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20 staining as dysplasia progresses in Barrett's esophagus
April 2000
AGAA1247
5707
5709
THE EFFECT OF H. PYLORI ERADICATION ON MUCOSAL IL·8 AND INFLAMMATION OF GASTRIC METAPLASIA AND GAS· TRODUODENAL MUCOSA IN PATIENTS WITH SCARRED DUODENAL ULCERS.
CHANGES IN CYTOKERATIN 7/20 STAINING AS DYSPLASIA PROGRESSES IN BARRETT'S ESOPHAGUS.
Su Jin Hong, Chang Beom Ryu, Jin Oh Kim, Joo Young Cho, Joon Seong Lee, Moon Sung Lee, So Young Jin, Chan Sup Shim, Institute for Digest Research, Soon Chun Hyang Univ, Seoul, South Korea. Background: The recurrence of duodenal ulcer disease is associated with gastric metaplasia and H. pylori infection. H. pylori-induced inflammatory responses are affected by chemokine in gastroduodenal mucosa. Aim: To evaluate the effect of H. pylori eradication on histological findings and IL-8 protein expression of gastroduodenal mucosa including gastric metaplasia. Methods: Thirty patients with scarred duodenal ulcers and ten volunteers for a control group were undergone endoscopy with methylene blue spray and biopsies. The biopsy specimens were taken from the antrum and unstained/stained duodenal mucosa by methylene blue, which were stained with H&E, Warthin-Starry, and alcian blue-PAS stains. The following features were evaluated and graded from 0 to 3: PMN infiltration, H. pylori density, and gastric metaplasia. Biopsy specimens from the same sites were homogenized in PBS(phosphate buffered saline, pH 7.4) and IL-8 protein was measured by ELISA. The patients with scarred duodenal ulcer and H. pylori infection were taken eradication treatment(OAC, I week)and reevaluated at 3 months(mean) later. Results: Histologically all patients with unstained areas by methylene blue had gastric metaplasia. None in the control group revealed gastric metaplasia. While the detection of duodenal H. pylori was only in the gastric metaplasia, it occurred in only 33.3% of the patients with gastric metaplasia. The grade of gastric metaplsia was no difference before and after eradication treatment. The PMN infiltration and IL-8 protein level of non-metaplastic duodenal mucosa, gastric metaplasia, and antral mucosa in pre-eradicated patients were significantly higher than those in both the control group(p<0.05) and post-eradicated patients(p<0.05). The IL-8 protein level in non-metaplastic duodenal mucosa was significantly lower than that of antrum and gastric metaplasia before eradication treatment(p
5708 DUODENAL ULCER HEALING ASSOCIATED WITH HELICO· BACTER PYLORI CLEARANCE AT THE END OF TREATMENT USING RANITIDINE BISMUTH CITRATE·BASED REGIMENS. Robert J. Hopkins, Cheryl A. Dixon, Joette M. Meyer, U S Food and Drug Admin, Rockville, MD. Background: A single previous study has demonstrated that antibiotics alone were more effective than placebo in healing duodenal ulcers. In addition, clearance of infection contributed significantly to ulcer healing. [Lam et aI., Gut 1997;41:43-8] Aim: To evaluate ulcer healing rates in relation to H. pylori clearance among ranitidine bismuth citrate (RBC) studies submitted to the FDA. Methods: Data from all clinical trials were combined. Patients were included if they had an active duodenal ulcer at baseline, defined as a break in the mucosa 20 5 mm. H. pylori clearance and absence of a duodenal ulcer was assessed at the end of a 4-week treatment. Absence of an ulcer was defined as complete epithelialization of duodenal ulcer and erosions present at the original site of ulcer. Study arms included: placebo, RBC, antibiotic (Abx), and RBC at a dose of 400 mg bid or 800 mg bid + Abx. The antibiotics studied were either amoxicillin or clarithromycin. The significance of differences in ulcer healing between patients with clearance of infection versus those with persistent (uncleared) infection was assessed using Fisher's Exact Test. Results: The inclusion of nine studies with 30 treatment arms resulted in 1381 evaluable patients. Conclusions: These data demonstrate that ulcer healing is increased among patients with cleared infection versus those with uncleared infection. All therapies, including antibiotics alone, demonstrated improved healing rates as compared with placebo.
