Direct Tumor Invasion in Colon Cancer: Correlation with Tumor Spread and Survival

Purpose  This study examined the correlation between depth of local invasion in colon cancer and tumor spread and patient survival. Methods  A cohort of 796 patients with a complete set of TNM staging information following an elective resection for colon cancer was selected. The rates of lymph node and distant metastasis, tumor differentiation, and extramural venous invasion for different tumor (T) categories were compared. The effects of initial tumor (T) category on overall patient survival were studied. Results  The depth of local tumor invasion correlated strongly with nodal involvement (P = 0.0001), rates of extramural venous invasion (P = 0.0002), poor differentiation (P = 0.0001), and distant metastasis (P = 0.0001). Fifty-seven percent of the patients remained lymph node-negative and distant metastasis-negative irrespective of their depth of tumor invasion had no impact on overall survival (P = 0.49). For patients with lymph node or distant metastasis (43 percent), depth of tumor invasion had significant impact on overall survival (P = 0.001). Thirteen percent of T3N1, 33 percent of T3N2, 40 percent of T4N1, and 68.percent of T4N2 cases had distant metastasis at presentation. Conclusion  Two types of colon cancer were observed: locally active and tendency to metastasize. For the latter, overall mortality and the risk of metastasis increased with depth of tumor invasion. Reprints are not available.     

ABCB1 gene polymorphisms and haplotype analysis in colorectal cancer

Purpose  The aim of this study was to determine the significance of three most common single-nucleotide polymorphisms (SNPs) of ABCB1 gene in the development of colorectal cancer and to estimate the influence of these SNPs to surviving patients' treatment combination adjuvant therapy 5-fluorouracil/leucovorin. Haplotype structure of ABCB1 was analysed, and degree of linkage disequilibrium (LD) between SNPs of ABCB1 was estimated. Materials and methods  Tumour specimens of 95 patients with colorectal cancer and blood samples of 95 healthy cases were studied. Genotyping of ABCB1 gene was performed by automated sequencing or polymerase chain reaction-restriction fragment length polymorphism method. Comparison of frequencies of alleles/genotypes/haplotypes between the studied group (colorectal cancer samples) and the control group (blood samples) were analysed. These results were correlated with the surviving patients after treatment of adjuvant chemotherapy. Results  Significant differences in ABCB1 _1236C>T (p = 0.00043) and ABCB1 _2677G>T/A (p = 0.04) genotype distribution and T₁₂₃₆ allele distribution (CT₁₂₃₆ or TT₁₂₃₆ vs CC₁₂₃₆; p = 0.0499, OR = 0.55, Fi–Yule coefficient = 0.14) were found. A strong LD between ABCB1 _1236C>T and ABCB1 _2677G>T/A SNPs (D′ = 0.621, r ² = 0.318) was detected. All SNPs were located in one haplotype block. There were significant differences in haplotype distributions between colorectal cancer patients and healthy population (p = 0.03). Significant differences in survival probability of colorectal cancer patients' treatment chemotherapy according to allele of ABCB1 _3435C>T was observed. Survival probability of patients with wild-type C₃₄₃₅ allele were higher than among patients without this allele (p = 0.04572). Conclusions  These results suggested that three studied SNPs of ABCB1 were located in one haplotype block. Differences in ABCB1 _1236C>T and ABCB1 _2677G>T/A genotypes and T₁₂₃₆ allele distribution between investigated populations indicate significant impact of these SNPs on risk of development of colorectal cancer. Polymorphism ABCB1 _3435C>T may be a prediction marker of cancer chemotherapy effectiveness. Differences in haplotype distributions between colorectal cancer patients and healthy population suggested that other potential SNPs, especially in regulatory region of ABCB1 gene, may influence P-glycoprotein expression and function.     

