Interleukin-6, tumour necrosis factor alpha and interleukin-1beta in patients with renal cell carcinoma

As regulators of malignant cell behaviour and communication with stroma, cytokines have proved useful in understanding cancer biology and developing novel therapies. In renal cell carcinoma, patients with inflammatory reactions are known to have poor prognosis. In order to elucidate the relation between renal cell carcinoma and the host, serum levels of inflammatory cytokines, interleukin-6, tumour necrosis factor alpha, interleukin-1beta, were measured. One hundred and twenty-two patients with renal cell carcinoma and 21 healthy control subjects were studied, and serum cytokine levels were measured using a highly sensitive ELISA kit. As a result, in the control group, interleukin-6, tumour necrosis factor alpha and interleukin-1beta levels were 1.79+/-2.03, 2.74+/-0.94 and 0.16+/-0.17 pg ml(-1), respectively. In the renal cell carcinoma patients, they were 8.91+/-13.12, 8.44+/-4.15 and 0.53+/-0.57 pg ml(-1), respectively, and significantly higher. In the comparison of stage, interleukin-6 level was significantly higher in the stage IV group compared to the other stage groups including the control group, while tumour necrosis factor alpha level was significantly higher in each stage group compared to the control group. As for grade, interleukin-6 level was significantly higher in the grade 3 group compared to the control, grade 1 and grade 2 groups, while tumour necrosis factor alpha level was significantly higher in each grade group compared to the control group. All cytokines had a positive correlation with tumour size. In regard to the correlation with CRP, all cytokines had a positive correlation with CRP, while interleukin-6 had a particularly strong correlation. In conclusion, interleukin-6 may be one of the factors for the poor prognosis of patients with renal cell carcinoma. In addition, tumour necrosis factor alpha may be useful in the early diagnosis of renal cell carcinoma and post-operative follow-up.     

Neuroendocrine Differentiation in Renal Cell Carcinoma: Evaluation of Chromogranin A and Neuron-Specific Enolase

Chromogranin A and neuron-specific enolase (NSE) as neuroendocrine markers were evaluated in 200 patients with renal cell carcinoma, and 15 patients with benign renal cysts. Immunoassays of serum levels and immunohistochemical staining of tumour tissue were performed. Serum chromogranin A was elevated in 28 (14%) patients with renal cell carcinoma, but the levels did not differ from those for patients with benign cysts. Serum NSE was elevated in 54 (27%) patients, significantly higher compared with controls (p=0.0002). Serum chromogranin A level was positively correlated to serum creatinine and age, but not to tumour stage or grade. Serum NSE level was positively correlated to tumour stage and grade, but not to serum creatinine or age. Immunohistochemical staining for chromogranin A was positive in 1 of 24 (4%), and for NSE in all 18 (100%) tumours analysed. In a multivariate analysis, tumour stage, grade, and serum NSE, but not chromogranin A, were significant predictors of prognosis.     

Increased serum cortisol levels are associated with high tumour grade in patients with renal cell carcinoma

Cortisol and dehydroepiandrosterone (DHEA) and its sulphate (DHEAS) are the major steroid hormones produced by the human adrenal cortex. The serum levels of cortisol and DHEAS were analysed in 211 consecutive patients with renal cell carcinoma before initiation of therapy. Serum cortisol was significantly higher in patients with renal cell carcinoma compared with that in patients with benign cysts (p < 0.0001). Serum cortisol was independent of disease stage, but positively correlated to tumour diameter and grade. The serum levels of DHEAS were higher in men than in women, and decreased with age, but did not correlate with disease stage, tumour diameter or grade. The prognosis of patients with elevated serum cortisol tended to be poorer (p = 0.06) than the prognosis of those with lower levels. In a multivariate analysis, disease stage and tumour grade were independent predictors of prognosis. Age, gender and serum levels of cortisol and DHEAS were of limited value for prognosis.     

Prognostic factors of common epithelial ovarian cancer treated by surgery and cisplatin based combination chemotherapy

Retrospective analysis of prognostic factors in 171 patients who had common epithelial ovarian cancer (WHO) and treated by surgeries and cisplatin based combination chemotherapies were performed by survival assay and multivariate analysis. In FIGO stage 3, the estimated parameter values were in following order: residual tumour age grade performance status histological type. On analysing Stage patients, histological grading and histological typing had an effect on prognosis. Patients with grade 2 or tumours had a worse prognosis than did those with grade 1 tumours, and patients with clear-cell carcinoma or undifferentiated adenocarcinoma showed a poor prognosis.     

