结直肠癌肺转移患者的临床回顾性分析

目的 了解结直肠癌肺转移患者的生存时间(OS)和结直肠癌根治术后发生肺转移的时间间隔并寻找相关影响因素.方法 对206例结直肠癌肺转移患者的各项临床参数、治疗方法、无转移间隔时间(DFI)和OS进行分析.结果 结直肠癌肺转移患者6个月、1年、2年、3年和5年的累积生存率分别为79%、46%、25%、20%和18%,中位OS为16个月.有或无特异性肺部及相关症状、性别、年龄、伴或不伴肝转移、肺转移灶单发或多发、是否存在纵隔和(或)肺门淋巴结转移均与OS无关(P值均＞0.05).单因素分析发现结直肠癌原发部位(P=0.020)、脉管浸润(P=0.022)和T分期(P=0.009)是影响肺转移患者中位OS的因素,但多因素分析未发现独立预后因子.接受肺转移灶切除术者相比单纯化学治疗者中位OS更长(分别为34和16个月),但因例数较少,差异尚无统计学意义(P=0.125).160例接受结直肠癌根治术者中,术后第1年和第2年各有48例患者出现肺转移,中位DFI为20个月.DFI与结直肠癌原发部位、形态类型、分化程度、T分期和N分期相关(P值均＜0.05),其中T分期是DFI的独立预测因子(P=0.023).结论 结直肠癌肺转移多发生在结直肠癌根治术后2年内,DFI、临床特征、病理特征和分期均不是独立的生存预后指标,但T分期是影响DFI的独立预测因子.     

A Prospective Study of Prognostic Value of Type IV Collagenase Activity in Colorectal Cancer Tissue

The purpose of this prospective study was toevaluate the prognostic value of the type IV collagenase(IVase) activity in colorectal cancer tissue ondisease-free and overall survival in 31 colorectalcancer patients. The clinicopathologic factors studiedfor prognostic value were age, tumor location, tumordifferentiation, preoperative serum levels ofcarcinoembryonic antigen, Dukes' stage, and IVaseactivity in colorectal cancer tissue. IVase activitiesin colorectal cancer tissue were significantly higher inthe group of patients with recurrences than in the groupwithout recurrences (P = 0.019). Patients with high IVase activity in colorectal cancer tissuehad a significantly shorter disease-free survival (P =0.0016) and overall survival (P = 0.022) time than thosewith low IVase activity. Univariate and multivariate analysis showed that significant prognosticfactors for disease-free survival were Dukes' stage (P= 0.029, P = 0.046, respectively) and IVase activitystatus (P = 0.0016, P = 0.0026, respectively). Withrespect to overall survival, only IVase activity statusprovided significant predictive value in multivariateanalysis (P = 0.041). This prospective study suggeststhat IVase activity is a valuable prognostic factor in colorectal cancer patients.     

Primary small intestinal malignant tumors: survival analysis of 48 postoperative patients

BACKGROUND: Primary small intestinal malignant tumor is relatively uncommon compared to gastric and colorectal cancer. It is difficult to make an early diagnosis due to the atypical primary symptoms and lack of effective diagnostic methods. GOALS: To analyze the relationship between the prognoses, histologic type, and therapeutic strategy in postoperative patients with small intestinal tumor. STUDY: The parameters that affect survival were evaluated using multivariate Cox analysis in 48 cases of small intestinal tumor (confirmed by operation and pathology) for the past 10 years. RESULTS: The overall survival (OS) of all 48 cases after surgery was 28 months. The 5-year postoperative survival rate for all of the 48 cases was 27.1%. The median OS for all the 20 stage II/III patients who received adjuvant chemotherapy was 28 months, whereas the median OS for the 15 patients who did not receive the therapy was 37 months (P=0.276). The median time to progression for 8 patients with adenocarcinoma who received 5-fluorouracil or platinum-based palliative chemotherapy was 7 months, whereas for the patients who did not receive the therapy it was 3 months (P=0.06). The result of multivariate analyses showed that only the clinical stage was significantly correlated with OS (P<0.001). CONCLUSIONS: The prognosis for small intestinal malignancies is associated with clinical stage, and palliative chemotherapy with a 5-fluorouracil or platinum-based regimen offers a potential benefit to patients with adenocarcinoma. Postoperative adjuvant chemotherapy seems to hold no therapeutic or survival benefit for patients with primary small bowel malignancies.     

