Management of potentially resectable colorectal cancer liver metastases

Colorectal cancer is a very common malignancy worldwide and development of liver metastases,both synchronous or metachronous,is a common event.Of all patients with metastatic colorectal cancer,up to 77% have a liver-only disease and approximately 10%-20% of patients with colorectal liver metastases are considered resectable at the time of diagnosis.Surgical resection of liver metastases remains the best treatment option and it is associated with a survival plateau and a 20%-25% of long-term survivors.Perioperative chemotherapy for resectable liver metastases may improve resecability of liver metastases and disease free survival,but its impact on overall survival is still unclear and more studies are needed.Moreover,preoperative chemotherapy can increase postoperative complications.Further studies are needed to define the role of adjuvant chemotherapy after a R0 resection of liver metastases and to define the criteria for a better selection of patients candidate to hepatectomy.New strategies such as targeted therapies are emerging with promising results.Optimal management requires a multidisciplinary approach,local and systemic,but it is a still pending question.Colorectal liver metastases represent a major challenge for oncologists and surgeons.In this review will be analyzed available data about assessment and management of the patients with potentially resectable colorectal liver metastases.     

结直肠癌伴同时性肝转移的治疗

Objective To investigate the clinical pathologic characters of colorectal cancer with simultaneous hepatic metastasis and the prognosis. Methods From Aug. 1994 to Dec. 2006, 2019 cases of colorectal carcinoma were admitted, among them there were 166 patients of colorectal cancer with synchronous liver metastases receiving surgical therapy. Results were analyzed retrospectively using the software of SPSS. Results These 166 patients with synchronous liver metastases from colorectal cancer accounted for 8.1% of all 2019 patients of colorectal cancer admitted. Multivariate analysis demonstrated that CEA level before surgery、depth of invasion、 pathological type and Ducks' stage were the key risk factors predicting simultaneous liver metastasis from colorectal cancer. The survival rates at 1, 3 and 5 years were 69%, 21%, and 9% respectively. There was significant difference among the different liver metastasis group of H1, H2 and H3(X2=23.35, P<0.01). The survival rates of patients undergoing radical resection was higher than those undergoing palliative resection (PR)and by-pass operation or feeding neostomy(BP/ FN)(X2= 21.18,P<0.01). PR improved short-term prognosis but did not improve long-term survival compared with BP/FN group(P=0.13). Conclusion Colorectal cancer with synchronous liver metastases has poor clinic pathological characters. Different degree of liver metastasis result in different prognosis.Radical resection leads to a better prognosis. Palliative resection can improve short-term prognosis and life quality but can't improve long-term survival.     

结直肠癌伴同时性肝转移的治疗

Objective To investigate the clinical pathologic characters of colorectal cancer with simultaneous hepatic metastasis and the prognosis. Methods From Aug. 1994 to Dec. 2006, 2019 cases of colorectal carcinoma were admitted, among them there were 166 patients of colorectal cancer with synchronous liver metastases receiving surgical therapy. Results were analyzed retrospectively using the software of SPSS. Results These 166 patients with synchronous liver metastases from colorectal cancer accounted for 8.1% of all 2019 patients of colorectal cancer admitted. Multivariate analysis demonstrated that CEA level before surgery、depth of invasion、 pathological type and Ducks' stage were the key risk factors predicting simultaneous liver metastasis from colorectal cancer. The survival rates at 1, 3 and 5 years were 69%, 21%, and 9% respectively. There was significant difference among the different liver metastasis group of H1, H2 and H3(X2=23.35, P<0.01). The survival rates of patients undergoing radical resection was higher than those undergoing palliative resection (PR)and by-pass operation or feeding neostomy(BP/ FN)(X2= 21.18,P<0.01). PR improved short-term prognosis but did not improve long-term survival compared with BP/FN group(P=0.13). Conclusion Colorectal cancer with synchronous liver metastases has poor clinic pathological characters. Different degree of liver metastasis result in different prognosis.Radical resection leads to a better prognosis. Palliative resection can improve short-term prognosis and life quality but can't improve long-term survival.     

