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The role of preoperative liver biopsy in the diagnosis of hepatocellular carcinoma
106
Poster Sessions
The aim of this work was to quantify by ultrastructural morphometry the percentage of mitochondria acting in hepatocyte apoptosis induced by Fas stimulation. Three adult mice per time were administered with an agonistic anti-Fas antibody (502) and sacrificed at 2, 4 and 6 hrs. Copntrol mice receiving saline were killed at the same times. Three liver blocks per animal were processed for electron microscopy and 10 randomly chosen hepatocyte cytoplasmic fields were photographied. Mitochondria were considered abnormal when presented matrix expansion, cistae rarefaction and outer membrane rupture. Caspase 3 cleavage was investigated by immunocytochemistry and Western-blot. Percentage of apoptotic hepatocytes was measured by image analysis on light microscopy. At 4 hrs, 15.5f2.7% mitochondria wee abnormal while this percentage was only of 5.3f2.5% at 2 hrs and did not increase at 6 hrs. No abnormal mitochondria were observed in control mice. Surprisingly the relative number of mitochondria per hepatocyte in treated mice increased significantly and was at 4 hrs of 27.0f4.5% vs 17.6f5.2% for control mice (pt0.001). Caspase 3 cleavage and percentage of aopoptotic hepatocytes were at their maximum at 4 hrs. In conclusion these results showed that hepatocyte apoptosis after Fas stimulation depends on a very low number of mitochondria. Moreover the increase in their number suggets a profound dysregulation of mitochondrion mechanism
I
1363
PROSPECTIVE STUDY ON LIVER SPACE OCCUPYING LESIONS. THE RISK FOR HEPATOCELLULAR CARCINOMA
E. Paulon, L.S. Croce, C.S. Ricci, S. Markovic, C. Tiribelli. University of Trieste, Italy; University of Ljubliana, Slovenia
Aim: To determine the prevalence and the nature of hepatic Space Occupying Lesions (SOL). Material and Methods: 764 consecutive patients with SOL at ultrasonography (US), prospectively enrolled from l/l/1994 to 12/31/1997, 395 in Trieste and 369 in Ljubljana. SOL was an incidental finding at US performed for different reasons; 40% were detected during a follow-up for liver disease. All lesions were biopsed with the exception of cysts and angiomas, confirmed by TC scan or RBC-Tc scintigraphy, respectively. Results: Distribution of lesions (%) was HCC (29), metastases (25), angiomas (24), cysts (12), focal steatosis (4), regenerative nodules (2.5). focal nodular hyperplasia (2), and adenoma (1.5). At an age lower than 60 years, 41% of SOL were angiomas, while over 60 years, 79% were HCC or metastasis. Chronic liver disease (CLD) was present in 37% of patients with SOL. HCC was found in 85%, with a Relative Risk for HCC of 11.2. Older than 60 years were 68% of females and 73% of males. RR of HCC was similar in males below or above 60 years (9.9 vs 10.3). In females, older age greatly increased the Risk (7 vs 19). Conclusions: US finding of SOL is frequent also in absence of any symptoms; SOL in presence of CLD and in patients older than 60 years shows an increased risk of HCC, particularly in females; finding of SOL in patients with CLD strongly suggests the presence of HCC.
I 1380
THE ROLE OF PREOPERATIVE LIVER BIOPSY IN THE DIAGNOSIS OF HEPATOCELLULAR CARCINOMA
M. Sherman, I. Levy, P.D. Greig, S. Gallinger, B. Langer. Medicine, University Health Network, Canada
Objective: To evaluate the need for a preoperative tumor biopsy of liver lesions suspicious for hepatocellular carcinoma (HCC). Summary Background Data: With the advance in imaging of the liver recent studies have suggested a very high accuracy of preoperative evaluation of liver masses suspicious of possibly HCC making preoperative tumor biopsy unnecessary.
Methods: A retrospective analysis of all liver resections for HCC at the Toronto General and Mt. Sinai Hospitals, Toronto, between 100994 and 1211998. Results: Sixty patients underwent 65 liver resections without a preoperative liver biopsy. The median age was 61 years. Sixty percent of the patients had cirrhosis, 38.5% had non-cirrhotic chronic hepatitis. HCC was confirmed histologically in the surgical specimen in 63 of the 65 cases (96.9%). Both patients without HCC had a significant risk factor for HCC, (chronic hepatitis C and alcohol in one and chronic hepatitis B and previous resection for HCC in the other). The lesions were 2 cm and 2.7 cm in diameter, and the alphafetoprotein (AFP) was low (t5 ng/ml and 22 @ml respectively). In such patients, with tumor 3 cm and AFP less than 100 ng/mI (10 patients) the false positive rate for the pre-operative diagnosis was UlO (20%). Conclusion: Pre-operative diagnosis of HCC was highly accurate in lesions > 3 cm. Tumor biopsy is not necessary in these patients. However, in a subgroup of patients with lesion less than 3 cm particularly those with AFP < 100 ng/ml, there is a higher false positive diagnostic rate and tumor biopsy should be considered.
