Insulin-like growth factor-I gene polymorphism and breast cancer risk in Chinese women

The evidence that high circulating levels of insulin-like growth factor-I (IGF-I) are associated with an increased risk of breast cancer among premenopausal women lends credence to the hypothesis that genetic polymorphisms in the IGF-I gene may be involved in the disease. A population-based case-control study was conducted to assess the association of IGF-I gene polymorphisms [(CA)n repeats in the promoter region] with breast cancer risk and plasma IGF-I level in Chinese women. The study included 1,041 incident breast cancer cases diagnosed from August 1996 through March 1998 in Shanghai and 1,086 randomly selected, age frequency-matched controls from the general population. Although no relation between plasma IGF-I levels and IGF-I genotypes was found, women who carried the genotypes containing the (CA)17 or (CA)19 allele were associated with a significantly decreased (OR = 0.80, 95% CI: 0.64-1.00) or increased (OR = 1.23, 95% CI: 1.04-1.47) risk of breast cancer, respectively, and women who carried the genotypes containing any of the 4 rare alleles, (CA)11, (CA)13, (CA)16 and (CA)23, were associated with a nonsignificantly increased risk of breast cancer (OR = 1.92, 95% CI: 0.92-4.02) compared to those who did not carry the specific alleles. The associations with the (CA)17 or (CA)19 allele were predominantly present among premenopausal women and in a dose-response manner. The meta-analysis results indicated that IGF-I genotypes containing the (CA)19 were consistently associated with increased risk of breast cancer across studies (overall OR = 1.22, 95% CI: 1.06-1.41, p for heterogeneity test = 0.524). The findings of this study support the hypothesis that IGF-I gene polymorphisms may be a significant genetic factor for breast cancer susceptibility.     

Five Strategies for Accelerating the War on Cancer in an Era of Budget Deficits

In recent years, the National Institutes of Health's largest institute, the National Cancer Institute (NCI), has adapted to difficult economic conditions by leveraging its robust infrastructure—which includes risk factor surveillance and population monitoring, research centers (focused on basic, translation, clinical, and behavioral sciences), clinical trials and health care research networks, and rigorously validated statistical models—to maximize the impact of scientific progress on the public health. To continue advancement and realize the opportunity of significant, population‐level changes in cancer mortality, the NCI recommends that five national‐level actions be taken: (1) significantly increase enrollment of Medicare patients into cancer clinical trials through adequate physician reimbursement, (2) increase NCI/Centers for Medicare and Medicaid Services collaboration on clinical trials research to evaluate the therapeutic efficacy of anticancer drugs, (3) establish a national outcomes research demonstration project to test strategies for measuring and improving health care quality and provide an evidence base for public policy, (4) leverage existing tobacco‐control collaborations and possible new authorities at the U.S. Food and Drug Administration to realize the outstanding health gains possible from a reduction in tobacco use, and (5) increase colorectal cancer screening rates though intensified collaboration between federal agencies working to address barriers to access and use of screening. These cost‐effective strategies provide the opportunity for extraordinary results in an era of budget deficits. Of the chronic diseases, cancer has the strongest national research infrastructure that can be leveraged to produce rapid results to inform budget prioritization and public policy, as well as mobilize new projects to answer critical public health questions.     

Assessment of Statistical Methodologies and Pitfalls of Dissertations Carried Out at National Cancer Institute,Cairo University

Purpose: To identify statistical errors and pitfalls in dissertations performed as part of the requirements for the Medical Doctorate (MD) degree at the National Cancer Institute (NCI), Cairo University (CU) to improve the quality of medical research. Methods: A critical assessment of 62 MD dissertations conducted in 3 departments at NCI, CU, between 2009 and 2013 was carried out regarding statistical methodology and presentation of the results. To detect differences in study characteristics over time, grouping was into two periods; 2009-2010 and 2011-2013. Results: Statistical methods were appropriate in only 13 studies (24.5%). The most common statistical tests applied were chi-square, log-rank, and Mann-Whitney tests. Four studies estimated sample size and/or power. Only 37.1% and 38.7% of dissertation results supported aims and answered the research questions, respectively. Most of results were misinterpreted (82.3%) with misuse of statistical terminology (77.4%). Tabular and graphical data display was independently informative in only 36 dissertations (58.1%) with accurate titles and labels in only 17 (27.4%). Statistical tests fulfilled the assumptions only in 29 studies; with evident misuse in 33. Ten dissertations reported non-significance regarding their primary outcome measure; the median power of the test was 35.5% (range: 6-60%). There was no significant change in the characteristics between the time periods. Conclusion: MD dissertations at NCI have many epidemiological and statistical defects that may compromise the external validity of the results. It is recommended to involve a biostatistician from the very start to improve study design, sample size calculation, end points estimation and measures.     

