Serum Alpha-fetoprotein Values Research Articles

Applicability of the multiplex quantitative antibody array system for early diagnosis of hepatocellular carcinoma

To develop an early and accurate detection method for hepatocellular carcinoma (HCC) based on detection of tumor-associated serum markers using a multiplex quantitative antibody array. The double-antibody sandwich principle was used to establish an antibody array composed of eight cancer-related serum markers, including alpha-fetoprotein (AFP), hepatocyte growth factor (HGF), insulin-like growth factor (IGF), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), transforming growth factor-beta 1 (TGF-b1), and vascular endothelial growth factor (VEGF). Serum samples from 160 cases of clinically diagnosed HCC and from 58 cases of liver cirrhosis (LC; controls) were obtained to test the array. Sixty percent of the samples were randomly selected for use as the training set (HCC, n = 96; LC, n = 36), and the remaining 40% was used as the test set (HCC, n = 64; LC, n = 22). The SPSS statistical software was used to perform logistic regression analysis and to create a diagnostic model. When used with the training set, the model had sensitivity of 93.3%, specificity of 83.3%, and accuracy of 90.9%. When used with the test set, the model had sensitivity of 89.0%, specificity of 77.3%, and accuracy of 86.0%. The traditional serum AFP value (cut-off value of 20 ng/mL) showed 70.0% diagnostic sensitivity, 59.0% specificity, and 64.0% accuracy. The newly developed multiplex quantitative antibody detection system has high sensitivity and specificity. The diagnostic model with AFP and seven other cancer-related factors was superior to the traditional AFP only approach for early diagnosis of liver cancer, indicating its potential clinical value.

Diagnostic utility and correlation of tumor markers in the serum and cerebrospinal fluid of children with intracranial germ cell tumors

In order to predict whether tumor markers assist in the histopathologic diagnosis of germ cell tumors (GCTs), we analyzed the correlation of beta human chorionic gonadotropin (βhCG) and alpha-fetoprotein (AFP) in serum and cerebrospinal fluid (CSF) samples at baseline and subsequent follow-up examinations. A retrospective study of patients diagnosed with intracranial GCTs between July 1985 and February 2011 at our institution was conducted to review clinical, surgical, radiological, laboratory, and histopathologic data. Of the 67 patients eligible for the study, 42 had germinomas and 25 non-germinomatous GCTs. At baseline, serum and CSF AFP agreed in 97.9 % of patients (Cohen's Kappa 0.93). Baseline βhCG samples agreed in only 72.5 % of patients (Cohen's Kappa 0.46). In most cases, values were higher in serum for AFP and in CSF for βhCG. ROC curves estimated from logistic regression model indicated that CSF and serum samples had almost equal diagnostic utility, and the DeLong test showed that the difference in area under curves was not statistically significant. During follow-up (185 paired CSF and serum values from 43 patients), 90.3 % of AFP values correlated between CSF and serum (Cohen's Kappa 0.22, showing fair agreement). For βhCG, 96.2 % of values agreed in serum and CSF (Cohen's Kappa 0.61). In some patients, intracranial GCTs can be diagnosed based solely upon positive serum AFP values. In addition, marker values from serum only may be sufficient to predict tumor relapse at interval follow-up examinations.

First-Trimester Screening for Neural Tube Defects Using Alpha-Fetoprotein

Objective: To assess the potential value of maternal serum alpha-fetoprotein (AFP) at 11–13 weeks’ gestation in early screening for fetal neural tube defects (NTDs). Methods: Maternal serum AFP at 11–13 weeks’ gestation was measured in 32 cases of fetal NTDs, including 18 cases of acrania and 14 cases of spina bifida, and 1,500 unaffected controls. The measured serum AFP was converted into multiple of the expected median (MoM) after adjustment for gestational age and maternal characteristics and Mann-Whitney test was used to determine the significance of difference in the mean MoM of serum AFP in the NTD group to that in the controls. Results: The mean AFP MoM in the NTD group (1.76, 95% CI 1.39–2.23) was significantly higher than in the controls (p < 0.0001). The mean AFP MoM was not significantly different between the cases of acrania and cases of spina bifida (1.78 vs. 1.75; p = 0.722). The detection rates of NTD in screening by serum AFP were 50.0% (95% CI 31.9–68.1) and 37.5% (95% CI 21.1–56.3) at fixed false-positive rates of 10 and 5%, respectively. Conclusion: Measurement ofmaternal serum AFP at 11–13 weeks’ gestation may be useful in screening for fetal NTDs.

