Elevated Serum Alpha-fetoprotein Research Articles

Hepatocellular carcinoma of diffuse type: MR imaging findings and clinical manifestations.

To assess MR imaging findings and clinical manifestations of diffuse-type hepatocellular carcinoma (HCC). We retrospectively reviewed our experience with diffuse HCC from November 1994 to October 2001. MR imaging findings and clinical features were assessed. Twenty-two consecutive patients with diffuse-type HCC (19 men and three women, age range 16-80 years [mean, 52 years]) were identified in a review of liver MR studies. This represented 13% of all patients with HCC imaged during this time period. Diffuse HCC showed a permeative, infiltrative pattern with ill-defined borders and no evidence of convex margination in all cases. At least 50% of the liver volume was involved with tumor. Diffuse-type HCC showed hypointensity in 15 patients, mixed intensity in three, and isointensity in four on T1-weighted images; heterogeneous hyperintensity in 16 patients; and homogeneous hyperintensity in six on T2-weighted MR images. Diffuse-type HCC showed patchy enhancement in 12 patients, miliary enhancement in nine, and minimal enhancement in one on postcontrast early-phase images, and showed heterogeneous wash-out in all patients on postcontrast late-phase images. Proximal portal venous tumor thrombosis was seen in all patients. Serum alpha-fetoprotein (AFP) value was elevated (>10 ng/mL) in 14 of 18 patients, and 13 showed a value greater than 500 ng/mL. The four patients who did not have elevated AFP had tumors which were indistinguishable from those in patients with elevated AFP; they also did not have a distinctive clinical history. Diffuse-type HCC was typically seen as an extensive, heterogeneous permeative hepatic tumor, with portal venous tumor thrombosis on MR images in all cases. Early enhancement, observed as patchy in 12 and miliary in nine of 22 patients, was a distinctive imaging feature. Elevated serum AFP value was a common finding; however, 22% had normal values.

Placental sonolucency and pregnancy outcome in women with elevated second trimester serum alpha-fetoprotein levels.

Women with unexplained elevation of serum alpha-fetoprotein (AFP) are at increased risk for adverse pregnancy outcomes, including small for gestational age neonate, preterm labor, abruptio placentae, preeclampsia, intrauterine fetal death, and congenital malformations. This study investigated the association between placental sonolucency, elevation of maternal serum AFP, and pregnancy outcomes. Singleton pregnancies (n = 168) with second trimester serum AFP level >/= 2.0 weight-adjusted multiples of the median (MoM) were recruited as the study group. Women with second trimester serum AFP level between 0.4 and 2.0 weight-adjusted MoM (n = 150) served as controls. A maternal Kleihauer-Betke stain was obtained for all participants. All participants were prospectively evaluated and the pregnancy complications were assessed by chart analysis after delivery. Compared with control subjects, women with placental sonolucent areas were not at increased risk for pregnancy complications, while women without sonolucent areas had higher risk of pregnancy complications. Singleton pregnancies with elevated serum AFP level had increased incidence of feto-maternal hemorrhage when placental sonolucency was observed. Our data suggest that feto-maternal hemorrhage may be the major factor contributing to elevated maternal serum AFP levels in pregnancies carrying placental sonolucencies. Screening for pregnancies with both elevated serum AFP and placental sonolucencies would help to identify the low-risk cases and facilitate cost-effective obstetric management.

Expression and prognostic role of tumor suppressor gene PTEN/MMAC1/TEP1 in hepatocellular carcinoma.

Inactivation of the tumor suppressor gene PTEN/MMAC1/TEP1, located on chromosome 10q23, is a common event in advanced stages of diverse human malignancies. However, the prognostic role of PTEN expression in patients with hepatocellular carcinoma (HCC) has not been characterized. One hundred five resected specimens were collected from patients with HCC. Expression levels of PTEN and p53 in clinical samples were analyzed by immunohistochemistry. Immunohistochemical analysis of 105 HCC tissue specimens revealed that decreased or absence of PTEN immunostaining was found in 43 specimens (40.9%). Reduced PTEN expression levels were correlated with increased tumor grade (P = 0.017), advanced disease stage (P = 0.016), and elevated serum alpha-fetoprotein (alphaFP) levels (P = 0.001). Kaplan-Meier analysis indicated that patients with reduced PTEN levels had shorter overall survival (P = 0.001) and higher recurrence rates (P = 0.0007) compared with patients who had intact PTEN expression. Examining p53 expression unveiled an inverse correlation between p53 overexpression and reduced PTEN expression in patients with HCC (P = 0.004). In addition, patients with p53 overexpression had shorter overall survival compared with patients who were without p53 overexpression (P = 0.0014). Univariate and multivariate analyses revealed that reduced PTEN expression was an independent prognostic factor for survival in patients with HCC. The current study demonstrated that reduced PTEN expression levels are involved in the pathogenesis of HCC. Moreover, decreased PTEN expression was correlated with tumor progression, high alphaFP levels, p53 overexpression, and poor prognosis in patients with HCC.

