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High prevalence of adenomas and microadenomas of the duodenal papilla and periampullary region in patients with familial adenomatous polyposis
STOMACH AND DUODENUM "[249
"251
REBAMIPIDE, A GASTROPROTECTIVE DRUG, IMPROVES QUALITY OF HEALING AND DECREASES RECURRENCE OF GASTRIC ULCER WITHOUT AFFECTING HELICOBACTER PYLORI STATUS. Tetsun Arakaw'a: Hkoko Nebiki,*, Kazuhide Higuehi, Kiyotaka Okawa,* Hideaki Yamada,* Shigeyoshi Harihara,* Kenji Ando, Toshiyuki Uchida, Hireyuki Ito, Takashi Fukuda, and Kenzo Kobayashi. Third Dept. of Internal Medicine, Osaka City University Medical School and *Dept. of Gastroenterology, Osaka City General Hospital, Osaka Japan Introduction: Rebamipide, a gastroprotective drug developed in Japan, administered during healing of experimental gastric ulcers reduces recurrence (Dig Dis Sci 1995; 40: 2469-2472). Aim: We examined the effects of rebamipide giving during healing of gastric ulcers on inflammatory cell infiltration at the ulcer site and ulcer recurrence. Methed : Sixtypatients with gastric ulcers not related to NSAID intake and with H. py/on" infection were randomly allocated to three treatment groups, Group O (n = 20) received 20 mg of omeprazole u .i.d. for 8 weeks, group OM (n = 20) received the same dose of omeprazole u,i.d, and 300 mg of rebamipide t.i.d, for 8 weeks, and group OA (n = 20) received the same dose of omeprazole for 8 weeks and 1500 mg of amoxicillin t.i.d, for the first 2 weeks. After this treatment ended no medication was given. An endoscopic examination were done at the end of therapy for calculation of the healing rate, 1 month later for the rate of cure of the infection with H.pylori, every 3 months of follow-op for the recurrence rate. At the end of therapy, biopsy specimens were taken from the gastric olccr scar and inspected under the microscope for ncutrophil infiltration, scored as 0 = none Idr 2 = moderatq and 3 = severe. Results: Gmap Healing rate of" Cure rate of H.pylori- Score for neotrophil ulcer infection infiltration O 19/20 (96%) 0/20 (0%) 1.6 • 1.1 OM 20/20 (100%) 0/20 (0%) 0.9 • 1.0" OA 20/20 (100%) 13/20 (65%) 0.8 • 1.0" *:p < 0.05 vs. group O (~ Conclusion: Rebamipide is almost ~lee ~ equipotent for reduction of recurrence of ulcers compared with amoxicillin 9 when administered with omeprazole.
FINAL RESULTS: R E B L E E D I N G F R O M P E P T I C ULCERS ASSOCIATED W I T H A D H E R E N T CLOTS: A P R O S P E C T I V E RANDOMIZED CONTROLLED STUDY COMPARING ENDOSCOPIC T H E R A P Y W I T H M E D I C A L THERAPY. C.J. Gostout, M.J. Shaw, R.F. Keate, W.V. Hat'ford, W. Bracy Jr, D. Magee, D.E. Fleischer and the Adherent Clot Study Group. University of Cincinnati Med Center, Cincinnati, OH; Mayo Clinic, Rochester, MN, and Scottsdale, AZ; Park Nicollet Med Center, Minneapolis, MN; VA and Parkland Memorial Hospitals, Dallas, TX; Georgetown University Med Center, Washington, DC. Gastrointestinal bleeding is a leading cause of morbidity and mortality. Rebleeding rates are low with clean ulcer bases and higher with adherent clots and visible vessels. Many endoscopists treat adherent clots hoping to reduce the incidence of rebleeding. It has been suggested that treatment with heater probe or injection may increase rebleeding compared with medical treatment. AIM: To study if treatment with injection followed with heater probe will reduce the incidence of rebleeding in patients with adherent clots. M~,.TJ:[.QD~: Patients at seven centers with gastrointestinal bleeding were consented prior to endoscopy and found to have fresh adherent clots with no active bleeding. Strict criteria were used to define adherent clots. The clot was irrigated with 200 cc of forcibly injected water. Patients were then stratified for center, age, NSAID use and ulcer location, and randomized into treatment with injection and heater probe or medical management. Those randomized to endoscopic therapy had the base of the adherent clot injected with 1/10,000 adrenaline in four quadrants with at least 1 cc in each quadrant. The clot was then removed. With the heater probe set at 30 joules a minimum of 3 coaptive pulses were used until cavitation and adequate coagulation was obtained. All patients received standard medical treatment including omeprazole 20 mg bid. Patients were evaluated for rebleeding for one month. RESULTS: 56 patients were enrolled. Rebleeding rates were 34.3% (12/35) in the medical treatment arm versus 4.8% (1/21) in the endoscopic treatment arm. Data analysis using the Fisher Exact two tailed test of treatment received vs. rehleed indicated significance (p<0.02). ~ : This study answers the question as to whether or not to treat nonbleeding densely adherent clots. Endoscopic treatment with injection of the base of the clot, clot removal, and heater probe coagulation significantly reduces rebleeding rates in patients with peptic ulcer disease with nonbleeding densely adherent clots. Funded in part by an unrestricted grant from Astra Merck.
