幽门狭窄对行D2根治术的进展期远端胃癌患者预后的影响

Objective To investigate the impact of pyloric stenosis on the prognosis after D2 radical resection for advanced distal gastric cancer.Methods Clinical data of 284 patients with advanced distal gastric cancer who underwent D2 radical resection from January 1998 to December 2004 were analyzed retrospectively.Clinicopathologic variables,survival outcomes,and postoperative morbidity and mortality were compared between patients who developed pyloric stenosis (n=69) and those without pyloric stenosis (n=215).Results The 5-year survival rate was 38.8% in patients with pyloric stenosis and 62.4% in those without pyloric stenosis,and the difference was statistically significant (P＜0.05).Cox regression model showed that pyloric stenosis,tumor size,depth of invasion,and lymph node involvement were independent predictors for survival.There were no significant differences between the two groups in postoperative morbidity (13.0% vs.10.2%,P＞0.05) or mortality (2.9% vs.1.4%,P＞0.05).Conclusions Pyloric stenosis is associated with poor survival for patients undergoing D2 radical resection for advanced distal gastric cancer.However,pyloric stenosis does not increase postoperative morbidity and mortality related to surgery.     

结肠癌与直肠癌根治术后复发的比较研究

Objective To explore the difference in tumor biological behaviors and prognosis between recurrent colon cancer and recurrent rectal cancer after radical operation. Methods Complete clinical and follow-up data of 132 patients with colorectal cancer developed recurrence,including 36 colon cancers and 96 rectal caners, after curative resection were retrospectively analyzed and compared with respect of clinical pathological features and prognosis between colon and rectal cancer.Results Significant differences were found in primary tumor gross type, histological type, tumor differentiation and lymph node metastasis between colon and rectal cancer (P＜0.05). Colon cancer recurred earlier than rectal cancer after radical surgery with the median time to recurrence being 14.0 months and 21.5 months, respectively (P=0.028). The difference in multiple sites recurrence was also found between colon (n=16,44.4%) and rectal cancer (n=65,67.7%)(P=0.014). The 3-year survival rate of recurrent rectal cancer was better than that of colon cancer (24.8% vs 15.6% ,P=0.026).Conclusion There are some differences in tumor biological behaviors between colon and rectal cancer,and the prognosis of rectal cancer with recurrence is better than that of colon cancer.     

结肠癌与直肠癌根治术后复发的比较研究

Objective To explore the difference in tumor biological behaviors and prognosis between recurrent colon cancer and recurrent rectal cancer after radical operation. Methods Complete clinical and follow-up data of 132 patients with colorectal cancer developed recurrence,including 36 colon cancers and 96 rectal caners, after curative resection were retrospectively analyzed and compared with respect of clinical pathological features and prognosis between colon and rectal cancer.Results Significant differences were found in primary tumor gross type, histological type, tumor differentiation and lymph node metastasis between colon and rectal cancer (P＜0.05). Colon cancer recurred earlier than rectal cancer after radical surgery with the median time to recurrence being 14.0 months and 21.5 months, respectively (P=0.028). The difference in multiple sites recurrence was also found between colon (n=16,44.4%) and rectal cancer (n=65,67.7%)(P=0.014). The 3-year survival rate of recurrent rectal cancer was better than that of colon cancer (24.8% vs 15.6% ,P=0.026).Conclusion There are some differences in tumor biological behaviors between colon and rectal cancer,and the prognosis of rectal cancer with recurrence is better than that of colon cancer.     

