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1010 Infection Rates in a Large Investigational Trial of Sacral Nerve Stimulation for Fecal Incontinence
LARS is an effective and durable treatment option for GERD. Success or failure cannot be defined in a single domain. A comprehensive analysis of outcomes requires categorization that includes symptom response, side-effects, patient's perception and objective measurement of acid exposure, mucosal integrity, and the need for additional medical or surgical treatment. Only then can patients and physicians better understand the role of LARS and make informed decisions.
1011 [18F]-Fluorodeoxyglucose-Positron Emission Tomography for the Assessment of Histopathologic Response and Prognosis After Completion of Neoadjuvant Chemotherapy in Gastric Cancer Daniel Vallbohmer, Arnulf H. Hölscher, Paul M. Schneider, Matthias Schmidt, Markus Dietlein, Elfriede Bollschweiler, Stephan E. Baldus, Jan Brabender, Ralf Metzger, Stefan Monig
819
Background: Neoadjuvant chemotherapy is frequently applied to improve the prognosis of patients with locally advanced gastric cancer. However, only a major histopathological response will provide a survival benefit in these patients. Recent studies suggest that [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET) significantly correlates with histopathological response and survival in patients with gastroesophageal adenocarcinomas undergoing neoadjuvant chemotherapy followed by surgical resection. Therefore, we evaluated the potential of FDG-PET) for the assessment of histopathologic response and prognosis in the multimodality treatment of patients with gastric cancer. Methods: Study patients were recruited from a prospective clinical observation trial on neoadjuvant chemotherapy for gastric cancer between 1997 and 2007. Forty-two patients with locally advanced gastric cancer (cT3-4, Nx, M0) were included (33 men, 9 women; median age 57 years). All patients received neoadjuvant chemotherapy according to the PLF-protocol (cisplatin, leucovorin, 5-FU; 2 cycles over 6 weeks) and subsequently 40 patients underwent standardized total gastrectomy while 2 patients received definitive chemotherapy because of tumor progression. Histomorphologic regression was defined as major histopathological response when resected specimens contained less than 10 % vital residual tumor cells. FDG-PET was performed before and 2 weeks after the end of neoadjuvant chemotherapy with assessment of the intratumoral FDG-uptake [pre-treatment standardized uptake value (SUV1); post-treatment standardized uptake value (SUV2); percentage change (SUVΔ%)]. These variables were correlated with histopathological response and survival. Results: Neoadjuvant chemoradiation led to a significant reduction of intratumoral FDG-uptake (p=0.0006). However, no significant correlations between SUV1, SUV2 or SUVΔ% and histopathological response or prognosis were found. Histomorphological tumor regression was confirmed as an important prognostic factor (p=0.04; log-rank test). Conclusion: Our study does not support recent reports that the metabolic response by FDG-PET is associated with histomorphological response or survival in patients with gastric cancer following neoadjuvant therapy and gastrectomy.
Is Laparoscopic Heller Myotomy Still Indicated in Stage IV Sigmoid Megaesophagus? Martina Ceolin, Mario Costantini, Renato Salvador, Lisa Zanatta, Emanuele Di Fratta, Elena Finotti, Christian Rizzetto, Loredana Nicoletti, Giovanni Zaninotto, Ermanno Ancona Background. Laparoscopic Heller-Dor (LapHD) is an effective treatment for esophageal achalasia, with good results in about 90% of patients. It may be argued whether such an operation is appropriate in case of dilated, sigmoid-shaped megaesophagus. The aim of our study was therefore to evaluate if the esophageal diameter and the presence of a sigmoidshaped megaesophagus could affect the outcome of LapHD procedure in patients with achalasia. Patients and Methods. From 1992 to October 2008, among 447 patients treated with LapHD for esophageal achalasia, 18 had a straight, larger than 6 cm in diameter esophagus (Group A, median age 47, range 19-80) and 15 had a sigmoid-shaped, larger than 6 cm in diameter esophagus (Group B, median age 43, range 18-78). These two groups formed the basis of this report. The findings of the remaining 414 patients, with the esophagus smaller than 6 cm in diameter, served as control group (Group C, median age 44, range 19-85). The percentage of patients who underwent a previous endoscopic treatment before the operation did non differ in the 3 groups (28%, 13% and 21% respectively for Group A, B and C, p=ns). Also other demographic and clinical parameters, such as symptom score or duration of symptoms, did not differ in the 3 groups. The operation was performed by 4 staff surgeons in a well standardized way, with the only addition of a wider isolation of the cardia in order to straighten the distal esophagus in the Group B patients. One patient in group A and 16 in group C experienced accidental mucosal perforation during surgery. Results. At a median follow-up of 30 months (IRQ 10.8-78.2) we obtained an excellent outcome in all but one of the Group A patients (94%). These results were similar to those obtained in Group C patients (382/414 good results, 92%), whereas in Group B only 9 patients out of 15 (60%) were relieved of their dysphagia (p<.01, Chi-square test). Two redo-myotomies and 2 esophagectomies were eventually required in 4 patients; other 2 patients are still undergoing periodical endoscopic dilations. Only 1 patient in group A required complementary dilations. Conclusions. In patients with a dilated (> 6 cm) but non-sigmoid in shape esophagus, LapHD allows results similar to those obtained in patients with earlier disease. In patients with late disease and a sigmoid-shaped esophagus, LapHD may still achieve good results by releaving dysphagia in more than half of the patients (60%). Therefore, laparoscopic myotomy may still be the first surgical option to be offered to these patients before esophagectomy.
