- Email: [email protected]
W1831 Polymorphism Arg290Arg in Esophageal Cancer Related Gene 1 (ECRG1) Is a Prognostic Factor for Survival in Esophageal Cancer
everolimus. Corrensponding to these data, the anastomotic “bursting pressure” is significantly reduced under treatment with everolimus. References: 1. Schaffer et al. 2005, J Invest Surg. 18: 71-79. 2. Dean et al. 2004, Transplantation 77:1555-1561;
frozen tissues. Two novel genes identified from a microarray study, CD151 (which encodes a protein that enhances cell motility, invasion and metastasis of cancer cells) and TCIRG1 (T-cell, immune regulator 1, ATPase, H+ transporting, lysosomal V0 subunit A3) were overexpressed in IM. Conclusions: Accurate mRNA comparative quantification, matching fresh frozen tissue results, can be obtained from even single small formalin-fixed, paraffinembedded Barrett's esophagus endoscopic biopsy tissues using a multiplex tandem PCR method.
W1830 Polyphenon E, An EGCG Containing Green Tea Extract That Inhibits Tumor Growth, Has No Impact On Wound Collagen Content or Clinical Rate of Wound Infection or Dehiscence Yet Has a Mild Inhibitory Effect On Healing As Judged By Tensometry Aviad Hoffman, Raymond Baxter, Abu Nasar, Thomas R. Gardner, Kumara H. Shantha, Keith Hoffman, Richard L. Whelan
W1833 KI-67 Antigen Is Overexpressed in Barrett's Carcinogenesis Bernardo Volkweis, Richard R. Gurski, Luise Meurer, Maria Isabel A. Edelweiss, Gustavo Morellato, Marcelo K. Schmidt
Introduction: Catechins in green tea, in particular EGCG (epigallocatechin-3-gallate), inhibit tumor growth in many murine models. Polyphenon E (PolyE) is a concentrated mixture of catechins (65% EGCG) with minimal side affects in humans that has stronger anti-cancer effects than tea alone. Surgery is associated with increased rates of tumor growth and metastases postoperatively(postop) in the murine setting. Perioperative (periop) administration of Poly E may limit surgery's tumor stimulatory effects. Prior to a Phase 1 study, PolyE's effects on wound healing must be studied. This study's purpose was to assess PolyE's impact on laparotomy wound strength and collagen content. Methods: Balb/C mice were randomized to plain water (Control, n=20) or a 1% PolyE solution (n=25) for drinking;10 days later all mice underwent sham laparotomy that was suture closed. Mice were sacrificed on postop days (PODs) 7 or 21 and the abdominal wall pelts were harvested. The peak force and total energy required to rupture each wound was determined via tensometry; wound collagen content was determined via a Sircol Collagen assay. Serum EGCG levels were determined in 3 PolyE mice on POD1, 7, and 21 to verify drug ingestion. Results are presented as mean ± SD; data was assessed using the student's t-test and Mann-Whitney U-test (significance, p<0.05). Results: No wound infections or dehiscences were noted in either group. The mean peak rupture force for each group was statistically similar on POD 7 and 21. There was no statistical difference in the total energy required for rupture on POD 7, however, on POD 21 the total energy required in the PolyE group (4.1 ± 0.78 N-mm) was significantly lower than for the control mice (5.6 ± 1.7 N-mm; p=0.026). When the 2 groups wound collagen results on POD 7 were compared there was no difference noted, the same was true for the POD 21 results. EGCG was detected in the PolyE mice serum on POD 1 and POD 7; on POD21 very low levels were detected. Conclusions: Perioperative PolyE administration was not associated with wound complications. The peak force for rupture and the collagen content was similar at both time points for the 2 groups as was total energy for rupture on POD 7; total energy on POD 21 was less for the PolyE group. PolyE warrants further study as a perioperative anti-cancer agent in the cancer setting.
