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FIBRONECTIN, A MARKER FOR MALIGNANT ASCITES
1104
platelet transfusion and the platelet count did not again descend a dangerous zone (figure). In future, if prenatal platelet transfusions are shown to be consistently effective, caesarean towards
TOTAL PROTEIN LEVEL
FIBRONECTIN LEVEL
section will not be necessary. The frequency of prenatal haemorrhage is difficult to assess. It is about 7% in our seriesand these accidents result in fetal or neonatal death or severe neurological sequelae. When a very low fetal platelet count is noted early during pregnancy do we wait or treat the fetus? In our hands repeated fetal blood sampling during pregnancy (49 cases) is possible without accident. This does require experienced obstetric, laboratory, and immunological teams used to working together, but such tight cooperation does open the door to true prenatal medicine, not only for diagnosis but also for treating the fetus before the appearance of irreversible sequelae. Department of Prenatal Diagnosis and Fetology, Hôpital Notre Dame de Bon Secours, 75014 Paris, France
Leucocyte Immunology Unit, Centre National de Transfusion Sanguine, Centre d’Hémobiologie Perinatale, Paris
F. DAFFOS F. FORESTIER Y. MULLER M. F. REZNIKOFF-ETIEVANT C. KAPLAN
J.
1 Muller JY, Reznikoff-Etievant MF, Patureau C, Dangu C, Chesnel N Thrombopénies néonatales alloimmunes Etudes clinique et biologique de 84 cas Nouv Presse Méd
(in press)
FIBRONECTIN, A MARKER FOR MALIGNANT ASCITES
SiR,—Cirrhotic and malignant ascites can be difficult to differentiate clinically, especially when protein level in ascites of cirrhotic patients is high. Several laboratory tests have been proposed, including the serum/ascites albumin concentration gradient.’ Since fibronectin is secreted into culture medium by malignant cell lines in vitro2we have assessed the value of measuring the fibronectin concentration of ascitic fluid in the diagnosis of malignant ascites. 56 consecutive patients with ascites were studied: 41 (group C) had cirrhosis of the liver with (9) or without (32) spontaneous bacterial pernonins and the other 15 (group MA) had malignant ascites caused by ovarian carcinoma (7), gastric adenocarcmoma (3), rectal carcinoma (1), endometnal carcinoma (1), peritoneal mesothelioma (1), or an unidentified primary carcinoma (2). Ascites cas sampled for cytology and for measurement of total protein and fibronectin concentrations. The plasma fibronectin concentration was also measured in 15 group C and 7 group MA patients and compared with the results in 70 agepaired controls. Total protein was measured by autoanalyser (’Astra-8’; Beckman) and fibronectin bv laser immunonephelometry with Behring Institute specific immune serum. The unpaired Student t-test was used for statistical analysis. Results are expressed in terms of mean±SD. The results are shown in the figure. No significant difference was observed between group C patients with and without infected ascites. Ascitic fibronectin concentrations were significantly higher in group MA than in group C (156-7+55-6 vs 41’9±35’2 2 mg/l, p<0-001) and exceeded 85 mg/1 in 14 (93Q7o) group MA patients but in only 1 group C patient. Ascitic total protein was also significantly greater in group MA than in group C (42 -2:tll’55 vs 18 -1 ± 12 -99 g/1, but whereas 14 (93%) group MA patients had a p<0-001) concentration exceeding 30 g/1 this was also true of 8 (19%) group C patients (bacterial peritonitis in 3). All MA patients with a high ascitic protein level had an ascitic fibronectin level above 85 mg/1 compared with only 1 of 8 group C patients. Malignant cells were found in ascites of 66% of the MA patients. Plasma fibronectin concentrations (215±74 mg/1 in group C and 414+246 mg/1 in group MA) were not significantly different though plasma fibronectin concentrations in group C were significantly lower than normal (381 ±46 mg/1, p<0-001). Ascitic fibronectin concentrations were some three times higher in malignant than in cirrhotic ascites, with a very small overlap between the two groups, offering a clearer discrimination than that provided by ascitic total protein. High concentrations of ascitic protein (>30 g/1) were noted in 19% of our cirrhotic patients, as others have found,but only 1 of these patients had a high fibronectin concentration. This result may be clinically useful,
especially
since,
despite repeated samplings (up
to seven
per
protein and fibronectin levels. C=cirrhotic ascites; 0 infected ascites; . sterile ascites; MA = malignant
Ascitic total
ascites. Mean±SD also shown.
patient), malignant cells lines were found in no more than 66% of patients with carcinoma. This low sensitivity accords with the 40-60% of positive cytological results reported elsewhere. 5,6 Falsepositive cytological results have also been reportedbut were not present in this series. Abnormally low plasma concentrations of fibronectin may be due to increased consumption of circulating fibronectin in cirrhotic patients’ and may help to explain why low ascitic fibronectin levels were observed in our cirrhotic patients. On the other hand, plasma fibronectin concentrations in our patients with malignant ascites were very variable and plasma fibronectin alone can not explain the constant rise of ascitic fibronectin level we found. This finding suggests that fibronectin originates from a local secretion, either by direct synthesis by malignant cellsor indirect production by reactive cells infiltrating surrounding connective tissue.9 Although the origin of ascitic fibronectin remains to be ascertained, this study leads us to believe that fibronectin may indeed be clinically helpful in the differential diagnosis of ascites, especially in patients with high ascitic protein levels.