1012 Transvaginal Cholecystectomy Without Laparoscopic Support Using Prototype Flexible Endoscopic Instruments Shean Satgunam, Brent W. Miedema, Klaus Thaler Purpose: Transvaginal cholecystectomy with laparoscopic assistance has been performed safely in humans. Cholecystectomy with Natural Orifice Translumenal Endoscopic Surgery (NOTES) without laparoscopic support will require new techniques and instruments for access, gallbladder retraction, dissection, and sealing of the cystic duct and artery. The aim was to develop a NOTES technique to perform transvaginal cholecystectomy without laparoscopic instruments using prototype flexible endoscopic devices. Methods: Cholecystectomies were performed in 88-97 lbs pigs with a planned two week survival. Prototype flexible instruments (NOTES Toolbox 1 provided by Ethicon Endo-Surgery Inc.) included a steerable overtube, bipolar hemostatic forceps, Maryland dissector, clip applier, grasper, rotating hook knife, scissor, and a tissue approximating system (TAS). A dual channel endoscope was passed transvaginally and pneumoperitoneum was established. Endoscope stabilization was achieved with the steerable trocar or a suture through a working channel of the endoscope and the abdominal wall. Sutures, endo-loops, or the TAS were attached to the gallbladder and externalized through the abdominal wall with a 1 mm suture passer for retraction. Dissection in the triangle of Calot to achieve the critical view was performed with endoscopic scissor, hook knife, or Maryland. The cystic duct was sealed with prototype clips and the artery was clipped or cauterized. The gallbladder was dissected off the liver with scissor and hook knife. The gallbladder was removed from the vagina under direct vision. The colpotomy was closed with 3-0 absorbable sutures. Results: Three out of the five pigs survived two weeks; two died early from liver bed hemorrhage. Operative times ranged from 115-275 minutes and the operative times decreased with experience. The critical view was established in all cases. Perforation of the gallbladder occurred in four pigs. At necropsy, all clips placed on the cystic duct were secure. The artery was secure when clipped in two or coagulated in three pigs. There was no evidence of bile leak or infection. Conclusions: NOTES cholecystectomy without laparoscopic support is feasible using prototype flexible endoscopic devices. The transvaginal steerable trocar gives consistent access to the gallbladder. Complete gallbladder dissection is possible and the clip applier is effective in controlling the cystic duct. The cystic artery can be controlled with clip or coagulation. The primary remaining difficulty is lack of precision during dissection. Techniques and instrumentation for pure NOTES cholecystectomy have improved, but further refinement is warranted.