n 1441
VEGF AND iNOS EXPRESSION IN HUMAN HEPATOCELLULAR CARCINOMA (HCC)
L. Boix, C. Armengol, M. Sole, W. Jimenez, J.M. Llovet, J. Rod&s, J. Bruix. BCLC Group; Liver Unit, H Clinic, IDIBAPS, Catalonia, Spain
The hypervascularization of HCC coincides with the transition to advanced and invasive stages. VEGF effects on endothelial cells are partially mediated by NO and simultaneously, NO production is modulated by VEGF. This study assesses VEGF and iNOS expression in a series of human HCC selected according to their degree of vascularization. Tumor and non-tumoral frozen surgical tissues from 20 cirrhotics (15 men, age 60.05 f 7.19 y) (10 of them exhibiting hypervascularization by imaging techniques) were studied. HCC measured 55 cm (mean 3 1 f 2 mm) and was solitary in 17 cases. VEGF and MOS mRNA expression was assessed by RT-PCR, while protein expression was assessed by immunohistochemistry. Both the HCC and the surrounding liver were positive for VEGF and iNOS in all but one case. The activation of VEGF and iNOS was not related to surgical manipulation since it did not differ pre and post-resection. VEGF splicing pattern was not different in HCC. Immunohistochemistry confirmed the cytoplasmic expression of VEGF and iNOS in hepatocytes and its magnitude was not related to HCC characteristics (size, capsule, differentiation pattern) or to vascularization degree, which was further character&d by cd34 expression. These results show that VEGF and iNOS are produced in HCC malignant liver tissue and that their expression is not related with the degree of vascularization or any other tumor characteristic.
I 1443
~27~“” IS AN INDEPENDENT PREDICTOR OF RECURRENCE AFTER SURGJCAL RESECTION OF HEPATOCELLULAR CARCINOMA (HCC)
C. Armengol, L. Boix, 0. Baths, M. Sole, J.M. Llovet, J. Rod&, J. Bruix. BCLC Group; Liver Unit, H Clinic, IDIBAPS, Catalonia, Spain ~27 W1 is a kinase inhibitor implicated in Gl arrest while cyclin E is a
regulator of entry into S phase. This study assesses if these proteins play a role in the development of HCC recurrence after surgical resection in 48 cirrhotic patients (Age: 61.35 f 1, 31 male, 46 Child A, 31 VHC). HCC size was 3.1 f 2.2 cm, 41 were solitary (7 with satellites) and 7 multifocal. Differentiation degree was moderate in 29 and poor in 4. ~27~r’ and cyclin E expression in frozen tumoral and non-tumoral
Poster Sessions
The aim of this work was to quantify by ultrastructural morphometry the percentage of mitochondria acting in hepatocyte apoptosis induced by Fas stimulation. Three adult mice per time were administered with an agonistic anti-Fas antibody (502) and sacrificed at 2, 4 and 6 hrs. Copntrol mice receiving saline were killed at the same times. Three liver blocks per animal were processed for electron microscopy and 10 randomly chosen hepatocyte cytoplasmic fields were photographied. Mitochondria were considered abnormal when presented matrix expansion, cistae rarefaction and outer membrane rupture. Caspase 3 cleavage was investigated by immunocytochemistry and Western-blot. Percentage of apoptotic hepatocytes was measured by image analysis on light microscopy. At 4 hrs, 15.5f2.7% mitochondria wee abnormal while this percentage was only of 5.3f2.5% at 2 hrs and did not increase at 6 hrs. No abnormal mitochondria were observed in control mice. Surprisingly the relative number of mitochondria per hepatocyte in treated mice increased significantly and was at 4 hrs of 27.0f4.5% vs 17.6f5.2% for control mice (pt0.001). Caspase 3 cleavage and percentage of aopoptotic hepatocytes were at their maximum at 4 hrs. In conclusion these results showed that hepatocyte apoptosis after Fas stimulation depends on a very low number of mitochondria. Moreover the increase in their number suggets a profound dysregulation of mitochondrion mechanism
I
1363
PROSPECTIVE STUDY ON LIVER SPACE OCCUPYING LESIONS. THE RISK FOR HEPATOCELLULAR CARCINOMA
E. Paulon, L.S. Croce, C.S. Ricci, S. Markovic, C. Tiribelli. University of Trieste, Italy; University of Ljubliana, Slovenia
Aim: To determine the prevalence and the nature of hepatic Space Occupying Lesions (SOL). Material and Methods: 764 consecutive patients with SOL at ultrasonography (US), prospectively enrolled from l/l/1994 to 12/31/1997, 395 in Trieste and 369 in Ljubljana. SOL was an incidental finding at US performed for different reasons; 40% were detected during a follow-up for liver disease. All lesions were biopsed with the exception of cysts and angiomas, confirmed by TC scan or RBC-Tc scintigraphy, respectively. Results: Distribution of lesions (%) was HCC (29), metastases (25), angiomas (24), cysts (12), focal steatosis (4), regenerative nodules (2.5). focal nodular hyperplasia (2), and adenoma (1.5). At an age lower than 60 years, 41% of SOL were angiomas, while over 60 years, 79% were HCC or metastasis. Chronic liver disease (CLD) was present in 37% of patients with SOL. HCC was found in 85%, with a Relative Risk for HCC of 11.2. Older than 60 years were 68% of females and 73% of males. RR of HCC was similar in males below or above 60 years (9.9 vs 10.3). In females, older age greatly increased the Risk (7 vs 19). Conclusions: US finding of SOL is frequent also in absence of any symptoms; SOL in presence of CLD and in patients older than 60 years shows an increased risk of HCC, particularly in females; finding of SOL in patients with CLD strongly suggests the presence of HCC.
