677
Ascitic Fluid Analysis in Hepatocellular
Carcinoma
Agosfino Colli, M.D., Massimo Cocciolo, M.D., Carlo Xiva, M.D.,
Loredana Marcassoli, Mariangela Pirola, Palma Di Gregorio, Biol.Sc.D.,
and Guglielmo Buccino, Bio1.Sc.D.
Background. Ascites in patients with hepatocellular
carcinoma (HCC) is a poorly characterized subgroup of
malignancy-related ascites. Not only the underlying liver
disease, but also the tumor growth and spread contrib-
utes to the ascites formation. The authors differentiated
ascites in HCC from other types of ascites.
Methods. The authors analyzed the ascitic fluid of
185 consecutive patients (89 liver cirrhosis, 33 HCC, 31
peritoneal carcinomatosis, 22 liver metastases, 10 sponta-
neous bacterial peritonitis).
Resulfs. Each subgroup showed a typical pattern.
Compared with the cirrhotic patients, those with HCC
showed a higher frequency of positive cytologic findings
(4 of 33 versus 0/89, P < 0.004), elevated fibronectin con-
centration (10/33 versus 8/89, P < 0.004), and elevated
polymorphonuclear cell count (10/33 versus 5/89 P <
0.004).
Conclusions. A significant number of patients with
ascites and HCC patients showed signs of peritoneal infil-
tration with positive cytologic findings and increased
concentration of fibronectin. Moreover, neutrocytic
ascites without signs of superinfection is relatively com-
mon (30%). Cancer 1993; 72677-82.
Key words: hepatocellular carcinoma, serum-ascites al-
bumin gradient, spontaneous bacterial peritonitis, fibro-
nectin, diagnostic paracentesis.
Hepatocellular carcinoma (HCC) is a common compli-
cation of long-standing liver disease and, at least in
Western Countries and in Japan, more than 80% of the
cases are overimposed on a cirrhotic liver.',2
Ascites in patients with HCC is considered a sign of
the severity of the underlying liver disease with portal
hypertension and hypoalbuminemia. Its response to
the treatment with diuretics depends, as in uncompli-
From Ospedale "C. Borella," Giussano (Milano), Italy.
Address for reprints: Agostino Colli, M.D., Divisione di Medi-
cina, Ospedale di Giussano, via Milano, 65, 20034 Giussano (Milano)
Italy.
Accepted for publication March 23, 1993.
cated cirrhosis, on the renal f ~ n c t i o n However,
.~ the
growth and spread of HCC could, at least hypotheti-
cally, worsen fluid accumulation into the peritoneal cav-
ity by increasing portal pressure with thrombosis or
compression of intrahepatic portal branches or by ob-
structing lymph channels and infiltrating the perito-
neum.
Despite the large amount of information about
ascitic fluid analysis and its diagnostic value, we have
not found any study devoted to characterize the ascitic
fluid in patients with HCC.
Recently, some biochemical parameters (serum-
ascites albumin gradient [SAAG], ascitic fibronectin,
cholesterol, sialic acid) have been reported to yield a
near-perfect discrimination between malignant and
nonmalignant ascites, even better than cytologic exami-
nation.4-" However, in these studies, patients with
HCC are not examined at all or are considered as a
small and marginal subgroup.
To differentiate ascites in HCC from other types of
ascites, particularly from sterile uncomplicated ascites
in cirrhosis of the liver, we analyzed, measuring these
new parameters (SAAG, fibronectin, cholesterol, and
sialic acid) a series of 185 consecutive ascites (33 from
patients with HCC overimposed on liver cirrhosis, 89
sterile uncomplicated ascites in cirrhosis of the liver, 31
peritoneal carcinomatosis, 22 from patients with liver
metastasis, and 10 spontaneous bacterial peritonitis).
Patients
We examined 185 consecutive patients with ascites ad-
mitted to our medical division between January 1986
and September 1991. We classified them into five
groups:
Group 1
Eighty-nine patients had sterile uncomplicated cirrhotic
ascites. Diagnosis of cirrhosis was based on clinical
678 CANCER August 1, 1993, Volume 72, No. 3
grounds and histologically confirmed in 5 1 of them. In
every patient, the serum alpha-fetoprotein was lower
than 10 ng/ml and the ultrasound (US) abdomen scan
showed no evidence of malignancy. Microbiologic cul-
tures of the fluid gave negative results.
Group 2
Thirty-three patients had ascites of 70 patients with
HCC in liver cirrhosis. The diagnosis was based on his-
