- Email: [email protected]
Telomerase and photodynamic therapy of Barrett’s esophagus
AJG – September, Suppl., 2002
Abstracts
Indication
N
Positive for GERD (%)
Document GERD prior to surgery Possible GERD with negative PPI trial (off Rx) Evaluate response to PPI (on Rx) Possible supraesophageal GERD Noncardiac chest pain Evaluate response to Stretta Prior failed pH test
8 6* 3 3 3 2 1
8 (100%) 2 (40%) 2 (66%) 0 (0%) 2 (66%) 1 (50%) 0 (0%)
* No data obtained due to data recorder failure in one patient in this group.
104 TELOMERASE AND PHOTODYNAMIC THERAPY OF BARRETT’S ESOPHAGUS Kenneth K. Wang, M.D.*, Marlys Anderson, B.S., Navtej S. Buttar, M.D., WongKeeSong Michel, M.D. and Luzke Lori. Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.
S35
symptom severity. Heartburn resolution by day 7 was defined as no heartburn for the 7 consecutive days after starting therapy. Esophagitis was graded according to a standardized scale. A multiple linear logistic regression with backward selection was used to identify factors that significantly influenced complete early heartburn resolution. Results: By day 7, 52% of patients had sustained heartburn resolution. There were statistically significant correlations between resolution of heartburn and gender (p⫽0.0001), baseline maximum heartburn severity (p⫽0.0001) and baseline grade of esophagitis (p⫽0.0058). No statistically significant correlations were noted between heartburn resolution and age or Hp status. The probability of early sustained resolution increased significantly in males, in subjects with milder day or nocturnal heartburn, and in those with a higher esophagitis grade (grade 3 or 4). Conclusions: In erosive esophagitis patients treated with PPIs, men with milder day or nocturnal heartburn and with severe erosive esopahgitis are most likely to have complete early symptom resolution.
106 Purpose: Photodynamic therapy (PDT) has been used to treat Barrett’s esophagus with high– grade dysplasia (HGD). However, the results can be difficult to predict and stricture rates are not inconsequential. The ability to better define patients suitable for treatment will be essential for greater progress with this therapy. Aim: To determine if telomerase activity may help predict responders to PDT in patients with high– grade dysplasia. Methods: Seven consecutive patients with histological confirmation of Barrett’s esophagus with HGD by two expert pathologists were studied. All were male, median age 74, who were treated with PDT using Photofrin 2 at a dose of 2.0 mg/kg administered intravenously 48 hours prior to photoradiation. Photoradiation was conducted at a dose of 200 joules/cm fiber with a 5 cm cylindrical diffusing fiber using a Diomed laser at a power output of 2 watts. All pts were placed on proton–pump inhibitors for relief of symptoms. Pts were monitored every 3 months to examine the results of PDT. Biopsies were taken in 4 – quadrants every cm. Telomerase activity was measured using TRAPeze(Intergen, Purchase, NY) Results: 6/7 (86%) were positive for hTERT activity prior to photodynamic therapy. Histology was only downgraded in 4/7 (57%) 3 months following the procedure while hTERT activity was still elevated in 5/7 (71%) of patients. The one patients who was hTERT negative before treatment became hTERT positive after treatment and had persistent HGD. Conclusions: PDT may eliminate HGD in some patients with Barrett’s esophagus. However, the presence of telomerase activity may be a predictor of patients who are less responsive to PDT. This may be the result of immortalized cell clones that are resistant to therapy.
105 BASELINE PREDICTORS OF EARLY SYMPTOM RESOLUTION IN EROSIVE ESOPHAGITIS Thomas G. Kovacs, M.D.*, Robyn L. Altman, B.S.N., Betsy Pilmer, R.N. and Bidan Huang, Ph.D. CURE/Digestive Diseases Research Center, UCLA, Los Angeles, CA; TAP Pharmaceutical Products Inc., Lake Forrest, IL and Abbott Laboratories, Abbott Park, IL. Purpose: Symptomatic improvement is the main therapeutic endpoint for gastroesophageal reflux disease (GERD). This study determined whether baseline factors such as heartburn severity, esophagitis grade, age, gender and Helicobacter pylori (Hp) status influenced early heartburn resolution in subjects with reflux esophagitis treated with proton pump inhibitors (PPIs). Methods: 3500 patients enrolled in an 8 –week blinded, randomized, multicenter trial comparing lansoprazole 30 mg to omeprazole 20 mg daily for the relief of heartburn in endoscopically documented erosive esophagitis were evaluated prospectively. Patients daily symptom scores prior to enrollment and after randomization were used to assess GERD–related
