- Email: [email protected]
Microwave coagulation therapy for hepatocellular carcinoma
April 1995
EFFICACY OF LOW DO6E ALFA INTERFERON THERAPY IN HBV R E L A T E D C H R O N I C L I V E R D I S E A S E IN A S I A N INDIANS: A R A N D O M I Z E D T R I A L S . K . S a r i n R.C.Guptan, V. Thakur, S. Malhotra, K. Banerjee, P. Khandekar, Dept. of G a s t r o e n t e r o l o g y , G . B . P a n t H o s p i t a l and Gene E x p r e s s i o n Lab, N e w Delhi. Interferon t h e r a p y has b e e n shown to be effective in 40-60% of the W e s t e r n p a t i e n t s w i t h chronic h e p a t i t i s d u e to h e p a t i t i s H viral (HBV) infection; but to a m u c h lesser d e g r e e in A s i a n Chinese. Its e f f i c a c y in the A s i a n Indian subjects with c h r o n i c H E V i n f e c t i o n is not known. 46 pat i e n t s w i t h H B V r e l a t e d c h r o n i c liver d i s e a s e w e r e r a n d o m i z e d to r e c e i v e e i t h e r (a) r e c o m b i n a n t alpha 2b i n t e r f e r o n (n=23) 3 MIU, sc, t h r i c e a week for 4 months, or (bl no t r e a t m e n t (n=23). The IFN and the control g r o u p s w e r e c o m p a r a b l e in age (27±15 vs. 36± 8 yr), sex (male : female: 18:5 in each group) and A L T levels (172±41 vs. 134±48, p=NS). All the p a t i e n t s c o m p l e t e d the therapy. The patients were followed-up for 12 m o r e months. Results: In t h e IFN g r o u p c o m p a r e d w i t h the control group, loss of H B V D N A (57% vs. 5%, p<0.01) and H B e A g (50% vs. 5%, p<0.05) was significantly higher. The s e r o c o n v e r s i o n to a n t i H B e was s e e n in 35% of the t r e a t e d a n d 5% of the control patients (p<0.05); s p e c i a l l y h i g h e r in p a t i e n t s w i t h chronic h e p a t i t i s t h a n w i t h cirrhosis. In the responders, A L T levels n e a r l y normalized. O n e y e a r after i n t e r f e r o n therapy, the o v e r a l l H B e A g a n d H H V DNA c l e a r a n c e was o b s e r v e d in 69% patients, w i t h H B s A g c l e a r a n c e in 16%. R e a c t i v a t i o n was not s e e n in a n y patient. S i d e - e f f e c t s w e r e t r a n s i e n t and minimal. Conclusion: (i) Recombinant alpha interferon therapy is quite e f f e c t i v e and safe in A s i a n Indians w i t h c h r o n i c liver d i s e a s e d u e to hepatitis B i n f e c t i o n (ii) low d o s e i n t e r f e r o n therapy is r e c o m m e n d e d for A s i a n Indian patients.