tologic study of adequate specimens obtained by US-
guided biopsy or laparoscopy or at necropsy. Multiple
tumor masses or a large single mass with a diameter > 5
cm were found in five patients. In all of the patients, the
finding of ascites was concomitant with the diagnosis
of HCC.
Group 3
Thirty-one patients had peritoneal carcinomatosis: 7
with and 24 without liver metastases. Diagnosis was
based on positive ascitic cytologic findings at paracente-
sis and surgical or laparoscopic findings of peritoneal
infiltration in patients with ovarian (13), colonic (6),
uterine (2), renal (2), pancreatic (l),breast (l), lym-
phoma (l),or unknown (5) malignancy.
Group 4
Twenty-two patients had liver metastases, no evidence
of liver cirrhosis, and negative ascitic cytologic results.
Diagnosis was made by histologic or cytologic study on
specimens obtained by US-guided biopsy or fine-nee-
dle aspiration of the liver metastases: 7 gastric carci-
noma, 4 colonic carcinoma, 2 pancreatic carcinoma, 2
lung carcinoma, 2 ovarian carcinoma, 2 lymphoma, 1
breast carcinoma, 1 renal carcinoma, and 1 adenocarci-
noma of unknown origin.
Group 5
Ten patients had spontaneous bacterial peritonitis with
positive bacteriologic culture of the ascites in absence of
evident visceral contamination. In all of the patients,
the polymorphonuclear cell (PMN) count was > 250/
mm3. Seven patients had cirrhosis of the liver, one had
HCC in cirrhosis, one had peritoneal carcinomatosis
from gastric carcinoma, and one had liver metastases
from colonic carcinoma and negative cytologic results.
To simplify the study, we excluded four patients
with ascites: one with tubercular peritonitis; one with
neoplastic infiltration of the pericardium and evidence
of constrictive pericarditis; one with amyloidosis, con-
gestive heart failure, nephrotic syndrome, and liver in-
filtration; and one with liver cirrhosis and abdominal
non-Hodgkin lymphoma.
Methods
In every patient, a diagnostic paracentesis was per-
formed within 24 hours from the admission to our hos-
pital, and usually before the beginning of any treat-
ment. Some patients were already in chronic treatment
with diuretics, but without oliguria and evidence of
fluid accumulation. None of the patients had received
antibiotic treatment before investigation.
Paracentesis was performed under aseptic condi-
tions using a 20-gauge needle and aspirating at least
350 ml of fluid: 20 ml were immediately injected, at
patients bedside, into blood culture bottles with aero-
bic and anaerobic culture media (Liquoid Brain Heart
Infusion and Thioglycollate, Roche, Basel, Switzerland)
and observed for an adequate period, up to a month.
The ascitic fluid was also cultured for Mycobacterium
tuberculosis in special media.
Leukocyte and PMN counts were performed by
nonautomated means. Cytologic examination was per-
formed within 1hour on stained smears of the sediment
of centrifuged 250 ml of fluid.
Chemical analyses (glucose, protein, albumin,
amylase, lactate dehydrogenase, triglyceride, choles-
terol) were performed by the techniques usually ap-
plied for blood samples. For alpha-fetoprotein and car-
cinoembryonic antigen determination, an immunoen-
zymatic assay was used (IMx AFP and 1Mx CEA,
Abbott GmbH Wiesbaden, Germany). The fibronectin
concentration was determined by nephelometric assay
with a specific immune serum (Behringwerke AG, Mar-
burg, W. Germany) in 5 ml of ascitic fluid freshly col-
lected in a plastic tube containing ethylenediamine tet-
raacetic acid. The sialic acid concentration was deter-
mined with enzymatic-colorimetric assay (Boehringer
Mannheim, W. Germany) in 5 ml of ascitic fluid. Serum
total protein and albumin concentrations were mea-
sured for determination of SAAG on a venous blood
sample taken immediately before paracentesis.
Statistical Analysis
For each parameter, a comparison among groups was
performed with analysis of variance and the Student-
Neuman-Keuls test. We preselected the cutoff values
for each parameter indicating complicated ascites ac-
cording to the data of previous studies: particularly
SAAG < 1.1 mg/dl, ascitic fibronectin > 75 mg/l, cho-
lesterol > 50 mg/dl, sialic acid > 30 mg/dl, leukocyte
count > 500/mm3, PMN > 250/mm3. We calculated
and analyzed the frequency rates exceeding the cutoff
Ascites in HCC/Colli et al. 679