Modification of breast cancer risk in young women by a polymorphic sequence in the egfr gene

The regulation of the epidermal growth factor receptor (egfr) gene in human cancer is not yet fully understood. Recent data on a polymorphic CA repeat located at the 5'-regulatory sequence in intron 1 of the egfr gene [egfr CA simple sequence repeat (SSR) I] point to a possible inheritance of cancer risk associated with the egfr gene. Furthermore, we have detected frequent allelic imbalances restricted to the egfr CA SSR I in breast cancer tissue and nontumorous breast tissue adjacent to invasive and in situ breast cancer representing amplifications. Therefore, we conducted a population-based case-control study to assess the relationship between the egfr polymorphism and breast cancer risk. Cases with a first primary breast cancer by age 50 years and age-matched population controls provided information on known and suspected risk factors. The allelic length of the egfr CA SSR was determined in 616 cases and 1072 population-sampled controls. Genotypes were categorized for analysis by allele length. Multivariate logistic regression was used to compare genotype distributions, accounting for other risk factors, and to investigate gene-environment interactions. We found a modifying effect, albeit no main effect, of the allelic length of the egfr polymorphism on breast cancer risk. The presence of two long alleles (>/==" BORDER="0">19 CA) was associated with a significantly elevated odds ratio (OR) of 10.4 [95% confidence interval (CI), 1.85-58.70] among women with a first-degree family history of breast cancer (P = 0.015 for interaction). The risk increase associated with high red meat consumption (OR, 10.68; 95% CI, 1.57-72.58) and the protective effect of high vegetable intake (OR, 0.07; 95% CI, 0.004-1.07) was also most pronounced among carriers of two long alleles (>/==" BORDER="0">19 CA). The length of the egfr CA SSR may increase the risk for familial breast cancers, and its effect could be modulated by dietary factors.     

胰腺癌术后生存率的影响因素

目的:探讨影响胰腺癌术后生存率的影响因素.方法:回顾性分析2010年1月至2012年12月本院178例行胰十二指肠切除术治疗的胰腺癌患者(研究组)以及81例同期健康体检者(对照组)的临床资料,分析术后生存率的影响因素.单因素分析采用Logistic二元回归模型,筛选有统计学意义的指标纳入COX风险回归模型进行多因素分析.结果:Kaplan-Meier结果显示,178例患者术后1年、2年、3年总体生存率分别为56.2%、18.0%、1.7%.单因素分析结果表明,性别、年龄、肿瘤位置与术后生存率无相关性(P>0.05);而肿瘤大小、肿瘤分化程度、临床分期、淋巴结转移、肝转移、血清sPLA2-ⅡA、CD44v6、整合素β1和CA19-9水平与术后生存率有相关性(P<0.05).COX多因素回归分析显示,临床分期、淋巴结转移、肝转移、血清sPLA2-ⅡA、CD44v6、整合素β1和CA19-9水平对患者术后生存率的影响差异有统计学意义(P<0.05),是影响术后生存率的独立危险因素.患者术前、术后1周血清sPLA2-ⅡA、CD44v6、整合素β1和CA19-9表达水平显著高于对照组(P<0.05),而术后1个月的表达水平与对照组差异均无统计学意义(P>0.05).患者术后血清sPLA2-ⅡA、CD44v6、整合素β1和CA19-9表达水平均逐渐下降,术后1个月的表达水平均显著低于术前(P<0.05).患者术后1个月 sPLA2-ⅡA、CD44v6、CA19-9表达水平显著低于术后1周(P<0.05),整合素β1表达水平和术后1周差异无统计学意义(P>0.05).sPLA2-ⅡA、CD44v6、整合素β1和CA19-9低表达患者的术后生存率均显著高于高表达的患者(P<0.05).结论:在进行胰腺癌治疗时应特别注意临床分期、淋巴结转移、肝转移、血清sPLA2-ⅡA、CD44v6、整合素β1和CA19-9水平等影响预后的独立危险因素,以提高生存率.     