Prognostic Value of Preoperative Serum Alpha-Fetoprotein Level in Resectable Gastric Cancer

Purpose: Alpha-fetoprotein (AFP) is widely accepted as a useful tumor marker for diagnosis of hepatocellular carcinomas. On rare occasions, however, an abnormal elevation of serum AFP also has been reported in an adenocarcinoma of the gastrointestinal tract. We evaluated the influence of preoperative abnormal elevation of serum AFP (AFP positivity) on the prognosis of resectable gastric cancers. Materials and Methods: 812 gastric cancer patients, who were investigated for serum AFP before their operations and who underwent gastric resections with D2 or more extended lymph node dissection, were enrolled in the study. The survival rates were calculated by using the Kaplan-Meier method and were compared by using the log-rank test. A multivariate analysis was performed using the Cox proportional hazards model. Results: Fifty patients () were AFP positive (10.1. 4322.6 ng/ml). The survival rate of the AFP positive group was significantly lower than that of the AFP negative group ( ; P=0.0002). The depth of tumor invasion, the degree of regional lymph node metastasis, distant metastases, the TNM stage, the gross type, differentiation, the extent of gastric resection, and the curability of the surgery also significantly influenced survival. Multivariate analysis revealed that the depth of tumor invasion, the degree of regional lymph node metastasis, the curability of the surgery, and AFP positivity were independent prognostic indicators. Conclusion: Preoperative serum AFP can be used as an independent prognostic factor of resectable gastric cancer.

Combined hepatocellular-cholangiocarcinoma: a histopathologic, immunohistochemical, and in situ hybridization study.

Combined hepatocellular-cholangiocarcinoma (CHC) forms a small but significant proportion of primary liver carcinomas. However, its diagnostic features are not well established, and this has possibly contributed to the variability in its reported clinical outcome in the literature. Many such tumors with features intermediate between hepatocellular carcinoma and cholangiocarcinoma (CC) may have been considered CC in the past based on positivity for "biliary differentiation" cytokeratins and the lack of availability of highly sensitive and specific hepatocellular markers. The utility of in situ hybridization for albumin mRNA, a recently available sensitive and specific hepatocellular marker, has not been reported in CHC. We investigated 27 CHCs with regard to their histomorphologic spectrum and association of these morphologies with immunohistochemical staining for different cytokeratins (CK7, CK19, and CK20; AE1; Cam 5.2), epithelial membrane antigen, polyclonal carcinoembryonic antigen and alpha-fetoprotein, and in situ hybridization for albumin mRNA. All 27 tumors contained areas morphologically intermediate between hepatocellular carcinoma and CC (transitional-type tumors), and in each case such areas formed at least 25% of the tumor. Nine (33%) tumors showed areas with "antler-like" morphology, a feature not previously described in CHC. Twenty-two of 23 tumors (96%) showed positive signals on in situ hybridization for albumin mRNA. Positivity for both hepatocellular (albumin mRNA) and biliary (keratin immunohistochemical profile) markers confirmed the light microscopic impression of biphenotypic differentiation in these tumors. Immunohistochemical positivity for all cytokeratins (except CK7) and epithelial membrane antigen, as well as the expression of albumin mRNA by in situ hybridization, did not show significant differences between hepatocellular carcinoma and CC-like areas. Based on the cytokeratin profile and results on polyclonal carcinoembryonic antigen/alpha-fetoprotein alone, many such tumors would be classified as CC. However, the positivity for albumin mRNA by in situ hybridization proves that such an interpretation would not have been accurate. Clinically, CHCs showed many differences from pure hepatocellular carcinoma, including the absence of cirrhosis (0 of 27), rarity of serum hepatitis B or C marker positivity (4 of 27), and normal to only mildly elevated serum alpha-fetoprotein levels (median 187 ng/mL). The tumor followed an aggressive clinical course, with overall 3-and 5-year survival rates of 30% and 18%, and in the resected cases of 38% and 24%, respectively.

