Association of Serum Uric Acid with 2-Hour Postload Glucose in Chinese with Impaired Fasting Plasma Glucose and/or HbA1c

Objective

To examine whether serum uric acid (SUA) is associated with 2-hour postload glucose (2-h PG) in Chinese with impaired fasting plasma glucose (IFG) and/or HbA1c (IA1C).

Research Design and Methods

Anthropometric and biochemical examinations, such as SUA concentration, were performed in 3763 individuals from all the villages in Baqiao County, China. A 75-g oral glucose tolerance test (OGTT) was conducted in 1197 Chinese with prediabetes as having IFG (110≤ fasting plasma glucose [FPG] <126 mg/dl and HbA1c <6.5%), IA1C (5.7% ≤ HbA1c <6.5% and FPG <126 mg/dl), or both.

Results

The present study included 1197 participants with IFG and/or IA1C (mean age 56.5±10.3 years; 50.6% men). In multivariate linear regression, after adjustment for gender, age, smoking and drinking, body mass index (BMI), systolic and diastolic blood pressure (SBP, DBP), lipid profiles, logarithmic transformed C-reactive protein (log-CRP), estimated glomerular filtration rate (e-GFR), FPG and HbA1c, with a 1-mg/dl increment of SUA, 2-h PG increased by 5.04±0.72 (P<0.001), 3.06±1.08 (P = 0.001), 5.40±1.26 (P<0.001), and 2.34±2.16 mg/dl (P = 0.056) in all participants, in participants with normal glucose tolerance (NGT), with impaired glucose tolerance (IGT), and with 2-h newly diagnosed diabetes (2-h NDM, with 2-h PG ≥200 mg/dl), respectively. In both men and women, 2-h PG increased progressively and significantly from the lower to the upper SUA tertiles (P<0.001). Moreover, in multivariate logistic regression, 1-standard deviation (SD; 1.53 mg/dl) increment of SUA was significantly associated with a 36% higher risk for 2-h NDM (Odds ratio [CI 95%]: 1.36 [1.09–1.99]; P = 0.03).

Conclusions

SUA is significantly associated with 2-h PG in Chinese with IFG and/or IA1C.     

A Propensity-Score Matched Comparison of Perioperative and Early Renal Functional Outcomes of Robotic versus Open Partial Nephrectomy

Objectives

To compare the perioperative and early renal functional outcomes of RPN with OPN for kidney tumors.

Materials and Methods

A total of 209 RPN or OPN patients with availability of preoperative cross-sectional imaging since 2009 at our center were included. To adjust for potential baseline confounders propensity-score matching was performed, which resulted in 94 OPNs matched to 51 RPNs. Perioperative and early renal functional outcomes were compared.

Results

In propensity-score matched analysis, RPN procedures were well tolerated and resulted in significant decreases in postoperative analgesic time (24 vs. 48 hr, p<0.001) and visual analog pain scale (3 vs. 4, p<0.001). Besides, the RPN patients had a significantly shorter LOS (9 vs. 11 days, p = 0.008) and less EBL (100 vs. 200 ml, p<0.001), but median operative time was significantly longer (229 vs. 182 min, p<0.001). Ischemia time, transfusion rates, complication rates, percentage eGFR decline and CKD upstaging were equivalent after RPN versus OPN. In multivariable logistic regression analysis, RPN patients were less likely to have a prolonged LOS (odds ratio [OR]: 0.409; p = 0.016), while more likely to experience a longer operative time (OR: 4.296; p = 0.001). However, the statistical significance for the protective effect of RPN versus OPN in EBL was not confirmed by examining the risk of EBL≥400 ml (OR: 0.488; p = 0.212).

Conclusions

When adjusted for potential selection biases, RPN offers comparable perioperative and early renal functional outcomes to those of OPN, with the added advantage of improved postoperative pain control and a shorter LOS.     

Lymphotoxin Alpha (LTA) Polymorphism Is Associated with Prognosis of Non-Hodgkin’s Lymphoma in a Chinese Population

Background

Non-Hodgkin’s lymphoma (NHL) has been widely reported to be associated with autoimmune and pro-inflammatory response, and genetic polymorphisms of candidate genes involved in autoimmune and pro-inflammatory response may influence the survival and prognosis of NHL patients. To evaluate the role of such genetic variations in prognosis of NHL, we conducted this study in a Chinese population.

