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Prothymosin alpha is an accurate prognostic factor for colon cancer survival
A1400 AGA ABSTRA CTS
GASTROENTEROLOGY Vol . 118, No.4
6360
6362
NE OADJUVANT ANTIANGIOGENIC THERAPY WITH TAMOXIFEN DO ES NO T IMPAIR GASTROINTESTINAL ANASTOMO TIC REPAIR IN THE RAT. Deborah A. McNamara. Elaine Kay. David J. Bouchier-H ayes, Th omas N. Wa lsh, Royal Coli of Surgeons in Ireland, Dublin, Ireland.
THE USEFULNESS OF 3D-CT AND VIRTUAL ENDOSCOPY BY HELICAL CT FOR DETECTION OF T UMORS OF GASTROINTERNAL T RA CT . Masatake Miura, Sabu ro Nakazawa, Junj i Yoshino, Kazu o Inui , Tak ao Waka bayashi, Kazu mu Okushima, Tak ashi Kobayashi, Ryuit i Kato, Yuta Nakamura , Sinya Wa tanabe, Fujita Health Univ, Nagaya, Japan .
Background: Antia ngiogenic therapy has the potent ial to moderate tumour and micrometastatic grow th. Its use in the perioperative period has further attractions but its potential to compro mise wound and anastomotic healing is a cause for concern . Tamo xifen has estrogen independent anti-angiogenic effects but its effect on wound healing is unkn own . Aims: The aim of this stud y was to examine the effec t of perioperative tamoxifen on wound and anastomotic integ rity in the rat. Methods: Ta moxife n was administered orally at anti-angiogen ic doses (20mgl ml arac his oil/animal/ day ) commencing two days prior to laparotomy and small bowel anastomosis. Treatment was contin ued until completion of the study . Results: Both tamoxifen treated animals and placebo treated controls lost weight post-operatively from day 3 but weight loss was significantly greate r in tamoxifen treated animals . There was no difference in mortality between the gro ups (Chi2 = 0.06, Idf, p=ns). Tamoxifen treated anima ls had fewe r com plica tions of skin wound healing than co ntrols (4.5% vs. 19.5%, Chi 2 4.65, 1df, p <0.05). The re was no significant differen ce in adhesion formation or macroscopic complications of anastomotic healing at any time point. Anastomotic bursting pressure was greater in tamoxifen treated animal at day 3 (39(4.4) vs. 22.5 (3.5)mmHg, p < O.OI) and equal to that of controls on day 5 (144.4(4 .4) vs127 .3 (l 0.9) mmHg , p =ns). PVA sponge gran uloma hydroxyproline (OHP) content at day 7 was higher in tamoxifen treated animal s (2.39 (0.4) vs. 1.4 (0.4) mg OHPlmg dry sponge we ight, p = O.03). Histological examination de monstrated a trend towards qual itative improvement in anastom otic repair in tamox ife n treated animals. Conclusio ns: Tamoxifen therapy has no demonstrable adverse effects on wound or anastomo tic repair and its is therefore safe to use in the perioperative period.
6363
6361 PROTHYMOSIN ALPHA IS AN ACCURATE PROGNOSTIC FACTOR FOR COLON CANCER SURVIVAL. Spyros Mich opoulos, Kalliopi Petr aki , Tina Papamarkaki, Michael Economou, Orestis Tsolas, Co nstantina Papadirnitriou, Georgios P. Stath opoulos, Alexandra Hosp Gastroenterology Dept, Athen s, Greece; Hippocrateion Hosp Pathology Dept, Athen s, Greece; Lab of Biology Chemistry Med Sch, Ioannin a, Greece; Alexandra Hosp, Athen s, Gree ce; Hippokrateion Hosp 2nd Med Div Univ Athen s, Athens, Greece. The nuclear protein proth ymosin alpha (Pro'Tajis thought to play a cri tical role in cellular proliferation. Transcri ption of the gene encoding prothymosin alpha has been show n to be activa ted by the proto-oncogen e c- rnyc, Also, prothymosin alpha mRNA express ion co rrela tes with that of c-rnyc in human co lon ca ncer (CC). The aim of our study was I) to explore if Pro'Tal is a prognostic fact or for CC and 2) to comp are its relationship with c-rnyc, Patient s and methods: 147 patients oper ated for CC (me an age 67.9 ± 0.9 years, 93men, 20 DukesA, 348, 67C, 26D). Mean surviv al was 17.2 ± 1.3 (0-59) months. During follow- up 27 deaths were record ed . 