Using Serum α-Fetoprotein for Prognostic Prediction in Patients with Hepatocellular Carcinoma: What is the Most Optimal Cutoff?

Background and Aims

The prognostic ability of α-fetoprotein (AFP) for patients with hepatocellular carcinoma (HCC) was examined by using different cutoff values. The optimal AFP cutoff level is still unclear.

Methods

A total of 2579 HCC patients were consecutively enrolled in Taiwan, where hepatitis B is the major etiology of chronic liver disease. Four frequently used AFP cutoff levels, 20, 200, 400, 1000 ng/mL, were investigated. One-to-one matched pairs between patients having AFP higher and lower than the cutoffs were selected by using the propensity model. The adjusted hazard ratios of survival difference were calculated with Cox proportional hazards model.

Results

Patients with a higher AFP level were associated with more severe cirrhosis, more frequent vascular invasion, higher tumor burden and poorer performance status (all p<0.0001). In the propensity model, 4 groups of paired patients were selected, and there was no difference found in the comparison of baseline characteristics (all p>0.05). Patients with AFP <20 ng/mL had significantly better long-term survival than patients with AFP ≧20 ng/mL (p<0.0001), and patients with AFP <400 ng/mL had significantly better overall outcome than patients with AFP ≧400 ng/mL (p = 0.0186). There was no difference of long-term survival between patients divided by AFP levels of 200 and 1000 ng/mL. The adjusted hazard ratios of AFP ≧20 ng/mL and AFP ≧400 ng/mL were 1.545 and 1.471 (95% confidence interval: 1.3–1.838 and 1.178–1.837), respectively.

Conclusions

This study shows the independently predictive ability of baseline serum AFP level in HCC patients. AFP levels of 20 and 400 ng/mL are considered feasible cutoffs to predict long-term outcome in unselected HCC patients.     

Results of pregnancies characterized by a decrease in the level of alpha-fetoprotein in the maternal blood

Pregnancy outcome was followed in 123 women showing maternal serum alpha-fetoprotein, less than or equal to 0.50 MOM. In 28 cases AFP was secondarily considered as normal either after ultrasonography and correction of gestation age or after a second sample normal result. In 95 cases AFP level was confirmed lowered; perinatal outcome was normal in 70 cases and abnormal in 25. Among these 25 cases, 3 autosomal trisomies occurred, 2 trisomies 18 and 1 trisomy 21; in the 22 other cases, we observed antepartum risk factors (10 cases with impending premature labor or premature labor, 9 cases with chronic hypertension, 2 cases with Ag HBs hepatitis and 1 case with diabetes).     

Epidemiology and factor analysis of obesity, type II diabetes, hypertension, and dyslipidemia (syndrome X) on the Island of Kosrae, Federated States of Micronesia

OBJECTIVES: Obesity, type II diabetes, hypertension, and dyslipidemia are major causes of morbidity and mortality throughout the world. Though these disorders often cluster in individuals and families and are collectively known as syndrome X, the basis for this aggregation is not well understood. To further understand the pathogenesis of syndrome X, a comprehensive epidemiological study was undertaken on the Pacific Island of Kosrae, Federated States of Micronesia (FSM). METHODS: The entire adult (>20 years of age) population of Kosrae underwent a clinical evaluation that included a questionnaire that noted the participants' sex, family data including listing of biological parents, siblings, and children, smoking status, village of residence, age and health status. The medical evaluation included: anthropometric measures (weight, height, waist, hip), serum chemistries (leptin, fasting blood sugar (FBS), insulin, total cholesterol (TC), triglycerides (TG), and apolipoproteins B and A-I (apo B and apo A-I) and blood pressure (BP) measurements. RESULTS: Obesity (BMI >/=35) was found in 24%, diabetes (FBS >/=126 or 2-hour oral glucose tolerance test >/=200) in 12%, hypertension (SBP >/=140 or DBP >/=90) in 17%, and dyslipidemia (TC >/=240 or TG >/=200 or apo B >/=120 or apo A-I 相似文献   

Triple Test Screening for Down Syndrome: An Egyptian-Tailored Study

Background

The incidence of Down syndrome (DS) in Egypt varies between 1∶555 and 1∶770 and its screening by triple test is becoming increasingly popular nowadays. Results, however, seem inaccurate due to the lack of Egyptian-specific information needed for risk calculation and a clear policy for programme implementation. Our study aimed at calculation and validation of the triple marker medians used in screening Egyptian females as well as to recommend programme conventions to unify screening in this country.

