Intracystic concentrations of tumour markers for the diagnosis of cystic liver lesions.

BACKGROUND: Imaging occasionally fails to differentiate hepatic simple cysts from malignant or premalignant mucinous cystic lesions such as biliary cystadenomas. Hepatic simple cysts can be treated conservatively, whereas malignant or premalignant cysts require complete resection. This study assessed the ability of intracystic tumour marker concentrations to differentiate these disease entities. METHODS: Intracystic fluid was sampled in patients undergoing partial or complete resection of a cystic lesion of the liver. The indication for surgery in hepatic simple cysts was symptoms or suspicion of a biliary cystadenoma. Intracystic concentrations of carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9 and tumour-associated glycoprotein (TAG) 72 were measured to assess the diagnostic accuracy of these tumour markers. Cut-off values were defined by receiver operating characteristic (ROC) curves. RESULTS: The study population comprised 118 patients (94 women) with a median age of 59 years. There were 75 patients with hepatic simple cysts, 27 with mucinous cysts (19 biliary cystadenomas, 4 biliary cystadenocarcinomas, 4 intraductal papillary mucinous neoplasms of the bile duct) and 16 with miscellaneous cysts. Unlike CEA and CA19-9, a TAG-72 concentration of more than 25 units/ml differentiated hepatic simple cysts from mucinous cysts with a sensitivity and a specificity of 0·79 and 0·97 respectively. The area under the ROC curve was 0·98 for mucinous versus hepatic simple cysts. CONCLUSION: The concentration of TAG-72 in cyst fluid accurately identified hepatic cysts that required complete resection.

Insulin resistance and geographical origin: major predictors of liver fibrosis and response to peginterferon and ribavirin in HCV-4.

BACKGROUND AND AIMS: Hepatitis C virus (HCV) genotype 4 (HCV-4) is increasing in prevalence in Western countries. However, little is known about the severity of the disease and response to treatment. The aim of this study was to assess the predictors (logistic regression) of severe fibrosis (METAVIR score F3-F4), and sustained virological response (SVR) to peginterferon and ribavirin in 226 consecutive HCV-4 patients (Egyptians 40%, Europeans 35% and Africans 24%). PATIENTS AND METHODS: Insulin resistance was assessed using the homeostasis model (HOMA-IR). Serum HCV-RNA level (bDNA) and subtypes of HCV (LiPA) were determined for all patients. RESULTS: Insulin resistance (HOMA-IR >3) was present in 105 patients (46%), and was associated with: age >45 years (OR, 2.614; 95% CI, 1.316 to 5.194), body mass index (BMI) >25 kg/m(2) (OR, 2.105; 95% CI, 1.048 to 4.229), serum HCV-RNA >800 000 IU/ml (OR, 3.143; 95% CI, 1.503 to 6.574), severe fibrosis (OR, 2.657; 95% CI, 1.214 to 5.818), and steatosis >30% (OR, 2.488; 95% CI, 1.105 to 5.602). Severe fibrosis was present in 67 patients (29%) and was associated with Egyptian origin (OR, 5.872; 95% CI, 2.747 to 12.553), excessive alcohol intake (OR, 5.311; 95% CI, 1.287 to 21.924), and HOMA-IR >3 (OR, 3.864; 95% CI, 1.859 to 8.034). 108 patients received a 48 week course of peginterferon plus ribavirin. SVR (undetectable serum HCV-RNA (TMA) 24 weeks after treatment stopping) was achieved in 59 patients (55%) and was associated with Egyptian origin (OR, 13.119; 95% CI, 3.089 to 55.706), HOMA-IR <2 (OR, 5.314; 95% CI, 1.953 to 14.459), and non-severe fibrosis (OR, 8.059; 95% CI, 2.512 to 25.855). CONCLUSION: Insulin resistance and geographical origin are major predictors of liver fibrosis and response to peginterferon and ribavirin in HCV-4 patients. Insulin resistance is frequently encountered in these patients, and correlated independently with serum HCV-RNA.

Differential diagnosis between chronic pancreatitis and pancreatic cancer: value of the detection of KRAS2 mutations in circulating DNA.