结直肠癌伴同时性肝转移的治疗

Objective To investigate the clinical pathologic characters of colorectal cancer with simultaneous hepatic metastasis and the prognosis. Methods From Aug. 1994 to Dec. 2006, 2019 cases of colorectal carcinoma were admitted, among them there were 166 patients of colorectal cancer with synchronous liver metastases receiving surgical therapy. Results were analyzed retrospectively using the software of SPSS. Results These 166 patients with synchronous liver metastases from colorectal cancer accounted for 8.1% of all 2019 patients of colorectal cancer admitted. Multivariate analysis demonstrated that CEA level before surgery、depth of invasion、 pathological type and Ducks' stage were the key risk factors predicting simultaneous liver metastasis from colorectal cancer. The survival rates at 1, 3 and 5 years were 69%, 21%, and 9% respectively. There was significant difference among the different liver metastasis group of H1, H2 and H3(X2=23.35, P<0.01). The survival rates of patients undergoing radical resection was higher than those undergoing palliative resection (PR)and by-pass operation or feeding neostomy(BP/ FN)(X2= 21.18,P<0.01). PR improved short-term prognosis but did not improve long-term survival compared with BP/FN group(P=0.13). Conclusion Colorectal cancer with synchronous liver metastases has poor clinic pathological characters. Different degree of liver metastasis result in different prognosis.Radical resection leads to a better prognosis. Palliative resection can improve short-term prognosis and life quality but can't improve long-term survival.     

结直肠癌伴同时性肝转移的治疗

Objective To investigate the clinical pathologic characters of colorectal cancer with simultaneous hepatic metastasis and the prognosis. Methods From Aug. 1994 to Dec. 2006, 2019 cases of colorectal carcinoma were admitted, among them there were 166 patients of colorectal cancer with synchronous liver metastases receiving surgical therapy. Results were analyzed retrospectively using the software of SPSS. Results These 166 patients with synchronous liver metastases from colorectal cancer accounted for 8.1% of all 2019 patients of colorectal cancer admitted. Multivariate analysis demonstrated that CEA level before surgery、depth of invasion、 pathological type and Ducks' stage were the key risk factors predicting simultaneous liver metastasis from colorectal cancer. The survival rates at 1, 3 and 5 years were 69%, 21%, and 9% respectively. There was significant difference among the different liver metastasis group of H1, H2 and H3(X2=23.35, P<0.01). The survival rates of patients undergoing radical resection was higher than those undergoing palliative resection (PR)and by-pass operation or feeding neostomy(BP/ FN)(X2= 21.18,P<0.01). PR improved short-term prognosis but did not improve long-term survival compared with BP/FN group(P=0.13). Conclusion Colorectal cancer with synchronous liver metastases has poor clinic pathological characters. Different degree of liver metastasis result in different prognosis.Radical resection leads to a better prognosis. Palliative resection can improve short-term prognosis and life quality but can't improve long-term survival.     

结直肠癌伴同时性肝转移的治疗

Objective To investigate the clinical pathologic characters of colorectal cancer with simultaneous hepatic metastasis and the prognosis. Methods From Aug. 1994 to Dec. 2006, 2019 cases of colorectal carcinoma were admitted, among them there were 166 patients of colorectal cancer with synchronous liver metastases receiving surgical therapy. Results were analyzed retrospectively using the software of SPSS. Results These 166 patients with synchronous liver metastases from colorectal cancer accounted for 8.1% of all 2019 patients of colorectal cancer admitted. Multivariate analysis demonstrated that CEA level before surgery、depth of invasion、 pathological type and Ducks' stage were the key risk factors predicting simultaneous liver metastasis from colorectal cancer. The survival rates at 1, 3 and 5 years were 69%, 21%, and 9% respectively. There was significant difference among the different liver metastasis group of H1, H2 and H3(X2=23.35, P<0.01). The survival rates of patients undergoing radical resection was higher than those undergoing palliative resection (PR)and by-pass operation or feeding neostomy(BP/ FN)(X2= 21.18,P<0.01). PR improved short-term prognosis but did not improve long-term survival compared with BP/FN group(P=0.13). Conclusion Colorectal cancer with synchronous liver metastases has poor clinic pathological characters. Different degree of liver metastasis result in different prognosis.Radical resection leads to a better prognosis. Palliative resection can improve short-term prognosis and life quality but can't improve long-term survival.     