Group
All Arms Placebo RBC400 1Abx RBC 400 + 1 Abx RBC 800 + 1Abx
UlcerHealing with Clearance ('!o)
UlcerHealing without Clearance ('!o)
P·value
693/872 (79) 0/0 105/120 (88) 17122 (77) 397/550 (72) 174/180 (97)
326/509 (64) 21/63 (33) 1701220 (77) 44/82 (54) 751123 (61) 16/21 (76)
< 0.001 0.022 0.054 0016 0002
1. David Horwhat, Daniel Cruser, Corinne Maydonovitch, Erich Gaertner, Fernando Ramos, Craig Shriver, Roy Kh Wong, Walter Reed Army Med Ctr, Washington, DC; Tripier Army Med Ctr, Honolulu, HI. Background: Recent work from Ormsby et al. (Hum Path 1999;30:288-94) has demonstrated clearly different CK 7/20 patterns for intestinal metaplasia (1M) of gastric versus Barrett's origin. They reported a 100% specificity/positive predictive value for discriminating biopsies with 1M of gastric versus Barrett's origin. These findings suggest the timing of future surveillance endoscopies may be determined by specific CK 7/20 patterns. Aim: To determine whether CK 7120 patterns are I) different between 1M, low-grade dysplasia (LGD), high-grade dysplasia (HGD) and cancer in Barrett's; 2) whether differences in CK 7120 patterns could help guide surveillance practices; and 3) whether methylene blue (MB) staining correlated with CK 7/20 patterns and the presence/degree of dysplasia. Method: An esophagectomy specimen from a 59 year old white male with HGD in a Barrett's esophagus was studied. Immediately upon resection, the esophagus was rinsed ex vivo with acetylcysteine for mucolysis, photographed, stained with MB and photographed again. The esophagus was sectioned into 42 quadrants for histologic diagnosis by H&E stain. The presence, degree and location of dysplasia and carcinoma was mapped onto an outline of the esophagus that displayed the MB staining intensity. 36 of the 42 tissue blocks were suitable to be stained for CK 7/20. Results: I) H&E diagnosed varying amounts of LGD (74%), HGD (69%) or carcinoma (5%) in 38 of 42 biopsies (90% overall). Three slides had only SIM and I only gastric mucosa. 2) As previously reported, superficial CK20 and superficial/deep CK7 staining was noted in the sections with SIM. 3) Interestingly, the CK7 stained all epithelium, (1M, LGD, HGD and carcinoma). 4) However, CK20 stained 1M and LGD but lost intensity in higher grades of dysplasia (HGD). CK20 was superficial or absent in areas with carcinoma. 5) The staining intensity of CK20 was significantly greater (p
5710 THE LONG-TERM OUTCOMES OF THE PATIENTS WITH ACHALASIA TREATED WITH PNEUMATIC DILATATION THE ORIENTAL (TAIWANESE) EXPERIENCE. Yi-Hsin Hsu, Kuo-Ching Yang, Jui-Hao Chen, Yuh-Hwa Liu, Gen-Ming Wang, Wei-Hsu Ko, Liang-Kuang Chen, Ker-Ming Huang, Shin-Kong Wu Ho-Su Memorial Hosp, Taipei, Taiwan, ROC. Back ground Although pneumatic dilatation (PD) has been established as a treatment for achalasia during decades, there are limited data on its long-term clinical efficacy, especially in the oriental countries. Here, we intended to utilize PD to treat Taiwanese patients with achalasia and analyze their long-term outcomes. Materials and Methods From June 1993 to May 1999, 30 patients (16 men, 14 women; mean age: 47 y/o, range: 23-73) with achalasia underwent the PD under the fluoroscopic guidance. A total of 33 PD were performed. The 30-rum Rigiflex achalasia dilator was used for the first PD in all cases, and it was applied for the 2nd PD in only 2 cases, one of these two cases received the 3rd PD with 35-mm dilator. All patients were followed up regularly after the PD. A symptom score was used to assess their clinical outcomes. Both good and excellent results are judged as treatment success. The success rate was analyzed with Kaplan-Meir statistic method. Results All cases tolerated the procedure well. The initial success rate after the first PD was 93.3% (28/30). Repeated dilatations failed to improve one non-responder and one recurrent patient. The one, two, three, four, and five years success rates for the initial responders were 96.0%, 84.9%, 84.9%, 84.9%, 84.9%, respectively. However, the excellent rates were 80.8%, 70.7%, 56.6%, 48.5%, 40.4%, respectively. No esophageal perforation occurred after the PD. Four patients (13%) progressed to GERD after the successful treatment. Conclusion Pneumatic dilatation is also a safe and effective therapy for the oriental people with achalasia. Although in most patients their outcomes remained good or excellent for more than 5 years, the effect tends to decrease during the follow-ups.
