Correlation between CA-125 serum level and response by RECIST in a phase III recurrent ovarian cancer study

Objectives

To evaluate in a large phase III recurrent ovarian cancer trial (OVA-301): 1) the concordance between CA-125 level vs. best overall response (OR) and progression-free survival (PFS) determined by radiological assessment 2) the impact of early CA-125 changes over the subsequent radiological response, and 3) the prognostic value of CA-125 response and CA-125 PFS to predict radiological response and PFS.

Methods

Assessment of response in the entire randomized population was performed by the Response Evaluation Criteria in Solid Tumors 1.0 (RECIST) and modified Rustin criteria for CA-125 determination.

Results

Most CA-125 decreases were observed in RECIST responders (82% of patients treated with the combination and 74% in the PLD alone). CA-125 progression preceded RECIST progression in 35% of patients with a median lead time of 8.4 weeks. A high concordance rate between CA-125 PFS status at 4 months (PFS4) and CA-125 response as a predictor of PFS4 (87%) and radiological response (79%) was found in the combination, with high positive predictive value for radiological PFS4 (92%) and high negative predictive value for OR (90%). An early CA-125 decrease was predictive for the ultimate response since it was found in a high rate of RECIST responders.

Conclusion

Radiological response was preceded by a favorable predictive CA-125 decrease in a high proportion of patients, suggesting that CA-125 evaluation may be an appropriate tool for tumor assessment in patients with ovarian cancer.     

Delphi as a method to establish consensus for diagnostic criteria

BACKGROUND/OBJECTIVES: To achieve a consensus, among a panel of experts, on the best clinical criteria for the clinical diagnosis of carpal tunnel syndrome (CTS). METHODS: Experts rated the diagnostic importance of items from the clinical history and physical examination for CTS. The ratings were expressed on a 10-cm visual analog scale. The average and standard deviation of the scores for each item were returned to the panelists. The panel members evaluated the items a second time with knowledge of the group responses from the first round. The scores were standardized to minimize scaling variations and, after the second round, the items were ranked in order of importance assigned by the group. Cronbach's alpha was used as a measure of homogeneity for the rankings. Increasing homogeneity was considered to be an indication of consensus among the panelists. RESULTS: Cronbach's alpha increased from 0.86 after the first round to 0.91 after the second iteration. Panelists who were relative outliers on the first round demonstrated a much higher correlation with the entire group after the second round. CONCLUSIONS: Delphi is an effective method of establishing consensus for certain clinical questions. Cronbach's alpha was a useful statistic for measuring the extent of consensus among the panel members. Delphi was chosen from the possible methods of group process because of its inherent feasibility. The absence of a need by the panelists to meet in person removed any constraint on the geographic location of the panel members. In addition, the anonymous nature of Delphi was thought to be a key factor in avoiding a result that might be skewed by one or more persuasive panelists. Both of these characteristics were felt to be particularly important to the topic on which consensus was sought, the clinical diagnostic criteria for CTS. This movement in the opinions of some of the panelists appeared to result from the feedback of information describing the group opinion.     

Comprehensive molecular characterisation of hereditary non-polyposis colorectal tumours with mismatch repair proficiency

BackgroundHereditary non-polyposis colorectal cancer (CRC) without mismatch repair (MMR) defects occurs in almost half of high-risk CRC families, but its genetic cause(s) is(are) still unknown. We aimed to identify unique molecular features that differentiate hereditary from sporadic MMR-proficient colorectal tumours.MethodsGenomic alterations in 16 tumours from 14 Amsterdam I–II families were studied using the genome-wide copy number OncoScan™ FFPE microarray. Somatic mutation hotspots in BRAF, KRAS, PIK3CA and TP53 were analysed in 37 colorectal tumours from 26 families and in 99 sporadic MMR-proficient CRCs, using direct automated sequencing and KASPar genotyping assays. CpG methylation index was studied in 25 tumours from 19 families by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA).ResultsOur findings indicate that hereditary MMR-proficient tumours have overlapping genomic profiles to those obtained in sporadic cases, both suggestive of high chromosomal instability, and no high CpG methylation index. Nevertheless, we identified a significant increase in the frequency of chromosome 2p and 2q gains, and of 10q loss in Amsterdam I families, as well as low frequency of >2 Mb copy-neutral or -gained loss of heterozygosity (LOH). No statistically significant differences in the frequency of BRAF, KRAS, PIK3CA and TP53 mutations or in the gene mutation patterns were observed. However, TP53 mutations appeared almost twice more frequently in sporadic tumours.ConclusionsOverall, hereditary MMR-proficient CRCs display similar molecular characteristics than their sporadic counterparts. However, the differences identified, such as the chromosome 2 gain, 10q loss, or the under-representation of TP53 mutations, if validated in larger series, might be of relevance in the clinical setting and/or in the identification of germline defects underlying some of these familial cases.     