Objectives: To evaluate the Ki-67 antigen expression in patients with Barrett's esophagus and esophageal adenocarcinoma and to analyse its correlation with the metaplasia-esophageal adenocarcinoma progression. Methods: Through imunohistochemical analysis we evaluated Ki-67 index in patients with Barrett's esophagus, esophageal adenocarcinoma and controls, assisted at Hospital de Clinicas de Porto Alegre between 2002 and 2005. We included patients with endoscopically visible columnar mucosa of the distal esophagus, whose biopsy proved specialized intestinal type metaplasia, patients with esophageal and esophagogastric tumors type I and II and patients with histologically normal gastric mucosa (control). Results: We studied 57 pacients. There was no statistically significant differences between the groups regarding age or race. Patients with cancer were predominantly men. Ki-67 index averaged 10±4% in patients with normal gastric mucosa (n=17), 21±15% in patients with Barrett's esophagus (n=21) and 38±16% in patients with cancer (n=19). Ki-67 expression was significantly different between all groups (P<0,05). There was strong linear correlation between Ki67 expression and metaplasia-adenocarcinoma sequence (P<0,01). In patients with cancer, Ki-67 was not associated with clinical or surgical staging. Conclusions: Ki-67 antigen has increased expression along the metaplasia-adenocarcinoma sequence. There is strong linear correlation between Ki-67 proliferative activity and Barrett's carcinogenesis.
W1831
Purpose: Esophageal cancer is one of the most frequent cancers worldwide and is associated with poor outcome. Besides clinicopathological data, few prognostic molecular markers exist. Esophageal Cancer Related Gene1 (ECRG1) short tandem repeats are associated with higher risk for developing esophageal squamous cell carcinoma. The aim of the present study was to evaluate the impact of DNA polymorphisms in the coding region of ECRG1 in esophageal carcinoma. Methods: Genomic DNA of 107 patients with esophageal cancer that underwent complete surgical resection between 1997 and 2005 and of 100 healthy controls was extracted. DNA was analyzed for ECRG1 polymorphisms Arg290Arg, Arg290Gln, and Gln290Gln by PCR and gel electrophoresis. Polymorphisms were correlated with survival data by the Kaplan-Meier method, multivariate Cox regression analysis, and odds ratio were determined. Results: Follow-up data of 102 patients with esophageal cancer were available after complete surgical resection for a mean follow-up time of 24.3 months. Polymorphism Arg290Arg was found in 47 patients (46.1%), Arg290Gln in 48 patients (47.0%) and Gln290Gln in 7 cases (6.9%). Arg290Arg polymorphism was significantly associated with reduced survival by the log-rank test (p=0.011). Multivariate regression analysis by Cox revealed polymorphism Arg290Arg to be a significant independent prognostic factor for survival (p=0.012). Conclusions: Polymorphism Arg290Arg in ECRG1 is associated with poor clinical outcome after complete surgical resection in patients with esophageal cancer. This genetic polymorphism might be used to predict the response to neoadjuvant treatment. The role of ECRG1 in esophageal cancer development has to be determined in future studies.
W1834 Enteral Immunonutrition with Long Chain Triglycerides Significantly Reduces the Recruitment of Immune Cells Into the Liver During Experimental Sepsis Maximilian Feilitzsch, Theo Maier, Judith Junginger, Tobias Meile, Markus A. Kueper, Alfred Koenigsrainer, Jorg Glatzle Background: There is strong evidence that hepatocellular injury during sepsis is initiated by inflammatory processes originated by both activated Kupffer cells and circulating blood cells which become adherent within the endotoxemic liver Recently, we have shown, that an enteral immunonutrition with long chain triglycerides significantly reduced lung injury during sepsis (Glatzle et al J. Gastrointest. Surg. 2007). Aim: To investigate, whether an enteral immunonutrition with long chain triglycerides reduces inflammatory response in the liver during sepsis. Methods: Mesenteric lymph was obtained from lymph fistula donor rats under control conditions (n=6, control lymph, CL) or during sepsis (n=6, LPS, 5mg/kg i.p., sepsis lymph, SL). Sepsis lymph was also collected during enteral immunonutrition with 1% olive oil (n=6, SL-OO) or 1% of fish oil (n=6, SL-FO). CL, SL, SL-OO, SL-FO were reinfused into the jugular vein of separate healthy recipient rats (n=4 each group). Thereafter, liver tissue was collected and the number of Kupffer cells (ED2) or recruited macrophages (ED1) were analyzed at t=90 and t=180min (n=30 optical sections per rat). Results: The release of TNFa from the gastrointestinal tract into mesenteric lymph was up to 200fold increased during sepsis. Infusion of sepsis lymph into separate recipient rats increased the number of ED1 positive cells by more than twice at t=180min, whereas no changes were observed after 90 min. Infusion of sepsis lymph did not change the number of ED2 positive cells in the liver of recipient rats. Interestingly, infusion of sepsis lymph collected during an enteral immunonutrition with either olive oil or fish oil, significantly reduced the number of recruited ED1 positive macrophages into the liver by more than 30% and 40% respectively (ED1 positive cells/optical field, t=180min: CL: 0.89±0.09, SL: 1.8±0.1*, SL-OO: 1.2±0.1#, SL-FO: 1.0±0.07#, *p<0.001vs. CL, #p<0.001 vs. SL). Conclusion: An enteral immunonutrition with long chain triglycerides during sepsis reduces inflammatory mediator release from the gastrointestinal tract and has a protective effect regarding inflammatory response of the liver during sepsis.
