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Notes Omental Patch Repair of Gastric Perforation Is Comparable to Laparoscopic Repair in a Porcine Model
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ASSOCIATION FOR ACADEMIC SURGERY AND SOCIETY OF UNIVERSITY SURGEONS—ABSTRACTS
a significant reduction in the glucose AUC in both groups at sacrifice, regardless weight changes (P < 0.05). Conclusion: The GK rat model of diabetes which is related to glucose-insulin uncoupling does not appear to be a good model to study T2DM found in humans with obesity.
28.13. Hypoglycemia after Roux-en-Y Gastric Bypass. The Role of Glucagon Like Peptide 1. A. Rabiee, T. J. Magruder, D. Elahi, D. K. Andersen; Johns Hopkins University, Baltimore, MD Introduction. Profound hypoglycemia occurs as a late complication in some patients after RYGB. Nesideoblastosis (N) has been found in patients requiring pancreatic resection, and the incretin hormone GLP-1 has been implicated as a cause. We investigated the role of GLP-1 in a 47 year old subject (S) who developed recurrent neuro-glycopenia accompanied by seizures and loss of consciousness 3 years after RYGB. METHODS. A standardized test meal (STM) and 2 hr hyperglycemic clamp with GLP-1 infusion (1.5 pmol/kg/min) during the second hr, before and during a 4 wk trial of octreotide (Oc) (400 ug/day) were administered. After cessation of glucose and GLP-1 infusion at the end of the 2 hr clamp, blood glucose levels were monitored until basal levels were maintained or symptoms occurred. Responses were compared to a control group of 6 subjects who were 12 mo s/p RYGB without hypoglycemic symptoms. RESULTS. During STM, both GLP-1 and insulin levels were 3-fold elevated in S compared to controls. Insulin responses to hyperglycemia alone and to GLP-1 infusion were comparable to controls, but after cessation of glucose infusion, glucose levels fell to 25 mg/dl and symptoms occurred. During Oc therapy, the GLP-1 and insulin responses to STM were reduced by more than 50%. During Oc, insulin response to hyperglycemia alone was reduced, but remained unchanged during GLP-1 infusion. Glucagon levels during hyperglycemia alone were suppressed and further suppressed during hyperglycemia with GLP-1 infusion. With termination of both glucose and GLP-1 infusion and the substantial drop in glucose, glucagon levels failed to rise. Oc treatment reduced basal glucagon levels further and the levels remained suppressed during hyperglycemia and GLP-1 infusion. Hypoglycemia persisted after cessation of glucose infusion during Oc treatment. Due to persistent symptoms, S underwent 85% distal pancreatectomy; N was present in resected tissue. Post-op, S was asymptomatic; blood glucose ranged from 119-220 mg/dl. CONCLUSIONS. GLP-1, which has been shown to be not only insulinotropic but also insulinotrophic and glucagonostatic, is the likely cause of postRYGB hypoglycemia. Exaggerated insulin responses to oral nutrients and a suppressed glucagon response to hypoglycemia due to striking hypersecretion of GLP-1 combine to create life-threatening hypoglycemia. Oc may be therapeutic in some patients. N is likely due to over-expression of the islet cell transcription factor, PDX-1, caused by prolonged hypersecretion of GLP-1, a known inducer of PDX-1 expression. The cause of persistently exaggerated GLP-1 secretion after RYGB is unclear, and may be avoidable by altered methods of gastroenteric reconstruction during RYGB. Pre-operative assessment of GLP-1 secretion may identify those patients at risk for post-RYGB hypoglycemia.