KRAS2 mutations in codon 12 have been detected in about 80% of pancreatic cancers. The aim of this study was to evaluate the value of KRAS2 mutations detection in circulating deoxyribo nucleic acid to differentiate pancreatic cancer from chronic pancreatitis. Circulating deoxyribonucleic acid was isolated from serum in 47 patients with histologically proven pancreatic adenocarcinomas (26 males, median age 65 years) and 31 controls with chronic pancreatitis (26 males, median age 48 years). Mutations at codon 12 of KRAS2 gene were searched for using polymerase chain reaction and allele specific amplification. Serum carbohydrate antigen 19.9 levels were also determined. KRAS2 mutations were found in 22 patients (47%) with pancreatic cancer and in four controls with chronic pancreatitis (13%) (P<0.002). None of the latter developed a pancreatic cancer within the 36 months of median follow-up. The sensitivity, specificity, positive and negative predictive values of serum serum KRAS2 mutations for the diagnosis of pancreatic cancer were 47, 87, 85 and 52%, respectively. KRAS2 mutations were not related to age, gender, smoking habit, tumour stage, or survival. Among the 26 patients with normal or non-contributive (due to cholestasis) serum carbohydrate antigen 19.9 levels, 14 (54%) had KRAS2 mutations. The combination of KRAS2 and carbohydrate antigen 19.9 gave a sensitivity, specificity, positive and negative predictive values for the diagnosis of pancreatic cancer of 98, 77, 87 and 96%, respectively. Detection of KRAS2 mutations in circulating deoxyribo nucleic acid has a low sensitivity but a specificity about 90% for the diagnosis of pancreatic cancer. It seems particularly useful when serum carbohydrate antigen 19.9 levels are normal or inconclusive. A combined normal serum carbohydrate antigen 19.9 and absence of circulating KRAS2 mutations makes the diagnosis of pancreatic cancer extremely unlikely.

[Enzyme calibrators: principle and practical use]. / Le calibrage en enzymologie clinique: principe, conditions d'application et résultats.

Results of catalytic activities of enzymes are highly dependent on the measurement procedures and on local conditions. Thus, only poorly marked improvement of interlaboratory comparability of results have been observed in clinical enzymology. To solve this problem, SFBC and IFCC have proposed to use "validated enzyme calibrators". Standardised operating procedures adapted to 37 C have been developed by IFCC for the most commonly used enzymes in clinical chemistry, and will be soon published. Reference materials which have been certified with these SOPs can be used as calibrators for a set of measurement methods which exhibit the same analytical specificity. Calibrators must be commutable, a property that must be checked experimentally. It is possible to produce stable and commutable materials for the calibration of a set of methods. Interest of this approach has been demonstrated for several enzymes. Results of two studies presented here show that the comparison of results to the upper limit of reference ranges does not improve the interlaboratory comparability of results in contrast to the calibration of different methods by a common calibrator which allowed to reach an interlaboratory CV close to 4% for ALT and gammaGT.

[Cirrhosis]. / La cirrhose.

Cirrhosis, a condition whose diagnosis is dependent on histology, is characterized by a combination of two main lesions, namely fibrosis and regeneration nodules. Alcohol abuse and viral infections are the two most common causes of cirrhosis. Symptoms and laboratory test abnormalities appear when hepatic failure and portal hypertension occur as a result of the cirrhosis. Ascites, gastrointestinal bleeding, encephalopathy, and bacterial infections are the main clinical manifestations. Hepatocellular carcinoma is a common and dreaded complication of cirrhosis. Serum albumin, serum bilirubin, and the prothrombin time are the most useful laboratory parameters. In combination with clinical criteria they allow determination of the Child-Pugh stage, which is largely used to evaluate the severity of cirrhosis, and evaluation of the prognosis. Recently, the early detection of cirrhosis has been shown to benefit from assays of serum markers for fibrosis, most notably hyaluronate. Quantitative tests evaluating the functional liver mass are helpful for monitoring cirrhosis and for selecting patients for liver transplantation, which is the only available treatment for end-stage cirrhosis.