Soluble vascular endothelial growth factor levels in patients with primary colorectal carcinoma. The Danish RANX05 Colorectal Cancer Study Group.

INTRODUCTION: Angiogenesis is decisive in tumour progression and metastasis. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor, and increased VEGF levels in patients with carcinomas may facilitate growth of both primary and secondary tumours. METHODS: Soluble (s) VEGF levels were determined in serum from 91 volunteer healthy blood donors and from 614 patients scheduled to undergo resection for primary colorectal cancer. None of the patients received pre- and/or post-operative chemo- and/or radiotherapy. The results of sVEGF were analysed with respect to Dukes> stage, gender, age and topographical tumour localization. RESULTS: Patients with colorectal cancer had significantly (P<0.0001) higher levels of sVEGF, compared to healthy blood donors. Patients with Dukes> stage D disease had significantly (P=0.01) higher values than patients with Dukes> stage A, B and C disease, who had comparable values. Patients with the primary tumour localized in the colon had significantly (P<0.0001) higher levels of sVEGF than patients with the primary tumour localized in the rectum. By classifying the patients into two groups, based on the upper limit of the 95(th)percentile of sVEGF of healthy individuals (sVEGF=465 pg/ml), we found a significantly (P<0.0001) reduced overall survival in patients with sVEGF >465 pg/ml compared to patients with sVEGF values below this level. Moreover, in the subgroup of patients with the carcinoma localized in the colon and sVEGF levels above 465 pg/ml, we found a significantly (P<0.0001) reduced overall survival compared to colon cancer patients with lower sVEGF values. In conclusion, data from the present study suggest a biological significance of VEGF in patients with colorectal cancer, and indicate that a high pre-operative sVEGF value is associated with poor outcome, but further research is needed to validate sVEGF as a cancer marker.     

Low levels of basic fibroblast growth factor (bFGF) are associated with a poor prognosis in human breast carcinoma.

It has been suggested that angiogenesis and angiogenic factors may be strong predictors of relapse in patients with breast carcinoma. We measured the levels of the angiogenic peptide basic fibroblast growth factor (bFGF) in 140 breast tumour cytosols using an immunoassay. There were no significant differences in bFGF levels between breast non-malignant lesions and primary carcinomas. In 124 cases with primary breast cancer, we observed an association of low bFGF levels (< 400 pg mg[-1]) with increasing tumour size (P = 0.023) and stage of disease (P = 0.002). bFGF levels did not correlate with other variables, including axillary nodes, hormone receptors, cathepsin D and the serum tumour markers CA15.3 and CEA. With a median follow-up of 44.0 months, breast cancer patients with low levels of bFGF had a significantly shorter disease-free survival (DFS) than patients with elevated bFGF (log-rank, P < 0.0001). In a multivariate analysis of DFS, only bFGF, T-stage and histological grade showed statistical significance. In a parallel evaluation of circulating bFGF, we did not observe a correlation between the serum and tissue bFGF levels in the 29 selected cases with matched determinations. Our results indicate that low bFGF levels in breast carcinoma are an independent prognostic indicator of poor prognosis and disease recurrence.     

肝细胞癌介入栓塞前后血管内皮生长因子和内皮抑素的变化与预后的关系

目的 探讨肝细胞癌患者肝动脉化疗栓塞术(TACE)前后血管内皮生长因子(VEGF)和内皮抑素(ES)变化规律与预后的关系.方法 酶联免疫吸附试验(ELISA)法检测患者TACE术前及术后1周血清VEGF和ES水平.结果 肿瘤直径≥5 cm的患者,ES在治疗前后分别为(43.35±9.80)ng/ml、(48.35±10.89)ng/ml;VEGF分别为(310.23±64.31)ng/ml、(369.10±60.11)ng/ml.肿瘤伴有门静脉癌栓的患者ES在治疗前后分别为(54.28±8.78)ng/ml、(50.28±7.51)ng/ml;VEGF分别为(331.26±63.38)ng/ml、(400.29±60.98)ng/ml.VEGF和ES水平与肿瘤大小、门静脉癌栓以及临床分期密切相关(P＜0.05).肝细胞癌患者临床分期越晚,TACE前、后VEGF和ES水平均越高.晚期肝癌患者VEGF/ES比值明显高于早期患者.VEGF/ES比值越低生存时间越长.结论 VEGF、ES、VEGF/ES比值可作为预测肝细胞癌治疗效果的指标.     

