Immohistochemical expression of cytokeratin 7 and 20 in long- (LSBE) and short- (SSBE) segment Barrett’s esophagus

Immohistochemical expression of cytokeratin 7 and 20 in long- (LSBE) and short- (SSBE) segment Barrett’s esophagus

AJG – September, 2000 LSBE n ⫽ 24 (%) SSBE n ⫽ 36 (%) GIM n ⫽ 35 (%) Sensitivity % Specificity % p-value Abstracts HHⴙ HPⴚ Incⴙ Villⴙ Combined*...

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AJG – September, 2000

LSBE n ⫽ 24 (%) SSBE n ⫽ 36 (%) GIM n ⫽ 35 (%) Sensitivity % Specificity % p-value

Abstracts

HHⴙ

HPⴚ

Incⴙ

Villⴙ

Combined*

23 (96) 27 (75) 3 (9) 83 91 ⬍.01

19 (79) 28 (77) 7 (20) 78 80 ⬍.01

23 (96) 31 (86) 10 (29) 90 71 ⬍.01

19 (79) 18 (50) 14 (40) 62 60 ⬍.01

24 (100) 35 (97) 23 (65) 98 35 ⬍.01

Conclusions: Clinicopathologic features are variably sensitive and specific for BE. The presence of at least one clinicopathologic feature is sensitive for a diagnosis of BE, however, at the expense of reduced specificity. These results highlight the need for an objective sensitive and specific marker of BE. This study may have application to the accurate diagnosis of BE in everyday clinical practice.

63 Pharmacologic stimulation of salivation: Its role in acid clearance William C. Orr*, Chien-Lin Chen, Sheldon Sloan. Lynn Institute for Healthcare Research, Oklahoma City, OK, United States. Purpose: It has been demonstrated that the inhibition of salivation leads to a marked prolongation of esophageal neutralization. To date, therapeutic options for GERD have not recognized the possible utility of promoting salivation as an effective treatment. Cisapride is a 5-HT4 agonist with cholinergic properties and is known to stimulate salivation. Its efficacy in the acid clearance process has not been explored. The aim of this study is to assess the efficacy of cisapride in facilitating acid clearance in older and younger cohorts with symptomatic GERD. Methods: Subjects were 15 older adults (mean age 72.2 years) and 15 younger adults (mean age 34.1 yrs.) with symptomatic GERD were studied. All subjects had symptoms of heartburn at least 4 days a week with antacid consumption at least once a week. The esophageal pH was measured from 5 cm above the manometrically determined proximal border of the lower esophageal sphincter. The basic acid clearance process involved the installation of 15 ml of 0.1 NHcl into the distal esophagus. The subject was required to swallow every 30 seconds, and the number of swallows required to produce an esophageal pH above 4.0 for 30 seconds was determined. This process was accomplished under normal conditions and while allowing a peppermint lozenge to dissolve in the mouth. These two conditions were repeated under a baseline condition and subsequent to one week of treatment with cisapride 10 mg, qid. Results: There was no significant difference in any of the parameters between the two groups and therefore group data are presented. The lozenge alone condition resulted in a significant decrease in the number of swallows required for acid clearance (mean ⫽ 9.07 vs. 6.27, P ⬍ .001). Cisapride alone produced a significant decrease in the number of swallows to acid clearance (9.07 vs. 6.76, P ⬍ .001). There was no difference between the number of swallows to clear comparing the lozenge condition without cisapride and cisapride alone (6.27 vs. 6.76 respectively). Conclusions: 1. Cholinergic stimulation of salivation is an effective means of facilitating esophageal acid clearance; 2. Salivary stimulation is equally efficacious in older and younger patient populations; 3. Drugs with cholinergic effects such as 5HT4 agonist should be considered potentially important compounds in the armamentarium to treat GERD.