Methods

We used the TaqMan assay to genotype six single nucleotide polymorphisms (SNPs) (TNF rs1799964T>C, LTA rs1800683G>A, IL-10 rs1800872T>G, LEP rs2167270G>A, LEPR rs1327118C>G, TNFAIP8 rs1045241C>T) for 215 NHL cases. Kaplan-Meier analysis was performed to compare progression free survival among two common genotypes. Cox proportional hazard models were used to identify independent risk factors.

Results

We observed that LTA rs1800683G>A was significantly associated with risk of progression or relapse in NHL patients (HR = 1.63, 95%CI = 1.06–2.51; P = 0.028), particularly in Diffuse large B cell lymphoma (DLBCL) cases (HR = 1.50, 95%CI = 1.10–2.04, P = 0.01). Both univariate and multivariate Cox regression analysis showed that in DLBCL patients, Ann Arbor stage III/IV, elevated LDH level before treatment and LTA rs1800683 AA genotype carrier were independent risk factors for progression or relapse. While in NK/T cell lymphoma, Ann Arbor stage III/IV and elevated β₂-MG level before treatment indicated poorer prognosis.

Conclusions

The polymorphism of LTA rs1800683G>A contributes to NHL prognosis in a Chinese population. Further large-scale and well-designed studies are needed to confirm these results.     

Wilm's Tumor-1 Protein Levels in Urinary Exosomes from Diabetic Patients with or without Proteinuria

Background

Podocyte injury is an early feature of diabetic nephropathy (DN). Recently, urinary exosomal Wilm''s tumor-1 protein (WT1), shed by renal epithelial cells, has been proposed as a novel biomarker for podocyte injury. However, its usefulness as biomarker for early diabetic nephropathy has not been verified yet. We investigated urinary exosomal WT1 in type-1 diabetic patients to confirm its role as a non-invasive biomarker for predicting early renal function decline.

Methods

The expression of WT1 protein in urinary exosomes from spot urine samples of type-1 diabetes mellitus patients (n = 48) and healthy controls (n = 25) were analyzed. Patients were divided based on their urinary albumin excretion, ACR (mg/g creatinine) into non- proteinuria group (ACR<30 mg/g, n = 30) and proteinuria group (ACR>30 mg/g, n = 18). Regression analysis was used to assess the association between urinary exosomal levels of WT1 with parameters for renal function. Receiver Operating Characteristic (ROC) curve analysis was used to determine the diagnostic performance of exosomal WT-1.

Results

WT1 protein was detected in 33 out of 48 diabetic patients and in only 1 healthy control. The levels of urinary exosomal WT1 protein is significantly higher (p = 0.001) in patients with proteinuria than in those without proteinuria. In addition, all the patients with proteinuria but only half of the patients without proteinuria were positive for exosomal WT1. We found that the level of exosomal WT1 were associated with a significant increase in urine protein-to-creatinine ratio, albumin-to-creatinine ratio, and serum creatinine as well as a decline in eGFR. Furthermore, patients exhibiting WT1-positive urinary exosomes had decreased renal function compared to WT1-negative patients. ROC analysis shows that WT-1 effectively predict GFR<60 ml. min-1/1.73 m².

Conclusion

The predominant presence of WT1 protein in urinary exosomes of diabetic patients and increase in its expression level with decline in renal function suggest that it could be useful as early non-invasive marker for diabetic nephropathy.     

The Pretreatment Albumin to Globulin Ratio Has Predictive Value for Long-Term Mortality in Nasopharyngeal Carcinoma

Background

Low serum albumin is predictive of poor survival in nasopharyngeal carcinoma (NPC). We evaluated the ability of the pretreatment albumin/globulin ratio (AGR) to predict long-term mortality in patients with NPC.

Methods

This retrospective study examined an unselected cohort of 694 patients with NPC who had documented pretreatment total serum protein and serum albumin levels (ALB). AGR was calculated as [AGR = ALB/(total serum protein - ALB)]. Survival analysis was used to evaluate the predictive value of AGR.