28.14. Notes Omental Patch Repair of Gastric Perforation Is Comparable to Laparoscopic Repair in a Porcine Model. E. A. Moran, M. Guebner, C. Gostout, J. Bingener; Mayo Clinic, Rochester, MN Background: Perforation accounts for over 70% of deaths associated with peptic ulcer disease. Post-interventional complications contribute to short-term patient outcome. Reduction of procedural impact may decrease morbidity and mortality. A natural orifice translumenal approach may decrease surgical physiologic impact. Hypothesis:
NOTES omental patch repair of full thickness gastrotomy is feasible with decreased physiologic impact compared to laparoscopy. Design: Randomized, dual arm, porcine 2-week survival trial. Setting: IACUC approved study with 28 swine. Methods: Twenty-eight swine were randomized to laparoscopic (n ¼ 14) or NOTES repair (n ¼ 14) of a 1 cm anterior wall gastrotomy. Gastrotomy was created laparoscopically followed by four hours wait (soilage) time. After peritoneal cavity irrigation, repair proceeded with laparoscopic omental patch (Lap) or NOTES approach. For NOTES repair, an endoscope was advanced into the stomach and through the perforation. Omentum was grasped with endoscopic biopsy forceps, pulled into the gastric lumen, and fixed with metallic clips. Procedure and clinical parameters including necropsy were recorded. Serum samples were collected for WBC count and TNF-a analysis using dual-sandwich ELISA. T -test, Wilcoxon Rank sum test, and Levene’s test were used for statistical analysis Results: NOTES repair failed in one animal (unable to exit perforation); this was repaired laparoscopically, data were analyzed as intention to treat. Twenty-four of 28 animals thrived to study completion. Two NOTES, 1 Lap swine succumbed to airway compromise in recovery; 1 NOTES animal failed to thrive on POD 7. No intra-abdominal cause for these deaths was found. At necropsy, all repairs were intact. Mean NOTES repair time was comparable to laparoscopy (NOTES: 28 min vs. Lap: 33 min, p ¼ 0.5). WBC counts from both groups were comparable on POD 1 (NOTES: 18.1 vs. Lap: 17.5, p ¼ 0.44). Mean TNF-a serum levels in the NOTES group on POD1 were not significantly different from laparoscopy (NOTES: 25.3 pg/nL vs. Lap: 51.5 pg/nL, p ¼ 0.12); a significant difference in TNF-a variation from baseline at procedure conclusion (p < 0.01) and POD 1(p ¼ 0.044) was noted between NOTES and Lap animals. Conclusion: Endoscopic perforated hollow viscus repair was technically feasible in this experimental model and may be slightly less invasive. Early results appear encouraging and warrant further evaluation.
28.15. A Role for Intestinal Alkaline Phosphatase in the Maintenance of Local Gut Immunity. K. T. Chen,1 M. Malo,2 L. K. Beasley-Topliffe,2 K. Poelstra,3 J. Millan,4 G. Mostafa,2 S. Alam,2 S. Ramasamy,2 H. Warren,2 E. Hohmann,2 R. A. Hodin2; 1University of Minnesota, Minneapolis, MN; 2 Massachusetts General Hospital, Boston, MA; 3University of Groningen, Groningen, Netherlands; 4Burnham Institue for Medical Research, La Jolla, CA Background and Aims: Intestinal alkaline phosphatase (IAP) is a gut mucosal defense factor known to dephosphorylate lipopolysaccharide (LPS); however, the role of IAP in the gut response to luminal bacteria remains undefined. We investigated immune responses of wildtype (WT) and IAP-knockout (IAP-KO) mice to LPS and Salmonella typhimurium challenges. Methods: Cryotstat sectioning and standard indirect immunohistochemical staining for MHC Class II molecules were performed on liver tissue from WT and IAP-KO mice. WT and IAP-KO mice were orally gavaged with S typhimurium; after 6 days, bacterial translocation to mesenteric nodes, liver, and spleen was determined by plating. WT and IAP-KO mice received intraperitoneal injections of LPS, with subsequent quantification of complete blood counts and serum Il-6 by ELISA. WT and IAPKO whole blood were plated and stimulated with LPS and Pam-3Cys, with Il-6 determination. Results: Immunohistologic liver exams showed increased expression of MHC Class II molecules in IAP-KO mice. Following S typhimurium challenge, WT mice appeared moribund compared to IAP-KO mice, with increased bacterial translocation. WT mice had >50% decrease (P<.005) in platelets and 1.8-fold (P<.05) increased serum Il-6 compared to IAP-KO mice in response to LPS injections. IAP-KO whole blood stimulation with LPS and Pam-3-Cys resulted in increased Il-6 and TNF secretion compared to WT. Conclusions: IAP-KO mice exhibit characteristics consistent with local LPS tolerance. Whole blood response of IAP-KO mice did not reflect a systemic tolerance.
