- Email: [email protected]
453 Quality-of-Life After Pancreatic Resection with Islet Cell Autotransplant for the Treatment of Severe Chronic Pancreatitis
that the improvement in hepatic steatosis after RYGB in obese rats is associated with an upregulation of the LKB1-AMPK signaling pathway. Methods: Obese Sprague-Dawley male rats underwent RYGB or sham. Liver tissue was obtained at 9 weeks postoperatively. Protein levels of LKB1, p-LKB1, AMPKα, p-AMPKα and p-PKC-ζ were measured. PKC-ζ mRNA levels were also measured. Protein associations of LKB1 with each of AMPKα and PKC-ζ were determined by both co-immunoprecipitation and co-immunofluorescent staining. Data are mean±SD; for t-test, p<0.05 was significant. Results: RYGB increased protein levels of both hepatic AMPKα and phosphorylated-AMPKα (p-AMPKα ) as compared to sham (5,431±150 vs 2,323±117; 3,665±120 vs 1,534±60; all p<0.001). While protein levels of hepatic LKB1 did not increase, phosphorylated-LKB1 increased significantly after RYGB (6,574±125 vs 3,265±89; p<0.001 vs. sham). PKC-ζ mRNA and phosphorylated-PKC-ζ did not change after RYGB (data not shown). However, interactions between LKB1 and AMPK were increased after RYGB (6,325±142 vs 2,132±87; p<0.001 vs. sham) as well as interactions of LKB1 and PKC-ζ (4,356±102 vs 2,354±78; p<0.001 vs. sham). Both LKB1-AMPK and LKB1-PKC-ζ co-localized most strongly in the cytoplasm of liver cells by co-immunofluoresence; LKB1-AMPK also co-localized in the nucleus to a lesser extent. Conclusion: RYGB increased hepatic levels of AMPK and p-AMPK. Increased phosphorylation of LKB1 after RYGB is associated with increased LKB1-AMPK interaction and co-localization within liver cells. While PKC-ζ levels were not increased after RYGB, PKC-ζ interaction and co-localization with LKB1 was increased. Further elucidation upstream signaling of the LKB1-AMPK pathway may provide greater clarity into the benefits of RYGB on Non-Alcoholic Fatty Liver Disease.
The level returned to baseline between 6-12 weeks, and normalized after 12 weeks. However, the levels did not return to normal in patients who experienced early recurrence. There were no correlation between the baseline level of HGF and the clinical and histological findings. Conclusion: The high sensitivity and specificity of plasma HGF in patients with PCA, suggest that HGF may be useful in the diagnosis of PAC. Furthermore, we have shown indirectly that HGF may not be secreted by the malignant cells per se. The higher immediate postoperative value compared to the baseline level reflected the stress of surgical resection. However, the sustained high level of plasma HGF following PD may be a factor related to early recurrence and metastasis. 455 Impact of Institutional Case Volume On Inpatient Morbidity and Mortality After Paraesophageal Hernia Repair Thai H. Pham, Kyle A. Perry, Eugene Y. Chang, Brian S. Diggs, James P. Dolan, John G. Hunter, Brett C. Sheppard Introduction: For many complex surgical procedures, high volume centers have been shown to have less morbidity and mortality than low volume centers. No studies to date have examined the affect of case volume on morbidity and mortality for paraesophageal hernia (PEH) repair. The aim of this population-based study is to assess the impact of hospital case volume on inpatient morbidity and mortality following PEH repair. Methods: The Nationwide Inpatient Sample database was queried from 1996-2006 by ICD-9 diagnosis and procedure codes for laparoscopic, transthoracic, and open abdominal approaches to PEH repair. Institutional volumes were classified by increasing case volume in increments of five cases per year. The corresponding morbidity and mortality was assessed for each increment. Data was analyzed using Rao-Scott Chi-Squared test. Results: 97,757 PEH repairs were performed during the study interval: 9,577 laparoscopic repairs, 74,949 repairs by laparatomy and 13,231 repairs were completed by