Lymphopenia Predicts Poor Prognosis in Patients With Esophageal Squamous Cell Carcinoma

Lymphopenia is a useful predictive factor in several cancers. The aim of this study was to determine the prognostic value of lymphopenia in patients with esophageal squamous cell carcinoma (ESCC).A retrospective analysis of 307 consecutive patients who had undergone esophagectomy for ESCC was conducted. In our study, a lymphocyte count (LC) of fewer than 1.0 Giga/L was defined as lymphopenia. Kaplan–Meier method was used to calculate the cancer-specific survival (CSS). Cox regression analyses were performed to evaluate the prognostic factors. Receiver operating characteristic (ROC) curve was also plotted to verify the accuracy of LC for CSS prediction.The mean LC was 1.55 ± 0.64 Giga/L (range 0.4–3.7 Giga/L). The incidence of lymphopenia (LC < 1.0 Giga/L) was 16.6% (51/307). Patients with lymphopenia (LC < 1.0 Giga/L) had a significantly shorter 5-year CSS (21.6% vs 43.8%, P = 0.004). On multivariate analysis, lymphopenia (LC < 1.0 Giga/L) was an independent prognostic factor in patients with ESCC (P = 0.013). Lymphopenia had a hazard ratio (HR) of 1.579 [95% confidence interval (CI): 1.100–2.265] for CSS. ROC curve demonstrated that lymphopenia (LC < 1.0 Giga/L) predicts survival with a sensitivity of 86.2% and a specificity of 27.2%.Lymphopenia (LC < 1.0 Giga/L) is still an independent predictive factor for long-term survival in patients with ESCC.     

Co-Expression of LGR5 and CD133 Cancer Stem Cell Predicts a Poor Prognosis in Patients With Gastric Cancer

BackgroundThe LGR5 and CD133 have been identified as cancer stem cells (CSCs) marker and prognostic marker in several cancers including gastric cancer. The purpose of the present study was to determine the association between co-expression of CSCs marker LGR5 and CD133 in patients with gastric cancer and their clinicopathological outcomes; to analyze the efficacy of co-expression of both markers in evaluating the prognosis of gastric cancer.Methods: LGR5 and CD133 expression were investigated in a total of 400 patients by using immunohistochemistry. Results were analyzed in association with patient characteristics outcomes. Overall survival was performed using Kaplan-Meier Curve analysis.ResultsLGR5 and CD133 were found positive in 219/400 (54.75%) and 251/400 (62.75%) respectively in gastric cancer tissues. Co-expression of LGR5 and CD 133 were significantly associated with poor clinicopathological outcomes, including lymphatic invasion, vascular invasion, higher pathological T stage, and higher TNM staging (stage IV) (P < .05). The overall survival of patients who were positive for LGR5 and CD133 had shorter than that of LGR5 and CD133-negative gastric cancer, especially in patients who were positive for both markers.ConclusionOur finding indicates that co-expression of LGR5 and CD133 could be used as a marker indicating poor prognosis, which can provide information for selected effective treatment and carried out of intensive follow-up in gastric cancer patients.     

White Blood Cell Count Predicts All-Cause Mortality in Patients with Suspected Peripheral Arterial Disease

Objective

We investigated whether markers of inflammation—white blood cell (WBC) count, C-reactive protein (CRP), and lipoprotein-associated phospholipase A2—are associated with mortality in patients referred for noninvasive lower-extremity arterial evaluation.

Methods

Participants (n = 242, mean age 68 years, 54% men) were followed for a median of 71 months. Ankle-brachial index (ABI), WBC count, plasma CRP, and lipoprotein-associated phospholipase A2 were measured at the start of the study. Factors associated with all-cause mortality were identified using Cox proportional hazards.

Results

During the follow-up period, 56 patients (25%) died. Factors associated with higher mortality were greater age, history of coronary artery disease/cerebrovascular disease, lower ABI, higher serum creatinine, and higher WBC count/plasma CRP. In stepwise multivariable regression analysis, ABI, serum creatinine, WBC count, and CRP were associated significantly with mortality. Patients in the top tertile of WBC count and CRP level had a relative risk of mortality of 3.37 (confidence interval [CI], 1.56-7.27) and 2.12 (CI, 0.97-4.62), respectively. However, only the WBC count contributed incrementally to prediction of mortality. Inferences were similar when analyses were limited to patients with peripheral arterial disease (ABI < 0.9, n = 114).