Services of Hepatogastroenterology, Biochemistry, and Morbid Anatomy, CHU Bernard, 86021 Poitiers, France
G. DEVERBIZIER M. BEAUCHANT A. CHAPRON G. TOUCHARD D. REISS
1. Pare P, Talbot J, Hoefs JC Serum-ascites albumin concentration gradient a physiologic approach to the differential diagnosis of ascites Gastroenterology 1983. 85: 240-44 2 Mosesson MW, Amrani DL The structure and biologic activities of plasma fibronectin Blood 1980; 56: 145-58 3 Pott G, Meyering M, Voss B, Karges HE, Sieber A. Rapid determination of fibronectin by laser-nephelometry. J Clin Chem Clin Biochem 1980; 18: 893-95. 4 Boyer TD, Kahn AM, Reynolds TB Diagnostic value of ascitic fluid lactic deshydrogenase, protein and WBC levels. Arch Intern Med 1978; 138: 1103-05. 5 Dekker A, Bupp PA. Cytology of serous effusions, an investigation into the usefulness of cell blocks versus smears Am J Clin Pathol 1978; 70: 855-60 6. Loewenstein MS, Rittgers RA, Feinerman AE, et al. Carcinoembryonic antigen assay of ascites and detection of malignancy. Ann Intern Med 1978; 88: 635-38 7 Matsuda M, Yamanaka T, Matsuda A Distribution of fibronectin in plasma and liver in liver diseases. Clin Chim Acta 1982; 118: 191-99. 8 Smith HS, Riggs JL, Mosesson MW. Production of fibronectin by human epithelial cells in culture Cancer Res 1979, 39: 4138-44 9. Stenman S, Vaheri A. Fibronectin in human solid tumours Int J Cancer 1981, 27: 427-35.
platelet transfusion and the platelet count did not again descend a dangerous zone (figure). In future, if prenatal platelet transfusions are shown to be consistently effective, caesarean towards
TOTAL PROTEIN LEVEL
FIBRONECTIN LEVEL
section will not be necessary. The frequency of prenatal haemorrhage is difficult to assess. It is about 7% in our seriesand these accidents result in fetal or neonatal death or severe neurological sequelae. When a very low fetal platelet count is noted early during pregnancy do we wait or treat the fetus? In our hands repeated fetal blood sampling during pregnancy (49 cases) is possible without accident. This does require experienced obstetric, laboratory, and immunological teams used to working together, but such tight cooperation does open the door to true prenatal medicine, not only for diagnosis but also for treating the fetus before the appearance of irreversible sequelae. Department of Prenatal Diagnosis and Fetology, Hôpital Notre Dame de Bon Secours, 75014 Paris, France
Leucocyte Immunology Unit, Centre National de Transfusion Sanguine, Centre d’Hémobiologie Perinatale, Paris
F. DAFFOS F. FORESTIER Y. MULLER M. F. REZNIKOFF-ETIEVANT C. KAPLAN
J.