Survival in patients with large-bowel cancer

Five-year survival data were obtained in 97 percent or 1105 of 1140 new patients with histologically confirmed colorectal adenocarcinoma during a 12-month period in 1981 and 1982, as part of a large comprehensive population-based study of colorectal cancer incidence, etiology, and survival, The Melbourne Colorectal Cancer Study. Fifteen percent of patients were Dukes' A stage, 32 percent were Dukes' B, 25 percent were Dukes' C, and 29 percent were Dukes' D. At five years after diagnosis, the observed survival rate was 36 percent and the adjusted rate was 42 percent. Dukes' staging was a highly discriminating factor in survival (P less than 0.001). Survival rates were better in women than in men and better for patients with colon cancer than for patients with rectal cancer. Survival by Dukes' staging was not affected by colon subsite or by the tumor being the first and single tumor, metachronous tumor, or synchronous tumor. The survival of younger patients was better for Dukes' stages A, B, and C, and worse for Dukes' D. Survival was worse in the presence of bowel perforation in Dukes' C and D stages. Within Dukes' D (incurable cases), survival was best in the absence of hepatic metastases, slightly worse when only hepatic metastases were present, and poorest in the presence of both hepatic and extrahepatic metastases. Statistical modeling of survival determinants other than staging indicated that cell differentiation had the largest effect (survival decreasing with poor cell differentiation), followed by site (survival worse for rectal cancer than colon cancer), then age (survival better for younger patients), while bowel perforation had the smallest effect on survival.     

Prognostic relevance of Fas (APO-1/CD95) ligand in human colorectal cancer

OBJECTIVE: Fas ligand (FasL) is an important mediator of immune function and induces apoptosis by binding to its receptor Fas on sensitized cells. It has recently been shown that malignancies may express FasL and acquire immune privilege by inducing apoptosis of lymphocytes. Acquired resistance to Fas mediated apoptosis is known to be an early event in carcinogenesis. The aim of this study was to determine the extent of FasL expression in patients with colorectal cancer and examine its relationship with several prognostic pathological features and survival. DESIGN AND METHODS: Sixty-eight patients (median age 66 years) with colorectal cancer, whose diagnosis was made between 1988 and 1991 and in whom long-term follow-up was available, were evaluated. The tumours were of varying stages at diagnosis (eight Dukes' A, 28 Dukes' B, 23 Dukes' C and nine Dukes' D). The expression of FasL was detected immunohistochemically with a rabbit polyclonal IgG using the DAKO EnVision+ System. The specificity of FasL binding was confirmed by pre-incubation of the antibody with the immunizing peptide prior to staining. The relationship with several pathological features was determined using Kendall's tau-b correlation. Overall survival was estimated using the Kaplan-Meier product limit curves. Differences in observed survival were tested for statistical significance using the Mantel-Haenszel log rank test. Both the extent and intensity of staining were graded by a blinded observer. RESULTS: FasL was predominantly expressed in tumour epithelial cells in 88% of the cases. The positive staining of tumours varied in extent. FasL staining was higher in earlier Dukes' stage tumours in that the extent of FasL staining negatively correlated with Dukes' stage (Kendall tau-b = -0.22, P = 0.038). Consistent with this, the overall survival was better with a greater extent of FasL expression (log rank chi2 = 5.68, P = 0.017). There was a lower extent of FasL expression in mucinous adenocarcinomas (Kendall tau-b = 0.288, P = 0.01) and in those tumours with neural invasion (Kendall tau-b = -0.26, P = 0.03). No relationship was detected between FasL and tumour site, size, margin, differentiation, vascular invasion, necrosis or Crohn's-like reaction. CONCLUSIONS: FasL is widely expressed in colorectal cancers. This finding suggests that the extent of FasL expression in colorectal tumours is directly related to patients' survival.     