• MICROWAVE COAGULATION THERAPY FOR HEPATOCELLULAR CARCINOMA. M. Sato. Y. Nakata, K. Kito, S. Horiuchi, T. Yamamoto, Y. Watanabe, S. Kimura. Dept. of Surgery II, University of Ehime, School of Medicine, Ehime, Japan The purpose of this study is to evaluate the efficacy of microwave coagulation therapy (MCT) for hepatocellular carcinoma (HCC) which was currently introduced as a new treatment option. Patients and Methods: Nineteen patients with HCC underwent MCT for 30 nodules. The indications were impaired hepatic function and/or scattered intrahepatic metastases (n=9), remaining satellite lesions after hepatic resection (n=5), reduction of tumor burden (n=3), etc. Sixteen patients had liver cirrhosis. The nodules were located in the right lobe in 9 patients, bilateral lobe in seven, and left in three. A microwave irradiation (Microtase, Osaka, Japan) at 70-80 watts, 30 sec., consistently creates a columnar necrosis, 10 mm in diameter, around a needle electrode. We repeated irradiation to create a segmental necrosis containing the main tumor and surrounding liver parenchyma which provides a tumor-free margin. When a treated area represents a sharply demarcated non-enhanced region on postoperative CT, MCT was considered to be complete. Results: The number of nodules treated with MCT was single in 13 patients, and 2-5 in six. The tumor sizes averaged 21 mm (4-90 mm). The approaches included laparotomy (n=l 1), taparoscopy (n=5), thoraco-laparotomy (n=2), and thoracotomy (n=l). Although liver enzymes temporally increased, there were no major complications. CT proves that 27 of the 30 lesions were completely treated. Of the 30 nodules, 28 developed no recurrence. Two nodules progressed because laparoscopic punctures failed to coagulate the entire lesion. Four patients died of hepatic insufficiency (n=2), intrahepatic recurrence (n=l), distant metastases (n=l). Fifteen patients including two long-term survivors are alive 3-52 mos after MCT. Conclusions: We concluded that MCT offers a promising new option as a curative treatment or an alternative to hepatic resection in the treatment of HCCs associated with liver cirrhosis because of its safety, feasibility, and validity.
AASLD
Al163
• R A N D O M I Z E D P R O S P E C T I V E TRIAL OF E N D O S C O P I C SCLEROTHERAPY (EST) VS. V A R I C E A L LIGATION (EVL) FOR B L E E D I N G E S O P H A G E A L VARICES: i n f l u e n c e o n g a s t r o p athy, g a s t r i c v a r i c e s a n d recurrence. S a r i n SK Govil A, Jain A, G u p t a n RC, Murthy NS. Dept. Gastroenterology, G . B . P a n t Hosp. & ICPO, Delhi EVL has b e e n r e c o m m e n d e d to be safer than EST for p r e v e n t i o n of variceal rebleeding. To assess the efficacy and influence on development of portal h y p e r t e n s i v e g a s t r o p a t h y (PGP) and gastric varices, 95 variceal b l e e d e r s w e r e r a n d o m i z e d to receive weekly EST w i t h alcohol (n=48) or EVL (n=47). The EST and EVL g r o u p s were comparable: (cirrhosis 31:34, n o n - c i r r h o t i c s 17:23), Child's grade (A 24:22; B 18:18; C 6:7) variceal grade (GrlI 1:2; grIII; 27:21; g r I V 20:15). Data was analyzed u s i n g acturial methods. Results: In the arrest of acute bleed, EST (6 of 7, 86%) a n d EVL (4 of 5, 80%) w e r e comparable. EVL compared to EST, could o b l i t e r a t e esophageal v a r i c e s in fewer treatment s e s s i o n s (4.1±1.2 vs. 5.2±1.8, p<0.01) and s h o r t e r time (4.4±1.3 vs. 6.9±3.4 wk, p<0.01). Three (6.4%) patients bled after EVL and I0 (20.8%) after EST (p<0.05). D u r i n g a m e a n followup of 8.5±4.4 mo, variceal r e c u r r e n c e w a s commoner after EVL (21.3%) than EST (6.3%,p<0.05). Esophageal s t r i c t u r e s o c c u r r e d in 5 (10.4%) patients after EST, but n o n e after EVL. Eight (8.4%) patients had PGP at presentation. Significant additional p a t i e n t s d e v e l o p e d PGP after EST than EVL (20.5% vs. 2.3%; p = 0.02). B o t h EST (50%) and EVL (53%) w e r e e f f e c t i v e in o b l i t e r a t i n g lesser curve gastric varices. Recurrence as gastric varices was seen in 4 (8.8%) p a t i e n t s in either group. 3 (6.3%) p a t i e n t s d i e d in e a c h group. Two died due to r e b l e e d in EST but n o n e in EVL group. Conclusions: (i) EVL a c h i e v e s variceal obliteration faster w i t h fewer s e s s i o n s (il) EVL had a lower f r e q u e n c y of r e b l e e d and d e v e l o p m e n t of PGP (iii) W h i l e b o t h t r e a t m e n t s are good for a r r e s t i n g acute b l e e d and g a s t r i c varices, v a r i c e a l recurrence is m o r e f o l l o w i n g EVL than EST.