Role and limitations of epidemiology in establishing a causal association

Cancer risk assessment is one of the most visible and controversial endeavors of epidemiology. Epidemiologic approaches are among the most influential of all disciplines that inform policy decisions to reduce cancer risk. The adoption of epidemiologic reasoning to define causal criteria beyond the realm of mechanistic concepts of cause-effect relationships in disease etiology has placed greater reliance on controlled observations of cancer risk as a function of putative exposures in populations. The advent of molecular epidemiology further expanded the field to allow more accurate exposure assessment, improved understanding of intermediate endpoints, and enhanced risk prediction by incorporating the knowledge on genetic susceptibility. We examine herein the role and limitations of epidemiology as a discipline concerned with the identification of carcinogens in the physical, chemical, and biological environment. We reviewed two examples of the application of epidemiologic approaches to aid in the discovery of the causative factors of two very important malignant diseases worldwide, stomach and cervical cancers. Both examples serve as paradigms of successful cooperation between epidemiologists and laboratory scientists in the pursuit of the understanding of cancer etiology.     

河南省兰考县农村地区功能性肠病的流行病学调查

目的：调查河南省兰考县农村地区功能性肠病（functionalboweldisorders,FBD）流行病学状况。方法：采用普查方法,对该地区6个村庄全部进行入户问卷调查,按照罗马III功能性胃肠病诊断标准统计FBD患病率,并按照性别、年龄、体质量指数和生活习惯等分组,进行相关危险因素分析。结果：实际共调查3032例,其中男性1531例,女性1501例;年龄18～109岁。共检出FBD137例（4．52％）,女性FBD患病率（5．13％）高于男性（3．92％）,但两者差异无统计学意义（P=0．108）;男性肠易激综合征（irritablebowelsyndrome,IBS）患病率显著低于女性（P〈0．05）;FBD患病率随年龄增长而升高,60岁以上组达高峰（8．50％,P〈0．001）,高龄是IBS、功能性腹泻的危险因素;功能性腹胀、IBS及FBD患病率均以消瘦组最高（P〈0．05）;较少规律进食与FBD有关,较少规律进食、较多进食生冷或辛辣食物是非特异性FBD的危险因素（P〈0．05）;多元回归分析发现高龄、焦虑和抑郁是FBD的危险因素。结论：河南省兰考县农村地区FBD患病率较低,年龄、不良生活方式是FBD的危险因素,FBD多伴焦虑、抑郁倾向。     

Improving the quality of general surgical operation notes in accordance with the Royal College of Surgeons guidelines: a prospective completed audit loop study

Aims and objectives Accurate documentation of surgical operation notes is crucial as it facilitates the post‐operative management of the patients. It also serves as an important medico‐legal document for any discrepancies or disputes. The objectives of this study were twofold: to compare operation note documentation against guidelines published in Good Surgical Practice by the Royal College of Surgeons of England (RCS Eng), 2008, and to improve adherence to these guidelines, through educating surgeons and the introduction of theatre aide‐memoires. Method We prospectively identified 100 general surgical patients operated between February 2010 and July 2010. Equal numbers of upper gastroenterology, colorectal and vascular patients were selected. We audited operation note documentation against the RCS Eng guidelines. Our findings were presented at the trust clinical governance meeting. Areas with deficient documentation were highlighted. In addition to educating surgeons, aide‐memoires were subsequently introduced in the operating theatres and our practice was re‐audited. Results A total of 18 RCS Eng guidelines were identified and audited. The first audit cycle revealed poor areas in documentation of ‘emergency/elective procedure’ (36%), ‘time of operation’ (36%), ‘date of operation’ (87%), ‘assistant’ (87%) and ‘post‐operative management’ (88%). After educating surgeons and introducing aide‐memoires in theatres, the results were re‐audited with an equal number of patients. The re‐audit demonstrated a clear improvement in four out of five deficient areas with compliance reaching almost up to 100%. Conclusion Operation note documentation is of paramount importance, it has medical and legal implications. Educating surgeons and providing aide‐memoires in theatres clearly improved documentation of operation notes in compliance with the RCS Eng guidelines.     

血细胞分析儿科复检规则的应用评价

目的对本室XS-800i血细胞五分类分析试行复检规则在儿科领域应用给予评价。方法参照国际实验血液学学会推荐的41条复检规则,结合儿科疾病诊疗的特点,参照SysmexXS-800i五分类血细胞分析仪异常报警提示信息,建立本室25条复检规则。随机选取1348份患儿抗凝全血标本,采用血细胞分析仪检测,同时进行血涂片人工镜检,对试行复检规则效果进行评估。定向选取184份标本对修订后的复检规则进行验证。结果试行版儿科复检规则评估复检率为30.2%,真阳性率为10.0%,假阳性率为20.2%,真阴性率为66.9%,假阴性率为2.9%。135份真阳性标本中第1位是异型淋巴细胞。272份假阳性标本中第1位是异型淋巴报警。修订复检规则将异型淋巴报警Q-Flags阈值从100调整到300,并增加红系IP信息报警"红细胞凝集"。修订复检规则验证结果表明真阳性率为20.7%,假阳性率为15.2%,真阴性率为62%,假阴性率为2.2%。结论通过对制定的儿科复检规则随机标本评估和复检规则临床实验有效验证,我室修订血细胞五分类分析复检规则可基本满足儿童医院专科特点,降低了常规血液检测假阳性率,血液病无漏诊。     