Factors predictive of survival in patients with node-positive colorectal cancer in Taiwan

BACKGROUND/AIMS: Preoperative CEA levels, depth of tumor penetration, and the number of positive lymph nodes were reported as independent factors prognostic of survival in colorectal cancer patients. This study was carried out in an effort to evaluate the prognostic significance of these three factors in patients with Dukes' C colorectal cancer in Taiwan. METHODOLOGY: Between 1992 and 1994, a total of 112 patients with node-positive colorectal cancer were evaluated retrospectively at the Veteran General Hospital-Taipei. All patients underwent potentially curative surgery and received 5-fluorouracil based adjuvant chemotherapy. Reference to the Dukes' classification was according to the classical criteria described in 1932 for carcinoma of the rectum and adapted for use in colonic tumors. Data on the location of the tumor, depth of penetration, number of positive lymph nodes, degree of tumor differentiation, and preoperative CEA levels were analyzed to understand their association with survival. Blood samples for CEA measurement were taken a few days before operation. A multivariate analysis using the Cox's proportional hazards regression model was then performed to determine the most important independent predictors of survival among all the possible variables. RESULTS: Using univariate analysis the number of positive lymph nodes (P < 0.001), penetration of the bowel wall (P < 0.001), and preoperative CEA levels (P < 0.001) were found as significant prognostic factors, while the degree of tumor differentiation, location of the tumor, age and sex were not significant. Using multivariate Cox analysis the number of positive lymph nodes, penetration of the bowel wall, and preoperative CEA levels were still found as independent prognostic factors in node-positive colorectal cancer patients. CONCLUSIONS: Data obtained from our study indicates that preoperative CEA levels, depth of tumor penetration, and the number of positive lymph nodes were independent prognostic factors in Dukes' C colorectal cancer patients. They could serve as appropriate modifications of the initial Dukes scheme in node-positive diseases.     

老年与青年晚期非小细胞肺癌患者的临床特点及预后分析

目的 回顾性分析老年及青年晚期非小细胞肺癌(NSCLC)患者的临床特点、治疗及预后因素的异同.方法 收集北京大学临床肿瘤学院胸部肿瘤内科1995年3月至2007年5月住院的晚期NSCLC 399例,其中老年(≥70岁)256例,男199例,女57例;青年(≤45岁)143例,男77例,女66例,均接受一线化疗.采用Kaplan-Meier及Cox回归法分析生存期及其影响因素,疗效相关性分析采用χ~2检验.结果 (1)青年组及老年组均以男性、腺癌、Ⅳ期患者居多,但青年组与老年组相比,女性[46.2%(66/143),22.3%(57/256)]、腺癌[71.3%(102/143),54.7%(105/256)]、Ⅳ期患者[72.7%(104/143),61.7%(158/256)]所占比例高;青年女性吸烟率高达95.5%(63/66);(2)一线治疗的疾病控制率与年龄无关;含铂联合化疗有利于疾病的控制,符合世界卫生组织毒性分级标准3-4度血液学毒性的病例数两组无差异;(3)老年组中位无进展生存期(PFS)为149 d(95%CI为119.5～178.5 d),青年组中位PFS为126 d(95%CI为84.0～168.0 d),两组比较差异无统计学意义;(4)老年组中位生存期为398 d(95%CI为330.3～465.7 d),青年组中位生存期为424 d(95%CI为359.7～488.3 d);(5)东方肿瘤合作组评分为0～1、一线治疗达到疾病控制、以三代新药或靶向治疗为二线治疗者等因素是有利于生存的独立预后因素.结论 青年组中,女性、腺癌、Ⅳ期患者所占比例较老年组高;青年女性NSCLC发生率的增加可能与吸烟有一定关系;年龄与一线治疗的疾病控制率、PFS及总生存期均无相关性.     

