Serum Alfa-fetoprotein Level Research Articles

Review on " Hepatocellular carcinoma"

Hepatocellular carcinoma is a problem for the world's Hepatocellular carcinoma, metabolic syndrome, stage of liver cancer local disease, liver cirrhosis, treatment. syndrome or diabetes mellitus is increasingly common in the west. Furthermore, HCC with non-alcoholic steatohepatitis-associated molecular pathogensis is distinct. A quarter of all HCCs have potentially treatable mutations that have not yet been applied in clinical settings. When clinical deterioration occurs, HCC is frequently detected, and survival is then assessed as a risk factor. utilizing alfa-fetoprotein (AFP), a serum maker, frequently in conjunction with ultrasound. The accuracy of monitoring is currently being improved by testing a number of other serologic indicators. More advanced imaging techniques, such CT scan and MRI, which have multiphasic contract enhancing capabilities, are frequently needed for the diagnosis of HCC. When serum AFP levels are significantly increased, which happens in less than half of cases at the time of diagnosis, it can be useful to use serum AFP alone. When the diagnosis of HCC is still undetermined, a liver biopsy might be used to confirm the diagnosis. The present requirement for molecular information, which necessitates tissue or liquid biopsies, challenges diagnosis based on non-invasive criteria. The management of patients with advanced HCC has been altered by recent significant developments. Checkpoint inhibitors, tyrosine, and even combinations of two immunotherapy treatments are among the combination medicines that new trials are investigating. The results of these trials are anticipated to alter the HCC management environment at all evolutionary stages.

Maternal Serum Alpha Feto Protein Level May Predict Morbidly Adherent Placenta in Women with Placenta Previa

Background: In situations of a morbidly adherent placenta, studies have shown that maternal serum alfa feto protein (AFP) is clinically high. Objective: To examine the association of morbidly adherent placenta (MAP) in pregnant women with placenta previa (PP) and their serum AFP biomarker. Methods: A prospective observational study that was conducted in the Department of Obstetrics and Gynecology at Azadi Teaching Hospital, Kirkuk, Iraq during the period from Feb. till Nov. 2019. It included 82 pregnant women those between 14-20 weeks of gestation with singleton pregnancy, viable fetus, and diagnosed with low lying placenta, with and without vaginal bleeding. A blood sample from all women was taken to investigate for serum AFP level after confirming the diagnosis of low-lying placenta by early abdominal ultrasound (U/S) scan. All the enrolled pregnant women were followed by Doppler U/S at gestational age 28-32 weeks, underwent targeted screening for MAP and were divided into two groups according to the status of placenta: MAP group included 11 pregnant women and PP group alone included 71 pregnant women. Results: In this study, MAP was diagnosed in 13.4% of cases. Mean of serum AFP biomarker in women with MAP was significantly higher than that in women with PP. Serum AFP biomarker in early pregnancy >200 ng/ml is predictive for diagnosis of MAP in late pregnancy. Conclusion: Maternal serum AFP biomarker may play an important role at early pregnancy in prediction of placental adherence at late pregnancy in cases of early low-lying placenta. Keywords: Morbidly adherent placenta, alpha feto protein, previa, pregnancy, Iraq Citation: Hassan SS, Ghalib AK. Maternal serum alpha feto protein level may predict morbidly adherent placenta in women with placenta previa. Iraqi JMS. 2022; 20(2): 278-285. doi: 10.22578/IJMS.20.2.16

High serum alpha-fetoprotein levels in primary infertile men.

