Comparison of various assays for detection of AFP in differentiating patients with primary hepatocellular carcinoma from controls.

Four assays for the detection of alphafetoprotein (AFP) in the diagnosis of primary hepatocellular carcinoma (HCC) were evaluated. The frequency of AFP detection was compared in 89 HCC patients and in 71 patients with chronic active hepatitis/cirrhosis. Of the four assays, immunodiffusion, counterimmunoelectrophoresis (CIE), supplement CIE, and radioimmunoassay, the best for differentiating patients with HCC from those with chronic active hepatitis and cirrhosis was CIE.

Local norms of maternal serum alpha-fetoprotein values in early second trimester: a prelude to a Down's syndrome screening programme incorporating maternal serum alpha-fetoprotein values.

Maternal alpha-fetoprotein in (MSAFP) has recently been proposed for screening of Down's syndrome. This is based on the association of a lowered MSAFP level at a given gestational age in Down's syndrome (DS) pregnancies. Most conventional 'screening' programmes in DS are based on the maternal age alone, selecting older mothers, who are at greater risk of having a DS infant born, for antenatal karyotyping. However, as 75% of DS infants are born to mothers less than 35 years old, a combination of blood tests including MSAFP and maternal age as independent risk factors would screen the younger mothers as a good cost-benefit ratio in selecting the 'at-risk' mothers for karyotyping. In this study, the gestational age was calculated from the first day of the last menstrual period (LMP) as well as from ultrasound cephalometry. The local MSAFP levels follow the same trend at a slightly higher level as those based on clinical evaluation of the Abbot AFP-EIA Monoclonal kits.

Prevalence of protein calorie malnutrition in general surgical patients.

The prevalence of protein calorie malnutrition (PCM) based on ten nutritional parameters was studied in 307 patients undergoing major elective surgical operations. These parameters included anthropometric measurements (weight/height, triceps skin fold thickness, arm muscle circumference) and biochemical (serum total proteins, albumin, transferrin, prealbumin, retinol binding protein) and immunological tests (total lymphocyte count and delayed hypersensitivity test). Using these criteria, the prevalence of PCM was high. Eighty-six percent of patients had at least one abnormal parameter. The prevalence of PCM as judged by weight/height and arm muscle circumference was 49% and 62% respectively. The incidence was higher in cancer than non cancer patients (63% vs 43%). Although serum albumin and total protein levels were normal in 93.5% of patients, acute serum protein markers such as transferrin, prealbumin and retinol binding protein were low in 20-30%. Lymphopenia of 1500 cells/cu mm or less was found in 18% and abnormal delayed hypersensitivity test in 60%. We found that only weight/height, serum protein, transferrin and lymphopenia had predictive values in postoperative morbidity and mortality. By identifying PCM patients early, adequate nutritional support can be given in order to reduce the risk of major surgical complications.

The predictive value of intraoperative ST-segment monitoring as a marker of myocardial injury.

AIM: To evaluate the usefulness of dynamic intraoperative ST-monitoring in high-risk patients comparing it to preoperative clinical assessment and concurrent biochemical markers of cardiac injury. MATERIALS AND METHODS: Twenty-three patients clinically assessed as being at high risk for perioperative cardiac complications were recruited into this prospective, observational study in a public hospital. All had serial ECGs, cardiac enzymes and troponin-T measurements. The sensitivity, specificity, positive and negative predictive value of ST-segment changes in terms of predicting cardiac complications were calculated. We investigated the relationship between ST changes and biochemical markers of ischaemia and the predictive value of nonspecific (ASA) and specific (Goldman) clinical scores for cardiac complications. RESULTS: When correlated with cardiac complications, ST-segment monitoring had sensitivity 45.4%, specificity 100%, positive predictive value 100% and negative predictive value 66.7%. The correlation with CK-MB and troponin T was sensitivity 16.7% and 25%, specificity 73.3% and 75%, positive predictive value 20% and 20%, and negative predictive value 68.8% and 80%, respectively. The percentage of patients with cardiac complications increased with poor Goldman and ASA clinical scores; 25%, 40%, 62.5% and 100% in Goldman risk index groups of 0-5, 6-12, 13-25 and > 25, respectively; and 33.3% and 52.6% in ASA II and ASA III, respectively. CONCLUSIONS: This study demonstrates the importance of the anaesthesiologist preoperative assessment of cardiac risk. The probability that a patient with significant ST-depression will develop subsequent cardiac complications is 100%, which reflects its usefulness in this high-risk pre-selected sample. However, the test has a low sensitivity (45.4%).