Colorectal cancer in patients younger than 40 years of age

To assess prognostic factors in patients who develop colorectal cancer before the age of 40 years, a 30-year experience from 1956 through 1985 was reviewed. There were 50 patients ranging in age from 7 to 39 years. Five cases were associated with either ulcerative colitis (2) or familial polyposis (3). The most common presenting symptoms were abdominal pain (66 percent), hermatochezia (60 percent), change in bowel habit (41 percent) and weight loss (30 percent). On pathologic staging (N=44), only 14 of 44 (31 percent) had a Dukes' stage A on B lesion, 20 (45 percent) had Dukes' stage C, and the remaining 10 (23 percent) had distant metastases at the time of surgery. Fiveyear survival rate was 28 percent with a disease-free survival rate of 18 percent. Median survival was only 28 months. Negative prognostic tactors were Dukes' stage C/D (P<0.01), symptom duration of longer than 3 months (P=01), noncaucasian ancestry (P=0.1), and poorly differentiated histology (P=06). In contrast to older patients with colorectal cancer, only 1 of 30 (3 percent) patients with stage C/D disease was disease-free at 5 years. In view of the poor survival rate associated with both delay in diagnosis and the presence of advanced disease, it was concluded that young patients presenting with the symptoms listed above need early, aggressive evabuation for possible colorectal cancer     

Effect of mucin production on survival in colorectal cancer： A case-control study

AIM： TO investigate the impact of mucin production on prognosis in colorectal cancer, in terms of overall survival （OS） and time to disease progression （TTP） in patients with mucinous compared to those with nonmucinous colorectal cancer （NMCRC）, matched for age, gender, and tumor stage. METHODS： Thirty five patients with mucinous colorectal cancer （MCRC） were matched for age, gender, and tumor stage with 35 controls having NMCRC. OS and TTP were compared among 4 groups divided according to mucin content： group A （50%-75% mucin）, group B （75%-100% mucin）, group C or controls （〈 50% mucin）. Group D consisted of all patients with tumors having 〈 75% mucin （controls and groups A together）. RESULTS： Median survival in MCRC and NMCRC groups was 46.2 and 112.9 mo, respectively （P = 0.26）. OS in groups A and B was 70.1 and 32.8 mo （P = 0.46）, and in groups B and D was 32.8 and 70.1 mo, respectively （P = 0.143）. TTP in MCRC and NMCRC was 50.17 and 44.77 too, respectively （P = 0.795）. TTP in groups A, B, and D was 70.1, 24.8, and 65.5 too, respectively. Twenty-eight percent of patients with MCRC had poorly differentiated adenocarcinoma versus 8.6% in NMCRC patients （P = 0.028）. CONCLUSION： MCRC is associated with a non-significant decrease in median survival and TTP, particularly when mucin content is 〉 75% of tumor volume. However, it tends to be more poorly differentiated. A larger study matching for stage and grade is needed.     

Prognostic value of pretreatment contrast-enhanced computed tomography in esophageal neuroendocrine carcinoma: A multicenter follow-up study

BACKGROUND The rare incidence of esophageal neuroendocrine carcinoma(NEC) and limited treatment experience result in insufficient clinical observations and unsuitable guidelines for its management.AIM To investigate the prognostic value of pretreatment contrast-enhanced computed tomography(CT) characteristics in patients with esophageal NEC.METHODS Seventy-seven esophageal NEC patients who received contrast-enhanced CT at two hospitals were enrolled in this study from June 2014 to December 2019. The clinical features and image characteristics were recorded accordingly. Univariate survival analysis was performed using the Kaplan-Meier method and log-rank test, and multivariate analysis was carried out with a Cox proportional hazards model.RESULTS The multivariate analysis performed using the Cox proportional hazards model showed that N stage, adjuvant chemotherapy, and degree of enhancement were independent prognostic factors for overall survival(OS). Meanwhile, adjuvant chemotherapy was an independent prognostic factor for progression-free survival (PFS). The hazard ratios(HRs) of N stage, adjuvant chemotherapy, and degree of enhancement(mild vs moderate/marked) for OS were 0.426(P = 0.024), 3.862(P = 0.006), and 2.169/0.809(P = 0.037), respectively. The HR of adjuvant chemotherapy for PFS was 6.432(P 0.001). Adjuvant chemotherapy was significantly associated with degree of enhancement(P = 0.018).CONCLUSION Adjuvant chemotherapy is an independent prognostic factor for OS and PFS. Additionally, N stage and degree of enhancement are prognostic factors for OS in patients with esophageal NEC.     