LONG–TERM SAFETY AND TOLERABILITY OF RABEPRAZOLE IN PATIENTS WITH EROSIVE OR ULCERATIVE GERD Frank Lanza, M.D.*, Antonio Caos, M.D., Yogeshwar Dayal, M.D., William Hahne, M.D. and Jay Barth, M.D. Houston Inst Clin Research, Houston, TX; Cntrl FL Clin Studies, Ocoee, FL; Dept Pathology, NE Med Cntr, Boston, MA and Clin R&D, Eisai Inc., Teaneck, NJ. Purpose: To compare long–term safety of rabeprazole (R) 20 mg qam, R 10 mg qam, and placebo (P) qam for maintenance treatment of patients previously diagnosed with erosive or ulcerative gastroesophageal reflux disease (GERD). Methods: 497 patients entered 2 multicenter, double– blind, placebo– controlled parallel–arm maintenance studies and were randomly assigned to R 10 mg, R 20 mg, or P. After 1 year of successful treatment, patients continued in an extension phase for up to 4 years (total ⫽ 5 years). Safety evaluations included treatment– emergent signs and symptoms (TESS); serious adverse events (SAEs); serum gastrin levels; histologic assessments of corpus mucosa; and Solcia classification of enterochromaffin–like (ECL) cell hyperplasia. Results: Mean duration of participation in the study was 864, 742, and 259 days for the R 20 mg, 10 mg, and P, respectively. Over 5 years, ⱖ1 TESS was reported by 90% of patients in the R 20 mg group; 87%, R 10 mg group; and 62%, P group (P⬍0.001, R vs P). Most TESS were mild, and only 42 patients (8%) reported TESS possibly related to the medication. More SAEs occurred in the R groups than the P group—R 20 mg, 24%; R 10 mg, 19%; P, 5% (P⬍0.001, R vs P); only 1 SAE was considered related to the study drug, which occurred in the P group. Over the study period, prevalence of hypergastrinemia (fasting serum gastin ⬎100 pg/mL) rose 10% to 20% with R treatment and decreased with P compared with baseline; at the end of 5 years, however, median serum gastrin values were in the normal range for all 3 groups. A small number of patients developed atrophy (R 20 mg, 7; R 10 mg, 4; P, 1) or metaplasia (R 20 mg, 3; R 10 mg, 1). In most cases, H pylori, inflammation, and infection–activity present at baseline did not progress during the study. A trend toward increased incidence of ECL hyperplasia was seen with both R groups, but in most cases, on–study progression in ECL hyperplasia did not occur. No biopsy in 5 years showed adenomatoid, dysplastic, or neoplastic changes in ECL cells. Conclusions: R proved safe and well tolerated in the maintenance of GERD healing. Long–term treatment was not associated with significant ECL– cell pathology or with changes in H pylori infection, inflammation, activity, atrophy or intestinal metaplasia. R only slightly elevated the prevalence of hypergastrinemia, and median serum gastrin remained within normal limits after 5 years.
Abstracts
Indication
N
Positive for GERD (%)
Document GERD prior to surgery Possible GERD with negative PPI trial (off Rx) Evaluate response to PPI (on Rx) Possible supraesophageal GERD Noncardiac chest pain Evaluate response to Stretta Prior failed pH test
8 6* 3 3 3 2 1
8 (100%) 2 (40%) 2 (66%) 0 (0%) 2 (66%) 1 (50%) 0 (0%)
* No data obtained due to data recorder failure in one patient in this group.
104 TELOMERASE AND PHOTODYNAMIC THERAPY OF BARRETT’S ESOPHAGUS Kenneth K. Wang, M.D.*, Marlys Anderson, B.S., Navtej S. Buttar, M.D., WongKeeSong Michel, M.D. and Luzke Lori. Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.
S35
symptom severity. Heartburn resolution by day 7 was defined as no heartburn for the 7 consecutive days after starting therapy. Esophagitis was graded according to a standardized scale. A multiple linear logistic regression with backward selection was used to identify factors that significantly influenced complete early heartburn resolution. Results: By day 7, 52% of patients had sustained heartburn resolution. There were statistically significant correlations between resolution of heartburn and gender (p⫽0.0001), baseline maximum heartburn severity (p⫽0.0001) and baseline grade of esophagitis (p⫽0.0058). No statistically significant correlations were noted between heartburn resolution and age or Hp status. The probability of early sustained resolution increased significantly in males, in subjects with milder day or nocturnal heartburn, and in those with a higher esophagitis grade (grade 3 or 4). Conclusions: In erosive esophagitis patients treated with PPIs, men with milder day or nocturnal heartburn and with severe erosive esopahgitis are most likely to have complete early symptom resolution.