Placental abruption.

Placental abruption complicates approximately 1% to 2% of all pregnancies and remains a significant cause of both maternal and fetal morbidity. Proposed pathophysiology of both acute placental abruption and the more common partial placental separation are discussed. The contribution of placental abruption to both preterm labor and preterm premature rupture of membranes is discussed. Recent evidence supporting maternal hypertensive disorders, maternal tobacco and cocaine use, age and parity, multiple gestations, maternal thrombophilias, and an unexplained elevated maternal serum alphafetoprotein as risk factors for abruption is reviewed. Emergency management of acute abruption is outlined. Finally, particular emphasis is given to the management of partial placental separation, including both immediate and delayed delivery and the use of tocolysis. Obstetricians and Gynecologists, Family Physicians. After completion of this article, the reader will be able to define the condition of placental abruption, list the conditions associated with abruption, and outline potential management options for patients with placental abruption.

Clinical use of tumor markers in childhood malignancies

Tumor markers are developmentally regulated proteins or carbohydrate molecules, which are expressed in specific tissues in the fetus during certain developmental periods. With malignant transformation, these molecules are re-expressed in neoplastic tissues. Some developmental or metabolic disorders can also lead to the expression of tumor marker genes; hereditary tyrosinaemia and ataxia teleangiectasia associating with elevated serum alpha-fetoprotein are examples of such conditions. In pediatric malignancies, the most common markers in clinical use are alpha-fetoprotein in liver and yolk sac tumors, chorionic gonadotropin in germ cell tumors, and catecholamines and neuron specific enolase in neuroblastoma. Several other molecules including carbohydrate antigens CA 19-9 and CA 125 may also have a role in the diagnosis and follow-up of distinct types of childhood malignancies. The non-specificity of several markers, such as tissue polypeptide antigen and sialic acid, greatly hampers their clinical use. In this review we will discuss the biology and current knowledge on the use of serum and urine tumor markers. We also highlight the putative future use of these molecules in cancer diagnosis and therapy, including the use of monoclonal antibodies directed against these antigens.

Clinicopathologic Features of Gastric Cancers Producing Alpha-Fetoprotein

Background: Patients with gastric cancers producing alpha-fetoprotein (AFP) were reported to have a poor prognosis with high rates of liver metastasis. The purpose of the present study was to clarify the clinicopathological features of AFP-producing gastric cancers, in particular characteristics of liver metastasis, and to evaluate treatment of these cancers. Methods: In 27 of the 29 cases with elevated preoperative serum AFP levels among a total of 974 primary gastric cancers, AFP production was confirmed in gastric cancer cells by immunohistochemistry. These cases were included in the AFP-positive gastric cancer group (AFP(+), 2.7%). The remaining 945 cases with normal serum AFP levels were designated the AFP-negative gastric cancer group (AFP(–)). Results: There was a higher incidence of lymph node metastasis, a deeper invasion of the gastric wall, a higher frequency of advanced stage, a more marked lymphatic invasion and a higher rate of liver metastasis in the AFP(+) group than in the AFP(–) group. The patients received curative resection in AFP(+) group had a significantly worse survival rates in comparison to that in AFP(–) group. With respect to liver metastasis (n = 17) in AFP(+) group, of 3 cases who received curative hepatic resection, 1 patient survived more than 3 years, while the remaining 2 died in less than 3 years due to multiple liver recurrence. The patients (n = 5) who received palliative resection for liver metastasis followed by transarterial continuous infusion chemotherapy all died in less than 1 year. Conclusion: AFP-producing gastric cancers had aggressive behavior and their clinical or biological features were quite different from the common AFP-negative gastric cancers. Surgical resection of liver metastasis from AFP-producing gastric cancers was unsatisfactory. The development of a novel multimodal therapy against AFP-producing gastric cancers is needed.

Small cell undifferentiated histology in hepatoblastoma may be unfavorable.