The novel combination of fat clearance and immunohistochemistry improves prediction of the outcome of patients with colorectal carcinomas: a preliminary study

To evaluate the significance of micrometastases in relation to survival rate, specimens from 48 colorectal carcinoma patients were analysed after fat clearance. The number and size of the lymph nodes harbouring metastases and the significance of micrometastases for patients' survival were assessed. We found that although the majority of metastatic lymph nodes (71.8%) were 5 mm or less in diameter, their size had no effect on survival. Immunohistochemical staining of lymph nodes revealed that 15 of 25 patients with Dukes' stage B diagnosed by routine staining had micrometastases, 86% of these lymph nodes being less than 5 mm in diameter. The survival rate of this subgroup was found to be considerably poorer than that of Dukes' stage B patients with no micrometastases. None of the three patients with Dukes' stage A carcinoma had micrometastases. Since most of the metastases and micrometastases occur in lymph nodes of 5 mm and less and can be easily missed by routine examination, we suggest that fat clearance and routine immunohistochemical analysis of Dukes' stage B improve the prediction of outcome of colorectal cancer patients. Accepted: 10 February 1998     

Colorectal carcinoma in patients less than 40 years of age

The mean incidence of colorectal carcinoma in persons under age 40 in Sweden is 1.74/100,000/year. Over a 30-year period, 1950 through 1979, 1061 patients with colorectal carcinoma were seen, 48 of whom were under age 40 (21 to 39 years) and in this study were compared with older patients. Carcinoma was superimposed upon ulcerative colitis in 18 patients. All patients treated for palliation died within two years. Curability rate, 67 per cent, and the proportion of Dukes' A lesions were the same as in older patients, whereas young patients had fewer B and more C lesions. Five-year survival was 33 per cent overall and 50 per cent in curable cases, not different from the rates in older patients (33 and 47 per cent). Five-year survival was 100 per cent in stage A, 50 per cent in stage B, and 33 per cent in stage C. The age factor had no impact upon survival, and colitic origin of a carcinoma did not decrease survival more than did carcinoma itself. It is concluded that colorectal carcinoma in patients under age 40 differs in no respect from the disease in older patients.     

Prognostic significance of recurrent chromosomal aberrations detected by comparative genomic hybridization in sporadic colorectal cancer

Colorectal carcinomas are characterized by frequent recurrent gains and losses of chromosomal material, especially gains of chromosome arms 20q and 13q, and losses of chromosome arms 18q and 4q. These may be important in the development and progression of colorectal carcinomas. Chromosomal aberrations detected by comparative genomic hybridization in 67 sporadic colorectal carcinomas were examined for their possible associations with patient survival. Dukes' stage, tumor DNA ploidy status, and TP53 genotype/phenotype were also examined for the same. Patients with losses of chromosomal arms 1p, 4q, 8p, 14q, or 18q or gain of chromosomal arm 20q had significantly shorter survival times than those without these aberrations (univariate relative risk 3.45, 2.71, 3.32, 3.26, 3.32, 3.91, respectively), as did patients with more than six chromosomal aberrations per tumor than those with fewer than six aberrations (univariate relative risk 3.26, P = 0.013). DNA aneuploidy and Dukes' stage C + D resulted in poor patient survival (univariate relative risk 3.58, 3.39, respectively). Dukes' stage C + D, 1p loss and 8p loss emerged as the only independent prognostic parameters (relative risk 3.22, 2.53, 2.45, respectively) when entered into multivariate survival analysis together with other significant parameters from univariate survival analysis. Loss of chromosome arm 1p, 4q, 8p, 14q, or 18q or gain of chromosome arm 20q thus results in shortened survival times in colorectal cancer patients. 1p loss and 8p loss were shown to be independent predictors of poor prognosis.     

