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Upright gastroesophageal reflux: Is surgery indicated?
GASTROENTEROLOGY VoL 114, No. 4
A1386 SSAT ABSTRACTS S0058
UPRIGHT GASTROESOPHAGEAL REFLUX: IS SURGERY INDICATED? T.R. Eubanks, S. Horn,an. R. T0bin, M. MacFarlane. C.E. Pone. and C.A. Pelle~,rini. Department of Surgery, University of Washington, Seattle, Washington. Pure upright gastroesophageal reflux has not been treated surgically in the past because it was seen as physiologic and is associated with aerophagia which may lead to gas bloat, postoperatively. We have identified patients with esophageal injury resulting from upright reflux, and for the past three years have treated these patients similarly to supine and mixed refluxers. The purpose of this study was to determine the extent of esophageal injury and assess the operative outcome of patients undergoing antireflux procedures for pure upright reflux. METHODS: A prospective analysis of symptoms, esophageal function, and esophageal injury was performed in all surgically treated patients found to have pure upright reflux (reflux time >8.2% in upright position and -<3% in the supine position). Postoperative outcome of pure upright refluxers was compared to all others having antireflux surgerY. RESULTS: Twenty five of 318 patients undergoing laparoscopic antireflux procedures were identified as having pure upright reflux. Preoperative symptoms were! heartburn (21), regurgitation (13), dysphagia (12), and chest pain (6). The average lower esophageal sphincter pressure was 10 mmHg (range 3-25), the average DeMeester score was 32 (range 17-100). Twelve patients had esophagitis, 2 had Barrett's metaplasia, and 5 had esophageal stricture. All procedures were completed laparoscopically without operative complications. Primary symptoms improved in all patients. Seven patients (28%) complained of abdominal distention in the early postoperative period which is comparable to the frequency in the comparison group (32%). In 2 patients these symptoms persisted for >3 months, but were noted only once a week and were easily relieved by medication and eructation. CONCLUSION: Pure uptight reflux can lead to esophageal mucosal injury. Operative therapy in patients with this condition is effective and can be accomplished with minimal morbidity. Postoperative gas bloat occurs with the same frequency in upright refluxers as it does in all others undergoing antireflux surgery. S0059
THE ADAPTIVE INTESTINAL RESPONSE TO MASSIVE ENTERECTOMY IS PRESERVED IN SRC-DEFICIENT MICE. RA Falcone Jr, CE Shin, CR Erwin. BW Warner- Division of Pediatric Surgery, Children's Hosnitai Medical Center, Cincinnati. OH. The Src family of protein tyrosine kinases have been implicated in the downstream mitogenic signaling of several ligands including epidermal growth factor (EGF). EGF is likely involved during adaptation after massive small bowel resection (SBR) since this response is impaired in mice with perturbed EGF receptor function. This study was designed to test the hypothesis that Src is required for intestinal adaptation following SBR. Methods - A 50% proximal SBR or sham operation (bowel transection and reanastomosis alone) was performed on heterozygous Src-knockout or wild type (C57bl/6) mice. The ileum was harvested after 3 days and wet weight and protein content noted. Comparisons were done using ANOVA and a p < 0.05 considered significant. Values are presented as mean ± SEM. Results - Adaptation occurred after SBR in the Src-deficient mice as demonstrated by increased ileal protein and wet weight (Graphs) similar to wild-type mice. PROTEIN
:8 5.~6
,
.WET WEIGHT
,
°.01 I a.s.
~
i
lO0
*p<0.05 hamvs SBR
~"4
2
20 L _ L _ L I _ L L I _ Src-Deficient Wild-Type
Sre-Defieient Wild-Type
Conclusions - The adaptive response of the intestine to massive small bowel
resection is preserved despite reduced expression of Src protein. The mitogenic signaling which characterizes intestinal adaptation and associated with receptor activation by EGF and/or other growth factors probably occurs by mechanism(s) independent of the Src family of protein tyrosine kinases. • S0060 I N V I T R O G R O W T H OF COLON TUMORS PREDICTS POORER
LONG-TERM SURVIVAL. TM Farrell, OS Pettem,ill. DS Lon~necker. K Sullivan. KH Cohn. Department of Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, NI-L Although histopathologic stage is a major prognostic determinant for patients with colorectal cancer, advanced stage is not always associated with poor survival. We attempted to immortalize colon tumors in tissue culture, and followed longitudinal patient outcomes, to determine if in vitro growth is associated with higher likelihood of eventual death from disseminated disease.