573: Abnormal second trimester serum analytes are more predictive of earlier and more severe variants of preeclampsia than mild preeclampsia

more predictive of earlier and more severe variants of preeclampsia than mild preeclampsia Richelle Olsen, Douglas Woelkers, Andrew Hull, Yvette LaCoursiere UCSD Medical Center, Department of Reproductive Medicine, San Diego, CA, University of California San Diego, Department of Reproductive Medicine, San Diego, CA OBJECTIVE: To determine the relative association of abnormal second trimester serum analytes with mild versus severe forms of preeclampsia-toxemia (PET) STUDY DESIGN: This is a retrospective cohort study of 7767 subjects undergoing second trimester serum aneuploidy screening from a single institution. Values of maternal serum alpha fetoprotein (AFP), beta hCG (HCG) and inhibin (INH) were independently calculated as gestational age specific multiples of the median (MoM) for each subject. Outcomes evaluated were gestational age at delivery and occurrence and severity of PET. Cases were classified as having preeclampsia with delivery 34 weeks ( 34 PET), preeclampsia with delivery 34 weeks ( 34 PET), or mild and severe preeclampsia (mPET and sPET) by usual clinical criteria (ACOG 1996, 2002). Results were analyzed using Students t-test, chi square and stepwise logistic regression. RESULTS: In this cohort, there were 459 (6.5%) cases of preeclampsia, of whom 65 (14%) delivered prior to 34 weeks and of whom 394 (86%) delivered after 34 weeks. Elevated concentrations of AFP, HCG and INH were significantly associated with the occurrence of any form of PET. For each abnormal analyte 2.0 MoM, the odds ratio was higher for the development of 34 PET (see Table 1). This association remained when comparing mPET and sPET. The higher the MoMs for each analyte the greater the likelihood of PET and the more likely that the PET would be severe. CONCLUSION: Elevated concentrations of AFP, HCG, and INH are more strongly predictive of severe and early variants of preeclampsia than of mild disease at term, and this risk differential increases as the concentration of the analytes rises. This information may help stratify women at higher risk for adverse outcomes who require more vigilant monitoring.

FDG PET Imaging in a Patient With Primary Seminoma of the Prostate

Primary seminoma of the prostate is extremely rare. We describe a case of a 35-year-old man who presented with difficulty in urinating. Physical findings were unremarkable, but a rectal examination revealed a slightly hardened prostate with a nodule in the right lobe. Blood parameters were normal; however, blood chemistry revealed slightly elevated lactic dehydrogenase, and microscopic hematuria was evident. Serum prostate acid phosphate, carcinoembryonic antigen, and alpha-fetoprotein values were within normal limits. Both computed tomography and magnetic resonance images revealed a large mass in the prostate gland. A prostatic sarcoma or malignant lymphoma was initially suspected. A systemic survey using 18-fluoro-2-deoxyglucose (F-18 FDG) positron emission tomography revealed focal FDG uptake in the prostate gland. A prostatic biopsy of the mass was histologically diagnosed to reveal an extragonadal seminoma.

MR imaging in diffuse-type hepatocellular carcinoma with synchronous portal vein thrombi

Diffuse or continuous multifocal tumors with accompanying portal vein thrombosis yield considerable changes in the magnetic resonance imaging findings of hepatocellular carcinoma. The overlapped imaging findings of these two co-existing pathologies may be confusing. We aimed to evaluate the magnetic resonance imaging findings of widespread hepatocellular carcinoma lesions complicated with portal vein thrombosis. Twenty-two patients (20 male, 2 female; mean age: 57 years) with portal vein thrombosis and diffuse-type hepatocellular carcinoma who underwent contrast-enhanced hepatic magnetic resonance imaging in our department between August 2001 and November 2008 were evaluated retrospectively. The unenhanced axial T1-weighted, T2-weighted, and post-contrast early- and late-phase images were reviewed in each patient. On T2-weighted magnetic resonance images, tumors were seen mildly hyperintense in 11 patients and heterogeneously hyperintense in 11 patients. Unenhanced T1-weighted images demonstrated homogeneous hypointensity in 15 patients and heterogeneous hypointensity in 7 patients. Post-contrast early-phase magnetic resonance images showed patchy enhancement in 12 patients, moth-eaten enhancement in 6 patients, strong enhancement in 1 patient, and minimal enhancement in 3 patients. Post-contrast late-phase magnetic resonance images demonstrated heterogeneous washout in all patients. Portal vein thrombosis was present in all patients. The mean diameter of main portal vein thrombi was 27 mm (range: 25-30 mm). Serum alpha-fetoprotein levels were elevated in all patients. In patients with chronic parenchymal liver disease, when portal vein thrombosis and high serum alpha-fetoprotein values co-exist, careful attention must be paid to the hepatic parenchymal changes, especially on contrast-enhanced images, in order to not overlook diffuse-type hepatocellular carcinoma.