Definite intensity-modulated radiotherapy with concurrent chemotherapy more than 4 cycles improved survival for patients with locally-advanced or inoperable esophageal squamous cell carcinoma

We investigated which prognostic factor could improve survival for esophageal cancer patients who received definite concurrent chemoradiation (CCRT). Eighty patients with age ≥18, Karnofsky Performance Scale (KPS) ≥ 60, and clinical stage T1-4N0-3M0 esophageal squamous cell carcinoma were enrolled from July 2004 to December 2015. They underwent definite intensity-modulated radiotherapy (IMRT) with or without simultaneous integrated boost to the primary tumor, and reception of concurrent chemotherapy ≥ 1 cycle. The primary endpoints were overall survival (OS), locoregional progression-free survival (LRPFS) and distant metastasis-free survival (DMFS). The median follow-up duration for alive patients was 21.5 months. The rates of 2-, 3- and 5-year OS/LRPFS/DMFS were 23.8%/53.5%/49.3%, 19.1%/44.6%/49.3%, and 13.0%/44.6%/43.9%, respectively. Only the non-clinical complete response (non-cCR) after CCRT was an independent poor prognostic factor in OS (HR 3.101, 95% CI 1.535–6.265, p = 0.0016). Radiation dose >50.4 Gy and chemotherapy ≥4 cycles significantly predicted better LRPFS (p = 0.0361 and 0.0163, respectively). Poorly differentiated tumor and stage III disease have poor DMFS (p = 0.0336 and 0.0411, respectively), and chemotherapy ≥ 4 cycles was a better predictor (p = 0.0004). In subgroup analysis, patients who received radiation dose ≤50.4 Gy with concurrent chemotherapy ≥4 cycles had the best survival outcome with 1-, 2-, 3- and 5-year survival rates of 73.7%, 39.4%, 31.5% and 17.5%, respectively. In conclusion, definite radiotherapy with concurrent chemotherapy ≥4 cycles improved the survival for patients with inoperable or locally-advanced esophageal squamous cell carcinoma.     

Gene-expression profiling predicts recurrence in Dukes' C colorectal cancer

BACKGROUND & AIMS: Although approximately 50% of Dukes' C colorectal cancer patients are surgically cured, it is currently not possible to distinguish these patients from those at high risk of recurrence. The recent advent of routine adjuvant chemotherapy for these patients has greatly complicated the identification of new markers predicting the response to surgery, which is now reliant on archived materials. Microarray analysis allows fine tumor classification but cannot be used with paraffin-embedded archival samples. METHODS: We used microarray analysis of a unique set of fresh-frozen tumor samples from Dukes' C patients who had surgery as the only form of treatment to identify molecular signatures that characterize tumors from patients with good and bad prognosis. RESULTS: Unsupervised hierarchical clustering and a K-nearest neighbors-based classifier identified groups of patients with significantly different survival (P = .019 and P = .0001). Expression profiling outperformed previously reported genetic markers of prognosis such as TP53 and K-RAS mutational status and allelic imbalance in chromosome 18q, which were of limited prognostic power in this study. Functional categories significantly enriched in gene-expression differences included protein transport and folding. The prognostic potential of the RAS homologue RHOA, one of the most differentially expressed genes, was further investigated using immunohistochemistry and a tissue microarray containing 137 independent Dukes' C tumor samples. Reduced RHOA expression was associated with significantly shorter survival (P = .01). CONCLUSIONS: This study shows that gene-expression profiling of surgical tumor samples can predict recurrence in Dukes' C patients. Therefore, this approach could be used to guide decisions concerning the clinical management of these patients.     