I 1380
THE ROLE OF PREOPERATIVE LIVER BIOPSY IN THE DIAGNOSIS OF HEPATOCELLULAR CARCINOMA
M. Sherman, I. Levy, P.D. Greig, S. Gallinger, B. Langer. Medicine, University Health Network, Canada
Objective: To evaluate the need for a preoperative tumor biopsy of liver lesions suspicious for hepatocellular carcinoma (HCC). Summary Background Data: With the advance in imaging of the liver recent studies have suggested a very high accuracy of preoperative evaluation of liver masses suspicious of possibly HCC making preoperative tumor biopsy unnecessary.
Methods: A retrospective analysis of all liver resections for HCC at the Toronto General and Mt. Sinai Hospitals, Toronto, between 100994 and 1211998. Results: Sixty patients underwent 65 liver resections without a preoperative liver biopsy. The median age was 61 years. Sixty percent of the patients had cirrhosis, 38.5% had non-cirrhotic chronic hepatitis. HCC was confirmed histologically in the surgical specimen in 63 of the 65 cases (96.9%). Both patients without HCC had a significant risk factor for HCC, (chronic hepatitis C and alcohol in one and chronic hepatitis B and previous resection for HCC in the other). The lesions were 2 cm and 2.7 cm in diameter, and the alphafetoprotein (AFP) was low (t5 ng/ml and 22 @ml respectively). In such patients, with tumor 3 cm and AFP less than 100 ng/mI (10 patients) the false positive rate for the pre-operative diagnosis was UlO (20%). Conclusion: Pre-operative diagnosis of HCC was highly accurate in lesions > 3 cm. Tumor biopsy is not necessary in these patients. However, in a subgroup of patients with lesion less than 3 cm particularly those with AFP < 100 ng/ml, there is a higher false positive diagnostic rate and tumor biopsy should be considered.
n 1441
VEGF AND iNOS EXPRESSION IN HUMAN HEPATOCELLULAR CARCINOMA (HCC)
L. Boix, C. Armengol, M. Sole, W. Jimenez, J.M. Llovet, J. Rod&s, J. Bruix. BCLC Group; Liver Unit, H Clinic, IDIBAPS, Catalonia, Spain
The hypervascularization of HCC coincides with the transition to advanced and invasive stages. VEGF effects on endothelial cells are partially mediated by NO and simultaneously, NO production is modulated by VEGF. This study assesses VEGF and iNOS expression in a series of human HCC selected according to their degree of vascularization. Tumor and non-tumoral frozen surgical tissues from 20 cirrhotics (15 men, age 60.05 f 7.19 y) (10 of them exhibiting hypervascularization by imaging techniques) were studied. HCC measured 55 cm (mean 3 1 f 2 mm) and was solitary in 17 cases. VEGF and MOS mRNA expression was assessed by RT-PCR, while protein expression was assessed by immunohistochemistry. Both the HCC and the surrounding liver were positive for VEGF and iNOS in all but one case. The activation of VEGF and iNOS was not related to surgical manipulation since it did not differ pre and post-resection. VEGF splicing pattern was not different in HCC. Immunohistochemistry confirmed the cytoplasmic expression of VEGF and iNOS in hepatocytes and its magnitude was not related to HCC characteristics (size, capsule, differentiation pattern) or to vascularization degree, which was further character&d by cd34 expression. These results show that VEGF and iNOS are produced in HCC malignant liver tissue and that their expression is not related with the degree of vascularization or any other tumor characteristic.
I 1443
~27~“” IS AN INDEPENDENT PREDICTOR OF RECURRENCE AFTER SURGJCAL RESECTION OF HEPATOCELLULAR CARCINOMA (HCC)
C. Armengol, L. Boix, 0. Baths, M. Sole, J.M. Llovet, J. Rod&, J. Bruix. BCLC Group; Liver Unit, H Clinic, IDIBAPS, Catalonia, Spain ~27 W1 is a kinase inhibitor implicated in Gl arrest while cyclin E is a
regulator of entry into S phase. This study assesses if these proteins play a role in the development of HCC recurrence after surgical resection in 48 cirrhotic patients (Age: 61.35 f 1, 31 male, 46 Child A, 31 VHC). HCC size was 3.1 f 2.2 cm, 41 were solitary (7 with satellites) and 7 multifocal. Differentiation degree was moderate in 29 and poor in 4. ~27~r’ and cyclin E expression in frozen tumoral and non-tumoral