Forty-one colorectal carcinomas were initiated in tissue culture. A cell line was defined as a continuously growing population of tumor cells without stromal cells. Cell lines were compared to parent tumors by immunohistochemical and ploidy analyses. Patient outcomes were followed for 3.1 to 4.8 years, and Kaplan-Meier survival analyses were performed. Overall, cell lines were generated from 11 (26.8%) of 41 carcinomas. Of 32 primary tumors, nine yielded cell lines. There was no significant association between tumor location (p=0.535, mid-P), degree of differentiation (p=0.850, mid-P) or histopathologic stage (p=0.400, mid-P), and the ability of cells to establish in culture. Primary tumors that yielded cell lines (dashed line) resulted in shorter mean overall survival than those tumors that did not (solid line) (808 ± 176 days vs. 1417± 111 days, p=0.025, logrank). This association also holds if the measured outcome includes only disease-specific deaths or if stage 1 and 4 tumors are excluded.
T ma ,s
1.0~,~____ •,4/
~
!_. ',
.7~
.....
L_
"I
L_.a
•51 0
/
'n
NO C e l l Lines
L___, 300
600
900
(.--'-':.3) 1200
1500
1800
Days We conclude that a colon cancer's adaptability to cell culture is associated with its biologic aggressiveness and therefore predicts poorer patient outcome. Funded by the Hitchcock Foundation, Hanover, NH. S0061
NISSEN AND TOUPET FUNDOPLICATIONS RESIST REFLUX INDEPENDENT OF NATURAL ANATOMIC RELATIONSHIPS. TM Farrell. RE Metreveli, WS Richard~0n, CD Smith, JG Hunter. Department of Surgery, Emory University School of Medicine, Atlanta, Georgia. Pathologic gastroesophageal (GE) reflux may result from lower esophageal sphincter (LES) dysfunction or anatomic dissociation of the GE junction and crural diaphragm, as in patients with hiatal hernia. We measured dynamic pressures across the GE junction during gastric distension to determine the effectiveness of Nissen (360 °) and Toupet (270 °) fundoplications, exclusive of in vivo anatomic relationships. Eight stomachs and distal esophagi were resected from fresh human cadavers. A multi-channel manometric pump (Mui Scientific, Mississauga, Ontario) and polygraph (PC Polygraph HR/Polygram for Windows software, version 1.11, Medtronic Synectics, Shoreview, MN) recorded coincident pressures from the distal esophagus, LES and gastric body during trans-pyloric distension of the stomach with water. Specimens were analyzed at ex vivo baseline, and after Nissen and Toupet fundoplications. Wraps were 2-cm long and fashioned around a 60-French dilator using interrupted 2-0 silk sutures, obtaining fullthickness bites of stomach and partial-thickness bites of esophagus. Before fundoplication, reflux occurred immediately in all explanted specimens. After Nissen fundoplication, stomachs never refluxed during distension, but rather ruptured at mean intragastric pressure (IGP) of 46.8 ± 15.0 mmHg. LES pressure averaged 2.0 ± 0.5 times IGP during gastric distension. After Toupet fundoplication, reflux was observed at low IGP (<2 mmHg), but ceased as IGP increased, and did not recur before gastric rupture at mean IGP of 49.9 ± 15.0 mmHg. LES pressure averaged 2.4 ± 1.0 times IGP during gastric distension. Nissen and Toupet fundoplications prevent reflux by increasing LES pressure in a linear fashion at 2-2.5 times IGP, independent of anatomic relationships between the GE junction and the crural diaphragm. At low IGP, Toupet fundoplication lacks the competency of Nissen fundoplication. Funded by Ethicon. S0062
THE MORPHOLOGY OF MYENTERIC PLEXUS OF THE HUMAN COLON IS ALTERED WITH AGE. Y. Fellim A. Vromen, R, Udassin. H.R. Freun& M. Hanani. Hebrew University-Hadassah Medical School, Jerusalem 91240, Israel. Aging is believed to cause a variety of gastrointestinal motility dysfunctions, most notably constipation. However, there is very little pathophysiological evidence for this claim. We investigated the effect of age on the structure of colonic myenteric plexus from 134 patients at ages 10 days to 88 years. We used the vital dye 4-Di-2-ASP, which selectively labels nerves in this tissue, to stain the myenteric plexus in whole mount preparations. We identified three types of ganglia: normal ones where neurons are closely packed; ganglia
A1386 SSAT ABSTRACTS S0058