64 H2-receptor antagonists not superior to proton pump inhibitors for nocturnal acid suppression: A prospective study Ours TM, Fackler WK, Richter JE, Vaczi MF. The Cleveland Clinic Foundation, Cleveland, Ohio. Proton pump inhibitors (PPI’s) are potent gastric acid suppressive agents. Recent studies suggest H2RA may be superior to PPI’s in decreasing nocturnal acid breakthrough. However, since gastric acidity is directly a

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result of proton pump function, we hypothesized more effective dosing interval for PPI’s may result in better gastric acid control. Aim: Compare degree of gastric acid control between equally spaced dosing of PPI therapy (Q8 hr) to combined PPI BID ⫹ H2RA HS. Methods: Eight subjects, 3 controls and 5 with GERD, were prospectively evaluated by combined 24-hour esophageal/gastric pH monitoring. All subjects had pH monitoring at baseline, after 4 wks of treatment with omeprazole (20 mg BID) plus ranitidine (300 mg HS), and after 2 wks of treatment with omeprazole (20 mg Q8 hrs). Dual pH probe placed 5 cm above and 10 cm below the LES for a minimum of 18 hrs. Total, upright, and supine acid values were compared between treatment regimens using Pairwise ANOVA on Ranks with Dunn’s correction for multiple comparisons. H. pylori serology tested in all subjects. Results: Five males and 3 females (mean age ⫾ SE; 39 yrs ⫾ 3.6 yrs; range 26 to 57 yrs) enrolled in study. Median (25% to 75%) upright % time gastric pH ⬍4 significantly (p ⫽ 0.03) lower with Q8hr PPI treatment than PPI BID ⫹ H2RA; 19.7% (8.5% to 34%) and 42.5% (22.8%– 69%), respectively. No statistical difference in median (25% to 75%) % supine time pH ⬍4 between two groups; 18.3% (0.3% to 44%) and 26.0% (21% to 32.2%), respectively (Figure). Seven of 8 subjects were H pylori negative. Conclusions: Treatment with omeprazole 20 mg Q8 hrs is equally effective as treatment with omeprazole 20 mg BID plus ranitidine 300 mg for supine gastric acid suppression and is more effective in the upright position.

65 Immohistochemical expression of cytokeratin 7 and 20 in long(LSBE) and short- (SSBE) segment Barrett’s esophagus Suhkdeep Padda MD, Ifat A Shah MD, Francisco C Ramirez MD, FACG, Michele A Young MD. VA Medical Center, Phoenix, AZ. The distinction between SSBE (intestinal metaplasia (IM) of the esophagus) and IM of the gastric cardia may be endoscopically difficult. Moreover, it is unknown whether these two conditions (both harboring IM), have similar risks for the development of carcinoma and therefore its distinction may have crucial implications for further surveillance. Aim: To determine the usefulness of CK7/CK20 immunoreactivity pattern in SSBE. Methods: Archival histological biopsy specimens endoscopically obtained from Pts with LSBE and SSBE were cut from tissue blocks fixed in formalin and embedded in paraffin. Biopsies were immunostained for CK7 (Dako OV-TL 12/30, 1/100) and CK20 (Dako Ks20.8, 1/200). The pattern of staining in the surface epithelium (S) and the deep glandular (G) areas was rated as diffuse (D), patchy (P) or absent (A) for CK7 and CK20. The intensity of the staining patterns was graded as strong, moderate, or weak by 2 independent blinded examiners. The characteristic reported staining pattern for LSBE is strong SD and GD for CK7 and strong SD and GP for CK20. The gastric CK7/CK20 pattern describes a CK7 stain, which is patchy and weak or void of immunoreactivity in the deep glands, and CK20 which stains SP and GP with variable intensity. Representative tissue from adenocarcinoma of the lung and colon served as positive controls for CK7 and CK20, respectively. Results: Specimens from 11 Pts with LSBE and 30 Pts with SSBE were processed and analyzed. All specimens from the LSBE Pts demonstrated the characteristic strong CK7 SD/GD and CK20 moderate/strong SD/GP staining pattern (100%). Specimens from 19 of 30 (63%) SSBE patients stained with the same characteristic esophageal CK7/CK20 pattern. In 11

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Abstracts

AJG – Vol. 95, No. 9, 2000

of 30 Pts (37%) the characteristic gastric IM pattern (CK7 GP and CK20 SP/GP) was demonstrated. Conclusions: LSBE demonstrates a distinct and reproducible CK7/CK20 pattern as described in the literature. Almost two-thirds of Pts with SSBE display cytokeratin staining consistent with esophageal IM. The remaining Pts with IM and suspected SSBE exhibit a characteristic gastric cardia pattern. Immunostaining may help to identify true SSBE from gastric cardia IM.

