Alpha-fetoprotein Estimation Research Articles

Virus induced hepatocellular carcinoma (HCC) and protein biomarkers

Hepatocellular carcinoma (HCC) is a standout amongst the most widely recognized cancers around the world, and just as the alcoholic liver disease it is also progressed by extreme viral hepatitis B or C. At the early stage of the disease, numerous patients are asymptomatic consequently late diagnosis of HCC occurs resulting in expensive surgical resection or transplantation. On the basis of the alpha fetoprotein (AFP) estimation, combined with the ultrasound and other sensitive imaging techniques used, the non-invasive detection systems are available. For early disease diagnosis and its use in the effective treatment of HCC patients, the identification of HCC biomarkers has provided a breakthrough utilizing the molecular genetics and proteomics. In the current article, most recent reports on the protein biomarkers of HBV or HCV-related HCC and their co-evolutionary association with liver cancer are reviewed.

Co-infection of hepatitis C virus infection as determinants of increased hepatotoxicity among tubrculosis patients in Enugu, Nigeria

Background: Tuberculosis is a devastating disease due to high rate of multidrug resistance. The coinfection with hepatitis C virus (HCV) may enhance the development of hepatotoxicity. There is paucity of data in Nigeria on impact of HCV and TB coinfection. This study was aimed to determine the prevalence of hepatitis C virus in tuberculosis patients and ascertain the association of drug induced hepatotoxicity. Methods & Materials: This is a cross-sectional study that enrolled 148 patients with laboratory confirmed pulmonary tuberculosis between March 2018 and February 2019. The patients were categorized into three groups: group 1, patients that were on DOTS therapy; group 2, those that were newly diagnosed of TB and group 3, those that had completed six months therapy. Information on alcohol intake, cigarette smoking and duration of DOTS (group 1) were obtained. A single blood sample was collected and used for detection of anti-HCV antibodies by recombinant-ELISA, and estimation of Alpha-fetoprotein and liver enzymes. The data obtained were analyzed by chi-square test and the strength of association were measured with logistic regression analysis. Results: The tuberculosis patients comprised of 56.1% (83/148) that were on DOTS, 33.8% (50/148) newly diagnosed and 10.1% (15/148) of those that had completed DOTS, with mean age of 35.7 ± 15.1. The overall prevalence rate of HCV infection in TB patients was 23.6% (35/148). The prevalence of HCV infection in group 1, group 2 and group 3 of the TB patients were 27.7%, 20% and 13.3% respectively. The occurrence of hepatotoxicity, due to increased liver enzymes, was more in patients coinfected with HCV, with 26.5%, 16.0% and 13.3% in group 1, group 2 and group 3 respectively. Severe hepatotoxicity, 2.4%, was observed among the DOTS group. Mild liver inflammation was observed in 18.0% of the TB patients infected with HCV and those not infected were 42.1%, as assessed by alpha-fetoprotein increase >11 ng/ml. The predicting factors for hepatotoxicity were age, alcohol intake and cigarette smoking. Conclusions: The findings in this study showed high prevalence of HCV in TB patients which may complicate the anti-TB drug metabolism in the liver resulting to drug induced hepatotoxicity and liver inflammation.

Pharmaceutical efficacy of harmalol in inhibiting hepatocellular carcinoma

BackgroundDiethylnitrosamine (DEN) promoted by carbon tetrachloride (CCl4) forms DNA adducts inducing hepatocellular carcinoma (HCC). Plant alkaloid, harmalol, is being used as a therapeutic agent against HCC due to its accessibility and efficacy by apoptosis and inhibiting proliferation of cancer epithelial cells.ResultSeven groups of Swiss albino mice were taken. Different stages of liver tissues and serum from various experimental groups were collected before and after harmalol treatment. The investigation was carried out by enzyme assay, bilirubin level in the blood, DNA, RNA, normal serum protein of liver tissue, and alpha-feto protein estimation of serum. Gross morphological assessment of liver, histological, and different apoptosis markers viz. p53, caspase3, and cytochrome C expression were analyzed by RT-PCR and Western blot.Harmalol (10 mg/kg B.W. per week, I.P.) for 9 weeks showed a significant reduction in hepatocellular foci, nodules, and carcinoma ultimately retaining the normal morphology. It further induces ROS-dependent apoptosis through mitochondrial cytochrome C release that induces p53 by caspase3 activation.ConclusionThe investigation will eventually help to develop more effective chemotherapeutic drugs from the natural source.