Hepatectomy for liver metastasis of colorectal cancer

Objective  The objective of this study was to investigate whether hepatic resection (HR) can increase the survival of liver metastasis of colorectal cancer (CRC). Materials and methods  CRC patients (n = 669) with liver metastasis treated at the Zhongshan Hospital, Fudan University from 1/2000 to 7/2007 were included in the study to investigate the relationship between HR and cancer survival. Results  CRC patients (n = 669) with liver metastases who had primary tumor resection were grouped in synchronous liver metastasis (SLM; 56.7%, n = 379) and metachronous liver metastasis (MLM) groups (43.3%, n = 290). Hepatic resection rates were lower (32.5%, n = 123) in the SLM than the MLM group (44.8%, n = 130, P < 0.05). The 30-day mortality rate in the MLM (2.3%) was significantly lower than SLM (2.4%) groups. The 5-year survival rates (36.6%) was same compared to SLM group (33.1%, P > 0.05). One-, 2-, and 3-year survival of stages I and II operation cases were 92.5% vs 86.5%, 0.7% vs 58.0%, and 42.1% vs 44.9% (P > 0.05) in the SLM group, respectively. Recurrence after first hepatic resection associated with a 2.23-fold increased risk of death (P < 0.01). Incision margins larger than 1 cm and HR for recurrence associated with 34% and 27% (P < 0.05) decreased death risk. Conclusions  Hepatic resection could help the survival of liver metastasis of colorectal cancer, and stage I surgery is safe for this disease. Xu Jianmin, Wei Ye, and Zhong Yunshi contributed equally to this paper.     

The CHADS2 and CHA2DS2-VASc scores predict adverse vascular function,ischemic stroke and cardiovascular death in high-risk patients without atrial fibrillation: Role of incorporating PR prolongation

Objectives

To investigate whether the CHADS₂ and CHA₂DS₂-VASc scores have clinical utility for prediction of adverse vascular function and vascular dysfunction-mediated incident cardiovascular (CV) events among high-risk patients without atrial fibrillation (AF), and the additional value of incorporating PR prolongation to the scores.

Methods

We analyzed 579 high-risk CV outpatients without clinical AF in a prospective cohort for new-onset ischemic stroke, myocardial infarction (MI), congestive heart failure (CHF), and CV death. Brachial flow-mediated dilation (FMD) and nitroglycerin-mediated dilatation (NMD), carotid intima-media thickness (IMT) and pulse wave velocity (PWV) were determined.

Results

Baseline CHADS₂ score was associated with lower FMD (Pearson r = −0.16, P < 0.001) and NMD (r = −0.17, P < 0.001), higher carotid IMT (r = 0.30, P < 0.001) and PWV (r = 0.35, P < 0.001; similar for CHA₂DS₂-VASc score: All P < 0.05). After follow-up of 63 ± 11 months, 82 patients (14.2%) developed combined CV endpoint. ROC curve analysis showed that both CHADS₂ and CHA₂DS₂-VASc scores were predictors for ischemic stroke (C-Statistic: CHADS₂ 0.70, P = 0.004; CHA₂DS₂-VASc 0.68, P = 0.010), MI (CHADS₂ 0.63, P = 0.030; CHA₂DS₂-VASc 0.70, P = 0.001), and CV death (CHADS₂ 0.63, P = 0.022; CHA₂DS₂-VASc 0.65, P = 0.011). Higher CHADS₂ score was associated with reduced event-free survival from combined CV endpoints (log-rank = 16.7, P < 0.001) with differences potentiated if stratified by CHA₂DS₂-VASc score (log-rank = 29.2, P < 0.001). Incorporating PR prolongation, the CHA₂DS₂-VASc-PR score achieved the highest C-Statistic for CV death prediction (0.70, P < 0.001) superior to the CHADS₂ score (chi-square: 12.1, P = 0.0005).

Conclusions

The CHADS₂ and CHA₂DS₂-VASc predict vascular dysfunction and cardiovascular events in high-risk CV patients without clinical AF, with further improved performance incorporating PR prolongation.     