117 CC were well or moderately different iated and the remain ing 30 poorly . On paraffin sec tions immun ohistochemistry was perfo rmed with the ABC method using polyclo nal Pro'Fa antibo dy (Lab Biological Chemistry , 10annina, Greece), c-rnyc (9E I l Novocastra®) and p-53 (DO-7 DAKO®)monoclonal antibod ies. Pro'Ta and p53 exp ressio n were co nsidered positive for nuclear staining of > 10% of cells while c-myc for cytoplasm ic ( > 10%). Stat: MUltiple sample test of survival. Results: Survival did not differ between stage s B and C. Pro'Ta and c- rnyc but not p53 exp ression discri minated surviva l rates for B and C stages (p <0.05). Agreement or not of Pro'Ta I c-myc expression related to Dukes stage, deaths recorded or survival > 24 months are resumed on the follow ing table: Pro'Ta and c-rnyc exp ression were positively correlated (p < 0.05) Histologi cal grade was neither predictive for survi val nor related to Pro'Ta, c-rnyc and p53. Conclusions: I) Pro'Ta expression is accurate as a poor prog nostic fact or for CC survival. 2) It discri minates better than Dukes stag ing surviva l rates between B and C 3) It has a goo d correlation with c-myc ex pressio n. When both are negative a high survival rate is expected (-1- 0 deaths).
Dukes A B C D Deaths >24 months
Aims: To evaluate the ability of diagnosis of 3D-CTN irtual End oscopy (VE) for detection of tumors of Gastrointernal (GI) tract by retros pective and prospective studies . Materials and Meth ods: The objects were patients with 37 gastric and 43 colorectal tumors confirmed by endo scopy in the retrospective study, and II patients who had abdominal symp tom s underwent 3D-CT in the prospective study . In the prospective study, all patient s underwent colonosco py after CT examin ation which serve d as the gold standard. GI trac t was filled with air enoughl y j ust before CT exa mination. Th ese CT examinations were performed using helical CT sca nner (Pro Seed SA Libra). These images were downloaded to a workstaion and performed by surface rendering method . 3D-CT images of malignant tumor were selected at random and interpreted by six gastroe nterogical spec ialists without all of patient' s informa tion. Results: In the retrospect ive study 3D-CTNE image was co nstructed at 92.5% (74/80) (75.7% in gastric and 81.4 % in colorectal lesions). Gastroent erogical spec ialists detected the lesions in 94 .6%, and correc t diagno sis of macro scopic type was made 65.6% in malignant tum or, on the other hand, only 20.8 % of early cancer were correctly diagnosed. In the prospective study, seven abnorm al findings in six patients were observed by 3D-CTNE (five polyp s, one type 2 advanced cance r, one submuco sal tum or), and the rest was norm al. In compari son with endoscopic findings, three polyps, one type 2 advanced ca ncer, one submucosal tumor coincided with eac h findings. In five norm al patients on 3D-CTN E, although four were norm al, one was detected a polyp in the rectum . As a results of this prospective study , sensitivity was 83.3% (5/6), specificity was 66.7% (4/6), acc uracy was 75.0 % (9/12). Conclusion: The retrospective and prospective studies showe d that 30CTNE was useful for assistance of diagnosis clinically.