Preoperative Serum Carcinoembryonic Antigen,Carbohydrate Antigen19-9 and Carbohydrate Antigen 125 as Prognostic Factors for Recurrence-free Survival in Colorectal Cancer

Objective: Colorectal cancer (CRC) is among the most common malignancies worldwide. Understanding CRCprognosis at the initial diagnosis is very important for therapeutic strategy selection. This study was conductedto evaluate the prognostic value of preoperative serum carbohydrate antigen 19-9 (CA19-9), carcinoembryonicantigen (CEA) and carbohydrate antigen 125 (CA125) for predicting 5-year recurrence-free survival (RFS) inCRC patients. Methods: Preoperative serum CA19-9, CEA and CA125 levels were detected by C12 proteinchip diagnostic system in 103 patients with CRC, and their correlations with the 5-year RFS were analyzed.Results: Patients with positive preoperative serum CA19-9, CEA and CA125 had higher 5-year recurrent rates(75.0% vs 41.0%, 65.6% vs 39.4%, and 87.5% vs 44.2% respectively, all p<0.05), and reduced median RFS (14vs 35 months, 20 vs 36 months, and 4 vs 35 months respectively, all p<0.05) compared with patients negative forcorresponding tumor marker (TM). The median RFS was 59 months (95% CI 28.9-89.1 months) with negativeTMs, 14 months (95% CI 4.5-23.5) for 1~2 positive TMs, and 4 months (95% CI 2.4-5.6) for all 3 positive TMs.Patients with simultaneously positive serum CA19-9, CEA and CA125 had the highest recurrence rate (100%)and the shortest RFS (median 4 months). Univariate analysis showed that stage and the preoperative singleTM or combined TMs correlated with RFS, whereas multivariate Cox regression model analysis revealed onlystage and preoperative serum status of CEA+CA19-9+CA125 to be independent prognostic factors. Conclusion:Preoperative serum CA19-9+CEA+CA125 can be used an independent prognostic factor for CRC 5-year RFS.     

Ⅲ期Ⅳ期非小细胞肺癌预后影响因素分析

目的　研究Ⅲ、Ⅳ期非小细胞肺癌 (NSCLC)患者的预后相关因素 ,建立具有临床实用性的预后模型。方法　采用Kaplan Meier和Cox回归方法分析 114例NSCLC患者治疗前血清神经元特异性烯醇化酶 (NSE)、癌胚抗原 (CEA)、Cyfra2 1 1、CA12 5、IL 2、sIL 2R等 6种肿瘤标记物的水平及常规临床因素 ,如年龄、性别、吸烟指数、KPS评分、临床分期等与生存率的关系。结果　单因素分析表明 ,临床分期、KPS评分、性别以及治疗前血清Cyfra2 1 1和CA12 5水平与NSCLC患者生存率有关。多因素分析表明 ,Cyfra2 1 1、临床分期及治疗情况是独立的预后影响因素 ,Cyfra2 1 1>3.5mg/L、临床分期为Ⅳ期、治疗少于 3周期时 ,相对危险性 (RR)分别为 1.6 91,2 .2 2 9和 3.0 35。化疗 3周期及以上的患者 ,Cyfra2 1 1、sIL 2R及临床分期是独立的预后影响因素。建立患者治疗前的预后指数 (PI)模型 :PI =Cyfra2 1 1 sIL 2R Stage。化疗 3周期及以上者 ,PI=0时 ,中位生存期 18个月 ;PI=1或 2时为 8个月 ,PI =3时为 5个月。结论　治疗前血清Cyfra2 1 1、sIL 2R和临床分期 ,是Ⅲ、Ⅳ期NSCLC患者独立的预后影响因素。采用患者治疗前血清Cyfra2 1 1、sIL 2R及临床分期建立的预后指数模型有实际应用价值。     

Immunological quantitation of thymidylate synthase using the monoclonal antibody TS 106 in 5-fluorouracil-sensitive and -resistant human cancer cell lines.