Camel milk inhibits murine hepatic carcinogenesis, initiated by diethylnitrosamine and promoted by phenobarbitone

This study was carried out in order to investigate the possible inhibitory effect of camel milk (CM) on induced hepatocarcinogenesis in rats. Twenty-eight male rats were assigned into 4 groups (7 rats per group). Group I served as control negative. Group II treated with camel milk. Group III was injected I/P with diethylnitrosamine (DENA) (200mg/kg) as a single dose and after one week received 500ppm phenobarbitone in drinking water. Group IV injected with DENA as group III and treated with camel milk. Estimation of AST, ALT, albumin, total protein and alpha fetoprotein (AFP) in the serum of euthanized rats was performed. Histopathological examination and immunohistochemical staining of AFP and placental glutathione s transferase of the liver were carried out. Biochemical result at 38th week revealed an increase in serum AFP and a decrease in serum albumin on group III although no significance was detected. Histopathologically, the size of altered hepatic foci was smaller in the milk treated group (group IV). The number of mitotic figures observed in group IV was lower than group III. Hepatocellular carcinoma developed only in group III but not group IV. Immunohistochemical staining of AFP demonstrated an intense positive staining in group III and a weak positive staining in group IV. Similarly, the area percent of preneoplastic P-GST positive foci in liver was higher in group III than group IV. In conclusion, camel milk halted the progression of hepatocellular carcinoma.

Management of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC), a common cause for cancer-related death, is increasing worldwide. Over the past decade, survival and quality of life of HCC patients have significantly improved due to better prevention strategies, early diagnosis, and improved treatment options. We performed this narrative review to synthesize current status on the HCC management. Literature search for publications especially over the last decade, which has changed the paradigm on the management of HCC. Hepatitis B vaccination and treatment of chronic hepatitis B and C are important measures for HCC prevention. Screening and surveillance for HCC using ultrasonogram and alpha-fetoprotein estimation are directed toward cirrhotics and hepatitis B patients at high risk of HCC. If detected at an early stage, curative treatments for HCC can be used such as tumor resection, ablation and liver transplantation. HCC patients without curative options are managed by loco-regional therapies and systemic chemotherapy. Loco-regional treatments include trans-arterial chemoembolization, radioembolization and combinations of loco-regional plus systemic therapies. Currently, sorafenib is the only FDA-approved systemic therapy and newer better chemotherapeutic agents are being investigated. Palliative care for terminally ill patients with metastatic disease and/or poor functional status focusses on comfort care and symptom control. In spite of significant advancement in HCC management, its incidence continues to rise. There remains an urgent need to continue refining understanding of HCC and develop strategies to increase utilization of the available preventive measures and curative treatment modalities for HCC.

New adjuvant design using layered double hydroxide for production of polyclonal antibodies in radioimmunoassay techniques

Various adjuvants have been used to enhance the immune response against specific antigens. So the objective of this work describes the immune stimulating activity of layered double hydroxide (LDH) particles incorporate with mineral oil as a new formulation of adjuvant as compared to known Freund’s adjuvant for production of alpha-fetoprotein polyclonal antibody (anti-AFP) for estimation of alpha fetoprotein (AFP) in human serum by radioimmunoassay technique. In this concern, the study comprised two groups of white New Zealand rabbits, 2−2.5 kg body weight and each group comprised three rabbits. The first group vaccinated with AFP antigen emulsified with Freund’s adjuvant and the second group vaccinated with AFP antigen emulsified with LDH formulation. The obtained data show that the highest displacement using LDH adjuvant reached (74.2, 61.7 and 66.5 %) while the corresponding values with Freund’s adjuvant recorded (64.8, 60.3 and 54.6 %) which indicates that the use of LDH adjuvant as a cellular vehicle is a more suitable choice. Also, the preparation of AFP tracer using lactoperoxidase oxidation method and its purification using gel chromatography on PD-10 column were carried out. Different factors affecting the optimization of the assay process were studied. Validation testes of the assay were carried out. The reproducibility as measured by the intra- and inter- assay variations is satisfactory. The recovery and dilution testes indicated accurate calibration and appropriate matrix. The present technique agreed well with the currently used commercial kit (Siemens, IRMA kit). In conclusion, the liquid phase double antibody RIA technique proved to be sensitive, specific, precis and accurate for routine laboratory use.

