Prognostic significance of serum vascular endothelial growth factor and endostatin in patients with hepatocellular carcinoma

BACKGROUND: Vascular endothelial growth factor (VEGF) and endostatin stimulate and inhibit tumour angiogenesis respectively. Recent studies have demonstrated the prognostic value of serum levels of both VEGF and endostatin in patients with various types of cancer. Their significance in patients with hepatocellular carcinoma (HCC) remains unclear. METHODS: Serum VEGF and endostatin levels were measured by enzyme immunoassay in 108 patients with HCC before surgical resection and in 20 healthy controls. Preoperative serum VEGF and endostatin levels were correlated with clinicopathological features and long-term survival. RESULTS: Serum VEGF levels in patients with HCC were significantly higher than those in controls, but serum levels of endostatin were similar in the two groups. High serum levels of VEGF, but not endostatin, were significantly associated with venous invasion and advanced tumour stage. Patients with a serum VEGF level higher than median (over 245.0 pg/ml) had significantly worse overall and disease-free survival than those with a lower level (P = 0.012 and P = 0.022 respectively). On multivariate analysis, serum VEGF level was an independent prognostic factor (hazard ratio 1.86 (95 per cent confidence interval 1.10 to 3.92); P = 0.032). Serum endostatin levels did not have significant prognostic influence on overall or disease-free survival. CONCLUSION: A high serum level of VEGF is a predictor of poor outcome after resection of HCC. Serum VEGF, but not endostatin, may be a useful prognostic marker in patients with HCC.     

Serum vascular endothelial growth factor predicts venous invasion in hepatocellular carcinoma: a prospective study

OBJECTIVE: To evaluate the correlation between serum vascular endothelial growth factor (VEGF) level and the clinicopathologic features in patients with hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: VEGF is an important angiogenic factor regulating tumor angiogenesis. A high serum VEGF level has been shown to be associated with tumor progression and metastasis in several human cancers, but its significance in HCC is unclear. The correlation between serum VEGF level and tumor pathologic features in patients with HCC has not been studied before. METHODS: Preoperative serum samples and tumor specimens were prospectively collected in 100 patients undergoing resection of HCC. Serum VEGF level was measured by enzyme-linked immunosorbent assay, and tumor VEGF expression was assessed by immunohistochemical study. Histopathologic examination was performed by a pathologist without prior knowledge of the serum VEGF level or tumor VEGF expression. RESULTS: Preoperative serum VEGF levels ranged from 15 to 1,789 pg/mL (median 269). When serum VEGF levels were compared between groups categorized by different clinicopathologic variables, significant correlation was found between a high serum VEGF level and absence of tumor capsule, presence of intrahepatic metastasis, presence of microscopic venous invasion, and advanced stage. There was a positive correlation between the serum VEGF level and tumor expression of VEGF as well as platelet count. When the 75th percentile serum VEGF level (500 pg/mL) was used as a cutoff level, the frequency of venous invasion in patients with a high serum VEGF level was significantly greater compared with patients with a low serum VEGF level. By multivariate analysis, a serum VEGF level of more than 500 pg/mL and tumor size more than 5 cm were independent preoperative factors predictive of microscopic venous invasion. During a median follow-up of 11.6 months, 48% of patients with a serum VEGF level of more than 500 pg/mL and 27% of those with a serum VEGF level of 500 pg/mL or less developed postoperative recurrence. CONCLUSIONS: These results show that a high preoperative serum VEGF level is a predictor of microscopic venous invasion in HCC, suggesting that the serum VEGF level may be useful as a biologic marker of tumor invasiveness and a prognostic factor in HCC.     