Allelic loss of chromosome 2p21-16.3 is associated with reduced survival in sporadic colorectal cancer

BACKGROUND: Since allelic loss of genes involved in the development of colorectal cancer could serve as prognostic markers, we examined the correlation between loss of markers linked to the hMSH2/hMSH6 (2p21-16.3), hMLH1 (3p21.3), APC (5q21-22), p53 (17p13.1) and DCC (18q21.3) loci and survival in a series of 64 consecutively collected colorectal cancers. METHODS: The association between allelic loss and survival was analysed by univariate and multivariate tests to identify independent variables of survival. RESULTS: Loss of chromosome 2p21-16.3 reduced the overall 5-year survival from 52% to 15% (P = 0.0003). The prognostic significance was evident in patients with Dukes' A + B as well as Dukes' C tumours. A multivariate analysis comparing Dukes' staging, age at diagnosis, tumour localization, sex, loss of chromosome 2p21-16.3, 3p21.3, 5q21-22, 17p13.1 or 18q21.3 and microsatellite instability showed that only Dukes' staging (hazard ratio 3.0; 1.4-6.5 with 95% confidence interval, P = 0.0065) and loss of 2p21-16.3 (hazard ratio 6.2; 2.3-16.8 with 95% confidence interval, P = 0.0006) were independent variables of survival. Loss of 2p21-16.3 was, moreover, associated with increased loss of the other tumour suppressor loci (P = 0.012). CONCLUSIONS: The results show that loss of 2p21-16.3 is an independent indicator of survival in patients with colorectal cancer.     

Correlation of N-myc downstream-regulated gene 1 expression with clinical outcomes of colorectal cancer patients of different race/ethnicity

AIM: To evaluate the role of N-myc downstream-regulated gene 1 (NDRG1) expression in prognosis and survival of colorectal cancer patients with different ethnic backgrounds. METHODS: Because NDRG1 is a downstream target of p53 and hypoxia inducible factor-1α (HIF-1α),we examined NDRG1 expression together with p53 and HIF-1α by immunohistochemistry. A total of 157 colorectal cancer specimens including 80 from Japanese patients and 77 from US patients were examined. The correlation between protein expression with clinicopathological features and survival after surgery was analyzed.in colorectal tumor compared with normal epithelium in both Japanese and US patient groups. Expression of NDRG1 protein was significantly correlated with lymphatic invasion,venous invasion,depth of invasion,histopathological type,and Dukes' stage in Japanese colorectal cancer patients. NDRG1 expression was correlated to histopathological type,Dukes' stage and HIF-1α expression in US-Caucasian patients but not in US-African American patients. Interestingly,Kaplan-Meier survival analysis demonstrated that NDRG1 expression correlated significantly with poorer survival in US-African American patients but not in other patient groups. However,in p53-positive US cases,NDRG1 positivity correlated significantly with better survival. In addition,NDRG1 expression also correlated significantly with improved survival in US patients with stages Ⅲ and Ⅳ tumors without chemotherapy. In Japanese patients with stages Ⅱ and Ⅲ tumors,strong NDRG1 staining in p53-positive tumors correlated significantly with improved survival but negatively in patients without chemotherapy. CONCLUSION: NDRG1 expression was correlated with various clinicopathological features and clinical outcomes in colorectal cancer depending on the race/ethnicity of the patients. NDRG1 may serve as a biological basis for the disparity of clinical outcomes of colorectal cancer patients with different ethnic backgrounds.     