结直肠癌伴同时性肝转移的治疗

Objective To investigate the clinical pathologic characters of colorectal cancer with simultaneous hepatic metastasis and the prognosis. Methods From Aug. 1994 to Dec. 2006, 2019 cases of colorectal carcinoma were admitted, among them there were 166 patients of colorectal cancer with synchronous liver metastases receiving surgical therapy. Results were analyzed retrospectively using the software of SPSS. Results These 166 patients with synchronous liver metastases from colorectal cancer accounted for 8.1% of all 2019 patients of colorectal cancer admitted. Multivariate analysis demonstrated that CEA level before surgery、depth of invasion、 pathological type and Ducks' stage were the key risk factors predicting simultaneous liver metastasis from colorectal cancer. The survival rates at 1, 3 and 5 years were 69%, 21%, and 9% respectively. There was significant difference among the different liver metastasis group of H1, H2 and H3(X2=23.35, P<0.01). The survival rates of patients undergoing radical resection was higher than those undergoing palliative resection (PR)and by-pass operation or feeding neostomy(BP/ FN)(X2= 21.18,P<0.01). PR improved short-term prognosis but did not improve long-term survival compared with BP/FN group(P=0.13). Conclusion Colorectal cancer with synchronous liver metastases has poor clinic pathological characters. Different degree of liver metastasis result in different prognosis.Radical resection leads to a better prognosis. Palliative resection can improve short-term prognosis and life quality but can't improve long-term survival.     

结直肠癌伴同时性肝转移的治疗

Objective To investigate the clinical pathologic characters of colorectal cancer with simultaneous hepatic metastasis and the prognosis. Methods From Aug. 1994 to Dec. 2006, 2019 cases of colorectal carcinoma were admitted, among them there were 166 patients of colorectal cancer with synchronous liver metastases receiving surgical therapy. Results were analyzed retrospectively using the software of SPSS. Results These 166 patients with synchronous liver metastases from colorectal cancer accounted for 8.1% of all 2019 patients of colorectal cancer admitted. Multivariate analysis demonstrated that CEA level before surgery、depth of invasion、 pathological type and Ducks' stage were the key risk factors predicting simultaneous liver metastasis from colorectal cancer. The survival rates at 1, 3 and 5 years were 69%, 21%, and 9% respectively. There was significant difference among the different liver metastasis group of H1, H2 and H3(X2=23.35, P<0.01). The survival rates of patients undergoing radical resection was higher than those undergoing palliative resection (PR)and by-pass operation or feeding neostomy(BP/ FN)(X2= 21.18,P<0.01). PR improved short-term prognosis but did not improve long-term survival compared with BP/FN group(P=0.13). Conclusion Colorectal cancer with synchronous liver metastases has poor clinic pathological characters. Different degree of liver metastasis result in different prognosis.Radical resection leads to a better prognosis. Palliative resection can improve short-term prognosis and life quality but can't improve long-term survival.     

结直肠癌伴同时性肝转移的治疗

Objective To investigate the clinical pathologic characters of colorectal cancer with simultaneous hepatic metastasis and the prognosis. Methods From Aug. 1994 to Dec. 2006, 2019 cases of colorectal carcinoma were admitted, among them there were 166 patients of colorectal cancer with synchronous liver metastases receiving surgical therapy. Results were analyzed retrospectively using the software of SPSS. Results These 166 patients with synchronous liver metastases from colorectal cancer accounted for 8.1% of all 2019 patients of colorectal cancer admitted. Multivariate analysis demonstrated that CEA level before surgery、depth of invasion、 pathological type and Ducks' stage were the key risk factors predicting simultaneous liver metastasis from colorectal cancer. The survival rates at 1, 3 and 5 years were 69%, 21%, and 9% respectively. There was significant difference among the different liver metastasis group of H1, H2 and H3(X2=23.35, P<0.01). The survival rates of patients undergoing radical resection was higher than those undergoing palliative resection (PR)and by-pass operation or feeding neostomy(BP/ FN)(X2= 21.18,P<0.01). PR improved short-term prognosis but did not improve long-term survival compared with BP/FN group(P=0.13). Conclusion Colorectal cancer with synchronous liver metastases has poor clinic pathological characters. Different degree of liver metastasis result in different prognosis.Radical resection leads to a better prognosis. Palliative resection can improve short-term prognosis and life quality but can't improve long-term survival.     