a transthoracic approach. Overall morbidity and mortality are shown and were significantly different across approaches, p<0.0001 and p=0.004 respectively (see table). For laparoscopic and open abdominal repairs, mortality was significantly different across the procedural increments. For the transthoracic approach, only morbidity was different. Hospitals that performed greater than 15 laparoscopic PEH repairs per year had no associated mortality compared to hospitals that performed 15 or fewer cases per year (p=0.004). Conclusion: This data demonstrates that institutional case volume impacts inpatient morbidity and mortality after PEH repairs. However, the impact of case volume is not equivalent for all surgical approaches. The laparoscopic approach had the lowest overall morbidity and mortality and had no associated mortality at institutions performing greater than 15 cases per year. These results suggest that for laparoscopic PEH repairs, the best morbidity and mortality are seen at institutions with annual volumes of greater than 15 cases per year. Outcomes by Annual Case Volume
453
SSAT Abstracts
Quality-of-Life After Pancreatic Resection with Islet Cell Autotransplant for the Treatment of Severe Chronic Pancreatitis Joshua L. Argo, Juan L. Contreras, Shyam S. Varadarajulu, Camille D. Blackledge, John D. Christein Background: Pancreatic resection can alleviate pain in properly selected patients with severe chronic pancreatitis, but often at the expense of inducing “brittle” diabetes. Islet cell autotransplantation (IAT) has been shown to decrease diabetes-related morbidity. Aim: To evaluate quality of life and severity of pain in patients undergoing pancreatic resection with IAT for chronic pancreatitis. Methods: All patients undergoing pancreatectomy with IAT from April 2005 to December 2008 were evaluated. Data were collected by chart review and query of hospital databases. Quality of life was measured by the Short Form-36 (SF36) and severity of pain was measured by the McGill Pain Questionnaire-Short Form (MPQSF). Surveys were completed preoperatively, at routine 6-month and 1-year follow-up visits, and after distribution by mail. Norm-based scoring was used for the SF-36 so scores were standardized to the general population mean. The MPQ-SF includes a visual analog scale in addition to written questions. Results are reported as median ± interquartile range or as a percentage. Statistical analyses were conducted with SAS version 9.3.1. Results: Forty-two consecutive patients who underwent 43 pancreatic resections with IAT were identified. For the 29 total pancreatectomy and 14 pancreatoduodenectomy cases, islet equivalents infused was 77,227 ± 179,429 and 13,889 ± 50,832 and islet equivalents per gram of pancreas was 2566 ± 3639 and 841 ± 2536 for each procedure, respectively. At median follow-up of 6.1 ± 11 months, cessation of narcotic use was reported by 70% of patients. SF-36 surveys were completed by 30, 17, and 14 patients and the MPQ-SF was completed by 30, 15, and 13 patients preoperatively, at 6-months, and at 1-year, respectively. SF-36 physical component scores were higher at 6-month and 1-year follow-up when compared with preoperative values (p=0.001) and improvement was observed in 5 of 8 scales (p<0.05). At 6-months and 1-year after surgery, 82% and 67% of patients felt that they were “better off than 1 year ago,” respectively (p<0.0001). MPQ-SF scores improved in all domains (p<0.005), including total score (p=0.001) and visual analog scale (p<0.001). No patients have been hospitalized for hypoglycemic complications and there was one unrelated death at 2 years. Conclusions: In appropriately selected patients with chronic pancreatitis, pancreatic resection with IAT is safe, provides effective pain relief, and improves quality of life. Patients with severe chronic pancreatitis should be considered for pancreatic resection with IAT at a center with this capability.