Differing Risk of Cancer Death Among Patients With Pathologic T3a Renal Cell Carcinoma: Identification of Risk Categories According to Fat Infiltration and Renal Vein Thrombosis

ObjectivesThe study objectives were to evaluate the prognostic impact of fat infiltration and renal vein thrombosis in patients with pT3a renal cell carcinoma (RCC) and to identify new prognostic groups.Material and MethodsWe analyzed 122 consecutive patients with pT3a who underwent radical nephrectomy for RCC between 2000 and 2011 at the University of Bologna. Cancer-specific survival (CSS) rates were estimated using Kaplan–Meier survival curves; univariable and multivariable analyses were performed with Cox analysis.ResultsThe mean follow-up was 41.7 ± 35.4 months. Patients with peritumoral/hilar fat infiltration (n = 63) and patients with renal vein thrombosis (n = 18) experienced comparable CSS rates, whereas patients with both fat infiltration plus renal vein thrombosis (n = 41) showed worse survival outcomes than the first group (P = .026). Patients were divided in 2 groups: group A, with fat invasion or renal vein thrombosis, and group B, with concomitant fat invasion and renal vein invasion. Group B showed worse cancer-specific survival than group A (P = .024). At multivariate analysis, this new risk-group stratification was found to be an independent prognostic predictor of CSS (P < .05).ConclusionsPatients with T3a RCC with both fat invasion and renal vein thrombosis experience worse survival rates when compared with those patients with only 1 prognostic factor. The TNM classification should consider the concomitant presence of those parameters as a different prognostic predictor.     

Parathyroid hormone-related protein and serum calcium in patients with renal cell carcinoma.

OBJECTIVE: To evaluate serum parathyroid hormone-related protein (PTHrP) in relation to serum calcium and clinical outcome of patients with renal cell carcinoma. METHODS: Sera from 243 patients with renal cell carcinoma were collected prior to therapy. Serum PTHrP was analyzed using an immunoradiometric assay. Tumour stage, nuclear grade, corrected serum calcium, and survival were assessed. RESULTS: Serum PTHrP was detectable in 37/243 sera (15%) and hypercalcaemia (> or =2.60 mmol/l) in 32/220 (15%). A positive correlation between serum PTHrP and serum calcium was found (r = 0.326; p < 0.01). Following subdivision of the material, based on storage time, the frequency of detectable serum PTHrP seemed to decrease with time. Serum calcium, but not serum PTHrP, was correlated to tumour stage (p < 0.001). Survival was similar for patients with detectable and undetectable PTHrP, but those with hypercalcaemia had a significantly shorter survival time compared to those with normal serum calcium (p < 0.001). A multivariate analysis showed that tumour stage and serum calcium were independent prognostic factors, but not grade or PTHrP. CONCLUSIONS: A positive relation of serum PTHrP to serum calcium was demonstrated in patients with renal cell carcinoma. Hypercalcaemia but not serum PTHrP predicted a worse prognosis.     

Serum insulin-like growth factor-1 is an independent predictor of prognosis in patients with renal cell carcinoma

Obesity is associated with an increased risk of certain cancers, including renal cell carcinoma. A possible mediator of this risk is insulin-like growth factor-1 (IGF-1). The authors evaluated the prognostic information of IGF-1, IGFBP-3, leptin, and prealbumin in sera sampled at diagnosis from 256 consecutive patients with renal cell carcinoma. Insulin-like growth factor-1 and leptin were positively correlated to body mass index (BMI). Insulin-like growth factor-1 and IGFBP-3 did not correlate to tumour stage or grade. Leptin and prealbumin were both inversely related to tumour stage and grade. When survival was analysed in patients with levels above a median of IGF-1, leptin, and prealbumin, prognosis was more favourable, compared with those with lower levels (p=0.017; p=0.024, and p<0.0001, respectively). In a multivariate analysis, tumour stage and serum IGF-1 levels were independent prognostic factors. The results indicate that serum IGF-1 at diagnosis is related to prognosis in renal cell carcinoma.     

