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QS72. Resolvin Reverses The Microvascular Fluid Loss Associated With Inflammation
ASSOCIATION FOR ACADEMIC SURGERY AND SOCIETY OF UNIVERSITY SURGEONS—ABSTRACTS 297 modates the inflow, the entire volume is returned while the chamber is off suction. In our initial experience with surgery for esophageal carcinoma, 100 kcal/ hour of enteral tube feeding was tolerated immediately following thoraco-abdominal resection, re-anastomosis, and complete truncal vagotomy. A total of only 100-200 ml/day of aspirate was discarded to achieve immediate safe nutrition. No complications were observed. “Clinical judgment” cannot substitute for monitoring and automatic timely response to overfeeding. The procedure is inherently safe, as is it delivers nothing to the patient in net fashion. A small quantity of degassed fluid is returned by gravity, back to essentially the same site from which it had been removed seconds earlier. Aspirate is not wasted, but is “refed” as tolerated. Fluid and electrolytes are conserved, and immune competence may be augmented by return of the contained secretory globulins, specific for gut organisms. Full enteral feeding can be initiated immediately postoperatively and/or after burns or trauma, safely approaching and achieving full nutritional goals.
receptor on the cell surface. Conclusions: 1. There was significantly more pStat1 in response to IFN␥ in the cells from patients with CD compared to the UC patients or non-diseased individuals. 2. This increase in pStat1 was not due to either an increase in IFN␥ receptor on the cell surface or to an increase in spontaneous release of IFN␥ from the cells themselves suggesting that the cells from CD patients have an increased sensitivity to IFN␥. 3. Elevated pStat1 in response to IFN␥ may help differentiate CD from UC and non-inflammatory diseases such as irritable bowel syndrome.
QS72. RESOLVIN REVERSES THE MICROVASCULAR FLUID LOSS ASSOCIATED WITH INFLAMMATION. Elizabeth L. Cureton, Javid Sadjadi, Alexander Q. Ereso, Brian Curran, Gregory P. Victorino; UCSF East Bay, Oakland, CA
QS71. ELEVATED PHOSPHORYLATED SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION-1 FROM B-LYMPHOCYTES IN PATIENTS WITH CROHN’S DISEASE. Lisa S. Poritz, Jennifer Thompson, Amanda Dowell, Walter A. Koltun; The Milton S. Hershey Medical Center, Hershey, PA Introduction: Interferon gamma (IFN␥) has been shown to be elevated in the tissues of some patients with Crohn’s disease (CD). Treatment of CD with antibody to IFN␥ is currently under investigation. IFN␥ exerts the majority of its effect through the IFN␥Signal transducer and activator of transcription-1 (Stat1) signaling pathway. Methods: Peripheral B-lymphocytes were obtained from 30 (10 with CD, 10 with UC, and 10 non-diseased) unrelated individuals. 2 x 10 6 cells from each individual were stimulated with and without 20ng/ml of IFN␥ for 90 minutes. Western blot of the nuclear proteins was performed for phosphorylated (pStat1) and unphosphorylated Stat1 and corrected for actin and Hela. 1 x 10 6 additional cells from each individual were incubated in 0.5 ml of media for 48 hours and supernatants assayed for IFN␥ by ELISA. An additional 1 x 10 6 cells were stained with PE-conjugated anti IFN␥ receptor antibody and analyzed on by FACS. Results were compared by ANOVA. Results: Baseline unstimulated expression of Stat1 was the same in patients with CD, UC, and non-diseased controls. pStat1 in response to IFN␥ stimulation was significantly elevated in the CD individuals compared to those with UC or non-diseased controls (see graph, *p⬍0.05 compared to non-diseased controls). pStat1 was also increased in UC compared to controls but not significantly so. There was no significant difference in either the amount of spontaneous IFN␥ secreted by the three groups of cells or the amount of IFN␥