Reference Intervals for Serum Alpha-Fetoprotein and Carcinoembryonic Antigen in Chinese Han Ethnic Males from the Fangchenggang Area Male Health and Examination Survey

We calculated upper 95% reference limits for serum alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) according to the CLSI/NCCLS C28-A3 guideline. Serum samples from 1400 healthy male subjects were collected from the Fangchenggang Area Male Health and Examination Survey (FAMHES). Serum AFP and CEA values were measured by electrochemiluminescence immunoassay on COBAS 6000 system E601 (Elecsys module) immunoassay analyzers. Serum AFP and CEA values were not normally distributed but log normally distributed. The upper 95% reference limits of the reference intervals were ≤ 4.76 IU/mL (nonparametric) or ≤ 4.56 IU/mL (parametric) for AFP and ≤ 5.57 ng/mL (nonparametric) or ≤ 5.82 ng/mL (parametric) for CEA. The distribution of AFP levels was found to be consistent between the non-smoking and smoking (p=0.740) and non-drinking and drinking groups (p=0.698). The distribution of serum CEA levels was significantly higher in the smoking than the non-smoking group (p<10⁵), whereas there was no significant difference in this respect between the non-drinking and drinking groups (p=0.147). A significant increase with age was found both for serum AFP and CEA levels, and the age-dependent reference intervals were calculated. The reference intervals for serum AFP and CEA show a slight deviation compared to previously reported reference levels. Distinct reference intervals of serum CEA must be established for smoking and non-smoking populations. In addition, age-dependent reference intervals should be implemented in clinical laboratories.

Low alpha‐fetoprotein hepatocellular carcinoma

A large proportion of hepatocellular carcinoma (HCC) patients do not secrete elevated levels of the tumor marker alpha-fetoprotein (AFP). There is little published guide to prognostic features of this patient subset. We interrogated a large HCC database in which all patients had been followed until death, to examine which features might be prognostically useful. We found 413 biopsy-proven unresectable HCC patients with low serum AFP values. Serum gamma glutamyl transpeptidase (GGTP) levels were one of the most significant factors for survival. This dichotomization into low and high GGTP levels separated the patients into distinctive survival ranges. Patients with GGTP levels < 110 U/100 mL and small tumors had longest survival > 795 days. Patients with GGTP > or = 110 U/mL and large tumors with the presence of portal vein thrombosis had the shortest survival range of 300-560 days. Serum levels of the onco-fetal protein GGTP represent a useful prognostic parameter in HCC patients with low AFP levels.

Alpha-Fetoprotein Response After Locoregional Therapy for Hepatocellular Carcinoma

TO THE EDITOR: We read with great interest the report by Riaz et al, in which they demonstrated that the response of serum alphafetoprotein (AFP) level after locoregional therapy in patients with hepatocellular carcinoma (HCC) was a useful surrogate marker to determinate tumor response and survival. In this study, AFP response was seen in 81 (64.8%) of 125 patients treated with chemoembolization and radioembolization. Also, the authors reported that AFP response was a prognostic factor for overall survival in univariate and multivariate analyses. It is still unclear whether serial AFP measurement or AFP/tumor volume for monitoring treatment response in patients with HCC should be used. Some studies have shown that serum AFP level might be used as a surrogate marker for response to systemic chemotherapy. A significant correlation between serum AFP levels and both size and number of HCC lesions has been reported. AFP/tumor volume may be a better prognostic indicator for patients with HCC than serum AFP value alone. Also, significant correlation between higher AFP levels and higher stages has been reported. Because the results of a multivariate analysis give important messages to readers, the analysis should be carefully used. For accurately interpreted results of a study, the sample size should be sufficient to perform multivariate analysis. Some authors have recommended that a minimum of 20 patients per predictor should be used for an accurately interpreted multivariate analysis. Also, each parameter considered to be a prognostic factor must be evaluated before univariate or multivariate analysis is performed, because one factor may interact with the others. We think that the statistical assessment is the most important limitation of the study by Riaz et al. The study included a total of 125 patients and six prognostic factors, such as stage, performance status, Child Pugh class, WHO response, European Association for the Study of the Liver response, and AFP response, which were evaluated for multivariate analysis. We think that the sample size of the study was quite small for multivariate analysis, and the interaction probability among prognostic factors analyzed in the study was quite high. We believe that this problematic issue may have affected the results presented in the report.