结直肠癌伴同时性肝转移的治疗

Objective To investigate the clinical pathologic characters of colorectal cancer with simultaneous hepatic metastasis and the prognosis. Methods From Aug. 1994 to Dec. 2006, 2019 cases of colorectal carcinoma were admitted, among them there were 166 patients of colorectal cancer with synchronous liver metastases receiving surgical therapy. Results were analyzed retrospectively using the software of SPSS. Results These 166 patients with synchronous liver metastases from colorectal cancer accounted for 8.1% of all 2019 patients of colorectal cancer admitted. Multivariate analysis demonstrated that CEA level before surgery、depth of invasion、 pathological type and Ducks' stage were the key risk factors predicting simultaneous liver metastasis from colorectal cancer. The survival rates at 1, 3 and 5 years were 69%, 21%, and 9% respectively. There was significant difference among the different liver metastasis group of H1, H2 and H3(X2=23.35, P<0.01). The survival rates of patients undergoing radical resection was higher than those undergoing palliative resection (PR)and by-pass operation or feeding neostomy(BP/ FN)(X2= 21.18,P<0.01). PR improved short-term prognosis but did not improve long-term survival compared with BP/FN group(P=0.13). Conclusion Colorectal cancer with synchronous liver metastases has poor clinic pathological characters. Different degree of liver metastasis result in different prognosis.Radical resection leads to a better prognosis. Palliative resection can improve short-term prognosis and life quality but can't improve long-term survival.     

K-ras基因突变与结直肠癌临床病理因素的关系

目的 建立K-ras基因简单、快捷、经济的检测方法,并将检测结果与临床病理因素进行相关性分析.方法 采用PCR-直接测序法和聚合酶链式反应-限制性片段长度多态性测序法(PCR-RFLP)同时检测40例结直肠癌肿瘤组织标本K-ras基因第12、13密码子突变情况;另113例患者仅用PCR-RFLP-测序法检测K-ras基因第12、13密码子突变情况.将K-ras基因突变检测结果与临床病理因素进行相关性分析.结果 40例结直肠癌患者的肿瘤组织经常规PCR扩增后直接测序无一例发现K-ras基因第12、13密码子的突变;而这40例标本经PCR-RFLP-测序法检测发现:8例含有K-ras基因第12密码子突变,3例含有K-ras基因第13密码子突变,总突变检出率为27.5%(11/40).153例结直肠癌肿瘤组织标本经PCR-RFLP-测序法检测共发现突变58例,突变率为37.9%(58/153),其中第12密码子突变46例,第13密码子突变12例.G→A是K-ras基因突变最常见的突变形式(25/58,43.1%).K-ras基因第12和13密码子突变与患者性别、肿瘤浸润深度、分化程度、与淋巴结转移、远处转移及分期无明显相关性(P＞0.05),与年龄、肿瘤发生部位密切相关(P＜0.05),年龄越大突变概率越低,突变最常发生的肿瘤部位为升结肠.结论 PCR-RFLP-测序法能够快捷、灵敏地检测出肿瘤组织中K-ras基因的突变,适合作为K-ras基因突变常规检测方法.K-ras基因第12和13密码子突变是结直肠癌中一个常见的分子事件,与患者年龄、肿瘤发生部位有相关性.     

"Field cancerization"--an additional phenomenon in development of colon tumors? K-ras codon 12 mutations in normal colonic mucosa of patients with colorectal neoplasms]

INTRODUCTION: The c-K-ras2-gene (K-ras) encodes the p21ras protein, which participates in the transduction of mitogenic signals from the cell surface to the nucleus. About 40-50% of colorectal cancers bear a point mutation of the K-ras codon 12 within exon I, leading to activation of the K-ras oncogene. METHODS: Using a polymerase chain reaction (PCR)-based two-step restriction fragment length polymorphism (2sRFLP)-technique, we assessed the frequency of point mutations in the first or second base of K-ras codon 12 in patients suffering from colorectal carcinoma, adenoma, and their normal colon mucosa, respectively. RESULTS: Similar to other investigators, we found mutations in 7 out of 17 (41%) colorectal carcinomas and 1 out of 4 (25%) adenomas. Using this very sensitive 2sRFLP technique (detection level = 0.2% of mutated cells), we were able to find K-ras codon 12 mutations in normal mucosa in 4 out of 18 (22.2%) patients with colorectal neoplasia. CONCLUSIONS: This result can be explained by the phenomenon of "field cancerization" or by a local micrometastasis of K-ras-positive tumor cells.     