UPRIGHT GASTROESOPHAGEAL REFLUX: IS SURGERY INDICATED? T.R. Eubanks, S. Horn,an. R. T0bin, M. MacFarlane. C.E. Pone. and C.A. Pelle~,rini. Department of Surgery, University of Washington, Seattle, Washington. Pure upright gastroesophageal reflux has not been treated surgically in the past because it was seen as physiologic and is associated with aerophagia which may lead to gas bloat, postoperatively. We have identified patients with esophageal injury resulting from upright reflux, and for the past three years have treated these patients similarly to supine and mixed refluxers. The purpose of this study was to determine the extent of esophageal injury and assess the operative outcome of patients undergoing antireflux procedures for pure upright reflux. METHODS: A prospective analysis of symptoms, esophageal function, and esophageal injury was performed in all surgically treated patients found to have pure upright reflux (reflux time >8.2% in upright position and -<3% in the supine position). Postoperative outcome of pure upright refluxers was compared to all others having antireflux surgerY. RESULTS: Twenty five of 318 patients undergoing laparoscopic antireflux procedures were identified as having pure upright reflux. Preoperative symptoms were! heartburn (21), regurgitation (13), dysphagia (12), and chest pain (6). The average lower esophageal sphincter pressure was 10 mmHg (range 3-25), the average DeMeester score was 32 (range 17-100). Twelve patients had esophagitis, 2 had Barrett's metaplasia, and 5 had esophageal stricture. All procedures were completed laparoscopically without operative complications. Primary symptoms improved in all patients. Seven patients (28%) complained of abdominal distention in the early postoperative period which is comparable to the frequency in the comparison group (32%). In 2 patients these symptoms persisted for >3 months, but were noted only once a week and were easily relieved by medication and eructation. CONCLUSION: Pure uptight reflux can lead to esophageal mucosal injury. Operative therapy in patients with this condition is effective and can be accomplished with minimal morbidity. Postoperative gas bloat occurs with the same frequency in upright refluxers as it does in all others undergoing antireflux surgery. S0059
THE ADAPTIVE INTESTINAL RESPONSE TO MASSIVE ENTERECTOMY IS PRESERVED IN SRC-DEFICIENT MICE. RA Falcone Jr, CE Shin, CR Erwin. BW Warner- Division of Pediatric Surgery, Children's Hosnitai Medical Center, Cincinnati. OH. The Src family of protein tyrosine kinases have been implicated in the downstream mitogenic signaling of several ligands including epidermal growth factor (EGF). EGF is likely involved during adaptation after massive small bowel resection (SBR) since this response is impaired in mice with perturbed EGF receptor function. This study was designed to test the hypothesis that Src is required for intestinal adaptation following SBR. Methods - A 50% proximal SBR or sham operation (bowel transection and reanastomosis alone) was performed on heterozygous Src-knockout or wild type (C57bl/6) mice. The ileum was harvested after 3 days and wet weight and protein content noted. Comparisons were done using ANOVA and a p < 0.05 considered significant. Values are presented as mean ± SEM. Results - Adaptation occurred after SBR in the Src-deficient mice as demonstrated by increased ileal protein and wet weight (Graphs) similar to wild-type mice. PROTEIN
:8 5.~6
,
.WET WEIGHT
,
°.01 I a.s.
~
i
lO0
*p<0.05 hamvs SBR
~"4
2
20 L _ L _ L I _ L L I _ Src-Deficient Wild-Type
Sre-Defieient Wild-Type
Conclusions - The adaptive response of the intestine to massive small bowel
resection is preserved despite reduced expression of Src protein. The mitogenic signaling which characterizes intestinal adaptation and associated with receptor activation by EGF and/or other growth factors probably occurs by mechanism(s) independent of the Src family of protein tyrosine kinases. • S0060 I N V I T R O G R O W T H OF COLON TUMORS PREDICTS POORER
LONG-TERM SURVIVAL. TM Farrell, OS Pettem,ill. DS Lon~necker. K Sullivan. KH Cohn. Department of Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, NI-L Although histopathologic stage is a major prognostic determinant for patients with colorectal cancer, advanced stage is not always associated with poor survival. We attempted to immortalize colon tumors in tissue culture, and followed longitudinal patient outcomes, to determine if in vitro growth is associated with higher likelihood of eventual death from disseminated disease.