Conclusion

WBC count, but not plasma CRP level, provides incremental information about the risk of death in patients referred for lower-extremity arterial evaluation and in the subset of these patients with peripheral arterial disease.     

Extent of Serosal Changes Predicts Peritoneal Recurrence and Poor Prognosis After Curative Surgery for Gastric Cancer

To investigate whether the width of gastric serosal lesions in advanced gastric cancer patients have a predictive value for peritoneal recurrence and the 5-year survival rate.A total of 1109 patients with advanced noncardia primary gastric adenocarcinoma, who underwent curative gastrectomy between January 1997 and December 2007, were included. Data about tumor size, longitudinal tumor location, resection type, serum albumin concentration, lymphatic/venous invasion, lymph node metastasis status, lesion size, histological and Borrmann type of tumor, as well as the recurrence rate and width of the gastric serosal lesions were collected and analyzed.The peritoneal recurrence rate in patients with gastric serosal lesions ≤3 cm was lower than in patients with gastric serosal lesions >3 cm. Multivariate analyses of the 5-year survival rate variables for all patients revealed significant correlations with serum albumin concentrations (HR 1.382, P = 0.002, 95% CI 1.123–1.701), width of serosa changes (HR 1.377, P = 0.020, 95% CI 1.053–1.802), depth of invasion (HR 1.529, P < 0.001, 95% CI 1.288–1.814), and lymph node metastasis (HR 1.551, P < 0.001, 95% CI 1.420–1.694), whereas for recurrent patients only serum albumin concentrations (HR 2.000, P < 0.001, 95% CI 1.425–2.805), width of serosa changes (HR 1.867, P = 0.002, 95% CI 1.248–2.793), and lymph node metastasis (HR 1.521, P < 0.001, 95% CI 1.249–1.852) correlated with the 5-year survival rate.Gastric serosal lesions >3 cm may indicate a high risk for peritoneal recurrence and serve as additional indicators for preventive postoperative adjuvant chemotherapies in patients with advanced gastric cancer.     

Improved Survival After Coronary Bypass Surgery In Patients With Poor Left Ventricular Function: Role of Intraaortic Balloon Counterpulsation

The operative mortality rate of aortocoronary bypass surgery in 23 patients with poor left ventricular function (ejection fraction 0.30 or less) operated on in 1973-74 was 34.7 percent. The incidence rate of operative myocardial infarction was 30.4 percent. In an attempt to improve survival, intraaortic balloon counterpulsation was used therafter in 25 similar patients. Counterpulsation was instituted preoperatively and continued intra- and postoperatively for 2 to 5 days. Preoperative studies revealed an "unloading" effect of the left ventricle, with significant reductions of systolic arterial blood pressure, end-diastolic pulmonary arterial pressure and end-diastolic left ventricular volume and pressure. Metabolic improvement was demonstrated by the lesser production of myocardial lactate after pacing-induced tachycardia when the ventricle was balloon-assisted. Intraoperatively, blood flow through the vein graft was found to increase with counterpulsation. The rate of operative myocardial infarction was reduced to 4 percent and the mortality rate to 8 percent. In patients who have sustained a significant loss of functioning myocardium, the beneficial hemodynamic and metabolic effects of intraaortic balloon counterpulsation appear to prevent furhter, possibly critical, myocardial damage in the perioperative period.     