癌组织K-ras基因突变和血清CEA的联合检测预测结直肠癌肝转移的意义

目的 观察结直肠癌组织中K-ras瑚基因突变,检测患者外周血清CEA水平,探讨两者与结直肠癌肝转移的关系.方法 应用实时荧光定量聚合酶链反应(PCR)方法和基因测序技术检测100例结直肠癌组织中K-ras基因1号外显子12、13密码子突变,化学发光法检测患者血清CEA水平,结合其临床资料分析.结果 100例结直肠癌组织中K-ras基因突变者39例(39.0%),其中12号密码子突变31例,13号密码子突变8例.36例肝转移组中K-ras基因突变23例(23/36,63.9%);64例无肝转移组中K-ras基因突变16例(16/64,25.0%).36例有肝转移患者外周血清CEA水平为(66.79±127.46)μg/L,其中25例(25/36,69.4%)出现不同程度CEA升高;64例无肝转移患者外周血清CEA水平为(4.93±4.62)μg/L,其中24例(24/64,37.5%)CEA升高.两个指标联合检测,肝转移组的阳性率(22/36,61.1%)明显高于无肝转移组的阳性率(5/64,7.8%),P<0.01.其预测结直肠癌肝转移的敏感性及特异性分别为61.1%和92.2%.结论 K-ras基因突变、血清CEA水平与结直肠癌肝脏转移有密切相关,联合检测癌组织K-ras基因突变和血清CEA水平可预测结直肠癌肝转移.     

Genetic detection of lymph node micrometastases: a selection criterion for liver transplantation in patients with liver metastases after colorectal cancer

BACKGROUND: Liver transplantation for nonresectable liver metastases from colorectal cancer was abandoned in 1994 on account of high recurrence rates. The aim of this study was to investigate whether the genetic detection of micrometastases in histologically negative lymph nodes of the primary colon cancer could be applied to select patients for liver transplantation. METHODS: We analyzed 21 patients with colorectal cancer who had undergone liver transplantation between 1983 and 1994 for liver metastases. Eleven patients were histologically lymph node negative at the time of surgery; ten patients with lymph node metastases served as control group. DNA sequencing was used to screen tumor material for p53 and K-ras mutations. Mutant allele-specific amplification (MASA) was then used to search for micrometastases in DNA from regional lymph nodes of the primary colorectal cancer. RESULTS: p53 and K-ras mutations were detected in 12 (57%) and 3 (14%) of 21 patients in the colorectal cancer, respectively. The mutations were confirmed in the corresponding liver metastases. Of 11 patients with histologically negative lymph nodes, nine were eligible for MASA due to presence of p53 or K-ras mutation. MASA revealed six of nine patients to be genetically positive for micrometastases. Three patients were both genetically and histologically negative. These three patients showed a significantly longer overall survival (P = 0.011) of 4, 5, and 20 years, respectively. CONCLUSIONS: We conclude that the genetic detection of micrometastases by MASA could be a powerful prognostic indicator for selecting patients with colorectal liver metastases who could benefit from liver transplantation.     