66 Multi-channel 24-hour pH monitoring and esophageal manometry in long (LSB)- and short-segment (SSB) Barrett’s, gastroesophageal reflux (GER) and asymptomatic subjects (AS) S Padda, MD, R Akins, LPN, MA Young, MD, FC Ramirez, MD, FACG. VA Medical Center, Phoenix, AZ. The determinants of the length of Barrett’s are unknown. Aim: To study manometry and 24-hour pH in SSB and LSB Pts and compare it to AS and GER. Methods: Pts with LSB and SSB Barrett’s. GER symptoms but no Barrett’s or esophagitis (GER) and AS had manometry and 24-hour pH with a 4-(5 cm apart) channel (proximal ⫽ P; mid-proximal ⫽ MP; mid-distal ⫽ MD and distal ⫽ D) probe (D: 5 cm above LES) off PPI/H2RA’s. Results: 61 subjects: 15 AS, 15 GER, 16 SSB and 15 LSB. Manometrically, AS, GER and SSB were similar. Except for ⬎ duration of contractions in the distal (DE) and mid esophagus (ME). GER was similar to SSB. LSB had significantly ⬍LESP (11.9 ⫾ 0.1 mmHg), ⬎uncoordinated contractions (48%), ⬍amplitude and ⬍% peristalsis in the DE (48.9 ⫾ 0.1 mmHg; 58%) and ME (41.6 ⫾ 0.1 mmHg; 55%) than AS and GER (p ⬍ 0.05). LSB and SSB were similar. Barrett’s length and height of acid refluxate correlated (p ⬍ 0.05). %time pH < 4.1 Total P MP MD D Supine P MP MD D Upright P MP MD D

AS (n ⴝ 15)

GER (n ⴝ 15)

SSB (n ⴝ 16)

LSB (n ⴝ 15)

1.3 ⫾ 0.6abc 2.1 ⫾ 0.4abc 2.6 ⫾ 0.6abc 4.3 ⫾ 0.8abc 1.3 ⫾ 1.2 0.9 ⫾ 0.6abc 0.7 ⫾ 0.3bc 1.9 ⫾ 0.9bc 1.5 ⫾ 0.4abc 3.0 ⫾ 0.6abc 4.1 ⫾ 0.9abc 6.5 ⫾ 1.2abc

4.0 ⫾ 0.9 7.2 ⫾ 1.3 9.2 ⫾ 2.0 14.5 ⫾ 3.7 3.1 ⫾ 1.4 7.0 ⫾ 2.0 7.9 ⫾ 3.3 12.4 ⫾ 5.0 4.5 ⫾ 1.1 6.7 ⫾ 1.4 9.5 ⫾ 1.8d 15.2 ⫾ 2.8d

5.4 ⫾ 1.3 9.9 ⫾ 1.8e 13.5 ⫾ 1.8e 20.7 ⫾ 3.4 3.9 ⫾ 1.6 8.3 ⫾ 2.9 10.7 ⫾ 3.2e 14.9 ⫾ 4.1e 6.0 ⫾ 1.5 10.4 ⫾ 1.7e 14.9 ⫾ 1.8e 24.1 ⫾ 3.2

6.5 ⫾ 1.6 18.2 ⫾ 3.3 27.6 ⫾ 5.3 36.4 ⫾ 7.2 7.9 ⫾ 3.3 19.8 ⫾ 5.2 27.2 ⫾ 5.8 37.2 ⫾ 8.9 6.1 ⫾ 1.3 17.7 ⫾ 2.5 28.0 ⫾ 5.1 36.7 ⫾ 6.2

p ⬍ 0.05; a: AS vs GER; b: AS vs SSB; c: AS vs LSB; d: GER vs SSB; e: SSB vs LSB.

Conclusions: 1) Manometry in LSB is different than AS and GER but similar to SSB; 2) Height of acid refluxate and length of Barrett’s correlate; 3) SSB had ⬎ total and upright acid contact time in the mid-proximal and mid-distal and ⬎ supine contact time in the distal and mid-distal channels than SSB Pts.