Impact of Blood Transfusions on Recurrence and Survival After Rectal Cancer Surgery

Purpose This study was designed to determine whether type or number of blood units transfused affected short-term and long-term outcome in patients undergoing surgery for rectal cancer. The number of perioperative blood units is associated with postoperative mortality and overall survival by some authors. In addition, allogenic perioperative blood transfusion has been postulated to produce host immunosuppression and has been reported to result in adverse outcome in patients with colorectal cancer. Autologous blood transfusion might improve results compared with allogenic transfusion. Methods Clinical outcome for 597 patients undergoing surgery for rectal cancer was analyzed according to their transfusion status. Results for type (autologous or allogenic) and number of blood units transfused were recorded. Results Blood transfusion was associated with increased postoperative mortality at 60 days. Patients who received > 3 units had a postoperative mortality of 6 percent compared with 1 percent for patients who received 1 to 3 units and 0 percent for patients who did not require transfusions. No difference was found between patients who received autologous or allogenic blood. Blood transfusions were also associated with impaired overall survival in a univariate analysis, but this finding was not confirmed in the multivariate analysis. The number or type of blood units transfused did not influence oncologic results. Local recurrence rates, distant metastases rates, and disease-free survival were not influenced by transfusion in our patients. Conclusions Increased numbers of blood units were associated with postoperative mortality. However, there is no reason, with respect to cancer recurrence or disease-free survival, to use a program of transfusion with autologous blood in patients undergoing surgery for rectal cancer. Reprints are not available.     

Red Blood Cell Distribution and Survival in Patients with Chronic Obstructive Pulmonary Disease

Abstract

Background: Cardiovascular disease (CVD) contributes significantly to mortality in chronic obstructive pulmonary disease (COPD). Red blood cell distribution width (RDW), an automated measure of red blood cell size heterogeneity that is largely overlooked, is a newly recognized mortality marker in patients with established CVD. It is unknown whether RDW is associated with mortality in COPD patients.

Aims: To study the prognostic value of RDW in patients with COPD and to compare the value of this measurement with cardiac, respiratory, and hemotological status. Method: We performed retrospective analyses of 270 patients stable with COPD who were admitted to our hospital between January 2007 and December 2009. Demographic, clinical, echocardiographic, and laboratory characteristics were registered and recorded COPD deaths were registered as outcomes. Results: In the overall patients, the RDW level had a mean value of 15.1 ± 2.4. RDW was positively correlated with C-reactive protein (CRP) (p = 0.008, r = 0.21), right ventricular dysfunction (RVD) (p < 0.001, r = 0.25), and pulmonary arterial hypertension (PAH) (p = 0.03, r = 0.14). Variables (p < 0.1) included in the univariate survival analysis were forced expiratory volume in 1 second (FEV1% predicted), RDW levels, age, PaCO2, albumine and CRP levels, presence of CVD, presence of anemia, presence of RVD, and presence of PAH. Subsequent multivariate analysis suggested that RDW levels (1.12; 95% CI, 1.01 to 1.24; p = 0.01), and presence of RVD (2.6; 95% CI, 1.19 to 5.8; p = 0.01) were independently related to mortality. Conclusion: Elevated RDW levels were associated with increased mortality risk in stable COPD patients.     

The Relationship of Red Cell Membrane Lipid Content to Red Cell Morphology and Survival in Patients with Liver Disease*

Summary: The relationship of red blood cell (RBC) membrane lipid content to RBC morphology and survival was studied in patients with liver disease. An increase in RBC cholesterol and phospholipid was detected in most patients with hepatocellular disease or cholestatic jaundice but the alteration in RBC lipid content did not correlate with RBC survival. The main abnormality of RBC morphology observed was the presence of macrocytes and target cells. In a small proportion of patients (approximately 3%) with severe hepatocellular disease, significant numbers of severely deformed (“spur”) cells were seen. In these patients haemolysis was moderately severe and the RBC lipid profile showed increased membrane cholesterol without a concomitant increase in phospholipids. It is concluded that only in patients with “spur” cell anaemia do the morphological alterations lead to premature removal of cells from the circulation. The cause of the shortened RBC survival in jaundiced patients without “spur” cells remains to be determined.     