W1832 Barrett's Intestinal Metaplasia mRNA Expression Profile in Formalin-Fixed, Paraffin-Embedded Endoscopic Biopsy Specimens Fiona I. Schneiders, Natalia K. Botelho, Reginald V. N. Lord Background and Aim: Widespread applicability of genetic testing for Barrett's esophagus depends on developing accurate methods for assaying archival formalin-fixed, paraffinembedded (FFPE) histopathology specimens taken at endoscopy. We sought to develop an accurate mRNA comparative quantification method for FFPE tissues that would detect disease even in patients with Barrett's intestinal metaplasia, who have small alterations in gene expression compared to patients with dysplasia or cancer. Methods: mRNA was isolated from formalin-fixed, paraffin-embedded (FFPE) small endoscopic biopsies from 10 patients with IM and 11 control patients with a normal squamous-lined esophagus. IM tissues included only small numbers of glands in a single endoscopic biopsy in some cases. Multiplex tandem PCR (MT-PCR) was used to quantitate genes of interest for Barrett's esophagus and control genes in duplicate using the Rotor-Gene 6000 system (Corbett Life Sciences). Results: Significantly increased expression of hTERT, ODC1, MYB, SPARC, RAR-A, and significantly decreased expression of GSTP1 and RAR-G were found in IM compared to normal tissues. The direction and magnitude of the differences were very similar to those found using fresh
A-911
SSAT Abstracts
SSAT Abstracts
Polymorphism Arg290Arg in Esophageal Cancer Related Gene 1 (ECRG1) Is a Prognostic Factor for Survival in Esophageal Cancer Kai Bachmann, Jussuf T. Kaifi, Paulus G. Schurr, Jakob R. Izbicki, Tim Strate
frozen tissues. Two novel genes identified from a microarray study, CD151 (which encodes a protein that enhances cell motility, invasion and metastasis of cancer cells) and TCIRG1 (T-cell, immune regulator 1, ATPase, H+ transporting, lysosomal V0 subunit A3) were overexpressed in IM. Conclusions: Accurate mRNA comparative quantification, matching fresh frozen tissue results, can be obtained from even single small formalin-fixed, paraffinembedded Barrett's esophagus endoscopic biopsy tissues using a multiplex tandem PCR method.
W1830 Polyphenon E, An EGCG Containing Green Tea Extract That Inhibits Tumor Growth, Has No Impact On Wound Collagen Content or Clinical Rate of Wound Infection or Dehiscence Yet Has a Mild Inhibitory Effect On Healing As Judged By Tensometry Aviad Hoffman, Raymond Baxter, Abu Nasar, Thomas R. Gardner, Kumara H. Shantha, Keith Hoffman, Richard L. Whelan
W1833 KI-67 Antigen Is Overexpressed in Barrett's Carcinogenesis Bernardo Volkweis, Richard R. Gurski, Luise Meurer, Maria Isabel A. Edelweiss, Gustavo Morellato, Marcelo K. Schmidt
Introduction: Catechins in green tea, in particular EGCG (epigallocatechin-3-gallate), inhibit tumor growth in many murine models. Polyphenon E (PolyE) is a concentrated mixture of catechins (65% EGCG) with minimal side affects in humans that has stronger anti-cancer effects than tea alone. Surgery is associated with increased rates of tumor growth and metastases postoperatively(postop) in the murine setting. Perioperative (periop) administration of Poly E may limit surgery's tumor stimulatory effects. Prior to a Phase 1 study, PolyE's effects on wound healing must be studied. This study's purpose was to assess PolyE's impact on laparotomy wound strength and collagen content. Methods: Balb/C mice were randomized to plain water (Control, n=20) or a 1% PolyE solution (n=25) for drinking;10 days later all mice underwent sham laparotomy that was suture closed. Mice were sacrificed on postop days (PODs) 7 or 21 and the abdominal wall pelts were harvested. The peak force and total energy required to rupture each wound was determined via tensometry; wound collagen content was determined via a Sircol Collagen assay. Serum EGCG levels were determined in 3 PolyE mice on POD1, 7, and 21 to verify drug ingestion. Results are presented as mean ± SD; data was assessed using the student's t-test and Mann-Whitney U-test (significance, p<0.05). Results: No wound infections or dehiscences were noted in either group. The mean peak rupture force for