Daysafteruk~rhcal~x~
be due to improvement of the quality of ulcer healing, seen in the suppression of inflammatory cell infiltration in the scarred tissoe, which results from both cure of//. pylori infection and treatment with a sastrnprotective drug such as rebamip~de.
t"250
HIGH PREVALENCE OF ADENOMAS AND MIEROADENOMAS OF THE DUODENAL PAPILLA AND PERIAMPULLARY REGION IN PATIENTS WITH FAMILIAL ADENOMATOUS POLYPOSIS
Gtor~o Bertonl*, Romano Smsatelll*, Evondro Ntgrlsolt~, Marco Pennazlo' , Paolo rcmstnl ^, Arrlgo Arrlgonf, Maurtxlo Ponz dc L~on~ Phmccsr P. RoaatnP and GtultanoBfdogm*. From the Disemive Eadoscopy (*) and I'athology ~) Smvicm, S. Maria Nuova l-Impital,. Re88io ~ ~ Endmmpy and Service ('3. Deparaz~ of Onenlegy, S. Giovam tlnapitel, Train; Dimion o~
ouuomu~ogy (^), c ~ ~aer~ Hospital, Viacem~ Inm~ut= of Intmua Medicine(o),Univer~ of Medina, Modem,rrALY.
Baclqp'oud/Aims: Patimts with ~ a d m m m o ~ polyposis flAP) are traditionally c~midemt at high risk for duodmal papilla and periampullmT n~phumm, ~ ! ma~nandm repreasating the ~ cause of death in prophylactically colectomized patients (1,2). We aimed at proepectieally evaluate the prevalence, histoingy and clinical sigaiflcance of papillary and periampuilmy macroscopic and micnau:opic almormalifies in a popolation of FAP patieuts, htiemm and methodu: Twenty-five affected patients affermt to three ~ l o g i c dq~rUnems of northm Italy were c a t t i l y investilptted over a 24-numth period by means of end-vinwin8 and side-viewing upper panmdeaonpy. Biopsies were performed of any represenlafive macrosmpic lesion and randomly on normal~.ppenring papillary and pex~mpullmy nmceea. Results: Sevea pationts showed macroscopic adca~nas of the duodenal papilla (DP), 3 of the periampullaW n ~ o n (PR) and 5 in both sites (camuintiv~ p~valence 40%). Six further patients showed macmadenonms in the rest of the duedenum (overall pt~deace 64%). Microscopic a d e ~ m s were identified in 9 and 2 patients in the DP and PR respectively, and in 3 in both sites (overall prevalence 44%), Thus, a total of 17 (68%) patients showed maero- or microndenom~ in these locations. The p~valence rai~d to 72% including a further patient with macrondenom~ in the rest of the duodem~m ouly. Malignancy was not en~mmtered and severe dysplasia was observed oaly in an 8 nun adenoma of the third d u ~ , a l portion. A higher frequency of macmadenomas in the DP and PR was significantly correlated to the presence and number of such lesions in the rest of the duodenum (p=0.04). No other significant association was detected either between micro-, or macroadenom~ in different sites or with the considered demographic, clinical and pathological features Conr study confirms that DP and PR are high p w v a l ~ sites of macro- and m i m i c ~ in FAP patients. H ~ , our data do not support a hi~er frequency and malignancy potential of SUch lesimm when onmpated to polyps in the rest of the duodimum. Nevertheless, these fiedings warrant a periodic, careful examination of the duodenum either with end-viewing or side-viewing endoscopy, the necessity of random biopsies of the DP and PR and the removal of any la~er or rapidly growing lesions detected.