碳酸酐酶IX表达在肾透明细胞癌预后评估中的价值

目的 评估肾透明细胞癌组织中碳酸酐酶IX(CA IX)表达在患者预后判断中的价值.方法 应用免疫组织化学P-V方法检测 120例肾透明细胞癌和25例正常肾组织石蜡标本中CA IX的表达.以肿瘤特异性生存率作为最终和主要的评估目标.运用Cox回归模型行CA IX表达与预后关系的单因素和多因素分析,以P＜0.05为差异有统计学意义.结果 112例(93.3%)获随访,随访6～94个月,中位时间45个月,无瘤生存75例,带瘤生存3例,死亡34例,其中死于肿瘤28例.正常肾组织均不表达CA IX.120例肾透明细胞癌组织中CA IX高表达89例(74.2%),高表达者中获随访82例,无瘤生存62例(75.6%),带瘤生存2例(2.4%),死亡18例(22.0%),死于肿瘤13例(15.9%),复发和(或)转移9例(11.0%),中位生存期为92个月.肾透明细胞癌CA IX低表达31例(25.8%),其中获随访30例,无瘤生存13例(43.3%),带瘤生存1例(3.3%),死亡16例(53.3%),死于肿瘤15例(50.0%),中位生存期为53个月,复发和(或)转移8例(26.7%).2组肿瘤特异性生存率比较经log-rank检验,差异有统计学意义(P=0.000,χ2=15.950),CA IX高表达组1、3、5、7年肿瘤特异性生存率分别为95.2%、83.9%、81.2%、78.2%,CA IX低表达组分别为89.5%、63.9%、46.8%、40.1%.2组术后肿瘤复发和(或)转移率比较差异有统计学意义(P=0.040,χ2=4.200).多因素Cox 回归模型分析显示CA IX表达是影响肾透明细胞癌预后的指标(RR=0.186).结论 CA IX高表达与肾透明细胞癌患者术后死亡率及肿瘤复发和(或)转移率呈负相关,CA IX可作为判断肾透明细胞癌预后的指标.

Abstract：

Objective To evaluate the prognostic significance of carbonic anhydrase IX (CA IX) expression in patients with clear cell renal cell carcinoma (ccRCC). Methods CA IX expression in a cohort of 120 patients with ccRCC was evaluated by P-V immunohistochemistry with a rabbit CA IX polyclonal antibody. Twenty-five normal kidney tissues were used as a control. The relationship between CA IX expression and prognosis was analyzed by univariate and multiple-factor analysis (Cox regression model). The primary end point was cancer specific survival. Results One hundred and twelve (93.3%) patients were followed up with the median follow-up time of 45 months (range, 6 to 94 months). Seventy-five patients survived without evidence of tumor recurrence, 3 patients survived with tumor recurrence, and 34 patients died, 28 of the 34 died of cancer. CA IX expression was negative in all normal renal tissue. High CA IX expression was observed in 89 (74.2%) patients, among which 82 patients were followed up, and the disease free survival was 75.6% (62/82). Two (2.4%) patients survived with tumor recurrence, and 18 (22.0%) patients died, of which 13 (15.9%) died of cancer. Tumor recurrence and (or) metastasis occurred in 9 (11.0%) patients, with a median survival of 92 months in this high expression group. Low CA IX expression was observed in 31 (25.8%) patients, among which 30 patients were followed up, and the disease free survival was 43.3% (13/30). One (3.3%) patient survived with tumor recurrence, and 16 (53.3%) patients died, of which 15 (50.0%) died of cancer. Tumor recurrence and (or) metastasis occurred in 8 (26.7%) patients with a median survival of 53 months in this low expression group. Cancer specific survival between CA IX high expression group and low expression group was significantly different (P=0.000, χ2=15.950), and tumor relapse and (or) metastasis rates were significantly different (P=0.040, χ2=4.200). The 1, 3, 5 and 7 year cancer specific survival rates were 95.2%, 83.9%, 81.2% and 78.2% respectively in the high CA IX expression group, and 89.5%, 63.9%, 46.8% and 40.1% respectively in the low expression group. Multivariate analysis with Cox regression model showed that CA IX expression was a prognostic factor (RR=0.186). Conclusions High CA IX expression is negatively correlated with postoperative mortality, relapse and (or) metastasis in ccRCC. CA IX expression could be used as a prognostic biomarker in ccRCC.     