R0 Liver Resections for Primary Malignant Liver Tumors in the Noncirrhotic Liver: A Diagnosis-Related Analysis

Background Primary liver cancer constitutes an increasingly malignancy in the Western world and one of the leading causes of cancer-related deaths worldwide. The purpose of this study was to evaluate and compare long-term outcomes after R0 resections in noncirrhotic livers for hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). Methods Between April 1998 and May 2006 a total of 102 patients with either ICC (n = 41, group 1) or HCC (n = 61, group 2) in the absence of cirrhosis underwent curative liver resection in our department. Demographic characteristics, operative details, perioperative complications, pathologic findings, tumor recurrence and survival were analyzed. Results Gender (P = 0.007), extent of liver resection (P = 0.036), additional surgical procedures (P < 0.001) and operative morbidity (P = 0.018) differed among the two groups. Following resection, after a median follow-up of 28 months, the calculated 5-year survival was 44% and 40% for ICC and HCC, respectively (P = 0.38). The corresponding recurrence-free survival was 25% for both ICC and HCC (P = 0.66). UICC stage was found to predict overall and recurrence-free survival in both types of tumors. Multifocality in the case of ICC, and tumor differentiation and vascular invasion in the case of HCC, were predictive factors for overall and recurrence-free survival, respectively. In multivariable analyses, vascular invasion for HCC was predictive for overall and recurrence-free survival, whereas in the case of ICC significant differences were detected in the recurrence analysis for multifocality and UICC stage. Conclusions R0 resections for both ICC and HCC result to similar long-term outcomes, which are characterized by good overall and acceptable recurrence-free survival rates.     

Lymphopenia following the completion of first-line therapy predicts early relapse in patients with diffuse large B cell lymphoma

Early relapse is a parameter that affects clinical outcomes in relapsed diffuse large B cell lymphoma (DLBCL). The prognostic value of lymphopenia following the completion of first-line therapy and the relationship between lymphopenia and early relapse are unknown. Therefore, we studied the role of absolute lymphocyte count (ALC) on early relapse. We retrospectively analyzed de novo DLBCL patients who were treated with rituximab-containing treatment between 2003 and 2010. The median age at the time of diagnosis of 59 DLBCL patients was 71 years. We identified no association between ALC at diagnosis and ALC following the completion of first-line therapy. Among all patients analyzed, 13 (22%) patients were confirmed to exhibit early relapse. Low ALC following the completion of first-line therapy was significantly associated with early relapse by univariate analysis [hazard ratio (HR) = 4.05; 95% confidence interval (CI), 1.11–14.73; P = 0.02] and multivariate analysis (HR = 4.66; 95% CI, 1.24–17.48; P = 0.023). The low ALC group tended to have worse outcomes than the high ALC group with lower rates of progression-free survival (66% and 74%, respectively; P = 0.13) and overall survival (74% and 86%, respectively; P = 0.09), but these differences did not reach statistically. Lymphopenia following the completion of first-line therapy can be used as a marker to predict early relapse.     

Effect of β-Blockers on β<Subscript>3</Subscript>-Adrenoceptor Expression in Chronic Heart Failure

Objectives To investigate the expression of β₃-adrenoceptors in rats with chronic heart failure, and to explore the effect of β-blockers on β₃-adrenoceptor expression. Materials and methods Thirty-two male Wistar rats were divided into Sham (n = 10) and heart failure (n = 22) groups. The heart failure group was treated with normal saline (Heart Failure Control, n = 6), Metoprolol (n = 8) or Carvedilol (n = 8) for 3 months. Results The left ventricular end systolic pressure (LVESP) and the absolute values of maximal rate of rise and fall of left ventricular pressure (±dP/dt max) in the heart failure group were lower than in the Sham group (P < 0.01), whereas the left ventricular end diastolic pressure (LVEDP) was higher (P < 0.01). The LVESP and dP/dtmax in the Carvedilol group were higher than the Metoprolol group whereas LVEDP was lower (P < 0.01). The left ventricular mass index (LVMI) in the Carvedilol group was less than the Metoprolol and Heart Failure Control groups (P < 0.01). The level of β₃-adrenoceptor expression in the study groups was significantly higher than the Sham group (P < 0.01). β₃-adrenoceptor expression in the Carvedilol group was lower than the Heart Failure Control and Metoprolol groups (P < 0.01). Conclusion β₃-adrenoceptor expression is increased in the failing ventricles in rats. Carvedilol is more effective than Metoprolol for improving the hemodynamics and in attenuating ventricular remodeling after heart failure. Carvedilol, rather than Metoprolol, diminishes β₃-adrenoceptor expression in the failing ventricles.     