Methods

The study was conducted on 668 Egyptian women, in weeks 15–20 of pregnancy as proven by sonar. Chorionic gonadotropin (CG), α-fetoprotein (AFP) and unconjugated oestriol (uE3) were measured on Siemens Immulite analyzer. Medians of the three parameters were calculated, regressed against gestational age (GA) and weighted by the number of participants/week. Equations were derived to adjust each parameter to the maternal weight and were centered on the median Egyptian weight. Prisca software was fed with the above data, multiples-of-median (MoM) and DS risks were calculated and the screening performance was evaluated at a mid-trimester risk cutoff of 1∶270.

Results

Log-linear [AFP/uE3 = 10^(A+B*^GA)] and exponential equations [CG = A*e ^(B*^GA)] were derived and the regressed medians were found to follow similar patterns to other Asian and Western medians. Oestriol was always lowest (even halved) while CG and AFP were intermediate. A linear reciprocal model best fitted weight distribution among Egyptians and successfully adjusted each parameter to a weight of 78.2 kg. Epidemiological monitoring of these recommendations revealed satisfactory performance in terms of 6.7% initial positive rate and 1.00 grand MoM.

Conclusions

Adoption of the above recommendations is hoped to pave the way to a successful DS screening programme tailored to Egyptian peculiarities.     

Variation in spontaneous chromosomal damage as a function of biologic rhythms in women

Summary The alphafetoprotein (AFP) concentration in maternal serum was determined before and after chorionic villus sampling (CVS). A significant increase of 20% or more in the pre-CVS level was noted immediately after sampling in 59% of 837 pregnancies indicating some degree of feto-maternal haemorrhage. The increase in the AFP concentration in maternal serum was correlated with the weight of the tissue sample but not with the number of sampling attempts. A correlation of AFP increase and frequency of spontaneous abortions following CVS was suggested only in the group with an AFP increase of more than 100% or with a continuing rise in the first hour following CVS. CVS in early pregnancy obviously did not interfere with maternal serum AFP screening for neural tube defects in the second trimester. Although AFP measurement before and after CVS seems to have no immediate diagnostic application, in the research phase of CVS it may help to identify those procedures that are the least traumatic.     

Postnatal development of rat pups after maternal exposure to diethanolamine

BACKGROUND: Diethanolamine (DEA), a widely used surfactant, was administered to pregnant mice at the oral LD10 resulting in failure of pups to grow and thrive through postnatal day (PND) 3 [National Toxicology Program, 1987; York et al., Teratology 37:503-504, 1988]. The toxicity profile for DEA differs among rodent species. This study investigated DEA-induced postnatal toxicity in a second species. METHODS: Timed-mated Sprague-Dawley rats were dosed (0, 50, 125, 200, 250, or 300 mg DEA/kg/day, p.o.) on gestational days (GD) 6-19. Dams and pups were monitored for body weight, feed/water intake, clinical signs, litter size, and sex ratio. At necropsy (PND 21), maternal liver and kidney weights and number of uterine implantation sites were recorded. RESULTS: The high-dose group was terminated early due to excessive toxicity. The estimated maternal LD10 was 218 mg/kg/day. Maternal effects included decreased body weight and relative feed intake (>or=200 mg/kg/day), transiently reduced relative water intake (125 and 250 mg/kg/day), and increased absolute kidney weight (>or=125 mg/kg/day). Postimplantation loss (PND 0) and pup mortality (PND 0-4) were increased (>or=200 and >or=125 mg/kg/day, respectively). Pup body weight was reduced (>or=200 mg/kg/day) as late as PND 21. CONCLUSIONS: This study demonstrates reduced postnatal growth and survival in a second species after gestational exposure to DEA, persistence of toxic effects through the end of lactation, possibly due to long elimination half-life, and maternal and developmental toxicity no-observed-adverse-effect level (NOAELs) (50 mg/kg/day) and lowest-observed-adverse-effect level (LOAELs) (125 mg/kg/day) for oral DEA exposure during embryo/fetal development in the rat.     