Alfa-fetoprotein (AFP) is a serum glycoprotein highly produced during fetal development. While AFP synthesis drops dramatically after birth, AFP production only persists or returns under specific pathological condition. We sought to investigate the rate of and the potential meaning of high AFP serum levels in men seeking first medical attention for couple's primary infertility. Socio-demographic and clinical data from 1803 non-Finnish, White-European primary infertile men were retrospectively analysed. AFP was routinely measured in each patient (high AFP was defined as>7ng/ml). Men with history of liver diseases, testicular cancer, or other known causes of increased AFP levels were excluded from the final analysis. Semen analyses were based on the 2010 World Health Organization reference criteria. Descriptive statistics and logistic regression models tested the association between serum AFP and clinical variables. Possible nonlinear relationships were graphically explored with locally estimated scatterplot smoothing method. Overall, high serum AFP level was found in 29 (1.7%) patients. Normal versus high AFP levels patients were comparable in terms of body mass index (BMI), Charlson Comorbidity Index, waist circumference, smoking habits, history of cryptorchidism, testicular volume, and serum hormones (i.e., follicle-stimulating hormone, luteinizing hormone, and total testosterone). Conversely, men with higher AFP levels were older (p=0.02), had lower sperm concentration (p=0.003), and were more frequently oligozoospermic and azoospermic (all p≤0.03). At multivariate analysis, high AFP levels were independently associated with oligozoospermia (OR 3.79; p=0.033) and azoospermia (OR 3.29; p=0.006). Likewise, if AFP levels increase, patients were found to be older, with higher BMI and to have more comorbidities (all p<0.05). Unexplained high AFP levels account for almost 2% of cases in primary infertile patients without a previous history of associated disorders. Higher serum AFP levels are linked with aberrant sperm counts, older age, obesity, and a greater amount of comorbid conditions. Despite the need for additional validation, these data suggest that serum AFP measurement might have a multifaceted role over the diagnostic work-up of males presenting for couple's infertility.

Significant response to atezolizumab plus bevacizumab treatment in unresectable hepatocellular carcinoma with major portal vein tumor thrombus: a case report

BackgroundHepatocellular carcinoma (HCC) with major portal vein tumor thrombus (Vp4 PVTT) is an extremely advanced tumor with limited treatment options. Systemic chemotherapy is the only recommended treatment option, and atezolizumab plus bevacizumab has recently emerged as a first-line treatment option.Case presentationWe describe the case of an 82-year-old man with unresectable advanced HCC with Vp4 PVTT who achieved a significant response to atezolizumab plus bevacizumab treatment. A single administration of atezolizumab plus bevacizumab ensured significant anti-tumor effects (regression in the tumor size and PVTT, portal vein recanalization, and serum alfa-fetoprotein levels decreased from 90,770 to 89 ng/mL). The patient continued with atezolizumab monotherapy, and after nine consecutive regimens, there was no apparent sign of residual tumor.ConclusionsThis case demonstrates the powerful anti-tumor effect of atezolizumab plus bevacizumab treatment for advanced HCC with Vp4 PVTT, suggesting that these agents can be a promising treatment option for such refractory tumors.

Correlation of Clinicopathological Profile, Prognostic Factors, and Survival Outcomes with Baseline Alfa-Fetoprotein Levels in Patients With Hepatocellular Carcinoma: A Biomarker that is Bruised but Not Broken

The role of Alfa-fetoprotein (AFP) in the management of hepatocellular carcinoma (HCC) is still debated, with differences in recommendations between international guidelines. We analyzed the relationship of the clinicopathological profile, prognostic features, and survival outcomes with baseline serum AFP levels in patients with HCC. Retrospective analysis of a prospectively accrued dataset of consecutive HCC patients was done. 508 treatment naive patients were included in the analysis. AFP at presentation was normal (<10ng/ml) in 18% patients. Patients with very high AFP (>400ng/ml) had poor hepatic reserves (higher mean serum bilirubin, AST, ALT, INR, and lower mean albumin) and advanced disease at presentation (higher incidence of extrahepatic metastasis, and less proportion of patients with well-differentiated tumors). AFP >400ng/ml was an independent predictor for presence of portal vein tumor thrombosis (PVTT) (OR, 4.08; 95% CI, 2.34-7.12; P<0.001), higher tumor size (OR, 2.19; 95% CI, 1.36-3.54, P= 0.001) and advanced BCLC stage (OR, 4.19; 95% CI, 2.51-7.03; P<0.001). Two-third of patients with small HCC (MTD <3cm) and more than half with early-stage HCC (BCLC stage 0/A) had elevated AFP levels. No significant relationship was seen between overall survival (OS) and baseline AFP in patients who underwent surgery, but median OS in patients subjected to nonsurgical therapies was 19.4,10.5 and 5.7 months in patients having AFP <10ng/ml, 10-400ng/ml and >400ng/ml respectively (P= 0.003). AFP >400ng/ml was an independent predictor of survival in patients receiving any form of therapy (HR=2.23; 95% CI=1.19-4.18, P= 0.012). AFP as a biomarker still has a significant role to play in the management of HCC patients and is here to stay till the search for an ideal biomarker in HCC is over.