Chemotherapy has improved the prognosis of hepatoblastoma demonstrably. It renders seemingly unresectable primary tumors amenable to surgery and can cure metastases. Some authors advocate preoperative chemotherapy for patients with tumors that are deemed resectable, relying solely on percutaneous biopsy or even on diagnostic imaging and elevated serum alpha-fetoprotein levels for diagnosis. However, certain cytologic features of hepatoblastoma appear to have important prognostic consequences. Well differentiated fetal hepatoblastomas that are confined to the liver and that have minimal mitotic activity may not require additional therapy if they are resected totally. In the current study 16 completely resected hepatoblastomas that exhibited partial or predominant small cell undifferentiated histology were identified retrospectively and correlated with patient outcome. Ten of 16 patients with completely resected tumors exhibiting small cell undifferentiated histology developed a disease recurrence. Five of these recurrences were fatal. Small cell undifferentiated histology may have an unfavorable effect on outcome in patients with completely resected hepatoblastoma. The focal distribution of small cell histology in the majority of these tumors suggests that treating hepatoblastoma based on limited preexcision biopsies may deprive some patients of appropriate therapy.

517 Elevated maternal serum alpha fetoprotein, but not maternal serum human chorionic gonadotropin is associated with preterm delivery

517 Elevated maternal serum alpha fetoprotein, but not maternal serum human chorionic gonadotropin is associated with preterm delivery

Factors associated with fetal demise in fetal echogenic bowel

Objective: The purpose of this study was to determine risk factors associated with intrauterine fetal demise in fetuses with unexplained echogenic bowel that is diagnosed in the second trimester. Study Design: A retrospective case-control study compared fetuses with echogenic bowel and fetal demise with fetuses with echogenic bowel who were live born. Fetuses affected with cystic fibrosis, aneuploidy, or congenital infection and fetuses diagnosed with major anomalies were excluded. Variables examined in the determination of risk factors for intrauterine fetal demise included intrauterine growth restriction, oligohydramnios, elevated maternal serum alpha-fetoprotein levels, and elevated maternal serum β-hCG levels. Statistical analysis was performed with the Fisher exact test, Student t test, and logistic regression analysis. Results: One hundred fifty-six fetuses met the inclusion criteria. There were 9 cases of intrauterine fetal demise and 147 live born control fetuses. The median gestational age of intrauterine fetal demise was 22.0 weeks (range, 17-39 weeks). Intrauterine growth restriction occurred more frequently in cases of intrauterine fetal demise than in live born infants (22.2% vs 0.7%; P =.009), as did oligohydramnios (44.4% vs 2.0%; P <.001) and elevated maternal serum alpha-fetoprotein levels (80.0% vs 7.7%; P: =.001). With the use of logistic regression analysis, elevated maternal serum alpha-fetoprotein was the strongest independent risk factor that was associated with intrauterine fetal demise (odds ratio, 39.48; 95% CI, 11.04%-141.25%). Conclusion: In our series, there was a 5.8% incidence of intrauterine fetal demise in fetuses with unexplained echogenic bowel. Elevated maternal serum alpha-fetoprotein is the strongest predictor of fetal demise in fetal echogenic bowel. (Am J Obstet Gynecol 2001;185:1039-43.)

Diagnostic difficulties before definitive treatment of an extragonadal retroperitoneal germ cell tumor

A primary extragonadal germ cell tumor of the retroperitoneum was diagnosed in a 47-year-old man without elevated serum alpha-fetoprotein, human chorionic gonadotropin, or lactate dehydrogenase levels. The diagnosis was made by histologic analysis after resection. The patient responded well to a combination of cisplatin, etoposide, and ifosfamide, achieving a partial response with four cycles. Residual tumor resection revealed necrotic tissue only. The patient was alive and disease free 24 months after diagnosis. The diagnostic difficulties of this particular situation are discussed.

Second-trimester maternal serum alpha-fetoprotein (MSAFP) is elevated in women with adverse pregnancy outcome associated with inherited thrombophilias.

