Birthmarks to worry about. Cutaneous markers of dysraphism

CYFRA 21-1 is a fragment of cytokeratin 19 (CK 19). Four patients with large intrahepatic (or peripheral) cholangiocarcinoma (CC) and high serum levels of CYFRA 21-1 (normal, < or = 2 ng/ml) are reported. CYFRA 21-1 levels exceeded 9 ng/ml in all 4 patients. Carcinoembryonic antigen (CEA), was high in 1 (CEA; normal range, < or = 5.0 ng/ml) and carbohydrate antigen 19-9 (CA 19-9) was high in 3 (CA19-9; normal range, < or = 36 U/ml). We also measured serum levels of CYFRA 21-1 in 13 patients with hepatocellular carcinoma (HCC) more than 5 cm in diameter. Levels of CYFRA 21-1 exceeded 2 ng/ml in 9 of the HCC patients and were higher than 9 ng/ml in 2 of the HCC patients. Levels of alpha fetoprotein (AFP) and/or protein induced by vitamin K absence or antagonist II (PIVKA II) were elevated in all HCC patients (AFP, PIVKA II, respectively; normal range, < or = 10.0 ng/ml and < or = 0.1 AU/ml) CYFRA 21-1 levels were measured twice or three times during the clinical course in 2 CC patients and in 6 HCC patients, and increased gradually with tumor growth in the 2 CC patients and in 3 of the 6 HCC patients. Marked increases in serum CYFRA 21-1 levels in patients with large liver cancers, particularly in those with normal levels of AFP and PIVKA II, would suggest the existence of intrahepatic CC rather than HCC.     

Usefulness of simultaneous determination of alpha-fetoprotein and des-gamma-carboxy prothrombin in hepatocellular carcinoma

Serum gamma-fetoprotein (AFP) and plasma des-gamma-carboxy prothrombin (DCP), a protein induced by vitamin K absence or antagonist II (PIVKA-II) levels, were measured in 197 patients with primary hepatocellular carcinoma (HCC). DCP levels were determined by conventional enzyme immunoassay kit (E-1023) and a newly developed high-sensitivity kit using the avidin-biotin complex method. Cut-off levels of AFP and DCP by the E-1023 kit and of DCP by the high-sensitivity kit were put at 100 ng/ml, 0.1 arbitrary unit (AU)/ml, and 0.004 AU/ml, respectively. Positive rate of AFP and DCP by the E-1023 kit and the high-sensitivity kit for HCC was 48%, 44%, and 57%, respectively. The positive rate by combination assay with AFP and DCP by the high-sensitivity kit increased up to 73%. There was no correlation between serum levels of AFP and those of plasma DCP. A significant correlation between tumor size and DCP levels was observed, but not with AFP. The postoperative disease-free survival rates of patients in the group with elevated levels of AFP and DCP were lower than those with normal levels of AFP and DCP. There were various patterns of change in the AFP and DCP levels at the time of recurrence compared with preoperative patterns. The combination assay of AFP and DCP levels is useful for the diagnosis, prognosis, and postoperative monitoring for recurrence of HCC.     

Serum des-gamma-carboxyprothrombin level by a modified enzyme immunoassay method in hepatocellular carcinoma: clinical significance in small hepatocellular carcinoma

BACKGROUND/AIMS: In the diagnosis of hepatocellular carcinoma (HCC), serum des-gamma-carboxyprothrombin (DCP) is a useful tumor marker. The conventional immunoassays for measurement of DCP levels, however, are not sensitive enough to detect small HCC. Therefore, we intended to elevate the minimal detection level of DCP by a modified enzyme linked immunosorbent assay method. METHODOLOGY: This modified assay method is similar to the conventional enzyme linked immunosorbent assay (ELISA) method, but the first reaction occurs overnight. As a result, the minimal detection levels of DCP varied from 0.06 AU/ml, by the conventional method, to 0.008 AU/ml, by the modified method. Two hundred and twenty five serum samples from 100 patients with HCC, 75 with liver cirrhosis and 50 with chronic hepatitis were subjected to the present study. Simultaneous determinations of serum DCP by the modified assay and a-fetoprotein (AFP) levels were performed. RESULTS: Eighty five of 100 patients with HCC had increased DCP levels of more than 0.008 AU/ml. This method yielded a sensitivity of 85%, a specificity of 90% and a total accuracy value of 88%. In 27 patients with small HCC (less than 30 mm in diameter), 12 had elevated DCP levels, resulting in a sensitivity of 44%. When the modified DCP assay together with AFP measurement (more than 20 ng/ml) were introduced, the sensitivity was 67% in the 27 patients with small HCC. CONCLUSIONS: This modified ELISA method increased the sensitivity in patients with small HCC, and the combination assay of serum DCP and AFP levels was more useful for the early diagnosis of HCC.     