Role of α-Fetoprotein in Hepatocellular Carcinoma: Prognostication, Treatment Monitoring or Both?

Despite recent breakthroughs in the treatment for both early and advanced hepatocellular carcinoma, the development of markers for prognostication and treatment monitoring remains to be explored. Serum alpha-fetoprotein has been frequently measured at diagnosis and serially during treatment by clinicians for decades, with an aim for prognostication of disease and monitoring of treatment response. In this review, the evidence regarding the prognostic value of serum alpha-fetoprotein and the value of serial alpha-fetoprotein in the monitoring of treatment efficacy will be discussed, with emphasis on recent data.

A risk-adapted study of cisplatin and etoposide, with or without ifosfamide, in patients with metastatic seminoma: Results of the GETUG S99 multicenter prospective study

5031 Background: Cisplatin plus etoposide-based chemotherapy is the recommended treatment and results in a high cure rate in patients (pts) with metastatic seminoma (Eur Urol 2008, 53: 478–96). Whether pts with good-prognosis and intermediate-prognosis metastatic seminoma should be treated differently or not has not been defined. Methods: From December 1999 to September 2008, pts with pure seminoma, a normal serum alpha-feto protein value, and evidence of metastases were included in this prospective study. Pts with a good prognosis according to the IGGCCG classification were treated with 4 cycles of EP (cisplatin 20 mg/m2/day and etoposide 100 mg/m2/day x 5 days, every 3 weeks). Pts with an intermediate prognosis according to the IGCCCG or MRC classifications (extra-pulmonary visceral metastases or supra-diaphragmatic metastases plus serum LDH&gt; 2 x N) (J Clin Oncol. 1997;15:594–603; Eur J Cancer. 1999;33:1347–1350) were treated with 4 cycles of VIP + G-CSF (cisplatin 20 mg/m2/day, ifosfamide 1.2 g/m2/day, and etoposide 75 mg/m2/day x 5 days, every 3 weeks + G-CSF). Toxicity was assessed using the NCI-CTC scale. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Results: 133 pts were included in this study. Median age was 36 years (20–66). The median follow-up is 3.6 years (0.4–9.1). 110 (83%) pts had good-prognosis metastatic seminoma and received EP. Grade 3–4 toxicity included mainly neutropenia (41%) and neutropenic fever (13%). The 3-year PFS rate in good-prognosis pts is 94% (87–97), and the OS rate is 99% (94–100). 23 (17%) pts had intermediate-prognosis disease and received VIP + G-CSF. Toxicity included grade 3–4 neutropenia (32%), neutropenic fever (18%), grade 3–4 thrombocytopenia (18%), and grade 3–4 anemia (19%). Platelet and erythrocyte transfusions were required in 32% and 36% of pts, respectively . The 3-year PFS rate is 86% (67–95), and the OS rate is 91% (72–97) in intermediate-prognosis pts. Overall, 92 pts (69%) had post-chemotherapy residual masses and 75 pts (56%) were managed with 18Flurorodeoxyglucose positron emission tomography. Conclusions: This risk-adapted chemotherapy yielded an excellent outcome with an OS rate of 97% in metastatic seminoma. No significant financial relationships to disclose.