ASSOCIATION FOR ACADEMIC SURGERY AND SOCIETY OF UNIVERSITY SURGEONS—ABSTRACTS
a significant reduction in the glucose AUC in both groups at sacrifice, regardless weight changes (P < 0.05). Conclusion: The GK rat model of diabetes which is related to glucose-insulin uncoupling does not appear to be a good model to study T2DM found in humans with obesity.
28.13. Hypoglycemia after Roux-en-Y Gastric Bypass. The Role of Glucagon Like Peptide 1. A. Rabiee, T. J. Magruder, D. Elahi, D. K. Andersen; Johns Hopkins University, Baltimore, MD Introduction. Profound hypoglycemia occurs as a late complication in some patients after RYGB. Nesideoblastosis (N) has been found in patients requiring pancreatic resection, and the incretin hormone GLP-1 has been implicated as a cause. We investigated the role of GLP-1 in a 47 year old subject (S) who developed recurrent neuro-glycopenia accompanied by seizures and loss of consciousness 3 years after RYGB. METHODS. A standardized test meal (STM) and 2 hr hyperglycemic clamp with GLP-1 infusion (1.5 pmol/kg/min) during the second hr, before and during a 4 wk trial of octreotide (Oc) (400 ug/day) were administered. After cessation of glucose and GLP-1 infusion at the end of the 2 hr clamp, blood glucose levels were monitored until basal levels were maintained or symptoms occurred. Responses were compared to a control group of 6 subjects who were 12 mo s/p RYGB without hypoglycemic symptoms. RESULTS. During STM, both GLP-1 and insulin levels were 3-fold elevated in S compared to controls. Insulin responses to hyperglycemia alone and to GLP-1 infusion were comparable to controls, but after cessation of glucose infusion, glucose levels fell to 25 mg/dl and symptoms occurred. During Oc therapy, the GLP-1 and insulin responses to STM were reduced by more than 50%. During Oc, insulin response to hyperglycemia alone was reduced, but remained unchanged during GLP-1 infusion. Glucagon levels during hyperglycemia alone were suppressed and further suppressed during hyperglycemia with GLP-1 infusion. With termination of both glucose and GLP-1 infusion and the substantial drop in glucose, glucagon levels failed to rise. Oc treatment reduced basal glucagon levels further and the levels remained suppressed during hyperglycemia and GLP-1 infusion. Hypoglycemia persisted after cessation of glucose infusion during Oc treatment. Due to persistent symptoms, S underwent 85% distal pancreatectomy; N was present in resected tissue. Post-op, S was asymptomatic; blood glucose ranged from 119-220 mg/dl. CONCLUSIONS. GLP-1, which has been shown to be not only insulinotropic but also insulinotrophic and glucagonostatic, is the likely cause of postRYGB hypoglycemia. Exaggerated insulin responses to oral nutrients and a suppressed glucagon response to hypoglycemia due to striking hypersecretion of GLP-1 combine to create life-threatening hypoglycemia. Oc may be therapeutic in some patients. N is likely due to over-expression of the islet cell transcription factor, PDX-1, caused by prolonged hypersecretion of GLP-1, a known inducer of PDX-1 expression. The cause of persistently exaggerated GLP-1 secretion after RYGB is unclear, and may be avoidable by altered methods of gastroenteric reconstruction during RYGB. Pre-operative assessment of GLP-1 secretion may identify those patients at risk for post-RYGB hypoglycemia.