Results

Multivariate analysis demonstrated that a low pretreatment serum AGR (<1.4) was an independent predictor of poor OS (P  = 0.029) and DMFS (P  = 0.033). A low AGR was significantly associated with advanced stage disease (P<0.001), high white blood cell count (P  = 0.033), high neutrophil count (P  = 0.047), high total serum protein (P<0.001) and low ALB (P<0.001).

Conclusion

The pretreatment AGR may represent a simple, potentially useful predictive biomarker for evaluating the long-term prognosis of patients with undifferentiated NPC.     

Albumin Antioxidant Response to Stress in Diabetic Nephropathy Progression

Background

A new component of the protein antioxidant capacity, designated Response Surplus (RS), was recently described. A major feature of this component is the close relationship between protein antioxidant capacity and molecular structure. Oxidative stress is associated with renal dysfunction in patients with renal failure, and plasma albumin is the target of massive oxidation in nephrotic syndrome and diabetic nephropathy. The aim of the present study was to explore the albumin redox state and the RS component of human albumin isolated from diabetic patients with progressive renal damage.

Methods/Principal Findings

Serum aliquots were collected and albumin isolated from 125 diabetic patients divided into 5 groups according to their estimated glomerular filtration rate (GFR). In addition to clinical and biochemical variables, the albumin redox state, including antioxidant capacity, thiol group content, and RS component, were evaluated. The albumin antioxidant capacity and thiol group content were reciprocally related to the RS component in association with GFR reduction. The GFR decline and RS component were significantly negatively correlated (R = –0.83, p<0.0001). Age, creatinine, thiol groups, and antioxidant capacity were also significantly related to the GFR decline (R = –0.47, p<0.001; R = –0.68, p<0.0001; R = 0.44, p<0.001; and R = 0.72, p<0.0001).

Conclusion/Significance

The response of human albumin to stress in relation to the progression of diabetic renal disease was evaluated. The findings confirm that the albumin molecular structure is closely related to its redox state, and is a key factor in the progression of diabetes nephropathy.     

Study of 320-Slice Dynamic Volume CT Perfusion in Different Pathologic Types of Kidney Tumor: Preliminary Results

Objective

To investigate microcirculatory differences between pathologic types of kidney tumor using 320-slice dynamic volume CT perfusion.

Methods

Perfusion imaging with 320-slice dynamic volume CT was prospectively performed in 85 patients with pathologically proven clear cell renal cell carcinoma (RCC) (n = 66), papillary RCC (n = 7), chromophobe RCC (n = 5), angiomyolipoma (AML) with minimal fat (n = 7), or RCC (n = 78). Equivalent blood volume (Equiv BV), permeability surface-area product (PS; clearance/unit volume = permeability), and blood flow (BF) of tumor and normal renal cortex were measured and analyzed. Effective radiation dose was calculated.

Results

There was a significant difference in all three parameters between tumor and normal renal cortex (P<0.001). Equiv BV was significantly different between RCC and AML with minimal fat (P = 0.038) and between clear cell RCC and AML with minimal fat (P<0.001). Mean Equiv BV and BF were significantly higher in clear cell RCC than in papillary RCC (P<0.001 for both) and mean Equiv BV was higher in clear cell RCC than in chromophobe RCC (P<0.001). The effective radiation dose of the CT perfusion protocol was 18.5 mSv.

Conclusion

Perfusion imaging using 320-slice dynamic volume CT can be used to evaluate hemodynamic features of the whole kidney and kidney tumors, which may be useful in the differential diagnosis of these four pathologic types of kidney tumor.     

Prognostic Value of Carbonic Anhydrase IX Immunohistochemical Expression in Renal Cell Carcinoma: A Meta-Analysis of the Literature

Background

Carbonic anhydrase IX (CAIX) protein has been correlated with progression and survival in patients with renal cell carcinoma (RCC). The prognostic value of CAIX in RCC however, remains inconclusive according to published works. This study aimed to analyze CAIX as a biological marker to predict RCC patient prognosis.