106 Purpose: Photodynamic therapy (PDT) has been used to treat Barrett’s esophagus with high– grade dysplasia (HGD). However, the results can be difficult to predict and stricture rates are not inconsequential. The ability to better define patients suitable for treatment will be essential for greater progress with this therapy. Aim: To determine if telomerase activity may help predict responders to PDT in patients with high– grade dysplasia. Methods: Seven consecutive patients with histological confirmation of Barrett’s esophagus with HGD by two expert pathologists were studied. All were male, median age 74, who were treated with PDT using Photofrin 2 at a dose of 2.0 mg/kg administered intravenously 48 hours prior to photoradiation. Photoradiation was conducted at a dose of 200 joules/cm fiber with a 5 cm cylindrical diffusing fiber using a Diomed laser at a power output of 2 watts. All pts were placed on proton–pump inhibitors for relief of symptoms. Pts were monitored every 3 months to examine the results of PDT. Biopsies were taken in 4 – quadrants every cm. Telomerase activity was measured using TRAPeze(Intergen, Purchase, NY) Results: 6/7 (86%) were positive for hTERT activity prior to photodynamic therapy. Histology was only downgraded in 4/7 (57%) 3 months following the procedure while hTERT activity was still elevated in 5/7 (71%) of patients. The one patients who was hTERT negative before treatment became hTERT positive after treatment and had persistent HGD. Conclusions: PDT may eliminate HGD in some patients with Barrett’s esophagus. However, the presence of telomerase activity may be a predictor of patients who are less responsive to PDT. This may be the result of immortalized cell clones that are resistant to therapy.
105 BASELINE PREDICTORS OF EARLY SYMPTOM RESOLUTION IN EROSIVE ESOPHAGITIS Thomas G. Kovacs, M.D.*, Robyn L. Altman, B.S.N., Betsy Pilmer, R.N. and Bidan Huang, Ph.D. CURE/Digestive Diseases Research Center, UCLA, Los Angeles, CA; TAP Pharmaceutical Products Inc., Lake Forrest, IL and Abbott Laboratories, Abbott Park, IL. Purpose: Symptomatic improvement is the main therapeutic endpoint for gastroesophageal reflux disease (GERD). This study determined whether baseline factors such as heartburn severity, esophagitis grade, age, gender and Helicobacter pylori (Hp) status influenced early heartburn resolution in subjects with reflux esophagitis treated with proton pump inhibitors (PPIs). Methods: 3500 patients enrolled in an 8 –week blinded, randomized, multicenter trial comparing lansoprazole 30 mg to omeprazole 20 mg daily for the relief of heartburn in endoscopically documented erosive esophagitis were evaluated prospectively. Patients daily symptom scores prior to enrollment and after randomization were used to assess GERD–related
LONG–TERM SAFETY AND TOLERABILITY OF RABEPRAZOLE IN PATIENTS WITH EROSIVE OR ULCERATIVE GERD Frank Lanza, M.D.*, Antonio Caos, M.D., Yogeshwar Dayal, M.D., William Hahne, M.D. and Jay Barth, M.D. Houston Inst Clin Research, Houston, TX; Cntrl FL Clin Studies, Ocoee, FL; Dept Pathology, NE Med Cntr, Boston, MA and Clin R&D, Eisai Inc., Teaneck, NJ. Purpose: To compare long–term safety of rabeprazole (R) 20 mg qam, R 10 mg qam, and placebo (P) qam for maintenance treatment of patients previously diagnosed with erosive or ulcerative gastroesophageal reflux disease (GERD). Methods: 497 patients entered 2 multicenter, double– blind, placebo– controlled parallel–arm maintenance studies and were randomly assigned to R 10 mg, R 20 mg, or P. After 1 year of successful treatment, patients continued in an extension phase for up to 4 years (total ⫽ 5 years). Safety evaluations included treatment– emergent signs and symptoms (TESS); serious adverse events (SAEs); serum gastrin levels; histologic assessments of corpus mucosa; and Solcia classification of enterochromaffin–like (ECL) cell hyperplasia. Results: Mean duration of participation in the study was 864, 742, and 259 days for the R 20 mg, 10 mg, and P, respectively. Over 5 years, ⱖ1 TESS was reported by 90% of patients in the R 20 mg group; 87%, R 10 mg group; and 62%, P group (P⬍0.001, R vs P). Most TESS were mild, and only 42 patients (8%) reported TESS possibly related to the medication. More SAEs occurred in the R groups than the P group—R 20 mg, 24%; R 10 mg, 19%; P, 5% (P⬍0.001, R vs P); only 1 SAE was considered related to the study drug, which occurred in the P group. Over the study period, prevalence of hypergastrinemia (fasting serum gastin ⬎100 pg/mL) rose 10% to 20% with R treatment and decreased with P compared with baseline; at the end of 5 years, however, median serum gastrin values were in the normal range for all 3 groups. A small number of patients developed atrophy (R 20 mg, 7; R 10 mg, 4; P, 1) or metaplasia (R 20 mg, 3; R 10 mg, 1). In most cases, H pylori, inflammation, and infection–activity present at baseline did not progress during the study. A trend toward increased incidence of ECL hyperplasia was seen with both R groups, but in most cases, on–study progression in ECL hyperplasia did not occur. No biopsy in 5 years showed adenomatoid, dysplastic, or neoplastic changes in ECL cells. Conclusions: R proved safe and well tolerated in the maintenance of GERD healing. Long–term treatment was not associated with significant ECL– cell pathology or with changes in H pylori infection, inflammation, activity, atrophy or intestinal metaplasia. R only slightly elevated the prevalence of hypergastrinemia, and median serum gastrin remained within normal limits after 5 years.