Clinical evaluation of autoantibodies to p53 protein in patients with chronic liver disease and hepatocellular carcinoma

In hepatocellular carcinoma (HCC) of patients from the Western hemisphere, mutations in the p53 tumour suppressor gene are present in up to 37% of cases. Conformational change and cellular accumulation can initiate an immune response with generation of circulating autoantibodies to p53 protein. In the present study, we investigated 711 consecutive patients with chronic liver disease to evaluate the sensitivity and specificity of autoantibodies to p53 protein as a serological marker for HCC. Detection of p53 autoantibodies was performed using an enzyme-linked immunosorbent assay with immobilised recombinant p53 protein. Liver cirrhosis was present in 259 patients (36.4%) and a HCC was diagnosed in 75 patients (10.6%). Autoantibodies to p53 protein were detectable in 15 of 377 patients with chronic liver disease (4.0%) and in 10 of 259 patients presenting with liver cirrhosis (3.9%). All 25 p53 autoantibody-positive/HCC-negative patients were carefully investigated and no underlying malignancy was clinically detected, suggesting that elevated p53 antibody levels may not exclusively be detectable in patients with malignant disease. In patients with clinically manifest HCC, p53 autoantibodies were detected in 17 of 75 cases, thus resulting in a sensitivity of 22.7% and a specificity of 96.1%. In contrast, assessment of serum alpha-fetoprotein (AFP) resulted in a sensitivity and specificity of 69.3 and 91.8% (AFP > 20 ng/ml) and 53.3 and 99.1% (AFP > 100 ng/ml) for the detection of HCC, respectively. The data of the present study reveal that the presence of p53 autoantibodies in patients with chronic liver disease is not completely specific for HCC. Moreover, we obtained no direct evidence that p53 autoantibody formation precedes the clinical diagnosis of HCC. However, serological screening for HCC might be improved by combining AFP and p53 autoantibody assays.     

Fibrolamellar carcinoma of the liver with a mixture of ordinary hepatocellular carcinoma: a case report

Fibrolamellar carcinoma (FLC) of the liver is a rare variant of hepatocellular carcinoma (HCC), and only 13 cases have been reported in Japan up to 1997. We described a histologically unusual case of FLC. A 52-yr-old man was admitted to our hospital for work-up of hepatic mass. Laboratory examinations revealed no abnormalities except elevated serum alpha-fetoprotein (AFP) (2098 ng/ml). A diagnosis of HCC was made by imaging findings, and left lobectomy of the liver was performed. Histologically, the tumor was composed of areas of FLC mixed with ordinary HCC and those of pure ordinary HCC. Staining for AFP was positive in the HCC component and negative in the FLC component. Some cases of such mixed tumors have been reported in Europe and the United States, but not in Japan. We regarded our case as the first of the mixed tumor in Japan.     

Vascular biology of the radial artery

Two cases with spontaneous regression of a histologically confirmed hepatocellular carcinoma (HCC) are presented. This rarely seen phenomenon of a spontaneous tumor involution is discussed and compared with the current literature. The clinical symptoms were very similar to that of a liver abscess. A 56-year-old male suffered from a multicentric, highly differentiated, trabecular HCC. First symptoms were epigastric pain, septic fever and arthritis. The tumor marker AFP was constantly normal and no hepatitis could be verified. A resection of the tumor was performed. In patient 2, a 74-year-old male, a multicentric, clear cell HCC was found. The patient had completely recovered from hepatitis type B and within the liver tissue no viruses could be identified. Clinical symptoms were mainly characterized by upper abdominal pain and septic fever. AFP was excessively elevated (3850 ng/ml) but returned to normal preoperatively. In both cases, the specimen showed a subtotal necrotic HCC with insignificant amounts of vital tumor cells. Neither patient had a liver cirrhosis macroscopically, however patient 2 had local periportal fibrosis histologically. After 24 and 41 months of follow-up, respectively, both patients are in good health     

The fucosylation index of alpha-fetoprotein as a possible prognostic indicator for patients with hepatocellular carcinoma