The key hypoxia regulated gene CAIX is upregulated in basal-like breast tumours and is associated with resistance to chemotherapy

Basal-like tumours account for 15% of invasive breast carcinomas and are associated with a poorer prognosis and resistance to therapy. We hypothesised that this aggressive phenotype is because of an intrinsically elevated hypoxic response. Microarrayed tumours from 188 patients were stained for hypoxia-inducible factor (HIF)-1α, prolyl hydroxylase (PHD)1, PHD2, PHD3 and factor inhibiting HIF (FIH)-1, and carbonic anhydrase (CA) IX stained in 456 breast tumours. Tumour subtypes were correlated with standard clincopathological parameters as well as hypoxic markers. Out of 456 tumours 62 (14%) tumours were basal-like. These tumours were positively correlated with high tumour grade (P<0.001) and were associated with a significantly worse disease-free survival compared with luminal tumours (P<0.001). Fifty percent of basal-like tumours expressed HIF-1α, and more than half expressed at least one of the PHD enzymes and FIH-1. Basal-like tumours were nine times more likely to be associated with CAIX expression (P<0.001) in a multivariate analysis. Carbonic anhydrase IX expression was positively correlated with tumour size (P=0.005), tumour grade (P<0.001) and oestrogen receptor (ER) negativity (P<0.001). Patients with any CAIX-positive breast tumour phenotype and in the basal tumour group had a significantly worse prognosis than CAIX-negative tumours when treated with chemotherapy (P<0.001 and P=0.03, respectively). The association between basal phenotype and CAIX suggests that the more aggressive behaviour of these tumours is partly due to an enhanced hypoxic response. Further, the association with chemoresistance in CAIX-positive breast tumours and basal-like tumours in particular raises the possibility that targeted therapy against HIF pathway or downstream genes such as CAs may be an approach to investigate for these patients.     

Circulating interleukin-6 predicts survival in patients with metastatic breast cancer

Interleukin-6 (IL-6) is a multifunctional cytokine produced by macrophages, T cells, B cells, endothelial cells and tumour cells. Interleukin-6 is able to promote tumour growth by upregulating anti-apoptotic and angiogenic proteins in tumour cells. In murine models it has been demonstrated that antibodies against IL-6 diminish tumour growth. Several reports have highlighted the prognostic importance of IL-6 in e.g., prostate and colon cancer. We addressed prospectively the prognostic significance of serum IL-6 (sIL-6), measured at diagnosis of metastasis, in 96 unselected and consecutive patients with progressive metastatic breast cancer before the initiation of systemic therapy. The median sIL-6 value for the breast cancer population was 6.6 +/- 2.1 pg/ml. Patients with 2 or more metastatic sites had higher sIL-6 values compared to those with only 1 metastatic site (respectively 8.15 +/- 1.7 pg/ml and 3.06 +/- 6.6 pg/ml; p < 0.001). Patients with liver metastasis (8.3 +/- 2.4 pg/ml), with pleural effusions (10.65 +/- 9.9 pg/ml) and with dominant visceral disease (8.15 +/- 3.3 pg/ml) had significantly higher values compared to those without liver metastases (4.5 +/- 3.4 pg/ml; p = 0.001), without pleural effusions (5.45 +/- 1.5 pg/ml; p = 0.0077) and with dominant bone disease (4.5 +/- 1.4 pg/ml; p = 0.007) respectively. No correlation between sIL-6 and age, menopausal status, performance status, tumour grade, body-mass index, histology and hormone receptor status was found. Multivariate analysis showed that high levels of serum IL-6 have independent prognostic value. We conclude that circulating IL-6 is associated with worse survival in patients with metastatic breast cancer and is correlated with the extent of disease.     