Increased prevalence of Solar Keratoses, Infectious diseases and rising Environmental Estrogen equating with aborted blood, contraceptive menstrual blood pollution with consequent ozone depletion

Background: Simultaneous ozone layer depletion, global warming resulting in solar keratoses, skin neoplasms, increased prevalence of infectious diseases and rising environmental estrogen documented as pollutant led to this analysis. Aims: New age practice of contraception, abortions, its probable association with increase in infectious diseases, ozone layer depletion, rising environmental estrogen is sought after. Methods: Retrospective analysis of the prevalence of actinic keratoses, skin tumors, cancers from 2006-2013 with the data of 79 patients was undertaken; analysis of prevalence of viral fungal, rickettsial, bacterial infections, drug resistance, and its association with contraception achievement from 1970-2013 was also undertaken. Estrogen was measured in three samples of river water near cape Comorian and four samples of sea water from four different seas namely Indian Ocean, Arabian Sea, Bay of Bengal near cape and Bay of Bengal near Union Territory of Pondicherry. Estimation of Fetal, adult hemoglobin in sea water was attempted by routine hemoglobin electrophoresis. Estimation of alpha feto protein and β Human chorionic gonado tropin in river and sea water was undertaken. Results: Solar Keratoses had increased 4 fold [p <0.0005], tumors of the skin had increased by 3 fold [p <0.0025], skin cancers had doubled [p <0.025], over the past decade, as implementation of contraception progressed; incidence of new viral infections, increased incidence of fungal infections, rickettsial diseases, drug resistant microbial infections, mosquito borne diseases were corresponding with progress in implementation of contraception since 1970s. Estrogen was detected in river water3-5pg/ml and sea water 0.3-1pg/ml. Fetal hemoglobin could not be detected as visible bands, by routine hemoglobin electrophoresis, capable of detecting values in grams only. Alpha feto protein was detected in sea, river water as <0.6ng/ml, β human chorionic gonado tropin was detected in sea and river water as <0.1miu/ml confirming further, aborted blood pollution of the sea, river. Conclusion: Concept is global practice of contraception, abortion, since 20 century ~1970, has resulted in innocent aborted blood, contraceptive menstrual blood environmental pollution, evidenced by rising environmental estrogen; [endogenous estrogen present in the blood, can reach environment, by spilt blood only]aborted blood with its hemoglobin, binds oxygen of the environment with high affinity, cannot be replaced by plants, depletes ozone, unlike emissions of live humans-chlorine, bromine, nitrous oxide, exhaled air with carbon dioxide, being essential for manure, photosynthesis of plants, which replace oxygen molecule by molecule; plants become fossil fuels, eco balanced cycle continues to self sustenance by life on earth; ozoneexisting oxygen envelope being depleted by aborted blood, radiations result in solar keratoses, skin neoplasms; environmental aborted blood pollution favors flourishing growth of microbes, infectious diseases and drug resistance.