Alpha-fetoprotein level to total tumor volume as a predictor of hepatocellular carcinoma recurrence after resection. A retrospective cohort study

BackgroundTotal tumor volume (TTV) and serum alfa fetoprotein (AFP) level are important risk factors linked with the high possibility of hepatocellular carcinoma (HCC) recurrence. The aim of the study was to evaluate the role of AFP/TTV ratio, as a prognostic marker, in the prediction of HCC recurrence after resection. MethodsPatients who underwent liver resection for HCC between 2010 and 2018 were retrospectively analyzed. Patients were divided into 2 groups; a group with AFP/TTV ≤2 and another group with AFP/TTV >2. Risk factors for HCC recurrence were recorded. ResultsA total of 286 HCC patients underwent liver resection (184 patients with AFP/TTV ≤ 2, and 102 patients with AFP/TTV > 2). There was a significant difference between the 2 groups in the preoperative total bilirubin level, serum AFP level, mean tumor diameter, TTV, operative blood loss, microvascular invasion and hospital stay (all P values < 0.05). The 1-, 3-, and 5-year tumor recurrence rates were 24.1%, 43%, and 57.6% respectively. The independent risk factors for tumor recurrence were AFP/TTV >2 (HR = 1.62, 95% CI = 1.29–1.98, P = 0.042), Macrovascular invasion (HR = 2.03, 95% CI = 2.17–2.38, P = 0.021, and microvascular invasion (HR = 1.36, 95% CI = 1.08–1.77, P = 0.019). ConclusionAFP/TTV ratio is a feasible prognostic marker for prediction of HCC recurrence after resection so, it can help in providing an intensive postoperative surveillance program to high risk patients for early detection and management of any recurrence.

Rehabilitation Approaches of a Bangladeshi Boy With Ataxia Telangectasia: A Case Report

Ataxia-Telangiectasia (AT) is a rare form of neurodegenerative disorder of hereditary origin. In Bangladesh we don’t have any epidemiological study. Till today there is no gold standard of the diagnosis, further to its wide clinical heterogeneity, it often leads physicians to an incorrect or missed diagnosis. So is the importance of the insight into this disease. We report a 10 years old male child who presented with history of difficulty in posture and walking associated with frequent fever, delayed slurred speech and abnormal eye movements. Physical examination revealed delayed milestones of development involving neck control, sitting, walking, unsteady supported swaying gait and speech language dysfunctions. MRI of brain showed cerebellar atrophy and a raised serum Alfafeto protein level. The child was diagnosed as a case of AT and was presented in a clinical meeting at Bangabandhu Sheikh Mujib Medical University for discussions and further managements including medical rehab. We offered him a course of combined rehabilitation therapy program and discharged home.&#x0D; JCMCTA 2019 ; 30 (1) : 64-67

Hepatocellular Carcinoma Surveillance: Benefit of Serum Alfa-fetoprotein in Real-world Practice.