[Biological examination in the diagnosis and monitoring of liver disease. Algorithms to aid the decision]. / Exploration biologique dans le diagnostic et la surveillance d'une maladie du foie. Schémas d'aide à la décision.

The goal of this article is to describe a rational step-wise strategy for using standard laboratory tests to obtain diagnostic orientation for a liver disorder; establish, support, or rule out a liver disorder; and monitor the course of treated and untreated patients with liver disorders.

Kinetics of serum tumor marker concentrations and usefulness in clinical monitoring.

Only a few markers have been instrumental in the diagnosis of cancer. In contrast, tumor markers play a critical role in the monitoring of patients. The patient's clinical status and response to treatment can be evaluated rapidly using the tumor marker half-life (t(1/2)) and the tumor marker doubling time (DT). This report reviews the interest of determining these kinetic parameters for prostate-specific antigen, human chorionic gonadotropin, alpha-fetoprotein, carcinoembryonic antigen, cancer antigen (CA) 125, and CA 15-3. A rise in tumor markers (DT) is a yardstick with which benign diseases can be distinguished from metastatic disease, and the DT can be used to assess the efficacy of treatments. A decline in the tumor marker concentration (t(1/2)) is a predictor of possible residual disease if the timing of blood sampling is soon after therapy. The discrepancies in results obtained by different groups may be attributable to the multiplicity of immunoassays, the intrinsic characteristics of each marker (e.g., antigen specificity, molecular heterogeneity, and associated forms), individual factors (e.g., nonspecific increases and renal and hepatic diseases) and methods used to calculate kinetics (e.g., exponential models and timing of blood sampling). This kinetic approach could be of interest to optimize patient management.

Diagnostic value of CA 72-4 and carcinoembryonic antigen determination in the fluid of pancreatic cystic lesions.

OBJECTIVE: Mucinous cystic tumours of the pancreas need to be distinguished from other cystic lesions because of their malignant potential. The aim of this study was to assess prospectively the reliability of CA 72-4 and carcinoembryonic antigen analysis in the fluid of cystic lesions of the pancreas obtained by fine-needle aspiration for pathological diagnosis. METHODS: CA 72-4 and carcinoembryonic antigen were measured in cyst fluid obtained preoperatively by fine-needle aspiration. The 91 lesions consisted of 16 serous cystadenomas, 16 mucinous cystadenomas, 14 cystadenocarcinomas and 45 pancreatic pseudocysts complicating well documented chronic pancreatitis. RESULTS: A CA 72-4 level of >40 U/ml had a 63% sensitivity and 98% specificity for distinguishing mucinous cystadenomas and cystadenocarcinomas from serous cystadenomas and pseudocysts. A carcinoembryonic antigen level of >400 ng/ml had a 57% sensitivity and a 100% specificity for distinguishing mucinous tumours and cystadenocarcinomas from pseudocysts. A carcinoembryonic antigen level of <4 ng/ml had a 100% sensitivity and a 93% specificity for distinguishing serous cystadenomas from mucinous cystadenomas, cystadenocarcinomas and pseudocysts. CONCLUSION: Combined measurement of CA 72-4 and carcinoembryonic antigen may be used to distinguish accurately mucinous cystadenomas and cystadenocarcinomas from serous cystadenomas and pseudocysts.

[Diagnostic value of serum Ca 19-9 antigen in chronic pancreatitis and pancreatic adenocarcinoma]. / Valeur diagnostique de l'antigène sérique Ca 19-9 au cours de la pancréatite chronique et de l'adénocarcinome pancréatique. Influence de leurs complications.