Clinical Spectrum of Hepatitis B Infection in Southern India

© 2011, INASL 8 Results: The IC50 of the monoherbal preparations found out to be 1 mg/mL, 20 uM and 10 uM for Phyllanthus amarus, Andrographis paniculata and Silybum marianum, respectively as obtained from the decline in viral load in the soups collected from HepG2 2.2.15 cell lines. Conclusion: The above monoherbal preparations found to have a significant decline in viral proliferating markers. In comparison with the control, herbal treatment proved to have an efficacious effect and IC50 was calculated for them. Thus the herbs could be beneficial against HBV with least side effects in comparison to synthetic drugs. However it’s a preliminary data and further studies are needed to prove it. Conflict of Interest: None Clinical Spectrum of Hepatitis B Infection in Southern India B Siva Subramaniam, V Arul Selvan, K Arun Kumar, V Jayanthi Department of Gastroenterology and Hepatology, Stanley Medical College and Hospital, Chennai Background: Hepatitis B is a global problem, affecting over 400 million populations. Large numbers of cases are referred to our center. Aim: To determine the spectrum of hepatitis B infection amongst patients attending the Liver Clinic at a tertiary GI and Hepatology center. Method: All patients who were diagnosed as HBsAg positive were included in the study. Baseline evaluation included LFT, ultrasound, alphafetoprotein estimation and virological profile for hepatitis B (HBeAg, quantification of HBsAg, HBV DNA), hepatitis C (anti-HCV antibody) and HIV status. Family members were also screened for the above markers if found to be HBsAg positive. Based on the viral profile, transaminase levels, patients were categorized into immunotolerant, inactive carriers, immune clearance and reactivation phase and risk factors were also looked for. Patients with incomplete virological profile were excluded from the study. Results: One hundred and thirteen patients were fulfilled the criteria. Among the 113 patients 38 (33.6%) patients were in immunotolerant phase, 15 (13.2%) patients in immune clearance phase, 57 (50.4%) patients were inactive carriers and 3 (2.6%) patients were in reactivation phase. Twenty patients had cirrhosis, 2 patients were presented with hepatocellular carcinoma and 7 patients were pregnant. HBV DNA levels are low in patients with cirrhosis and HCC. Table Different phases of HBV infection Variables Immunotolerant Immune clearance Inactive carrier Reactivation phase (n = 38) (33.6%) (n = 15) (13.2%) (n = 57) (50.4%) (n = 3) (2.6%) Mean age 32 (median) 40 (mean) 36 (mean) 55.33 (mean) Sex ratio 24:14 (M:F) 13:2 (M:F) 19:38 (M:F) 3 males ALT 52.4 137.3 34.7 174.6 HBsAg quantification 10905.4 3206.567 5885.958 9368.615 HBV DNA 2672419 856432 313.9963 4491218 Conclusion: The spectrum of hepatitis B infection observed in Southern India was similar to the spectrum seen in West. The immunotolerant phase extends up to 32 years and virus starts clearing in between 32 and 40 years. So far, no similar data is available from South India. Conflict of Interest: None Frequency of Hepatitis B Virus Surface Gene Variant Circulating Among HBsAg Negative Individuals in Coastal Eastern India: A Preliminary Report MK Panigrahi, SK Kar, B Misra, SP Singh, HS Das, C Panda Department of Gastroenterology, SCB Medical College, Cuttack, Orissa, India Background: Genetic mutation might account for the presence of hepatitis B virus (HBV) DNA among HBsAg negative individuals. The aim of the study was to assess the prevalence and significance of surface gene mutations among HBsAg negative chronic liver disease cases (CLD) who attended the Gastroenterology OPD at SCB Medical College, Cuttack. Methods: Twenty HBsAg negative CLD sera of adults (mean age 44.8 ± 12.1; range 28–70 years) were included in this study. Surface gene region were amplified and surface gene was analyzed after direct sequencing. Results: Out of the total 20 CLD cases studied, only 5 samples were found to be HBV DNA positive (5/20; 25.0%). Genotype D was the prevalent genotype found in the study with no prevalence of other genotypes. In all 5 patients, substitutions within as well as outside 03_JCEH-Abstract.indd 8 3/18/2011 11:13:03 AM

Frequency of Hepatitis B Virus Surface Gene Variant Circulating Among HBsAg Negative Individuals in Coastal Eastern India: A Preliminary Report

