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Indications for local resection for gastric leiomyosarcoma
A488
AGA ABSTRACTS
INTERFERONBLOCKINGACTIVITYINSERUMOF CANCERPATIENTS. K.D. Karmaniolas,Th. S. Papalambros,E.D. Papavassiliou.NIMTS Hospital, Athens, Greece. INTRODUCTION : The anticancer activity of interferon A varies among the differenttyposof canc~i:The causeof this is unknown.In the presentstudywe evaluated whetherendogenous~n~erferonsand/orinterferoninhibitorsin the serumof cancerpatients accountfor the variabilityof interferonresponsein cancer. METHODS: The sera of 90 patientswith gastriccancer (8), coloncancer (12), hapatocellulai"cancer (11), pancreaticcancer (8), lung cancer (34)i renal cancer (6), prostaticcancer(5) andbreastcancer(6) wereexamined.Serafrom 37 healthyindividuals were usedas control;:' The presenceof interferon blockingactivitywas determinedby assaying the inhibitiqnof the virus specific cytopathiceffect (CPE) of the vesicular stomatitisvirusin the ~tistinalcell line407. RESULTS:,Therewasne endogenousinterferonin any of the serumsamplesof patientsor controls.I~terferonblockingactivitywasdetectedin 25%of gastriccancer,25% of coloncancer,9%~f hepatocellutarcancer,0%of pancreaticcancer,23% of lungcancer, 33%of renalcancer,20%of prostaticcancerand 33%of breastcancer.No controlsample hadinterferonblockingactivity. CONCLUSIONS: Interferonblockingactivitywas detectedin the serumof up to onethirdof the patientswitha varietyof humangastrointestinalandothercancers,with the exceptionof pancreaticcancer. No endogenousinterferonwas detectedin eithercancer patientsor controls.The presenceof interferonblockingactivityin cancerpatientsmay contributeto theirvariableresponseto interferontreatment.
• INDICATIONS FOR LOCAL RESECTION FOR GASTRIC LEIOMYOSARCOMA H.KATAI,M.SASAKO,T.SANO,K.OKAJIMA,K.MARUYAMA, A.OCHIAI*. Depts.of Surgical Oncology & Pathology*, National Cancer Center Hospital,Tokyo,Japan Gastric leiomyosarcoma is a rare disease and common strategy for treatment has not been established yet. We have previously shown that the incidence of lymph node metastasis was rare. Since 1982, we have performed local resection for tumors less than 5 cm. In this study we report our experience after local resection for gastric leiomyosarcoma and attempt to define the indications. Ninety two patients were treated for histologically proven leiomyosarcoma in our institution between 1972 and 1994. Tumor tended to occur proximally in the stomach. Gastrectomies were performed in 32 patients. Fifty nine patients had local resection and one had enucleation of tumor. Nodal involvement was not observed in patients, who underwent systematic lymph node dissection. The lymph nodes involved with tumor were r e c o g n i z e d in only one patient. During follow-up, Eight patients died of recurrence. Six patients had recurrence in liver. Local, but lymph node-free recurrence was observed in only one patient. It is reasonable to limit the indication for local resection to tumors less than 5 cm by its low incidence of lymph node metastasis.