28.14. Notes Omental Patch Repair of Gastric Perforation Is Comparable to Laparoscopic Repair in a Porcine Model. E. A. Moran, M. Guebner, C. Gostout, J. Bingener; Mayo Clinic, Rochester, MN Background: Perforation accounts for over 70% of deaths associated with peptic ulcer disease. Post-interventional complications contribute to short-term patient outcome. Reduction of procedural impact may decrease morbidity and mortality. A natural orifice translumenal approach may decrease surgical physiologic impact. Hypothesis:
NOTES omental patch repair of full thickness gastrotomy is feasible with decreased physiologic impact compared to laparoscopy. Design: Randomized, dual arm, porcine 2-week survival trial. Setting: IACUC approved study with 28 swine. Methods: Twenty-eight swine were randomized to laparoscopic (n ¼ 14) or NOTES repair (n ¼ 14) of a 1 cm anterior wall gastrotomy. Gastrotomy was created laparoscopically followed by four hours wait (soilage) time. After peritoneal cavity irrigation, repair proceeded with laparoscopic omental patch (Lap) or NOTES approach. For NOTES repair, an endoscope was advanced into the stomach and through the perforation. Omentum was grasped with endoscopic biopsy forceps, pulled into the gastric lumen, and fixed with metallic clips. Procedure and clinical parameters including necropsy were recorded. Serum samples were collected for WBC count and TNF-a analysis using dual-sandwich ELISA. T -test, Wilcoxon Rank sum test, and Levene’s test were used for statistical analysis Results: NOTES repair failed in one animal (unable to exit perforation); this was repaired laparoscopically, data were analyzed as intention to treat. Twenty-four of 28 animals thrived to study completion. Two NOTES, 1 Lap swine succumbed to airway compromise in recovery; 1 NOTES animal failed to thrive on POD 7. No intra-abdominal cause for these deaths was found. At necropsy, all repairs were intact. Mean NOTES repair time was comparable to laparoscopy (NOTES: 28 min vs. Lap: 33 min, p ¼ 0.5). WBC counts from both groups were comparable on POD 1 (NOTES: 18.1 vs. Lap: 17.5, p ¼ 0.44). Mean TNF-a serum levels in the NOTES group on POD1 were not significantly different from laparoscopy (NOTES: 25.3 pg/nL vs. Lap: 51.5 pg/nL, p ¼ 0.12); a significant difference in TNF-a variation from baseline at procedure conclusion (p < 0.01) and POD 1(p ¼ 0.044) was noted between NOTES and Lap animals. Conclusion: Endoscopic perforated hollow viscus repair was technically feasible in this experimental model and may be slightly less invasive. Early results appear encouraging and warrant further evaluation.
28.15. A Role for Intestinal Alkaline Phosphatase in the Maintenance of Local Gut Immunity. K. T. Chen,1 M. Malo,2 L. K. Beasley-Topliffe,2 K. Poelstra,3 J. Millan,4 G. Mostafa,2 S. Alam,2 S. Ramasamy,2 H. Warren,2 E. Hohmann,2 R. A. Hodin2; 1University of Minnesota, Minneapolis, MN; 2 Massachusetts General Hospital, Boston, MA; 3University of Groningen, Groningen, Netherlands; 4Burnham Institue for Medical Research, La Jolla, CA Background and Aims: Intestinal alkaline phosphatase (IAP) is a gut mucosal defense factor known to dephosphorylate lipopolysaccharide (LPS); however, the role of IAP in the gut response to luminal bacteria remains undefined. We investigated immune responses of wildtype (WT) and IAP-knockout (IAP-KO) mice to LPS and Salmonella typhimurium challenges. Methods: Cryotstat sectioning and standard indirect immunohistochemical staining for MHC Class II molecules were performed on liver tissue from WT and IAP-KO mice. WT and IAP-KO mice were orally gavaged with S typhimurium; after 6 days, bacterial translocation to mesenteric nodes, liver, and spleen was determined by plating. WT and IAP-KO mice received intraperitoneal injections of LPS, with subsequent quantification of complete blood counts and serum Il-6 by ELISA. WT and IAPKO whole blood were plated and stimulated with LPS and Pam-3Cys, with Il-6 determination. Results: Immunohistologic liver exams showed increased expression of MHC Class II molecules in IAP-KO mice. Following S typhimurium challenge, WT mice appeared moribund compared to IAP-KO mice, with increased bacterial translocation. WT mice had >50% decrease (P<.005) in platelets and 1.8-fold (P<.05) increased serum Il-6 compared to IAP-KO mice in response to LPS injections. IAP-KO whole blood stimulation with LPS and Pam-3-Cys resulted in increased Il-6 and TNF secretion compared to WT. Conclusions: IAP-KO mice exhibit characteristics consistent with local LPS tolerance. Whole blood response of IAP-KO mice did not reflect a systemic tolerance.