Table 1. Results of Ascitic Fluid Analysis in 175 Patients With Ascites and Comparison Between Sterile
Uncomplicated Cirrhotic Ascites and Malignancy-Related Ascites Subgroups
Group 1 Group 2 Group 3 Group 4

(n = 89) (n = 33) (n = 31) (n = 22)

Parameter Mean 2 S D Mean f SD P versus 1 Mean ? SD P versus 1 Mean f SD P versus 1
Serum-ascites albumin
gradient (g/dl) 1.9 f 0.5 2.1 f 0.7 NS 0.8 f 0.7 < 0.01 1.5 f 0.8 NS
Fibronectin (mg/l) 32.1 f 30.1 *
29.0 62.8 NS 204.2 f 93.0 < 0.01 84.9 -+ 74.4 < 0.01
Sialic acid (mg/dl) 16.2 f 88.1 21.0 f 18.1 NS 59.0 f 18.4 < 0.01 34.7 2 137.6 < 0.01
Cholesterol (mg/dl) 30.1 k 33.9 24.7 f 26.4 NS 93.4 f 26.2 < 0.01 68.2 f 44.3 NS
Leukocyte count
(cells/mm3) 422 f 571 809 f 860 NS 3011 f 2294 < 0.01 1055 2 1595 NS
Polymorphonuclear cell
count (cells/mm3) 103 f 102 765 f 768 NS 1622 f 1066 < 0.01 55 -+ 39 NS
Group 1: sterile uncomplicated cirrhotic ascites; Group 2: hepatocellular carcinoma in liver cirrhosis; Group 3: peritoneal carcinomatosis; Group 4: liver metastases;
SD: standard deviation.

