Electrical stimulation of the vagus nerve in disordered esophageal motility: an animal model of achalasia

Pronpera~e p m m t m LES i m ~ r r

(.mOe)

HLES 9 GERD (,,,8)

HIES ,~ paramophag~l I ~ l a (n,,4)

HIES only (n=4)

28.3 (27.3 -46.8)

47.4 (39A-

3/8

2/4

2/4

8/8 (3cm)

n/a

4/4 (2cm)

medlm mm Hg 30.6 (27.4-40.4)

Hyl~tu~ve body conUa~ flons (>180mmHg) Typed hlatal hernia (median size)

opossums (Didelphis virginiana) were divided in to three groups. In Group1 (n = 6) a loose Gore-Tex band (110% of the esophageal circumference) was placed around the gastroesophageal junction to prevent relaxation of the lower esophageal sphincter (LES) during swallowing. In Group2 (n = 6) a relatively tighter band (90% of the esophageal circumference) was used to further elevate the LES pressure. At six weeks following manometric and radiolologic confirmation of achalasia, electrical stimulation of the esophagus was performed before and after removal of the band using a graduated square wave electrical stimulus. Sham surgery was performed on three anunals (Group3). Changes in esophageal neural plexi were assessed histologically. Results: Animals in Gmupl demonstrated a vigorous variety of achalasia (high amplitude simultaneous, repetitive contractions), moderate esophageal dilatation, and degeneration of 10%-50% of nerve plexi. In Group2 animals developed amotile achalasia with typical low amplitude simultaneous (mirror image) contractions, severely dilated (bird's beak) esophagus and degeneration of 40% -65% of nerve plexi. Vagal stimulation in Group 1 demonstrated a significant increase in the amplitude of contractions (p<0.001), and return of peristaltic activity in 30% of swallows before band removal. After band removal all the contractions were peristaltic. In Group2, vagal stimulation before and after removal of the band demonstrated sigmficant increase in amplitude of contractions (p<0.001) but no return of propagative peristalsis. Conclusion: Electrical stimulation of the vagus nerve improves the force of esophageal contractions irrespective of the severity of the disease; however, peristaltic activity returns back to normal only in vigorous (milder) variety of achalasia. Whether chronic stimulation in case of amotile achalasia will lead to return of normal peristaltic activity needs to be investigated.

56.8)

686 Effect of Endoluminal Gastroplication in Patients with Classic Reflux Symptoms and Minimally Abnormal Esophageal pH Studies Linda S. Lee, Julia J. kin, David k. Carr-Locke, John R. Saltzman Purpose: Traditionally patients with classic reflux symptoms but minimally abnormal esophageal pH studies have not been considered ideal surgical candidates. Endolummal gastroplication (ELGP) has been shown to improve clinical outcome in patients with gastroesophageal disease (GERD) but it remains unclear if equally impressive improvements occur in this patient population. The aim of this study is to evaluate symptomatic outcome after ELGP in patients with reflux symptoms and minimally abnormal pH studies. Methods: Patients with GERD and minimally abnormal DeMeester scores defined as less than or equal to 30 were included. Between July 2001-July 2002, 23 patients who underwent ELGP for GERD met this criterion. All ELGPs were performed with 2 or 3 plications placed 1 to 2 cm below the gastroesophageal junction. Follow-up data included weight, BMI, heartburn frequency score (HFS), heartburn severity (HSV), heartburn symptom score (HSS), regurgitation frequency (RFS), and medication use; in 3 patients manometries, pH studies, and upper endoscopy findings were obtained at variable intervals after ELGP. Results: For the 23 patients, average age was 51 with 11 men, 12 women and average BMI 28. Nine of 23 patients had a history of previous surgical fundoplication. Only 1 patient was not on medication'before or after the ELGP. On average at baseline patients reported only a 36% improvement in symptoms on medications. Average baseline lower esophageal sphincter pressure (LESP) was low at 17.4 +/-8.6mmHg with DeMeester scores of 18.5+/-9.0. Mean follow up was 4.3 months. For all symptom scores, improvement occurred POst-ELGP (all p<0.02): HFS (0-3) from 2.4 to 1.2, HSS (0-96) from 48 to 19, HSV (0-32) from 18 to 10, and RFS (0-3) from 1.9 to 0.6. After ELGP, 68% of patients were off medications, 9% had decreased usage of medications, and 23% had no change in medications. Extraesophageal symptoms also improved: 100% of nocturnal symptoms (5 of 5), 75% of atypical chest pain (3 of 4) and cough (3 of 4), and 50% of hoarseness (2 of 4) resolved. The trend after ELGP for manometry, pH study, and upper endoscopy data was improvement: LESP from 18 to 21.75 mmHg, % time pH<4 from 3.4 to 2.2, and DeMeester scores from 14.6 to 7.9. None of the 3 patients with post-ELGP endoscopies had Barrett's but esophagitis in one patient had healed after ELGP. Conclusions: ELGP significantly improves clinical outcome in patients with GERD and persistent symptoms on medical therapy even with minimally abnormal pH studies.