Thymidylate synthase (TS) (EC 2.1.1.45) is an important cellular target for the fluoropyrimidine cytotoxic drugs that are widely used in the treatment of solid tumors. Using the TS 106 monoclonal antibody to human TS, we have compared the immunological quantitation of TS by Western immunoblot and immunofluorescent techniques to the conventional biochemical 5-fluorodeoxyuridine monophosphate binding assay in a panel of 5-fluorouracil (5-FU)-sensitive and -resistant human cancer cell lines. Densitometric quantitation of TS 106-labeled Western immunoblot analysis of cell lysates from two 5-FU-resistant colon carcinoma cell lines, NCI H630R1 and NCI H630R10, revealed 12.8- and 16-fold increases in TS, respectively, compared to the parent 5-FU-sensitive NCI H630 colon cell line. By biochemical analysis, the TS level was 15- and 23-fold higher, respectively, in these resistant cell lines. Similarly, immunoblot analysis of cell lysates from two 5-FU-resistant breast cancer cell lines, MCF-Ad5 and MCF-Ad10, detected a 2.3- and 6.3-fold increase in TS, respectively, compared to the parent MCF-7 cell line. By biochemical assay the TS activity was 1.8- and 7.0-fold higher in these resistant breast cell lines. Western immunoblotting analysis revealed a 35-fold range of TS protein concentrations among the 10 cell lines examined, compared to a 38-fold range demonstrated by the biochemical assay. Direct comparison of Western blotting and the biochemical assay revealed a highly significant correlation (r2 = 0.93) between the two assays. Moreover, using the monoclonal antibody TS 106, the Western blotting technique was capable of detecting TS protein levels as low as 0.3 fmol in cellular lysates. Quantitation of TS in intact cells by immunofluorescent TS labeling and flow cytometric analysis was performed using three of the cell lines, NCI H630, NCI H630R10, and MCF-Ad10. This revealed a 26-fold increase in TS in the 5-FU-resistant NCI H630R10 line compared to the parent NCI H630 line and a 3.5-fold increase in TS compared to the 5-FU-resistant MCF-Ad10 breast cell line. The 5-FU-resistant MCF-Ad10 breast cell line, in turn, displayed a 7.7-fold increase in TS, compared to the 5-FU-sensitive NCI H630 cell lines. TS immunofluorescent analysis was capable of measuring TS within individual cells. The development of these immunological assays using an anti-TS monoclonal antibody will facilitate the quantitation of TS in cell lines and tissue samples.     

Prognostic factors for progression of childhood optic pathway glioma: a systematic review

A systematic literature review was carried out to evaluate best existing evidence on prognostic factors for progression of childhood optic pathway glioma. Databases were searched for relevant articles and articles selected independently by two authors. Information about study design, population, treatment, outcome and prognostic analysis were abstracted and the quality of each article was assessed. A total of 23 articles met the inclusion criteria. Many studies had important methodological limitations, regarding external and internal validity. Eleven studies evaluated possible prognostic factors in a multivariate analysis. Three high-quality studies indicated age<1 year as an independent prognostic factor for a worse progression-free survival. Three studies with multivariate analysis, including one high-quality study, found that children with neurofibromatosis type 1 (NF-1) have a better progression-free survival than those without NF-1. Two studies with multivariate analysis found tumour site to be a prognostic factor, both with some methodological limitations. In conclusion, this systematic review demonstrates that only a few of the prognostic factors proposed have been proven to be clinically relevant. Age<1 year is a clear and independent prognostic factor for progression-free survival. Other prognostic factors, such as NF-1, tumour site and others, are suggested, but are still without solid evidence and need further high-quality studies to be clearly proven.     

Elevated CA19-9 as the most significant prognostic factor in advanced colorectal carcinoma.