for each group of ascites with chi-square test, with
Yates modification, and the Bonferroni adjustment
where needed; a P value < 0.05 was considered signifi-
cant. We excluded from the comparisons the 10 pa-
tients with spontaneous bacterial peritonitis (SBP).
ResuIts
Results are expressed as mean k SD unless otherwise
indicated.
None of the parameters considered showed a signif-
icant difference between HCC and sterile uncompli-
cated cirrhotic ascites, comparing the mean values; how-
ever, the comparison of the rates of frequency of values
exceeding the cutoffs showed a significant difference
for fibronectin, cytologic findings, leukocyte count, and
PMN count ( P < 0.001).
In patients with other subtypes of malignancy-re-
lated ascites (groups 3 and 4), not only fibronectin but
also sialic acid and cholesterol concentrations were
higher than in group 1. SAAG was lower in patients
with peritoneal carcinomatosis.
Table 1 shows the mean value and SD in groups 1
to 4. In Table 2 the rates of SAAG, fibronectin, sialic
acid, cholesterol, leukocyte count, PMN count exceed-
ing the cutoff values and the results of cytologic exami-
nation in each group are shown. Table 3 shows the
diagnostic value of fibronectin, leukocyte count, PMN
count, and cytologic findings in the differential diagno-
sis between HCC and sterile uncomplicated cirrhotic
ascites. Table 4 shows the results of ascitic fluid analysis
in the 10 patients with SBP (group 5).
Serum alpha-fetoprotein was elevated (> 200 ng/
ml) in 21 of 33 patients with HCC and always normal,
by definition, in patients with cirrhosis and in those
with other malignancies. Ascitic concentration was >15
ng/dl only in patients with elevated serum concentra-
tion; in all of the patients, the concentration in the asci-
tic fluid was lower than serum concentration.
SAAG was lower than 1.1 g/dl in the exudative
range, in 21 of 31 patients with peritoneal carcinomato-
sis, in 3 of 33 with HCC, in 7 of 22 with liver metas-
tases, and in only 1 of 89 patients with cirrhosis. Con-
comitant liver metastases (seven) or liver cirrhosis (one)
were demonstrated by US abdomen scan or biopsy or
both in the patients with peritoneal carcinomatosis and
SAAG > 1.1.
Ascitic sialic acid was elevated in 30 of 31 patients
with peritoneal carcinomatosis and in 10 of 22 patients
with liver metastases (P < 0.004 versus group 1).
Ascitic cholesterol was elevated in 16 of 89 cirrhotic
and in all 31 peritoneal carcinomatosis.
Fibronectin was elevated in 8 of 89 patients with
cirrhosis, 10 of 33 HCC, 2 of 22 metastases, and in 30 of
3 1 peritoneal carcinomatosis.
Leukocyte count and PMN count were elevated in
all patients with the infected ascites (SBP)in which cul-
ture was always positive. However, an increase in PMN
count with a negative culture was found in 24 of 31
patients with carcinomatosis and in 10 of 33 HCC, with
a significant difference with group 1 (cirrhosis of the
liver) and group 4 (liver metastases).
Finally, cytologic study was positive in 4 of 33 pa-
tients with HCC, with no false-positive results in group
1. Positive cytologic findings were, in every case, con-
firmed by an adequate liver biopsy.
Figure 1 shows the results of PMN count, cytologic
examination, and fibronectin concentration in the pa-
tients with HCC (group 2).
680 CANCER August 1, 1993, Volume 7 2 , No. 3

Table 2. Frequency Rate of Patients With Parameters That Exceed the Cutoff Values and Comparison Between Sterile
Uncomplicated Cirrhotic Ascites and Malignancy-Related Ascites Subgroups
Group 1 (YO) Group 2 (%) Group 3 (%) Group 4 (YO)
Parameter (n = 89) (n = 33) P versus I (n = 31) P versus 1 (n = 22) P versus 1
Serum-ascites albumin gradient
(< 1.1g/dl) 1(1) 3 (9) NS 21 (68) < 0.004 7 (32) NS
Fibronectin (> 75 mg/l) 8 (9) 10 (30) < 0.04 30 (97) < 0.004 8 (37) < 0.04
Sialic acid (> 30 mg/dl) 7 (8) 6 (18) NS 30 (97) < 0.004 15 (68) < 0.02
Cholesterol (> 50 mg/dl) 16 (18) 3 (9) NS 31 (100) < 0.004 15 (68) < 0.02
Leukocyte count (> 500/mm3) 26 (29) 19 (58) < 0.04 31 (100) < 0.004 11 (50) < 0.02
Polymorphonuclear cell count
(> 250/mm3) 5 (6) 10 (30) < 0.004 24 (77) < 0.004 0 NS
Positive cytologic results 0 4 (12.1) < 0.04 31 (100) < 0.004 0 NS
Group 1: sterile uncomplicated cirrhotic ascites; Group 2: hepatocellular carcinoma in liver cirrhosis; Group 3: peritoneal carcinomatosis; Group 4: liver metastases.