BACKGROUND: The aim of this study was to elucidate the usefulness of measuring the fucosylation index (FI) of alpha-fetoprotein (AFP) before the initiation of therapy as a new prognostic indicator for patients with hepatocellular carcinoma (HCC). METHODS: One hundred twelve patients with HCC who underwent transcatheter arterial embolization, chemoembolization, and/or percutaneous ethanol injection were examined in the current study. FI was determined by crossed immunoaffino-electrophoresis in the presence of Lens culinaris agglutinin. RESULTS: When the tentative discriminating value of FI was set at 18%, the mean survival rate for the group whose FI was higher than 18% was significantly lower than that for the group whose FI was equal to or less than 18%, according to the generalized Wilcoxon test (P = 0.0117) and the log rank test (P = 0.0183). The survival rate for HCC patients with AFP concentrations of more than 200 ng/mL was also significantly lower than that for patients with AFP in the range of 21-200 ng/mL, according to the generalized Wilcoxon test (P = 0.0017) and the log rank test (P = 0.0018). When FI was combined with AFP concentration, a highly significant difference was observed between the group with FI >18% and AFP >200 ng/mL and another group with FI < or =18% and AFP < or =200 ng/mL, as determined by the generalized Wilcoxon test (P < 0.0001) and the log rank test (P = 0.0003). An analysis of multiple covariates in the prognostic factors with the Cox proportional hazards model showed that FI was one of the independent prognostic factors. CONCLUSIONS: The current study indicates that measuring FI from sera before the initiation of treatment serves as a new prognostic factor and may improve prognostic estimates and appraisal of therapeutic outcomes for patients with HCC.     

Cirrhosis of the liver as a precancerous condition

Cirrhosis of the liver can be regarded as premalignant state, since more than 80 percent of hepatocellular carcinoma (HCC) in the western world develop in a cirrhotic liver. The risk to develop this malignancy depends on the activity of the underlying cirrhosis, its etiology and the duration of the disease. Patients suffering from cirrhosis of the liver due to HBV-, HCV- or HDV-infection and patients with genetic hemochromatosis exhibit a high risk for HCC. This risk is further increased by cocarcinogens, such as alcohol, nicotine and toxins. Ultrasound and AFP-studies aim to diagnose HCC early. The sensitivity of AFP in the serum is remarkably low (about 64%). In contrast a normal AFP-concentration (< 20 ng/ml) carries a high negative prognostic value (> 90%). Patients suspected to suffer from HCC according to the results of screening procedures should be subjected to additional radiologic investigations, such as CT-arterioportography or lipiodol-angiography.     

Alpha feto-protein and albumin in ascitic fluid in hepatocellular carcinoma patients

Alpha-feto-protein (AFP) is the most popular tumor marker for hepatocellular carcinoma (HCC). It is used in diagnosis and follow up of cases by estimating its rise in the serum. The aim of this work is to study the value of estimating AFP in ascitic fluid of HCC patients with ascites. This work is a case control study on 32 patients, including 22 cases with ascites and HCC and 10 control group with ascites due to liver cirrhosis without HCC. The level of AFP was estimated in serum and in ascitic fluid by Radio-immuno assay RIA. The serum ascites albumin gradient (SAAG) was assessed by measuring albumin in all samples using bromocresole green dye binding. Guided aspiration liver biopsy and ascitic fluid cytology was done, stained with H & E. It was found that, AFP level in serum was elevated in 72.7% of HCC patients, and in ascitic fluid was elevated 63.6% HCC patients. Also, there was a highly significant, direct positive correlation between elevation of AFP in serum and in ascitic fluid (r = 0.778). No elevation of AFP in serum and in ascitic fluid was detected in control group. Ascitic fluid cytology showed malignant cells in one case only. SAAG was significantly lower in the HCC group 0.83 gm/dl than the control group 2.43 gm/dl (p-value < 0.001). Elevation of AFP in ascitic fluid is of high importance in evaluation of HCC, and is as significant as serum and runs parallel to it. Estimation of AFP in ascitic fluid is much more significant in evaluation of HCC cases than ascitic fluid cytology.     