Methods

A literature search of the PubMed and Web of Knowledge databases was performed to retrieve original studies from their inception to December of 2013. Fifteen studies, collectively including a total of 2611 patients with renal cell carcinoma, were carefully reviewed. Standard meta-analysis methods were applied to evaluate the prognostic impact of CAIX expression on patient prognosis. The hazard ratio (HR) and its 95% confidence interval (CI) were recorded for the relationship between CAIX expression and survival, and the data were analyzed using Review Manager 5.2 software and Stata software 11.0.

Results

In patients with RCC, low CAIX expression was associated with poor disease-specific survival (HR = 1.89, 95% CI: 1.20–2.98, P = 0.006), unfavorable progression-free survival (HR = 2.62, 95% CI: 1.14–6.05, P = 0.02) and worse overall survival (HR = 2.03, 95% CI: 1.28–3.21, P = 0.002). Furthermore, low CAIX expression was significantly associated with the presence of lymph node metastases (odds ratio (OR) = 0.31, 95% CI = 0.15–0.62, P = 0.0009) and distant metastases (OR = 0.66, 95% CI = 0.46–0.96, P = 0.03) and predicted a higher tumor grade (OR = 0.41, 95% CI = 0.31–0.54, P<0.00001).

Conclusions

Low CAIX expression most likely indicates poor prognosis in RCC patients. Moreover, low CAIX expression was significantly associated with unfavorable clinicopathological factors. To strengthen our findings, further well-designed prospective studies should be conducted to investigate the role of CAIX expression in RCC.     

Patient Age and the Prognosis of Idiopathic Membranous Nephropathy

Background

Idiopathic membranous nephropathy (IMN) is increasingly seen in older patients. However, differences in disease presentation and outcomes between older and younger IMN patients remain controversial. We compared patient characteristics between younger and older IMN patients.

Methods

We recruited 171 Japanese patients with IMN, including 90 (52.6%) patients <65 years old, 40 (23.4%) patients 65–70 years, and 41 (24.0%) patients ≥71 years. Clinical characteristics and outcomes were compared between younger and older IMN patients.

Results

During a median observation period of 37 months, 103 (60.2%) patients achieved complete proteinuria remission, which was not significantly associated with patient age (P = 0.831). However, 13 (7.6%) patients were hospitalized because of infection. Multivariate Cox proportional hazards models identified older age [adjusted hazard ratio (HR) = 3.11, 95% confidence interval (CI): 1.45–7.49, per 10 years; P = 0.003], prednisolone use (adjusted HR = 11.8, 95% CI: 1.59–242.5; P = 0.014), and cyclosporine used in combination with prednisolone (adjusted HR = 10.3, 95% CI: 1.59–204.4; P = 0.012) as significant predictors of infection. A <25% decrease in proteinuria at 1 month after immunosuppressive therapy initiation also predicted infection (adjusted HR = 6.72, 95% CI: 1.51–37.8; P = 0.012).

Conclusions

Younger and older IMN patients had similar renal outcomes. However, older patients were more likely to develop infection when using immunosuppressants. Patients with a poor response in the first month following the initiation of immunosuppressive therapy should be carefully monitored for infection and may require a faster prednisolone taper.     

Association of E/E′ and NT-proBNP with Renal Function in Patients with Essential Hypertension

Objectives

To evaluate the association of left ventricular (LV) diastolic function and N-terminal pro-brain natriuretic peptide (NT-proBNP) with renal function in essential hypertension.

Methods

LV diastolic function was estimated by the ratio of early diastolic velocities (E) from transmitral inflow to early diastolic velocities (E′) of tissue Doppler at mitral annulus (septal corner); NT-proBNP was measured in 207 hypertensive patients (mean age 56±14 years). The subjects were classified into 3 groups: E/E′≤10 group (n = 48), 10<E/E′≤15 group (n = 109) and E/E′>15 group (n = 50). The renal function was estimated by glomerular filtration rate (GFR) with ^99mTc-DTPA. GFR from 30 to 59 ml/min/1.73 m² was defined as Stage 3 chronic kidney disease (CKD). GFR was also estimated using the modified MDRD equation. Albuminuria was defined by urinary albumin/creatinine ratio (UACR).