Vascular endothelial growth factor as prognostic factor in renal cell carcinoma

PURPOSE: Vascular endothelial growth factor (VEGF) has been recognized as an important constituent of vascularization and growth of solid tumors. Serum VEGF levels were evaluated and correlated to clinicopathologic findings and clinical outcome in patients with renal cell carcinoma (RCC). MATERIALS AND METHODS: Serum samples were collected before surgery in 164 patients with RCC. Levels of VEGF165 protein in sera were measured using a quantitative ELISA. Univariate and multivariate analyses were performed. RESULTS: The VEGF165 level in serum was significantly increased (p = 0.0001) in patients with RCC (median 343.4 pg./ml.) compared with the control patients (median 103.8 pg./ml.). The level of VEGF165 in serum correlated to clinical stage and histopathological grade. Patients with VEGF165 levels below median value had significantly longer survival time than patients with higher levels (p = 0.0001). This was also shown when VEGF165 was analyzed in univariate Cox regression (p = 0.0001). The impact of VEGF165 on survival was especially shown in patients having tumors with vein invasion (pT3b-c N0 M0) and in patients with clinical stages I - III (p = 0.0240 and p = 0.0023, respectively). When using multivariate analysis, only tumor stage and grade remained as independent prognostic variables. CONCLUSIONS: In RCC, serum VEGF165 level was significantly correlated to tumor stage and grade. Increased levels were correlated to adverse survival. Although, VEGF did not remain as an independent prognostic factor in multivariate analysis the levels of VEGF165 in serum was found useful for the identification of patients with potentially progressive disease especially for those with vein invasion.     

Elevated serum vascular endothelial growth factor and decreased survival in advanced laryngeal carcinoma

PURPOSE: The purpose of this study was to determine whether serum vascular endothelial growth factor (s-VEGF) levels at the time of diagnosis correlate with any known tumor variables and overall survival in patients with advanced laryngeal squamous cell carcinoma. Comparisons with a cohort of normal healthy controls were also performed to determine the potential usefulness of s-VEGF as a screening tool. EXPERIMENTAL DESIGN: Serum from patients enrolled in the VA Laryngeal Cooperative Study #258 (n = 183), as well as normal healthy controls (n = 40) was used in this analysis. Quantitative enzyme-linked immunosorbent assays (ELISA) for VEGF were performed in duplicate on each serum sample. Demographic and survival data were available for each patient enrolled in the study. Univariate analyses, multivariate Cox regression analyses, and Kaplan-Meier survival analysis were used. RESULTS: The mean serum concentration of s-VEGF for the healthy control group was 47.83 +/- 0.13 pg/mL. For all patients enrolled in the VA Cooperative Study, regardless of treatment group, the mean s-VEGF level was 317.22 +/- 25.46 pg/mL. The patients randomly assigned to the surgical arm (n = 97) had a mean value of 315.44 +/- 30.44 pg/mL. Those randomly assigned to the induction chemotherapy arm (n = 86) had a mean s-VEGF level of 319.22 +/- 42.11 pg/mL. Serum VEGF levels were significantly elevated in patients with laryngeal carcinoma compared with healthy controls (p < .001). The serum VEGF levels in each arm of the trial were also elevated versus the healthy controls (p < .001, surgery arm plus radiotherapy; p < .001, chemotherapy plus radiotherapy). In a univariate analysis, elevated s-VEGF correlated with poor Karnofsky performance status for all patients with advanced laryngeal carcinoma (p < .008). High s-VEGF levels also correlated with a poor performance score in patients on the chemotherapy arm of the VA Laryngeal Trial (p < .004). Elevated s-VEGF levels in the surgical plus radiotherapy arm correlated with node-positive disease (p = .047) and supraglottic location of the tumor (p = .022). In a multivariate analysis using all known tumor variables and s-VEGF levels, elevated s-VEGF levels and infiltrating growth pattern correlated with decreased survival for all evaluated patients with advanced laryngeal carcinoma (p = .065, and p = .018, respectively). CONCLUSIONS: Serum VEGF levels are significantly elevated in patients with advanced laryngeal carcinoma versus healthy controls. Elevated pretreatment s-VEGF levels tended to indicate a more aggressive disease state and a poorer overall survival in advanced laryngeal carcinoma.     