IntroductionBetter treatment outcome of early-stage hepatocellular carcinoma (HCC) warrants employment of screening programs, in which ultrasonography (US) and serum alfa-fetoprotein (AFP) have been recommended. Considering cost-effectiveness, serum AFP has recently been withdrawn from several guidelines for HCC surveillance. However, there were limited studies on benefits of AFP for HCC surveillance in Thailand.Materials and methodsThis is a retrospective study of a proportion of HCC cases in which a diagnostic study was triggered by high serum AFP levels, but US failed to detect the lesion. Patients who received diagnostic imaging for HCC at Siriraj Hospital between January 1, 2012 and December 31, 2014 were included. All the patients must fulfill criteria for HCC surveillance according to American Association for the Study of Liver Diseases (AASLD) practice guidelines on the management of HCC 2010 or European Association for the Study of the Liver-European Organisation for Research and Treatment of Cancer (EASL-EORTC) Clinical Practice Guidelines: Management of HCC 2012. Previous diagnosis of any liver malignancy was excluded. Demographic data, underlying liver diseases, screening of AFP and US results, and definite diagnosis of HCC were recorded.ResultsOf the 452 cases who fulfilled inclusion and exclusion criteria, chronic hepatitis B, C, and alcoholic cirrhosis were accountable for 53.8, 25.9, and 7.3% respectively. Totally, 150 cases were diagnosed with HCC. Additional HCC detection rate by high serum AFP but failed US of 15.3% was demonstrated. Subgroup analysis revealed significant benefit of AFP in cirrhotic patients with chronic hepatitis B and C (p-value 0.004 and 0.002). No significant benefit was observed in cirrhosis of other causes and in noncirrhotic chronic hepatitis B.ConclusionWe reported a 15.3% additional benefit of serum AFP for HCC surveillance in conjunction with US of liver. Chronic hepatitis B and C with cirrhosis significantly derived the benefit from serum AFP screening.How to cite this article: Lersritwimanmaen P, Nimanong S. Hepatocellular Carcinoma Surveillance: Benefit of Serum Alfa-fetoprotein in Real-world Practice. Euroasian J Hepato-Gastroenterol 2018;8(1):83-87.

Liver transplant for hepatocellular carcinoma associated with very high serum alfa-fetoprotein

Objective: Selection of patients with hepatocellular carcinoma (HCC) for liver transplant is still debatable, Milan criteria remain the gold standard. However, some centers consider biological behavior of HCC, as reflected by serum Alfa-fetoprotein (AFP), in patient selection. AFP higher than 400 IU/mL was considered as an exclusion criterion. Here, we present a case of HCC associated with very high levels of AFP that had loco-regional treatment followed by liver transplant with no tumor recurrence 24 months post-transplant. Methods: Results: This is a case of a 55-year-old male who had end-stage liver disease due to Hepatitis C Virus (HCV) infection since 2008, and was treated with ribavirin and interferon. He was diagnosed with HCC lesion 2.6 cm in the maximal diameter in April 2014. AFP was 341 IU/mL that jumped to 2599 IU/mL. He underwent transarterial chemoembolization that showed a dramatic drop of AFP down to 21 IU/mL after six weeks. The patient was listed for liver transplant as HCC was within Milan criteria. He underwent liver transplant in September 2014 when AFP was 9 IU/mL. He had an uneventful liver transplant with uncomplicated post-operative course and was discharged in a good condition on the twelfth post-operative day. Serial follow-up of the patient with dynamic magnetic resonance imaging and serum AFP for 24 months post-transplant showed no recurrence of HCC with normal levels of AFP. Conclusion: Exclusion of patients based on their initial serum Alfa-fetoprotein levels at time of diagnosis of HCC could preclude patients with potentially favorable outcome.

Comparative study of tumor markers in patients with colorectal carcinoma before and after chemotherapy.

Colorectal carcinoma (CRC), the second leading cause of cancer-related deaths in US, has a rising time-trend in India. Tumour markers in CRC are extensively researched, and there's still debate on their diagnostic and prognostic values. In this hospital-based longitudinal study in north India, 51 male diagnosed CRC cases (pre-chemotherapy) were contrasted against 50 age and sex matched controls. Nine biomarkers: carcinoembryonic antigen (CEA), prolactin (PRL), alfa feto protein (AFP), total human chorionic gonadotropin (hCG), cancer antigen-125 (CA-125), serum testosterone, prostate specific antigen (PSA) and ferritin were measured by direct chemiluminescence technique. Further, follow-up was done on 47 cases after treatment with six cycles of 5-flurouracil (5-FU) and oxaliplatin. Mean serum CEA (case: 5.94±8.27 ng/mL, control: 2.5±0.79 ng/mL, P<0.05), PRL (case: 28.12±13.39 ng/mL, control: 14.24±13.13 ng/mL, P<0.0001), AFP (case: 10.9±6.65 ng/mL, control: 4.02±1.26 ng/mL, P<0.0001) levels were significantly raised in CRC cases compared to controls. On the contrary, mean testosterone level (P<0.05) was lower among the cases. After chemotherapy, the mean serum CEA (P<0.05), AFP (P<0.0001) and CA-125 (P<0.05) levels among the cases decreased significantly compared to their pretreatment levels. The present study strongly indicates the role of CEA, PRL, AFP, CA-125 and testosterone as important biomarkers in male CRC patients from north India. Further, AFP, CA-125 and CEA may be used to assess the effectiveness of chemotherapy in such patients.