GASTROENTEROLOGY, Vol. 108, No. 4
ANTICARCINOGENIC ORGANIC ISOTHIOCYANATES COORDINATELY INDUCE M U L T I P L E X E N O B I O T I C M E T A B O L I Z I N G ENZYMES IN LIVER A N D S M A L L INTESTINE. K. K a s h f ~ , E.K. Yang*, Y. Zhang ÷, P. T a l a l a y ÷ and A.J. Dannenberg*. "Dept. of Medicine, Cornell Med. Coll. and S t r a n g Cancer Prevention Ctr., NY, NY and *Dept. of Pharmacology, Johns H o p k i n s Univ. School of Med., Baltimore, MD. O r g a n i c isothiocyanates, also k n o w n as m u s t a r d oils, a r e w i d e l y d i s t r i b u t e d in plants, and are present in s u b s t a n t i a l q u a n t i t i e s in h u m a n diets. These c o m p o u n d s p r o t e c t l a b o r a t o r y animals a g a i n s t the induction of tumors by a v a r i e t y of chemical carcinogens. A m o n g s t p o s s i b l e mechanisms, p r o t e c t i o n against c h e m i c a l c a r c i n o g e n e s i s c o u l d be m e d i a t e d via induction of d e t o x i f y i n g enzymes. Therefore, we investigated t h e e f f e c t s of two isothiocyanates, benzyl i s o t h i o c y a n a t e (BITC) and sulforaphane, on UDP-glucuronosyltransferase (UGT), g l u t a t h i o n e St r a n s f e r a s e (GST) and q u f n o n e reductase (QR) in a murine h e p a t o m a cell line (Hepa iclc7). T r e a t m e n t of Hepa iclc7 cells for 24h w i t h BITC (i0 ~M) and sulforaphane (2 ~M) induced the a c t i v i t i e s of UGT (60%,80%), GST (247%,126%) and Q R (252%,243%), respectively. ~ To evaluate the effects of isothiocyanates in vivo, male W i s t a r rats (200-225g, n=12) were p a i r - f e d a control diet or a diet containing BITC (0.5%, w/w) for 2 wks. BITC increased the a c t i v i t i e s of UGT (73%,154%), GST (159%,310%) and Q R (237%,1006%) in liver and small intestine, respectively. I m m u n o b l o t s showed that BITC increased the amounts of UGT, GST-Ya and G S T - Y b l in liver and small intestine c o r r e s p o n d i n g to the changes in e n z y m e activities. CONCLUSIONS: O r g a n i c i s o t h i o c y a n a t e s c o o r d i n a t e l y induced the a c t i v i t i e s of m u l t i p l e p h a s e 2 x e n o b i o t i c m e t a b o l i z i n g enzymes in liver and small i n t e s t i n e . I n d u c t i o n was g r e a t e r in the small intestine than the liver. The m a g n i t u d e of induction was g r e a t e s t for quinone reductase and least for U D P - g l u c u r o n o s y l t r a n s f e r a s e . Our results are likely to be important for u n d e r s t a n d i n g the known c h e m o p r e v e n t i v e p r o p e r t i e s of isothiocyanates.
• DOES CYCLIN GENE METHYLATION IN NORMAL SlGMOID COLON PREDICT THE PRESENCE OF COLONIC NEOPLASIA? I Kelberman. PP Claudio, D Trate, E Haig, A Giordano. GI Section and Fels Institute, Temple Univ., Philadelphia, PA. Intro: Abnormalities of cyclin expression are observed in several malignancies, including colon cancer. Hypomethylation of genomic DNA occurs early as adenomatous polyps progress to colon cancer, and is believed to be involved in regulating gene expression. Aim: Correlate cyclin gene methylation in normal sigmoid mucosa with the presence of colonic neoplasia. Methods: Cyclin gene methylation was determined in DNA extracted from biopsy specimens of normal appearing sigmoid colon in patients undergoing c01onoscopy independent of the Study. Southern blots of Mspl and Hpall digests were performed using cyclin D2 and cyclin E cDNA probes, Mspl and Hpall both cleave DNA at -CCGG-; however, Hpall will not cut if the internal -C- is methylated. Methylation was estimated as.the percentage of hybridizing fragments in Mspl digests which were preserved in Hpall digests. Results: Cyclin E probe revealed two restriction patterns: (a)40% preservation of Mspl fragments in Hpall digest and (b)0% Mspl fragments in Hpall digests. Cyclin D2 revealed three patterns: (c)100% preservation of Mspl fragments in Hpall. digests, (d)67 oY. of fragments present and (e)25% of fragments present. The number of patients with each pattern follows: Cyclin E cvclin D2 ( a / 4 0 % (b)0% (c)1 00% (d)67% (E/25% Normal 0/11 1 1/11 3/11 2/11 6/11 Adenom a 019 9/9 2/9 2/9 5/9 Cancer 1/6 5/6 2/6 3/6 !/6 Conclusions: Cyctin E is extensively methylated in normal mucosa of patients with and without neoplasia. Cyclin D2 exhibits unmethylated sites, but did not distinguish between groups with and without neoplasia, although DNA of cancer patients tended toward hypomethylation.