Clinical significance of preoperative serum vascular endothelial growth factor levels in patients with colorectal cancer and the effect of tumor surgery

BACKGROUND: Vascular endothelial growth factor (VEGF) is an angiogenic cytokine involved in the progression of solid tumors. In this study we evaluated the clinical usefulness of preoperative serum VEGF concentrations in patients with colorectal cancer. The changes in serum VEGF levels after tumor surgery were also evaluated. METHODS: Serum VEGF levels were determined by an enzyme-linked immunosorbent assay in the sera of 61 healthy control subjects and 67 patients with colorectal cancer preoperatively and 7 and 30 days after surgery. RESULTS: Serum VEGF levels in patients with colorectal cancer (median, 492 pg/mL; interquartile range, 281 to 737 pg/mL) were higher (P <.0001) than in control subjects (median, 186 pg/mL; interquartile range, 100 to 273 pg/mL). There was a significant association between serum VEGF levels and disease stage, invasion depth of the tumor, the presence of lymph node and distant metastases, and the degree of differentiation. Curative but not palliative resection of the primary tumor resulted in a significant decrease of preoperative serum VEGF levels but normalized in only 72% of patients. Failure of a return of VEGF to normal after resection for cure was associated with an increased although not statistically significant risk of metastasis during follow-up. Univariate analysis showed a lower survival rate for patients with increased preoperative serum VEGF levels (P <.002). Multivariate regression analysis showed that the prognostic value of serum VEGF level was not independent of tumor stage. CONCLUSIONS: These findings suggest that VEGF plays an important role in tumor progression and the formation of distant metastases in colorectal cancer. It is at present unclear whether serial estimation of serum VEGF is clinically useful in the prediction of tumor relapse.     

γ-Glutamyltranspeptidase is a Prognostic Marker of Survival and Recurrence in Radiofrequency-Ablation Treatment of Hepatocellular Carcinoma

Purpose

Serum γ-glutamyltranspeptidase (GGT) level, which is often elevated in hepatocellular carcinoma (HCC), has now been found to be an oxidative stress marker which correlates with inflammation in the extracellular hepatic microenvironment. The aim of this study was to investigate the prognostic significance of GGT serum levels in patients undergoing radiofrequency ablation (RFA) therapy for the treatment of HCC.

Methods

This retrospective study included 254 patients with small liver cancer (tumor of ≤5 cm in diameter and nodule of ≤3 cm) who had been treated with RFA. Baseline serum GGT was examined before therapy, and overall survival (OS) and recurrence-free survival were evaluated by the Kaplan–Meier method. Univariate and multivariate analyses were used to analyze the significance of GGT and other serum markers as prognostic factors.

Results

After a median follow-up of 27 months, 51 patients had died and 123 had hepatic recurrence. After treatment with RFA, HCC patients with elevated GGT had a shorter OS versus those with normal GGT level (p = 0.001); they also had higher recurrence (p = 0.001). On multivariate analysis, albumin (p = 0.003), GGT (p = 0.035), and tumor size (p = 0.027) were independent risk factors for survival, and GGT (p = 0.010) and tumor size (p = 0.026) were significant risk factors for recurrence.

Conclusions

Serum GGT is a convenient prognostic biomarker related to OS and recurrence in HCC patients undergoing RFA treatment.     

Circulating VEGF levels in the serum of gastric cancer patients: correlation with pathological variables,patient survival,and tumor surgery

OBJECTIVE: To evaluate the clinical usefulness of serum vascular endothelial growth factor (VEGF) levels in gastric cancer patients. SUMMARY BACKGROUND DATA: Vascular endothelial growth factor plays an important role in the formation of new blood vessels involved in the growth and metastatic spread of solid tumors, but there is limited information regarding the clinical significance of serum VEGF levels in cancer patients. METHODS: Serum VEGF concentrations were measured by an enzyme linked immunosorbent assay in 61 healthy controls and in 58 gastric cancer patients before surgery, and then again at 7 and 30 days after surgery. The association between preoperative serum VEGF levels, clinicopathological features and patient survival, and their changes following surgery were evaluated. RESULTS: Serum VEGF levels in gastric cancer patients were significantly higher than those in controls. There was a significant association between serum VEGF levels and disease stage, as well as invasion depth of the tumor and the presence of distant metastases. Serum VEGF levels decreased significantly after radical resection of the primary tumor and increased in patients with unresectable tumors. Multivariate regression analysis showed that serum VEGF level is an independent prognostic factor for survival. CONCLUSIONS: Serum VEGF levels in gastric patients are significantly higher compared with normal controls and correlate with local tumor extent, disease stage, and the presence of distant metastases. Preoperative serum VEGF concentration decreases significantly after radical resection of the primary tumor and is an independent prognostic factor for patient survival suggesting that determination of serum VEGF levels may be clinically useful.     