© 2011, INASL 8 Results: The IC50 of the monoherbal preparations found out to be 1 mg/mL, 20 uM and 10 uM for Phyllanthus amarus, Andrographis paniculata and Silybum marianum, respectively as obtained from the decline in viral load in the soups collected from HepG2 2.2.15 cell lines. Conclusion: The above monoherbal preparations found to have a significant decline in viral proliferating markers. In comparison with the control, herbal treatment proved to have an efficacious effect and IC50 was calculated for them. Thus the herbs could be beneficial against HBV with least side effects in comparison to synthetic drugs. However it’s a preliminary data and further studies are needed to prove it. Conflict of Interest: None Clinical Spectrum of Hepatitis B Infection in Southern India B Siva Subramaniam, V Arul Selvan, K Arun Kumar, V Jayanthi Department of Gastroenterology and Hepatology, Stanley Medical College and Hospital, Chennai Background: Hepatitis B is a global problem, affecting over 400 million populations. Large numbers of cases are referred to our center. Aim: To determine the spectrum of hepatitis B infection amongst patients attending the Liver Clinic at a tertiary GI and Hepatology center. Method: All patients who were diagnosed as HBsAg positive were included in the study. Baseline evaluation included LFT, ultrasound, alphafetoprotein estimation and virological profile for hepatitis B (HBeAg, quantification of HBsAg, HBV DNA), hepatitis C (anti-HCV antibody) and HIV status. Family members were also screened for the above markers if found to be HBsAg positive. Based on the viral profile, transaminase levels, patients were categorized into immunotolerant, inactive carriers, immune clearance and reactivation phase and risk factors were also looked for. Patients with incomplete virological profile were excluded from the study. Results: One hundred and thirteen patients were fulfilled the criteria. Among the 113 patients 38 (33.6%) patients were in immunotolerant phase, 15 (13.2%) patients in immune clearance phase, 57 (50.4%) patients were inactive carriers and 3 (2.6%) patients were in reactivation phase. Twenty patients had cirrhosis, 2 patients were presented with hepatocellular carcinoma and 7 patients were pregnant. HBV DNA levels are low in patients with cirrhosis and HCC. Table Different phases of HBV infection Variables Immunotolerant Immune clearance Inactive carrier Reactivation phase (n = 38) (33.6%) (n = 15) (13.2%) (n = 57) (50.4%) (n = 3) (2.6%) Mean age 32 (median) 40 (mean) 36 (mean) 55.33 (mean) Sex ratio 24:14 (M:F) 13:2 (M:F) 19:38 (M:F) 3 males ALT 52.4 137.3 34.7 174.6 HBsAg quantification 10905.4 3206.567 5885.958 9368.615 HBV DNA 2672419 856432 313.9963 4491218 Conclusion: The spectrum of hepatitis B infection observed in Southern India was similar to the spectrum seen in West. The immunotolerant phase extends up to 32 years and virus starts clearing in between 32 and 40 years. So far, no similar data is available from South India. Conflict of Interest: None Frequency of Hepatitis B Virus Surface Gene Variant Circulating Among HBsAg Negative Individuals in Coastal Eastern India: A Preliminary Report MK Panigrahi, SK Kar, B Misra, SP Singh, HS Das, C Panda Department of Gastroenterology, SCB Medical College, Cuttack, Orissa, India Background: Genetic mutation might account for the presence of hepatitis B virus (HBV) DNA among HBsAg negative individuals. The aim of the study was to assess the prevalence and significance of surface gene mutations among HBsAg negative chronic liver disease cases (CLD) who attended the Gastroenterology OPD at SCB Medical College, Cuttack. Methods: Twenty HBsAg negative CLD sera of adults (mean age 44.8 ± 12.1; range 28–70 years) were included in this study. Surface gene region were amplified and surface gene was analyzed after direct sequencing. Results: Out of the total 20 CLD cases studied, only 5 samples were found to be HBV DNA positive (5/20; 25.0%). Genotype D was the prevalent genotype found in the study with no prevalence of other genotypes. In all 5 patients, substitutions within as well as outside 03_JCEH-Abstract.indd 8 3/18/2011 11:13:03 AM

A Study of Neural Tube Defects

Congenital anomalies are of greater interest to Anatomists, Obstetricians, Paediatricians, &; Radiologists. Risk assessment is a part of prenatal care and should begin prior to conception and continue during antenatal period. Our goal should be to prevent the birth of babies with congenital anomalies, such as Neural Tube Defects [NTDs] by supplementing Folic acid &; Vitamin B12 during periconceptional period, and early diagnosis by the available screening protocols such as estimation of Alpha Feto Protein [AFP] in amniotic fluid &; maternal serum and diagnostic USG, so that clinician can counsel the couple regarding the outcome.The present study was under taken to know the incidence of congenital anomalies, in Cheluvamba Hospital attached to Mysore Medical College &; Research Institute Mysore. Among 3000 births during May September 1999, there were 61 babies with congenital anomalies, among these, 32 babies had neural tube defects. Results were analysed and compared with other studies reported in the literature. Overall incidence of congenital anomalies was 2.03 %, incidence of CNS anomalies was 49.19% and incidence of Neural Tube Defects was 1.06 %.

Economic evaluation of a surveillance program of hepatocellular carcinoma (HCC) in India.