胆囊癌不同手术方式的疗效分析

Objective To investigate the therapeutic effects of different surgical procedures for the treatment of gallbladder cancer. Methods The clinical data of 81 patients with gallbladder cancer who were admitted to the West China Hospital of Sichuan University from January 2000 to October 2009 were retrospectively analyzed.The efficacies of different surgical procedures for the treatment of gallbladder cancer, and the relationship between T stage and lymph node metastasis were investigated. The postoperative survival rates of patients in different TNM stages were analyzed and compared using the Kaplan-Meier method and Log-rank test, respectively. Results The median survival times of patients in stage Ⅰ , Ⅱ ,Ⅲ and Ⅳ were 68, 18, 7 and 5 months, respectively. The 1-,3-, 5-year survival rates were 100%, 80% and 60% for patients in stage Ⅰ, 57%, 29% and 14% for patients in stage Ⅱ, 27%, 7% and 0 for patients in stage Ⅲ and 11%, 4% and 0 for patients in stage Ⅳ. There were significant differences in the survivals of patients in different TNM stages ( P ＜ 0.05 ). Of the 81 patients, 67 received surgical treatment. The 5-year survival rate was 100% for patients in stage T1b who received standard radical resection and 0 for patients who received simple cholecystectomy. The median survival time was 45 months for patients in stage Ⅱ who received standard radical resection and 12 months for patients in stage Ⅱ who received simple cholecystectomy, and their 1-, 3-, 5-year survival rates were 67%, 33%, 33% and 50%, 0, 0, respectively, with significant differences ( P ＜ 0. 05 ). The 1-, 3-, 5-year survival rates of patients in stage Ⅲ who received standard radical resection were 33%, 17% and 6%, respectively. The survival time of patients who received extended radical resection was longer than 12 months, while the survival time of patients who received standard radical resection or other palliative therapy was shorter than 12 months. The 1-, 3-, 5-year survival rates of patients in stage Ⅳ who received extended radical resection and standard radical resection were 38%, 12%, 0and 14%, 0, 0, respectively. The survival time of patients in stage Ⅳ who received other treatments was shorter than 12 months. Lymph node metastasis were identified in 7 patients in stage T2(n = 15), 7 patients in stage T3(n = 14), and 12 patients in stage T4(n = 13), no patient in stage T1 (n =2) was found with lymph node metastasis. Conclusions Lymph node metastasis is significantly influenced by the depth of invasion of the gallbladder cancer. For patients in stage T1b, Ⅱ and Ⅲ, radical resection of gallbladder cancer is necessary; for patients in stage Ⅳ, although the incidence of complication is higher, the survival time is much longer when compared with other treatments.     

影响T1～2期结直肠癌淋巴结转移和预后的因素分析

Objective To investigate factors associated with lymph node metastasis and prognosis in patients with T1-2 colorectal cancer. Methods Patients with pT1-2 colorectal cancer between January 1999 to January 2005 were included. Chi-square test and multivariable logistic analysis were performed to evaluate risk factors associated with lymph node metastasis. Survival outcomes were analyzed using Kaplan-Meier and Cox regression model. Results Tumor location and depth of invasion were independent risk factors for lymph node metastasis (P＜0.01 and P＜0.05). Gender, age, tumorgross pattern, tumor differentiation, carcinoembryonic antigen level, and tumor diameter were notassociated with lymph node metastasis. Lymph node metastasis and distant metastasis on postoperative follow-up were independent risk factors for survival (P＜0.05 and P＜0.01). Conclusion Factors associated with lymph node metastasis in pT1-2 colorectal cancer do not affect the survival. However,lymph node metastasis and distant metastasis are predictive for survival.     

140例胃间质瘤的外科治疗分析

Objective To analyze the outcome of the patients with gastric gastrointestinal stromal tumor (GIST) after surgical treatment and identify the associated risk factors. Methods Clinical data and the tissue slices including immunohistochemistry staining of 140 patients with gastric GIST from January 1990 to December 2008 were retrospectively reviewed. SPSS 16.0 for Windows software package was used for statistical analysis. Results The overall survival rates of 1-, 3-, 5-year were 96.8%,86.7% and 79.3%, respectively. The survival rates of 1-, 3-, 5-year were 98.1%, 90.0% and 85.4% in patients who underwent complete tumor resection. But the survival rates of 1-, 3-, 5-year were 38.1%, 0 and 0 in patients with incomplete tumor resection. The differences were statistically significant (P＜0.05). Gender, preoperative metastasis, tumor size, pathology type, karyokinesis, recurrence and metastasis were associated with survival rates in patients with complete tumor resection by univariate analysis. However, only tumor size, karyokinesis, recurrence and metastasis were associated with survival rates by Cox regression multivariable analysis (P＜0.05). Conclusion Surgery remains the main treatment for gastric GIST. Local complete resection is the principal treatment.     