Correlation of serum basic fibroblast growth factor levels with clinicopathologic features and postoperative recurrence in hepatocellular carcinoma

BACKGROUND: Basic fibroblast growth factor (bFGF) is an important positive regulator of tumor angiogenesis. This study evaluated the role of serum bFGF as a biological marker of tumor invasiveness and postresection recurrence in hepatocellular carcinoma (HCC). METHODS: Concentrations of bFGF in preoperative serum samples in 88 patients undergoing resection of HCC were measured by a quantitative enzyme-linked immunosorbent assay. A single pathologist performed histopathologic examination of all tumor specimens. All patients were prospectively monitored for tumor recurrence. RESULTS: The preoperative serum bFGF levels ranged from <0.22 to 71.2 pg/mL (median 10.8 pg/mL). There was significant correlation between high serum bFGF levels and large tumor >5 cm, presence of venous invasion or advanced pTNM stage. Patients with a serum bFGF level >10.8 pg/mL had worse disease-free survival than those with a level <10.8 pg/mL (median disease-free survival 11.2 versus 20 months, P = 0.044). Serum bFGF level >10.8 pg/mL (P = 0.035) and tumor size >5 cm (P = 0.004) were independent preoperative factors that predicted early recurrence after resection of HCC. CONCLUSIONS: This study supports a role of bFGF in tumor growth and invasion in HCC. A high preoperative serum bFGF level appears to be predictive of invasive tumor and early postoperative recurrence. The clinical implications of serum bFGF level in HCC warrant further investigation.     

Preoperative Low Serum Calcium Levels Predict Poor Prognosis for Patients with Esophageal Cancer

Purpose: Hypercalcemia has been reported as a poor prognostic factor in malignant tumors. However, no report has shown the clinical impact of serum calcium levels on patients with esophageal cancer. We evaluated the prognostic impact of preoperative serum calcium levels on patients with esophageal cancer.Methods: We evaluated 240 patients (197 men, 43 women; mean age, 66 years; age range, 34–85 years) with esophageal cancer who underwent radical surgery between September 2008 and December 2017. After assigning the patients to two groups (high calcium group, 8.8 mg/dL or more and low calcium group, 8.7 mg/dL or less), we compared the groups’ overall survival and the clinicopathological features. The clinicopathological and prognostic significance of preoperative serum calcium levels were evaluated in a univariate and multivariate analysis.Results: The patients with deep tumors showed low serum calcium levels significantly more frequently (P <0.05). The low calcium group showed a significantly worse prognosis than the high calcium group (P <0.05). However, low serum calcium level was not an independent poor prognostic factor.Conclusions: Preoperative low serum calcium levels were associated with advanced tumors. Low serum calcium might be associated with esophageal cancer progression.     

Serum levels of vascular endothelial growth factor (VEGF) and endostatin in renal cell carcinoma patients compared to a control group