癌组织K-ras基因突变、术前血清CEA水平与结直肠癌临床病理特点的关系

目的观察结直肠癌组织中K-ras基因突变情况,术前检测患者血清CEA水平,探讨两者与结直肠癌临床病理的关系。方法应用实时荧光定量PCR方法和基因测序技术检测100例结直肠癌组织中K-ras基因12、13密码子突变情况,化学发光法检测患者血清CEA水平,结合其临床病理资料进行统计学分析。结果 K-ras基因突变者39例(39.0%),其中12号密码子突变31例,13号密码子突变8例。有淋巴结转移者K-ras基因突变率(57.8%)明显高于无淋巴结转移者(23.6%),有肝脏转移者K-ras基因突变率(62.5%)明显高于无肝转移者(34.5%),TNM分期Ⅲ、Ⅳ期K-ras基因突变率(56.5%)明显高于Ⅰ、Ⅱ期(24.1%)。K-ras基因突变率与肿瘤大小、部位、肿瘤浸润深度、分化程度无密切关系。49例CEA水平超出正常范围(49.0%)。有淋巴结转移或肝转移患者CEA水平显著高于无淋巴结或肝转移患者(P0.05)。在肿瘤不同的临床病理分期(Duke's、TNM分期)间CEA水平差异有统计学意义,Duke's D期和TNMⅢ、Ⅳ期出现高阳性率。CEA水平在肿瘤不同浸润深度、体积及分化程度上无明显差异。结论癌组织K-ras基因突变和血清CEA水平超出正常水平预示结直肠癌可能合并淋巴结转移或肝转移,是预后不良的指标。     

直肠癌术前放疗前后K-ras基因突变的研究

目的检测直肠癌术前放疗前后原癌基因Kirsten大鼠肉瘤病毒转化基因(K-ras基因)突变率的变化,从细胞遗传学方面深入研究放射治疗对直肠癌的作用。方法pTNM Ⅱ期和Ⅲ期直肠癌病人40例。病人术前行40 Gy放疗,放疗前和术中分别取癌组织、距边缘2、4和6cm正常黏膜采用聚合酶链反应-单链构象多态性分析(PCR-SSCP)法检测K-ras基因第12密码子突变。结果癌组织中K-ras基因突变率显著高于癌周正常黏膜,同时距癌边缘2cm黏膜的K-ras基因突变率显著高于距癌边缘4、6cm黏膜的。放疗后癌组织和距癌边缘2cm黏膜的K-瑚基因突变率与放疗前相比显著降低。结论距肿瘤2cm之内的黏膜有较高的K—ras基因突变率,向恶性转化的可能较大,放疗后癌组织和癌旁黏膜K-ras基因突变率显著降低,因此,放疗可能抑制癌旁黏膜恶变的早期事件,这可能是放疗能增加手术切除率和保肛率的原因。     

K-ras mutational analysis of polyclonal colorectal cancers identifies uniclonal circulating tumor cells

The clonal development of colorectal carcinoma resulting from specific mutations in certain oncogenes and/or tumor suppressor genes is a well-accepted model. It is increasingly recognized that a majority of colorectal cancers are polyclonal on the basis of molecular analysis that demonstrates cells with different mutations within a given oncogene or tumor suppressor gene in the same tumor. This polyclonal pattern may occur as a result of either clonal convergence or divergence during the many steps of oncogenesis. Further complicating this picture is the fact that metastatic lesions may arise from only one of the clonal populations within a tumor and thereby present only a partial molecular make-up of the whole tumor. There are few data available that define clonal selection or specificity of circulating tumor cells in patients undergoing curative resection of colorectal carcinoma. The purpose of this paper is to describe the clonal distribution of circulating tumor cells in four patients with multiple K-ras mutations present in the primary lesion. Patients were selected who were known to have polyclonal primary colorectal cancers resected for cure. All patients had multiple mutations present in exon one, codon 12 and/or 13, of the K-ras gene. Blood samples were drawn immediately before surgery and at 2-week to 6-month intervals postoperatively. Epithelial cells were isolated from peripheral blood mononuclear cells using Dynal Immunobeads coated with antiepithelial antibodies. DNA was extracted from these cells and analyzed for all K-ras mutations present in codons 12 and 13 of the patient's primary tumor using allele-specific polymerase chain reaction followed by Microwell Array Diagonal Gel Electrophoresis. Circulating tumor cells were identified in all four patients. However, in each case of positive circulating cells the only mutation identified was an aspartic acid mutation at codon 13. Once positive the circulating tumor cells persisted in subsequent multiple blood samples. These results provide further strength for the theory of polyclonal progression in primary colorectal cancers, although there may be specific mutational patterns that confer the ability to metastasize. The significance of this persistence of the glycine-to-aspartic acid mutation at codon 13 remains to be defined given that none of these patients has clinical evidence of recurrent cancer at the time of this report.     