Surveillance of patients of cirrhosis of liver is practiced for early detection of HCC. No data from any developing country on cost-effectiveness of such a program are available. Economic evaluation of HCC surveillance was embedded in a prospective study undertaken to estimate the incidence of HCC in 194 cirrhotics. The protocol consisted of 6 monthly abdominal ultrasound (US) and serum alphafetoprotein (AFP) estimation, and yearly triple phase CT. Cost was estimated from the hospital and patient perspectives. Cost-effectiveness ratios for detecting a case of HCC were estimated. Modeling was done to estimate cost effectiveness with different combinations of diagnostic tests. Cost-effectiveness ratios of HCC surveillance program per HCC case detected were estimated as US$ 280 from the hospital perspective. From patient perspective, these were US$ 9,965 for outstation and US$ 2,808 for local patients. Cost-effectiveness ratio for direct medical cost per case of HCC detected by 6 monthly US and AFP, the EASL protocol, was estimated to be US$ 1,510 in the private sector. The cost of HCC surveillance program is exorbitant for India (gross national income per capita US$ 620) and possibly other low/middle income countries.

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.

Differentiation of hepatocellular carcinoma from metastatic carcinoma of the liver - clinical and cytological features

Differentiation of hepatocellular carcinoma (HCC) from metastatic carcinoma in liver may be difficult on fine needle aspiration cytology (FNAC), when both appear as moderate to poorly differentiated tumours. The present study was done to assess clinical, serological, biochemical, radiological and detailed cytomorphological features to distinguish HCC from metastatic carcinoma in FNAC of the liver masses. The individual cytomorphological features which helped in differentiating HCC from metastatic carcinoma were: hepatocytic appearance of cells (92%), trabecular pattern (92%), naked nuclei (76%), intranuclear inclusions (52%) and bile (40%). The most common clinical presentation in HCC cases was pain abdomen (40%). Positivity for HBsAg was found in 7 (33.3%) cases while anti HCV antibody was detected in 4 (19%) cases. The level of serum alpha fetoprotein (AFP) was elevated in 88.9% cases, but 40% cases showed mild elevation of AFP level. 17/25 cases of HCC had solitary space occupying lesion (SOL) and 8 cases had multiple SOLs. The present study reveals that most useful cytomorphological features in the distinction of HCC from metastatic carcinoma include trabecular pattern, hepatocytic cells, bile pigment, intranuclear inclusions and atypical stripped nuclei in HCC. Viral markers and alpha-fetoprotein estimation can supplement the results.

Five-year Survival of Patients with Hepatocellular Carcinoma Treated with Laparoscopic Microwave Coagulation Therapy

Hepatocellular carcinomas (HCCs) that are located near the liver surface are difficult to treat with percutaneous locoregional therapies, so we have performed laparoscopic microwave coagulation therapy (LMCT) for these HCCs. We assessed the long-term survival of patients with HCCs treated with LMCT, the factors related to their survival, and the rates and causes of local and distant recurrences. Participants were 68 patients with HCC treated in the past 8 years with LMCT under local or general anesthesia. LMCT was done using microwave electrodes with tips ranging from 15 to 45 mm in length; the effectiveness of LMCT was confirmed using contrast-enhanced computed tomography (CT) within 2 weeks of the LMCT procedure while patients were still in hospital, and within 1-3 months after the procedure in an outpatient setting; and the follow-up study was performed periodically by CT, ultrasonography, or magnetic resonance imaging (MRI) in addition to estimation of alpha fetoprotein. Factors contributing to survival were analyzed statistically. The mean lengths of the major and minor axes of the 71 HCC nodules in 68 patients were 20 mm and 18 mm, respectively, and the mean lengths of the major and minor axes of the coagulated areas were 43 mm and 29 mm, respectively. At dynamic CT after the LMCT procedure, treatment in 62 of the 68 patients (91%) was judged to have been completely effective; the remaining six patients underwent additional therapy while still in hospital. Eight of the 68 patients (12%) had local recurrences, 39 of them (57%) had distant recurrences, and 21 of them (31%) had no recurrence up to December 31, 2003. A total of 14 patients (21%) died during the 16-56 months after LMCT. When the survival rate was assessed for all patients treated with LMCT, 1-year survival was 97 %, 3-year survival was 81%, and 5-year survival was 43%. Whether the therapy was for primary or secondary HCC strongly influenced survival. LMCT is a useful modality in clinical practice for treatment of HCC nodules located near the liver surface, and it can be safely performed, in its entirety, under direct visual guidance.