Introduction: Resolvins are omega-3 fatty acid derivatives associated with the resolution phase of inflammation and have been shown to protect against colitis and peritonitis. Lipopolysaccharide (LPS) and platelet-activating factor (PAF) are major inflammatory mediators that are associated with gastrointestinal infection, peritonitis and sepsis. Our hypothesis was that resolvin (RvE1) reverses the increase in microvascular fluid leak that occurs during inflammation. The purposes of this study are: 1) to determine the effect of RvE1 on microvascular fluid leak, 2) to determine the effect of LPSinduced and PAF-induced inflammation on microvascular fluid leak, and 3) to determine if RvE1 reverses the increase in microvascular fluid leak induced by LPS- and PAF-induced inflammation. Methods: A micro-cannulation technique was used to determine microvascular fluid leak or hydraulic permeability (Lp) in rat mesenteric venules. Upon initial cannulation of the study venule, baseline Lp measurements were obtained. Then Lp was measured during the following conditions: 1) RvE1 alone: RvE1 (100 nM) was continuously perfused and Lp measured every 5 minutes (n⫽3), 2) LPS-induced and PAF-induced inflammation: LPS was given as a systemic bolus (10 mg/kg) followed by a continuous LPS perfusion (0.5 mg/ml) and Lp measured every 5 minutes (n⫽5), and PAF (10 nM) was perfused continuously and Lp measured every 5 minutes (n⫽4), and 3) RvE1 treatment after LPS-induced and PAF-induced inflammation: after inflammation was induced by LPS or PAF as above, RvE1 (100 nM) was administered as a continuous perfusion and Lp measured every 5 minutes (n⫽3 each). Results: There was a small initial increase in Lp due to RvE1 alone (from 1.02 ⫾ 0.007 to 1.23 ⫾ 0.06, p⬍0.004), but by 10 minutes Lp had returned to baseline. LPS-induced inflammation increased Lp two-fold (1.20 ⫾ 0.13 to 2.27 ⫾ 0.13; p⬍0.002). PAF-induced inflammation increased Lp four-fold (from 1.20 ⫾ 0.13 to 4.49 ⫾ 0.95, p⬍0.001). Compared with LPS alone, treatment with RvE1 after LPS-induced inflammation decreased Lp by 44% (from 2.27 ⫾ 0.13 to 1.13 ⫾ 0.03, p⬍0.004). Compared to PAF alone, treatment with RvE1 after PAF-induced inflammation decreased Lp by 42% (from 4.94 ⫾ 0.95 to 2.86 ⫾ 0.28). Units for Lp are cm-sec
298 ASSOCIATION FOR ACADEMIC SURGERY AND SOCIETY OF UNIVERSITY SURGEONS—ABSTRACTS /cm-H 2O x10 ⫺7. Conclusions: Resolvins are endogenously released anti-inflammatory mediators that are upregulated during the resolution phase of inflammation and have been shown to protect against colitis and peritonitis. We found that resolvin reversed the microvascular fluid leak that occurs during LPS- and PAF-induced inflammation. Resolvin may be useful therapeutically for the management of microvascular fluid loss associated with inflammation and shock due to gastrointestinal infections and peritonitis. QS73. WHAT=S IN A NAME? THE CLINICAL IMPORTANCE OF ACCURATE HISTOLOGICAL CLASSIFICATION OF SERRATED COLORECTAL POLYPS. Craig A. Messick, Ana Bennett, Julian A. Sanchez, James M. Church, Matthew F. Kalady; The Cleveland Clinic, Cleveland, OH Introduction: Colorectal hyperplastic polyps are serrated lesions that are generally considered benign. However, mounting evidence suggests a subset of these polyps (large, right-sided) serves as precursors to malignancy via the serrated pathway to oncogenesis. Members of the serrated family include progressive changes from hyperplastic polyps to sessile serrated polyps (hyperplastic polyps with abnormal proliferation) to serrated adenomas (hyperplastic polyps with dysplasia). This study evaluates a set of previously reviewed large hyperplastic colorectal polyps and analyzes changes in histologic diagnosis given newly understood biology of these lesions and applying up-to-date definitions. Methods: An IRB-approved colorectal polyp database was queried for hyperplastic polyps greater than 20 mm in size between 1994 and 2005. Diagnoses were taken from pathology reports and both patient and polyp characteristics were reviewed. A gastroenterology-specialized pathologist blindly reviewed H&E slides from large, previously diagnosed hyperplastic polyps and rendered histologic diagnoses based upon currently employed classification criteria. Results were analyzed to see if there was a change in histologic diagnosis between the initial and subsequent review using the new criteria. Results: 38 hyperplastic polyps from 37 patients were reviewed. Median age of patients was 62 years (range 33-86). Twenty-one patients were female (57%) and 16 were male (43%). Thirty-four polyps (89%) were right-sided and 4 (11%) were located in the left colon. Median polyp size was 22.5 mm (range 20-40 mm). Of the 38 polyps originally designated hyperplastic, 10 (26%) remained classified as such. Twenty-eight polyps (74%) subsequently had their histologic nomenclature reclassified as sessile serrated polyps. Two patients whose histologic classification changed to sessile serrated polyps subsequently developed colon adenocarcinoma. Conclusion: Lesions that appear to be benign hyperplastic polyps during colonoscopy represent a spectrum of polyps that may carry malignant potential. Change in histologic diagnosis for nearly three-fourths of previously called hyperplastic polyps underscores a new approach and understanding of these lesions as part of the serrated pathway to colorectal carcinoma. Surgeons and endoscopists must have a heightened awareness of the clinical significance of these sessile serrated polyps.
4,701 patients with rectal carcinoid tumors from 1977 to 2004. Patients were analyzed by size, depth of invasion, lymph node involvement, and metastatic disease; a staging system was created according to these parameters. Patients were analyzed for all clinicopathologic factors and a Tumor (T1⬍ 1cm or submucosa, T2 ⱖ 1cm but ⬍2cm or muscularis propria invasion, T3 ⱖ2cm or serosa) stage, lymph Node (N0 no nodal mets, N1 nodal disease) stage, and Metastatic (M0 no mets, M1 metastasis) stage, staging system was created according to these parameters. The staging system was analyzed both within and between stages to assure statistical significance. Data points were compared using Kaplan Meier and Cox Proportional Hazards.
Results: Of the 4,701 patients in the database, 2,329 were female and 2,372 were male. Average age at diagnosis was 56.4 years (14-94). Average size of primary tumor was 1.03 cm (0.1-25), with 4% having lymph node metastasis. One primary tumor was found in 82% (3,857) patients, with synchronous metastatic disease present in 2% of patients. Survival was statistically significant between stages (p⬍0.0001), and not significant within stages. Stage I disease was seen in 91.3% patients, 4% with Stage II, 2% with Stage III, and 3% patients in Stage IV. 5 year survival was 97.8%, 64.3%, 54.2%, and 20% for Stages I-IV respectively. Size of primary tumor and depth of invasion were the most powerful predictors of survival on multivariate analysis (p⬍0.0001). Conclusion: Our newly developed staging system accurately predicts disease prognosis in rectal carcinoids. Incorporation of rectal carcinoids into the American Joint Committee on Cancer is needed to both educate all physicians and to follow trends in prognosis.