Primary refractory Hodgkin's lymphoma: outcome after high-dose chemotherapy and autologous SCT and impact of various prognostic factors on overall and event-free survival. A single institution result of 66 patients

We report our experience with high-dose chemotherapy (HDC) and autologous SCT (ASCT) in 66 patients with primary refractory Hodgkin's lymphoma (PR-HL) who received salvage chemotherapy followed by BEAM as HDC. Median age at ASCT was 23 years. Before salvage chemotherapy, stages I:II:III:IV were 2:21:14:29, bulky disease 27%, involvement of mediastinum 79%, spleen 26% and extranodal site 47%, 92% had ESHAP as salvage. Post-ASCT evaluation showed response in 50 patients (76%); complete response (CR) 37 (56%), partial response 14 (21%), no response or stable disease 3 (5%) and progressive disease in 10 (15%). Another five patients achieved CR after radiation therapy and one after surgery, making total CR 43 (65%). From diagnosis and HDC, median follow-up is 38.5 and 22.8 months and median overall survival (OS) 78 and 57 months, respectively. Event-free survival (EFS) and OS are 36 and 64%, respectively. In all, 47% patients are in CR. Twenty-two patients (33%) died due to disease. Multivariate analysis showed elevated lactate dehydrogenase (LDH) for EFS (P=0.041) and mediastinal involvement for OS (P=0.038) as negative prognostic factors. In conclusion, EFS and OS are only 36 and 64%, respectively. Elevated LDH and mediastinal involvement are poor prognostic factors.     

Clinicopathologic characteristics of colorectal neuroendocrine tumor]

BACKGROUND/AIMS: Colorectal neuroendocrine carcinoma is a rare neoplasm exhibiting fulminant progression and having poor prognosis. The purpose of this study is to verify the clinicopathologic characteristics of colorectal neuroendocrine carcinoma. METHODS: From June 1997 to December 2004 at Asan Medical Center, ten patients were originally identified as colorectal neuroendocrine carcinoma on the basis of H&E and immunohistochemical staining (IHC). Carcinoid tumors were excluded in this study. Medical records of thirteen patients were reviewed retrospectively. RESULTS: Ten patients (0.2%) with colorectal neuroendocrine tumors were identified from 4,512 patients with colorectal cancer; ten neuroendocrine carcinomas and three adenocarcinomas with neuroendocrine differentiation. Their median age was 60 (41-83) years. The subjects consisted of six males and seven females. Nine tumors were located in the rectum, two in the sigmoid, and each one in the transverse colon and cecum, respectively. Nine of ten neuroendocrine carcinomas expressed synaptophysin, but chromogranin A were expressed in four. All patients were advanced at the time of diagnosis, with AJCC TNM staging: stage IIIB (n=2), stage IIIC (n=3), and stage IV (n=8). The median survival for ten neuroendocrine carcinomas and three adenocarcinomas with neuroendocrine differentiation were 16.4 months and 30 months, respectively. Five patients who received chemotherapy showed median survival of 32 months (stage III) and 17.5 months (stage IV), whereas other five patients without chemotherapy died with a median survival of 6.2 months. CONCLUSIONS: Colorectal neuroendocrine tumors are extremely rare showing aggressive behavior biologically, i.e fulminant early distant metastasis. Nevertheless, improved survival may be achieved by aggressive multimodality therapy.     

Circular tumor growth: a prognostic factor in stage II colorectal carcinoma

BACKGROUND/AIMS: Almost all patients with stage II colorectal cancer are spared adjuvant chemotherapy, yet a considerable number of these patients die from the disease. The aim of this retrospective study was to identify factors negatively affecting survival of patients with stage II colorectal cancer treated by curative resection. METHODOLOGY: Study subjects were 88 patients who had undergone curative resection for stage II colorectal cancers at Miyazaki University Hospital during the period from 1987-1999. Patients were followed up for a minimum of 5 years or until death. The influence of clinical and pathologic variables on 5-year cancer-specific survival was assessed by uni variate and multivariate analyses. RESULTS: The 5-year cancer-specific survival rate was 83.4%. Univariate analysis showed circular tumor growth to be significantly associated with decreased survival (p=0.0047). Furthermore, multivariate analysis showed that circular tumor growth significantly affected long-term cancer-specific survival of patients with stage II colorectal cancer (hazard ratio 1.184, p=0.025). CONCLUSIONS: Circular tumor growth is an independent prognostic factor for patients with stage II colorectal cancer. The long-term prognosis of stage II colorectal cancer patients with circular-type carcinoma appear to be poor.