Tumor markers such as carcinoembryonic antigen (CEA) and CA19-9 were analyzed as response indicators and prognostic factors in advanced colorectal carcinoma. Eighty-five patients participated in a phase II chemotherapy study from October 1984 to July 1990. A three-drug schedule was administered including low dose epirubicin and sequential methotrexate 5-fluorouracil, followed by leucovorin rescue. Serum specimens for CEA and CA19-9 were obtained prior to the initiation of chemotherapy, and subsequently at 4-6 weeks' intervals. In univariate analysis Karnofsky, the site of the primary tumor, the extent of metastases, the presence of abdominal or liver metastases, serum CEA (cut-off of 20 micrograms/l), and CA19-9 levels correlated with survival. In stepwise multivariate analysis an elevated CA19-9 level, a poor Karnofsky, and the presence of liver metastases were independent adverse prognostic factors. Tumors originating from the left colon had a better prognosis than the others. This was related to a higher response rate in this patient group. Serum CA19-9 level was the most significant prognostic factor whether it was entered as a continuous or as a dichotomized variable into the model. The median survival of patients with a normal CA19-9 level was 30.0 months (lower 95% confidence interval: 16.4 months; upper limit was not calculable), and with an elevated CA19-9 value 10.3 months (8.0-12.6 months, 95% confidence interval). Five of 85 patients had a complete response and 20 a partial response, the overall response rate being 29%. When compared with tumor shrinkage, "CEA response" and "CA19-9 response" had a sensitivity of 84% and 88% and specificity of 77% and 67%, respectively. In conclusion, serum CEA value seems to be the best tumor marker for response prediction, while CA19-9 level is one of the best available prognostic indicators in advanced colorectal carcinoma.     

Serum HCG beta and CA 72-4 are stronger prognostic factors than CEA, CA 19-9 and CA 242 in pancreatic cancer

OBJECTIVE: In pancreatic cancer, the extent of the spread of the disease is considered to be the strongest prognostic factor. In addition, tumor markers, particularly CA 19-9, may also provide prognostic information. In this study, we evaluated the prognostic value of serum tumor markers CEA, CA 19-9, CA 242, CA 72-4 and hCG beta in pancreatic cancer. METHODS: Preoperative serum samples were obtained from 160 patients with pancreatic cancer, including 10 with stage I, 25 with stage II, 24 with stage III and 101 patients with stage IV cancer. Quantitation of CEA, CA 19-9, CA 242, and CA 72-4 in serum was performed with commercial assays. HCG beta was measured with an in-house immunofluorometric assay based on monoclonal antibodies specific for the free beta-subunit of hCG. Survival analysis was performed with univariate Kaplan-Meier life-tables and log-rank test, and with multivariate Cox regression analysis. RESULTS: Of the tumor markers studied, CA 19-9 was most frequently elevated. Overall 2-year survival was 10%. Stage, tumor location and size, curative resection, and CEA, CA 72-4 and hCG beta were all found to be prognostic factors (p < 0.026) in univariate analysis. In multivariate analysis, each marker had independent prognostic value (p < 0.011) when analyzed individually but adjusting for stage. When all the covariates were included in the same model, the strongest prognostic factor was hCG beta followed by CA 72-4 and stage. The other clinical characteristics and serum tumor markers contributed insignificant prognostic information. CONCLUSIONS: All the tumor markers studied (CEA, CA 19-9, CA 242, CA 72-4, and hCG beta) had prognostic value in pancreatic cancer, and hCG beta, CA 72-4, and stage were the strongest independent prognostic factors in this study.     

Relationships between Breast Cancer and Common Non-Communicable Disease Risk Factors: an Ecological Study

Background: Breast cancer is one the most common cause of cancer-related deaths among women worldwide.The aims of this study were to investigate the impact of dietary factors and health status indicators on breastcancer (BC) incidence. Materials and Methods: Risk factor data (RFD) of 89,404 individuals (15-64 years old)were gathered by questionnaire and laboratory examinations through a cross sectional study from the Non-Communicable Disease Surveillance Centre (NCDSC) of Iran. BC incidences of all provinces through 2001-2006segregated by age and gender were obtained from the Cancer Registry Ministry of Health (CRMH). Results:a significant positive relationship was seen between diabetes mellitus, fish consumption, percent of academiceducation and non-consumption of fruit, and breast cancer in women. However, non fish consumption, percentage illiteracy and taking fruit showed a significant negative relationship with the incidence of breast cancer. Inaddition, multiple linear regression analysis showed associations among percentage with academic education,fruit consumption and diabetes. Conclusions: We conclude that dietary factors such as fish and fruit consumption,dairy products, health status indicators, academic education, and some diseases like diabetes mellitus can affectthe BC incidence, although the results of ecologic studies like this must naturally be interpreted with caution.     