Improvement in Health-related Quality of Life After Hospitalization Predicts Event-free Survival in Patients With Advanced Heart Failure

BackgroundHealth-related quality of life (HRQOL) is a major clinical outcome for heart failure (HF) patients. We aimed to determine the frequency, durability, and prognostic significance of improved HRQOL after hospitalization for decompensated HF.Methods and ResultsWe analyzed HRQOL, measured serially using the Minnesota Living with Heart Failure Questionnaire (MLHFQ), for 425 patients who survived to discharge in a multicenter randomized clinical trial of pulmonary artery catheter versus clinical assessment to guide therapy for patients with advanced HF. All patients enrolled had 1 or more prior HF hospitalizations or chronic high diuretic doses and 1 or more symptom and 1 sign of fluid overload at admission. Improvement, defined as a decrease of more than 5 points in MLHFQ total score, occurred in 68% of patients by 1 month and stabilized. The degree of 1-month improvement differed (P < .0001 group × time interaction) between 6-month survivors and non-survivors. In a Cox regression model, after adjustment for traditional risk factors for HF morbidity and mortality, improvement in HRQOL by 1 month compared to worsening at 1 month or no change predicted time to subsequent event-free survival (P = .013).ConclusionsIn patients hospitalized with severe HF decompensation, HRQOL is seriously impaired but improves substantially within 1 month for most patients and remains improved for 6 months. Patients for whom HRQOL does not improve by 1 month after hospital admission merit specific attention both to improve HRQOL and to address high risk for poor event-free survival.     

Sarcopenia Predicts Reduced Survival in Patients with Hepatocellular Carcinoma at First Diagnosis

BackgroundSarcopenia is a complication and independent risk factor for mortality in patients with liver cirrhosis.AimTo assess the prevalence and influence of sarcopenia on overall survival in a cohort of cirrhotic patients with hepatocellular carcinoma managed in a tertiary center.Material and MethodsAbdominal computed tomography of 92 consecutive hepatocellular carcinoma cirrhotic patients, enrolled and followed from 2004 to 2014, were retrospectively studied with a software analyzing the cross-sectional areas of muscles at third lumbar vertebra level. Data was normalized for height, skeletal muscle index (SMI) calculated and presence of Sarcopenia measured. Sarcopenia was defined by SMI ≤ 41 cm²/m² for women and ≤ 53 cm²/m² for men with body mass index (BMI) ≥ 25, and ≤ 43 cm²/m² for men and women with BMI < 25, respectively.ResultsMedian age at diagnosis was 71.9 years (30.7-86.4) and BMI 24.7 (17.5-36.7), comparable in women 23.1, (17.5-36.7) and men 24.7 (18.4-36.7). A class of CHILD score and BCLC A prevailed (55.4% and 41.3%, respectively); metastatic disease was found in 12% of cases. Sarcopenia was present in 40.2% of cases, mostly in females (62.9%; p = 0.005). Mean overall survival was reduced in sarcopenic patients, 66 (95% CI 47 to 84) vs. 123 (95% CI 98 to 150) weeks (p = 0.001). At multivariate analysis, sarcopenia was a predictor of reduced overall survival, independent of age (p = 0.0027).ConclusionsThis retrospective study shows high prevalence of sarcopenia among cirrhotic patients with hepatocellular carcinoma. Presence of sarcopenia was identified as independent predictor of reduced overall survival. As easily measurable by CT, sarcopenia should be determined for prognostic purposes in this patient population.     

High Expression of Cell Division Cycle 42 Promotes Pancreatic Cancer Growth and Predicts Poor Outcome of Pancreatic Cancer Patients

Background

Cell division cycle 42 (CDC42), an important member of the Rho family, is overexpressed in various human cancers. However, its expression and role in pancreatic cancer (PC) are not well understood.

Aim

The present study was designed to investigate the expression patterns and underlying cellular mechanisms of CDC42 in PC.

Methods

First, immunohistochemical analysis, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were performed to detect CDC42 expression in clinical pancreatic carcinoma and adjacent tissues. Second, differential expression of CDC42 between PC cells and normal cells was evaluated by qRT-PCR and Western blotting. Third, the correlation between CDC42 expression as well as clinicopathological characteristics and patient survival was analyzed. Finally, CDC42 was knocked down to examine its role both in vivo and in vitro.