Obstetric complications, such as severe pre-eclampsia, fetal growth restriction, abruptio placentae, or stillbirth are associated with abnormally elevated second-trimester maternal serum alpha-fetoprotein (MSAFP) and beta subunit of human chorionic gonadotrophin (betahCG). This has been attributed to placental abnormalities. Women with thrombophilias have been shown to have abnormalities of the placenta resulting in adverse pregnancy outcome in these patients. The purpose of the present study was to evaluate whether women with pregnancy complications and inherited thrombophilias have abnormally elevated second-trimester MSAFP or betahCG. Sixty-two women with pregnancy complications were tested for inherited thrombophilias several months after delivery. The thrombophilia group included 29 women with pregnancy complications and an inherited thrombophilia and the control group included 33 other patients without thrombophilia. Patients in the thrombophilia group had a higher median MoM MSAFP compared to the controls (1.337 vs. 1.086, p=0.0516). The incidence of abnormally elevated MSAFP (>2.5 MoM) was also significantly higher in the thrombophilia group compared to controls (21% vs. 3%, p=0.04). Neither the median MoM betahCG nor the incidence of abnormally elevated betahCG were significantly different between the groups. We conclude that second trimester MSAFP, but not betahCG, is abnormally elevated in patients with thrombophilia and obstetric complications.

Prognostic factors for survival in patients with compensated cirrhosis and small hepatocellular carcinoma after percutaneous ethanol injection therapy

The objective of this study was to identify clinical, biochemical, ultrasound, and/or pathologic parameters capable of predicting survival in a cohort of patients with well compensated cirrhosis and small hepatocellular carcinoma (HCC) who were treated with percutaneous ethanol injection (PEI). The study group included 111 patients with Child--Pugh Class A cirrhosis and with one (93 patients) or two (18 patients) HCC nodules measuring < 5 cm in greatest dimension. All patients underwent multisession PEI. The prognostic values of pretreatment and post-treatment variables were analyzed using the Kaplan-Meier method. The overall 3-year and 5-year survival rates of 62% and 41%, respectively, were not influenced by age, gender, duration of chronic hepatitis, serum albumin, prothrombin time ratio, total bilirubin, gamma-glutamyl transferase, hepatitis B surface antigen, antihepatitis C virus, HCC size, HCC ultrasound pattern, HCC histologic or cytologic grading, greatest spleen dimension, esophageal varices, or ascites. Levels of alpha-fetoprotein (AFP) > 14 ng/mL (P < 0.006), alanine aminotransferase > 75 IU/L (P < 0.04), and aspartate aminotransferase > 80 IU/L (P < 0.009) and platelet count < 92 x 10(9)/L (P < 0.02) before treatment were independent predictors of decreased survival. Among post-treatment parameters, AFP levels 6 months after PEI > 13.3 ng/mL (P < 0.003) and HCC recurrence in another segment of the liver (P < 0.04) were linked to decreased survival in univariate analysis. Among patients with Child--Pugh Class A cirrhosis with small uninodular or binodular HCC who are treated with multisession PEI, those with elevated serum AFP and transaminase levels and low platelet count before treatment are characterized by decreased survival. During follow-up, intrahepatic recurrence of the tumor is the main factor affecting survival.

Clinical, Virologic, and Pathologic Significance of Elevated Serum Alpha-fetoprotein Levels in Patients with Chronic Hepatitis C

Elevated serum alpha-fetoprotein (AFP) in patients with chronic hepatitis C is not uncommonly seen, but the pathogenesis of this phenomenon remains unclear. The aims of this study were to assess the prevalence of elevated serum AFP in patients with chronic hepatitis C and to evaluate the clinical, virologic, and histopathologic significance of this phenomenon. One hundred and fifteen Chinese patients with a histologic diagnosis of chronic hepatitis C were enrolled. None had evidence of hepatocellular carcinoma by image study at enrollment and for at least 2 years' follow-up. Of the 115 patients, 33 (29%) had elevated serum AFP (more than 12 ng/mL). There was a significantly lower mean serum albumin (4.0 +/- 0.1 vs. 4.3 +/- 0.1 gm/dL, p <0.001) and higher mean scores for periportal necroinflammation (3.3 +/- 0.3 vs. 2.3 +/- 0.2, p = 0.007) and fibrosis (2.3 +/- 0.2 vs. 1.1 +/- 0.1, p < 0.001) in patients with elevated serum AFP when compared with patients without elevated serum AFP. Patients with elevated serum AFP had significantly more incidences of genotype 1b infection when compared with patients without elevated serum AFP (77% vs. 51%, p = 0.021). Mean serum hepatitis C virus (HCV) RNA titer showed no significant difference between the two groups. Multivariate logistic regression analysis showed that as serum albumin of less than 4.2 gm/dL, a histology fibrotic score of more than 3, and HCV genotype 1b infection were significantly independent predictors associated with elevated serum AFP. In conclusion, elevated serum AFP levels were significantly correlated with lower serum albumin levels, advanced fibrosis/cirrhosis, and genotype 1b infection in patients with chronic hepatitis C.