V O L U M E 45, NO. 4, 1997
252 GASTRIC CANCER PREVENTION: MAINLY BAD NEWS. L. Buri and M. Melato, Unit of Endoscopy and Section of Pathological Anatomy of the Dept. of Biomedical Science of the University of Trieste, Maggiore Hospital, ! 34100 Trieste, Italy in the frame of an in-depth study on the epidemiology of gastric cancer (GC) in the Trieste Province (in North-East Italy, at the border with Sloveina), we reconsidered the relationship between Hellcobacter priori infection and GC outbreak. Our sample confirmed that, although much progress in the knowledge of GC pathogenesis has been achieved in the last few years, an effective early diagnosis of the disease is still remote. We took into consideration 258 cases, with fully available clinical data, out of 300 cases of GC diagnosed for the first time by biopsy (65.5%) or at autopsy (34.5%) in the years 1986/88, when ~pylori infection was not treated. If we consider that in the Province about 70% of all deaths undergo autopsy and that all biopsies are centralized in the same Institute, the sample has to be Considered highly represantativc of GC epidcmiology in the geographic area. in all cases the gastric biopsies performed before the diagnosis of GC were obtained from the Pathology Department files; if they were negative for malignancy they were reconsidered with special regard to the presence of H.pylort and other lesions such as inflammation, atrophy, ulcer, intestinal mctaplasia, and dysplasia. Surprisingly, although the Gastroenterology Dopartmcnt is very active in our Province, especially as regards prevention, out of 258 patients only 27 had undergone a gastric biopsy before the positive one for GC; H. pylori was present in 12 cases, inflammation in 16 cases, atrophy in 7 cases, ulcer in 13 cases, intestinal mctaplasia in 9 cases, and dysplasia in 10 cases. On the basis of our data, which relate to an European area with an effective Health System, we may state that in the Trieste Province only 10.5% of all the patients who developed GC in the years 1986/88, had previously undergone endoscopy with biopsy in the presumably long period when they were candidate to, but not affected by, GC. in our opinion, this is explained by the absence of early symptoms in most patients. In conclusion, in our Province, but also in Europe, where an effective prevention of GC is still more a speculative maUer than a real strategy, an effort is needed to identify at least suitable criteria for an earlier diagnosis of this very aggressive disease.