67 Clinical impact of endoscopic ultrasound guided fine needle aspiration in the management of esophageal carcinoma K Parmar MD, J Zwischenberger MD, I Waxman MD. Gastrointestinal Cancer Center, The University of Texas Medical Branch, Galveston, Texas. Purpose: Endoscopic Ultrasound (EUS) has become the most accurate modality for local regional staging of gastrointestinal cancer. Our purpose was to determine whether EUS guided fine needle aspiration (FNA) had any impact on the management of esophageal carcinoma in terms of resectability and neoadjuvant therapy (chemotherapy/radiation).

Methods: The records of 33 consecutive patients diagnosed with esophageal cancer who were referred to our department for EUS staging were reviewed. Their CT scan findings, EUS stage, including involvement celiac node (M1a stage), surgical pathology and subsequent treatment were noted. Results: There were 19 (58%) FNA biopsies done from a total of 33 procedures. Thirteen (68%) EUS guided FNA were done on the celiac nodes. In this group 11 (85%) were positive for malignancy, which went for chemo/radiation treatment and two (15%) FNA were negative for malignancy, these underwent surgical resection. The CT scan was able to detect only 5 (38%) cases of enlarged celiac lymph nodes out of which 4 (80%) were positive. M1a stage

Sensitivity

Specificity

Accuracy

CT EUS EUS FNA

36% 100% 100%

50% 50% 100%

38% 87% 100%

Conclusion: 1. EUS guided FNA changed management in 100% of patients with enlarged celiac nodes and esophageal cancer by selecting patients who could benefit from up-front chemotherapy/radiation or surgery. 2. EUS guided FNA was superior to EUS by down-staging 2 patients with celiac nodes on imaging. 3. In addition, EUS guided FNA is definitely a superior to CT scan at predicting M1a disease. In summary EUS guided FNA has an important role in esophageal cancer when used in conjunction with stage oriented treatment protocols.

68 Endoscopic therapy for gastroesophageal reflux disease (GERD): Initial experience with Bard endoscopic suturing system (BESS) and Stretta Heiko Pohl, MD, Kim M Wood, RN, Richard I Rothstein, MD, FACG*. Dartmouth Hitchcock Medical Center, Lebanon, NH, United States. Purpose: Two novel endoscopic therapies have recently been approved for the treatment of GERD. Previous options for patients with GERD have been limited to long-term use of anti-secretory medications or surgical interventions. The surgical approach most commonly used is laparoscopic Nissen fundoplication, which requires general anesthesia, admission to hospital, post-op limitation on lifestyle for days to weeks, and some post-op morbidity and side-effects. We reviewed our initial series of patients treated with BESS or Stretta with respect to initial performance characteristics: time to perform procedures, anesthesia requirements and procedure related morbidities. Methods: For all patients undergoing BESS or Stretta treatments at our institution, data was collected on the time to perform the complete procedure, the anesthesia required, and procedure-related complications, among other parameters. We compared the time to perform procedures and medication useage between BESS and Stretta patients utilizing the Student t-test for two-tailed distribution and two-sample unequal variance. Results: Our initial experience with endoscopic GERD therapy was in 21 patients (BESS 2F/11M, Stretta 4F/4M). Mean age for BESS was 50.85 yrs (range 33–76) and that for Stretta was 49.75 (range 21–79). The mean time to perform the BESS procedure was 63.23 ⫾ 19.78 minutes, and that for Stretta was 75.75 ⫾ 8.38, (p ⫽ 0.06). Meperidine and midazolam conscious sedation was used for all procedures. Mean dosage of meperidine for BESS was 230.77 ⫾ 76.48 mg and for Stretta was 228.13 ⫾ 64.69, (p ⫽ 0.19). Mean dose of midazolam for BESS was 2.04 ⫾ 0.32 mg, and for Stretta was 2.69 ⫾ 1.25, (p ⫽ 0.19). No significant complications followed either procedure type, and all subjects were treated in a same day outpatient setting. One BESS patient experienced nausea and vomiting following the procedure, attributed to the anesthesia, and required additional hours of iv fluids and observation, while all other patients were discharged following 1 to 3 hours of post-procedural observation. No restrictions on lifestyle were instituted following the procedures. Conclusions: These two new endoscopic therapies for GERD can safely be performed in outpatient settings utilizing conscious sedation for anesthesia.