140例胃间质瘤的外科治疗分析

Objective To analyze the outcome of the patients with gastric gastrointestinal stromal tumor (GIST) after surgical treatment and identify the associated risk factors. Methods Clinical data and the tissue slices including immunohistochemistry staining of 140 patients with gastric GIST from January 1990 to December 2008 were retrospectively reviewed. SPSS 16.0 for Windows software package was used for statistical analysis. Results The overall survival rates of 1-, 3-, 5-year were 96.8%,86.7% and 79.3%, respectively. The survival rates of 1-, 3-, 5-year were 98.1%, 90.0% and 85.4% in patients who underwent complete tumor resection. But the survival rates of 1-, 3-, 5-year were 38.1%, 0 and 0 in patients with incomplete tumor resection. The differences were statistically significant (P＜0.05). Gender, preoperative metastasis, tumor size, pathology type, karyokinesis, recurrence and metastasis were associated with survival rates in patients with complete tumor resection by univariate analysis. However, only tumor size, karyokinesis, recurrence and metastasis were associated with survival rates by Cox regression multivariable analysis (P＜0.05). Conclusion Surgery remains the main treatment for gastric GIST. Local complete resection is the principal treatment.     

TROP2基因mRNA在左半结肠癌和右半结肠癌组织中的表达及其临床意义

Objective To investigate the expression of TROP2 in the left-sided and right-sided colon cancer and its clinical significance. Methods A total of eighty patients, who received radical resection of colon cancer between June 2001 and April 2005 and were staged as Ⅱ and Ⅲ, were identified, including forty with left-sided colon cancer(LSCC)and forty with right-sided colon cancer (RSCC). The expression of TROP2 was detected by real-time quantitative RT-PCR in paired cancer and normal tissue. Subsequently, the relationship between TROP2 expessian and clinicopathoiogical variables as well as the effect on the patients' prognosis were analyzed. Results The expression of TROP2 mRNA in the cancer tissue was significantly higher than that in normal tissue (P<0.01, paired Wilcoxon test). However, its expression in LSCC was markedly higher than that in RSCC with significant difference (P=0.009, Mann-Whitney U test). The patients with TROP2 high expression were found more frequently in LSCC than in RSCC (67.5% vs 32.5%, P=0.002, χ2 test). Cancer-related mortality of the patients with TROP2 high expression was four times as high as low expression (40% vs 10%, P=0.002, χ2 test). From the stratified survival analysis through Kaplan-Meier curve, the TBOP2 high expression group had a significantly poorer median survival time than the low expression group for the patients with LSCC (45.9:63.1 months, P=0.032, log-rank test). By contrast, for the patients with RSCC, TROP2 expression had no marked effect on the survival time (P=0.235, log-rank test). In multivariable analysis, for the cohort of the present study, serosal invasion and lymphatic/vascular invasion were the independent prognostic factors of RSCC. Serosal invasion, lymph node metastasis and lymphatic/vascular invasion were the independent prognostic factors of LSCC. TROP2 high expression showed marginal significance (RR:6.244, 95% CI:0.755-51.636, P=0.089). Conclusion (1)TROP2 is a differentially expressed gene between RSCC and LSCC. (2)TROP2 high expression is closely related to the factors indicating poor prognosis. (3)TROP2 has distinct clinical significance to the patients with different tumor sites. TROP2 high expression is potentially an independent prognostic factor of LSCC. (4)LSCC and RSCC seem to be two distinct diseases with significant molecular heterogeneity.     