Results

GFR was lower and UACR was higher in E/E′ >15 group than in 10< E/E′ ≤15 group or E/E′ ≤10 group (p<0.0001), GFR was significantly negative and UACR was positive correlated with E/E′ and NT-proBNP (p<0.0001). In multivariate stepwise linear analysis, GFR had significant correlation with age (p = 0.001), gender (p = 0.003), E/E′ (p = 0.03), lgNT-proBNP (p = 0.001) and lgUACR (p = 0.01), while eGFR had no significant correlation with E/E′ or lgNT-proBNP. Multivariate logistic regression analysis, adjusted for potential confounding factors, showed that participants in E/E′>15 group were more likely to have Stage 3 CKD compared with those in E/E′≤10 group with an adjusted odds ratio of 8.31 (p = 0.0036).

Conclusions

LV diastolic function, assessed with E/E′ and NT-proBNP is associated with renal function in essential hypertension.     

Ventilation/Perfusion Scintigraphy in Children with Post-Infectious Bronchiolitis Obliterans: A Pilot Study

Purpose

Childhood post-infectious bronchiolitis obliterans (BO) is an infrequent lung disease leading to narrowing and/or complete obliteration of small airways. Ventilation and perfusion (V/Q) scan can provide both regional and global pulmonary information. However, only few retrospective researches investigating post-infectious BO involved V/Q scan, the clinical value of this method is unknown. This preliminary prospective study was aimed to evaluate the correlation of V/Q scan with disease severity, pulmonary function test results, and prognosis in children with post-infectious BO.

Methods

Twenty-five post-infectious BO children (18 boys and 7 girls; mean age, 41 months) underwent V/Q scan and pulmonary function tests. Patients were followed after their inclusion. Ventilation index and perfusion index obtained from V/Q scan were used to measure pulmonary abnormalities. Spearman''s rank correlation test of ventilation index and perfusion index on disease severity, lung function tests indices, and follow-up results were performed.

Results

The median follow-up period was 4.6 years (range, 2.2 to 5.0 years). Ventilation index and perfusion index were both correlated with disease severity (r = 0.72, p<0.01 and r = 0.73, p<0.01), but only ventilation index was related to pulmonary function tests results (all p<0.05). In addition, Spearman test yielded significant correlations between perfusion index and prognosis (r = 0.77, p<0.01), and ventilation index and prognosis (r = 0.63, p = 0.01).

Conclusions

For children with post-infectious BO, the present study preliminarily indicated that the degree of ventilation and perfusion abnormalities evaluated by V/Q scan may be used to assess disease severity, and may be predictive of patient''s outcome.     

Comprehensive Clinic-Pathological Characteristics of Cervical Cancer in Southwestern China and the Clinical Significance of Histological Type and Lymph Node Metastases in Young Patients

Objective

To analyze the clinic-pathological characteristics of women with cervical cancers in southwestern China and discuss the features and prognosis of young patients.

Methods

A retrospective study was performed, which consisted of 1,543 patients diagnosed with cervical cancer and underwent treatment at West China Second University Hospital between November 2005 and December 2010. Among them, 154 young patients with surgical procedures between November 2005 and December 2008 were selected for a 5-year follow-up and prognostic analysis.

Results

The proportion of advanced FIGO stage in patients aged over 35 years was higher than in patients aged 35 years or younger (55.1% vs 38.8%, P<0.001), and strong correlation was found between FIGO stages and the postoperative pathological risk factors (P<0.05). 312 patients (20.2%) were under 35 years old in the last 5 years. The proportion of cervical adenocarcinoma remained high in young patients (13.6%), and young women with adenocarcinoma had a higher rate of LN metastases, comparing with those with squamous cell carcinoma (42.9% vs 15.8%, P = 0.004). Young patients with adenocarcinoma had shorter progression-free survival than those who had squamous cell carcinoma (P = 0.024). Patients aged 35 years or younger with positive postoperative pathological risk factors had shorter progression-free survival, comparing with those with negative factors (P<0.01).