SSAT Abstracts
1010 Infection Rates in a Large Investigational Trial of Sacral Nerve Stimulation for Fecal Incontinence Steven Wexner, Richard McCallum, Anders Mellgren, John A. Coller, Ghislain Devroede, Tracy L. Hull, Jennifer Ayscue, Michael J. England, David A. Margolin, S. Abbas Shobeiri, Howard S. Kaufman, William J. Snape, Ece Mutlu, Paul Pettit, Joe Tjandra Introduction: Treatment options for patients with fecal incontinence (FI) are limited, and irreversible surgical treatments can be associated with high rates of infection and other complications. One treatment, sacral nerve stimulation (SNS), is approved for FI in Europe and was recently submitted to the FDA for approval of this indication in the US. In that trial, 83% of subjects showed ≥50% reduction in the number of incontinent episodes per week at 12 months compared to baseline. The objective of this analysis is to present infection rates in the recently completed clinical trail assessing the safety and efficacy of SNS for FI in a large population. Methods: Adult patients with greater than two FI episodes per week received implantation of an SNS device following a successful test of the therapy. During test stimulation, test leads and a temporary external stimulator are used to evaluate the patient's response to the therapy prior to implantation of the neurostimulator. Adverse events were reported by investigators at each study site and were coded. Terms such as infection, redness, or seroma were coded as infection regardless of whether the event was related to the therapy. These rates were compared to the rates of infection after the other fda approved treatment for end stage fecal incontinence - the artificial bowel sphincter (ABS). Results: One hundred twenty subjects (92% female, 60.5+12.5 years old) received a chronically implanted InterStim® Therapy (Minneapolis, MN) device. Subjects were followed for an average of 23 (range 2.2 - 61) months. Of the 120 implanted subjects, 13 (10.8%) reported infection during the implant phase. One infection resolved on its own and five were successfully treated with medication. Seven infections (5.8%) required surgical intervention, with infections in five patients requiring full system explant. Test stimulation surgical duration was similar between the infected group (74 min) and the non-infected group (68 min). Reported rates of infection after ABS ranged from 20-25%. Discussion: Reported infection rates from a clinical trial of a currently marketed artificial sphincter were 20-25%. Ultimately, post-operative complications required the complete explant of that artificial sphincter device in 30% of subjects. In contrast, only 4% of the subjects in the current study underwent infection-related device explant. Conclusion: SNS for FI, resulted in a relatively low infection rate compared to the only other FDA approved treatment for end stage for FI. Combined with the high therapeutic success rate shown in this study, these data present a positive risk/benefit profile. Sponsor: Medtronic
SSAT Abstracts
1013 Immunonutrition with Long Chain Fatty Acids Prevents Activation of Macrophages in the Gut Wall Petra Jacob, Julia Frick, Maximilian Feilitzsch, Mario H. Mueller, Markus A. Küper, Helen Raybould, Alfred Konigsrainer, Jorg Glatzle Background: Gut derived mediators and immune cells released into the mesenteric lymph during abdominal sepsis cause severe pulmonary dysfunction including activation of macrophages (Glatzle JOGS 2007). Long chain fatty acids absorbed in the gut activate a vagovagal reflex pathway, the so called “cholinergic anti-inflammatory pathway”, which controls the activity of macrophages in the gut wall (Wang Nat. Med. 2004). Aim: To investigate whether an enteral immunonutrition with long chain fatty acids prevents the activation of macrophages in the gut wall. Methods: Mesenteric lymph was obtained from lymph fistula
A-882
1011 [18F]-Fluorodeoxyglucose-Positron Emission Tomography for the Assessment of Histopathologic Response and Prognosis After Completion of Neoadjuvant Chemotherapy in Gastric Cancer Daniel Vallbohmer, Arnulf H. Hölscher, Paul M. Schneider, Matthias Schmidt, Markus Dietlein, Elfriede Bollschweiler, Stephan E. Baldus, Jan Brabender, Ralf Metzger, Stefan Monig
819
Background: Neoadjuvant chemotherapy is frequently applied to improve the prognosis of patients with locally advanced gastric cancer. However, only a major histopathological response will provide a survival benefit in these patients. Recent studies suggest that [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET) significantly correlates with histopathological response and survival in patients with gastroesophageal adenocarcinomas undergoing neoadjuvant chemotherapy followed by surgical resection. Therefore, we evaluated the potential of FDG-PET) for the assessment of histopathologic response and prognosis in the multimodality treatment of patients with gastric cancer. Methods: Study patients were recruited from a prospective clinical observation trial on neoadjuvant chemotherapy for gastric cancer between 1997 and 2007. Forty-two patients with locally advanced gastric cancer (cT3-4, Nx, M0) were included (33 men, 9 women; median age 57 years). All patients received neoadjuvant chemotherapy according to the PLF-protocol (cisplatin, leucovorin, 5-FU; 2 cycles over 6 weeks) and subsequently 40 patients underwent standardized total gastrectomy while 2 patients received definitive chemotherapy because of tumor progression. Histomorphologic regression was defined as major histopathological response when resected specimens contained less than 10 % vital residual tumor cells. FDG-PET was performed before and 2 weeks after the end of neoadjuvant chemotherapy with assessment of the intratumoral FDG-uptake [pre-treatment standardized uptake value (SUV1); post-treatment standardized uptake value (SUV2); percentage change (SUVΔ%)]. These variables were correlated with histopathological response and survival. Results: Neoadjuvant chemoradiation led to a significant reduction of intratumoral FDG-uptake (p=0.0006). However, no significant correlations between SUV1, SUV2 or SUVΔ% and histopathological response or prognosis were found. Histomorphological tumor regression was confirmed as an important prognostic factor (p=0.04; log-rank test). Conclusion: Our study does not support recent reports that the metabolic response by FDG-PET is associated with histomorphological response or survival in patients with gastric cancer following neoadjuvant therapy and gastrectomy.
