Cholecystectomy does not predispose to esophageal adenocarcinoma

Namberof patkmtz Ikau age (range) Pre.el~ratlvetumor stage 0EUS/CT) 1"2:"r3:T4 NI Polt4xautmsctresidualtumor Salvlgeauophagsctomy ~ce' (%) /diveat 25 months*

Esupklgsctomy 22 64.0 (48-76)

Chemo4rnKliatlon 19 58.7 (42-68)

4: 16: 2 13

4 : 13:2 11 3 (15.8%) 2 (1 recurrence) 6 (31.5%) 10/19 (52.6%}

3 (13,6%) t 7/22 (77.3%)

Number of patlln~ Comldetudftutment Pre-trutment tumor stage TI:T2:T3:T4 N1 : MI Post-treatment endoscopy No macroscopictumor Post.treatmenttumor stage T0:TI:T2:T3:T4 N1 : MI Median survival moMhs 5 year survival

* P > 0.05

Localized d l u u e 24 20

Metastaticdkleue 23 22

1:1:9:13 9:0

0:1:9:13 16 : 23

15 (76%)

13 (59.1%)

1:3:0:6:10

1:1:1:7:12

11:2

12:2

15,5 (4-49) 21%

9.5 (4-51) 13%

M1050 Cholecysteetomy Does Not Predispose to Esophageal Adenocardnoma Pankaj Singh, Tahir B. Mughal, Deepak Agarwal, Julia Mandelblatt, Diahanne Ennis, Simmy Bank, Alfred Neugut, Michael V. Sivak Jr., Amitabh Chak

M1052 Administration of a Substance P Receptor Antagonist (SPRA) Increases the Expression of Peritoneal Tissue Plasminogen Activator (tPA) in a Rat Model of Intraabdorainai Adhesions Karen L. Reed, Jill F. Lehrmann, Arthur F. Stucchi, Adam C. Gower, Susan E. Leeman, James M. Becker

Background: Cfiolecystectomized patients have an increased incidence of duodenogastroesophageaI (DGER) reflux of bile juice. A recent study suggested that this may increase the nsk for esophageal adenocarcinoma. Aim: To determine whether prior cholecystectomy is associated with the development of esophageal adenocarcinoma. Method: A case control study was conducted in two tertiary care medical centers. The case group (Group I) comprised of consecutive patients diagnosed with esophageal adenoearcinoma from 1990 to 2002. The control group comprised of two different subsets of patients: Group II A -consecutive patients diagnosed with squamous cell cancer of esophagus, and Group IIB - patients referred to the hospital for benign medical problems (prostatic hyperphsia or uterine fibroids). Patient medical records were reviewed for relevant information. Chi-sqnare test, univariate and multivariate logistic regression analysis was conducted. Results: There was no difference in the cholecystectomy rate between esophageal adenocarcinoma and the two control groups. Multivariatelogistic regression analysis showed Caucasian race,increasedbody weight,smoking, alcohol intake, history of GERD, duration of GERD, and presence of Barrett's esophagus to be independent predictors of development of esophageal adenocarcinoma. Conclusion: Priorcholecystectomyis not a significant risk factor for subsequent development of esophageal adenocarcinoma in the United States. Caucasian race, increased body weight, smoking, alcohol intake, history of GERD, duration of GERD and presence of Barrett's esophagus are strong risk factors for esophageal adenocarcinoma.

Cor

Degradation of fibrin deposits within 48 hours of abdominal surgeryis critical to preventing adhesion formation. Substance P (SP) is emerging as a key factor in the early molecular events associated with intraabdominal adhesion formation. Recent studies from our lab showed that a SPRA significantly reduced intraabdominal adhesion formation in rats; however, the mechanism(s) remains unknown. The aim of this study was to determine if SPRA affects expression of the proinflammatory molecules TNFce and ICAM-1, and the fibrinolytic molecules, tPA and plasminogen activator inhibitor (PAl). Methods: lntraabdominal adhesions were induced in 24 rats by creating ischemic buttons on the peritoneal sidewall. Twelve animals were randomly selected to receive daily doses (2.5 mg/kg; BID) of the SPRA CJ-12,255 and an intra-peritoneal dose at the tzme of surgery. Six animals from each group, with (+ SPRA) or without (-SPRA), and 6 non-operated controls, were sacrificed either 24hrs or 7-days post-surgery. Peritoneal tissue dtssected from the sites of adhesion development was assayed by semi-quantitative RT-PCR for TNFa, 1CAM-l, tPA and PAL Results: At 24 hrs, TNFa, ICAM-1 and tPA mRNA expression levels were not different compared to nonoperated control levels. Administration of the SPRA, while not effecting TNFa or ICAM-1 mRNA levels, led to a marked increase in tPA mRNA levels. PAl mRNA levels were significantly increased at 24 hrs with and without SPRA administration. At 7 days, mRNA levels for TNFa, 1CAM-1, tPA and PAl were significantly elevated above non-operated.controls. Administration of the SPRA for 7 days significantly reduced TNFa, 1CAM-1 and tPA mRNA levels, but had no affect on PAl levels. Conclusions: These data suggest that a mechanism of action of SP in promoting adhesion formation may be by inhibiting the synthesis of tPA. If in the presence of the SPRA tPA activity were increased, this increase in fibrinolytic activity in the peritoneum would diminish adhesion formation.

of EsophagealAdGmocerclnomawith SquamousC~I Cancer and HaulthControls Adenocarcinoma

Numberof Subjects MeauAge (yaur=)

(M) Walght (lb@

AIr GERD GERDduratlo, (year=)

Race(Caucasian) CholK'ystsctomy

217

Control Group SquamousCell Healthy Controls Cancer (Gp, II A) (Gp. II B) 149 512

65,8,11.8

66,8 ~12

67 ~10

181 (83%) t I[

101 (68%)

368 (72%)

174~34~:

148,36

90 (44.5%)~ 66 (33%)~ 94 (44%)~

84 (64%) 65 (49.6%) 37 (26%)

12 ~12~t

3,4 ~4.9

186 (93%)~

99 (71%)

124 (24%) 40 (7.6%) 14 (2.7%)

Effect of a SPRA on Pedto~eal mRNA Expression 24 Hour= mRNA* TNFa

396 (77%)

18 (8.6%) 16 (11.3%) 48 (9.3 %) Bam~s uo~agus 66 (37%)~t 9 (6,4%) -significantdifference(p