The use of serum transferrin in the evaluation of protein-calorie malnutrition in cancer patients.

Forty-five patients with various malignancies of the gastrointestinal tract had their nutritional status assessed pre-operatively to determine the prevalence of malnutrition and to establish the correlation of malnutrition with post-operative outcome. Ten nutritional parameters were assessed. Based on these markers, we found a significant degree of malnutrition. Half of the study population developed some form of post-operative complication and nearly one quarter died. Of the ten nutritional markers studied, only serum transferrin had predictive value in determining post-operative outcome. The mean level of serum transferrin for patients with major complications was 162.0 mg/dl as compared with 221.2 mg/dl for those with none or minor complications. Patients with a serum transferrin level below the reference range of 200 mg/dl had most of the major life threatening complications and deaths. The other nutritional markers studied did not correlate well with post-operative outcome. We feel that serum transferrin is a useful nutritional marker to predict post-operative outcome and also to monitor the effect of nutritional support. However, based on a preliminary study, nutritional support may be required for periods longer than two weeks to show significant improvement in protein-calorie malnutrition. We will consider giving adequate support for a longer period on a further study using serum transferrin as a marker to determine its value in monitoring any reversal of malnutrition.

The evaluation of tumour marker proteins in the diagnosis of primary hepatocellular carcinoma.

The sera of 122 patients with biopsy confirmed primary hepatocellular carcinoma (PHC) were examined for the presence of alphafoetoprotein (AFP), alpha 1antitrypsin 1 (AAT), alpha 1acidglycoprotein (AGP) 1, gammaglutamyl transpeptidase (GGT), carcinoemryonic antigen (Roche) (CEA) and the "Hepatoma-Liver antigen" H-L Ag). 83% of patients had elevation of AFP of more than 18 ng/ml 7.4% and 15.5% had levels between 19--100 ng/ml and 100-500 ng/ml respectively. Raised AAT, AGP, GGT, CEA and HL Ag were found in many patients with PHC. Grossly elevated AFP were usually diagnostic of PHC. The combination of AAT, AGP, CEA and HL Ag were useful in the diagnosis of AFP negative cases.

A pilot study on the screening of primary hepatocellular carcinoma in selected high risk groups in the population using multiple tumour markers.

A prospective one year study on groups of 377 high risk individuals was done using alphafoetoprotein (AFP), alpha 1antitrypsin (A1AT), alpha 1-acidglycoprotein 1 (A1GP), gammaglutamyltraspeptidase (GGT) and isocitrate dehydrogenase (ICD) to detect hepatocellular carcinoma (HCC). The high risk groups screened were: cirrhosis, unexplanable hepatomegalies, chronic hepatitis B surface antigen (HBsAg) carrier, family members of afflicted HCC cases, individuals on hormonal therapy and males over the age of 30 years. 58/377 (15%) were found to have HCC. This consisted of 16/43 (37%) clinical cirrhosis, 40/71 (56%) unexplanable hepatomegalies, 1/33 (3%) chronic HBsAg, 1/156 (0.6%) family members. AFP remained the most useful test but the others such as A1AT, A1Gp, GGT and ICD recognised both malignant and asymptomatic nonmalignant diseases. Only 4 (7%) patients had resectible tumours detected and 1 patient was found to have liver dysplasia. HBsAg positivity and persistently raised AFP. The significance of HBsAg amongst family members and other group is discussed in terms of genetic susceptibility, environmental oncogenic vulnerability and ultimate screening.

Adriamycin in the treatment of resectible and irresectible primary hepatocellular carcinoma.