Ten-year follow-up of Southwest Oncology Group 8269: a phase II trial of concomitant cisplatin-etoposide and daily thoracic radiotherapy in limited small-cell lung cancer

Angiogenesis is controlled by inhibitors and angiogenic factors. Among these, basic fibroblast growth factor (bFGF) is closely involved in cancer proliferation and has been related to progression and prognosis of various cancers, including lung cancer. To evaluate the role of bFGF, we measured serum levels of bFGF from healthy controls (Ctrl) and 106 patients with lung cancer, including 31 adenocarcinomas (AD), 29 squamous cell carcinomas (SQ), and 46 small cell carcinomas (SCLC), by enzyme-linked immunosorbent assays. Moreover, we evaluated the relationship between serum levels of bFGF and clinical outcome. Serum levels of bFGF in AD, SQ, SCLC, and Ctrl were 7.6 (0.5-32.5) (median (range)), 7.4 (0.5-36.7), 7.1 (0.5-34.8) and 3.0 (1.5-6.0) pg/ml, respectively (P<0.05). Serum bFGF levels did not differ between clinical stages in non-small cell lung cancer (NSCLC; AD+SQ). In SCLC, we found a significant difference in serum levels of bFGF between chemotherapy (and/or radiotherapy) responders (complete response+partial response) and non-responders (no change+progressive disease) (9.2 (0.6-34.8), 4.4 (0.5-17.4) pg/ml, respectively (P=0.018)), whereas there was no difference in NSCLC. Moreover, serum bFGF levels in SCLC patients had significant impact in prognosis by uni and multivariate analysis (P=0.014, 0.018, respectively). We concluded that bFGF has an important role in the prognosis of patients with SCLC.     

Elevated levels of the angiogenic cytokines basic fibroblast growth factor and vascular endothelial growth factor in sera of cancer patients.

The concentration of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) was determined in the serum of 90 untreated and 42 treated metastatic cancer patients, including patients with colorectal, breast, ovarian and renal carcinomas, with an enzyme-linked immunosorbent assay (ELISA). Levels higher than the 95th percentile of the concentrations of a control group, i.e. 7.5 pg ml(-1) for bFGF and 500 pg ml(-1) for VEGF, were identified as ''elevated''. One measurement during follow-up was included into the analysis per patient. For 19 treated patients, consecutive serum samples were analysed. Fifty-seven per cent of all untreated patients had elevated serum levels of one or both angiogenic factors. The fraction of patients with elevated serum levels of bFGF and/or VEGF was similar in the different tumour types. Agreement of bFGF levels and VEGF levels, classified in relation to their respective cut-off values, was present in 67% of all patients. Fifty-eight per cent of the patients with progressive disease during treatment compared with 15% of the patients showing response to treatment (chi-squared test P < 0.05) had elevated bFGF and/or VEGF serum levels. When consecutive serum samples were analysed, two-thirds of the patients showing progressive disease had increasing serum levels of the angiogenic factors compared with less than one-tenth of the patients showing response (chi-squared test P < 0.05). The lack of association between the serum bFGF and VEGF levels and the tumour type may suggest an aspecific host reaction responsible for solid tumour-related angiogenesis. The main determinants of the serum bFGF and VEGF concentration are the progression kinetics of the metastatic carcinomas.     

Methylation level of the RASSF1A promoter is an independent prognostic factor for clear-cell renal cell carcinoma

BackgroundRas association domain family 1A (RASSF1A) is a tumor suppressor that regulates the cell cycle, apoptosis, and microtubule stability. The association between the methylation levels of RASSF1A and the prognosis of clear-cell renal cell carcinoma (CCRCC) remains unclear. Therefore, we investigated this relationship to determine the prognostic value of RASSF1A methylation levels for CCRCC.Patients and methodsThe study comprised 179 Japanese patients who underwent radical or partial nephrectomy for CCRCC. The methylation level of 5′ CpG islands in the RASSF1A was evaluated using combined bisulfite restriction analysis and bisulfite sequencing.ResultsHigh levels of methylation in the RASSF1A promoter were significantly more frequent in grade 3 compared with grade 1 or 2 tumors (P = 0.028) and in patients with stage III or IV compared with patients with stage I or II (P = 0.043). Patients with high methylation levels had a significantly less favorable prognosis compared with those with low methylation levels (P = 0.040). Higher methylation levels were independently associated with a poor prognosis following multivariate analysis (P = 0.0053).ConclusionThese results indicate that quantitative promoter methylation levels of the RASSF1A gene may be a useful marker to predict the prognosis of CCRCC.     