Microvascular invasion (MVI) is a poorer prognostic predictor for small hepatocellular carcinoma

BackgroundSmall hepatocellular carcinoma (SHCC) is a special type of hepatocellular carcinoma with the maximum tumor diameter ≤ 3 cm and excellent long-term outcomes. However, the prognostic factors for SHCC remain controversial. The purpose of this study is to clarify the predictive factors of SHCC.MethodsThe study population consisted of 458 patients underwent hepatectomy for single SHCC between January 2006 and December 2008. Clinical data (included age, gender, virus infection, serum alfa-fetoprotein level, cirrhosis, capsule, border), histopathologic features (included differentiation, morphology subtype, microvascular invasion, tumor infiltrative lymphocytes (TIL), inflammatory injury grade and fibrosis stage of surrounding liver), were evaluated to identify prognostic factors influencing SHCC patients’ survival and microvascular invasion.ResultsThere were 384 males (83.8%) and 74 (16.2%) females with median ages of 52 years. The median progression-free survival (PFS) and overall survival (OS) durations were 53 and 54 months, respectively. About 91.9% (n = 421) SHCC were infected by Hepatitis B. One hundred forty-seven of the 446 (33.0%) patients with pre-operation serum AFP level record had serum alfa-fetoprotein (AFP) level ≥ 200 ug/ml and 178 of the 280 (63.8%) patients with post-operation serum AFP level record had AFP level ≥ 20 ug/ml. Liver cirrhosis was present in 411 cases (89.7%), while 434 (97.3%) tumors had clear border, and 250 (55.6%) tumors were encapsulated.MVI was identified in 83 patients (18.1%). In univariate analysis, a significant association between the presence of MVI and shortened PFS and OS was found (p = 0.012, 0.028, respectively). Histological differentiation had strong relationship with MVI (p = 0.009), in terms of MVI was more easily presented in patients with worse histological differentiation. In patients with MVI, worse survival was correlated with female patients, patients with G2 or G3 histological differentiation, pre-operation serum AFP level ≥ 200 ug/ml or post-operation serum AFP level ≥ 20 ug/ml, and TIL ≥ 50/HPF.ConclusionsMVI is an independent poorer prognostic factor for PFS and OS of single SHCC patients. Tumor histological differentiation was closely related with MVI.

A Re-Emerging Marker for Prognosis in Hepatocellular Carcinoma: The Add-Value of FISHing c-myc Gene for Early Relapse

Hepatocellular carcinoma is one leading cause of cancer-related death and surgical resection is still one of the major curative therapies. Recently, there has been a major effort to find mechanisms involved in carcinogenesis and early relapse. c-myc gene abnormality is found in hepatocarcinogenesis. Our aim was to analyze the role of c-myc as prognostic factor in terms of overall survival and disease-free survival and to investigate if c-myc may be an important target for therapy. We studied sixty-five hepatocellular carcinomas submitted to surgical resection with curative intent. Size, macro-microvascular invasion, necrosis, number of nodules, grading and serum alfa-fetoprotein level were registered for all cases. We evaluated the c-myc aberrations by using break-apart FISH probes. Probes specific for the centromeric part of chromosome 8 and for the locus specific c-myc gene (8q24) were used to assess disomy, gains of chromosomes (polysomy due to polyploidy) and amplification. c-myc gene amplification was scored as 8q24/CEP8 > 2. Statistical analysis for disease-free survival and overall survival were performed. At molecular level, c-myc was amplified in 19% of hepatocellular carcinoma, whereas showed gains in 55% and set wild in 26% of cases. The 1- and 3-year disease-free survival and overall survival for disomic, polysomic and amplified groups were significantly different (p=0.020 and p=.018 respectively). Multivariate analysis verified that the AFP and c-myc status (amplified vs. not amplified) were significant prognostic factors for overall patients survival. c-myc gene amplification is significantly correlated with disease-free survival and overall survival in patients with hepatocellular carcinoma after surgical resection and this model identifies patients with risk of early relapse (≤12 months). We suggest that c-myc assessment may be introduced in the clinical practice for improving prognostication (high and low risk of relapse) routinely and may have be proposed as biomarker of efficacy to anti-c-myc targeted drugs in clinical trials.