731 Right Hepatic Artery Injury Associated with Laparoscopic Bile Duct Injuries:

Incidence, Mechanism, and Consequences Lygia Stewart, Thomas N. Robinson, Crystine M. Lee, Kingsway Liu, Karen Whang, Lawrence W. Way Purpose: The most common forms of bile duct injury (BDI) involve damage at the level of the common hepatic duct. Because it is so close, the right hepatic artery (RHA) may also be harmed. Reports on the frequency and significance of RHA injury (RHAI) associated with BDI are sparse. What is available suggests that the combination substantially decreases the success of the bile duct repair and increases the mortality rate. In this large series we examined the incidence, mechanism, and consequences of RHA1 accompanying malor BDI from laparoscopic cholecystectomy. Methods: 246 cases of laparoscopic BDI were referred for evaluation. The status of the RHA was discemable in 213 cases, which constituted the study group. Based on anatomic pattern, the BDI were: Class l, 8%; Class II, 26%; Class Ill, 55%; and Class IV, 11%. There were 168 women and 45 men, whose average age was 46 years. Complications associated with RHA1 were identified. Results: RHAI was present in 66 cases (31%). The association of RHAI by BDI Class was: Class I, 6%; Class 1I, 16%; Class ill, 33% (P < 0.05 vs Class I or If, X2); and Class IV, 71% (P < 0.002 vs Class I, II or Ill, X2). RHAI had no influence on the success of the BDI repair or the mortality rate (see Table). RHA1 was more commonly associated with abscess formation, intra-operative bleeding, post-op bleeding, bemobilia, right hepatic lobe ischemia, and subsequent need for hepatectomy (see Table). Overall, 61% of patients with RHAI, compared with 11% of patients without RHAI, suffered one or more of these complications (P < 0.0001, X2). Excluding intra-op bleeding, 40% of patients with RHAI, compared with 3% of those without RHAI, had one or more of these complications (P < 0.0001, X~). Conclusions: RHA1 occurred more often with Class ll[ and IV BDI, but less often with Class I1 BD1, which reflects differences in the mode of injury between these categories. RHAI did not increase the mortality rate or decrease the success of the biliary repair. Nevertheless, RHA1 was more often (40%) followed by abscess formation, bleeding, hemobilia, hepatic ischemia, and the need for hepatic resection. This is the first large series that clearly delineates these important relationships.