The Role of Serum Alpha-Fetoprotein estimation in the Diagnosis and Management of Hepatocellular Carcinoma

Forty years after its discovery, estimation of serum AFP remains a useful test for clinicians involved in management of patients with HCC or chronic liver disease. The test, when used with the conventional cut-off point of 500 ng/mL, has a sensitivity of about 50% and a specificity of more than 90% in detecting the presence of HCC in a patient with coexisting liver disease. New tests that can significantly increase the specificity at lower levels (i.e., between 10 and 500 ng/mL) are available but have, to date, been too complex to be widely applied in clinical practice. Serum AFP estimation may also be useful in monitoring response to therapy, particularly as more effective systemic regimens are becoming available. Indeed, there is preliminary evidence that changes in serum AFP may be a more accurate and sensitive way of determining the degree of response to treatment than conventional imaging procedures that rely on physical determination of tumor size. It may, perhaps, be time to add changes in serum AFP to the conventional imaging criteria for assessing response in clinical trials.

Audit of a screening service for fetal abnormalities using early ultrasound scanning and maternal serum alpha-fetoprotein estimation combined with selective detailed scanning.

The objective of the study was the evaluation of a screening service for fetal abnormality using early ultrasound scanning to date and establish viability of the pregnancy combined with maternal serum alpha-fetoprotein estimation at 16 weeks and thereafter selective detailed scanning at 18-20 weeks based on clinical indication. The study was designed to be retrospective, emphasizing the possibility of diagnosis. Early scans were performed by radiographers and radiologists, detailed ones by radiologists and obstetricians with subspecialty training in prenatal diagnosis. The study was carried out in the ultrasound department of a large University Hospital. The subjects studied were all cases of abnormality identified pre- or postnatally in women delivering in the hospital over 4 years and to whom the screening service applied. Information was obtained from ultrasound and maternity records, birth notifications, pathology and autopsy reports and a special needs register. Cases were classified as not detectable, potentially detectable and usually detectable. Major fetal anomalies numbered 255 (total deliveries 19,497), a prevalence of 1.3%; 130 (51%) were diagnosed by ultrasound with 64% before 24 weeks and 36% later. Eleven chromosomal anomalies (4%) were diagnosed by genetic methods and 114 (45%) anomalies were not diagnosed antenatally. The sensitivity of the program was 37% before 24 weeks. Chromosomal anomalies, lesions of the central nervous system and cardiac defects were most common, followed by lesions of the gastrointestinal and urinary tracts. A large proportion of the detected and detectable anomalies were lethal.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnostic testing during pregnancy: a descriptive analysis of utilisation data

To describe patterns of diagnostic testing during the antenatal period and to assess the potential benefit of using Medicare claims data in monitoring testing practice, we examined the matched claims data (with identifying details removed) on approximately 10,000 women having a confinement for which a Medicare benefit was claimed between 1 July and 30 September 1990. The results showed that almost all the women included in the study sample had an ultrasound and blood group and antibody examination. A smaller proportion had serological tests for syphilis (77 per cent), rubella (51 per cent) and hepatitis B carriage (73 per cent). Two-thirds had urine microscopy and culture, and under half (40 per cent) had serum alpha-fetoprotein estimation. Few (18 per cent) had a claim processed for microscopy and culture of a genital swab and fewer than 8 per cent claimed for any other pathology tests. There were differences in the proportions having tests, depending on whether the clinician managing the confinement was a specialist obstetrician or a general practitioner, and depending on geographic area and age group. While the data do not represent all women having a confinement in New South Wales, the selective use of antenatal diagnostic tests found in this study is of considerable public health importance and analysis of claims data can provide useful information for health professionals.

Analysis of cost-effectiveness of different strategies for hepatocellular carcinoma screening in hepatitis B virus carriers.