TROP2基因mRNA在左半结肠癌和右半结肠癌组织中的表达及其临床意义

Objective To investigate the expression of TROP2 in the left-sided and right-sided colon cancer and its clinical significance. Methods A total of eighty patients, who received radical resection of colon cancer between June 2001 and April 2005 and were staged as Ⅱ and Ⅲ, were identified, including forty with left-sided colon cancer(LSCC)and forty with right-sided colon cancer (RSCC). The expression of TROP2 was detected by real-time quantitative RT-PCR in paired cancer and normal tissue. Subsequently, the relationship between TROP2 expessian and clinicopathoiogical variables as well as the effect on the patients' prognosis were analyzed. Results The expression of TROP2 mRNA in the cancer tissue was significantly higher than that in normal tissue (P<0.01, paired Wilcoxon test). However, its expression in LSCC was markedly higher than that in RSCC with significant difference (P=0.009, Mann-Whitney U test). The patients with TROP2 high expression were found more frequently in LSCC than in RSCC (67.5% vs 32.5%, P=0.002, χ2 test). Cancer-related mortality of the patients with TROP2 high expression was four times as high as low expression (40% vs 10%, P=0.002, χ2 test). From the stratified survival analysis through Kaplan-Meier curve, the TBOP2 high expression group had a significantly poorer median survival time than the low expression group for the patients with LSCC (45.9:63.1 months, P=0.032, log-rank test). By contrast, for the patients with RSCC, TROP2 expression had no marked effect on the survival time (P=0.235, log-rank test). In multivariable analysis, for the cohort of the present study, serosal invasion and lymphatic/vascular invasion were the independent prognostic factors of RSCC. Serosal invasion, lymph node metastasis and lymphatic/vascular invasion were the independent prognostic factors of LSCC. TROP2 high expression showed marginal significance (RR:6.244, 95% CI:0.755-51.636, P=0.089). Conclusion (1)TROP2 is a differentially expressed gene between RSCC and LSCC. (2)TROP2 high expression is closely related to the factors indicating poor prognosis. (3)TROP2 has distinct clinical significance to the patients with different tumor sites. TROP2 high expression is potentially an independent prognostic factor of LSCC. (4)LSCC and RSCC seem to be two distinct diseases with significant molecular heterogeneity.     

微卫星不稳定性和肝细胞生长因子对结直肠癌患者生存状况的影响

目的探讨微卫星不稳定性(MSI)和肝细胞生长因子(HGF)对结直肠癌患者生存状况的影响。方法选取2012年1月至2014年5月收治的82例结直肠癌患者为研究对象。采用免疫组织化学法检测MSI及HGF表达情况。所有资料采用SPSS 20.0进行分析处理,计量资料采用均数±标准差表示并行t检验,MSI及HGF表达阳性率采用χ2检验,多因素分析采用Cox回归分析,生存分析采用Kaplan-Meier法,MSI与HGF表达的关系采用spearman相关性分析。P0.05作为差异有统计学意义。结果 MSI阳性患者32例,占39.0%;HGF表达阳性58例,占70.7%。MSI与分化程度相关(P0.05),与年龄、性别、肿瘤部位、肿瘤大小、组织学类型、大体类型、淋巴转移无关(P0.05)。HGF表达与上述指标均无关(P0.05)。MSI与HGF表达之间具有明显负相关性(r=-0.6531,P=0.032)。年龄、淋巴转移、MSI和HGF表达阳性是结直肠癌患者总生存期的独立影响因素(P0.05)。结论HGF在结直肠癌中表达较MSI更明显,MSI和HGF表达水平与结直肠癌患者生存期相关。     

Comparison of microsatellite instability and chromosomal instability in predicting survival of patients with T3N0 colorectal cancer