+/+
-/-
+/-
-'+
0 2 22 19 19 6
5 17 27 4
0 2
8
15 13 10
3 5 10
3 7
a
25
a
GROWTH PATTERN OF SUPERFICIAL SQUAMOUS CELL CARCINOMA OF THE ESOPHAGUS - MACROSCOPIC-MICROSCOPIC CORRELATION-. HIdeo Miyake , Junich i Kamiya , Masato Nagino, Norihiro Yuasa, Katsuhiko Uesaka, Koji Oda, Tsuyoshi Sano, Yuji Nirnura, Nagoya Univ Sch of Med icine, Nagoya, Japan. Background: Macroscop ic features, as well as cli nical course, are quit e different between mucosa l and submucosa l lesions in superficia l squamous cell carcinoma of the esophagus. In this study, we eva luate the growth patte rn, with macroscopic-microscopic correlatio n, of superficial carci nomas of the esop hagus. Methods: Consecutive 50 resected superficial squamous cell esop hagea l carcinomas were studied. Macroscopic featur es of these 50 lesions were classified into 3 types by the predominant co mponen t: I) protruded lesio ns (n = 18); pro trusio n > I mm in height , 2) depressed lesions (n= 13); depression > I mm in depth, and 3) flat lesions (n = 19) without protru sion nor depression. Histologically, size of cancer nest and stro mal reaction were investigated. Small nest ind icated cancer nest below 20 JLmm in size. Concerning stroma l reaction, fibrou s desmoplastic reaction was estimated using Azan-staining meth od . Proliferative activity was also estimated with Ki-67 labeling index that was calculated immunohistochemically using MIB-l monocl onal antibody (Immnotech). Results: Sixtee n (84 %) out of 19 flat lesions were mucosal carcinomas, whereas all of 13 depressed and 18 elev ated lesion s were submucosal carcinomas . Histologically, flat lesions consisted of monotonous large cance r nest with scanty fibrous stroma . Seven teen (94%) of 18 protruded lesions showed large cancer nest with scan ty fibrous stro ma mimicking flat lesion s, and rema ining one lesion showed large nest with fibro us stroma. In all of 18 depressed lesions, the promin ent histologic feature was sma ll ca ncer nest with markedly thickened fibro us stroma. Ki-67 label ing index of elevated lesions and depr essed lesions was 31.8± 8.34 and 40.5 ±9.61, respectively. and was significantly higher than that of flat lesions (l4.7± 5.64, p
6364 HISTOLOGICAL TYPES OF ESOPHAGEAL CARCINOMA IN THE RELATED WITH THE DEGREE OF THE DUODENAL REFLUX IN RATS. Tom oharu Miyashita, Koich i Miwa , Hisatoshi Nakag awara, Takashi Fuj imura, Takanori Hattori, Kanazawa Univ, Kanazawa, Japan ; Siga U niv of Med Sci, Ohtsu, Japan . sPurpose : Duodenoesophageal reflux induces esophagea l squamous cell carcinoma(SCC) or adenocarcinoma (ADC ) in rats. This stud y was designed to investigate how degree of duoden o-esophageal reflux is associated with histological types of eso phag eal carcinoma . Animals and Methods : Male Fischer 344 rats, weighing approx imately 180g. underwent surgery that resulted in duodeno-forestomach reflux (DFR) , duodenoesophageal reflux (DER), for comparison with 3 control procedu res, Roux-
GASTROENTEROLOGY Vol . 118, No.4
6360
6362
NE OADJUVANT ANTIANGIOGENIC THERAPY WITH TAMOXIFEN DO ES NO T IMPAIR GASTROINTESTINAL ANASTOMO TIC REPAIR IN THE RAT. Deborah A. McNamara. Elaine Kay. David J. Bouchier-H ayes, Th omas N. Wa lsh, Royal Coli of Surgeons in Ireland, Dublin, Ireland.
THE USEFULNESS OF 3D-CT AND VIRTUAL ENDOSCOPY BY HELICAL CT FOR DETECTION OF T UMORS OF GASTROINTERNAL T RA CT . Masatake Miura, Sabu ro Nakazawa, Junj i Yoshino, Kazu o Inui , Tak ao Waka bayashi, Kazu mu Okushima, Tak ashi Kobayashi, Ryuit i Kato, Yuta Nakamura , Sinya Wa tanabe, Fujita Health Univ, Nagaya, Japan .
Background: Antia ngiogenic therapy has the potent ial to moderate tumour and micrometastatic grow th. Its use in the perioperative period has further attractions but its potential to compro mise wound and anastomotic healing is a cause for concern . Tamo xifen has estrogen independent anti-angiogenic effects but its effect on wound healing is unkn own . Aims: The aim of this stud y was to examine the effec t of perioperative tamoxifen on wound and anastomotic integ rity in the rat. Methods: Ta moxife n was administered orally at anti-angiogen ic doses (20mgl ml arac his oil/animal/ day ) commencing two days prior to laparotomy and small bowel anastomosis. Treatment was contin ued until completion of the study . Results: Both tamoxifen treated animals and placebo treated controls lost weight post-operatively from day 3 but weight loss was significantly greate r in tamoxifen treated animals . There was no difference in mortality between the gro ups (Chi2 = 0.06, Idf, p=ns). Tamoxifen treated anima ls had fewe r com plica tions of skin wound healing than co ntrols (4.5% vs. 19.5%, Chi 2 4.65, 1df, p <0.05). The re was no significant differen ce in adhesion formation or macroscopic complications of anastomotic healing at any time point. Anastomotic bursting pressure was greater in tamoxifen treated animal at day 3 (39(4.4) vs. 22.5 (3.5)mmHg, p < O.OI) and equal to that of controls on day 5 (144.4(4 .4) vs127 .3 (l 0.9) mmHg , p =ns). PVA sponge gran uloma hydroxyproline (OHP) content at day 7 was higher in tamoxifen treated animal s (2.39 (0.4) vs. 1.4 (0.4) mg OHPlmg dry sponge we ight, p = O.03). Histological examination de monstrated a trend towards qual itative improvement in anastom otic repair in tamox ife n treated animals. Conclusio ns: Tamoxifen therapy has no demonstrable adverse effects on wound or anastomo tic repair and its is therefore safe to use in the perioperative period.