A precocious cerebellar ataxia and frequent Fever episodes in a 16-month-old infant revealing ataxia-telangiectasia syndrome.

Ataxia-telangiectasia (AT) is the most frequent progressive cerebellar ataxia in infancy and childhood. Immunodeficiency which includes both cellular and humoral arms has variable severity. Since the clinical presentation is extremely variable, a high clinical suspicion will allow an early diagnosis. Serum alpha-fetoprotein is elevated in 80–85% of patients and therefore could be used as a screening tool. Here, we present a case of a 5-year-old female infant who was admitted to our department at the age of 16 months because of gait disorders and febrile episodes that had begun at 5 months after the cessation of breastfeeding. Serum alfa-fetoprotein level was elevated. Other investigations showed leukocytopenia with lymphopenia, reduced IgG2 and IgA levels, and low titers of specific postimmunization antibodies against tetanus toxoid and Haemophilus B polysaccharide. Peripheral lymphocytes subsets showed reduction of T cells with a marked predominance of T cells with a memory phenotype and a corresponding reduction of naïve T cells; NK cells were very increased (41%) with normal activity. The characterization of the ATM gene mutations revealed 2 specific mutations (c.5692C > T/c.7630-2A > C) compatible with AT diagnosis. It was concluded that AT syndrome should be considered in children with precocious signs of cerebellar ataxia and recurrent fever episodes.

Recurrent hepatocellular carcinoma after liver transplantation - an emerging clinical challenge

In western countries, hepatocellular carcinoma (HCC) is a major reason for orthotopic liver transplantation (OLT) with estimated recurrence rates between 15% and 20%. This selective literature review addresses follow-up care after OLT in HCC and current treatment options. Recurrence prediction is based on pathological tumor stage, vascular invasion, serum alfafetoprotein levels, and histological differentiation, but further advances are expected by molecular profiling techniques. Lower levels of immunosuppressive agents are associated with a lower risk for HCC recurrence. Retrospective studies indicate that mammalian target of rapamycin (mTOR) inhibitors as immunosuppression reduce the risk of HCC recurrence. However, prospective studies supporting this potential advantage of mTOR inhibitors are still lacking, and higher rejection rates were reported for sirolimus after OLT in HCC. Prognosis is poor in recurrent HCC, a longer interval between OLT and recurrence and feasibility of surgical resection are associated with improved survival. Systemic treatment with sorafenib is the current standard of care in patients with advanced-stage HCC not suitable for locoregional therapy. After OLT, combination of an mTOR inhibitor with sorafenib is feasible and frequently used in clinical practice. As safety and efficacy data are still limited, close clinical monitoring is mandatory.

Evaluation of Risk Factors and Clinicopathologic Features for Intrahepatic Cholangiocarcinoma in Southern China: A Possible Role of Hepatitis B Virus

Recent efforts suggest an etiologic role of hepatitis B virus (HBV) infection in intrahepatic cholangiocarcinoma (ICC) and the involvement of hepatic progenitor cell in ICC development, without definitive conclusions. This case-control study was undertaken to investigate risk factors for ICC, and clinicopathological features of HBV-associated ICC were analyzed. The report comprised 98 patients with pathologically confirmed ICC and 196 healthy control subjects. Logistic regression was used to determine odds ratios and 95% confidence intervals. The sex and age distributions of HBV-related and unrelated ICC patients were compared respectively with those of 882 HBV-associated hepatocellular carcinoma patients from a random selection, and the clinicopathological data of 62 ICC patients with or without HBV infection undergoing surgical resection were compared. There was an association between ICC and each of HBV infection, liver cirrhosis, hepatolithiasis, and liver fluke infestation with the odds ratios (95% confidence intervals) of 2.75 (1.27-5.95), 8.42 (2.50-28.37), 22.81 (7.16-72.68), and 3.55 (1.60-7.89), respectively, with a marked synergism of cirrhosis and HBV infection (20.67; 5.40-79.06). Compared with HBV-unrelated ICC patients, HBV-related ICC patients were more common in male and younger subjects, had a higher incidence of abnormal serum alfa-fetoprotein level, cirrhosis, and neutrophilic infiltration, and had a lower proportion of elevated carbohydrate antigen 19-9 (CA19-9) values. The independent association of HBV infection with ICC, synergy between cirrhosis and HBV infection, and some clinicopathological similarities between HBV-related ICC and hepatocellular carcinoma suggests that both may share similar or common tumorigenic process and may possibly originate from malignant transformation of hepatic progenitor cell.