A Prospective Study of Hypofractionated Proton Beam Therapy for Patients With Hepatocellular Carcinoma

To evaluate the efficacy and safety of hypofractionated proton beam therapy for patients with hepatocellular carcinoma (HCC). Between September 2001 and August 2004, 51 patients with HCC greater than 2 cm away from the porta hepatis or gastrointestinal tract were treated with proton beam therapy to 66 Gy-equivalents (GyE) in 10 fractions. Overall survival rates were 49.2 and 38.7% at 3 and 5 years after treatment. Local control rates were 94.5 and 87.8% at 3 and 5 years after treatment. Posttreatment serum alpha-fetoprotein values were significantly reduced when compared with pretreatment values (p < 0.0001). Patients experienced only minor acute reactions of Grade 1 or less, and 3 patients experienced late sequelae of Grade 2 or higher. However, there were no treatment-related deaths. Hypofractionated proton beam therapy is safe and well-tolerated by patients with HCC located greater than 2 cm away from the porta hepatis or gastrointestinal tract and may be effective alternative to other modalities.

α-Fetoprotein and human chorionic gonadotrophin-β as prognostic markers in neuroendocrine tumour patients

Serum chromogranin A is the most useful general and prognostic tumour marker available for neuroendocrine tumour (NET) patients. The role of other tumour markers is less clear. In order to determine the diagnostic and prognostic value of serum α-fetoprotein (AFP) and human chorionic gonadotrophin-β (hCGβ) in NETs, a database containing biochemical, histological, and survival data on 360 NET patients was constructed. This data was statistically assessed, using Statistical Package for the Social Sciences, to determine the utility of commonly measured tumour markers with particular emphasis on AFP and hCGβ. α-Fetoprotein and hCGβ were raised in 9.5 and 12.3% of patients respectively and jointly raised in 9.1% of patients in whom it was measured. α-Fetoprotein levels associated strongly and positively with tumour grade, serum CgA and hCGβ levels, and worse survival. Human chorionic gonadotrophin-β levels also associated strongly and positively with serum CgA and AFP levels, and worsening survival. α-Fetoprotein and hCGβ are elevated in high-grade NETs, with a rapidly progressive course and poorer survival. They also correlate with chromogranin-A, which is known to be a marker of tumour burden and to have prognostic value. Thus AFP and hCGβ are clinically important in NETs and when elevated are poor prognostic markers.

Maternal serum alpha-fetoprotein values in type 1 and type 2 diabetic patients

Maternal serum alpha-fetoprotein (MSAFP) values are reported to be lower in type 1 diabetic patients, and a correction factor is often applied. We sought to determine whether type 2 diabetic patients require the same MSAFP adjustments as type 1 diabetic patients. We performed a retrospective review of MSAFP levels from a university laboratory in type 1 and type 2 diabetic patients between July 2000 and August 2006, matched 1:2 with controls. Groups were compared using analysis of variance and Student t testing. Seventy-seven type 1 and 75 type 2 diabetic patients were compared with 304 controls. Type 1 and type 2 diabetic patients differed significantly from each other and controls before corrections. Diabetic patients were similar to each other, but significantly lower than controls, after weight corrections. These differences were eliminated by a 10% correction factor. Type 1 and type 2 diabetic patients require both weight and diabetes corrections to adjust MSAFP values to nondiabetic levels.

Evaluating Patients with Cirrhosis for Hepatocellular Carcinoma: Value of Clinical Symptomatology, Imaging and Alpha-Fetoprotein

Objective: This study was undertaken to assess the value of clinical symptomatology, abdominal ultrasound (US), triple-phase CT (TPCT) and serum alpha-fetoprotein (AFP) estimation in predicting presence of hepatocellular carcinoma (HCC) among patients with cirrhosis. Materials and Methods: In this cross-sectional study, Child’s A/B cirrhosis patients were subjected to clinical evaluation, US, TPCT and serum AFP estimation. Sensitivity and specificity of clinical symptoms and of AFP at different cut-off levels were determined. Detection rate of HCC and agreement between US and TPCT was estimated. Results: A high proportion of enrolled subjects had HCC at first presentation (40.7%). Significantly higher prevalence of abdominal pain, weight loss, and anorexia was seen in patients with cirrhosis with HCC compared to those without HCC. Sensitivity and specificity of any of these symptoms was 73 and 79%, respectively (positive and negative predictive values of 65 and 85%, respectively). A 100% agreement between TPCT and US was observed for diagnosing HCC cases. However, TPCT detected a greater number of smaller HCCs. Sensitivity of AFP at 400 ng/ml cut-off was only 25.7%, too low to be useful. Best mix of sensitivity (77.2%) and specificity (78.1%) of AFP was found to be at 10.7 ng/ml cut-off which falls within the conventional limits of normalcy. Conclusion: The study highlights the importance of symptomatology of weight loss, abdominal pain or anorexia as markers for HCC in patients with cirrhosis. AFP was not found to be a useful screening test. TPCT should be undertaken in all cirrhotics presenting to the hospital for the first time.