AGA ABSTRACTS
INTERFERONBLOCKINGACTIVITYINSERUMOF CANCERPATIENTS. K.D. Karmaniolas,Th. S. Papalambros,E.D. Papavassiliou.NIMTS Hospital, Athens, Greece. INTRODUCTION : The anticancer activity of interferon A varies among the differenttyposof canc~i:The causeof this is unknown.In the presentstudywe evaluated whetherendogenous~n~erferonsand/orinterferoninhibitorsin the serumof cancerpatients accountfor the variabilityof interferonresponsein cancer. METHODS: The sera of 90 patientswith gastriccancer (8), coloncancer (12), hapatocellulai"cancer (11), pancreaticcancer (8), lung cancer (34)i renal cancer (6), prostaticcancer(5) andbreastcancer(6) wereexamined.Serafrom 37 healthyindividuals were usedas control;:' The presenceof interferon blockingactivitywas determinedby assaying the inhibitiqnof the virus specific cytopathiceffect (CPE) of the vesicular stomatitisvirusin the ~tistinalcell line407. RESULTS:,Therewasne endogenousinterferonin any of the serumsamplesof patientsor controls.I~terferonblockingactivitywasdetectedin 25%of gastriccancer,25% of coloncancer,9%~f hepatocellutarcancer,0%of pancreaticcancer,23% of lungcancer, 33%of renalcancer,20%of prostaticcancerand 33%of breastcancer.No controlsample hadinterferonblockingactivity. CONCLUSIONS: Interferonblockingactivitywas detectedin the serumof up to onethirdof the patientswitha varietyof humangastrointestinalandothercancers,with the exceptionof pancreaticcancer. No endogenousinterferonwas detectedin eithercancer patientsor controls.The presenceof interferonblockingactivityin cancerpatientsmay contributeto theirvariableresponseto interferontreatment.
• INDICATIONS FOR LOCAL RESECTION FOR GASTRIC LEIOMYOSARCOMA H.KATAI,M.SASAKO,T.SANO,K.OKAJIMA,K.MARUYAMA, A.OCHIAI*. Depts.of Surgical Oncology & Pathology*, National Cancer Center Hospital,Tokyo,Japan Gastric leiomyosarcoma is a rare disease and common strategy for treatment has not been established yet. We have previously shown that the incidence of lymph node metastasis was rare. Since 1982, we have performed local resection for tumors less than 5 cm. In this study we report our experience after local resection for gastric leiomyosarcoma and attempt to define the indications. Ninety two patients were treated for histologically proven leiomyosarcoma in our institution between 1972 and 1994. Tumor tended to occur proximally in the stomach. Gastrectomies were performed in 32 patients. Fifty nine patients had local resection and one had enucleation of tumor. Nodal involvement was not observed in patients, who underwent systematic lymph node dissection. The lymph nodes involved with tumor were r e c o g n i z e d in only one patient. During follow-up, Eight patients died of recurrence. Six patients had recurrence in liver. Local, but lymph node-free recurrence was observed in only one patient. It is reasonable to limit the indication for local resection to tumors less than 5 cm by its low incidence of lymph node metastasis.