Effect of anti-epileptic drugs in pregnancy and teratogenesis.

Epilepsy raises special concern in women during pregnancy. Antiepileptic drugs are known to induce major and minor malformations in the foetus. Aim of the study was to find an association between maternal serum alpha fetoprotein levels, foetal abnormalities and antiepileptic drugs mediated teratogenicity. Maternal serum alpha feto protein levels, kidney and liver function tests in age matched normal pregnant women and seizure free epileptic pregnant women during 12-14 weeks of gestation were estimated. Cases were subjected to ultrasonography at 11(th)-14(th) week of pregnancy and again at 20(th) week of pregnancy. maternal serum alfa feto protein was assayed by a specific Electro Chemiluminescence Immuno Assay test. There was no significant difference in kidney and liver function tests in cases as compared to controls. There were elevated levels of alpha feto protein in cases as compared to controls but this was not statistically significant. No anomalies were detected in ultrasound reports. Most women had normal full term delivery with healthy children but of low birth weight. No correlation was seen between maternal serum alfa feto protein levels and antiepileptic drug leading to teratogenesis.

Polyembryoma of Testis

Polyembryoma is a rare neoplasm composed exclusively of embryoid bodies arranged in a pattern resembling the presomite embryo prior to day 18 of development. Patients who present with these tumors often have substantially elevated serum alpha-fetoprotein levels. Furthermore, these neoplasms exhibit the same malignant behavior as other non-seminomatous germ cell tumors. We report a case of polyembryoma of testis in a 38-year-old man who presented with a 2-month history of right-sided scrotal enlargement. Primary clinical examination revealed a solid, markedly enlarged right testis and an elevated serum alfafetoprotein level (247.1 mg/mL). The patient underwent a radical orchiectomy of the right testis and received 3 cycles of chemotherapy after the operation. The patient was well at 4-year follow-up.

Changing disease burden of hepatocellular carcinoma in the Far East and Southeast Asia

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world, and has a marked difference in geographic distribution. More than 80% of HCC cases occur in developing countries, especially the Far East and Southeast Asia. Although immunization has been successful against hepatitis B virus (HBV), a changing disease burden of HCC has been observed in many parts of the world because of the increasing prevalence and duration of hepatitis C virus (HCV) infection in these countries. In addition, the age-specific incidence of HCC has progressively shifted toward younger people. Hepatitis B genotypes B and C are prevalent in the Far East and Southeast Asia, and the clinical relevance of HBV genotypes has become increasingly recognized. Compared with genotype C, genotype B is associated with earlier hepatitis B e antigen seroconversion, slower progression to cirrhosis and less frequent development of HCC. By using periodic examinations of serum alfa-fetoprotein levels and abdominal ultrasonography, small HCC can be detected and treated earlier. However, prevention of HBV and HCV infections as well as effective treatment of the chronic viral infections with timely interventions are still needed for the global control of HCC, particularly in the Far East and Southeast Asia.