History of Intentional and Unintentional Weight Loss in a Population-Based Sample of Women Aged 55 to 69 Years

FRENCH, SIMONE A, ROBERT W JEFFERY, AARON R FOLSOM, DAVID F WILLIAMSON AND TIM BYERS. History of intentional and unintentional weight loss in a population-based sample of women aged 55 to 69 years. Obes Res. 1995;3:163–170. Although both overweight and body weight fluctuation are related to chronic disease risk, little is known about the history of and reasons for body weight change in the general population. This paper reports the incidence of intentional and unintentional weight loss episodes during adulthood in a population-based sample of 26, 261 women aged 55 to 69 years. Intentional weight loss episodes of each of four amounts (5–9, 10–19, 20–49, 50+ lbs.) and unintentional weight loss episodes of 20 or more lbs. were recalled for each of three age periods (18–39, 40–54, 55+ years). At least one intentional weight loss episode of 5 or more lbs. was reported by 69% of women, 46% reported at least one intentional weight loss episode of 10 or more lbs, and 25% reported at least one intentional weight loss episode 20 or more lbs. At least one unintentional weight loss episode of 20 or more lbs. was reported by 29% of the women. Reasons for weight losses of 20 or more lbs. were also recalled. Women who had intentionally lost 20 or more lbs. were more likely to report weight losses due to low-calorie diets, exercise and weight loss groups, while women who had unintentionally lost 20 or more lbs. were more likely to report weight losses due to depression or stress. These findings question the common assumption that weight losses in adult women are primarily intentional and emphasize the need to distinguish the reasons for weight loss in studies examining the relationship between body weight changes and health outcomes.     

Birth weight,adult body size,and risk of colorectal cancer

BackgroundEvidence suggests that birth weight may be associated with colorectal cancer (CRC) risk later in life. Whether the association is mediated by adult body size remains unexamined.MethodCox proportional hazards models (Hazard Ratio (HR) and 95 % Confidence Intervals (CI)) were used to evaluate the association between self-reported birth weight (<6 lbs, 6-<8 lbs, ≥8 lbs) and CRC risk among 70,397 postmenopausal women from the Women’s Health Initiative. Further, we assessed whether this association was mediated by adult body size using multiple mediation analyses.ResultsCompared with birth weights of 6-< 8 lbs, birth weight ≥ 8 lbs was associated with higher CRC risk in postmenopausal women (HR = 1.31, 95 % CI 1.16–1.48). This association was significantly mediated by adult height (proportion mediated =11.4 %), weight (11.2 %), waist circumference (10.9 %), and body mass index at baseline (4.0 %). The joint effect of adult height and weight explained 21.6 % of this positive association.ConclusionOur data support the hypothesis that the intrauterine environment and fetal development may be related to the risk of developing CRC later in life. While adult body size partially explains this association, further investigation is required to identify other factors that mediate the link between birth weight and CRC.     

Arsenite and its biomethylated metabolites interfere with the formation and repair of stable BPDE-induced DNA adducts in human cells and impair XPAzf and Fpg

The underlying mechanisms of arsenic carcinogenicity are only poorly understood and especially the role of biomethylation is still a matter of debate. Besides the induction of oxidative DNA damage the interference with DNA repair processes have been proposed to contribute to arsenic-induced carcinogenicity. Within the present study the effects of arsenite and its mono- and dimethylated trivalent and pentavalent metabolites on BPDE-induced DNA adduct formation and repair has been investigated and compared in cultured human lung cells. Whereas only arsenite and MMA(III) increased BPDE-DNA adduct formation, arsenite (>/=5 microM), the trivalent (>/=2.5 microM) and the pentavalent (>/=250 microM) metabolites diminished their repair at non-cytotoxic concentrations. As potential molecular targets, interactions with the zinc finger domain of the human XPA protein (XPAzf) and the Escherichia coli zinc finger protein Fpg, involved in NER and BER, respectively, have been investigated. All trivalent arsenicals were able to release zinc from XPAzf; furthermore, MMA(III) and DMA(III) inhibited the activity of isolated Fpg. Altogether the results suggest that besides arsenite, especially the trivalent methylated metabolites may contribute to diminished NER at low concentrations.     