each group was statistically similar on POD 7 and 21. There was no statistical difference in the total energy required for rupture on POD 7, however, on POD 21 the total energy required in the PolyE group (4.1 ± 0.78 N-mm) was significantly lower than for the control mice (5.6 ± 1.7 N-mm; p=0.026). When the 2 groups wound collagen results on POD 7 were compared there was no difference noted, the same was true for the POD 21 results. EGCG was detected in the PolyE mice serum on POD 1 and POD 7; on POD21 very low levels were detected. Conclusions: Perioperative PolyE administration was not associated with wound complications. The peak force for rupture and the collagen content was similar at both time points for the 2 groups as was total energy for rupture on POD 7; total energy on POD 21 was less for the PolyE group. PolyE warrants further study as a perioperative anti-cancer agent in the cancer setting.
Objectives: To evaluate the Ki-67 antigen expression in patients with Barrett's esophagus and esophageal adenocarcinoma and to analyse its correlation with the metaplasia-esophageal adenocarcinoma progression. Methods: Through imunohistochemical analysis we evaluated Ki-67 index in patients with Barrett's esophagus, esophageal adenocarcinoma and controls, assisted at Hospital de Clinicas de Porto Alegre between 2002 and 2005. We included patients with endoscopically visible columnar mucosa of the distal esophagus, whose biopsy proved specialized intestinal type metaplasia, patients with esophageal and esophagogastric tumors type I and II and patients with histologically normal gastric mucosa (control). Results: We studied 57 pacients. There was no statistically significant differences between the groups regarding age or race. Patients with cancer were predominantly men. Ki-67 index averaged 10±4% in patients with normal gastric mucosa (n=17), 21±15% in patients with Barrett's esophagus (n=21) and 38±16% in patients with cancer (n=19). Ki-67 expression was significantly different between all groups (P<0,05). There was strong linear correlation between Ki67 expression and metaplasia-adenocarcinoma sequence (P<0,01). In patients with cancer, Ki-67 was not associated with clinical or surgical staging. Conclusions: Ki-67 antigen has increased expression along the metaplasia-adenocarcinoma sequence. There is strong linear correlation between Ki-67 proliferative activity and Barrett's carcinogenesis.
W1831
Purpose: Esophageal cancer is one of the most frequent cancers worldwide and is associated with poor outcome. Besides clinicopathological data, few prognostic molecular markers exist. Esophageal Cancer Related Gene1 (ECRG1) short tandem repeats are associated with higher risk for developing esophageal squamous cell carcinoma. The aim of the present study was to evaluate the impact of DNA polymorphisms in the coding region of ECRG1 in esophageal carcinoma. Methods: Genomic DNA of 107 patients with esophageal cancer that underwent complete surgical resection between 1997 and 2005 and of 100 healthy controls was extracted. DNA was analyzed for ECRG1 polymorphisms Arg290Arg, Arg290Gln, and Gln290Gln by PCR and gel electrophoresis. Polymorphisms were correlated with survival data by the Kaplan-Meier method, multivariate Cox regression analysis, and odds ratio were determined. Results: Follow-up data of 102 patients with esophageal cancer were available after complete surgical resection for a mean follow-up time of 24.3 months. Polymorphism Arg290Arg was found in 47 patients (46.1%), Arg290Gln in 48 patients (47.0%) and Gln290Gln in 7 cases (6.9%). Arg290Arg polymorphism was significantly associated with reduced survival by the log-rank test (p=0.011). Multivariate regression analysis by Cox revealed polymorphism Arg290Arg to be a significant independent prognostic factor for survival (p=0.012). Conclusions: Polymorphism Arg290Arg in ECRG1 is associated with poor clinical outcome after complete surgical resection in patients with esophageal cancer. This genetic polymorphism might be used to predict the response to neoadjuvant treatment. The role of ECRG1 in esophageal cancer development has to be determined in future studies.