Serum HCG beta,CA 72-4 and CEA are independent prognostic factors in colorectal cancer

In colorectal cancer, stage is considered to be the strongest prognostic factor, but also serum tumour markers have been reported to be of prognostic value. The aim of our study was to investigate the prognostic value of serum carcinoembryonic antigen (CEA), CA 19-9, CA 242, CA 72-4 and free beta subunit of human chorionic gonadotropin (hCG beta) in colorectal cancer. Preoperative serum samples were obtained from 204 colorectal cancer patients, including 31 patients with Dukes' A, 70 with Dukes' B, 49 with Dukes' C and 54 with Dukes' D cancer. The serum levels of CEA, CA 19-9, CA 242 and CA 72-4 were measured with commercial kits with cut-off values of 5 microg/L for CEA, 37 kU/L for CA 19-9, 20 kU/L for CA 242 and 6 kU/L for CA 72-4. The serum hCG beta was quantitated by an immunofluorometric assay (IFMA) with 2 pmol/L as a cut-off value. Survival analyses were performed with Kaplan-Meier life tables, log-rank test and Cox proportional hazards model. The sensitivity was 44% for CEA, 26% for CA 19-9, 36% for CA 242, 27% for CA 72-4 and 16% for hCG beta. The overall 5-year survival was 55%, and in Dukes' A, B, C and D cancers the survival was 89%, 77%, 52% and 3%, respectively. Elevated serum values of all markers correlated with worse survival (p < 0.001). In Cox multivariate analysis, the strongest prognostic factor was Dukes' stage (p < 0.001), followed by tumour location (p = 0.002) and preoperative serum markers hCG beta (p = 0.002), CA 72-4 (p = 0.003) and CEA (p = 0.005). In conclusion, elevated CEA, CA 19-9, CA 242, CA 72-4 and hCG beta relate to poor outcome in colorectal cancer. In multivariate analysis, independent prognostic significance was observed with hCG beta, CA 72-4 and CEA.     

Delay of adjuvant chemotherapy initiation following breast cancer surgery among elderly women

SummaryBackground Delay in the diagnosis of breast cancer is associated with worse stage distribution at diagnosis and decreased survival. However, the occurrence of delay in the delivery of adjuvant therapy and its impact on prognosis is not well understood.Methods To investigate the timeliness of initiation of adjuvant chemotherapy following surgery for breast cancer, we used data from the Surveillance, Epidemiology, and End-Results (SEER)–Medicare database. Among women ≥ 65 years diagnosed between 1992 and 1999 with stages I–II breast cancer, we used linear regression and Cox proportional hazards models to investigate the time intervals between surgery and initiation of adjuvant chemotherapy, factors associated with delay, and the effect of delay on survival.Results Our sample consisted of 5003 women who received adjuvant chemotherapy. Of these, 47% initiated chemotherapy within 1 month, 37% between 1 and 2 months, 6% between 2 and 3 months and 10% >3 months (delay) following surgery. Delay was associated with increasing age, residing in a rural location, being unmarried, earlier tumor stage, hormone receptor positivity, mastectomy, and non-receipt of radiation therapy. Survival did not differ among patients who initiated chemotherapy within 1, 2, or 3 months after surgery. Delay beyond 3 months was, however, associated with increased disease-specific mortality (HR 1.69; 95% CI 1.31–2.19) and overall mortality (HR 1.46; 95% CI 1.21–1.75).Conclusions Among older patients, moderate delays in the receipt of adjuvant chemotherapy occur frequently, but long delays (>3 months) are uncommon. While early initiation of therapy is no benefit, significant delays are associated with increased mortality. Whether this reflects the medical impact of the delay of chemotherapy or factors associated with delay is unclear, but until this is clarified, patients should be encouraged to initiate treatment without significant delay.Dr Hershman is the recipient of an American Society of Clinical Oncology Career Development Award and a K07 Award from the NCI (CA95597).Dr Neugut is the recipient of a K05 Award from the NCI (CA89155) and a grant from the American Cancer Society (RSGT-01-024-04-CPHPS), and a Department of Defense Breast Cancer Center of Excellence Award (BC043120).Mr McBride is the recipient of a T32 fellowship from NCI (CA09529).This study used the linked SEER–Medicare database. The interpretation and reporting of these data are the sole responsibility of the authors.     