Effectiveness and Complications of Ultrasound Guided Fine Needle Aspiration for Primary Liver Cancer in a Chinese Population with Serum α-Fetoprotein Levels ≤200 ng/ml - A Study Based on 4,312 Patients

Background

Hepatocellular carcinoma (HCC) can be diagnosed by noninvasive approaches with serum α-fetoprotein (AFP) levels >200 ng/ml and/or a radiological imaging study of tumor mass >2 cm in patients with chronic liver disease. Percutaneous fine needle aspiration (FNA) under ultrasound (US) guidance has a diagnostic specificity of 95% and is superior to radiological imaging studies.

Aim

The aim of this study is to elucidate the effectiveness and complications of fine needle aspiration in a Chinese population with primary liver cancer and AFP levels ≤200 ng/ml.

Materials and Methods

A retrospective study was conducted over a period of 28 years. This selection period included patients with a suspected diagnosis of primary liver cancer whose AFP levels were ≤200 ng/ml and who underwent US-FNA. This data was then analyzed with cytomorphological features correlating with medical history, radiological imaging, AFP, and follow-up information.

Results

Of the 1,929 cases with AFP ≤200 mg/ml, 1,756 underwent FNA. Of these, 1,590 cases were determined malignant and the remaining 166 were determined benign. Further, 1,478 malignant cases were diagnosed by FNA alone, and of these, 1,138 were diagnosed as PLC. The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of the diagnoses were 92.96%, 100%, 100%, 59.71%, and 93.62% respectively. There was no significant difference in the sensitivity, specificity, PPV and NPV between the subgroups with tumor size<2 cm and ≥2 cm. Major complications included implantation metastasis and hemorrhage.

Conclusion

Patients with PLC, especially those who present with an AFP ≤200 ng/ml, should undergo FNA. If negative results are obtained by FNA, it still could be HCC and repeated FNA procedure may be needed if highly suspicious of HCC on imaging study. The superiority of FNA in overall accuracy may outweigh its potential complications, such like hemorrhage and implantation metastasis.     

Gender- and height-related limits of muscle strength in world weightlifting champions.

To assess factors that limit human muscle strength and growth, we examined the relationship between performance and body dimensions in the world weightlifting champions of 1993-1997. Weight lifted varied almost exactly with height squared (Ht(2.16)), suggesting that muscle mass scaled almost exactly with height cubed (Ht(3.16)) and that muscle cross-sectional area was closely correlated with body height, possibly because height and the numbers of muscle fibers in cross section are determined by a common factor during maturation. Further height limitations of muscle strength were shown by only one male champion >/=183 cm and no female champions >/=175 cm. The ratio of weight lifted to mean body cross-sectional area was approximately constant for body-weight classes 相似文献   

长期施肥对水稻土有机碳分布及化学结合形态的影响

采用湖南省4个23年连续施肥的稻田长期定位试验,研究了施肥对湖南省水稻土有机碳分布及化学键合形态的影响。试验设不施肥(CK)、化肥(NPK)、中量有机肥(MOM)和高量有机肥(HOM)4个处理。结果表明:在所有施肥处理中,水稳性团聚体均以0.25～1mm和2～5mm粒径含量最高,分别达全土总量的18%～43%和13%～48%。中、高量有机肥处理显著增加了>1mm大团聚体含量以及有机碳在大团聚体中的分配,其中0.25～1mm和1～2mm粒径团聚体中有机碳含量均略高于其余粒径组。与不施肥比较,钙结合态有机碳(Ca-SOC)占总有机碳的比例在2%～4%左右且随有机肥施用呈下降趋势,而铁铝结合态有机碳Fe(Al)-SOC占总有机碳的18%～33%呈上升趋势。有机肥施用条件下,有机碳在大团聚体中的分布的增加、Fe(Al)-SOC的提升以及Ca-SOC的降低意味着土壤有机碳物理和化学保护作用的增强,有利于稻田土壤有机碳的积累,是有机肥施用条件下保持稻田土壤较高固碳速率的重要原因。     