GASTROENTEROLOGY, Vol. 108, No. 4
ANTICARCINOGENIC ORGANIC ISOTHIOCYANATES COORDINATELY INDUCE M U L T I P L E X E N O B I O T I C M E T A B O L I Z I N G ENZYMES IN LIVER A N D S M A L L INTESTINE. K. K a s h f ~ , E.K. Yang*, Y. Zhang ÷, P. T a l a l a y ÷ and A.J. Dannenberg*. "Dept. of Medicine, Cornell Med. Coll. and S t r a n g Cancer Prevention Ctr., NY, NY and *Dept. of Pharmacology, Johns H o p k i n s Univ. School of Med., Baltimore, MD. O r g a n i c isothiocyanates, also k n o w n as m u s t a r d oils, a r e w i d e l y d i s t r i b u t e d in plants, and are present in s u b s t a n t i a l q u a n t i t i e s in h u m a n diets. These c o m p o u n d s p r o t e c t l a b o r a t o r y animals a g a i n s t the induction of tumors by a v a r i e t y of chemical carcinogens. A m o n g s t p o s s i b l e mechanisms, p r o t e c t i o n against c h e m i c a l c a r c i n o g e n e s i s c o u l d be m e d i a t e d via induction of d e t o x i f y i n g enzymes. Therefore, we investigated t h e e f f e c t s of two isothiocyanates, benzyl i s o t h i o c y a n a t e (BITC) and sulforaphane, on UDP-glucuronosyltransferase (UGT), g l u t a t h i o n e St r a n s f e r a s e (GST) and q u f n o n e reductase (QR) in a murine h e p a t o m a cell line (Hepa iclc7). T r e a t m e n t of Hepa iclc7 cells for 24h w i t h BITC (i0 ~M) and sulforaphane (2 ~M) induced the a c t i v i t i e s of UGT (60%,80%), GST (247%,126%) and Q R (252%,243%), respectively. ~ To evaluate the effects of isothiocyanates in vivo, male W i s t a r rats (200-225g, n=12) were p a i r - f e d a control diet or a diet containing BITC (0.5%, w/w) for 2 wks. BITC increased the a c t i v i t i e s of UGT (73%,154%), GST (159%,310%) and Q R (237%,1006%) in liver and small intestine, respectively. I m m u n o b l o t s showed that BITC increased the amounts of UGT, GST-Ya and G S T - Y b l in liver and small intestine c o r r e s p o n d i n g to the changes in e n z y m e activities. CONCLUSIONS: O r g a n i c i s o t h i o c y a n a t e s c o o r d i n a t e l y induced the a c t i v i t i e s of m u l t i p l e p h a s e 2 x e n o b i o t i c m e t a b o l i z i n g enzymes in liver and small i n t e s t i n e . I n d u c t i o n was g r e a t e r in the small intestine than the liver. The m a g n i t u d e of induction was g r e a t e s t for quinone reductase and least for U D P - g l u c u r o n o s y l t r a n s f e r a s e . Our results are likely to be important for u n d e r s t a n d i n g the known c h e m o p r e v e n t i v e p r o p e r t i e s of isothiocyanates.
• DOES CYCLIN GENE METHYLATION IN NORMAL SlGMOID COLON PREDICT THE PRESENCE OF COLONIC NEOPLASIA? I Kelberman. PP Claudio, D Trate, E Haig, A Giordano. GI Section and Fels Institute, Temple Univ., Philadelphia, PA. Intro: Abnormalities of cyclin expression are observed in several malignancies, including colon cancer. Hypomethylation of genomic DNA occurs early as adenomatous polyps progress to colon cancer, and is believed to be involved in regulating gene expression. Aim: Correlate cyclin gene methylation in normal sigmoid mucosa with the presence of colonic neoplasia. Methods: Cyclin gene methylation was determined in DNA extracted from biopsy specimens of normal appearing sigmoid colon in patients undergoing c01onoscopy independent of the Study. Southern blots of Mspl and Hpall digests were performed using cyclin D2 and cyclin E cDNA probes, Mspl and Hpall both cleave DNA at -CCGG-; however, Hpall will not cut if the internal -C- is methylated. Methylation was estimated as.the percentage of hybridizing fragments in Mspl digests which were preserved in Hpall digests. Results: Cyclin E probe revealed two restriction patterns: (a)40% preservation of Mspl fragments in Hpall digest and (b)0% Mspl fragments in Hpall digests. Cyclin D2 revealed three patterns: (c)100% preservation of Mspl fragments in Hpall. digests, (d)67 oY. of fragments present and (e)25% of fragments present. The number of patients with each pattern follows: Cyclin E cvclin D2 ( a / 4 0 % (b)0% (c)1 00% (d)67% (E/25% Normal 0/11 1 1/11 3/11 2/11 6/11 Adenom a 019 9/9 2/9 2/9 5/9 Cancer 1/6 5/6 2/6 3/6 !/6 Conclusions: Cyctin E is extensively methylated in normal mucosa of patients with and without neoplasia. Cyclin D2 exhibits unmethylated sites, but did not distinguish between groups with and without neoplasia, although DNA of cancer patients tended toward hypomethylation.