Chromosome 9p deletion in clear cell renal cell carcinoma predicts recurrence and survival following surgery

Background:

Wider clinical applications of 9p status in clear cell renal cell carcinoma (ccRCC) are limited owing to the lack of validation and consensus for interphase fluorescent in situ hybridisation (I-FISH) scoring technique. The aim of this study was to analytically validate the applicability of I-FISH in assessing 9p deletion in ccRCC and to clinically assess its long-term prognostic impact following surgical excision of ccRCC.

Methods:

Tissue microarrays were constructed from 108 renal cell carcinoma (RCC) tumour paraffin blocks. Interphase fluorescent in situ hybridisation analysis was undertaken based on preset criteria by two independent observers to assess interobserver variability. 9p status in ccRCC tumours was determined and correlated to clinicopathological variables, recurrence-free survival and disease-specific survival.

Results:

There were 80 ccRCCs with valid 9p scoring and a median follow-up of 95 months. Kappa statistic for interobserver variability was 0.71 (good agreement). 9p deletion was detected in 44% of ccRCCs. 9p loss was associated with higher stage, larger tumours, necrosis, microvascular and renal vein invasion, and higher SSIGN (stage, size, grade and necrosis) score. Patients with 9p-deleted ccRCC were at a higher risk of recurrence (P=0.008) and RCC-specific mortality (P=0.001). On multivariate analysis, 9p deletion was an independent predictor of recurrence (hazard ratio 4.323; P=0.021) and RCC-specific mortality (hazard ratio 4.603; P=0.007). The predictive accuracy of SSIGN score improved from 87.7% to 93.1% by integrating 9p status to the model (P=0.001).

Conclusions:

Loss of 9p is associated with aggressive ccRCC and worse prognosis in patients following surgery. Our findings independently confirm the findings of previous reports relying on I-FISH to detect 9p (CDKN2A) deletion.     

The free beta-subunit of human chorionic gonadotropin as a prognostic factor in renal cell carcinoma

The free beta-subunit of human chorionic gonadotropin beta is expressed in several nontrophoblastic tumours and this is usually associated with aggressive disease. Little is known about human chorionic gonadotropin beta expression in renal cancer. We determined the pretreatment levels of human chorionic gonadotropin beta in serum of patients with renal cell carcinoma, and studied whether elevated levels predicted the clinical outcome. Serum samples were collected before surgery from 177 patients with renal cell carcinoma and from 84 apparently healthy controls. Human chorionic gonadotropin beta in serum was measured by a highly sensitive time-resolved immunofluorometric assay. The prognostic value of human chorionic gonadotropin beta, and of usual clinical and pathological variables was analyzed by the Kaplan-Meier method, the log rank test and Cox multiple hazard regression. The serum concentrations of human chorionic gonadotropin beta were increased in 23% of the renal cell carcinoma patients and they were significantly higher in patients with renal cell carcinoma than in controls (P<0.0001). The concentrations did not correlate with clinical stage and histopathological grade, but patients with increased human chorionic gonadotropin beta levels had significantly shorter survival time than those with levels below the median (cut-off 1.2 pmol l(-1), P=0.0029). In multivariate analysis human chorionic gonadotropin beta, tumour stage and grade were independent prognostic variables. The serum concentration of human chorionic gonadotropin beta is an independent prognostic variable in renal cell carcinoma. The preoperative value of human chorionic gonadotropin beta in serum may be used to identify patents with increased risk of progressive disease.     

Pro-neoangiogenic cytokines (VEGF and bFGF) and anemia in solid tumor patients

Using a commercial ELISA assay, we evaluated circulating VEGF and bFGF levels in 203 consecutive patients with solid tumors, and sought a correlation between them and with the grade of anemia. Serum VEGF values were within the normal range in 128 patients (63.05%), with a mean value of 675.04 pg/ml (median, 571.00; range, 0-2796.54). The analysis of VEGF values per tumor group did not provide any statistically significant difference. Regarding bFGF, 143 patients (70.44%) had measurable, and thus abnormal, bFGF values. Overall, mean bFGF serum value was 57.14 pg/ml (median, 8.30; range, 0-4334.71), with the highest bFGF levels found in breast carcinoma patients. As expected, a large number of our patients was fairly anemic, mean hemoglobin level being 11.47 g/dl (median, 11.30; range, 7.1-19.20), the lowest titers being observed in prostate carcinoma patients. No statistically significant correlation was found between serum VEGF and hemoglobin values (r=0.004) but a significant negative correlation was seen between serum bFGF and hemoglobin (r=-0.22, p<0.05). Considering the different tumor groups, a statistically significant negative correlation between bFGF and hemoglobin becomes even more apparent in the subgroup of renal carcinoma patients (r=-0.55, p<0.05). In conclusion, our results demonstrate that there is a statistically significant correlation between systemic hypoxia (evaluated in terms of hemoglobin levels) and circulating bFGF values, but not VEGF; this correlation may lead to therapeutic interventions.     