GASTROINTESTINAL ENDOSCOPY
AB87
"251
REBAMIPIDE, A GASTROPROTECTIVE DRUG, IMPROVES QUALITY OF HEALING AND DECREASES RECURRENCE OF GASTRIC ULCER WITHOUT AFFECTING HELICOBACTER PYLORI STATUS. Tetsun Arakaw'a: Hkoko Nebiki,*, Kazuhide Higuehi, Kiyotaka Okawa,* Hideaki Yamada,* Shigeyoshi Harihara,* Kenji Ando, Toshiyuki Uchida, Hireyuki Ito, Takashi Fukuda, and Kenzo Kobayashi. Third Dept. of Internal Medicine, Osaka City University Medical School and *Dept. of Gastroenterology, Osaka City General Hospital, Osaka Japan Introduction: Rebamipide, a gastroprotective drug developed in Japan, administered during healing of experimental gastric ulcers reduces recurrence (Dig Dis Sci 1995; 40: 2469-2472). Aim: We examined the effects of rebamipide giving during healing of gastric ulcers on inflammatory cell infiltration at the ulcer site and ulcer recurrence. Methed : Sixtypatients with gastric ulcers not related to NSAID intake and with H. py/on" infection were randomly allocated to three treatment groups, Group O (n = 20) received 20 mg of omeprazole u .i.d. for 8 weeks, group OM (n = 20) received the same dose of omeprazole u,i.d, and 300 mg of rebamipide t.i.d, for 8 weeks, and group OA (n = 20) received the same dose of omeprazole for 8 weeks and 1500 mg of amoxicillin t.i.d, for the first 2 weeks. After this treatment ended no medication was given. An endoscopic examination were done at the end of therapy for calculation of the healing rate, 1 month later for the rate of cure of the infection with H.pylori, every 3 months of follow-op for the recurrence rate. At the end of therapy, biopsy specimens were taken from the gastric olccr scar and inspected under the microscope for ncutrophil infiltration, scored as 0 = none Idr 2 = moderatq and 3 = severe. Results: Gmap Healing rate of" Cure rate of H.pylori- Score for neotrophil ulcer infection infiltration O 19/20 (96%) 0/20 (0%) 1.6 • 1.1 OM 20/20 (100%) 0/20 (0%) 0.9 • 1.0" OA 20/20 (100%) 13/20 (65%) 0.8 • 1.0" *:p < 0.05 vs. group O (~ Conclusion: Rebamipide is almost ~lee ~ equipotent for reduction of recurrence of ulcers compared with amoxicillin 9 when administered with omeprazole.
FINAL RESULTS: R E B L E E D I N G F R O M P E P T I C ULCERS ASSOCIATED W I T H A D H E R E N T CLOTS: A P R O S P E C T I V E RANDOMIZED CONTROLLED STUDY COMPARING ENDOSCOPIC T H E R A P Y W I T H M E D I C A L THERAPY. C.J. Gostout, M.J. Shaw, R.F. Keate, W.V. Hat'ford, W. Bracy Jr, D. Magee, D.E. Fleischer and the Adherent Clot Study Group. University of Cincinnati Med Center, Cincinnati, OH; Mayo Clinic, Rochester, MN, and Scottsdale, AZ; Park Nicollet Med Center, Minneapolis, MN; VA and Parkland Memorial Hospitals, Dallas, TX; Georgetown University Med Center, Washington, DC. Gastrointestinal bleeding is a leading cause of morbidity and mortality. Rebleeding rates are low with clean ulcer bases and higher with adherent clots and visible vessels. Many endoscopists treat adherent clots hoping to reduce the incidence of rebleeding. It has been suggested that treatment with heater probe or injection may increase rebleeding compared with medical treatment. AIM: To study if treatment with injection followed with heater probe will reduce the incidence of rebleeding in patients with adherent clots. M~,.TJ:[.QD~: Patients at seven centers with gastrointestinal bleeding were consented prior to endoscopy and found to have fresh adherent clots with no active bleeding. Strict criteria were used to define adherent clots. The clot was irrigated with 200 cc of forcibly injected water. Patients were then stratified for center, age, NSAID use and ulcer location, and randomized into treatment with injection and heater probe or medical management. Those randomized to endoscopic therapy had the base of the adherent clot injected with 1/10,000 adrenaline in four quadrants with at least 1 cc in each quadrant. The clot was then removed. With the heater probe set at 30 joules a minimum of 3 coaptive pulses were used until cavitation and adequate coagulation was obtained. All patients received standard medical treatment including omeprazole 20 mg bid. Patients were evaluated for rebleeding for one month. RESULTS: 56 patients were enrolled. Rebleeding rates were 34.3% (12/35) in the medical treatment arm versus 4.8% (1/21) in the endoscopic treatment arm. Data analysis using the Fisher Exact two tailed test of treatment received vs. rehleed indicated significance (p<0.02). ~ : This study answers the question as to whether or not to treat nonbleeding densely adherent clots. Endoscopic treatment with injection of the base of the clot, clot removal, and heater probe coagulation significantly reduces rebleeding rates in patients with peptic ulcer disease with nonbleeding densely adherent clots. Funded in part by an unrestricted grant from Astra Merck.
