly the MRR exhibited a stronger ability in predicting poor prognosis of colorectal cancer, especially at the early stage.

Analysis of Preoperative Metabolic Risk Factors Affecting the Prognosis of Patients with Esophageal Squamous Cell Carcinoma: The Fujian Prospective Investigation of Cancer (FIESTA) Study.

Some metabolic factors have been shown to be associated with an increased risk of esophageal cancer; however the association with its prognosis is rarely reported. Here, we assessed the prediction of preoperative metabolic syndrome and its single components for esophageal cancer mortality by analyzing a subset of data from the ongoing Fujian prospective investigation of cancer (FIESTA) study. Between 2000 and 2010, patients who underwent three-field lymphadenectomy were eligible for inclusion. Blood/tissue specimens, demographic and clinicopathologic data were collected at baseline. Metabolic syndrome is defined by the criteria proposed by Chinese Diabetes Society. In this study, analysis was restricted to esophageal squamous cell carcinoma (ESCC) due to the limited number of other histological types. The median follow-up in 2396 ESCC patients (males/females: 1822/574) was 38.2months (range, 0.5-180months). The multivariate-adjusted hazard ratio (HR) of metabolic syndrome for ESCC mortality was statistically significant in males (HR, 95% confidence interval, P: 1.45, 1.14-1.83, 0.002), but not in females (1.46, 0.92-2.31, 0.107). For single metabolic components, the multivariate-adjusted HRs were significant for hyperglycemia (1.98, 1.68-2.33, <0.001) and dyslipidemia (1.41, 1.20-1.65, <0.001) in males and for hyperglycemia (1.76, 1.23-2.51, <0.001) in females, independent of clinicopathologic characteristics and obesity. In tree-structured survival analysis, the top splitting factor in both genders was tumor-node-metastasis stage, followed by regional lymph node metastasis. Taken together, our findings demonstrate that preoperative metabolic syndrome was a significant independent predictor of ESCC mortality in males, and this effect was largely mediated by glyeolipid metabolism disorder.

Preoperative blood-routine markers and prognosis of esophageal squamous cell carcinoma: The Fujian prospective investigation of cancer (FIESTA) study.

This prospective study was designed to investigate the prognosis of preoperative blood-routine markers for esophageal cancer mortality by using data from the ongoing Fujian prospective investigation of cancer (FIESTA) study. Patients who received three-field lymphadenectomy for esophageal cancer between 2000 and 2010 were enrolled. Of 2535 patients with complete survival data, esophageal squamous cell carcinoma (ESCC) accounted for 94.5% (n = 2396). Here, only ESCC patients were analyzed, with the median follow-up time of 38.2 months (range: 0.5 to 180 months). Of 10 blood-routine markers evaluated, platelet count and red cell distribution width (RDW) were two significant predictors for ESCC mortality in men (adjusted hazard ratio or HR = 1.25 and 0.84, 95% confidence interval or CI: 1.08-1.22 and 0.75-0.93, P < 0.001 and P = 0.001, respectively), while in women only lymphocyte showed marginal significance. Based on individual results, a new derivate calculated as platelet count to RDW ratio (PRR) was created, and it was superior over other widely-evaluated derivates in men after adjustment (HR = 1.21, 95% CI: 1.13-1.30, P < 0.001), while there was no observable significance in women. In further stratified analyses, the prognosis of PRR for ESCC mortality was reinforced in men with tumor-node-metastasis stage III (HR, 95% CI, P: 1.18, 1.09-1.28, 0.001), invasion depth T3-T4 (1.17, 1.08-1.26, <0.001) or positive lymph node metastasis (1.37, 1.18-1.59, <0.001). Taken together, we created a new derivate PRR that was proven to be superior over other blood-routine markers and exhibited strong prognostic capability for ESCC mortality in Chinese men.

Preoperative Metabolic Syndrome Is Predictive of Significant Gastric Cancer Mortality after Gastrectomy: The Fujian Prospective Investigation of Cancer (FIESTA) Study.