OBJECTIVES: Renal cell carcinoma (RCC) is a vascularised neoplasm. The importance of the angiogenic process in its growth and metastatic spreading is widely recognised. We assessed serum levels of endogenous endostatin and vascular endothelial growth factor (VEGF) in RCC patients and healthy volunteers, and evaluated the factors' prognostic role for patients' survival, distinguishing histologic subtypes with respect to correlation with tumour stage, grade, and size. METHODS: We considered 146 consecutive patients with RCC and 110 healthy volunteers. Serum samples from all subjects were analysed for endostatin and VEGF by using competitive enzyme immunoassays. RCC samples were compared with serum from the control group and with clinicopathologic factors and clinical outcome. RESULTS: Mean age was 63 years (range: 37-85 years) in RCC patients and 62 years (range: 23-88 years) in the control group. VEGF levels (median: 3.6 ng/ml+/-6.97; range: 0-48.4 ng/mL) were significantly higher in RCC patients, compared with controls (p=0.001). Endostatin levels did not differ significantly between the two groups (p=0.9) without correlation between endostatin and VEGF levels (p=0.09). No significant difference was found in the endostatin levels among the histologic subtypes (p=0.973) and VEGF (p=0.232). The median follow-up was 27 months (range: 1-57 months). CONCLUSIONS: Serum VEGF levels are elevated in RCC patients, compared with controls, and do not correlate significantly with circulating endostatin levels. No difference in preoperative serum VEGF and endostatin levels among the different histologic subtypes was found. In multivariate analysis VEGF and endostatin failed to be prognostic; only tumour stage and grade remained independent predictors of survival.     

Serum IL-6 level is associated with clinical outcome of intravesical gemcitabine therapy in T1 non-muscle–invasive bladder cancer

PurposeSerum biomarkers are valuable tools to predict the prognosis of anticancer therapies. This study aimed to evaluate the impact of serum interleukin-6 (IL-6) level on the clinical outcome of intravesical gemcitabine (GEM) therapy in non-muscle–invasive bladder cancer (NMIBC).MethodsThis retrospective study enrolled 71 patients initially diagnosed with T1 NMIBC who underwent intravesical GEM therapy between 2017 and 2019. The expression of IL-6 gene was examined by real-time PCR. Serum IL-6 level was determined by enzyme-linked immunosorbent assay (ELISA). The cell viability after gemcitabine treatment was measured by CCK-8 assay. The optimal serum IL-6 cutoff values for recurrence prediction were calculated using receiver-operating characteristic curve analysis with reference to cancer recurrence. Recurrence-free survival was compared by the log-rank test. Univariate and multivariate Cox regression analysis was conducted to identify the prognostic factors influencing recurrence-free survival after treatment with intravesical GEM.ResultsIncreased expression and secretion of IL-6 were observed in GEM-resistant sublines compared with parental bladder cancer cell lines. Serum IL-6 level rendered a sensitivity of 82.6% and a specificity of 77.1% to correlate with the cancer recurrence after intravesical GEM. Patients with a high serum IL-6 level exhibited shorter recurrence-free survival after intravesical GEM. Moreover, serum IL-6 level in our NMIBC cohort was significantly associated with clinicopathological characteristics, such as tumor diameter, multifocality, concomitant CIS, and grade. Serum IL-6 level was an independent prognostic factor for recurrence-free survival in NMIBC patients treated with intravesical GEM.ConclusionGiven that it was significantly associated with clinical outcome of intravesical GEM therapy, serum IL-6 level might be used as a potential prognostic biomarker for intravesical GEM in T1 NMIBC.     

Serum levels of vascular endothelial growth factor as a prognostic factor in bladder cancer

PURPOSE: Vascular endothelial growth factor is an overriding growth factor mediating tumor angiogenesis. We correlated serum vascular endothelial growth factor in patients with bladder cancer with clinical parameters. MATERIALS AND METHODS: Serum vascular endothelial growth factor in 58 patients with bladder cancer, including superficial and invasive tumors in 42 and 16, respectively, and 41 healthy controls was measured by sandwich enzyme immunoassay. RESULTS: Significant differences in serum vascular endothelial growth factor were observed in healthy controls and patients with bladder cancer (mean 248 versus 100 pg./ml., p <0.001). The serum level was significantly associated with tumor stage (p <0.0001), grade (p <0.002), vascular invasion (p <0.001) and carcinoma in situ (p <0.01). Patients with metastasis had a significantly higher levels than those with localized diseases (mean 582 versus 194 pg./ml., p <0.0001). At a cut-off of 400 pg./ml. the sensitivity and specificity of the test for differentiating patients with and without metastatic diseases was 87.5% and 98%, respectively (p <0.0001). Univariate statistical analysis showed that an increase in serum vascular endothelial growth factor level greater than 400 pg./ml. was significantly related to disease-free survival. On multivariate analysis only stage remained as an independent prognostic factor. CONCLUSIONS: Although vascular endothelial growth factor did not remain an independent prognostic factor on multivariate analysis, our data indicate that the level of vascular endothelial growth factor may be a valuable angiogenic marker for identifying metastatic bladder cancer. It may be used as a new predictor of disease.     