Conclusion

Patients over 35 years were preliminarily diagnosed as advanced FIGO stage and they were more likely to have deep stromal invasion, LVSI, LN metastases, parametrial and surgical margin involvement. Regarding to young patients, cervical adenocarcinoma increased the risk of LN metastases and positive postoperative pathological risk factors could apparently worsen the prognosis. Histological type and LN metastases were independent prognostic factors for young patients in southwestern China. We re-emphasize the importance of health education and regular smear screening for elder women, and more attention should be paid to young patients with adenocarcinoma or LN metastases.     

Increased Expression of Pregnancy Up-Regulated Non-Ubiquitous Calmodulin Kinase Is Associated with Poor Prognosis in Clear Cell Renal Cell Carcinoma

Purpose

The aims of this study were to evaluate the clinical significance and potential prognostic value of pregnancy up-regulated non-ubiquitous calmodulin kinase (PNCK) in clear cell renal cell carcinoma (ccRCC) patients.

Materials and Methods

The expression of PNCK mRNA was determined in 24 paired samples of ccRCCs and adjacent normal tissues using real-time RT-PCR. The expression of PNCK was determined in 248 samples of ccRCCs and 92 paired samples of adjacent normal tissues by immunohistochemical analysis. Statistical analysis was performed to define the relationship between PNCK expression and the clinical features of ccRCC.

Results

The mRNA level of PNCK was significantly higher in tumorous tissues than in the adjacent non-tumorous tissues (p<0.001). An immunohistochemical analysis of 92 paired tissue specimens showed that PNCK expression was higher in tumorous tissues than in the adjacent non-tumorous tissues (p<0.001). Moreover, there was a significant correlation between the PNCK expression and various clinicopathological parameters such as Fuhrman grade (p = 0.011), tumor size (p<0.001), T stage (p<0.001) and N stage (p = 0.015). Patients with higher PNCK expression had shorter overall survival time than those with lower PNCK expression (p<0.001). Multivariate analysis indicated that PNCK expression was an independent predictor for poor survival of ccRCC patients.

Conclusions

To our knowledge, this is the first study that determines the relationship between PNCK and prognosis in ccRCC. We found that increased PNCK expression is associated with poor prognosis in ccRCC. PNCK may represent a novel prognostic marker for ccRCC.     

Optimal Proteinuria Target for Renoprotection in Patients with IgA Nephropathy

Background

Proteinuria is a target for renoprotection in kidney diseases. However, optimal level of proteinuria reduction in IgA nephropathy (IgAN) is unknown.

Methods

We conducted a retrospective observational study in 500 patients with biopsy-proven IgAN. Time-averaged proteinuria (TA-P) was calculated as the mean of every 6 month period of measurements of spot urine protein-to-creatinine ratio. The study endpoints were a 50% decline in estimated glomerular filtration rate (eGFR), onset of end-stage renal disease (ESRD), and slope of eGFR.

Results

During a median follow-up duration of 65 (12–154) months, a 50% decline in eGFR occurred in 1 (0.8%) patient with TA-P of <0.3 g/g compared to 6 (2.7%) patients with TA-P of 0.3–0.99 g/g (hazard ratio, 2.82; P = 0.35). Risk of reaching a 50% decline in eGFR markedly increased in patients with TA-P of 1.0–2.99 g/g (P = 0.002) and those with TA-P≥3.0 g/g (P<0.001). ESRD did not occur in patients with TA-P<1.0 g/g compared to 26 (20.0%) and 8 (57.1%) patients with TA-P of 1.0–2.99 and ≥3.0 g/g, respectively. Kidney function of these two groups deteriorated faster than those with TA-P<1.0 g/g (P<0.001). However, patients with TA-P of 0.3–0.99 g/g had a greater decline of eGFR than patients with TA-P<0.3 g/g (−0.41±1.68 vs. −0.73±2.82 ml/min/1.73 m²/year, P = 0.03).

Conclusion

In this study, patients with TA-P<1.0 g/g show favorable outcomes. However, given the faster eGFR decline in patients with TA-P of 0.3–0.99 g/g than in patients with TA-P<0.3 g/g, the ultimate optimal goal of proteinuria reduction can be lowered in the management of IgAN.     