Results

The results showed significantly increased CDC42 expression in pancreatic tumor tissues compared with adjacent normal tissues, as revealed by qRT-PCR, Western blotting and immunostaining. Compared to PanC-1 cells, CDC42 expression was downregulated in HPDE6-C7 cells as shown by qRT-PCR and Western blotting. High CDC42 expression was observed in 69.2% (83/120) of pancreatic adenocarcinoma patients and was significantly associated with tumor differentiation (p = 0.013), median tumor size (p = 0.005), tumor infiltration (pT stage, p = 0.04), lymph nodal status (pN stage, p = 0.044) and TNM staging (p = 0.003). Multivariate Cox regression analysis revealed CDC42 expression to be an independent predictor of survival of PC patients (HR 3.0, 95% CI 1.60–5.61, p = 0.001). Finally, we found that CDC42 promoted the proliferation of PanC-1 cells both in vivo and in vitro.

Conclusions

Our findings reveal that CDC42 might play an important role in promoting PC development, and the findings suggest that CDC42 might serve as a potential prognostic indicator of PC.

     

Factors Associated with Survival of Patients With Severe Acute-On-Chronic Liver Failure Before and After Liver Transplantation

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Reduced Survival of Rectal Cancer Patients With Increased Tumor Epidermal Growth Factor Receptor Levels

PURPOSE: The epidermal growth factor receptor and its various ligands (epidermal growth factor, transforming growth factor-alpha, amphiregulin, heparin-binding epidermal growth factor, heregulin, and betacellulin) have been implicated in growth and regeneration of intestinal mucosa and might be related to the development and progression of gastrointestinal tumors. Although some studies have investigated levels of epidermal growth factor receptor by radioligand binding studies, none of them have further analyzed these levels in patients with rectal cancer and investigated their prognostic value. METHODS: We quantitatively determined tumor epidermal growth factor receptor levels in 38 patients with colorectal cancer compared with adjacent normal mucosa by iodine-125–labeled epidermal growth factor binding studies and Scatchard analysis. Patients were followed up for 49.5 ± 32.2 (range, 2–120) months. RESULTS: Epidermal growth factor receptor capacity was increased in invasive colorectal carcinomas according to T classification (P < 0.001), tumors with lymph node infiltration (P = 0.038), and advanced International Union Against Cancer stage (P < 0.001). Survival of colorectal cancer was reduced in patients with advanced International Union Against Cancer stage (P < 0.001), tumors with positive lymph nodes (P < 0.001), and tumors with elevated epidermal growth factor receptor levels (P = 0.024). In rectal cancer patients, poor prognosis was associated with advanced International Union Against Cancer stage (P = 0.029), tumors with lymph node infiltration (P = 0.040), and increased epidermal growth factor receptor levels (P = 0.002). Multivariate Cox regression analysis indicated that elevated levels of epidermal growth factor receptor were an independent predictor of reduced survival in patients with rectal cancer (P = 0.005). CONCLUSION: The epidermal growth factor receptor/ligand system appears to be involved in tumor development and tumor progression of colorectal carcinomas, with prognostic implication especially in patients with invasive rectal carcinomas. These patients might take advantage of therapies that specifically block epidermal growth factor receptor–mediated signal transduction.     

Decreased Blood Platelet Volume and Count in Patients with Liver Disease

Mean platelet volume (MPV) and count (PLT) were assessed in patients with moderately affected liver function. PLT was significantly decreased in patients with liver disease (197 · 10⁹ 1^-1 ± 87 (SD), no. = 79) compared with that of controls (273 · 10⁹ 1^-1 ± 53 (SD), no. = 37, P < 0.001). MPV in patients with liver disease (9.25 ± 1.14 fl) was significantly lower than that of controls (10.52 ± 0.74 fl. P < 0.001). In control subjects MPV and PLT were inversely correlated (r = -0.48, P < 0.01), but statistical significance was not found in patients with liver disease (r = -0.2, 0.05 < P < 0.1). It is concluded that the low MPV and PLT are compatible with an intravascular activation (loss of granules) and increased consumption of platelets, which may take place in the diseased liver even in patients with a relatively well preserved liver function.