BACKGROUND: At least 2 apparently independent mechanisms, microsatellite instability (MSI) and chromosomal instability, are implicated in colorectal tumorigenesis. Their respective roles in predicting clinical outcomes of patients with T3N0 colorectal cancer remain unknown. METHODS: Eighty-eight patients with a sporadic T3N0 colon or rectal adenocarcinoma were followed up for a median of 67 months. For chromosomal instability analysis, Ki-ras mutations were determined by single-strand polymerase chain reaction, and p53 protein staining was studied by immunohistochemistry. For MSI analysis, DNA was amplified by polymerase chain reaction at 7 microsatellite targets (BAT25, BAT26, D17S250, D2S123, D5S346, transforming growth factor receptor II, and BAX). RESULTS: Overall 5-year survival rate was 72%. p53 protein nuclear staining was detected in 39 patients (44%), and MSI was detected in 21 patients (24%). MSI correlated with proximal location (P <.001) and mucinous content (P <.001). In a multivariate analysis, p53 protein expression carried a significant risk of death (relative risk = 4.0, 95% CI = 1.6 to 10.1, P =.004). By comparison, MSI was not a statistically significant prognostic factor for survival in this group (relative risk = 2.2, 95% CI = 0.6 to 7.3, P =.21). CONCLUSIONS: p53 protein overexpression provides better prognostic discrimination than MSI in predicting survival of patients with T3N0 colorectal cancer. Although MSI is associated with specific clinicopathologic parameters, it did not predict overall survival in this group. Assessment of p53 protein expression by immunocytochemistry provides a simple means to identify a subset of T3N0 patients with a 4-times increased risk for death.     

Prognostic significance of extensive microsatellite instability in sporadic clinicopathological stage C colorectal cancer

BACKGROUND: Colorectal cancers exhibiting microsatellite instability (MSI) appear to have unique biological behaviour. This study analyses the association between extensive MSI (MSI-H), clinicopathological features and survival in an unselected group of patients with sporadic Australian Clinico-Pathological Stage (ACPS) C (tumour node metastasis stage III) colorectal cancer. METHODS: Some 255 patients who underwent resection for sporadic ACPS C colorectal cancer between 1986 and 1992 were studied. No patient had received chemotherapy. Minimum follow-up for all patients was 5 years. Archival normal and tumour DNA was extracted and amplified by polymerase chain reaction using a radioactive labelling technique. MSI-H was defined as instability in 40 per cent or more of seven markers. RESULTS: Twenty-one patients showed MSI-H. No association was found between MSI and age or sex. Tumours exhibiting MSI-H were more commonly right sided (P<0.00001), larger (P = 0.002) and more likely to be high grade (P = 0.049). After adjustment for age, sex and other pathological variables, patients whose cancers exhibited MSI-H had improved survival (P = 0.015). CONCLUSION: Recognition of MSI-H in sporadic ACPS C tumours identifies a subset of cancers with improved prognosis. Such stratification should be considered in trials of adjuvant therapy and may be relevant to therapeutic decision making.     

Microsatellite instability in gastric cancer is associated with better prognosis in only stage II cancers

BACKGROUND: The assessment of microsatellite instability (MSI) is not included yet in the routine evaluation of patients with gastric cancer, as controversial data exist regarding its prognostic value. METHODS: We determined the clinical significance of MSI in 510 sporadic gastric cancers, using the mononucleotide markers BAT25 and BAT26. The results were compared with the immunohistochemical expression of the mismatch repair proteins Mlh1 and Msh2. RESULTS: MSI was present in 83 (16%) cancers and correlated with better survival (P < .001). Multivariate analysis showed that the MSI phenotype was an independent factor (P = .005) and added prognostic information to TNM stage, location, and age. The relative risk of death for MSI cancer patients was 0.6 (95% confidence interval [CI], 0.4-0.8). Moreover, when grouped according to stage, only stage II cancers showed a significant effect of MSI status on survival (P = .011; hazard ratio = 0.3; 95% CI, 0.1-0.8). MSI also correlated with older age (P = .002), female gender (P < .001), intestinal histotype (P = .011), lower T stage (P = .018), and less lymph node involvement (P < .001). Finally, comparison of the results of immunohistochemical expression of the mismatch repair proteins Mlh1 and Msh2 with microsatellite analysis showed concordant results in 95% of neoplasms, with a sensitivity of 82% and specificity of 98%. CONCLUSIONS: Microsatellite analysis of gastric cancer has clinical utility in determination of prognosis, but should be determined in only stage II neoplasms in a routine clinical setting. Immunohistochemistry may be considered sufficient, although microsatellite analysis is preferable.     