Macroscopic portal vein tumor thrombi of liver metastasis from colorectal cancer

We present a case of multiple colorectal liver metastases with macroscopic portal vein thrombi. A 55-year-old woman presented to us with rectosigmoid cancer and presented with two liver metastases. The tumor in the posterior sector was associated with invasion of first order branches of the portal vein. We performed low anterior resection, hepatic posterior sectorectomy and partial left anterior sectorectomy. Both the colorectal cancer and liver tumors exhibited histological characteristics of moderately differentiated adenocarcinoma with a substantial amount of mucin production. The liver metastases were associated with prominent tumor thrombi in many branches of the portal vein. Stronger staining for endoglin (CD 105) than for Fas ligand (Fas L) and matrix metalloproteinase (MMP-2) was observed in both the colorectal cancer and metastatic liver tumor cells. Expression of the vascular endothelial growth factor within the tumor cells was seen in both the colorectal cancer as well as the metastatic liver tumor cells. Six months after the operation, she was diagnosed to have multiple, more than about 20 liver metastases, and in 9 months after the operation, the patient died. The colorectal cancer with liver metastases associated with portal vein tumor thrombosis was poor prognosis, found neoplastic microvessel formation.     

Clinical Significance of K-Ras Mutations in Intraoperative Tumor Drainage Blood From Patients With Colorectal Carcinoma

Background: Recurrent and metastatic carcinoma of the colorectum remains a major problem. This may be ascribed to the presence of micrometastasis at diagnosis. The purpose of this study was to analyze prospectively the clinical value of detecting K-ras mutations in the perioperative circulating blood from patients with colorectal carcinoma.Methods: Twenty-four patients whose tumor carried mutations in codon 12 of the K-ras gene were studied for the presence of cancer cells in perioperative blood samples, in particular, tumor drainage samples. A detection assay using CD45 immunomagnetic separation plus nested mutant allele specific amplification (MASA) was performed.Results: K-ras mutations in CD45 negative cells in tumor drainage blood were detected in 7 (29.2%) of 24 patients. There was no significant relationship between the presence of a K-ras mutation and clinicopathological features. Four (57.1%) of the seven patients with a positive K-ras mutation in drainage blood had early recurrent disease. Of the 17 patients with no K-ras mutation, none developed metastatic disease. The recurrence rate of the K-ras mutation positive group was higher than that of the K-ras mutation negative group (P < .01). There was a significant difference, regarding prognosis, between K-ras mutation positive and negative groups (P < .01).Conclusions: This preliminary study demonstrates that the detection of circulating cancer cells in the tumor drainage blood by our new assay system may provide a predictor of recurrence and metastasis of colorectal cancer.     

Carcinoembryonic antigen (CEA) levels of peripheral and portal blood and tumor histopathology in colorectal cancer

Correlation between CEA levels of peripheral and portal blood and 9 histopathologic variables were examined in 66 patients with colorectal cancer. CEA levels of portal blood (mean 26.6ng/ml and positive rate more than 5ng/ml, 59.1%) were significantly higher than those (8.1ng/ml and 33.3%) of peripheral blood. Elevation of CEA levels in portal and peripheral blood were most highly correlated with the grade of vein invasion and its location in the layer of colorectal wall, although the levels were related to the other 8 histopathologic variables such as tumor size, the grade of node metastases, Dukes stage and so on. CEA levels of portal blood elevated from 19.4ng/ml and 40% to 43.6ng/ml and 90.2% respectively following operative stimuli to cancer lesions with vein invasion, but the levels did not elevated in the lesions without its invasion. CEA levels of peripheral blood were as low as 5ng/ml in 3 out of 8 patients with liver metastases. However, the levels in portal blood were much higher than 5ng/ml in all the patients. These results suggested that CEA might be hematogenously drained by portal system from cancer cells in the invasive veins, but not by thoracic duct of lymphatic system, and also that the measurement of CEA in portal blood might be available to predict the vein invasion of cancer lesions and liver metastases in patients with colorectal cancer.