Association of Serum MicroRNA Expression in Hepatocellular Carcinomas Treated with Transarterial Chemoembolization and Patient Survival

Background and Aim

Hepatocellular carcinoma (HCC) is one of the most deadly tumors. Transarterial chemoembolization (TACE) is effective for unresectable HCC. In recent years, miRNAs have been proposed as novel diagnostic and prognostic tools for HCC. This study aimed to identify whether microRNAs (miRNAs) can serve as biomarkers to reliably predict outcome before HCC patients are treated with TACE.

Methods

Eleven miRNAs (miR-, miR-19a, miR-101-3p, miR-199a-5p, miR-200a, miR-21, miR-214, miR-221, miR-222, miR-223 and miR-, -5p) were quantified by quantitative real-time PCR (qRT-PCR) in 136 HCC patients’ serum before they received TACE therapy. Univariate and multivariate analysis were used to identify the prognostic value of clinical parameters and miRNAs. Area under the receiver operating characteristic curve (AUC) was used to evaluate the prediction potency.

Results

The levels of some miRNAs were dramatically associated with clinicopathologic features regarding Child-Puge class, AFP, tumor size and satellite nodules. Univariate analysis revealed that miR-200a, miR-21, miR-122 and miR-224-5p were significantly associated with patients’ survival. Multivariate analysis demonstrated that AFP, satellite nodules and miR-200a were the independent prognostic factors associated with survival in this cohort (p = 0.000, 0.001, 0.000, respectively). The probability of the prognostic accuracy of miR-200a was 81.64% (74.47% specificity and 88.76% sensitivity), which was higher than the classifier established by combination of AFP and satellite nodules (76.87% probability, 70.21% specificity and 69.66% sensitivity). Furthermore, the combination of AFP, satellite nodules and miR-200a demonstrated as a classifier for HCC prognosis, yielding a ROC curve area of 88.19% (93.62% specificity and 68.54% sensitivity).

Conclusions

Our study indicated that serum miR-200a may prognosticate disease outcome in HCC patients with TACE therapy. Therefore, miR-200a can potentially guide individualized treatment for HCC patients with a high risk of TACE treatment failures.     

The mouse teratogen dinocap has lower A/D ratios and is not teratogenic in the rat and hamster

The fungicide dinocap is currently used in the control of powdery mildew. We have reported that dinocap is teratogenic in the CD-1 mouse, causing cleft palate, otolith defects, and fetal weight deficits well below maternotoxic dose levels. In this study the maternal and fetal toxicity of dinocap was determined in the Sprague-Dawley rat and Syrian golden hamster, and adult-to-developmental (A/D) toxicity ratios were calculated and compared with the previously established A/D ratio of dinocap in the mouse. Dinocap in corn oil was administered by gavage to pregnant rats on gestation days 7-20 (0, 100, 150, 200 mg/kg/day) and to hamsters on gestation days 7-14 (0, 12.5, 25, 50, 75, 100, 200 mg/kg/day). Dams were killed on day 21 (rat) or day 15 (hamster), and litters were removed, counted, and weighed; half of each litter was necropsied for soft tissue defects, and the remaining half was processed for skeletal examination. In the rat, maternal extrauterine weight gain was significantly affected at 150 and 200 mg/kg/day, relative liver weight was elevated at 100 mg/kg/day and above, and fetal weight was lower at 150 and 200 mg/kg/day. In the hamster, maternal extrauterine weight was lower at 12.5 mg/kg/day and above; fetal weight was reduced, and the incidence of dilated renal pelvis was higher, at 25 mg/kg/day and above. Thus the A/D ratios for dinocap in the rat and hamster are similar, approximately 1.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regulation of cell cycle transition and induction of apoptosis in HL-60 leukemia cells by lipoic acid: role in cancer prevention and therapy

 

The most common semiquantitative method of evaluation of pulmonary lesions using ¹⁸F-FDG PET is FDG standardized uptake value (SUV). An SUV cutoff of 2.5 or greater has been used to differentiate between benign and malignant nodules. The goal of our study was to investigate the correlation between the size of pulmonary nodules and the SUV for benign as well as for malignant nodules.