Metabolic syndrome (MetS) has been shown to be associated with an increased risk of gastric cancer. However, the impact of MetS on gastric cancer mortality remains largely unknown. Here, we prospectively examined the prediction of preoperative MetS for gastric cancer mortality by analyzing a subset of data from the ongoing Fujian prospective investigation of cancer (FIESTA) study. This study was conducted among 3012 patients with gastric cancer who received radical gastrectomy between 2000 and 2010. The latest follow-up was completed in 2015. Blood/tissue specimens, demographic and clinicopathologic characteristics were collected at baseline. During 15-year follow-up, 1331 of 3012 patients died of gastric cancer. The median survival time (MST) of patients with MetS was 31.3months, which was significantly shorter than that of MetS-free patients (157.1months). The coexistence of MetS before surgery was associated with a 2.3-fold increased risk for gastric cancer mortality (P<0.001). The multivariate-adjusted hazard ratios (HRs) were increased with invasion depth T1/T2 (HR=2.78, P<0.001), regional lymph node metastasis N0 (HR=2.65, P<0.001), positive distant metastasis (HR=2.53, P<0.001), TNM stage I/II (HR=3.00, P<0.001), intestinal type (HR=2.96, P<0.001), negative tumor embolus (HR=2.34, P<0.001), and tumor size ≤4.5cm (HR=2.49, P<0.001). Further survival tree analysis confirmed the top splitting role of TNM stage, followed by MetS or hyperglycemia with remarkable discrimination ability. In this large cohort study, preoperative MetS, especially hyperglycemia, was predictive of significant gastric cancer mortality in patients with radical gastrectomy, especially for early stage of gastric cancer.

The elevated preoperative fasting blood glucose predicts a poor prognosis in patients with esophageal squamous cell carcinoma: The Fujian prospective investigation of cancer (FIESTA) study.

Diabetes as a latent risk factor for cancer has been extensively investigated, while its postoperative prognosis for esophageal cancer is rarely reported. We therefore sought to assess whether the elevated fasting blood glucose before surgery was associated with poor survival in esophageal cancer patients by eliciting a subset of data from the ongoing Fujian prospective investigation of cancer (FIESTA) study. Over 15-year follow-up, 2535 patients receiving three-field lymphadenectomy were assessable. Only patients with esophageal squamous cell carcinoma (ESCC) (n=2396) were analyzed due to the lower prevalence of the other histological types. In ESCC patients, the follow-up duration ranged from 0.5 to 180 months (median 38.2 months). The median survival time (MST) was remarkably shorter in males than in females (80.7 vs. 180+ months, Log-rank test: P<0.001). In males, the survival was worse in patients with diabetes than those without (MST: 27.9 vs. 111.1 months, Log-rank test: P<0.001). In females, the survivor was improved in patients with diabetes (MST: 71.5 months), but was still worse than patients without diabetes (MST: 180+ months, Log-rank test: P<0.001). The overall multivariate hazard ratio for per unit increment in fasting blood glucose was 1.11 (95% confidence interval or CI: 1.09-1.14, P<0.001) and 1.08 (95% CI: 1.03-1.13, P=0.002) in males and females, respectively. Further survival tree analysis consolidated the discrimination ability of fasting blood glucose for the survival of ESCC patients. Taken together, our findings convincingly demonstrated that the elevated preoperative fasting blood glucose can predict poor survival of ESCC patients, especially in males.

Preoperative metabolic syndrome and prognosis after radical resection for colorectal cancer: The Fujian prospective investigation of cancer (FIESTA) study.

This prospective study sought to investigate the prediction of preoperative metabolic syndrome and its components for the risk of colorectal cancer (CRC) mortality by analyzing a subset of data from the ongoing Fujian prospective investigation of cancer (FIESTA) study. In total, 1,318 CRC patients who received radical resection were consecutively enrolled between January 2000 and December 2008. The median follow-up time was 58.6 months, with 412 deaths from CRC. The CRC patients with metabolic syndrome had significantly shorter median survival time (MST) than those without (50.9 vs. 170.3 months, p < 0.001). Among four components of metabolic syndrome, hyperglycemia was the strongest predictor and its presence was associated with shorter MST than its absence (44.4 vs. 170.3 months, p < 0.001). Moreover, the complication of metabolic syndrome in CRC patients was associated with a 2.98-fold increased risk of CRC mortality (hazard ratio [HR] = 2.98, 95% confidence interval [CI]: 2.40-3.69, p < 0.001) after adjusting for confounding factors. The magnitude of this association was especially potentiated in CRC patients with tumor-node-metastasis stage I/II (HR = 3.94, 95% CI: 2.65-5.85, p < 0.001), invasion depth T1/T2 (HR = 5.41, 95% CI: 2.54-11.50, p < 0.001), regional lymph node metastasis N0 (HR = 4.06, 95% CI: 2.85-5.80, p < 0.001) and negative distant metastasis (HR = 3.23, 95% CI: 2.53-4.12, p < 0.001). Further survival tree analysis reinforced the prognostic capability of fasting blood glucose in CRC survival. Our findings convincingly demonstrated that preoperative metabolic syndrome, especially hyperglycemia, was a robust predictor for CRC mortality, and the protection was more obvious in patients with Stage I/II.