6363
6361 PROTHYMOSIN ALPHA IS AN ACCURATE PROGNOSTIC FACTOR FOR COLON CANCER SURVIVAL. Spyros Mich opoulos, Kalliopi Petr aki , Tina Papamarkaki, Michael Economou, Orestis Tsolas, Co nstantina Papadirnitriou, Georgios P. Stath opoulos, Alexandra Hosp Gastroenterology Dept, Athen s, Greece; Hippocrateion Hosp Pathology Dept, Athen s, Greece; Lab of Biology Chemistry Med Sch, Ioannin a, Greece; Alexandra Hosp, Athen s, Gree ce; Hippokrateion Hosp 2nd Med Div Univ Athen s, Athens, Greece. The nuclear protein proth ymosin alpha (Pro'Tajis thought to play a cri tical role in cellular proliferation. Transcri ption of the gene encoding prothymosin alpha has been show n to be activa ted by the proto-oncogen e c- rnyc, Also, prothymosin alpha mRNA express ion co rrela tes with that of c-rnyc in human co lon ca ncer (CC). The aim of our study was I) to explore if Pro'Tal is a prognostic fact or for CC and 2) to comp are its relationship with c-rnyc, Patient s and methods: 147 patients oper ated for CC (me an age 67.9 ± 0.9 years, 93men, 20 DukesA, 348, 67C, 26D). Mean surviv al was 17.2 ± 1.3 (0-59) months. During follow- up 27 deaths were record ed . 117 CC were well or moderately different iated and the remain ing 30 poorly . On paraffin sec tions immun ohistochemistry was perfo rmed with the ABC method using polyclo nal Pro'Fa antibo dy (Lab Biological Chemistry , 10annina, Greece), c-rnyc (9E I l Novocastra®) and p-53 (DO-7 DAKO®)monoclonal antibod ies. Pro'Ta and p53 exp ressio n were co nsidered positive for nuclear staining of > 10% of cells while c-myc for cytoplasm ic ( > 10%). Stat: MUltiple sample test of survival. Results: Survival did not differ between stage s B and C. Pro'Ta and c- rnyc but not p53 exp ression discri minated surviva l rates for B and C stages (p <0.05). Agreement or not of Pro'Ta I c-myc expression related to Dukes stage, deaths recorded or survival > 24 months are resumed on the follow ing table: Pro'Ta and c-rnyc exp ression were positively correlated (p < 0.05) Histologi cal grade was neither predictive for survi val nor related to Pro'Ta, c-rnyc and p53. Conclusions: I) Pro'Ta expression is accurate as a poor prog nostic fact or for CC survival. 2) It discri minates better than Dukes stag ing surviva l rates between B and C 3) It has a goo d correlation with c-myc ex pressio n. When both are negative a high survival rate is expected (-1- 0 deaths).