OBJECTIVES: The value of serum Ca 19-9 dosage for pancreatic carcinoma diagnosis has been studied in heterogeneous series. The effect of the complications of chronic pancreatitis and pancreatic carcinoma on serum Ca 19-9 value has not been assessed precisely. The aims of this study were to assess: a) the value of Ca 19-9 to differentiate benign from malignant pancreatic disease; b) the influence of complications (particularly, cholestasis). METHODS: The studied population included 179 patients: 126 with chronic pancreatitis (25 females, 101 males, 45 with cholestasis) and 53 with pancreatic carcinoma (27 females, 26 males, 37 with cholestasis). RESULTS: At 37 UI/mL threshold, the specificity and sensitivity of Ca 19-9 were 53 and 95%, respectively. Cholestasis was associated with a significant increase of Ca 19-9 in patients with chronic pancreatitis but not in those with pancreatic carcinoma. At 300 UI/mL threshold, the specificity and sensitivity of Ca 19-9 were 95 and 81% in patients without cholestasis and 87 and 81% in those with cholestasis, respectively. Diabetes mellitus was associated with a significant increase of Ca 19-9 only in patients with chronic pancreatitis without cholestasis. Pancreatic calcifications, pseudocysts, cirrhosis, pleural effusion or ascites were not associated with significant variation of Ca 19-9. CONCLUSION: In patients with pancreatic disease, 300 UI/mL threshold is the most accurate to differentiate benign from malignant disease, whatever the presence of cholestasis.

Detection of gastric mucins (M1 antigens) in cyst fluid for the diagnosis of cystic lesions of the pancreas.

Mucinous cystic tumors of the pancreas must be distinguished from other cystic lesions because of their potential malignancy. Our purpose was to assess the reliability of gastric M1 mucin analysis in the fluid of cystic lesions of the pancreas in comparison or association with carcinoembryonic antigen. M1 mucin and carcinoembryonic antigen were measured in cyst fluid obtained preoperatively by fine-needle aspiration. The lesions consisted of 12 serous cystadenomas, 9 mucinous cystadenomas, 8 cystadenocarcinomas and 6 intraductal mucinous hypersecreting neoplasms. Thirty pancreatic pseudocysts complicating well-documented chronic pancreatitis were also examined. In addition, M1 mucins were localized by immunoperoxidase staining in fetal and normal adult pancreas and in mucinous and serous tumors. Carcinoembryonic values of > 20 ng/ml and M1 mucin values of > 50 U M1/ml represented 82 and 78% sensitivity, respectively, as well as 100% specificity for distinguishing mucinous lesions from serous cystadenomas; the sensitivity for this purpose was 100% using these criteria in combination. Carcinoembryonic antigen values of > 300 ng/ml and M1 mucin values of > 1,200 U M1/ml represented 56 and 30% sensitivity, respectively, as well as 100% specificity for distinguishing mucinous lesions from pseudocysts; the sensitivity for this purpose was 60% using these criteria in combination. By immunohistology, M1 mucins were detected in the wall of mucinous lesions but not in fetal and normal adult pancreas and in serous cystadenomas. Measurement of M1 mucin antigen in cyst fluid could thus improve the diagnosis of mucinous cystic lesions of the pancreas.

Preoperative cyst fluid analysis is useful for the differential diagnosis of cystic lesions of the pancreas.

BACKGROUND/AIMS: It has been suggested that activity of pancreatic enzymes and concentrations of tumoral markers in cyst fluid may help to distinguish pseudocyst, serous, and mucinous cystadenomas. The aim of this study was to prospectively assess the reliability of preoperative biochemical and tumor marker analysis in cyst fluids obtained by fine-needle aspiration for pathological diagnosis. METHODS: Cyst fluid was obtained preoperatively by fine-needle aspiration, and biochemical and tumoral marker values were measured. The diagnosis of cystic tumors (7 serous cystadenomas and 12 mucinous tumors) was established by surgical specimen analysis. Thirty-one pancreatic pseudocysts complicating well-documented chronic pancreatitis were also studied. RESULTS: Carbohydrate antigen 19.9 levels of > 50,000 U/mL had a 75% sensitivity and a 90% specificity for distinguishing mucinous tumors from other cystic lesions. Carcinoembryonic antigen levels of < 5 ng/mL had a 100% sensitivity and an 86% specificity for distinguishing serous cystadenomas from other cystic lesions. Amylase levels of > 5000 U/mL had a 94% sensitivity and a 74% specificity for distinguishing pseudocysts from other cystic lesions. CONCLUSIONS: High carbohydrate antigen 19.9, low carcinoembryonic antigen, and high amylase levels in cyst fluid are very indicative of mucinous tumors, serous cystadenomas, and pseudocysts, respectively.