Discussion is an intracellular matrix glycoprotein released from ma-

Malignancy-related ascites is classified into five main
subgroups on pathophysiologic basis: (1) peritoneal
carcinomatosis without liver metastases; (2) peritoneal
carcinomatosis with liver metastases; (3) massive liver
metastases without peritoneal infiltration; (4)chylous
ascites (rare); and (5) HCC. Every subgroup is expected
to have a characteristic cytologic and biochemical pat-
tern.13 To make it easy, if peritoneal infiltration cyto-
logic results are positive and if liver metastases occur,
SAAG is > 1.1g/dl.
Our data fail to demonstrate a typical pattern in the
subgroup of patients with HCC (Tables I and 2). The
SAAG-that is, the oncotic gradient between serum
and ascites correlated with portal hypertension (the hy-
drostatic counterbalancing pre~sure)'~-as expected,
almost always produced elevated (30/33,91 YO)results.
Cytologic findings were positive in four cases (12%),
according to the autopsy findings of peritoneal infiltra-
tion in another series.I5 Moreover, ascitic fibronectin
concentration was elevated in 10 of 33 patients (3 of
which had positive cytologic findings). In a recent re-
port, ascitic fibronectin was elevated in 3 of 16 patients
with HCC without peritoneal metastases.' Fibronectin
lignant cells dissociating into the peritoneal cavity.l 6 It
was found in elevated concentrations in peritoneal car-
cinomatosis (30/31, 97% in our series). However, two
other markers of malignant implants in the
peritoneum-cholesterol" and sialic acid"-showed a
lower sensitivity (3/33, or 9%; and 6/33, or IS%, re-
spectively) in patients with HCC.
Alpha-fetoprotein concentration in ascites was ele-
vated (> 15 ng/rn1)l3 in 12 of 33 (36%) patients with
HCC but only in 50% of patients with elevated serum
level (> 200 ng/ml: 21/33, 63%). Thus its measure-
ment in the ascites seems not to yield additive informa-
tion.
Finally, we found a statistically significant increase
in frequency of an elevated leukocyte count and PMN
count in ascites of patients with HCC compared with
sterile uncomplicated cirrhotic ascites. Increased leuko-
cyte count is a nonspecific finding often related to di-
uretic therapy and concentration of ascitic fluid.17 On
the contrary, increased PMN count (> 250/mm3) in
ascitic fluid is regarded as the most accurate index of
superinfection and dictate antibiotic therapy." Apart
from 10 cases of SBP (7 in cirrhosis, 1 in HCC, 1 in
massive metastasis, and 1in peritoneal carcinomatosis),

Table 3. Sensitivity, Specificity, and Diagnostic Accuracy of Fibronectin, Leukocyte Count, and Polymorphonuclear
Count in Differential Diagnosis Between Sterile Uncomplicated Cirrhotic Ascites and Ascites
in Hepatocellular Carcinoma
Group 1 Group 2 Diagnostic
Parameter (n = 89) (n = 33) Sensitivity Specificity (YO) accuracy (YO)
Fibronectin (> 75 mg/l) 8 10 30.3% 91 74.6
Leukocyte count (> 500/mm3) 26 19 57.6% 70.8 75.3
Polymorphonuclear cell count
(> 250/mm3) 5 10 30.3% 94.4 77
Positive cytologic findings 0 4 12.1% 100 85.3
Group 1: sterile uncomplicated cirrhotic ascites; Group 2: hepatocellular carcinoma in h e r cirrhosis.
Ascites in HCC/Colli et al. 681

Table 4. Ascitic Fluid Analysis in 10 Patients With Spontaneous Bacterial Peritonitis

Polymorphonuclear
Type of Fibronectin Leukocyte count cell count
ascites (ml/@ (cells/m3) (cells/mm3) Culture
Cirrhosis 60 1100 1000 Escherichia coli
Cirrhosis 26 1900 1600 E. coli
Cirrhosis 39 2700 2160 E. coli
Cirrhosis 10 6000 5400 Diplococcus pneumoniae
Cirrhosis 10 900 855 E. coli
Cirrhosis 56 2800 2576 Yersinia enferocolitica
Cirrhosis 60 26600 26000 E. coli
Hepatocellular
carcinoma 5 11500 11270 E. coli
Peritoneal
carcinomatosis 129 6000 5400 E. coli
Liver metastases 38 300 290 Proteus niirabilis