Determinants of morbidity and survival after elective non-curative resection of stage IV colon and rectal cancer

Purpose  The benefit of elective primary tumor resection for non-curable stage IV colorectal cancer (CRC) remains largely undefined. We wanted to identify risk factors for postoperative complications and short survival. Methods  Using a prospective database, we analyzed potential risk factors in 233 patients, who were electively operated for non-curable stage IV CRC between 1996 and 2002. Patients with recurrent tumors, resectable metastases, emergency operations, and non-resective surgery were excluded. Risk factors for increased postoperative morbidity and limited postoperative survival were identified by multivariate analyses. Results  Patients with colon cancer (CC = 156) and rectal cancer (RC = 77) were comparable with regard to age, sex, comorbidity, American Society of Anesthesiologists score, carcinoembryonic antigen levels, hepatic spread, tumor grade, resection margins, 30-day mortality (CC 5.1%, RC 3.9%) and postoperative chemotherapy. pT4 tumors, carcinomatosis, and non-anatomical resections were more common in colon cancer patients, whereas enterostomies (CC 1.3%, RC 67.5%, p < 0.0001), anastomotic leaks (CC 7.7%, RC 24.2%, p = 0.002), and total surgical complications (CC 19.9%, RC 40.3%, p = 0.001) were more frequent after rectal surgery. Independent determinants of an increased postoperative morbidity were primary rectal cancer, hepatic tumor load >50%, and comorbidity >1 organ. Prognostic factors for limited postoperative survival were hepatic tumor load >50%, pT4 tumors, lymphatic spread, R1–2 resection, and lack of chemotherapy. Conclusions  Palliative resection is associated with a particularly unfavorable outcome in rectal cancer patients presenting with a locally advanced tumor (pT4, expected R2 resection) or an extensive comorbidity, and in all CRC patients who show a hepatic tumor load >50%. For such patients, surgery might be contraindicated unless the tumor is immediately life-threatening. Financial support  Neither one of the authors nor the institutions from which the work originated have asked for, accepted, or received any direct or indirect financial support from a third party regarding the matter and materials discussed in this paper.     

Predictive value of vascular endothelial growth factor overexpression in early relapse of colorectal cancer patients after curative resection

Background

Preclinical and clinical studies have indicated that vascular endothelial growth factor (VEGF) is the predominant angiogenic factor. Recently, there was a consistent trend of poorer survival rates in colorectal cancer (CRC) patients of earlier relapse. The purpose of this study was to investigate novel predictors of early relapse in stage I–III CRC and further to determine their correlation with disease outcomes.

Materials and methods

We retrospectively analyzed clinicopathological features and VEGF expression by immunohistochemical staining in 100 stage I–III CRC patients undergoing curative resection to identify predictors of postoperative early relapse.

Results

Among 100 patients, 40 patients were classified into early relapse group, and 60 patients were categorized into non-early relapse group. A multivariate logistic regression analysis showed that vascular invasion (P?=?0.048), perineural invasion (P?=?0.042), VEGF overexpression (P?=?0.023), and high postoperative carcinoembryonic antigen (CEA) levels (P?=?0.004) were independent predictors of early relapse. Additionally, we found that with more predictors such as the combined incidence of vascular invasion, perineural invasion, VEGF overexpression, and postoperative CEA levels are involved, the incidence of early postoperative relapse increases. Moreover, VEGF overexpression predicted not only early postoperative relapse but also disease-free survival (P?<?0.001) and overall survival (P?=?0.002).