Forty-one colorectal carcinomas were initiated in tissue culture. A cell line was defined as a continuously growing population of tumor cells without stromal cells. Cell lines were compared to parent tumors by immunohistochemical and ploidy analyses. Patient outcomes were followed for 3.1 to 4.8 years, and Kaplan-Meier survival analyses were performed. Overall, cell lines were generated from 11 (26.8%) of 41 carcinomas. Of 32 primary tumors, nine yielded cell lines. There was no significant association between tumor location (p=0.535, mid-P), degree of differentiation (p=0.850, mid-P) or histopathologic stage (p=0.400, mid-P), and the ability of cells to establish in culture. Primary tumors that yielded cell lines (dashed line) resulted in shorter mean overall survival than those tumors that did not (solid line) (808 ± 176 days vs. 1417± 111 days, p=0.025, logrank). This association also holds if the measured outcome includes only disease-specific deaths or if stage 1 and 4 tumors are excluded.
T ma ,s
1.0~,~____ •,4/
~
!_. ',
.7~
.....
L_
"I
L_.a
•51 0
/
'n
NO C e l l Lines
L___, 300
600
900
(.--'-':.3) 1200
1500
1800
Days We conclude that a colon cancer's adaptability to cell culture is associated with its biologic aggressiveness and therefore predicts poorer patient outcome. Funded by the Hitchcock Foundation, Hanover, NH. S0061
NISSEN AND TOUPET FUNDOPLICATIONS RESIST REFLUX INDEPENDENT OF NATURAL ANATOMIC RELATIONSHIPS. TM Farrell. RE Metreveli, WS Richard~0n, CD Smith, JG Hunter. Department of Surgery, Emory University School of Medicine, Atlanta, Georgia. Pathologic gastroesophageal (GE) reflux may result from lower esophageal sphincter (LES) dysfunction or anatomic dissociation of the GE junction and crural diaphragm, as in patients with hiatal hernia. We measured dynamic pressures across the GE junction during gastric distension to determine the effectiveness of Nissen (360 °) and Toupet (270 °) fundoplications, exclusive of in vivo anatomic relationships. Eight stomachs and distal esophagi were resected from fresh human cadavers. A multi-channel manometric pump (Mui Scientific, Mississauga, Ontario) and polygraph (PC Polygraph HR/Polygram for Windows software, version 1.11, Medtronic Synectics, Shoreview, MN) recorded coincident pressures from the distal esophagus, LES and gastric body during trans-pyloric distension of the stomach with water. Specimens were analyzed at ex vivo baseline, and after Nissen and Toupet fundoplications. Wraps were 2-cm long and fashioned around a 60-French dilator using interrupted 2-0 silk sutures, obtaining fullthickness bites of stomach and partial-thickness bites of esophagus. Before fundoplication, reflux occurred immediately in all explanted specimens. After Nissen fundoplication, stomachs never refluxed during distension, but rather ruptured at mean intragastric pressure (IGP) of 46.8 ± 15.0 mmHg. LES pressure averaged 2.0 ± 0.5 times IGP during gastric distension. After Toupet fundoplication, reflux was observed at low IGP (<2 mmHg), but ceased as IGP increased, and did not recur before gastric rupture at mean IGP of 49.9 ± 15.0 mmHg. LES pressure averaged 2.4 ± 1.0 times IGP during gastric distension. Nissen and Toupet fundoplications prevent reflux by increasing LES pressure in a linear fashion at 2-2.5 times IGP, independent of anatomic relationships between the GE junction and the crural diaphragm. At low IGP, Toupet fundoplication lacks the competency of Nissen fundoplication. Funded by Ethicon. S0062
THE MORPHOLOGY OF MYENTERIC PLEXUS OF THE HUMAN COLON IS ALTERED WITH AGE. Y. Fellim A. Vromen, R, Udassin. H.R. Freun& M. Hanani. Hebrew University-Hadassah Medical School, Jerusalem 91240, Israel. Aging is believed to cause a variety of gastrointestinal motility dysfunctions, most notably constipation. However, there is very little pathophysiological evidence for this claim. We investigated the effect of age on the structure of colonic myenteric plexus from 134 patients at ages 10 days to 88 years. We used the vital dye 4-Di-2-ASP, which selectively labels nerves in this tissue, to stain the myenteric plexus in whole mount preparations. We identified three types of ganglia: normal ones where neurons are closely packed; ganglia