Is Laparoscopic Heller Myotomy Still Indicated in Stage IV Sigmoid Megaesophagus? Martina Ceolin, Mario Costantini, Renato Salvador, Lisa Zanatta, Emanuele Di Fratta, Elena Finotti, Christian Rizzetto, Loredana Nicoletti, Giovanni Zaninotto, Ermanno Ancona Background. Laparoscopic Heller-Dor (LapHD) is an effective treatment for esophageal achalasia, with good results in about 90% of patients. It may be argued whether such an operation is appropriate in case of dilated, sigmoid-shaped megaesophagus. The aim of our study was therefore to evaluate if the esophageal diameter and the presence of a sigmoidshaped megaesophagus could affect the outcome of LapHD procedure in patients with achalasia. Patients and Methods. From 1992 to October 2008, among 447 patients treated with LapHD for esophageal achalasia, 18 had a straight, larger than 6 cm in diameter esophagus (Group A, median age 47, range 19-80) and 15 had a sigmoid-shaped, larger than 6 cm in diameter esophagus (Group B, median age 43, range 18-78). These two groups formed the basis of this report. The findings of the remaining 414 patients, with the esophagus smaller than 6 cm in diameter, served as control group (Group C, median age 44, range 19-85). The percentage of patients who underwent a previous endoscopic treatment before the operation did non differ in the 3 groups (28%, 13% and 21% respectively for Group A, B and C, p=ns). Also other demographic and clinical parameters, such as symptom score or duration of symptoms, did not differ in the 3 groups. The operation was performed by 4 staff surgeons in a well standardized way, with the only addition of a wider isolation of the cardia in order to straighten the distal esophagus in the Group B patients. One patient in group A and 16 in group C experienced accidental mucosal perforation during surgery. Results. At a median follow-up of 30 months (IRQ 10.8-78.2) we obtained an excellent outcome in all but one of the Group A patients (94%). These results were similar to those obtained in Group C patients (382/414 good results, 92%), whereas in Group B only 9 patients out of 15 (60%) were relieved of their dysphagia (p<.01, Chi-square test). Two redo-myotomies and 2 esophagectomies were eventually required in 4 patients; other 2 patients are still undergoing periodical endoscopic dilations. Only 1 patient in group A required complementary dilations. Conclusions. In patients with a dilated (> 6 cm) but non-sigmoid in shape esophagus, LapHD allows results similar to those obtained in patients with earlier disease. In patients with late disease and a sigmoid-shaped esophagus, LapHD may still achieve good results by releaving dysphagia in more than half of the patients (60%). Therefore, laparoscopic myotomy may still be the first surgical option to be offered to these patients before esophagectomy.
1012 Transvaginal Cholecystectomy Without Laparoscopic Support Using Prototype Flexible Endoscopic Instruments Shean Satgunam, Brent W. Miedema, Klaus Thaler Purpose: Transvaginal cholecystectomy with laparoscopic assistance has been performed safely in humans. Cholecystectomy with Natural Orifice Translumenal Endoscopic Surgery (NOTES) without laparoscopic support will require new techniques and instruments for access, gallbladder retraction, dissection, and sealing of the cystic duct and artery. The aim was to develop a NOTES technique to perform transvaginal cholecystectomy without laparoscopic instruments using prototype flexible endoscopic devices. Methods: Cholecystectomies were performed in 88-97 lbs pigs with a planned two week survival. Prototype flexible instruments (NOTES Toolbox 1 provided by Ethicon Endo-Surgery Inc.) included a steerable overtube, bipolar hemostatic forceps, Maryland dissector, clip applier, grasper, rotating hook knife, scissor, and a tissue approximating system (TAS). A dual channel endoscope was passed transvaginally and pneumoperitoneum was established. Endoscope stabilization was achieved with the steerable trocar or a suture through a working channel of the endoscope and the abdominal wall. Sutures, endo-loops, or the TAS were attached to the gallbladder and externalized through the abdominal wall with a 1 mm suture passer for retraction. Dissection in the triangle of Calot to achieve the critical view was performed with endoscopic scissor, hook knife, or Maryland. The cystic duct was sealed with prototype clips and the artery was clipped or cauterized. The gallbladder was dissected off the liver with scissor and hook knife. The gallbladder was removed from the vagina under direct vision. The colpotomy was closed with 3-0 absorbable sutures. Results: Three out of the five pigs survived two weeks; two died early from liver bed hemorrhage. Operative times ranged from 115-275 minutes and the operative times decreased with experience. The critical view was established in all cases. Perforation of the gallbladder occurred in four pigs. At necropsy, all clips placed on the cystic duct were secure. The artery was secure when clipped in two or coagulated in three pigs. There was no evidence of bile leak or infection. Conclusions: NOTES cholecystectomy without laparoscopic support is feasible using prototype flexible endoscopic devices. The transvaginal steerable trocar gives consistent access to the gallbladder. Complete gallbladder dissection is possible and the clip applier is effective in controlling the cystic duct. The cystic artery can be controlled with clip or coagulation. The primary remaining difficulty is lack of precision during dissection. Techniques and instrumentation for pure NOTES cholecystectomy have improved, but further refinement is warranted.