[Diagnosis of cystadenomas and cystadenocarcinomas of the pancreas. Study of 35 cases]. / Diagnostic des cystadénomes et cystadénocarcinomes du pancréas. Etude de 35 cas.

OBJECTIVES: The aims of this study were to assess the circumstances of diagnosis and accuracy of imaging procedures in patients with cystic pancreatic tumours. METHODS: Thirty-five consecutive patients with cystic pancreatic tumours (serous cystadenomas: n = 19, mucinous cystadenomas: n = 9, cystadenocarcinomas: n = 7) were studied from 1988 to 1993. Respective diagnostic values of ultrasonography, endoscopic ultrasonography, CT scan and analysis of cyst fluid were evaluated. RESULTS: The circumstances of diagnosis were abdominal pain (74%), weight loss (23%), jaundice (8%), abdominal mass (6%), asymptomatic (6%). Initial diagnosis of cystadenoma was correctly made by ultrasonography, CT scan and endoscopic ultrasonography in 63%, 77% and 84%, and the type of cystadenoma was correctly diagnosed in 20%, 51% and 55%. A pseudocyst was falsely diagnosed in 28%, 12% and 3%, respectively. After blind review of CT scans and endoscopic ultrasonography records, the type of cystadenoma was correctly diagnosed in 82% by both procedures. Cytological examination of cyst fluid of 18 cystic tumours gave correct diagnosis in 10 cases with sufficient material. A low CEA (P < 0.002), Ca 19.9 (P < 0.003) and absence of mucins (P < 0.002) in cyst fluid was evocative of serous cystadenoma. CONCLUSIONS: Abdominal pain was the main circumstance of diagnosis in cases of pancreatic cystadenomas. The type of cystadenoma was correctly diagnosed in 82% by CT scan and endoscopic ultrasonography. Cytological examination, tumoural marker and mucin levels in cyst fluid were helpful for an accurate diagnosis of cystic tumours.

[Recent aspects of liver biochemistry: from physiopathology to functional liver exploration]. / Aspects récents de la biochimie hépatique: de la physiopathologie á l'exploration functionnelle du foie.

The advent of liver transplantation and the availability of effective medical therapeutics have recently made possible treatments of chronic liver diseases. These improvements have evidenced new needs for evaluation of the treated patients. In this review, authors present new biochemical liver tests proposed for a better monitoring in the course of the disease, to assess the therapeutic response in clinical trials and to reduce the number of liver biopsies. The different aspects of this paper concern the evaluation of hepatic uptake and biliary elimination, cholestasis, jaundice, cellular injury, fibrosis and liver tumor.

[Proteinuria after infusion of gelatin. Comparison of Plasmion and Haemaccel]. / Protéinurie après perfusion de gélatine. Comparaison entre Plasmion et Haemaccel.

Modified gelatin are said without deleterious effect on kidney, an important proteinuria as been seen however in surgical patients after gelatin perfusion. A study in 15 patients scheduled for abdominal surgery compared the renal effects of two modified gelatin: Plasmion (gr P) and Haemaccel (gr H) administered in a similar manner. In the two groups proteinuria appears as soon as perfusion begins with at the third hour a peak which may be as high as 6 g/l. In the same time low molecular weight proteinuria (less than 30 kdalton) appears. The beta 2 microglobulinuria (beta 2m) is significatively enhanced (p less than 0,001). Albuminuria is also enhanced but without statistic signification. Comparison between the two groups reveals that in gr P proteinuria is of the same importance, but delayed, with a significatively smaller elimination of beta 2m (1,8 mg/mmol creatininuria versus 8,6,p less than 0,001). Enzymuria increases in a variable fashion. Proteinuria is probably due to tubular reabsorption inhibition of filtered protein induced by gelatin, particularly by amino acids arginine and lysin which become free after gelatin hydrolysis. If this phenomenon is pathologic or not is unclear and gelatin cannot be said absolutely innocuous. However this phenomenon must be known when proteinuria specially beta 2m is to be interpreted.