Cystic hygroma and mid-trimester maternal serum screening

To investigate the relationship between maternal serum screening markers and pregnancy outcome in fetuses with cystic hygroma at 15-18 weeks of gestation. We retrospectively reviewed case-notes of 34 consecutive singleton fetuses with cystic hygroma referred at 15-18 weeks of gestation. All cases had maternal blood sampled for triple screening at the time of the ultrasound scan. In total, 62% of fetuses with cystic hygroma had abnormal chromosome complements and 80% had a poor outcome. Six fetuses presenting normal values of human chorionic gonadotropin (0.5-2.5 MoM [multiples of the median]), serum alpha-fetoprotein (0.5-2.5 MoM) and unconjugated estriol (>0.5 MoM), normal karyotype and absence of associated structural anomalies had an uneventful outcome. Our data demonstrated that cystic hygroma at 15-18 weeks has a strong association with chromosomal abnormalities. In euploid fetuses, maternal serum screening results may have a role in the diagnostic work-up of the pregnancy.

The association of triple-marker test results with adverse pregnancy outcomes in low-risk pregnancies with healthy newborns

This study was designed to investigate the relationship between the second trimester maternal serum markers and adverse pregnancy outcomes in healthy newborns. A total of 749 women who delivered in our institution with complete follow up and second-trimester triple marker test data available were included in the study. Women with multiple pregnancies, chronic diseases, diabetes mellitus, obesity, smokers and infants with chromosomal and congenital abnormalities were excluded. Maternal serum alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG) and unconjugated estriol (uE(3)) values were investigated in our cohort who developed preeclampsia (n = 28), gestational diabetes (GM) (n = 69), preterm labor-birth (n = 100), oligohydramnios (n = 37) and macrosomia (n = 59) by using receiver operating characteristic (ROC) curve analysis, with chi-square and Pearson's correlation tests. Women with uE(3) < or = 1.26 MoM (P = 0.001, AUC = 0.666), HCG > 1.04 MoM (P = 0.032, AUC = 0.599) or AFP < or = 0.69 MoM (P = 0.049, AUC = 0.600) values significantly developed oligohydramnios. Also, macrosomic infants were observed in women who had HCG values > 0.86 MoM (P = 0.047, AUC = 0.578). Patients with HCG > 1.04 MoM (P = 0.04, AUC = 0.565) and uE(3) < or =0.88 MoM (P = 0.049, AUC = 0.571) developed GDM. HCG levels > or =2.5 or > or =3 MoM were significantly associated with the development of oligohydramnios [P = 0.005; OR = 4 (95% CI: 1.7-9.7)], [P = 0.008; OR = 4.9 (95% CI: 1.7-13.7)], respectively. When women with adverse (n = 237) and normal (n = 512) outcomes were compared there were significant differences in maternal serum AFP (1.40 +/- 0.84 vs. 1.23 +/- 0.75 MoM, P = 0.006) and uE(3) values (1.38 +/- 1.42 vs. 1.45 +/- 0.98 MoM, P = 0.001). Serum estriol, AFP or HCG values in triple test results may be associated with development of oligohydramnios, gestational diabetes and macrosomia in women with healthy and normal appearing fetuses.

Cushing’s Syndrome in a Child with Pancreatic Acinar Cell Carcinoma

A case of pancreatic acinar cell tumor (ACC) is presented in a 10-year-old boy. The tumor manifested clinically with Cushing's syndrome, high serum adrenocorticotropic hormone (ACTH) and cortisol concentrations. In addition, excessive serum levels of alpha-fetoprotein (AFP) were detected. Surgical resection was not possible due to retroperitoneal invasion. Biopsy of the mass showed a solid, poorly differentiated ACC of the pancreas. Periodic acid Schiff positive cytoplasmic granules, trypsinogen, keratins, alpha-1-antitrypsin, and AFP were identified in the tumor cells. Electron microscopy demonstrated zymogen granules as well as isolated dense core granules. Using immunochemiluminometric assay, a high quantity of ACTH was found in the fresh frozen tumor extract. ACTH, chromogranin A, and corticotropin-releasing factor were identified only in a few cells by immunohistochemistry. Combined radiochemotherapy was temporarily effective in reducing the tumor mass and serum AFP. Serum ACTH and cortisol levels dropped progressively and definitively to normal values after chemotherapy, and the Cushing's syndrome subsided. Two years later, the patient died with metastatic disease. The presented case of ACC is interesting due to high serum AFP values and ectopic ACTH secretion resulting in Cushing's syndrome.