456 454
Endoluminal Fundoplication (ELF) for GERD - 12 Month Follow Up Riccardo Rosati, Uberto Fumagalli, Roberta Barbera, Alberto Malesci, Alessandro Repici
The Clinical Value of Hepatocyte Growth Factor in Patients with PeriAmpullary Cancer Before and After Pancreaticoduodenectomy Omar Barakat, Gabriela C. Rodriguez, Isaac Raijman, Paul M. Allison, Javier Nieto, Claire F. Ozaki, Robert P. Wood
Aim: to evaluate the short term results of EndoLuminal Fundoplication (ELF) with EsophyxTM in a group of patients treated for gastroesophageal reflux disease. Method: 64 patients presenting during the period June 2006 - April 2008 with a history of chronic reflux esophagitis (>6 months), with either endoscopic or pH-metric diagnosis, needing long term acid suppressive therapy, were asked to take part to the study. Patients with a hiatal hernia larger than 3 cm or Barrett esophagus were excluded. Twenty patients (median age 47.5 yrs) were included into the study. ELF procedures were performed under general anesthesia with orotracheal intubation by expert endoscopist and surgeon. Results: Twelve patients (60%) had a small hiatal hernia (<3 cm); 5 had LA grade B/C esophagitis. The median total reflux time was 2.5%. The mean duration of the procedure to construct a 220° valve (range 180-270°) was 62 minutes. A median of 14 fasteners (range 6-18) were placed. There were no major intraoperative complications. Two patients had an haematemesis on the 1st and 8th postoperative day, which needed prolonged or re-hospitalization and were treated conservatively (major complication: 10%). Fifteen patients have reached a 6 month follow up and 7 a 12 month follow up. Symptom improvement was 60% at 6 months and 57.1% at 12 months. GERD-HRQL score decreased from a median of 43 to a median of 7 (p <0.005, Mann-Whitney U test); one patient still had grade B esophagitis at 6 month follow up; at physiopatologic evaluation improvement was recorded in 16.6% of cases, while 16.6% remained unchanged, and 66.7% worsened at one year follow up. Six patients (30%) with persistent symptomatic reflux underwent laparoscopic Nissen fundoplication with good results. Conclusion ELF is maybe the most attractive endoscopic technique for GERD. Patients treated with the procedure had a symptom improvement but laboratory results at 6 and 12 months on gastro-esophageal reflux are unsatisfactory and there is a high number of reoperations. We therefore conclude that ELF with EsophyxTM is an investigational procedure with no role in routine treament of GERD.
Background/Aims. Hepatocyte Growth factor (HGF) is widely expressed growth factor that plays crucial role in invasion and metastasis of tumor cells through interaction with c-met receptor, which is frequently expressed in pancreatic cancer. However, the significance of HGF as a tumor marker to diagnose peri-ampullary cancer (PAC) is not clear at present. The purpose of this study is to: 1- determine the sensitivity, and specificity of plasma HGF in patients with PAC. 2- study the dynamic changes of HGF following pancreaticoduodenectomy (PD), which has not been described before. 3- Analyze the relationship between the preoperative and postoperative levels, and various clinical and histopathological parameters to determine the prognostic value of HGF. Methods: Plasma level of HGF was measured using ELISA kit in patients with PAC (n=57), benign periampullary tumors (BPT) (n=21), chronic pancreatitis (CP) (n=20), and in 20 healthy individuals who served as normal control (NC). The plasma samples were assayed in duplicate using 3 different dilutions. Following PD, plasma HGF level was further measured at 1, 6, 12, 24, and 48 weeks. A retrospective cohort study was conducted to analyze the relationships between HGF profiles and different clinical and histological parameters. Results: Patients with PAC had significantly higher plasma level of HGF compared to NC, patients with BPT, and CP (1574± 625 pg/ml; 670±185 pg/ml; 781±257 pg/ml; 881±303 pg/ml; P= 0.0001). At a cutoff value of 1120 pg/ml, 48/57 (84.2%) patients with PAC, none of the NC and BPT individuals, and only 4/20 (20%) patients with CP were positive. Receiver operating characteristics analyses for discrimination of PAC from BPT and CP provided an area under the curve of 0.919± 0.03 (95% CI, 0.82-0.97, P=0.0001) with a sensitivity of 84% and specificity of 89%. Following curative PD, HGF levels were higher at 1, and 6 weeks compared to the preoperative value.