Importance of achieving complete necrosis during the first treatment for hepatocellular carcinoma to prevent bone metastasis: a prospective study.

Recent advances in the treatment of hepatocellular carcinoma (HCC) have changed the importance of bone metastasis during the follow up of such patients. In the present study, we investigated risk factors for bone metastasis after treatment for HCC. Two hundred and two patients with HCC were diagnosed as free of bone metastasis by technecium 99m-methylene diphosphonate bone scintigraphy and were followed prospectively after treatment of the primary lesions (follow-up period 2-146 months; median 20 months). We statistically analyzed the risk factors for bone metastasis using the clinical characteristics at the time of first treatment. Multiple tumors (P < 0.005), main tumor size > 5 cm in diameter (P < 0.005), the presence of distant metastasis (P < 0.005), elevation of serum alpha-fetoprotein (> 100 ng/mL; P < 0.05), chemotherapy (P < 0.05) and insufficient therapeutic response (P < 0.0005) were identified as risk factors for bone metastasis by univariate analyses. Insufficient therapeutic response and main tumor size > 5 cm in diameter (both P < 0.05) were identified as independent predisposing factors for bone metastasis. Complete necrosis of primary HCC during the first treatment is important to prevent subsequent bone metastasis.

Clinical significance of elevated alpha-fetoprotein in adults and children.

The aim of the current study is to identify underlying pathology associated with elevated serum alpha-fetoprotein (AFP; >20 ng/ml) among patients referred to a tertiary-care academic medical center with emphasis in liver diseases, hepatobiliary surgery, and liver transplantation. From May 1992 to April 1997, 386 patients (320 adults and 66 children) with elevated AFP (>20 ng/ml) were identified from the Medical Archival System (MARS) database at the University of Pittsburgh Medical Center. The medical records from all these patients were retrospectively reviewed. Radiological, pathological, and biochemical profiles were obtained at the time of documented elevated AFP. These patients included: 218 adults with malignancies, 102 adults without malignancies, 18 children and infants with malignancies, and 48 children and infants without malignancies. Thirty-two percent of adults were found to have raised AFP with liver disease and without hepatocellular carcinoma and 78% had some type of malignancy, predominantly hepatocellular carcinoma. Seventy-three percent of infants and children had elevated AFP without malignancy. Based on our findings, we recommend that all patients (adults, infants and children) with raised AFP of >20 ng/ml should undergo thorough evaluation to rule out malignant disease.

TREATMENT OF ALPHA-FETOPROTEIN SECRETING HEPATOBLASTOMA BY RESPONSE OF SERUM ALPHA-FETOPROTEIN LEVELS: A New Concept

Hepatoblastoma, thecommonest primary malignant livertumorin infants and children, is usually associated with elevated serum alpha-fetoprotein (AFP) levels. The authors sought to determine if AFP levels can be used to modify treatment, thereby avoiding the wait for formal imaging studies and prolonged suboptimal treatment and limiting the use of effective but toxic chemotherapy. From April 1984 to December 1997, 8 children were diagnosed with AFP-secreting hepatoblastoma. Serum AFP levels were measured weekly. If AFP levels failed to improve, or increased on at least 2 successive examinations, the chemotherapy protocol was changed. When an excellent response was achieved, less toxic chemotherapy was substituted. Six patients (75%) were disease-free for at least 2 years, some with high-risk or metastatic disease. Two patients died. Six of the 7 nonmetastatic patients (86%) remain disease-free (only one had a resectable tumor). Chemotherapy changes resulted in reduced AFP levels in 7 patients. This study supports the use of AFP monitoring to modify treatment in hepatoblastoma responding to therapy with less toxic drugs and the use of nonstandard therapy when suboptimal responses are obtained.

Congenital nephrotic syndrome.