DIFFERENT AFFINITY TO LENS CULINARIS AGGLUTININ ( LCA ) BETWEEN HEPATOCELLULAR CARCINOMA(HCC) AND NON-HCC CELL J Satoi, A Sanjo, Y Takekuma, T Nekohashi, T Abe, K Komiyama, T Ui, S Morimoto, T Tanaka Department of Internal Medicine ( I ) , Daisan Hospital, The Jikei University School of Medicine, Tokyo, Japan Previous studies have reported that serum glycoprotein of c(-fetoprotein, PIVKA-II, or 0tl-antitrypsin has microheterogeneity in affinity to lectins in patients having malignant tumor, which induce the accurate diagnosis of malignant tumor. This heterogeneity indicates changing in the carbohydrate moiety during the progress toward malignant tumor. In present study, we investigated the affinity of LCA between parenchymal liver non-tumor and tumor cell using histochemical techniques. Biopsied non-tumor and tumor tissues were obtained from 92 patients with chronic liver disease complicated with HCC, and biotinylated LCA were applied to these paraffin-embedded tissues, being followed by ABC staining. Positive staining of LCA in cytoplasm of parenchymal cells was examined light -microscopically. Chronic inflammatory changes (CI) including cirrhosis, adenomatous hyperplasia (AH), well-differentiated HCC (W-HCC), and moderately-differentiated HCC (M-HCC) were histologically diagnosed. Some tissues were stained with biotinylated LCA and then with gold-conjugated streptavidin, and were examined by a electron microscope. These results are shown as follows: Po~sitiv~
CI A H W-HCC [M-HCC LCA staining 92 12 20 0 [Negative LCA staining 0 0 23 37 Both above light- and electron- microscopic observations suggest that CI, AH and some of W-HCC had more positive LCA staining than W-HCC and M-HCC. In conclusion, HCC is likely to be sequentially developed from inflammatory conditions and thus the carbohydrate recognized by LCA decrease during the progress toward HCC.
EFFICACY OF LOW DO6E ALFA INTERFERON THERAPY IN HBV R E L A T E D C H R O N I C L I V E R D I S E A S E IN A S I A N INDIANS: A R A N D O M I Z E D T R I A L S . K . S a r i n R.C.Guptan, V. Thakur, S. Malhotra, K. Banerjee, P. Khandekar, Dept. of G a s t r o e n t e r o l o g y , G . B . P a n t H o s p i t a l and Gene E x p r e s s i o n Lab, N e w Delhi. Interferon t h e r a p y has b e e n shown to be effective in 40-60% of the W e s t e r n p a t i e n t s w i t h chronic h e p a t i t i s d u e to h e p a t i t i s H viral (HBV) infection; but to a m u c h lesser d e g r e e in A s i a n Chinese. Its e f f i c a c y in the A s i a n Indian subjects with c h r o n i c H E V i n f e c t i o n is not known. 46 pat i e n t s w i t h H B V r e l a t e d c h r o n i c liver d i s e a s e w e r e r a n d o m i z e d to r e c e i v e e i t h e r (a) r e c o m b i n a n t alpha 2b i n t e r f e r o n (n=23) 3 MIU, sc, t h r i c e a week for 4 months, or (bl no t r e a t m e n t (n=23). The IFN and the control g r o u p s w e r e c o m p a r a b l e in age (27±15 vs. 36± 8 yr), sex (male : female: 18:5 in each group) and A L T levels (172±41 vs. 134±48, p=NS). All the p a t i e n t s c o m p l e t e d the therapy. The patients were followed-up for 12 m o r e months. Results: In t h e IFN g r o u p c o m p a r e d w i t h the control group, loss of H B V D N A (57% vs. 5%, p<0.01) and H B e A g (50% vs. 5%, p<0.05) was significantly higher. The s e r o c o n v e r s i o n to a n t i H B e was s e e n in 35% of the t r e a t e d a n d 5% of the control patients (p<0.05); s p e c i a l l y h i g h e r in p a t i e n t s w i t h chronic h e p a t i t i s t h a n w i t h cirrhosis. In the responders, A L T levels n e a r l y normalized. O n e y e a r after i n t e r f e r o n therapy, the o v e r a l l H B e A g a n d H H V DNA c l e a r a n c e was o b s e r v e d in 69% patients, w i t h H B s A g c l e a r a n c e in 16%. R e a c t i v a t i o n was not s e e n in a n y patient. S i d e - e f f e c t s w e r e t r a n s i e n t and minimal. Conclusion: (i) Recombinant alpha interferon therapy is quite e f f e c t i v e and safe in A s i a n Indians w i t h c h r o n i c liver d i s e a s e d u e to hepatitis B i n f e c t i o n (ii) low d o s e i n t e r f e r o n therapy is r e c o m m e n d e d for A s i a n Indian patients.