Cases from the Osler Medical Service at Johns Hopkins University

Presenting features A 66-year-old man with a history of alcohol-induced cirrhosis was admitted to the Johns Hopkins Hospital with the chief complaints of jaundice and lower extremity swelling. Three weeks before admission, he first noticed gradually worsening jaundice and leg swelling, as well as abdominal distension, fatigue, and anorexia. He denied nausea, vomiting, fevers, night sweats, diarrhea, abdominal pain, hematemesis, hematochezia, and melena. His past medical history was remarkable only for the diagnosis of cirrhosis 8 years before admission, when he had presented with a bleeding esophageal varix. At that time, he decided to abstain from alcohol permanently but to continue smoking cigarettes. His medications at the time of the current admission included spironolactone, megestrol acetate, furosemide, propranolol, pantoprazole, and metoclopramide. On physical examination, he appeared markedly jaundiced and fatigued. He had both scleral and sublingual icterus as well as multiple facial telangiectasias and a right epicanthal xanthoma. His heart and lung examinations were unremarkable. His abdomen was distended but soft and nontender with no organomegaly. He had a palpable fluid wave, shifting dullness, and caput medusae, but no spider angiomata or gynecomastia. His lower extremities showed 2+ pitting edema extending to the lower abdomen. There was no palmar erythema, asterixis, or evidence of hepatic encephalopathy. Initial laboratory studies revealed the following: serum sodium, 130 mEq/L; chloride, 93 mEq/L; ammonia, 97.1 μg/dL; aspartate aminotransferase, 250 U/L; alanine aminotransferase, 102 U/L; alkaline phosphatase, 672 U/L; albumin, 2.8 g/dL; and total bilirubin, 23.6 mg/dL, with a direct fraction of 17.2 mg/dL. The hematocrit was 36.4% with a normal mean corpuscular volume and normal coagulation times. Paracentesis revealed transudative fluid with 303 white blood cells (67% neutrophils), a lactate dehydrogenase level of 93 U/L, a total protein level of 1.4 g/dL, and an albumin level of 0.7 g/dL (serum ascites to albumin gradient, 2.1 g/dL). Hepatitis serologies were negative and the serum alfa-fetoprotein level was 52 ng/mL. A right upper quadrant ultrasound showed ascites around a shrunken, nodular liver with a coarse, heterogeneous echo texture, as well as echogenic material in the region of the portal vein with no portal blood flow. A computed tomographic (CT) scan of the abdomen with three-dimensional reconstruction following the administration of intravenous contrast material (Figures 1 and 2) revealed innumerable indeterminate hypodense lesions measuring 1 cm or less scattered diffusely throughout the liver. In addition, the portal vein was markedly dilated with evidence of thrombus extending both intrahepatically and extrahepatically to the portal confluence. What is the diagnosis?

Soluble interleukin-2 receptor levels in hepatocellular cancer: a more sensitive marker than alfa fetoprotein.

Worldwide, the majority of cases of hepatocellular cancer (HCC) arise in individuals with chronic hepatitis B or C virus infections. Early detection of HCC in these patients provides the best chance for curative treatment, but serum alfa fetoprotein (AFP) levels are frequently normal in patients with small HCCs. The purpose of this study was to determine: (1) whether soluble interleukin-2 receptor (sIL-2R) levels are elevated more frequently than AFP levels in HCC patients and (2) whether sIL-2R levels are useful as a marker of successful treatment and recurrence of disease. We are performing a prospective screening program with high-risk, chronic hepatitis virus-infected patients to detect HCC. Patients are screened by using abdominal ultrasonography, serum AFP measurements, and serum sIL-2R measurements. Normal serum sIL-2R levels were established using results from 174 healthy volunteers with no evidence of hepatitis virus infection or HCC. HCC has been diagnosed in 99 patients from a cohort of 1520 screened patients. Serum AFP levels were elevated in 79 patients (80%), whereas sIL-2R levels were elevated in 98 of the 99 patients (99%, P < .01, chi2 test). For 27 of the 99 patients (27%), HCC was diagnosed at an early stage and complete resection or ablation was performed. Serum sIL-2R levels returned to normal in all 27 patients after treatment, whereas AFP levels remained slightly elevated in 5 of the 27 (18%). Among the 16 patients in this group of 27 who developed recurrent HCC, sIL-2R levels became elevated in all 16, whereas AFP levels were elevated at diagnosis of recurrence for only 10 (P < .05). This study with chronic hepatitis B or C virus-infected patients indicates that (1) serum sIL-2R levels are abnormal in patients with HCC with a significantly greater frequency, compared with AFP levels, and (2) sIL-2R levels are a more sensitive marker of successful treatment and recurrence of HCC. Based on these findings, we now use serum sIL-2R measurements both to screen high-risk patients and to monitor treatment responses in patients with hepatitis who develop HCC.