in which culture was positive, we found neutrocytic
ascites only in 5 of 89 (6%) patients with cirrhosis and
in 10 of 33 (30%)with HCC ( P < 0.004). None of these
patients showed symptoms indicative of peritoneal in-
fection at paracentesis and during follow-up. We per-
formed insemination and microbiologic cultures ac-
cording to the recommended thus un-
detected infection seems improbable. In another small
series, ascitic leukocyte and PMN counts were signifi-
cantly higher in patients with HCC (4/6 and 3/6, re-
spectively) than in cirrhotic patients (O/2O).I3 More-
over, the reported prevalence of sterile neutrocytic
ascites in cirrhosis is about 3% to 8%;18higher preva-
lence (28% with a cutoff value of 150 PMN/mm3) was
reported in a study which gathered in a single group
cirrhosis and HCC2 In peritoneal carcinomatosis, too,
we noticed an elevated leukocyte count in 31 of 31 pa-
1 a 0
0 0
0 ity in detection of malignancy-related as cite^.'-^," We
0 cannot exclude minimal peritoneal infiltration without
0
tients, and an elevated PMN count in 24 of 31 (P <
0.004, with respect to sterile uncomplicated cirrhotic
ascites), thus we suggest that the increase in the leuko-
cyte count, more specifically, in the PMN count in
ascites may represent a phlogistic reaction to neoplastic
implant in the peritoneum or on the liver surface. In our
series and in another recent report, superinfection of
ascitic fluid seems not to increase fibronectin ascitic
concentration. In our series of 10 cases of SBP, the only
patient with elevated fibronectin (> 75 mg/l) had peri-
toneal carcinomatosis (Table 3). On the contrary, other
reports emphasized the lack of specificity of increased
ascitic fibronectin concentration demonstrating high
concentration in SBP2*and in tubercular p e r i t ~ n i t i s . ~ ~
We found only 1patient (from 190 patients with ascites
admitted to our medical division in 5 years) with tuber-
cular ascites and she had elevated ascitic fibronectin
(230 mg/l).
In summary, ascitic fluid in a significant fraction of
patients with HCC differentiates from sterile uncompli-
cated cirrhotic ascites (Table 4 and Fig. 1) showing signs
of peritoneal infiltration (positive cytologic findings),
aseptic increase of PMN count, and elevated concentra-
tion of fibronectin, a glycoprotein released from malig-
nant cells. Ascitic fibronectin also was elevated in 8 of
22 (36%) patients with massive liver metastases and
negative cytologic findings, confirming a high sensitiv-
neoplastic cells shedding and, thus, these ascites should