Amplification of the c-myc gene in human hepatocellular carcinoma: biologic significance

To elucidate the prevalence and biologic significance of the c-myc gene in human hepatocellular carcinoma (HCC), DNA samples were taken from the paired tumorous and nontumorous tissues of 77 cases of resected primary HCC and were analyzed by Southern blot hybridization. We demonstrated modest, but significant c-myc amplification (group A) in 28 (36.4%) of the cases: 1.6- to 2.0-fold in 18, 2.1- to 3.0-fold in four, and > 3.0-fold in six. Compared to HCC without c-myc amplification (group B), group A HCC occurred more often in patients < 50 years old (54.5% vs 29.1%, p < 0.02) with serum alpha-fetoprotein (AFP) levels > 320 ng/mL (61.1% vs 14.6%, p < 0.00002). Group A HCC occurred more frequently in patients with hepatitis B virus infection than in those with hepatitis C virus infection (p < 0.03). Group A HCC was more likely to be poorly differentiated (44.8% vs 10.5%, p < 0.004) and associated with intrahepatic portal vein spread (57.1% vs 28.6%, p < 0.02). The c-myc amplification did not correlate with sex or tumor size. For small HCC, group A had a worse one-year survival rate than group B (72.2% vs 90.9%, p < 0.04). These findings suggest that c-myc amplification is not an uncommon event in human hepatocarcinogenesis, occurs more frequently in young patients who have an elevated serum AFP level or HBV infection, and is related to the biologic behavior of HCC.     

High serum alpha-fetoprotein concentration associated with pseudoinfarction of a cirrhotic liver: report of a case

We report herein the case of a 65-year-old man with cirrhosis of the liver in whom a portal vein thrombus was found to be the cause of a marked elevation in serum alpha-fetoprotein (AFP). The patient presented with fever and abdominal pain, and a diagnostic work-up revealed a liver mass and an increased serum AFP concentration of 91,000 ng/ml. The mass gradually regressed, and the AFP concentration simultaneously decreased to 163 ng/ml. However, because hepatocellular carcinoma (HCC) could not be ruled out, a partial hepatectomy was performed. Histological examination of the resected specimen revealed a thrombus of the portal vein surrounded by the fibrosis associated with liver cirrhosis, but no neoplastic lesion was found. Thus, portal thrombus associated with liver cirrhosis might induce an extremely high level of AFP production.     

Protein induced by vitamin K absence or antagonist II as a prognostic marker in hepatocellular carcinoma. Comparison with alpha-fetoprotein

BACKGROUND: Protein induced by vitamin K absence or antagonist II (PIVKA-II) was widely used as a diagnostic marker for hepatocellular carcinoma (HCC), however, its prognostic value is unclear. The authors evaluated PIVKA-II clinicopathologically as a prognostic marker for HCC. METHODS: The relationship between pathologic prognostic factors and plasma PIVKA-II and alpha-fetoprotein (AFP) was investigated in 72 patients with resectable HCC measuring less than 6 cm in greatest dimension. RESULTS: PIVKA-II shows significantly lower sensitivity, but higher specificity than AFP, and the use of these two complementary markers appears to be useful in the diagnosis of HCC. The frequencies of intrahepatic metastasis, portal vein tumor thrombus, hepatic vein tumor thrombus, and capsular infiltration were significantly higher in patients with positive PIVKA-II than in those with negative-PIVKA-II, and the recurrence-free rate was significantly lower in patients with positive rather than with negative PIVKA-II. However, there were no significant differences between the patients who were AFP positive and those who were AFP negative in pathologic prognostic factors and the recurrence-free rate. From univariate and multivariate analyses, the authors find that PIVKA-II is one of the risk factors for recurrence of HCC after hepatectomy. CONCLUSIONS: PIVKA-II may be a useful marker for the prediction of intrahepatic spread and for the prognosis of HCC. In addition, PIVKA-II-positive patients, thus, need aggressive postoperative adjuvant therapy for undetectable residual tumors and careful postoperative monitoring to enable the early recognition of recurrence.     

Contents of alpha-fetoprotein in the blood of pregnant women as a criterion of the presence of congenital heart defects in the fetus

alpha-Fetoprotein (AFP) was measured in the blood of 16 women pregnant with twins at various terms of gestation and 24 pregnant women whose fetuses were found to have anencephaly, patent spina bifida, gastroschisis, renal polycystosis, or Down's disease. In Down's disease AFP level was 7 ng/ml (0.17 multiple of medians, MoM) at 17 weeks gestation and 6 ng/ml (0.12 MoM) at 19 weeks. In the fetal abnormalities studied AFP level was 372 ng/ml on average (6.8 MoM) at 16 to 18 weeks gestation, this being about 10 times higher than the normal level. AFP level in twin pregnancy at the same period was 2.3 MoM. AFP measurements are important for the prenatal diagnosis of fetal status in order to plan follow-up of pregnancy and labor management.     