• MICROWAVE COAGULATION THERAPY FOR HEPATOCELLULAR CARCINOMA. M. Sato. Y. Nakata, K. Kito, S. Horiuchi, T. Yamamoto, Y. Watanabe, S. Kimura. Dept. of Surgery II, University of Ehime, School of Medicine, Ehime, Japan The purpose of this study is to evaluate the efficacy of microwave coagulation therapy (MCT) for hepatocellular carcinoma (HCC) which was currently introduced as a new treatment option. Patients and Methods: Nineteen patients with HCC underwent MCT for 30 nodules. The indications were impaired hepatic function and/or scattered intrahepatic metastases (n=9), remaining satellite lesions after hepatic resection (n=5), reduction of tumor burden (n=3), etc. Sixteen patients had liver cirrhosis. The nodules were located in the right lobe in 9 patients, bilateral lobe in seven, and left in three. A microwave irradiation (Microtase, Osaka, Japan) at 70-80 watts, 30 sec., consistently creates a columnar necrosis, 10 mm in diameter, around a needle electrode. We repeated irradiation to create a segmental necrosis containing the main tumor and surrounding liver parenchyma which provides a tumor-free margin. When a treated area represents a sharply demarcated non-enhanced region on postoperative CT, MCT was considered to be complete. Results: The number of nodules treated with MCT was single in 13 patients, and 2-5 in six. The tumor sizes averaged 21 mm (4-90 mm). The approaches included laparotomy (n=l 1), taparoscopy (n=5), thoraco-laparotomy (n=2), and thoracotomy (n=l). Although liver enzymes temporally increased, there were no major complications. CT proves that 27 of the 30 lesions were completely treated. Of the 30 nodules, 28 developed no recurrence. Two nodules progressed because laparoscopic punctures failed to coagulate the entire lesion. Four patients died of hepatic insufficiency (n=2), intrahepatic recurrence (n=l), distant metastases (n=l). Fifteen patients including two long-term survivors are alive 3-52 mos after MCT. Conclusions: We concluded that MCT offers a promising new option as a curative treatment or an alternative to hepatic resection in the treatment of HCCs associated with liver cirrhosis because of its safety, feasibility, and validity.