Dukes A B C D Deaths >24 months
Aims: To evaluate the ability of diagnosis of 3D-CTN irtual End oscopy (VE) for detection of tumors of Gastrointernal (GI) tract by retros pective and prospective studies . Materials and Meth ods: The objects were patients with 37 gastric and 43 colorectal tumors confirmed by endo scopy in the retrospective study, and II patients who had abdominal symp tom s underwent 3D-CT in the prospective study . In the prospective study, all patient s underwent colonosco py after CT examin ation which serve d as the gold standard. GI trac t was filled with air enoughl y j ust before CT exa mination. Th ese CT examinations were performed using helical CT sca nner (Pro Seed SA Libra). These images were downloaded to a workstaion and performed by surface rendering method . 3D-CT images of malignant tumor were selected at random and interpreted by six gastroe nterogical spec ialists without all of patient' s informa tion. Results: In the retrospect ive study 3D-CTNE image was co nstructed at 92.5% (74/80) (75.7% in gastric and 81.4 % in colorectal lesions). Gastroent erogical spec ialists detected the lesions in 94 .6%, and correc t diagno sis of macro scopic type was made 65.6% in malignant tum or, on the other hand, only 20.8 % of early cancer were correctly diagnosed. In the prospective study, seven abnorm al findings in six patients were observed by 3D-CTNE (five polyp s, one type 2 advanced cance r, one submuco sal tum or), and the rest was norm al. In compari son with endoscopic findings, three polyps, one type 2 advanced ca ncer, one submucosal tumor coincided with eac h findings. In five norm al patients on 3D-CTN E, although four were norm al, one was detected a polyp in the rectum . As a results of this prospective study , sensitivity was 83.3% (5/6), specificity was 66.7% (4/6), acc uracy was 75.0 % (9/12). Conclusion: The retrospective and prospective studies showe d that 30CTNE was useful for assistance of diagnosis clinically.
+/+
-/-
+/-
-'+
0 2 22 19 19 6
5 17 27 4
0 2
8
15 13 10
3 5 10
3 7
a
25
a
GROWTH PATTERN OF SUPERFICIAL SQUAMOUS CELL CARCINOMA OF THE ESOPHAGUS - MACROSCOPIC-MICROSCOPIC CORRELATION-. HIdeo Miyake , Junich i Kamiya , Masato Nagino, Norihiro Yuasa, Katsuhiko Uesaka, Koji Oda, Tsuyoshi Sano, Yuji Nirnura, Nagoya Univ Sch of Med icine, Nagoya, Japan. Background: Macroscop ic features, as well as cli nical course, are quit e different between mucosa l and submucosa l lesions in superficia l squamous cell carcinoma of the esophagus. In this study, we eva luate the growth patte rn, with macroscopic-microscopic correlatio n, of superficial carci nomas of the esop hagus. Methods: Consecutive 50 resected superficial squamous cell esop hagea l carcinomas were studied. Macroscopic featur es of these 50 lesions were classified into 3 types by the predominant co mponen t: I) protruded lesio ns (n = 18); pro trusio n > I mm in height , 2) depressed lesions (n= 13); depression > I mm in depth, and 3) flat lesions (n = 19) without protru sion nor depression. Histologically, size of cancer nest and stro mal reaction were investigated. Small nest ind icated cancer nest below 20 JLmm in size. Concerning stroma l reaction, fibrou s desmoplastic reaction was estimated using Azan-staining meth od . Proliferative activity was also estimated with Ki-67 labeling index that was calculated immunohistochemically using MIB-l monocl onal antibody (Immnotech). Results: Sixtee n (84 %) out of 19 flat lesions were mucosal carcinomas, whereas all of 13 depressed and 18 elev ated lesion s were submucosal carcinomas . Histologically, flat lesions consisted of monotonous large cance r nest with scanty fibrous stroma . Seven teen (94%) of 18 protruded lesions showed large cancer nest with scan ty fibrous stro ma mimicking flat lesion s, and rema ining one lesion showed large nest with fibro us stroma. In all of 18 depressed lesions, the promin ent histologic feature was sma ll ca ncer nest with markedly thickened fibro us stroma. Ki-67 label ing index of elevated lesions and depr essed lesions was 31.8± 8.34 and 40.5 ±9.61, respectively. and was significantly higher than that of flat lesions (l4.7± 5.64, p
6364 HISTOLOGICAL TYPES OF ESOPHAGEAL CARCINOMA IN THE RELATED WITH THE DEGREE OF THE DUODENAL REFLUX IN RATS. Tom oharu Miyashita, Koich i Miwa , Hisatoshi Nakag awara, Takashi Fuj imura, Takanori Hattori, Kanazawa Univ, Kanazawa, Japan ; Siga U niv of Med Sci, Ohtsu, Japan . sPurpose : Duodenoesophageal reflux induces esophagea l squamous cell carcinoma(SCC) or adenocarcinoma (ADC ) in rats. This stud y was designed to investigate how degree of duoden o-esophageal reflux is associated with histological types of eso phag eal carcinoma . Animals and Methods : Male Fischer 344 rats, weighing approx imately 180g. underwent surgery that resulted in duodeno-forestomach reflux (DFR) , duodenoesophageal reflux (DER), for comparison with 3 control procedu res, Roux-