Percutaneous Radiofrequency Ablation for Recurrent Hepatocellular Carcinoma After Hepatectomy: Long-term Results and Prognostic Factors

Background We evaluated the long-term survival results and safety of percutaneous radiofrequency ablation (RFA) for recurrent hepatocellular carcinoma (HCC) after hepatectomy, and assessed the prognostic factors that can influence its long-term therapeutic results. Methods One hundred and two patients, who had 119 recurrent HCC in their livers, underwent ultrasound-guided percutaneous RFA. All the patients had a history of hepatic resection as a first-line treatment modality for HCC. The mean diameter of the recurrent tumors was 2.0 cm (range, 0.8–5.0 cm). We evaluated the effectiveness rates, local tumor progression rates, survival rates, and complications. We also assessed the prognostic factors of the survival rates by using Cox proportional hazard models. Results The primary effectiveness rate was 93.3% (111 of 119). The cumulative rates of local tumor progression at 1, 3, and 5 years were 6.0, 8.6, and 11.9%, respectively. The cumulative survival rates at 1, 2, 3, 4, and 5 years were 93.9, 83.7, 65.7, 56.6, and 51.6%, respectively. Patients with a lower serum α-fetoprotein (AFP) level (≤100 μg/L) before RFA or with small resected tumors (≤5 cm) demonstrated better survival results (P < .05). There was only one major complication (liver abscess, 1.0% per treatment) during the follow-up period. There were no procedure-related deaths. Conclusions Percutaneous RFA is an effective and safe treatment modality for intrahepatic recurrent HCC after hepatectomy. Serum AFP level before RFA and resected tumor size were significant prognostic predictors of long-term survival.     

射频消融治疗肝细胞癌的生存率及预后因素分析

目的探讨射频消融(RFA)治疗肝细胞癌(HCC)的总生存率、无局部复发生存率和无瘤生存率及其预后因素。方法192例HCC患者行超声引导下RFA治疗。男151例,女41例。平均年龄59.2岁(24～87岁)。肿瘤平均大小(3.9±1.3)cm(1.2～8.0cm)。肝功能ChildPugh分级A、B、C级分别为106、77和9例。根据UICCTNM分期,Ⅰ、Ⅱ、Ⅲ、Ⅳ期肝癌分别为57、85、44和6例。单因素分析采用KaplanMeier及Logrank时序检验,多因素采用COX比例风险模型。结果192例HCC患者治疗后1、2、3、4年总生存率为84.9%、69.1%、60.4%和52.8%;无局部复发生存率为75.1%、53.8%、43.9%和40.8%;无瘤生存率为64.3%、43.2%、37.1%和25.0%。多因素分析获得的预后因素为:(1)总生存期:ChildPugh分级,规范化方案治疗和UICCTNM分期。(2)无局部复发生存期:ChildPugh分级,UICCTNM分期。(3)无瘤生存期:UICCTNM分期,ChildPugh分级,卫星灶。其中,ChildPugh分级和UICCTNM分期在3种生存率的预后分析中均为独立预后因素。结论根据RFA治疗结果分析,HCC肿瘤进展程度(UICCTNM分期和有无卫星灶)、患者肝功能以及治疗方法(是否应用规范化方案)是影响疗效的重要因素,此结果有助于在RFA治疗前、中和后3个环节中采取相应措施,以改善生存期。     