Glutathione S-transferases in carcinogenesis and diagnosis of liver cancer

We studied the relations between glutathione S-transferases (GSTs) from human liver and hepatic cancer and preneoplastic lesions in high risk area of Qidong city and Beijing. A biotin-avidin enzyme-linked immunoassay (BA-ELISA) for serum level of GSTs was developed. The results showed that the GSTs level of normal controls in Qidong city (0.66 +/- 0.54 ng/ml) was higher than that in Beijing (0.37 +/- 0.27 ng/ml). The members of high cancer families, HBVsAg carries and patients having a low level fluctuating pattern of serum AFP were the population with high risk of liver cancer; their serum level of GSTs was 1.25 +/- 1.46, 1.43 +/- 1.44 and 2.81 +/- 1.76 ng/ml respectively, and it was significantly higher than in the normal controls. The content of GSTs of hepatic cancer patients in Qidong city and Beijing was 3.03 +/- 3.35 and 3.60 +/- 3.70 ng/ml respectively, but the positive rate (97%) of GSTs in Qidong city was higher than that (82%) in Beijing. The results suggested that serum expression of GSTs can be used as an enzyme marker for hepatic cancer and preneoplastic lesions. Possible roles of these forms in hepatic carcinogenesis induced by chemical carcinogenesis were discussed.     

Coagulation and fibrinolytic responses of human peritoneal fluid and plasma to bacterial peritonitis

Significantly higher (P < 0.05) thrombin-antithrombin III complex levels were found in the abdominal exudate of patients with peritonitis (median 5500 ng/ml) than in that of controls (median 89 ng/ml). In patients, peritoneal fluid concentrations of tissue and urokinase-type plasminogen activator were increased by factors of 65 and 10 respectively (P < 0.05). The concentration of plasminogen activator inhibitor (PAI) 1 was increased by a factor of about 800 (median 395 versus 0.5 ng/ml, P < 0.05). Despite markedly raised concentrations of PAI, peritoneal fluid displayed fibrinolytic activity as demonstrated by significantly increased (P < 0.05) concentrations of plasmin-alpha 2-antiplasmin complex (median 10,952 versus 57 ng/ml) and fibrin degradation products (median 40,360 versus 126 ng/ml). There was no correlation between plasma and peritoneal fluid concentrations. Intraabdominal coagulation and fibrinolysis are stimulated in the abdominal cavity of patients with bacterial peritonitis.     

Acute suppurative parotitis with spread to the deep neck spaces

The occurrence of hepatocellular carcinoma (HCC) in renal transplant recipients has typically been associated with hepatitis B or C infection. We encountered two cases of HCC in renal transplant recipients with negative hepatitis B and C markers and no underlying liver pathology, in whom immunosuppression therapy consisted of prednisone and azathioprine (AZA). Patient no. 1 is a 66-year-old man with diabetes who underwent cadaveric renal transplantation 13 years before presentation. An ultrasound obtained for evaluation of a prolonged prothrombin time and decreased serum albumin level showed a suspicious nodular lesion in the left lobe of the liver. A computed tomographic (CT) scan confirmed a 4- x 5- x 5-cm mass that, on biopsy, was determined to be well-differentiated HCC. There was no evidence of metastasis, and the results of random biopsies of the surrounding parenchyma were normal. The patient underwent a left lateral segmentectomy, did well, and an initial alpha-fetoprotein (AFP) level of 85995 ng/mL decreased to 9 ng/mL. Approximately 20 months postoperatively, however, a surveillance CT scan showed three hypervascular lesions in the right lobe of the liver and the AFP level increased to 28,370 ng/mL. Subsequent percutaneous alcohol injections yielded good results, and the patient is alive and well 13 months later. Patient no. 2 is a 57-year-old man who underwent cadaveric renal transplantation 24 years earlier. A CT scan of the abdomen obtained for evaluation of lower abdominal pain showed a 4- x 4- x 6.5-cm mass in the right lobe of the liver that, on biopsy, was found to be poorly differentiated HCC. Multiple biopsies of adjacent liver parenchyma showed no evidence of cirrhosis, AFP level was normal, and imaging studies showed no evidence of tumor spread. The patient underwent a right hepatic lobectomy and is doing well without evidence of recurrence 27 months postoperatively. Our two patients had no evidence of viral hepatitis, cirrhosis, or metabolic liver disease, yet both developed HCC. The use of AZA may have had a role in the development of HCC. In renal transplant recipients on long-term immunosuppression therapy, particularly AZA, it is prudent to maintain a high index of suspicion for HCC when liver enzyme level or function abnormalities are encountered.     