Number of lymph nodes examined and prognosis of TNM stage II colorectal cancer

The diagnosis of a lymph node-negative colorectal carcinoma should imply a good prognosis; however, the outcomes for TNM stage II patients remain variable. Few studies have examined the relationship of the number of lymph nodes examined to the prognosis of this stage. The aim of this study was to determine whether the number of lymph nodes examined has an effect on prognosis of a relatively large sample of patients undergoing curative surgery for stage II colorectal cancer at a single institution. Data on patients who underwent surgery for colorectal cancer between January 1980 and April 2000 were prospectively collected in a database. Patients with TNM stage II or stage III tumours who were treated with curative intent were removed. Patients over 80 years of age were excluded from the survival analysis. Survival comparisons were made using Kaplan-Meier curves and the log-rank test. Multivariate analysis was performed using a Cox regression model. A total of 625 cases of TNM stage II cases and, for comparison purposes, 415 stage III cases, were analysed. Lymph node retrieval in stage II cases was affected by the patient's age (P=0.04) and gender (P=0.02), tumour grade (P<0.0001), tumour site (P<0.0001), and necessity to carry out extended resection (P<0.0001). In stage III cases, lymph node retrieval was affected by patient age (P<0.0001), tumour grade (P=0.02), and tumour site (P=0.002). Decreased lymph node detection was associated with increasing hazard ratios among the 480 TNM stage II patients under 80 years of age, but not among the 345 patients with TNM stage III tumours. Five year survival rate for patients with stage III tumours with only 1-3 positive lymph nodes (52.6%) was similar to that of patients with stage II tumour who had nine or fewer lymph nodes examined (51.3%). These results demonstrate that the prognosis of TNM stage II colorectal cancer is dependent on the number of lymph nodes examined. Patients with few nodes examined have a poorer prognosis. It is possible that a smaller number of lymph nodes examined reflects a diminished immune response. It can be presumed that those patients with stage II tumour with only a few nodes examined should be offered postoperative chemotherapy on a routine basis.     

The clinical value of serum hepatocyte growth factor levels in patients undergoing primary radiotherapy for glioma: effect on progression-free survival

Hepatocyte growth factor (HGF) has been shown to be overexpressed in gliomas, and high-grade gliomas (glioblastoma multiforme) express more HGF than lower-grade astrocytoma, and HGF enhances their resistance to radiotherapy. To examine the effect of serum HGF levels on the likelihood of response to radiotherapy and the disease-free survival in patients with glioma, the blood samples of the patients were collected before commencing treatment and serum HGF was measured by quantitative ELISA in 48 patients with glioma grade I–IV, and all patients underwent primary conventionally fractionated radiotherapy. For statistical analysis, SPSS Version 13.0 software was used. Thirty-eight of the 48 patients had a response to treatment, and ten patients had persistent disease at 3 months. Overall, the median serum HGF level was 1,219.5 pg/ml (range 650.4–2,264.7 pg/ml). Eight patients with local failure had HGF levels >1,219.5 pg/ml, and 28 patients with response had serum HGF level of ≤1,219.5 pg/ml (P = 0.01). The median time to progression was 6 months in patients with HGF level of >1,219.5 pg/ml compared with 17 months in patients with HGF level of ≤1,219.5 pg/ml (log-rank, P = 0.041). In multivariate analysis, serum HGF, the KPS, tumour size and pathological grade, but not the patient’s age, gender and oligodendroglial component influenced the progression-free survival. Elevated pre-therapeutic serum HGF levels are associated with poor response and a shorter time to progression in patients with glioma undergoing primary radiotherapy.