Genomic instability and tissue expression of angiogenic growth factors in sporadic colorectal cancer

BACKGROUND: Chromosomal instability evidenced by a loss of heterozygosity (LOH) is implicated as a predictor of poor survival in patients with colorectal cancer, whereas microsatellite instability (MSI) is associated with improved survival rates. We investigated the relationship between tumor expression of angiogenic growth factors and genomic alterations in colorectal cancer. METHODS: Two genotypes, LOH and MSI, determined by microsatellite markers in the 4 cancer-related chromosomes 2p, 3p, 17p, and 18q, were analyzed in 73 patients with colorectal cancer. The tumor-specific expression of vascular endothelial growth factor and hepatocyte growth factor (HGF) were quantified, and the interleukin-6 network also was evaluated. RESULTS: MSI-positive neoplasms showed a lesser expression of both tumor growth factors and interleukin-6. In contrast, LOH-positive neoplasms showed a greater expression of HGF and a lesser expression of interleukin-1-receptor antagonist. MSI neoplasms were correlated with favorable prognosis in agreement with previous findings. CONCLUSIONS: The suppressed production of angiogenic growth factors in MSI cancers partly might explain the better prognosis in MSI-positive patients. The interleukin-6 network, which upregulates production of vascular endothelial growth factor and HGF, might be involved in this mechanism.     

Transitional cell carcinoma of the upper urinary tract new concepts in management

Transitional cell carcinomas of the upper urinary tract (UUT-TCCs) are rare: they account for approximately 5% of all urothelial carcinomas. 30% of patients with UUT-TCC have a history of bladder TCC, but fewer than 2% of patients with bladder TCC have UUT-TCC. Tumor microsatellite instability (MSI) is an indicator of the clonal expansion of neoplasms; it was first identified in tumors from patients with hereditary non-polyposis colorectal carcinoma (HNPCC). UUT-TCC occurs in 5% of patients with HNPCC. High-frequency microsatellite instability is present in almost 20% of cases of sporadic UUT-TCC. In cases of UUT-TCC with high-frequency MSI, hereditary cancer must be sought, especially if the patient is younger than 60 years or has a personal or family history of an HNPCC-related cancer: such patients should undergo DNA sequencing for the MSH2 gene germline mutation. Invasive UUT-TCC has a poor prognosis. 5-year survival is less than 50% for stage T2-T3 tumors and less than 10% for T4 or N+/M+ tumors. The main prognostic factors are age and tumor stage and grade. High-frequency MSI is a positive prognostic factor, especially in patients younger than 70 years with T2/T3/N0-M0 tumors.     

复发性结直肠癌的临床病理特征和预后

目的探讨复发性结直肠癌的临床病理特征和预后。方法对进行根治性切除的993例结直肠癌患者中235例复发患者的临床资料进行总结，并分析术后复发的影响因素。结果根治术后全组总体5、10年生存率分别为67．7％和55．8％；术后复发组则分别为43．9％和28．1％；差异有统计学意义（P〈0．001）。复发组患者中，再次行根治性切除者的5、10年生存率分别为50．2％和32．7％；而予以姑息手术或保守治疗者则分别为25．8％和0；差异亦有统计学意义（P〈0．001）。单因素分析显示，复发的结直肠癌患者年龄、癌性肠梗阻和腹水、淋巴结转移及肿瘤大体分型、侵袭程度及病理分期与术后复发密切相关；而多因素分析则显示，癌性肠梗阻和腹水、肿瘤大体分型及病理分期与术后复发和转移密切相关。结论根治术后结直肠癌患者的复发和转移与癌性肠梗阻和腹水及肿瘤病理分期密切相关；再次手术切除可以提高复发转移患者的生存率。     