A mathematical model was used to calculate the efficacy of screening to detect hepatocellular carcinoma at a resectable stage in hepatitis B virus carriers. Data relating to tumour incidence, efficacy of screening tests and tumour growth times were obtained from a literature review. Various tests were costed according to charges currently prevailing at the authors' institution. The cost per early tumour detected is inversely proportional to tumour incidence. It is relatively low for populations with high incidences of hepatocellular carcinoma for example, male carriers over the age of 30. Both the costs and the proportions of early tumour detected increase with increasing frequency of screening. However, the use of ultrasonography at 10 monthly intervals or both ultrasonography and alpha-fetoprotein estimation at yearly intervals will detect 90% of tumours early at a cost of S$20,000 (US$11,800) per early tumour detected. The results would be significantly altered if tumour growth times were markedly different from those reported in the literature.

Current Concepts in Rational Therapy for Haemochromatosis

Genetic haemochromatosis is characterised by an inappropriately high rate of iron absorption by the small intestine. The disease is transmitted as an autosomal recessive condition. The gene frequency in the Caucasian population is approximately 1 in 20 and the disease frequency is 1 in 400. Excessive iron deposition occurs in the liver, pancreas, heart, pituitary and joints and hepatic iron concentrations above approximately 400 mumol/g dry weight are always associated with fibrosis and usually with cirrhosis and progressive liver failure. Accurate diagnosis depends upon the demonstration of elevated hepatic iron stores. An hepatic iron index [hepatic iron concentration (in mumol/g dry weight) divided by patient age] of greater than 2.0 distinguishes homozygous subjects from the other conditions in which slight increases in hepatic iron concentration may occur, e.g. in a subject heterozygous for haemochromatosis or alcoholic liver disease. If cirrhosis is present, patients are at a high risk of developing hepatocellular carcinoma. Therefore, they should undergo regular abdominal ultrasound and alpha-fetoprotein estimation. In the absence of cirrhosis, phlebotomy restores life expectancy to normal. Venesection should be continued until all excess iron stores are removed as judged by failure of a rise in haemoglobin concentration on cessation of phlebotomy. Screening of first degree relatives should commence from a young age (e.g. 10 years). If serum ferritin or transferrin saturation are abnormal, liver biopsy should be undertaken. HLA typing of the family allows for the identification of those siblings who are most likely to develop the disease. Secondary iron overload is often multifactorial in origin. Iron chelation therapy with subcutaneous deferoxamine (desferrioxamine) should only commence after careful consideration of the potential benefits in each individual patient.

Risk-Benefit Assessment of Anticonvulsants in Women of Child-Bearing Potential

Problems with anticonvulsants in women of child-bearing potential include potential adverse effects on appearance, contraception and pregnancy. These effects must be weighed against the overwhelming benefits of anticonvulsant treatment in the majority of women with epilepsy. Coarsened features, hirsutism and acne may occur in both men and women, particularly if they are exposed to phenytoin. Valproic acid may cause weight gain and hair loss, while carbamazepine treatment carries a significant risk of skin rashes. Anticonvulsants which are liver enzyme inducers (phenytoin, phenobarbital, primidone and carbamazepine) reduce the efficacy of the oral contraceptive pill. No 'pill failure' has been reported with valproic acid. There is a risk of increased seizure frequency in pregnancy irrespective of whether anticonvulsant treatment is taken. Individual seizures carry little risk to the mother or the fetus but status epilepticus has a significant maternal and fetal mortality. The risk of status epilepticus must be taken into account when deciding whether to stop anticonvulsant treatment before pregnancy. There is a 2 to 3 times increased malformation rate in the offspring of epileptic women on treatment. This is primarily due to the drug treatment, but epilepsy itself may also increase the malformation rate. Most malformations are mild and include facial clefts, congenital heart disease and skeletal abnormalities. Valproic acid, however, carries a 1% risk of causing neural tube defects: women receiving this drug who become pregnant should have an ultrasound and alpha-fetoprotein estimation at 16 to 18 weeks of pregnancy. If any abnormality is detected then amniocentesis should be carried out. Women with epilepsy should be counselled before conception and during pregnancy. Before achieving pregnancy a women should be on optimum treatment, preferably on one anticonvulsant. Consideration should be given to withdrawal of anticonvulsant drugs in any woman who has been seizure free for 2 years or who has only mild and infrequent seizures. Folate supplementation should be started prior to conception and should continue during pregnancy. There is a tendency for anticonvulsant drug concentrations to fall during pregnancy, and the dose may need to be increased if clinically indicated. Over 90% of epileptic women who become pregnant will have uneventful pregnancies and will produce healthy infants.