肝内胆管结石合并肝内胆管癌术后生存率的影响因素分析

目的：探讨影响肝内胆管结石合并肝内胆管癌术后生存率的影响因素。方法：回顾性分析2007年8月至2014年7月本院手术治疗的107例肝内胆管结石合并肝内胆管癌患者的临床资料,分析术后生存率的影响因素。单因素分析采用 Logistic 二元回归模型,筛选有统计学意义的指标纳入 COX 风险回归模型进行多因素分析。结果：Kaplan －Meier 结果显示,107例患者术后1、3、5年总体生存率分别为51．4％、28．0％、9．3％;进行 R0、R1、R2等不同手术方式和仅进行肿瘤活检的患者生存时间有显著性差异（P ＜0．005）。单因素分析结果表明,性别、年龄、肿瘤大小、肿瘤组织分型、肿瘤分化程度、TNM分期、肝内转移与术后生存率无相关性（P ＞0．05）;而淋巴结转移、门静脉浸润、手术切缘和血清 CA19－9水平与术后生存率有相关性（P ＜0．05）;COX 风险回归模型进行多因素分析结果显示,手术切缘和血清 CA19－9水平对患者生存时间的影响差异有统计学意义（P ＜0．05）,是影响术后生存率的独立危险因素。结论：根治性手术切除是肝内胆管结石合并肝内胆管癌最有效的治疗方法,治疗时应特别注意手术切缘和血清 CA19－9水平等影响预后的独立危险因素,以提高生存率。     

Pharmacokinetics of irinotecan and its metabolites in pediatric cancer patients: a report from the children’s oncology group

Objective  To develop a population pharmacokinetic model of irinotecan and its major metabolites in children with cancer and to identify covariates that predict variability in disposition. Methods  A population pharmacokinetic model was developed using plasma concentration data from 82 patients participating in a multicenter Pediatric Oncology Group (POG) single agent phase II clinical trial. Patients between 1 and 21 years of age with solid tumors refractory to standard therapy received irinotecan, 50 mg/m², as a 60-min intravenous infusion for 5 consecutive days every 3 weeks. Blood samples were collected and analyzed for irinotecan and three metabolites (SN-38, SN-38G, and APC). The population model was developed with NONMEM. Clearance and volume were scaled allometrically using corrected body weight. Exponential error models were used to describe the interindividual variance in pharmacokinetic parameters, and the residual error was described with a proportional model. Significant covariate effects were identified graphically using S-PLUS and were added to the base-model. The final model was evaluated by simulating data from two other POG trials. Results  The best structural model for irinotecan and its metabolites consisted of six-compartments: two compartments for irinotecan and SN-38, and one each for APC and SN-38G. Age and bilirubin were found to be significant covariates affecting SN-38 clearance. SN-38 clearance was greater in patients less than 10 years of age and lower in patients with a total serum bilirubin >0.6 mg/dL. Simulations revealed that the model was able to predict drug and metabolite exposure (AUC) for patients receiving the same or similar doses (30–65 mg/m²) of irinotecan. Conclusions  This population model accurately describes the pharmacokinetics of irinotecan and its primary metabolites. The model, which includes age and bilirubin as covariate effects on SN-38 clearance, is the first population model to describe the pharmacokinetics of irinotecan and its major metabolites in children. Supported in part by: NICHD 5 U10 HD037242-09, NIH M01 RR000188-43, NCI U01 CA57745, NCI U10 CA98453, NCRR M01 RR00188-37, The Mitchell Ross Children’s Cancer Fund, Pharmacia/Upjohn.     