两种药物性肝损伤诊断评分标准的临床应用比较

目的比较我国药物性肝损伤常用的两种诊断方法的临床应用价值。方法分别用国内新标准和Danan标准,对212例临床诊断为药物性肝损伤的患者进行重新诊断,比较两种诊断方法之间的差异及一致性。结果 212例病例中,按国内新标准初步诊断确诊112例(52.8%),疑似病例91例(42.9%),排除9例(4.2%);疑似病例进行RUCAM简化评分系统再评分:极有可能7例,很可能有关50例,可能有关32例,可能无关2例,分别占疑似病例的7.7%、54.9%、35.2%、2.2%;按Danan标准诊断:极有可能48例(22.6%),很可能有关113例(53.3%),可能有关41例(19.3%),可能无关0例,无关10例(4.7%)。两种诊断标准比较差异有统计学意义(P<0.05),且一致性一般,故仍有偏差存在,主要原因为国内新标准仅节选了部分RUCAM评分系统。结论国内新标准较Danan标准简便易行且准确性较高,更适于我国药物性肝损伤的临床应用,但仍有需要改进之处。     

A comparative study of the different diagnostic criteria of gestational diabetes mellitus and its incidence

Background

High prevalence of diabetes and genetic predisposition to metabolic syndrome among Indians places Indian women at risk to develop gestational diabetes mellitus (GDM) and its complications. Literature defines multiple criteria for GDM. This prospective study compares available diagnostic criteria for GDM in Indian women and their correlation with perinatal morbidity.

Method

Nine hundred and forty-eight consecutive voluntary nondiabetic pregnant women were recruited for the study. Seven hundred and twenty-three of these (mean age 23.45 years; 75.7% < 25 years) who reported for the follow-up were screened for GDM at 24–28 weeks gestation by American College of Obstetrics and Gynaecology (ACOG) guidelines and World Health Organization (WHO) criteria. Glycated haemoglobin (HbA_1c) and fasting and two-hours postglucose plasma insulin levels were also analysed. Pregnancy outcome was known for 291 of these. Concordance of risk factors and perinatal complications was analysed with respect to GDM.

Results

Prevalence of GDM at 24–28 weeks gestation was found to be 4.8% by WHO criteria, 6.36% by Carpenter and Coustan's criteria, and 3.5% by O'Sullivan's criteria. Prevalence was marginally higher in women of higher age, having past history of abortion or family history of diabetes mellitus (DM) (P > 0.05). None of these women had HbA_1c > 6%. Relative risk of abnormal delivery (pregnancy outcome) was 1.93, 1.39, and 1.17 in women with GDM by O'Sullivan's, WHO, and Carpenter's criteria, respectively (P > 0.05). Abnormal deliveries were marginally higher in women with high postglucose load insulin levels. Mean weight of the newborns was essentially the same in GDM and nonGDM women by any of the criteria. One-hour and two-hours postglucose values were more sensitive in diagnosing GDM by O'Sullivan's criteria while fasting plasma glucose value had the poorest specificity with 2.5% of nonGDM women having values above the cut-off. Modifications of these criteria did not im-prove their predictive value for abnormal delivery over that of O'Sullivan's criteria.

Conclusion

Prevalence of GDM and abnormal delivery in women < 35 years of age is low. Therefore, global screening for GDM may not be very useful in women < 25 years of age unless family history of DM or past history of abortion is present. Existing evidence is inadequate to justify the switchover from O'Sullivan's criteria for diagnosis of GDM.     

CD3700血细胞分析仪复检规则的建立与应用评价

目的建立CD3700血细胞分析仪的复检规则,保证血细胞分析仪检测结果的准确性,以利临床疾病的诊断和治疗。方法应用CD3700血细胞分析仪检测654份血常规标本,同时通过人工镜检法进行血细胞计数和形态学检查。对检测结果进行统计学分析,参考国际血液学复检专家组制定的"41条"规则并进行适当调整建立新的复检规则。结果根据国际血细胞分析仪复检规则进行统计分析,CD3700血细胞分析仪检测的654份标本真阳性率为24.9%,假阳性率为27.7%,真阴性率为45.6%,假阴性率为1.8%,符合率为70.5%,复检率为52.6%,漏检率为1.8%,无血液恶性肿瘤漏诊。调整新的复检规则后,重新进行统计分析,真阳性率为15.3%,假阳性率为11.0%,真阴性率为69.4%,假阴性率为3.8%,符合率为84.7%,复检率为26.3%,漏检率为3.8%,无血液恶性肿瘤漏诊。结论为了既保证血细胞分析仪的分析质量,又能减少不必要的工作负担,各临床实验室有必要根据自己所用仪器的特点制定出合理的复检规则。