Combined hepatocellular and cholangiocarcinoma: clinical features and prognostic study in a Thai population

Combined hepatocellular and cholangiocarcinoma (HCC-CC) is an uncommon subtype of primary liver cancer, the clinicopathological features of which have rarely been reported in detail. Some authors believe that HCC-CC behaves like HCC, but biliary differentiation may be associated with poorer prognosis. Moreover, CC has more frequent lymph node metastases. In this study, we aimed to determine the clinical course and survival outcome of HCC-CC patients in a Thai population by comparing them with patients with ordinary HCC. The clinicopathological features of patients who were diagnosed with HCC-CC at Ramathibodi Hospital during 2000-2004 were retrospectively studied by comparing them with the features of patients suffering from ordinary HCC. Twenty-five patients who were diagnosed with HCC-CC were included in this study, and subsequently 50 patients with HCC who had tissues taken during the same period were selected randomly from among 148 HCC patients. Statistical analysis was done by using SPSS version 10.0. The Kaplan-Meier method was used to assess the survival rate. Multiple logistic regression analysis was performed to assess correlations. A value of P < 0.05 was considered statistically significant. There were no significant differences in etiologic risk factors between HCC-CC and HCC patients: cirrhosis (50% vs 44%), chronic alcohol abuse (36% vs 43%), presence of hepatitis B surface antigen (HBsAg; 66% vs 78%) and presence of hepatitis C virus (HCV) antibody (13% vs 3%). The serum alpha-fetoprotein (AFP) value in the HCC-CC group was lower than that in the HCC group (5.87 vs 41.46 ng/ml). No differences in tumor characteristics or liver status (tumor size, presence of multinodular lesions, portal vein thrombosis, intrahepatic bile duct dilatation, intraabdominal lymphadenopathy, extrahepatic metastasis, liver cirrhosis, portal hypertension, and ascites) between these two groups were found. The overall median survival of HCC-CC patients was 38 weeks while that of HCC patients was 54 weeks. Multivariate analysis showed that elevated carbohydrate antigen (CA)19-9 (>/=80 U/ml) and the presence of intrahepatic bile duct dilatation were independent risk factors for worse survival. The demographic and clinical features of patients with combined HCC-CC were similar to those of patients with HCC. The presence of cholangiocellular differentiation appeared to worsen the prognosis when compared with pure HCC, although this difference did not reach statistical significance. An increased CA19-9 level and intrahepatic bile duct dilatation in patients with HCC-CC were considered to be independent factors that suggested poor prognosis.

Routine Ultrasonography Compared With Maternal Serum Alpha-fetoprotein for Neural Tube Defect Screening

This study was done to estimate the value of prenatal maternal serum alpha-fetoprotein (MSAFP) screening compared with that of routine ultrasonography in the diagnosis of neural tube defects (NTDs). An integrated database was used retrospectively to identify cases of NTDs among 219,000 consecutive pregnancy outcomes observed during a 7-year period at 40 Kaiser Permanente facilities in Northern California. We specifically examined types of NTD and the tests used to diagnose cases. We identified 189 NTD cases, 102 of which had received MSAFP screening. Results of MSAFP testing were negative in 25 (25%) of these 102 cases. Without other testing, these 25 NTD diagnoses would have been missed. These included 15 (38%) of the 40 spina bifida cases screened, 6 (67%) of the 9 encephalocele cases screened, and 4 (8%) of the 53 anencephaly cases screened. Of the 186 NTD cases diagnosed prenatally, 115 (62%) were initially detected by routine ultrasonography administered during the second trimester without knowledge of MSAFP values; 69 (37%) were diagnosed by targeted ultrasonography after MSAFP screening indicated a higher risk for NTD; and 2 (1%) were diagnosed by pathology examination after miscarriage. Compared with MSAFP performed alone for screening, routine second-trimester ultrasonography was more likely to discover an NTD.