SSAT Abstracts
A-872
The level returned to baseline between 6-12 weeks, and normalized after 12 weeks. However, the levels did not return to normal in patients who experienced early recurrence. There were no correlation between the baseline level of HGF and the clinical and histological findings. Conclusion: The high sensitivity and specificity of plasma HGF in patients with PCA, suggest that HGF may be useful in the diagnosis of PAC. Furthermore, we have shown indirectly that HGF may not be secreted by the malignant cells per se. The higher immediate postoperative value compared to the baseline level reflected the stress of surgical resection. However, the sustained high level of plasma HGF following PD may be a factor related to early recurrence and metastasis. 455 Impact of Institutional Case Volume On Inpatient Morbidity and Mortality After Paraesophageal Hernia Repair Thai H. Pham, Kyle A. Perry, Eugene Y. Chang, Brian S. Diggs, James P. Dolan, John G. Hunter, Brett C. Sheppard Introduction: For many complex surgical procedures, high volume centers have been shown to have less morbidity and mortality than low volume centers. No studies to date have examined the affect of case volume on morbidity and mortality for paraesophageal hernia (PEH) repair. The aim of this population-based study is to assess the impact of hospital case volume on inpatient morbidity and mortality following PEH repair. Methods: The Nationwide Inpatient Sample database was queried from 1996-2006 by ICD-9 diagnosis and procedure codes for laparoscopic, transthoracic, and open abdominal approaches to PEH repair. Institutional volumes were classified by increasing case volume in increments of five cases per year. The corresponding morbidity and mortality was assessed for each increment. Data was analyzed using Rao-Scott Chi-Squared test. Results: 97,757 PEH repairs were performed during the study interval: 9,577 laparoscopic repairs, 74,949 repairs by laparatomy and 13,231 repairs were completed by a transthoracic approach. Overall morbidity and mortality are shown and were significantly different across approaches, p<0.0001 and p=0.004 respectively (see table). For laparoscopic and open abdominal repairs, mortality was significantly different across the procedural increments. For the transthoracic approach, only morbidity was different. Hospitals that performed greater than 15 laparoscopic PEH repairs per year had no associated mortality compared to hospitals that performed 15 or fewer cases per year (p=0.004). Conclusion: This data demonstrates that institutional case volume impacts inpatient morbidity and mortality after PEH repairs. However, the impact of case volume is not equivalent for all surgical approaches. The laparoscopic approach had the lowest overall morbidity and mortality and had no associated mortality at institutions performing greater than 15 cases per year. These results suggest that for laparoscopic PEH repairs, the best morbidity and mortality are seen at institutions with annual volumes of greater than 15 cases per year. Outcomes by Annual Case Volume
453
SSAT Abstracts
Quality-of-Life After Pancreatic Resection with Islet Cell Autotransplant for the Treatment of Severe Chronic Pancreatitis Joshua L. Argo, Juan L. Contreras, Shyam S. Varadarajulu, Camille D. Blackledge, John D. Christein Background: Pancreatic resection can alleviate pain in properly selected patients with severe chronic pancreatitis, but often at the expense of inducing “brittle” diabetes. Islet cell autotransplantation (IAT) has been shown to decrease diabetes-related morbidity. Aim: To evaluate quality of life and severity of pain in patients undergoing pancreatic resection with IAT for chronic pancreatitis. Methods: All patients undergoing pancreatectomy with IAT from April 2005 to December 2008 were evaluated. Data were collected by chart review and query of hospital databases. Quality of life was measured by the Short Form-36 (SF36) and severity of pain was measured by the McGill Pain Questionnaire-Short Form (MPQSF). Surveys were completed preoperatively, at routine 6-month and 1-year follow-up visits, and after distribution by mail. Norm-based scoring was used for the SF-36 so scores were standardized to the general population mean. The MPQ-SF includes a visual analog scale in addition to written questions. Results are reported as median ± interquartile range or as a percentage. Statistical analyses were conducted with SAS version 9.3.1. Results: Forty-two consecutive patients who underwent 43 pancreatic resections with IAT were identified. For the 29 total pancreatectomy and 14 pancreatoduodenectomy cases, islet equivalents infused was 77,227 ± 179,429 and 13,889 ± 50,832 and islet equivalents per gram of pancreas was 2566 ± 3639 and 841 ± 2536 for each procedure, respectively. At median follow-up of 6.1 ± 11 months, cessation of narcotic use was reported by 70% of patients. SF-36 surveys were completed by 30, 17, and 14 patients and the MPQ-SF was completed by 30, 15, and 13 patients preoperatively, at 6-months, and at 1-year, respectively. SF-36 physical component scores were higher at 6-month and 1-year follow-up when compared with preoperative values (p=0.001) and improvement was observed in 5 of 8 scales (p<0.05). At 6-months and 1-year after surgery, 82% and 67% of patients felt that they were “better off than 1 year ago,” respectively (p<0.0001). MPQ-SF scores improved in all domains (p<0.005), including total score (p=0.001) and visual analog scale (p<0.001). No patients have been hospitalized for hypoglycemic complications and there was one unrelated death at 2 years. Conclusions: In appropriately selected patients with chronic pancreatitis, pancreatic resection with IAT is safe, provides effective pain relief, and improves quality of life. Patients with severe chronic pancreatitis should be considered for pancreatic resection with IAT at a center with this capability.