New Insight into Ki67 Expression at the Invasive Front in Breast Cancer

Purpose

To investigate the distribution of Ki67+ cells in breast cancer in relation to clinical-pathological parameters and prognosis.

Materials and Methods

Ki67 expression status was detected in 1,086 breast cancer specimens using immunohistochemistry staining and examining the relationship between the Ki67+ cells'' location. Subsequently, clinical-pathological parameters and prognosis were determined.

Results

In total, Ki67 protein expression was found in 781 (71.92%) of the 1,086 breast cancer specimens. Among the 781 Ki67+ cases, 461 were defined as diffuse type and 320 were defined as borderline type. After universal correlation analysis, significant differences were observed in age, histological grade, metastatic nodes, postoperative distant metastasis, and molecular subtype between Ki67+ and Ki67− cases (P = 0.01, 0.001, 0.001, 0.001, and 0.001, respectively). After subgroup analysis, the borderline cases were found to be characterized by a high distant metastasis rate compared to the diffuse cases as well as the Ki67− cases (P = 0.001). No differences were observed between diffuse type or Ki67− cases (P = 0.105). Multivariate analysis showed that age, tumor size, histological grade, lymph node metastasis, molecular subtype, and the Ki67 distribution pattern were observed to be related to postoperative distant metastasis (all P<0.05). Furthermore, borderline type was shown to attain a significantly more distant bone and liver metastasis and worse disease-specific survival than the other types (P = 0.001). In the Cox regression test, the Ki67 distribution pattern was detected as an independent prognostic factor (P = 0.001).

Conclusion

The distribution pattern of Ki67 may be a new independent prognostic factor for breast cancer.     

Vitreous and Plasma VEGF Levels as Predictive Factors in the Progression of Proliferative Diabetic Retinopathy after Vitrectomy

Purpose

To investigate the vitreous and plasma levels of vascular endothelial growth factor (VEGF) in patients with proliferative diabetic retinopathy (PDR) and to determine whether they predict a disease prognosis after primary vitrectomy.

Methods

Fifty patients (50 eyes) with PDR who underwent pars plana vitrectomy (PPV) and 56 healthy controls (56 eyes) were enrolled in this retrospective study. Clinical data were collected and analyzed. Vitreous and plasma VEGF concentrations were measured using enzyme-linked immunosorbent assays. VEGF levels and clinical data were compared and analyzed to see if they provide a prognosis of PDR progression after primary vitrectomy at more than 6 months follow-up. Correlation of VEGF concentrations between vitreous fluid and plasma was analyzed.

Results

The average BCVA was significantly improved after surgery (P<0.001). Vitreous and plasma VEGF levels were significantly elevated in PDR patients than those in healthy controls (P _vitreous<0.001; P _plasma<0.001). Both vitreous and plasma VEGF levels were significantly higher in PDR progression group than in stable group (P _vitreous<0.001; P _plasma = 0.004). Multivariate logistic regression analyses showed that the increased vitreous VEGF level was associated with the progression of PDR after primary PPV (OR = 1.539; P = 0.036). Vitreous VEGF level was positively associated with plasma VEGF level in PDR patients (P<0.001).

Conclusion

The increased VEGF level in vitreous fluid may be identified as a significant predictive factor for the outcome of vitrectomy in patients with PDR.     

A High Degree of LINE-1 Hypomethylation Is a Unique Feature of Early-Onset Colorectal Cancer

Objective

Early-onset colorectal cancer (CRC) represents a clinically distinct form of CRC that is often associated with a poor prognosis. Methylation levels of genomic repeats such as LINE-1 elements have been recognized as independent factors for increased cancer-related mortality. The methylation status of LINE-1 elements in early-onset CRC has not been analyzed previously.

Design

We analyzed 343 CRC tissues and 32 normal colonic mucosa samples, including 2 independent cohorts of CRC diagnosed ≤50 years old (n = 188), a group of sporadic CRC >50 years (MSS n = 89; MSI n = 46), and a group of Lynch syndrome CRCs (n = 20). Tumor mismatch repair protein expression, microsatellite instability status, LINE-1 and MLH1 methylation, somatic BRAF V600E mutation, and germline MUTYH mutations were evaluated.