1 Muller JY, Reznikoff-Etievant MF, Patureau C, Dangu C, Chesnel N Thrombopénies néonatales alloimmunes Etudes clinique et biologique de 84 cas Nouv Presse Méd
(in press)
FIBRONECTIN, A MARKER FOR MALIGNANT ASCITES
SiR,—Cirrhotic and malignant ascites can be difficult to differentiate clinically, especially when protein level in ascites of cirrhotic patients is high. Several laboratory tests have been proposed, including the serum/ascites albumin concentration gradient.’ Since fibronectin is secreted into culture medium by malignant cell lines in vitro2we have assessed the value of measuring the fibronectin concentration of ascitic fluid in the diagnosis of malignant ascites. 56 consecutive patients with ascites were studied: 41 (group C) had cirrhosis of the liver with (9) or without (32) spontaneous bacterial pernonins and the other 15 (group MA) had malignant ascites caused by ovarian carcinoma (7), gastric adenocarcmoma (3), rectal carcinoma (1), endometnal carcinoma (1), peritoneal mesothelioma (1), or an unidentified primary carcinoma (2). Ascites cas sampled for cytology and for measurement of total protein and fibronectin concentrations. The plasma fibronectin concentration was also measured in 15 group C and 7 group MA patients and compared with the results in 70 agepaired controls. Total protein was measured by autoanalyser (’Astra-8’; Beckman) and fibronectin bv laser immunonephelometry with Behring Institute specific immune serum. The unpaired Student t-test was used for statistical analysis. Results are expressed in terms of mean±SD. The results are shown in the figure. No significant difference was observed between group C patients with and without infected ascites. Ascitic fibronectin concentrations were significantly higher in group MA than in group C (156-7+55-6 vs 41’9±35’2 2 mg/l, p<0-001) and exceeded 85 mg/1 in 14 (93Q7o) group MA patients but in only 1 group C patient. Ascitic total protein was also significantly greater in group MA than in group C (42 -2:tll’55 vs 18 -1 ± 12 -99 g/1, but whereas 14 (93%) group MA patients had a p<0-001) concentration exceeding 30 g/1 this was also true of 8 (19%) group C patients (bacterial peritonitis in 3). All MA patients with a high ascitic protein level had an ascitic fibronectin level above 85 mg/1 compared with only 1 of 8 group C patients. Malignant cells were found in ascites of 66% of the MA patients. Plasma fibronectin concentrations (215±74 mg/1 in group C and 414+246 mg/1 in group MA) were not significantly different though plasma fibronectin concentrations in group C were significantly lower than normal (381 ±46 mg/1, p<0-001). Ascitic fibronectin concentrations were some three times higher in malignant than in cirrhotic ascites, with a very small overlap between the two groups, offering a clearer discrimination than that provided by ascitic total protein. High concentrations of ascitic protein (>30 g/1) were noted in 19% of our cirrhotic patients, as others have found,but only 1 of these patients had a high fibronectin concentration. This result may be clinically useful,
especially
since,
despite repeated samplings (up
to seven
per
protein and fibronectin levels. C=cirrhotic ascites; 0 infected ascites; . sterile ascites; MA = malignant
Ascitic total
ascites. Mean±SD also shown.
patient), malignant cells lines were found in no more than 66% of patients with carcinoma. This low sensitivity accords with the 40-60% of positive cytological results reported elsewhere. 5,6 Falsepositive cytological results have also been reportedbut were not present in this series. Abnormally low plasma concentrations of fibronectin may be due to increased consumption of circulating fibronectin in cirrhotic patients’ and may help to explain why low ascitic fibronectin levels were observed in our cirrhotic patients. On the other hand, plasma fibronectin concentrations in our patients with malignant ascites were very variable and plasma fibronectin alone can not explain the constant rise of ascitic fibronectin level we found. This finding suggests that fibronectin originates from a local secretion, either by direct synthesis by malignant cellsor indirect production by reactive cells infiltrating surrounding connective tissue.9 Although the origin of ascitic fibronectin remains to be ascertained, this study leads us to believe that fibronectin may indeed be clinically helpful in the differential diagnosis of ascites, especially in patients with high ascitic protein levels.
Services of Hepatogastroenterology, Biochemistry, and Morbid Anatomy, CHU Bernard, 86021 Poitiers, France
G. DEVERBIZIER M. BEAUCHANT A. CHAPRON G. TOUCHARD D. REISS
1. Pare P, Talbot J, Hoefs JC Serum-ascites albumin concentration gradient a physiologic approach to the differential diagnosis of ascites Gastroenterology 1983. 85: 240-44 2 Mosesson MW, Amrani DL The structure and biologic activities of plasma fibronectin Blood 1980; 56: 145-58 3 Pott G, Meyering M, Voss B, Karges HE, Sieber A. Rapid determination of fibronectin by laser-nephelometry. J Clin Chem Clin Biochem 1980; 18: 893-95. 4 Boyer TD, Kahn AM, Reynolds TB Diagnostic value of ascitic fluid lactic deshydrogenase, protein and WBC levels. Arch Intern Med 1978; 138: 1103-05. 5 Dekker A, Bupp PA. Cytology of serous effusions, an investigation into the usefulness of cell blocks versus smears Am J Clin Pathol 1978; 70: 855-60 6. Loewenstein MS, Rittgers RA, Feinerman AE, et al. Carcinoembryonic antigen assay of ascites and detection of malignancy. Ann Intern Med 1978; 88: 635-38 7 Matsuda M, Yamanaka T, Matsuda A Distribution of fibronectin in plasma and liver in liver diseases. Clin Chim Acta 1982; 118: 191-99. 8 Smith HS, Riggs JL, Mosesson MW. Production of fibronectin by human epithelial cells in culture Cancer Res 1979, 39: 4138-44 9. Stenman S, Vaheri A. Fibronectin in human solid tumours Int J Cancer 1981, 27: 427-35.