AGAA1247
5707
5709
THE EFFECT OF H. PYLORI ERADICATION ON MUCOSAL IL·8 AND INFLAMMATION OF GASTRIC METAPLASIA AND GAS· TRODUODENAL MUCOSA IN PATIENTS WITH SCARRED DUODENAL ULCERS.
CHANGES IN CYTOKERATIN 7/20 STAINING AS DYSPLASIA PROGRESSES IN BARRETT'S ESOPHAGUS.
Su Jin Hong, Chang Beom Ryu, Jin Oh Kim, Joo Young Cho, Joon Seong Lee, Moon Sung Lee, So Young Jin, Chan Sup Shim, Institute for Digest Research, Soon Chun Hyang Univ, Seoul, South Korea. Background: The recurrence of duodenal ulcer disease is associated with gastric metaplasia and H. pylori infection. H. pylori-induced inflammatory responses are affected by chemokine in gastroduodenal mucosa. Aim: To evaluate the effect of H. pylori eradication on histological findings and IL-8 protein expression of gastroduodenal mucosa including gastric metaplasia. Methods: Thirty patients with scarred duodenal ulcers and ten volunteers for a control group were undergone endoscopy with methylene blue spray and biopsies. The biopsy specimens were taken from the antrum and unstained/stained duodenal mucosa by methylene blue, which were stained with H&E, Warthin-Starry, and alcian blue-PAS stains. The following features were evaluated and graded from 0 to 3: PMN infiltration, H. pylori density, and gastric metaplasia. Biopsy specimens from the same sites were homogenized in PBS(phosphate buffered saline, pH 7.4) and IL-8 protein was measured by ELISA. The patients with scarred duodenal ulcer and H. pylori infection were taken eradication treatment(OAC, I week)and reevaluated at 3 months(mean) later. Results: Histologically all patients with unstained areas by methylene blue had gastric metaplasia. None in the control group revealed gastric metaplasia. While the detection of duodenal H. pylori was only in the gastric metaplasia, it occurred in only 33.3% of the patients with gastric metaplasia. The grade of gastric metaplsia was no difference before and after eradication treatment. The PMN infiltration and IL-8 protein level of non-metaplastic duodenal mucosa, gastric metaplasia, and antral mucosa in pre-eradicated patients were significantly higher than those in both the control group(p<0.05) and post-eradicated patients(p<0.05). The IL-8 protein level in non-metaplastic duodenal mucosa was significantly lower than that of antrum and gastric metaplasia before eradication treatment(p
5708 DUODENAL ULCER HEALING ASSOCIATED WITH HELICO· BACTER PYLORI CLEARANCE AT THE END OF TREATMENT USING RANITIDINE BISMUTH CITRATE·BASED REGIMENS. Robert J. Hopkins, Cheryl A. Dixon, Joette M. Meyer, U S Food and Drug Admin, Rockville, MD. Background: A single previous study has demonstrated that antibiotics alone were more effective than placebo in healing duodenal ulcers. In addition, clearance of infection contributed significantly to ulcer healing. [Lam et aI., Gut 1997;41:43-8] Aim: To evaluate ulcer healing rates in relation to H. pylori clearance among ranitidine bismuth citrate (RBC) studies submitted to the FDA. Methods: Data from all clinical trials were combined. Patients were included if they had an active duodenal ulcer at baseline, defined as a break in the mucosa 20 5 mm. H. pylori clearance and absence of a duodenal ulcer was assessed at the end of a 4-week treatment. Absence of an ulcer was defined as complete epithelialization of duodenal ulcer and erosions present at the original site of ulcer. Study arms included: placebo, RBC, antibiotic (Abx), and RBC at a dose of 400 mg bid or 800 mg bid + Abx. The antibiotics studied were either amoxicillin or clarithromycin. The significance of differences in ulcer healing between patients with clearance of infection versus those with persistent (uncleared) infection was assessed using Fisher's Exact Test. Results: The inclusion of nine studies with 30 treatment arms resulted in 1381 evaluable patients. Conclusions: These data demonstrate that ulcer healing is increased among patients with cleared infection versus those with uncleared infection. All therapies, including antibiotics alone, demonstrated improved healing rates as compared with placebo.