Disseminated cutaneous sporotrichosis as the initial manifestation of acquired immunodeficiency syndrome--case report

Two patients with ectopic liver are described. In one patient, a small ectopic liver attached to the gastric serosa developed hepatocellular carcinoma (HCC). The preoperative diagnosis was an alpha-fetoprotein (AFP)-producing carcinoma and a malignant ulcer of the stomach. Total gastrectomy and esophago-jejunostomy were performed. The tumor that measured 4 x 2 x 2 cm contained an AFP-producing HCC and normal liver tissue. In another patient who had alcoholic cirrhosis, ectopic liver on the serosa of the gallbladder was found to have the same histological changes as the mother liver. A survey of the literature disclosed more than 20 cases in which HCC developed outside the liver; the liver did not have HCC. By contrast, there was only one report on HCC occurring in the liver in the presence of a noncancerous, relatively large accessory liver lobe. Because ectopic liver does not have a complete vascular and ductal system as a normal liver, it is perhaps functionally handicapped and more prone to hepatocarcinogenesis.     

Bone matrix proteins

Seminomas account for 50% of testicular germ-cell tumors, and more than 90% of these are classic seminomas. When patients with a histologically pure testicular seminoma show an elevated level of serum á-fetoprotein (AFP), it is generally assumed that an undetected focus of yolk sac tumor (YST) is present and the patient is managed with a treatment regimen for non-seminomatous tumor. We studied 10 cases of histologically pure seminoma with elevated levels of serum AFP in an attempt to identify any distinctive clinical, histopathologic, or immunohistochemical features. The patients ranged in age from 27 to 48 years (mean, 31 years). Eight patients had primary tumors of the testis, and two presented with supraclavicular and ileal tumors. The clinical stage at presentation varied: four tumors were stage I, four were stage II, and two were stage III. Serum levels of AFP were elevated in all patients at ranges of 10.4 to 16 ng/ml (mean, 12.0 ng/ml). In all patients, the primary tumors and metastases when present exhibited classic seminoma histology without other germ-cell components. The tumor cells expressed keratin in seven cases. The pattern of keratin immunoreactivity ranged from focal staining in five cases to moderate staining in two cases. All cases were negative for AFP, and the nine cases in which staining for CD30 (Ki-1) was performed were also negative. All four patients with stage I tumors underwent the conventional therapy for pure seminoma, i.e., orchiectomy and subsequent radiation therapy. Five patients received treatment for non-seminomatous tumors, i.e., chemotherapy after orchiectomy. Extensive work-up failed to detect the primary tumor in one patient, and he was treated for a non-seminomatous tumor, undergoing chemotherapy and irradiation. All patients are alive and well, and none has developed evidence of YST at a mean follow-up of 6 years (range, 6 months to 10 years). However, one patient who presented with an ileal metastasis recently developed a second primary extragonadal mediastinal mixed germ-cell tumor with YST and embryonal carcinoma components and an elevated serum level of AFP (27,000 ng/ml) after a 10-year disease-free follow-up. This study strongly suggests that minor elevations (相似文献   

The importance of measuring plasma carcinoembryonic antigen in small-cell anaplastic carcinoma

The clinical value of the serum biomarker carcinoembryonic antigen (CEA) was evaluated prospectively in 118 patients with small cell lung cancer (SCLC) entered chemotherapy protocol between 1986 and 1992. Five quantitative categories were determined: less than 2.5 ng/ml and 2.6-5.0 ng/ml (the standard normal), 5.1-20.0 ng/ml, 20.1-100 ng/ml and greater than 100 ng/ml. 70% of patients had levels less than 5 ng/ml and only 19% had levels greater than 20 ng/ml. There was no clearcut relationship of plasma CEA level to stage of disease, in which 61% of patients with extensive disease (59 patients) had levels less than 5 ng/ml and 22% of patients with limited disease (59 patients) had levels greater than 5 ng/ml. There was a modest relationship of CEA levels to presence of metastases, in that 50% of patients with metastases had levels greater than 20 ng/ml. The average survival for the pathologic and normal category was almost similar, ranging from 13.27 to 16.81 months. The correlation between disease extent and survival was more sensitive for lactate dehydrogenase (LDH) than for CEA. So CEA as a tumor marker for SCLC must be applied in conjunction with other biomarkers, particularly LDH and neuron specific enolase (NSE) and is meaningful in only a small proportion of patients.