Methods

Retrospectively, 173 patients were selected from 420 referrals for evaluation of pulmonary lesions. All patients selected had a positive CT and PET scans and histopathology biopsy. A linear regression equation was fitted to a scatter plot of size and SUV_max for malignant and benign nodules together. A dot diagram was created to calculate the sensitivity, specificity, and accuracy using an SUV_max cutoff of 2.5.

Results

The linear regression equations and (R²)s as well as the trendlines for malignant and benign nodules demonstrated that the slope of the regression line is greater for malignant than for benign nodules. Twenty-eight nodules of group one (≤ 1.0 cm) are plotted in a dot diagram using an SUV_max cutoff of 2.5. The sensitivity, specificity, and accuracy were calculated to be 85%, 36% and 54% respectively. Similarly, sensitivity, specificity, and accuracy were calculated for an SUV_max cutoff of 2.5 and found to be 91%, 47%, and 79% respectively for group 2 (1.1–2.0 cm); 94%, 23%, and 76%, respectively for group 3 (2.1–3.0 cm); and 100%, 17%, and 82%,, respectively for group 4 (> 3.0 cm). The previous results of the dot diagram indicating that the sensitivity and the accuracy of the test using an SUV_max cutoff of 2.5 are increased with an increase in the diameter of pulmonary nodules.

Conclusion

The slope of the regression line is greater for malignant than for benign nodules. Although, the SUV_max cutoff of 2.5 is a useful tool in the evaluation of large pulmonary nodules (> 1.0 cm), it has no or minimal value in the evaluation of small pulmonary nodules (≤ 1.0 cm).     

Developmental toxicity of carbon black oil in mice

BACKGROUND: Carbon black oil (CBO) is a refinery side-stream product used to produce asphalt and other commercial products. CBO contains several classes of hydrocarbons, several of which are known to exhibit systemic and gestational toxicities, making this mixture a candidate for causing reproductive toxicity. METHODS: Swiss-Webster mice were administered CBO (300, 350, 400 mg/kg/day) via oral gavage in a dosage volume of 10 microl/g body weight on gestation days (GD) 6-15. Uterine contents were evaluated on GD 18. RESULTS: Treatment with CBO at all dosage levels resulted in a high frequency of maternal clinical symptoms and a decrease in maternal weight gain. Decreased fetal viability was observed, manifested as a decrease in viable implants and, in a high percentage of treated dams, as early resorption of the entire litter. A significant reduction in fetal weight was also observed. However, neither structural malformations nor developmental delays in ossification were observed in any of the living offspring. To minimize maternal toxicity, the dosage range was lowered (100, 200, 300 mg/kg/day), and the concentration was adjusted such that the volume administered to each dam was decreased by 20%. In this trial, the only maternal effect observed was an increase in maternal liver weight at 200 and 300 mg/kg. The fetal lethality effects observed previously were reduced substantially. Nevertheless, the frequency of resorption among all treatment groups was higher statistically than in controls. CONCLUSIONS: These data support the hypothesis that CBO is reproductively toxic in Swiss-Webster mice at oral doses of >/=100 mg/kg/day.     

Maternal serum alpha-fetoprotein levels in multiple pregnancy.

Maternal serum alpha-fetoprotein (AFP) levels were higher in 10 twin pregnancies and one triplet pregnancy than in 22 control singleton pregnancies matched for maternal age, parity, and the time of gestation at which the serum sample was taken. In twin pregnancies the average AFP levels were double those found in singleton pregnancies and the level in the triplet pregnancy was even higher. Raised maternal serum AFP values due to multiple pregnancy should not cause unnecessary amniocentesis in the diagnosis of anencephaly or spina bifida if an ultrasound investigation is routinely performed first.     