Évaluation d’un score prédictif de dénutrition chez les patients pris en charge par irradiation pour un cancer des voies aérodigestives supérieures : étude rétrospective chez 127 patients

PurposeThe purpose of this study was to establish a pre-therapeutic score that could predict which patients would be at high risk of enteral tube feeding during (chemo)-radiotherapy for head and neck cancer.Patients and methodsA monocentric study was conducted retrospectively on patients receiving a radiotherapy or concurrent chemoradiotherapy for a head and neck cancer. A logistic model was performed in order to assess clinical or therapeutic risk factors for required artificial nutrition during treatment. Significant parameters, issued from multivariate analysis, were summed and weighted in a score aiming at estimating a malnutrition risk during radiotherapy.ResultsAmong the 127 evaluated patients, 59 patients required artificial nutrition during radiotherapy. In multivariate analysis, predictive factors for malnutrition were weight loss superior to 5% in the 3 months before radiotherapy, advanced tumor stage (III–IV vs. I–II), and pain requiring strong analgesics (step II–III vs. I). Concurrent chemotherapy was identified as a significant risk factor also, but it was strongly correlated with the tumor stage. The score, estimated from these previous factors, allowed a prediction of a risk of enteral feeding with a sensitivity of 90% and a specificity of 85%.ConclusionA predictive score of enteral nutrition before radiotherapy of head and neck cancer should be a useful clinical tool to target the patients who would need a prophylactic gastrostomy. Our study evidenced some risk factors of malnutrition requiring artificial feeding. However, we need a prospective study to confirm the validity of this score.     

The influence of Fluosol-DA and carbogen breathing on the antitumor effects of cyclophosphamide in vivo

Summary The effects of Fluosol-DA, an oxygen-carrying perfluorochemical emulsion, and carbogen breathing alone or in combination on the antitumor activity of cyclo-phosphamide (CTX) in vivo were investigated. The addition of 12 ml/kg Fluosol-DA immediately prior to CTX treatment exerted no effect on the antitumor effect of CTX on the RIF-1 tumor in C3H mice. On the other hand, carbogen breathing alone for 8 h significantly enhanced the antitumor effect of CTX, with a dose-modification factor of 1.29±0.07. The combination of Fluosol-DA and carbogen breathing further increased the effect of CTX, with a dose-modification factor of 1.63±0.05. There was no significant difference in animal lethality within the treatment groups. It was concluded that Fluosol-DA in combination with carbogen breathing may be useful for the enhancement of CTX chemotherapy of human neoplasmsThis work was supported by NCI grant CA13353     

CA 125 reliability in predicting ovarian cancer recurrence

The predictive value of CA 125 assay for recurrence in ovarian cancer patients in follow-up was analyzed in a study from April 1984 through June 1987. Forty-two patients with no evidence of disease (NED), with positive antigen levels at diagnosis and negative at the end of active treatment, were considered eligible for the analysis. Median follow-up time was 16 months (range, 5-34). Outcome analysis revealed 19 cases still NED: 16 had normal CA 125 levels (less than 35 U/ml). The 3 patients with positive antigen titers were intensively investigated with no evidence of recurrence. Twenty-three cases had disease recurrence: 13 of them had elevated marker levels prior to relapse diagnosis, with a median lead time of 5 months (range, 2-13). In contrast, 10 patients had positive titers at or soon after the recurrence. Test sensitivity was therefore 56% and specificity 84%. Predictive value for recurrence of elevated CA 125 levels was 0.81.     

Use of monoclonal antibodies in the treatment of cancer of the pancreas: towards new progress?

Pancreatic cancers rank amongst the most deadly malignant diseases with a 5 year-survival percentage less than 2% and few therapeutic approaches are hitherto available. This study presents the recent attempts to construct antibodies for therapy. The characterization of pancreatic tumor-associated antigens which might serve as target antigens for antibody therapy is the limiting factor before considering the treatment of pancreatic cancer with antibodies. Antigens such as CA 19-9, BW 494 and DU-PAN-2 have been reported to be associated with pancreatic cancers. However, monoclonal antibodies directed to these antigens was not proven to be specific enough to warrant therapeutic utilization and new tumor-associated antigens must be identified. Remarkable progress has been made recently in the construction of antibodies for therapy. Amongst these antibodies are "chimeric" antibodies, antibody heteroconjugates or hybrid antibodies. The in vivo utilization of those antibodies may well result in effective tumor-cell destruction.