散发性结直肠癌CpG岛甲基子表型和基因组遗传学不稳定性的关系

目的探讨散发性结直肠癌CpG岛甲基子表型和基因组不稳定性的关系。方法对采用甲基化特异性PCR的方法对71例散发性结直肠癌组织进行P14^ARF、hMLH1、P16^INK4a、MGMT和MINT1共5个基因启动子甲基化的检测,确定CpG岛甲基子表型;选择BAT25和BAT26两个位点进行微卫星不稳定检测和流式细胞术检测分析倍体类型;分析散发性结直肠癌中CpG岛甲基子表型和微卫星不稳定、染色体不稳定的关系。结果全组结直肠癌组织中CpG岛甲基子表型的阳性率为21.1%（15/71）;微卫星不稳定的阳性率为9.9%（7/71）;异倍体的阳性率为73.5%（50/68）。CpG岛甲基子表型阳性者,微卫星不稳定的阳性率高于阴性者（20.0%vs7.1%）,但差异无统计学意义（P=0.158）。hMLH1基因启动子甲基化阳性者微卫星不稳定的比例为57.1%,高于阴性者的4.7%（P=0.001）。CpG岛甲基子表型阳性者二倍体的比例高于阴性者（61.5%vs.18.2%,P=0.003）。结论CpG岛甲基子表型阳性的散发性结直肠癌具有显著的二倍体倾向,多基因同时甲基化和染色体不稳定可能是两种相互独立的基础性发病机制。     

The mechanism of microsatellite instability is different in synchronous and metachronous colorectal cancer

MLH1 promoter hypermethylation has been described as the primary mechanism for high-frequency microsatellite instability (MSI-H) in sporadic colorectal cancers (CRCs). The underlying molecular mechanism for microsatellite instability (MSI) in synchronous and metachronous CRCs is not well described. A total of 33 metachronous CRC patients and 77 synchronous CRC patients were identified from 2884 consecutive patients undergoing cancer surgery in an academic center. Evaluable tumors were tested for MSI, immunohistochemistry for MLH1 and MSH2 protein expression, and hypermethylation of the MLH1 promoter. MSI-H tumors were found in 12 (36%) metachronous CRC patients and 29 (38%) synchronous CRC patients. MSI-H metachronous CRC patients were younger at index cancer diagnosis (64 vs. 76 years, P = 0.01) and more often were diagnosed before 50 years of age (4 of 12 vs. 0 of 29, P = 0.005). Loss of MLH1 expression associated with promoter hypermethylation was common in all patients, although more common in MSI-H synchronous patients (50% metachronous vs. 83% synchronous, P = 0.03). Overall, MLH1 promoter hypermethylation was seen in 7 of 17 (41%) metachronous and 44 of 54 (81%) synchronous MSI-H CRCs tested (P = 0.004). Although MSI occurred with equal frequency among patients with synchronous and metachronous CRCs, the underlying mechanism for MSI was different. Observed differences in MLH1 promoter hypermethylation and patient characteristics suggest most MSI-H synchronous CRCs in our population were sporadic in origin. In contrast, more MSI-H metachronous CRCs were associated with patient and tumor characteristics suggestive of underlying hereditary nonpolyposis CRC. Presented as a poster at Digestive Disease Week 2001, Atlanta, Georgia, May 20–23, 2001.     

多重荧光PCR方法对结直肠癌进行微卫星不稳定检测及其临床价值

目的探讨多重荧光PCR方法检测结直肠癌微卫星不稳定（MSI）及其临床意义。方法将2004-2005年间进行手术治疗的110例结直肠癌患者建立队列，以多重荧光PCR方法检测结直肠癌MSI，并对MSI和微卫星稳定（MSS）结直肠癌患者的临床病理特点进行比较。结果多重荧光PCR方法扩增出所有患者的5个微卫星序列。其中MSI．H10例（8．1％），MSI-L13例（11．8％），MSS为87例（79．1％）。共检测BAT．26变异9例（8．2％）、BAT．25变异11例（10．0％）、D2S123变异11例（10．0％）、D5S346变异6例（5．5％）和D17S250变异8例（7．3％）。MSI-L、MSI．H和MSS组结直肠癌患者年龄比较，差异有统计学意义（P〈0．05）；其他临床病理特点差异无统计学意义（P〉0．05）。结论多重荧光PCR方法检测MSI结果稳定，宜于临床应用；MSI和MSS结直肠癌患者临床病理特点比较未见差异。