687 Laparoscopic Nissen Fundoplication Versus lh'oton Pump Inhibitor Maintenance for Severe Gastro-Oesophageal Reflux Disease: Trial Based Analysis Of LongTerm Cost And Cost-Effectiveness Richard Cookson, Chris Flood, Brendan C. Koo, David Mahon, Michael Rhodes Objective: To compare long-term cost-effectiveness of laparoscopic UlSSen fundoplication (LNF) versus proton pump inhibitor (PPI) maintenance for severe gastro-oesophageal reflux disease (GORD). Methods: Patient level data on costs and outcomes up to 12-month follow up were obtained from the first 100 patients in a randomised control trial comparing LNF and PPl, based at the Norfolk and Norwich University Hospital. Detailed costing was performed from an NHS perspective. Costs were extrapolated to future years with oneway sensitivity analysis on modelling assumptions. Incremental cost-effectiveness ratios and confidence intervals were estimated using bootstrap simulation. Results: LNF was more effective than PP1 and s more costly in year one, with a cost of s compared with s ($818). LNF is cost saving by year 7, irrespective of changes in modelling assumptions such as the relapse rate and the future price of medication. A 10% change in surgical costs changes the "break-even" point by 1 year. In year 1, cost per patient returned to a normal DeMeester score (<13.9 at 3 months) was s ranging from s to s and cost per percentage point improvement in GastroIntestinal and Psychological Well-being quality of life score was s with a range of s to s By year 5, cost per physiologically normal patient was s and cost per percentage point improvement in quality of life was s Conclusion: From the perspective of a public sector payer (UK National Health Service), LNF surgery in this trial was cost-effective at a time horizon of 3-5 years; and likely to become cost saving after 7 years.

Consequences of RHA Injury A I ~ s formation InVa-op binding Pont-op bleeding Hemobflte Hepatic I ~ h ~ i a Need for hepatectomy Succmmfulblllary repair Mortality rate

RHA I.ju~/ 18% 35% 23% 9% 8% 8% 94% 1.5%

No RHA Injury 3% 7% 1% 0% 0% 0% 95% 0,6%

P Value (X2} P < 0.0001 P < 0.0001 P < 0.0001 P = 0.001 P: 0.004 P : 0.004

P = 0.98 P = 0.85

732 Novel combination of a COX-2 inhibitor, NS398, and MEK inhibitor, U0126, in human hepatocellular carcinoma provides synergistic increase in apoptosis C. Max Schmidt, Yulang Wang, Chad Wiesenauer, Michele Yip-Schneider, Min Wu Cyclooxygenase-2 inhibitors exert anti-tumor actions in human bepatocellular carcinoma (HCC) cells. The anti-tumor mechanism, however, is unlikely to be entirely due to COX2 inhibition. Extracelhilar regulated kinases (Erkl/Erk2) play an important role in HCC mitogenesis and may be inhibited by COX-2 inhibitors. We investigated the effect of the COX-2 inhibitor, NS398, on ERK1/2 kinase (MEK) activity and Erkl/Erk2 expression in HepG2 and Hep3B cells. Total Erkl and Erk2 expression as determined by immunoblot did not change with NS398 treatment. Surprisingly, Erkl/2 phosphorylation (MEK activity) was increased in a concemration-dependent fashion ([NS398]: 1-100 uM). We hypothesized that inhibition of this COX-2 inhibitor-induced Erkl/2 activation may improve the antitumor actions of COX-2 inhibitors. Human HCC cells (HepG2 and Hep3B) were treated with the COX-2 inhibitor, NS398, in the presence or absence of U0126 (MEK inhibitor). U0126 effectively suppressed Erkl/2 phosphorylation as determined by phospho-specific Erkl/2 immunohlot. In Hep3B cells, apoptosis as determined-by DNA fragmentation ELISA was unchanged with NS398 (1-50 uM) or U0126 (0.1-5 uM) alone. The combination of

688 Electrical Stimulation of the Vagus Nerve in Disordered Esophageal Motility: an Animal Model of Achalasia Yashodhan S. Khajanchee, Michael J. Barra, Roger Van Andel, Paul D. Hansen, Lee L. Swanstrom Objective: Esophageal peristalsis generally does not return to normal following surgical treatment of achalasia. Electrical stimulation of the vagus nerve is known to produce antegrade peristalsis in the normal opossum esophagus; however, it is not known whether electrical stimulation will induce return of peristalsis once an achalasia-like disorder has been established. The objective of this study is to see whether electrical stimulation of the vagal nerve can reinstitute antegrade peristalsis in an animal model of achalasia. Method: Fifteen adult

A-793

SSAT Abstracts