QS74. ANALYSIS OF 4,701 RECTAL CARCINOID TUMORS FOR A PROPOSED STAGING SYSTEM. Christine S. Landry, Charles R. Scoggins, Charles Woodall, Kelly M. McMasters, Robert CG Martin II; University of Louisville, Louisville, KY
QS75. ANALYSIS OF 2,459 COLON CARCINOID TUMORS FOR A PROPOSED STAGING SYSTEM. Christine S. Landry, Charles R. Scoggins, Kelly M. McMasters, Robert Martin; University of Louisville, Louisville, KY
Background: The purpose of this study was to determine prognostic factors important in the overall survival of rectal carcinoid tumors. To date, no staging system exists for these tumors and thus little is known regarding appropriate management and follow up. Therefore, we sought to investigate prognostic factors associated with rectal carcinoid tumors and create a predictive staging system to accurately estimate prognosis. Methods: A search of 15,983 patients with carcinoid tumors from the National Cancer Institute’s SEER (Surveillance Epidemiology and End Results) database identified
Background: Colon carcinoid remains an uncommon finding during screening endoscopy or surgery, with a little known about the long term prognosis. The reasons for this uncertainty is that no staging system exists in order to appropriately risk stratify or follow these patients for overall survival. This limitation has led to the inability to compare outcomes, or to even establish appropirate treatment algorithims in these patients. Therefore, we sought to investigate prognostic factors associated with colon carcinoid tumors and create a predictive staging system to accurately estimate prognosis. Meth-
receptor on the cell surface. Conclusions: 1. There was significantly more pStat1 in response to IFN␥ in the cells from patients with CD compared to the UC patients or non-diseased individuals. 2. This increase in pStat1 was not due to either an increase in IFN␥ receptor on the cell surface or to an increase in spontaneous release of IFN␥ from the cells themselves suggesting that the cells from CD patients have an increased sensitivity to IFN␥. 3. Elevated pStat1 in response to IFN␥ may help differentiate CD from UC and non-inflammatory diseases such as irritable bowel syndrome.
QS72. RESOLVIN REVERSES THE MICROVASCULAR FLUID LOSS ASSOCIATED WITH INFLAMMATION. Elizabeth L. Cureton, Javid Sadjadi, Alexander Q. Ereso, Brian Curran, Gregory P. Victorino; UCSF East Bay, Oakland, CA
QS71. ELEVATED PHOSPHORYLATED SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION-1 FROM B-LYMPHOCYTES IN PATIENTS WITH CROHN’S DISEASE. Lisa S. Poritz, Jennifer Thompson, Amanda Dowell, Walter A. Koltun; The Milton S. Hershey Medical Center, Hershey, PA Introduction: Interferon gamma (IFN␥) has been shown to be elevated in the tissues of some patients with Crohn’s disease (CD). Treatment of CD with antibody to IFN␥ is currently under investigation. IFN␥ exerts the majority of its effect through the IFN␥Signal transducer and activator of transcription-1 (Stat1) signaling pathway. Methods: Peripheral B-lymphocytes were obtained from 30 (10 with CD, 10 with UC, and 10 non-diseased) unrelated individuals. 2 x 10 6 cells from each individual were stimulated with and without 20ng/ml of IFN␥ for 90 minutes. Western blot of the nuclear proteins was performed for phosphorylated (pStat1) and unphosphorylated Stat1 and corrected for actin and Hela. 1 x 10 6 additional cells from each individual were incubated in 0.5 ml of media for 48 hours and supernatants assayed for IFN␥ by ELISA. An additional 1 x 10 6 cells were stained with PE-conjugated anti IFN␥ receptor antibody and analyzed on by FACS. Results were compared by ANOVA. Results: Baseline unstimulated expression of Stat1 was the same in patients with CD, UC, and non-diseased controls. pStat1 in response to IFN␥ stimulation was significantly elevated in the CD individuals compared to those with UC or non-diseased controls (see graph, *p⬍0.05 compared to non-diseased controls). pStat1 was also increased in UC compared to controls but not significantly so. There was no significant difference in either the amount of spontaneous IFN␥ secreted by the three groups of cells or the amount of IFN␥