W1834 Enteral Immunonutrition with Long Chain Triglycerides Significantly Reduces the Recruitment of Immune Cells Into the Liver During Experimental Sepsis Maximilian Feilitzsch, Theo Maier, Judith Junginger, Tobias Meile, Markus A. Kueper, Alfred Koenigsrainer, Jorg Glatzle Background: There is strong evidence that hepatocellular injury during sepsis is initiated by inflammatory processes originated by both activated Kupffer cells and circulating blood cells which become adherent within the endotoxemic liver Recently, we have shown, that an enteral immunonutrition with long chain triglycerides significantly reduced lung injury during sepsis (Glatzle et al J. Gastrointest. Surg. 2007). Aim: To investigate, whether an enteral immunonutrition with long chain triglycerides reduces inflammatory response in the liver during sepsis. Methods: Mesenteric lymph was obtained from lymph fistula donor rats under control conditions (n=6, control lymph, CL) or during sepsis (n=6, LPS, 5mg/kg i.p., sepsis lymph, SL). Sepsis lymph was also collected during enteral immunonutrition with 1% olive oil (n=6, SL-OO) or 1% of fish oil (n=6, SL-FO). CL, SL, SL-OO, SL-FO were reinfused into the jugular vein of separate healthy recipient rats (n=4 each group). Thereafter, liver tissue was collected and the number of Kupffer cells (ED2) or recruited macrophages (ED1) were analyzed at t=90 and t=180min (n=30 optical sections per rat). Results: The release of TNFa from the gastrointestinal tract into mesenteric lymph was up to 200fold increased during sepsis. Infusion of sepsis lymph into separate recipient rats increased the number of ED1 positive cells by more than twice at t=180min, whereas no changes were observed after 90 min. Infusion of sepsis lymph did not change the number of ED2 positive cells in the liver of recipient rats. Interestingly, infusion of sepsis lymph collected during an enteral immunonutrition with either olive oil or fish oil, significantly reduced the number of recruited ED1 positive macrophages into the liver by more than 30% and 40% respectively (ED1 positive cells/optical field, t=180min: CL: 0.89±0.09, SL: 1.8±0.1*, SL-OO: 1.2±0.1#, SL-FO: 1.0±0.07#, *p<0.001vs. CL, #p<0.001 vs. SL). Conclusion: An enteral immunonutrition with long chain triglycerides during sepsis reduces inflammatory mediator release from the gastrointestinal tract and has a protective effect regarding inflammatory response of the liver during sepsis.
W1832 Barrett's Intestinal Metaplasia mRNA Expression Profile in Formalin-Fixed, Paraffin-Embedded Endoscopic Biopsy Specimens Fiona I. Schneiders, Natalia K. Botelho, Reginald V. N. Lord Background and Aim: Widespread applicability of genetic testing for Barrett's esophagus depends on developing accurate methods for assaying archival formalin-fixed, paraffinembedded (FFPE) histopathology specimens taken at endoscopy. We sought to develop an accurate mRNA comparative quantification method for FFPE tissues that would detect disease even in patients with Barrett's intestinal metaplasia, who have small alterations in gene expression compared to patients with dysplasia or cancer. Methods: mRNA was isolated from formalin-fixed, paraffin-embedded (FFPE) small endoscopic biopsies from 10 patients with IM and 11 control patients with a normal squamous-lined esophagus. IM tissues included only small numbers of glands in a single endoscopic biopsy in some cases. Multiplex tandem PCR (MT-PCR) was used to quantitate genes of interest for Barrett's esophagus and control genes in duplicate using the Rotor-Gene 6000 system (Corbett Life Sciences). Results: Significantly increased expression of hTERT, ODC1, MYB, SPARC, RAR-A, and significantly decreased expression of GSTP1 and RAR-G were found in IM compared to normal tissues. The direction and magnitude of the differences were very similar to those found using fresh
A-911
SSAT Abstracts
SSAT Abstracts
Polymorphism Arg290Arg in Esophageal Cancer Related Gene 1 (ECRG1) Is a Prognostic Factor for Survival in Esophageal Cancer Kai Bachmann, Jussuf T. Kaifi, Paulus G. Schurr, Jakob R. Izbicki, Tim Strate