: : have been correctly classified in the peritoneal carcino-

m so0 Rlp5
Figure 1. Polymorphonuclear cell (PMN) count and fibronectin
concentration in 33 patients with hepatocellular carcinoma (HCC,
group 2) with positive (0)and negative ( 0 )cytologic examination.
matosis group by more invasive diagnostic procedures
(laparoscopy or laparotomy) or at autopsy, in spite of
negative cytologic results.
In clinical practice, in case of ascites of unknown
cause, paracentesis and ascitic fluid analysis is informa-
tive. A neutrocytic ascites (with sterile adequate cul-
682 CANCER August 1, 1993, Volume 72, No. 3
tures) or elevated concentration of fibronectin or both
suggests the diagnosis of malignancy-related ascites,
particularly HCC or massive liver metastases if the
SAAG is elevated; a positive cytologic result is diagnos-
tic for peritoneal infiltration, with liver metastases or
cirrhosis if SAAG elevated.
References
1. Okuda K. Early recognition of hepatocellular carcinoma. Hepa-
tology 1986; 61729-38.
2. Colombo M, De Franchis R, Del Ninno E, Sangiovanni A, De
Fazio C, Tommasini M, et al. Hepatocellular carcinoma in Italian
patients with cirrhosis. N Engl ] Med 1991; 325:675-80.
3. Mas A, Arroyo V, Rodes J, Bosch J. Ascites and renal failure in
primary liver cell carcinoma. Br Med J 1975; 3:629-33.
4. Par6 P, Talbot J, Hoefs JC. Serum-ascites albumin concentration
gradient: a physiologic approach to the differential diagnosis of
ascites. Gastroenterology 1983; 85:240-44.
5 Rector WJ, Reynolds IB. Superiority of the serum-ascites albu-
min difference over the ascites total protein concentration in
separation of "transudative" and "exudative" ascites. Am J Med
1984; 77:83-5.
6 Albillos A, Cuervas-Mons V, Mill5 I, Cant6 T, Montes J, Barrios
C, et al. Ascitic fluid polymorphonuclear cell count and serum to
ascites albumin gradient in the diagnosis of bacterial peritonitis.
Gastroenterology 1990; 98:134-40.
7 Scholmerich J, Volk BA, Kottgen E, Ehlers S, Gerok W. Fibronec-
tin concentration in ascites differentiates between malignant
and nonmalignant ascites. Gastroenterology 1984; 87:1160-4.
8 Colli A, Buccino G, Cocciolo M, Parravicini R, Mariani F, Scal-
trini GC. Diagnostic accuracy of fibronectin in the differential
diagnosis of ascites. Cancer 1986; 58:2489-93.
9 Prieto M, Gbez-Lecho MJ, Hoyos M, Castell JV, Carrasco D,
Berenguer J. Diagnosis of malignant ascites: comparison of asci-
tic fibronectin, cholesterol and serum-ascites albumin differ-
ence. Dig Dis Sci 1988; 33:833-8.
10. Jungst D, Gerbes AL, Martin R, Paumgartner G. Value of ascitic
lipids in the differentiation between cirrhotic and malignant
ascites. Hepatology 1986; 6:239-43.
11, Colli A, Buccino G, Cocciolo M, Parravicini R, Mariani F, Scal-
trini GC. Diagnostic accuracy of sialic acid in the diagnosis of
malignant ascites. Cancer 1989; 63:912-6.
12. Zar 11-1.The binomial distribution. In: Zar JH.Biostatistical analy-
sis. Englewood Cliffs, NJ: Prentice-Hall 1974:495-8.
13. Runyon BA, Hoefs JC, Morgan TR. Ascitic fluid analysis in ma-
lignancy-related ascites. Hepatology 1988; 8:1104-9.
14. Hoefs JC. Serum protein concentration and portal pressure de-
termine the ascitic fluid protein concentration in patients with
chronic liver disease. 1 Lab Cliii Med 1983; 102:260-73.
15. Yuki K, Hirohashi 5, Sakamoto M, Kanai T, Shimosato Y.
Growth and spread of hepatocellular carcinoma. Cancer 1990;
66~2174-9.
16. Klaubert W, Hafter R, Gollwitzer R, Willmanns W, Graeff H.
Klinische wertigkeit von fibrin(ogen)-reaktionsprodukten und
fibronektin in der differentialdiagnose von aszites. Z Gastroen-
terol 1985; 23:458-62.
17. Hoefs JC. Increase in ascites white blood cell and protein con-
centration during diuresis in patients with chronic liver disease.
HepatoLogy 1981; 1:249-54.
18. Hoefs JC. Diagnostic paracentesis: a potent clinical tool. Gastro-
enterology 1990; 98:230-6.
19. Runyon BA, Canawati HN, Akriviadis EA. Optimization of asci-
tic fluid culture technique. Gastroenterology 1988; 95:1351-5.
20. Runyon BA, Umland ET, Merlin T. Inoculation of blood culture
bottles with ascitic fluid: improved detection of spontaneous bac-
terial peritonitis. Arch I n t e r n Med 1986; 147:73-6.
21. Pinzello G, Verdone R, Lojacono F, Ciambra M, Dardanoni G,
Fiorentino G, et al. Is the ascitic fluid a reliable index in making
the presumptive diagnosis of spontaneous bacterial peritonitis?
Hepatology 1986; 6:244-7.
22. Runyon BA. Elevated ascitic fluid fibronectin concentration: a
non-specific finding. I Hepatoi 1986; 3:219-22.
23. Villar M, Garcia-Bragado F, Vilardell M, Biosca M, Rodrigo MJ,
Schwartz 5.Fibronectin concentration does not differentiate be-
tween malignant and nonmalignant ascites. Gastroenterology
1988; 44:556-7.