Risk factors and outcomes of maternal obesity and excessive weight gain during pregnancy

Objective:

The prevalence of overweight and obesity among women of reproductive age is increasing. We aimed to determine risk factors and maternal, fetal and childhood consequences of maternal obesity and excessive gestational weight gain.

Design and Methods:

The study was embedded in a population‐based prospective cohort study among 6959 mothers and their children. The study was based in Rotterdam, The Netherlands (2001–2005).

Results:

Maternal lower educational level, lower household income, multiparity, and FTO risk allel were associated with an increased risk of maternal obesity, whereas maternal European ethnicity, nulliparity, higher total energy intake, and smoking during pregnancy were associated with an increased risk of excessive gestational weight gain (all p‐values <0.05). As compared to normal weight, maternal obesity was associated with increased risks of gestational hypertension (OR 6.31 (95% CI 4.30, 9.26)), preeclampsia (OR (3.61, (95% CI 2.04, 6.39)), gestational diabetes (OR 6.28 (95%CI 3.01, 13.06)), caesarean delivery (OR 1.91 (95% CI 1.46, 2.50)), delivering large size for gestational age infants (OR 2.97 (95% CI 2.16, 4.08)), and childhood obesity (OR 5.02 (95% CI:2.97, 8.45)). Weaker associations of excessive gestational weight gain with maternal, fetal and childhood outcomes were observed, with the strongest effects for first trimester weight gain.

Conclusions:

Our study shows that maternal obesity and excessive weight gain during pregnancy are associated with socio‐demographic, lifestyle, and genetic factors and with increased risks of adverse maternal, fetal and childhood outcomes. As compared to prepregnancy overweight and obesity, excessive gestational weight gain has a limited influence on adverse pregnancy outcomes.     

Measurement of Glycosylated Alpha-Fetoprotein Improves Diagnostic Power over the Native Form in Hepatocellular Carcinoma

Serum alpha-fetoprotein (AFP) has long been used as a diagnostic marker for hepatocellular carcinoma (HCC), albeit controversially. Although it remains widely used in clinics, the value of AFP in HCC diagnosis has recently been challenged due to its significant rates of false positive and false negative findings. To improve the efficacy of AFP as HCC diagnostic marker, we developed a method of measuring total and glycosylated AFP by multiple reaction monitoring (MRM)-MS. In this study, we verified the total amount of AFP (nonglycopeptide levels) and the degree of glycosylated AFP (deglycopeptide levels) in 60 normal (41 men and 19 women; mean age 53 years; range 32–74 years), 35 LC (23 men and 12 women; mean age 56 years; range 43–78 years; HBV-related), and 60 HCC subjects (42 men and 18 women; mean age 58 years; range 38–76 years; HBV-related; 30 stage I, 15 stage II, and 10 stage III). By MRM-MS analysis, the nonglycopeptide had 56.7% sensitivity, 68.3% specificity, and an AUC of 0.687 [cutoff value: ≥0.02 (light/heavy ratio)], comparing the normal and HCC group, whereas the deglycopeptide had 93.3% sensitivity, 68.3% specificity, and an AUC of 0.859 [cutoff value: ≥0.02 (light/heavy ratio)]. In comparing the stage I HCC subgroup with the LC group, the nonglycopeptide had a sensitivity of 66.7%, specificity of 80.0%, and an AUC of 0.712 [cutoff value: ≥0.02 (light/heavy ratio)], whereas the deglycopeptide had a sensitivity of 96.7%, specificity of 80.0%, and an AUC of 0.918 [cutoff value: ≥0.02 (light/heavy ratio)]. These data demonstrate that the discriminatory power of the deglycopeptide is greater than that of the nonglycopeptide. We conclude that deglycopeptide can distinguish cancer status between normal subjects and HCC patients better than nonglycopeptide.