Introduction: Resolvins are omega-3 fatty acid derivatives associated with the resolution phase of inflammation and have been shown to protect against colitis and peritonitis. Lipopolysaccharide (LPS) and platelet-activating factor (PAF) are major inflammatory mediators that are associated with gastrointestinal infection, peritonitis and sepsis. Our hypothesis was that resolvin (RvE1) reverses the increase in microvascular fluid leak that occurs during inflammation. The purposes of this study are: 1) to determine the effect of RvE1 on microvascular fluid leak, 2) to determine the effect of LPSinduced and PAF-induced inflammation on microvascular fluid leak, and 3) to determine if RvE1 reverses the increase in microvascular fluid leak induced by LPS- and PAF-induced inflammation. Methods: A micro-cannulation technique was used to determine microvascular fluid leak or hydraulic permeability (Lp) in rat mesenteric venules. Upon initial cannulation of the study venule, baseline Lp measurements were obtained. Then Lp was measured during the following conditions: 1) RvE1 alone: RvE1 (100 nM) was continuously perfused and Lp measured every 5 minutes (n⫽3), 2) LPS-induced and PAF-induced inflammation: LPS was given as a systemic bolus (10 mg/kg) followed by a continuous LPS perfusion (0.5 mg/ml) and Lp measured every 5 minutes (n⫽5), and PAF (10 nM) was perfused continuously and Lp measured every 5 minutes (n⫽4), and 3) RvE1 treatment after LPS-induced and PAF-induced inflammation: after inflammation was induced by LPS or PAF as above, RvE1 (100 nM) was administered as a continuous perfusion and Lp measured every 5 minutes (n⫽3 each). Results: There was a small initial increase in Lp due to RvE1 alone (from 1.02 ⫾ 0.007 to 1.23 ⫾ 0.06, p⬍0.004), but by 10 minutes Lp had returned to baseline. LPS-induced inflammation increased Lp two-fold (1.20 ⫾ 0.13 to 2.27 ⫾ 0.13; p⬍0.002). PAF-induced inflammation increased Lp four-fold (from 1.20 ⫾ 0.13 to 4.49 ⫾ 0.95, p⬍0.001). Compared with LPS alone, treatment with RvE1 after LPS-induced inflammation decreased Lp by 44% (from 2.27 ⫾ 0.13 to 1.13 ⫾ 0.03, p⬍0.004). Compared to PAF alone, treatment with RvE1 after PAF-induced inflammation decreased Lp by 42% (from 4.94 ⫾ 0.95 to 2.86 ⫾ 0.28). Units for Lp are cm-sec
298 ASSOCIATION FOR ACADEMIC SURGERY AND SOCIETY OF UNIVERSITY SURGEONS—ABSTRACTS /cm-H 2O x10 ⫺7. Conclusions: Resolvins are endogenously released anti-inflammatory mediators that are upregulated during the resolution phase of inflammation and have been shown to protect against colitis and peritonitis. We found that resolvin reversed the microvascular fluid leak that occurs during LPS- and PAF-induced inflammation. Resolvin may be useful therapeutically for the management of microvascular fluid loss associated with inflammation and shock due to gastrointestinal infections and peritonitis. QS73. WHAT=S IN A NAME? THE CLINICAL IMPORTANCE OF ACCURATE HISTOLOGICAL CLASSIFICATION OF SERRATED COLORECTAL POLYPS. Craig A. Messick, Ana Bennett, Julian A. Sanchez, James M. Church, Matthew F. Kalady; The Cleveland Clinic, Cleveland, OH Introduction: Colorectal hyperplastic polyps are serrated lesions that are generally considered benign. However, mounting evidence suggests a subset of these polyps (large, right-sided) serves as precursors to malignancy via the serrated pathway to oncogenesis. Members of the serrated family include progressive changes from hyperplastic polyps to sessile serrated polyps (hyperplastic polyps with abnormal proliferation) to serrated adenomas (hyperplastic polyps with dysplasia). This study evaluates a set of previously reviewed large hyperplastic colorectal polyps and analyzes changes in histologic diagnosis given newly understood biology of these lesions and applying up-to-date definitions. Methods: An IRB-approved colorectal polyp database was queried for hyperplastic polyps greater than 20 mm in size between 1994 and 2005. Diagnoses were taken from pathology reports and both patient and polyp characteristics were reviewed. A gastroenterology-specialized pathologist blindly reviewed H&E slides from large, previously diagnosed hyperplastic polyps and rendered histologic diagnoses based upon currently employed classification criteria. Results were analyzed to see if there was a change in histologic diagnosis between the initial and subsequent review using the new criteria. Results: 38 hyperplastic polyps from 37 patients were reviewed. Median age of patients was 62 years (range 33-86). Twenty-one patients were female (57%) and 16 were male (43%). Thirty-four polyps (89%) were right-sided and 4 (11%) were located in the left colon. Median polyp size was 22.5 mm (range 20-40 mm). Of the 38 polyps originally designated hyperplastic, 10 (26%) remained classified as such. Twenty-eight polyps (74%) subsequently had their histologic nomenclature reclassified as sessile serrated polyps. Two patients whose histologic classification changed to sessile serrated polyps subsequently developed colon adenocarcinoma. Conclusion: Lesions that appear to be benign hyperplastic polyps during colonoscopy represent a spectrum of polyps that may carry malignant potential. Change in histologic diagnosis for nearly three-fourths of previously called hyperplastic polyps underscores a new approach and understanding of these lesions as part of the serrated pathway to colorectal carcinoma. Surgeons and endoscopists must have a heightened awareness of the clinical significance of these sessile serrated polyps.