血管内皮细胞生长因子是预测肝细胞癌患者术后转移复发的潜在指标

目的　检测肝细胞癌（ＨＣＣ） 患者术前血清血管内皮细胞生长因子（ＶＥＧＦ）水平与ＨＣＣ切除术后转移复发的关系。方法　采用ＥＬＩＳＡ法检测ＨＣＣ患者血清ＶＥＧＦ水平,同时应用Ｗｅｓｔｅｒｎ Ｂｌｏｔ方法对２４ 例相应ＨＣＣ组织ＶＥＧＦ表达水平进行定量分析。结果　高转移复发倾向组ＨＣＣ 患者术前血清ＶＥＧＦ水平（２８３．３３±２６３ ．１５） ｎｇ／Ｌ显著高于低转移复发倾向组（１４７．０４ ±１３２ ．６８） ｎｇ／Ｌ（ Ｐ＜ ０ ．０５） 。Ｗｅｓｔｅｒｎ Ｂｌｏｔ 显示,ＨＣＣ患者血清ＶＥＧＦ水平变化与其对应肿瘤组织ＶＥＧＦ表达变化一致。结论　ＨＣＣ患者术前血清ＶＥＧＦ水平可作为预测ＨＣＣ切除术后转移复发的指标。ＨＣＣ患者血清ＶＥＧＦ水平升高是其对应肿瘤组织高表达的结果。     

Increased vascular endothelial growth factor in patients with cyanotic congenital heart diseases may not be normalized after a Fontan type operation

Background

To determine the change of serum concentration of vascular endothelial growth factor (VEGF) in patients with cyanotic congenital heart disease (C-CHD).

Methods

Patients conmprised four groups: group A, 19 patients without cyanosis; group B, 24 patients with C-CHD; group C, 17 patients who had C-CHD and underwent biventricular repair; and group D, 15 patients who had single ventricle and underwent a Fontan type operation. Blood samples were obtained from upper arm veins and serum VEGF was determined. We determined correlation between serum VEGF and arterial oxygen saturation and compared levels of serum VEGF among groups. In addition, age and hemodynamic variables derived from cardiac catheterization were analyzed in terms of correlation with serum VEGF.

Results

Serum VEGF significantly negatively correlated with arterial oxygen saturation (r = −0.62, p < 0.0001). Serum VEGF in B and D were significantly higher than those in A and C (median = 443 pg/mL in B and 302 pg/mL in D vs 180 pg/mL in A and 216 pg/mL in C, respectively). Serum VEGF was significantly negatively correlated with patient's age (p = 0.54, p < 0.04) in D, but significantly positively correlated with systemic venous pressure (p = 0.45, p < 0.01) in pooled data.

Conclusions

Patients with C-CHD have increased serum VEGF in parallel with the degree of cyanosis. With biventricular repair, cyanosis and serum VEGF are normalized. However, with a Fontan type operation, cyanosis disappears but serum VEGF may not be normalized because of elevated venous pressure in association with younger age.     

Serum VEGF level is associated with the outcome of patients with hepatocellular carcinoma: a meta-analysis

Background

Hepatocellular carcinoma (HCC) is a highly vascular tumor that expresses vascular endothelial growth factor (VEGF). Various studies have evaluated the prognostic value of VEGF levels in HCC, but yielded conflicting results.

Methods

Electronic databases updated to June 2013 were searched to find relevant studies. A meta-analysis was conducted with eligible studies which quantitatively evaluated the relationship between serum VEGF level and survival of patients with HCC. Survival data were aggregated and quantitatively analyzed.

Results

We performed a meta-analysis of 11 studies that evaluated the correlation between serum VEGF level and survival in patients with HCC. Combined hazard ratios suggested that serum VEGF level had an unfavorable impact on overall survival (OS) [hazard ratio (HR) =1.88, 95% confidence interval (CI): 1.46-2.30], and disease free survival (DFS) (HR=2.27, 95% CI: 1.55-2.98) in patients with HCC. No significant heterogeneity was observed among all studies.