Conclusions

This study suggests that VEGF overexpression is an important predictor of early postoperative relapse in patients with stage I–III CRC and may help identify patients who would benefit from intensive follow-up and therapeutic programs.     

Clinical outcome of autologous peripheral blood stem cell transplantation in opticospinal and conventional forms of secondary progressive multiple sclerosis in a Chinese population

To evaluate clinical outcomes of autologous peripheral blood stem cell transplantation (APBCST) between opticospinal multiple sclerosis (OSMS) and conventional multiple sclerosis (CMS) during disease progressive stage in a Chinese population. Thirty-six secondary progressive MS patients, among whom 21 were with OSMS and 15 with CMS, underwent APBSCT and were followed up for an average of 48.92 months (range, 10–91 months). Peripheral blood stem cells were obtained by leukapheresis after mobilization with granulocyte colony-stimulating factor. Modified BEAM conditioning regimen (Tiniposide, melphalan, carmustin, and cytosine arabinoside) were administered. Outcomes were evaluated using the expanded disability status scale (EDSS). No maintenance treatment was administered if there was no disease progression. No treatment-related mortality occurred. Among the 36 patients, one OSMS patient dropped during the follow-up. Among the 22 relapse-free patients, 20 were with continuous neurological improvement without any relapse events, and two remained in neurologically stable states. Among the 13 relapse patients, seven had experienced of neurological relapse, but with no progression during the follow-up period; and six experienced neurological deterioration after transplantation and needed further immunosuppressant treatment. The confirmed relapse-free survival rate was 62.9% and progression-free survival rate was 83.3% after 91 months according to Kaplan and Meier survival curves. Eleven of the 20 OSMS patients (55%) and two of the 15 CMS patients (13.3%) stayed in disease active group (P = 0.014). For the 20 OSMS patients, the overall EDSS score decreased significantly after transplantation (P = 0.016), while visual functions had no significant improvement (P = 0.716). Progressive OSMS has a higher relapse rate than CMS following APBSCT.     

Effect of Mosapride on Recovery of Intestinal Motility After Hand-Assisted Laparoscopic Colectomy for Carcinoma

Purpose  Mosapride citrate (mosapride) is a serotonin 5-hydroxytryptamine 4 receptor agonist known to promote gastric emptying and large-intestine motility. We assessed the effect of mosapride on postoperative ileus following colon surgery. Methods  Forty patients with colon cancer undergoing hand-assisted laparoscopic colectomy were randomly assigned to a mosapride group or a control group. The mosapride group received 15 mg of mosapride by mouth with 50 ml of water three times a day, starting on postoperative day 1. The control group received 50 ml of water on the same schedule. Patients were allowed to resume oral feeding on the evening of postoperative day 2. Postoperative time to first bowel movement was evaluated by one investigator blinded to treatment. Postoperative gastric emptying was evaluated with the [¹³C]-acetate breath test at 24 and 48 hours after the operation. Results  Postoperative time to first bowel movement was significantly shorter in the mosapride group than in the control group (48.5 vs. 69.3 hours, P = 0.0149). The time to maximal gastric emptying rate as determined by the breath test was significantly shorter in the mosapride group than in the control group at the 48-hour time point (27.9 vs. 35.3 minutes, P = 0.0294). Postoperative hospital stay was shorter in patients receiving mosapride than in controls (6.7 vs. 8.4 days, P = 0.0398). No adverse effects were observed with mosapride. Conclusions  Gastric emptying was improved by mosapride. The results suggested that the period of postoperative ileus following hand-assisted laparoscopic colectomy can be shortened by treatment with mosapride.     