4,701 patients with rectal carcinoid tumors from 1977 to 2004. Patients were analyzed by size, depth of invasion, lymph node involvement, and metastatic disease; a staging system was created according to these parameters. Patients were analyzed for all clinicopathologic factors and a Tumor (T1⬍ 1cm or submucosa, T2 ⱖ 1cm but ⬍2cm or muscularis propria invasion, T3 ⱖ2cm or serosa) stage, lymph Node (N0 no nodal mets, N1 nodal disease) stage, and Metastatic (M0 no mets, M1 metastasis) stage, staging system was created according to these parameters. The staging system was analyzed both within and between stages to assure statistical significance. Data points were compared using Kaplan Meier and Cox Proportional Hazards.
Results: Of the 4,701 patients in the database, 2,329 were female and 2,372 were male. Average age at diagnosis was 56.4 years (14-94). Average size of primary tumor was 1.03 cm (0.1-25), with 4% having lymph node metastasis. One primary tumor was found in 82% (3,857) patients, with synchronous metastatic disease present in 2% of patients. Survival was statistically significant between stages (p⬍0.0001), and not significant within stages. Stage I disease was seen in 91.3% patients, 4% with Stage II, 2% with Stage III, and 3% patients in Stage IV. 5 year survival was 97.8%, 64.3%, 54.2%, and 20% for Stages I-IV respectively. Size of primary tumor and depth of invasion were the most powerful predictors of survival on multivariate analysis (p⬍0.0001). Conclusion: Our newly developed staging system accurately predicts disease prognosis in rectal carcinoids. Incorporation of rectal carcinoids into the American Joint Committee on Cancer is needed to both educate all physicians and to follow trends in prognosis.
QS74. ANALYSIS OF 4,701 RECTAL CARCINOID TUMORS FOR A PROPOSED STAGING SYSTEM. Christine S. Landry, Charles R. Scoggins, Charles Woodall, Kelly M. McMasters, Robert CG Martin II; University of Louisville, Louisville, KY
QS75. ANALYSIS OF 2,459 COLON CARCINOID TUMORS FOR A PROPOSED STAGING SYSTEM. Christine S. Landry, Charles R. Scoggins, Kelly M. McMasters, Robert Martin; University of Louisville, Louisville, KY
Background: The purpose of this study was to determine prognostic factors important in the overall survival of rectal carcinoid tumors. To date, no staging system exists for these tumors and thus little is known regarding appropriate management and follow up. Therefore, we sought to investigate prognostic factors associated with rectal carcinoid tumors and create a predictive staging system to accurately estimate prognosis. Methods: A search of 15,983 patients with carcinoid tumors from the National Cancer Institute’s SEER (Surveillance Epidemiology and End Results) database identified
Background: Colon carcinoid remains an uncommon finding during screening endoscopy or surgery, with a little known about the long term prognosis. The reasons for this uncertainty is that no staging system exists in order to appropriately risk stratify or follow these patients for overall survival. This limitation has led to the inability to compare outcomes, or to even establish appropirate treatment algorithims in these patients. Therefore, we sought to investigate prognostic factors associated with colon carcinoid tumors and create a predictive staging system to accurately estimate prognosis. Meth-