Conclusions

Serum high VEGF level indicates a poor prognosis for patients with hepatocellular carcinoma.Key Words: Vascular endothelial growth factor (VEGF), hepatocellular carcinoma (HCC), prognosis, meta-analysis     

Correlation between serum immunosuppressive substance and clinico-pathological findings in patients with gastric carcinoma

Serum levels of immunosuppressive substance (IS) were determined in 99 patients with gastric cancer and in 32 healthy individuals. The serum IS levels in the patients (769.6±314.8 μg/ml) were significantly higher than those in the healthy individuals (549.7±104.7 μg/ml). A multivariate analysis on the correlation between serum IS levels and clinicopathological findings in the patients disclosed that there was a close correlation between the serum IS levels and the depth of invasion, in particular, the prognostic serosal invasion, metastasis to the distal lymph nodes and peritoneal dissemination. There was, however, no correlation between the serum IS level and hepatic metastasis. Serum IS levels were higher in patients with well-differentiated adenocarcinoma than in those with poorly differentiated adenocarcinoma or signet ring cell carcinoma. A serum IS level higher than 1000 μg/ml indicates the possibility that the tumor is only palliatively resectable because of involvement of the distal lymph nodes or peritoneal dissemination.     

Incomplete Ablation After Radiofrequency Ablation of Hepatocellular Carcinoma: Analysis of Risk Factors and Prognostic Factors

Background Complete ablation rates after a single session of radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) vary from 48% to 97%. Limited data are available regarding risk factors and prognostic significance of incomplete ablation. Methods Between April 2001 and March 2006, 298 patients underwent RFA of 393 HCC nodules with an intent of complete ablation after a single session. Risk factors for incomplete ablation and its effect on overall survival were analyzed. Results Two hundred seventy-three (91.6%) underwent complete tumor ablation, whereas the other 25 (8.4%) underwent incomplete tumor ablation after a single session of RFA. By multivariate analysis, tumor size >3 cm (P = .049) was found to be the only independent risk factor for incomplete ablation. There was no statistically significant difference in overall survival between patients with complete and incomplete ablation. By univariate analysis, no previous transarterial chemoembolization (TACE), preoperative serum alfa-fetoprotein ≤100 μg/mL, and complete response after further treatment of incomplete ablation were associated with better overall survival in patients with incomplete ablation. Conclusions This study demonstrated that incomplete ablation after RFA of HCC was associated with tumor size >3 cm. Our data also suggest that aggressive further treatment of tumors with incomplete ablation aiming at complete tumor response improves overall survival.     

The prognostic significance of percentage of tumour involvement according to disease risk group in men treated with radical prostatectomy

We investigated the prognostic significance of percentage of tumour involvement (PTI) according to the clinicopathological features of prostate cancer among patients who underwent radical prostatectomy (RP). A retrospective study of 534 patients who underwent RP between September 2003 and March 2008 without any neoadjuvant or adjuvant therapy was performed. The associations of PTI with various clinicopathological features and biochemical recurrence-free survival were examined via uni- and multivariate analyses. The predictive accuracy of the multivariate model was assessed with a receiver operating characteristics-derived area under the curve. PTI was demonstrated to be significantly associated with preoperative prostate-specific antigen (PSA) level (P=0.001), pathological Gleason score (P<0.001), extraprostatic tumour extension (P<0.001), seminal vesicle invasion (P<0.001) and positive surgical margin (P<0.001) in univariate analyses. When patients were stratified into disease risk groups, PTI was an independent predictor of biochemical recurrence-free survival in multivariate analysis only among the low-risk group (P=0.033) but not the intermediate- (P=0.287) or the high-risk groups (P=0.828). The addition of the PTI did not significantly increase the accuracy of the multivariate model devised for the prediction of biochemical recurrence-free survival among both total patients (P=0.459) and the low-risk group (P=0.268), respectively. In conclusion, although PTI appeared to be a more significant prognostic factor among patients with low-risk disease than among those with higher risk diseases, overall, the PTI may not provide additional prognostic information beyond what can already be obtained via established prognostic factors.