Tumor-infiltrating macrophages can predict favorable prognosis in hepatocellular carcinoma after resection

Purpose  To evaluate the prognostic value of tumor-associated macrophages (TAM), individually or synergistically with CD45RO + memory T cells (T_M), in hepatocellular carcinoma (HCC) patients following resection. Methods  The infiltration of TAM and T_M was assessed by immunohistochemistry in tissue microarray containing 302 HCC specimens. Correlations between TAM/T_M infiltration and clinicopathologic features, disease-free survival (DFS) and overall survival (OS) were statistically analyzed. Results  High TAM infiltration was associated with both improved DFS (P = 0.0021) and OS (P = 0.0481). Multivariate analysis identified TAM infiltration as independent prognostic factor for DFS (P = 0.004) and OS (P = 0.049). A second analysis clarified the synergistic effect of TAM&T_M infiltration for DFS (P = 0.004) and OS (P = 0.040). Conclusions  Both TAM infiltration alone and concomitant infiltration of TAM&T_M are associated with improved DFS/OS, suggesting that TAM could protect HCC patients from recurrence/metastasis and prolong survival by distinct mechanisms. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. This is an original work by all the authors and no previous presentations, reports, or publications contain any material that appears in the article. Yi-Wei Li and Shuang-Jian Qiu contributed equally to this work.     

Oxidative stress in fibromyalgia and its relationship to symptoms

Oxidative stress is thought to play a role in the pathogenesis of fibromyalgia. We examined the hypothesis that oxidative stress was increased in patients with fibromyalgia and related to the severity of symptoms. Urinary F₂-isoprostane excretion was measured in 48 patients with fibromyalgia and compared to those of 96 control subjects. In patients, we examined the association between oxidative stress and symptoms. Patients with fibromyalgia were significantly more symptomatic than control subjects, but urinary F₂-isoprostane excretion did not differ significantly (2.3 ± 1.9 vs. 2.8 ± 2.2 ng/mg creatinine, p = 0.16). In patients with fibromyalgia, F₂-isoprostane excretion was associated with fatigue visual analog scale (rho = 0.30, p = 0.04) but not with pain, quality of life, functional capacity, depression, number of tender points, or overall impact of fibromyalgia. Oxidative stress is not increased in patients with fibromyalgia, but as was previously found in patients with systemic lupus erythematosus, oxidative stress was associated with fatigue. Jason D. Morrow: deceased     

Variants in KCNQ1 are associated with susceptibility to type 2 diabetes in the population of mainland China

Aims/hypothesis  Two recent genome-wide association studies have identified several novel type 2 diabetes susceptibility variants in intron 15 of the KCNQ1 gene. We aimed to evaluate the effects of the variants in KCNQ1 on type 2 diabetes and metabolic traits in the population of mainland China. Methods  Three candidate single nucleotide polymorphisms were genotyped in 1,912 individuals with type 2 diabetes and 2,041 normal controls using the ligase detection reaction method. Results  We confirmed the association of KCNQ1 with type 2 diabetes in the population of mainland China. Allele frequency ORs of the three single nucleotide polymorphisms (SNPs) were: rs2237892 (OR 1.19, 95% CI 1.08–1.31, p = 3.0 × 10⁻⁴); rs2237895 (OR 1.20, 95% CI 1.09–1.32, p = 1.9 × 10⁻⁴); and rs2237897 (OR 1.24, 95% CI 1.13–1.36, p = 3.9 × 10⁻⁵). We also found a significant difference in the distribution of the global haplotypes between the type 2 diabetes group and the normal control group (p = 2.6 × 10⁻⁵). In addition, in the control group SNP rs2237892 was marginally associated with increasing fasting plasma glucose and SNPs rs2237892 and rs2237897 were associated with HbA_1c. Furthermore, for all three variants, homozygous carriers of the diabetes-associated allele had significantly decreased BMI and waist circumferences. Conclusions/interpretation  Our investigation confirmed the effects of KCNQ1 variants on type 2 diabetes risk in the Chinese population. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorised users. Y. Liu and D. Z. Zhou contributed equally to this study.     