Congenital nephrotic syndrome (CNS) is a rare disorder that presents within 3 months of birth. It is characterized by massive proteinuria, edema,hypoalbuminemia, hyperlipidemia,hypogammaglobulinemia, and hypercoaguability. Without meticulous medical care and eventual renal transplantation, affected infants generally die by 6 months of age.CNS can have primary and secondary etiologies. The most common is CNS of the Finnish type. As a primary etiology, its cause remains unknown. Less common primary etiologies include diffuse mesangial sclerosis, minimal change nephrotic syndrome, and focal segmental glomerulosclerosis. Secondary CNS consists of known etiologies for which specific therapy is aimed at the underlying disease. These include infections, such as syphilis,toxoplasmosis, cytomegalovirus, hepatitis, and human immunodeficiency virus. Other secondary causes are mercury intoxication, genetic malformation syndromes such as XY gonadal dysgenesis, and systemic illnesses such as systemic lupus erythematosus and amyloidosis.Congenital nephrotic syndrome in Finland (CNF) constitutes the majority of CNS cases in the world. Infants who have idiopathic CNS in other parts of the world follow a similar course as infants who have CNF. Those who have CNF are born preterm, are small for gestational age, and have large placentas that comprise more than 25% of the birthweight. Affected infants develop proteinuria prenatally, and most exhibit edema within the first week of life. Distinctive physical features include wide cranial sutures, large open fontanelles, small nose, wide-set eyes,low-set ears, and umbilical hernia. In general, they feed and grow poorly because of substantial loss of proteins, effects of edema, and increased incidence of pyloric stenosis and reflux. They require early diagnosis and aggressive medical and surgical intervention.Diagnosis can be initiated prenatally. Elevated maternal serum and amniotic fluid alpha-fetoprotein (AFP)levels during the 15th to 20th weeks of gestation may identify those at risk,particularly in families that have a prior history. Because an elevated AFP level is nonspecific and can indicate many other obstetric complications,ultrasonography is helpful. Genetic analysis provides a definitive diagnosis. CNF has been linked to a defect in chromosome 19q13.1 and more specifically, to the“nephrin” gene. The product of this gene is a protein associated with the function of the glomerular filtration barrier. Mutations cause CNF and may be implicated in other diseases that involve proteinuria. Genetic analysis also differentiates patients who are carriers from those who ultimately develop CNF.Treatment for infants who have CNF focuses on reaching an ideal weight and nutritional status for renal transplantation, the only cure for the condition. Medical management includes providing a high-calorie and high-protein diet, vitamin supplementation,albumin administration, and diuretic therapy. Attention is directed at preventing and treating infections and thromboembolic events for which these infants are at high risk. Patients eventually need bilateral nephrectomy combined with peritoneal dialysis for ultimate renal transplantation. CNF does not recur following renal transplantation, and catch-up growth and normalization of development can be achieved.Infants in whom CNS is not treated have a complex and bleak clinical course. In vitro genetic analysis offers new hope for recognition and early intervention. Further, improvements in medical care and solid organ transplantation extend the hope for cure and normalization of growth and development. For some patients, CNS is no longer a fatal disease.Inheritance of this rare disorder usually is autosomal recessive,but sporadic cases have been found. Localization of the nephrin gene and association of CNF with mutations have allowed for improved prenatal diagnosis and medical intervention.

Small cell undifferentiated histology in hepatoblastoma may be unfavorable

Chemotherapy has improved the prognosis of hepatoblastoma demonstrably. It renders seemingly unresectable primary tumors amenable to surgery and can cure metastases. Some authors advocate preoperative chemotherapy for patients with tumors that are deemed resectable, relying solely on percutaneous biopsy or even on diagnostic imaging and elevated serum alpha-fetoprotein levels for diagnosis. However, certain cytologic features of hepatoblastoma appear to have important prognostic consequences. Well differentiated fetal hepatoblastomas that are confined to the liver and that have minimal mitotic activity may not require additional therapy if they are resected totally.In the current study 16 completely resected hepatoblastomas that exhibited partial or predominant small cell undifferentiated histology were identified retrospectively and correlated with patient outcome.Ten of 16 patients with completely resected tumors exhibiting small cell undifferentiated histology developed a disease recurrence. Five of these recurrences were fatal.Small cell undifferentiated histology may have an unfavorable effect on outcome in patients with completely resected hepatoblastoma. The focal distribution of small cell histology in the majority of these tumors suggests that treating hepatoblastoma based on limited preexcision biopsies may deprive some patients of appropriate therapy.