AASLD
Al163
• R A N D O M I Z E D P R O S P E C T I V E TRIAL OF E N D O S C O P I C SCLEROTHERAPY (EST) VS. V A R I C E A L LIGATION (EVL) FOR B L E E D I N G E S O P H A G E A L VARICES: i n f l u e n c e o n g a s t r o p athy, g a s t r i c v a r i c e s a n d recurrence. S a r i n SK Govil A, Jain A, G u p t a n RC, Murthy NS. Dept. Gastroenterology, G . B . P a n t Hosp. & ICPO, Delhi EVL has b e e n r e c o m m e n d e d to be safer than EST for p r e v e n t i o n of variceal rebleeding. To assess the efficacy and influence on development of portal h y p e r t e n s i v e g a s t r o p a t h y (PGP) and gastric varices, 95 variceal b l e e d e r s w e r e r a n d o m i z e d to receive weekly EST w i t h alcohol (n=48) or EVL (n=47). The EST and EVL g r o u p s were comparable: (cirrhosis 31:34, n o n - c i r r h o t i c s 17:23), Child's grade (A 24:22; B 18:18; C 6:7) variceal grade (GrlI 1:2; grIII; 27:21; g r I V 20:15). Data was analyzed u s i n g acturial methods. Results: In the arrest of acute bleed, EST (6 of 7, 86%) a n d EVL (4 of 5, 80%) w e r e comparable. EVL compared to EST, could o b l i t e r a t e esophageal v a r i c e s in fewer treatment s e s s i o n s (4.1±1.2 vs. 5.2±1.8, p<0.01) and s h o r t e r time (4.4±1.3 vs. 6.9±3.4 wk, p<0.01). Three (6.4%) patients bled after EVL and I0 (20.8%) after EST (p<0.05). D u r i n g a m e a n followup of 8.5±4.4 mo, variceal r e c u r r e n c e w a s commoner after EVL (21.3%) than EST (6.3%,p<0.05). Esophageal s t r i c t u r e s o c c u r r e d in 5 (10.4%) patients after EST, but n o n e after EVL. Eight (8.4%) patients had PGP at presentation. Significant additional p a t i e n t s d e v e l o p e d PGP after EST than EVL (20.5% vs. 2.3%; p = 0.02). B o t h EST (50%) and EVL (53%) w e r e e f f e c t i v e in o b l i t e r a t i n g lesser curve gastric varices. Recurrence as gastric varices was seen in 4 (8.8%) p a t i e n t s in either group. 3 (6.3%) p a t i e n t s d i e d in e a c h group. Two died due to r e b l e e d in EST but n o n e in EVL group. Conclusions: (i) EVL a c h i e v e s variceal obliteration faster w i t h fewer s e s s i o n s (il) EVL had a lower f r e q u e n c y of r e b l e e d and d e v e l o p m e n t of PGP (iii) W h i l e b o t h t r e a t m e n t s are good for a r r e s t i n g acute b l e e d and g a s t r i c varices, v a r i c e a l recurrence is m o r e f o l l o w i n g EVL than EST.
DIFFERENT AFFINITY TO LENS CULINARIS AGGLUTININ ( LCA ) BETWEEN HEPATOCELLULAR CARCINOMA(HCC) AND NON-HCC CELL J Satoi, A Sanjo, Y Takekuma, T Nekohashi, T Abe, K Komiyama, T Ui, S Morimoto, T Tanaka Department of Internal Medicine ( I ) , Daisan Hospital, The Jikei University School of Medicine, Tokyo, Japan Previous studies have reported that serum glycoprotein of c(-fetoprotein, PIVKA-II, or 0tl-antitrypsin has microheterogeneity in affinity to lectins in patients having malignant tumor, which induce the accurate diagnosis of malignant tumor. This heterogeneity indicates changing in the carbohydrate moiety during the progress toward malignant tumor. In present study, we investigated the affinity of LCA between parenchymal liver non-tumor and tumor cell using histochemical techniques. Biopsied non-tumor and tumor tissues were obtained from 92 patients with chronic liver disease complicated with HCC, and biotinylated LCA were applied to these paraffin-embedded tissues, being followed by ABC staining. Positive staining of LCA in cytoplasm of parenchymal cells was examined light -microscopically. Chronic inflammatory changes (CI) including cirrhosis, adenomatous hyperplasia (AH), well-differentiated HCC (W-HCC), and moderately-differentiated HCC (M-HCC) were histologically diagnosed. Some tissues were stained with biotinylated LCA and then with gold-conjugated streptavidin, and were examined by a electron microscope. These results are shown as follows: Po~sitiv~
CI A H W-HCC [M-HCC LCA staining 92 12 20 0 [Negative LCA staining 0 0 23 37 Both above light- and electron- microscopic observations suggest that CI, AH and some of W-HCC had more positive LCA staining than W-HCC and M-HCC. In conclusion, HCC is likely to be sequentially developed from inflammatory conditions and thus the carbohydrate recognized by LCA decrease during the progress toward HCC.