Expression of miR-146a and miR-155 in the urinary sediment of systemic lupus erythematosus

We studied the levels of miR-146a and miR-155 in the urine sediment of SLE patients. The levels of miR-146a and miR-155 in the urine sediment of 40 SLE patients who were receiving calcitriol treatment and 13 healthy controls were determined with real-time quantitative polymerase chain reaction. The levels of urinary miR-146a and miR-155 in patients with SLE were significantly higher than that in healthy controls. Calcitriol treatment reduced the levels of urinary miR-155 in patients with SLE. The level of urinary miR-146a significantly correlated with estimated glomerular filtration rate (r = 0.242, P = 0.008). The level of urinary miR-155 significantly correlated with proteinuria (r = 0.407, P < 0.001) and systemic lupus erythematosus disease activity index (r = 0.278, P = 0.002). The level of urinary miR-146a reversely correlated with the urinary expression of TNF-α (r = −0.247, P = 0.012). Our results suggested that miR-146a and miR-155 might play important roles in the pathophysiology of SLE and the levels of urinary miR-146a and miR-155 could be used as potential markers for diagnosis, disease activity, and therapeutic response.     

Survival Stratification Panel of Colorectal Carcinoma with Combined Expression of Carcinoembryonic Antigen,Matrix Metalloproteinases-2, and p27<Superscript>kip1</Superscript>

Purpose The prognosis varies greatly in colorectal carcinoma patients, even in the same stage. We examined the association between the expression of matrix metalloproteinases-2, carcinoembryonic antigen, p27^kip1, and clinicopathologic features in patients with colorectal carcinoma to identify a possible panel of tumor markers in predicting prognosis of colorectal carcinoma. Methods The expressions of three individual markers in 127 colorectal carcinoma cases were analyzed by immunohistochemistry method. Univariate and multivariate analysis were performed to analyze the expression with the disease-free survival time in colorectal carcinoma. Results High expression of matrix metalloproteinases-2, carcinoembryonic antigen, and low expression of p27^kip1 were related to poor prognosis in univariate analysis (P = 0.0002; P < 0.0001; P = 0.0008). The expression of matrix metalloproteinases-2, carcinoembryonic antigen, p27^kip1, and tumor differentiation were independent prognostic factors for disease-free survival by Cox regression analysis. The coexpression panel of matrix metalloproteinases-2, carcinoembryonic antigen, and p27^kip had significant prognostic value in all patients (P_AB = 0.0103; P_BC = 0.0068; P_CD = 0.0117). Multivariate analysis with Cox regression reveals that coexpression of matrix metalloproteinases-2, carcinoembryonic antigen, and p27^kip1 were independent prognostic factors as tumor differentiation in colorectal carcinoma. In different stages, coexpression tumor markers functioned in Stages II and III but not in the 19 cases of Stage I. The reason might be the number of patients was too small. Conclusions The results of this study provided further evidence that the combination of tumor markers of matrix metalloproteinases-2, carcinoembryonic antigen, and p27^kip1 was more informative than any single tumor marker alone for the disease-free survival stratification of colorectal carcinoma. Coexpression of matrix metalloproteinases-2, carcinoembryonic antigen, and p27^kip1 might be a useful survival stratification panel for clinical management. Supported by the Research fund of the Beijing Municipal Science & Technology Commission (Grant H020920030390); Beijing New Star Project on Science & Technology (Grant 2006B55). Poster presentation at Digestive Disease Week, Los Angeles, California, May 20 to 25, 2006.     