The treatment of 205 patients with primary hepatocellular carcinoma in Singapore from 1975 to 1980 is reviewed. Adriamycin given at a dose of 40 mg/m(2) intravenously every 4 weeks for irresectible tumours achieved a response rate of 32% alone and has significantly prolonged the median survival time to 4 1/2 months (135 days) in these individuals. Despite this response only 1/34 (3%) patient showed complete remission and is alive at 2 1/2 years. Use of other combinations with Adriamycin e.g. 5 Fluorouracil and Vincristine produced a significant response in the first 16 weeks (p < 0.005) but not thereafter, when completed with the historical group. To improve the response and to consolidate this response, split doses of total hepatic irradiation (to a maximum of 3,150 rads) and alternate day administration of intravenous Adriamycin 10 mg (to a maximum of 90 mg) were given. 12/23 patients (50%) responded. This was followed by a four weekly Adriamycin, 5 F.U. and Vincristine. Median survival time was 5 1/2 months (165 days). Relapse occurred in all patients. Similarly in 5 patients who had resections, early recurrences occurred in 3/5 (60%) within 3 months, inspite of postoperative chemotherapy with Adriamycin, 5 F.U., Vincristine and Cyclophosphamide given every four weeks. In view of the high recurrence rate following effective treatment, further studies on the biological behaviour of these abnormal livers is required.

Primary hepatocellular carcinoma developing in a female patient on long term oral contraceptives--a case report.

The association between hepatic tumours and oestrogen and progestogen therapy is well established. The risk of developing primary hepatocellular carcinoma (PHC) is small. In Africa and Asia where hepatitis B virus (HBV) infections are common, the development of PHC is also high. The presence of Hepatitis B core antibody indicates previous exposure to HBV and carries a risk of developing PHC by more than 34 times of non-infected normal. A Chinese female 29 years who had been on oral oestrogen and progestogen contraceptives continuously for 8 years developed PHC. She had no known illness due to HBV but was found to have concomitantly positive Hepatitis B core antibody in her sera. The presence of this HB core antibody and the long term consumption of oestrogen/progesterone derivatives may have been responsible for the early presentation of PHC in this patient. It is the first report in this country of PHC developing in a pill consumer since the introduction of oral contraceptives a decade ago In view of the prevalence of Hepatitis B in the region, this case finding warrants further study to determine whether (a) there is a higher frequency in pill consumers (b) an earlier age of presentation of hepatic malignancy. Meanwhile, it may be prudent to recommend alternative methods of birth control in individuals known to have been previously exposed to HBV infection, clinically or otherwise.

Use of prostate specific antigen (PSA) and transrectal ultrasound (TRUS) in the diagnosis of prostate cancer--a local experience.

Prostate specific antigen (PSA) and transrectal ultrasound (TRUS) are two new modalities added to improve our ability to diagnose prostate cancer at an early stage. We reviewed our own experience of 100 cancers among 579 men from August 1991 to October1994. The detection rate was 17.3%. Digital rectal examination (DRE) alone had a positive predictive value (PPV) of 39.9%. The PPV for PSA was 23%. The combination of PSA and DRE gave a PPV of 47.2%. TRUS had a PPV of 30.6%. Features of cancer on TRUS may be both hypoechoic or hyperechoic nodules which appeared to have almost equal proportions associated with cancer. The addition of age-specific ranges did not affect the PPV of PSA. The PPV of the combination of TRUS and DRE was 53%. With all 3 modalities combined, the PPV was 58.8%. An interesting finding from the study was the higher average PSA for benign and malignant disease in the local population and cases of acute retention of urine. There was a higher incidence of prostatitis and lower incidence of cancer in cases with retention of urine.

The effect of recombinant growth hormone on nitrogen balance in malnourished patients after major abdominal surgery.

The effect of recombinant growth hormone (rGH) on nitrogen balance was studied in malnourished patients receiving total parenteral nutrition after major abdominal surgery. Fifteen patients were randomized to receive either subcutaneous rGH (0.2 iu/kg) or placebo (saline) injection daily for seven days after surgery. Positive nitrogen balance was achieved throughout the treatment period with rGH administration and was significant on days 3 and 6. This was associated with increase in mid-arm muscle circumference and significant weight gain. Plasma insulin-like growth factor-1 (IGF-1) concentration was significantly raised in the rGH group at day 7, suggesting its role in the anabolic effect of growth hormone. Plasma pre-albumin and retinol-binding protein concentrations were raised in both the rGH and control groups, indicating improvement in the nutritional status. We conclude that the postoperative catabolic response can be attenuated using recombinant growth hormone.