456 454
Endoluminal Fundoplication (ELF) for GERD - 12 Month Follow Up Riccardo Rosati, Uberto Fumagalli, Roberta Barbera, Alberto Malesci, Alessandro Repici
The Clinical Value of Hepatocyte Growth Factor in Patients with PeriAmpullary Cancer Before and After Pancreaticoduodenectomy Omar Barakat, Gabriela C. Rodriguez, Isaac Raijman, Paul M. Allison, Javier Nieto, Claire F. Ozaki, Robert P. Wood
Aim: to evaluate the short term results of EndoLuminal Fundoplication (ELF) with EsophyxTM in a group of patients treated for gastroesophageal reflux disease. Method: 64 patients presenting during the period June 2006 - April 2008 with a history of chronic reflux esophagitis (>6 months), with either endoscopic or pH-metric diagnosis, needing long term acid suppressive therapy, were asked to take part to the study. Patients with a hiatal hernia larger than 3 cm or Barrett esophagus were excluded. Twenty patients (median age 47.5 yrs) were included into the study. ELF procedures were performed under general anesthesia with orotracheal intubation by expert endoscopist and surgeon. Results: Twelve patients (60%) had a small hiatal hernia (<3 cm); 5 had LA grade B/C esophagitis. The median total reflux time was 2.5%. The mean duration of the procedure to construct a 220° valve (range 180-270°) was 62 minutes. A median of 14 fasteners (range 6-18) were placed. There were no major intraoperative complications. Two patients had an haematemesis on the 1st and 8th postoperative day, which needed prolonged or re-hospitalization and were treated conservatively (major complication: 10%). Fifteen patients have reached a 6 month follow up and 7 a 12 month follow up. Symptom improvement was 60% at 6 months and 57.1% at 12 months. GERD-HRQL score decreased from a median of 43 to a median of 7 (p <0.005, Mann-Whitney U test); one patient still had grade B esophagitis at 6 month follow up; at physiopatologic evaluation improvement was recorded in 16.6% of cases, while 16.6% remained unchanged, and 66.7% worsened at one year follow up. Six patients (30%) with persistent symptomatic reflux underwent laparoscopic Nissen fundoplication with good results. Conclusion ELF is maybe the most attractive endoscopic technique for GERD. Patients treated with the procedure had a symptom improvement but laboratory results at 6 and 12 months on gastro-esophageal reflux are unsatisfactory and there is a high number of reoperations. We therefore conclude that ELF with EsophyxTM is an investigational procedure with no role in routine treament of GERD.
Background/Aims. Hepatocyte Growth factor (HGF) is widely expressed growth factor that plays crucial role in invasion and metastasis of tumor cells through interaction with c-met receptor, which is frequently expressed in pancreatic cancer. However, the significance of HGF as a tumor marker to diagnose peri-ampullary cancer (PAC) is not clear at present. The purpose of this study is to: 1- determine the sensitivity, and specificity of plasma HGF in patients with PAC. 2- study the dynamic changes of HGF following pancreaticoduodenectomy (PD), which has not been described before. 3- Analyze the relationship between the preoperative and postoperative levels, and various clinical and histopathological parameters to determine the prognostic value of HGF. Methods: Plasma level of HGF was measured using ELISA kit in patients with PAC (n=57), benign periampullary tumors (BPT) (n=21), chronic pancreatitis (CP) (n=20), and in 20 healthy individuals who served as normal control (NC). The plasma samples were assayed in duplicate using 3 different dilutions. Following PD, plasma HGF level was further measured at 1, 6, 12, 24, and 48 weeks. A retrospective cohort study was conducted to analyze the relationships between HGF profiles and different clinical and histological parameters. Results: Patients with PAC had significantly higher plasma level of HGF compared to NC, patients with BPT, and CP (1574± 625 pg/ml; 670±185 pg/ml; 781±257 pg/ml; 881±303 pg/ml; P= 0.0001). At a cutoff value of 1120 pg/ml, 48/57 (84.2%) patients with PAC, none of the NC and BPT individuals, and only 4/20 (20%) patients with CP were positive. Receiver operating characteristics analyses for discrimination of PAC from BPT and CP provided an area under the curve of 0.919± 0.03 (95% CI, 0.82-0.97, P=0.0001) with a sensitivity of 84% and specificity of 89%. Following curative PD, HGF levels were higher at 1, and 6 weeks compared to the preoperative value.
SSAT Abstracts
A-872