Preoperative serum levels of serum VEGF-C is associated with distant metastasis in colorectal cancer patients

Purpose  Vascular endothelial growth factor-C (VEGF-C) is one of the most potent lymphangiogenic members of the VEGF family that has been associated with lymph node metastasis and poor prognosis in patients with colorectal cancer (CRC). In this study, we evaluated the relationship of preoperative serum VEGF-C (sVEGF-C) and survival in CRC patients. Materials and methods  sVEGF-C levels were determined, prior to resection, in a cohort of 120 newly presenting patients with CRC by quantitative ELISA. Results  Patients who had positive lymph node involvement and higher Dukes’ staging (C&D) were associated with shorter time to metastases as expected (p = 0.002 and 0.001, respectively). Patients with distant metastasis had significantly lower levels of sVEGF-C than those without histopathologically proven disease (p = 0.004). However, there was no significant difference in the median sVEGF-C level in patients with or without lymph node metastatic involvement (91 pg/ml vs. 124 pg/ml; p = 0.81). Patients with a sVEGF-C concentration less than the median value (103 pg/ml) showed a poorer overall survival than patients with sVEGF-C levels greater than the median; but this was not statistically significant. Conclusions  In this study, low sVEGF-C levels are associated with distant metastasis; hence, preoperative levels may aid in the selection of CRC patients who require further investigation.     

Survival rates for stage II colon cancer patients treated with or without chemotherapy in a population-based setting

Background and aims There is considerable uncertainty as to whether adjuvant 5-fluorouracil-based chemotherapy provides survival benefit for colon cancer patients with stage II disease. Consequently, the current rates of chemotherapy use for this disease are low despite 5-year survival rates of only 70–80%. The aim of the present study is to compare the survival rate of stage II colon cancer patients treated by surgery alone with that of patients also treated by chemotherapy. Patients and methods A population-based observational study was conducted on the survival of stage II colon cancer patients (n = 812) diagnosed in Western Australia from 1993 to 2003. The study was restricted to patients aged ≤75 years, of whom 18% (n = 142) were treated with chemotherapy. Only 0.9% of patients older than 75 years received chemotherapy. Results Patients who received chemotherapy were significantly younger (mean age 6 years) than those treated by surgery alone (65 years, P < 0.001), and their tumors were more often positive for vascular invasion (P = 0.007). Multivariate analysis that included all prognostic factors revealed adjuvant chemotherapy was associated with improved survival (HR = 0.62, 95% CI [0.39–0.98], P = 0.043), with women gaining more benefit (HR = 0.48, 95% CI [0.20–1.22], P = 0.09) than men (HR = 0.94, 95% CI [0.54–1.64], P = 0.8). Conclusions In view of the apparent survival benefit from chemotherapy for stage II colon cancer, the present study raises concerns about the current low rates of adjuvant treatment for this disease in the community, particularly for female patients. Melinda Morris was supported by a Surgeon–Scientist scholarship from the Royal Australasian College of Surgeons.     

Portal vein thrombosis in hepatocellular carcinoma: age and sex distribution in an autopsy study

The purpose of this work was to investigate the prevalence, associated features and effect on survival of portal vein thrombosis (PVT) complicating hepatocellular carcinoma (HCC). The autopsy data of a series of 72 consecutive patients (57 male, 15 female) with HCC were reviewed. PVT was found in 32/72 patients (44%), and tended to be more common in female patients (10/15 versus 22/57, P = 0.052). Stratifying the data according to gender, it appeared that the mean age of patients with PVT compared to those without was greater in woman (71.9 ± 5.9 versus 63.2 ± 6.9 years, P = 0.024) and younger in men (58.8 ± 8.9 versus 66.0 ± 9.9 years, P = 0.007). When PVT was present, it was more likely that a definite diagnosis of HCC had been obtained before autopsy (P = 0.0001) and that death had been caused by bleeding complications (P = 0.007). Median survival times were similar, irrespective of the presence of PVT. During the natural history of HCC, PVT occurs in a substantial proportion of patients. Hormonal factors may have a permissive role in thrombus formation or neoplastic vascular invasion. Although in the presence of PVT a diagnosis of HCC is rarely missed and bleeding complications are likely to occur, patient survival does not seem to be significantly affected. Received: 30 September 1997 / Accepted: 4 April 1998