Prevalence of gestational thyrotoxicosis in Asian women evaluated in the 8th to 14th weeks of pregnancy: correlations with total and free beta human chorionic gonadotrophin.

OBJECTIVES: The prevalence of gestational transient thyrotoxicosis (GTT) in Europeans evaluated during the 8th to 14th weeks of pregnancy is 2-3%. However, there is evidence that GTT may be more common in some Asian populations. The aims of this study were to evaluate the prevalence of thyroid hormone abnormalities in Asian women in their 8th to 14th weeks of pregnancy using highly sensitive free T4 and TSH assays and to correlate these with total and free beta-hCG levels. DESIGN AND PATIENTS: One hundred and eighty-four consecutive unselected Asian (Singaporean) pregnant women seen at ante-natal clinics for the first time and who were in their 8th to 14th weeks of pregnancy were tested. MEASUREMENTS: Serum free T4, free T3, TSH, total beta-hCG and free beta-HCG levels were measured on the Vitros ECi system (Johnson & Johnson Ortho-Clinical Diagnostics, Amersham, UK) which employs chemiluminescent immunochemical technology. This free T4 assay is free of biases related to serum binding capacity. The TSH assay used was a third generation assay. Thyrotrophin-receptor antibody (TRAb) levels were measured using LUMItest TRAK (BRAHMS Diagnostica, Berlin, Germany). RESULTS: Two subjects (1.1%) were found to have Graves' disease. Elevated free T4, free T3, total T3 and suppressed TSH were seen in 14.8%, 3.3%, 26.4% and 33.0% of the remaining 182 pregnant women, respectively. Total and free beta-hCG correlated negatively with TSH (r = -0.30, P < 0.0001 and r = -0.29, P < 0.0001, respectively), positively with fT4 (r = 0.283, P < 0.001 and r = 0.253, P < 0.001) and fT3 (r = 0.273, P < 0.001 and r = 0.204, P < 0.01). 11.0% of cases had gestational thyrotoxicosis (GT) defined as elevated free T4 (> 19.1 pmol/l), suppressed TSH (< 0.36 mIU/l) and TRAb levels within the reference interval (0-0.9 U/l). The prevalence of GT was significantly higher in patients tested at 8-11 weeks compared to those evaluated at 12-14 weeks (14.4% vs. 4.7%, P < 0.05). Total beta-hCG (P = 0.0002), free beta-hCG (P < 0.0001) and free T4 (P = 0.02) levels were higher and TSH levels (P = 0.01) lower in patients tested at 8-11 weeks. Significant positive correlations between both total and free beta-hCG with free T4 were seen at 8-11 weeks but not in patients tested at 12 weeks or later. TT3 levels were similar in the two groups. CONCLUSIONS: Using sensitive assays, the prevalence of gestational thyrotoxicosis in Asian women was found to be 11.0% and was significantly higher in subjects at 8-11 weeks of gestation than at 12-14 weeks. The positive correlation between hCG and free T4 seen in patients tested at 8-11 weeks was absent in patients tested at later stages of the first trimester. Future studies investigating the entity of gestational thyrotoxicosis, at least in Asian patients, should focus on patients at earlier stages of gestation than currently practised.

Molecular epidemiology of hepatitis B virus vaccine variants in Singapore.

Perinatal infection with variants of hepatitis B virus occurs despite combined immunoprophylaxis with hepatitis B immunoglobulin and currently licensed plasma-derived and recombinant yeast hepatitis B vaccines. Several variants have been detected during a large study of infants born to carrier mothers in Singapore. The most frequent variant was a virus in which a single amino acid substitution Gly to Arg occurred at amino acid position 145 of the outer protein coat of the virus. Similar mutations have been described in Italy, Japan, the USA and a number of other countries. The emergence of antibody escape mutants is a cause for concern for the detection of virus and possibly for future immunization programmes.