Group
All Arms Placebo RBC400 1Abx RBC 400 + 1 Abx RBC 800 + 1Abx
UlcerHealing with Clearance ('!o)
UlcerHealing without Clearance ('!o)
P·value
693/872 (79) 0/0 105/120 (88) 17122 (77) 397/550 (72) 174/180 (97)
326/509 (64) 21/63 (33) 1701220 (77) 44/82 (54) 751123 (61) 16/21 (76)
< 0.001 0.022 0.054 0016 0002
1. David Horwhat, Daniel Cruser, Corinne Maydonovitch, Erich Gaertner, Fernando Ramos, Craig Shriver, Roy Kh Wong, Walter Reed Army Med Ctr, Washington, DC; Tripier Army Med Ctr, Honolulu, HI. Background: Recent work from Ormsby et al. (Hum Path 1999;30:288-94) has demonstrated clearly different CK 7/20 patterns for intestinal metaplasia (1M) of gastric versus Barrett's origin. They reported a 100% specificity/positive predictive value for discriminating biopsies with 1M of gastric versus Barrett's origin. These findings suggest the timing of future surveillance endoscopies may be determined by specific CK 7/20 patterns. Aim: To determine whether CK 7120 patterns are I) different between 1M, low-grade dysplasia (LGD), high-grade dysplasia (HGD) and cancer in Barrett's; 2) whether differences in CK 7120 patterns could help guide surveillance practices; and 3) whether methylene blue (MB) staining correlated with CK 7/20 patterns and the presence/degree of dysplasia. Method: An esophagectomy specimen from a 59 year old white male with HGD in a Barrett's esophagus was studied. Immediately upon resection, the esophagus was rinsed ex vivo with acetylcysteine for mucolysis, photographed, stained with MB and photographed again. The esophagus was sectioned into 42 quadrants for histologic diagnosis by H&E stain. The presence, degree and location of dysplasia and carcinoma was mapped onto an outline of the esophagus that displayed the MB staining intensity. 36 of the 42 tissue blocks were suitable to be stained for CK 7/20. Results: I) H&E diagnosed varying amounts of LGD (74%), HGD (69%) or carcinoma (5%) in 38 of 42 biopsies (90% overall). Three slides had only SIM and I only gastric mucosa. 2) As previously reported, superficial CK20 and superficial/deep CK7 staining was noted in the sections with SIM. 3) Interestingly, the CK7 stained all epithelium, (1M, LGD, HGD and carcinoma). 4) However, CK20 stained 1M and LGD but lost intensity in higher grades of dysplasia (HGD). CK20 was superficial or absent in areas with carcinoma. 5) The staining intensity of CK20 was significantly greater (p
5710 THE LONG-TERM OUTCOMES OF THE PATIENTS WITH ACHALASIA TREATED WITH PNEUMATIC DILATATION THE ORIENTAL (TAIWANESE) EXPERIENCE. Yi-Hsin Hsu, Kuo-Ching Yang, Jui-Hao Chen, Yuh-Hwa Liu, Gen-Ming Wang, Wei-Hsu Ko, Liang-Kuang Chen, Ker-Ming Huang, Shin-Kong Wu Ho-Su Memorial Hosp, Taipei, Taiwan, ROC. Back ground Although pneumatic dilatation (PD) has been established as a treatment for achalasia during decades, there are limited data on its long-term clinical efficacy, especially in the oriental countries. Here, we intended to utilize PD to treat Taiwanese patients with achalasia and analyze their long-term outcomes. Materials and Methods From June 1993 to May 1999, 30 patients (16 men, 14 women; mean age: 47 y/o, range: 23-73) with achalasia underwent the PD under the fluoroscopic guidance. A total of 33 PD were performed. The 30-rum Rigiflex achalasia dilator was used for the first PD in all cases, and it was applied for the 2nd PD in only 2 cases, one of these two cases received the 3rd PD with 35-mm dilator. All patients were followed up regularly after the PD. A symptom score was used to assess their clinical outcomes. Both good and excellent results are judged as treatment success. The success rate was analyzed with Kaplan-Meir statistic method. Results All cases tolerated the procedure well. The initial success rate after the first PD was 93.3% (28/30). Repeated dilatations failed to improve one non-responder and one recurrent patient. The one, two, three, four, and five years success rates for the initial responders were 96.0%, 84.9%, 84.9%, 84.9%, 84.9%, respectively. However, the excellent rates were 80.8%, 70.7%, 56.6%, 48.5%, 40.4%, respectively. No esophageal perforation occurred after the PD. Four patients (13%) progressed to GERD after the successful treatment. Conclusion Pneumatic dilatation is also a safe and effective therapy for the oriental people with achalasia. Although in most patients their outcomes remained good or excellent for more than 5 years, the effect tends to decrease during the follow-ups.