SSAT Abstracts
1010 Infection Rates in a Large Investigational Trial of Sacral Nerve Stimulation for Fecal Incontinence Steven Wexner, Richard McCallum, Anders Mellgren, John A. Coller, Ghislain Devroede, Tracy L. Hull, Jennifer Ayscue, Michael J. England, David A. Margolin, S. Abbas Shobeiri, Howard S. Kaufman, William J. Snape, Ece Mutlu, Paul Pettit, Joe Tjandra Introduction: Treatment options for patients with fecal incontinence (FI) are limited, and irreversible surgical treatments can be associated with high rates of infection and other complications. One treatment, sacral nerve stimulation (SNS), is approved for FI in Europe and was recently submitted to the FDA for approval of this indication in the US. In that trial, 83% of subjects showed ≥50% reduction in the number of incontinent episodes per week at 12 months compared to baseline. The objective of this analysis is to present infection rates in the recently completed clinical trail assessing the safety and efficacy of SNS for FI in a large population. Methods: Adult patients with greater than two FI episodes per week received implantation of an SNS device following a successful test of the therapy. During test stimulation, test leads and a temporary external stimulator are used to evaluate the patient's response to the therapy prior to implantation of the neurostimulator. Adverse events were reported by investigators at each study site and were coded. Terms such as infection, redness, or seroma were coded as infection regardless of whether the event was related to the therapy. These rates were compared to the rates of infection after the other fda approved treatment for end stage fecal incontinence - the artificial bowel sphincter (ABS). Results: One hundred twenty subjects (92% female, 60.5+12.5 years old) received a chronically implanted InterStim® Therapy (Minneapolis, MN) device. Subjects were followed for an average of 23 (range 2.2 - 61) months. Of the 120 implanted subjects, 13 (10.8%) reported infection during the implant phase. One infection resolved on its own and five were successfully treated with medication. Seven infections (5.8%) required surgical intervention, with infections in five patients requiring full system explant. Test stimulation surgical duration was similar between the infected group (74 min) and the non-infected group (68 min). Reported rates of infection after ABS ranged from 20-25%. Discussion: Reported infection rates from a clinical trial of a currently marketed artificial sphincter were 20-25%. Ultimately, post-operative complications required the complete explant of that artificial sphincter device in 30% of subjects. In contrast, only 4% of the subjects in the current study underwent infection-related device explant. Conclusion: SNS for FI, resulted in a relatively low infection rate compared to the only other FDA approved treatment for end stage for FI. Combined with the high therapeutic success rate shown in this study, these data present a positive risk/benefit profile. Sponsor: Medtronic
SSAT Abstracts
1013 Immunonutrition with Long Chain Fatty Acids Prevents Activation of Macrophages in the Gut Wall Petra Jacob, Julia Frick, Maximilian Feilitzsch, Mario H. Mueller, Markus A. Küper, Helen Raybould, Alfred Konigsrainer, Jorg Glatzle Background: Gut derived mediators and immune cells released into the mesenteric lymph during abdominal sepsis cause severe pulmonary dysfunction including activation of macrophages (Glatzle JOGS 2007). Long chain fatty acids absorbed in the gut activate a vagovagal reflex pathway, the so called “cholinergic anti-inflammatory pathway”, which controls the activity of macrophages in the gut wall (Wang Nat. Med. 2004). Aim: To investigate whether an enteral immunonutrition with long chain fatty acids prevents the activation of macrophages in the gut wall. Methods: Mesenteric lymph was obtained from lymph fistula
A-882