Results

Mean LINE-1 methylation levels (±SD) in the five study groups were early-onset CRC, 56.6% (8.6); sporadic MSI, 67.1% (5.5); sporadic MSS, 65.1% (6.3); Lynch syndrome, 66.3% (4.5) and normal mucosa, 76.5% (1.5). Early-onset CRC had significantly lower LINE-1 methylation than any other group (p<0.0001). Compared to patients with <65% LINE-1 methylation in tumors, those with ≥65% LINE-1 methylation had significantly better overall survival (p = 0.026, log rank test).

Conclusions

LINE-1 hypomethylation constitutes a potentially important feature of early-onset CRC, and suggests a distinct molecular subtype. Further studies are needed to assess the potential of LINE-1 methylation status as a prognostic biomarker for young people with CRC.     

FoxM1 Is Associated with Poor Prognosis of Non-Small Cell Lung Cancer Patients through Promoting Tumor Metastasis

Background

FoxM1 has been reported to be important in initiation and progression of various tumors. However, whether FoxM1 has any indication for prognosis in non-small cell lung cancer patients remains unclear.

Methodology/Principal Findings

In this study, FoxM1 expression in tumor cells was examined first by immunohistochemistry in 175 NSCLC specimens, the result of which showed that FoxM1 overexpression was significantly associated with positive smoking status (P = 0.001), poorer tissue differentiation (P = 0.0052), higher TNM stage (P<0.0001), lymph node metastasis (P<0.0001), advanced tumor stage (P<0.0001), and poorer prognosis (P<0.0001). Multivariable analysis showed that FoxM1 expression increased the hazard of death (hazard ratio, 1.899; 95% CI, 1.016–3.551). Furthermore, by various in vitro and in vivo experiments, we showed that targeted knockdown of FoxM1 expression could inhibit the migratory and invasive abilities of NSCLC cells, whereas enforced expression of FoxM1 could increased the invasion and migration of NSCLC cells. Finally, we found that one of the cellular mechanisms by which FoxM1 promotes tumor metastasis is through inducing epithelial-mesenchymal transition (EMT) program.

Conclusions

These results suggested that FoxM1 overexpression in tumor tissues is significantly associated with the poor prognosis of NSCLC patients through promoting tumor metastasis.     

Occult and Overt HBV Co-Infections Independently Predict Postoperative Prognosis in HCV-Associated Hepatocellular Carcinoma

Objective and Background

The roles of chronic hepatitis B virus (HBV) co-infection (CI) in carcinogenesis of hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC) remained controversial. To gain new insights into this issue, we investigated the postoperative prognostic value of HBVCI in HCV-associated HCC.

Methods

A study cohort of 115 liver tissues obtained from the noncancerous parts of surgically removed HCV-associated HCCs were subjected to virological analysis in a tertiary care setting. Assayed factors included clinicopathological variables, tissue amounts of viral genomes, genotypic characterization of viruses, as well as the presence of overt (serum HBsAg positive) or occult (serum HBsAg negative but tissue HBV-DNA positive) HBVCI. Cox proportional hazard model was used to estimate postoperative survivals.

Results

Of the 115 patients, overt and occult HBVCIs were detected in 35 and 16 patients, respectively. Multivariate analysis revealed that tumor size >3 cm (adjusted hazard ratio (AHR), 2.079 [95% confidence interval, 1.149∼3.761]), alpha-fetoprotein >8 ng/mL (AHR, 5.976 [2.007∼17.794]) albumin <4 g/dL(AHR, 2.539 [1.399∼4.606]), ALT >50 U/L (AHR,1.086 [1.006∼1.172]), presence of occult HBVCI (AHR, 2.708 [1.317∼5.566]), and absence of overt HBVCI (AHR, 2.216 [1.15∼4.269]) were independently associated with unfavorable disease-free survival. Patients with occult HBVCI had a shorter disease-free (P = 0.002), a shorter overall survival (P = 0.026), a higher bilirubin level (P = 0.003) and a higher prevalence of precore G1896A mutation (P = 0.006) compared with those with overt HBVCI.

Conclusion

Occult and overt HBVCI served as independent predictors for postoperative survival in HCV-associated HCC.