Daysafteruk~rhcal~x~
be due to improvement of the quality of ulcer healing, seen in the suppression of inflammatory cell infiltration in the scarred tissoe, which results from both cure of//. pylori infection and treatment with a sastrnprotective drug such as rebamip~de.
t"250
HIGH PREVALENCE OF ADENOMAS AND MIEROADENOMAS OF THE DUODENAL PAPILLA AND PERIAMPULLARY REGION IN PATIENTS WITH FAMILIAL ADENOMATOUS POLYPOSIS
Gtor~o Bertonl*, Romano Smsatelll*, Evondro Ntgrlsolt~, Marco Pennazlo' , Paolo rcmstnl ^, Arrlgo Arrlgonf, Maurtxlo Ponz dc L~on~ Phmccsr P. RoaatnP and GtultanoBfdogm*. From the Disemive Eadoscopy (*) and I'athology ~) Smvicm, S. Maria Nuova l-Impital,. Re88io ~ ~ Endmmpy and Service ('3. Deparaz~ of Onenlegy, S. Giovam tlnapitel, Train; Dimion o~
ouuomu~ogy (^), c ~ ~aer~ Hospital, Viacem~ Inm~ut= of Intmua Medicine(o),Univer~ of Medina, Modem,rrALY.
Baclqp'oud/Aims: Patimts with ~ a d m m m o ~ polyposis flAP) are traditionally c~midemt at high risk for duodmal papilla and periampullmT n~phumm, ~ ! ma~nandm repreasating the ~ cause of death in prophylactically colectomized patients (1,2). We aimed at proepectieally evaluate the prevalence, histoingy and clinical sigaiflcance of papillary and periampuilmy macroscopic and micnau:opic almormalifies in a popolation of FAP patieuts, htiemm and methodu: Twenty-five affected patients affermt to three ~ l o g i c dq~rUnems of northm Italy were c a t t i l y investilptted over a 24-numth period by means of end-vinwin8 and side-viewing upper panmdeaonpy. Biopsies were performed of any represenlafive macrosmpic lesion and randomly on normal~.ppenring papillary and pex~mpullmy nmceea. Results: Sevea pationts showed macroscopic adca~nas of the duodenal papilla (DP), 3 of the periampullaW n ~ o n (PR) and 5 in both sites (camuintiv~ p~valence 40%). Six further patients showed macmadenonms in the rest of the duedenum (overall pt~deace 64%). Microscopic a d e ~ m s were identified in 9 and 2 patients in the DP and PR respectively, and in 3 in both sites (overall prevalence 44%), Thus, a total of 17 (68%) patients showed maero- or microndenom~ in these locations. The p~valence rai~d to 72% including a further patient with macrondenom~ in the rest of the duodem~m ouly. Malignancy was not en~mmtered and severe dysplasia was observed oaly in an 8 nun adenoma of the third d u ~ , a l portion. A higher frequency of macmadenomas in the DP and PR was significantly correlated to the presence and number of such lesions in the rest of the duodenum (p=0.04). No other significant association was detected either between micro-, or macroadenom~ in different sites or with the considered demographic, clinical and pathological features Conr study confirms that DP and PR are high p w v a l ~ sites of macro- and m i m i c ~ in FAP patients. H ~ , our data do not support a hi~er frequency and malignancy potential of SUch lesimm when onmpated to polyps in the rest of the duodimum. Nevertheless, these fiedings warrant a periodic, careful examination of the duodenum either with end-viewing or side-viewing endoscopy, the necessity of random biopsies of the DP and PR and the removal of any la~er or rapidly growing lesions detected.
V O L U M E 45, NO. 4, 1997
252 GASTRIC CANCER PREVENTION: MAINLY BAD NEWS. L. Buri and M. Melato, Unit of Endoscopy and Section of Pathological Anatomy of the Dept. of Biomedical Science of the University of Trieste, Maggiore Hospital, ! 34100 Trieste, Italy in the frame of an in-depth study on the epidemiology of gastric cancer (GC) in the Trieste Province (in North-East Italy, at the border with Sloveina), we reconsidered the relationship between Hellcobacter priori infection and GC outbreak. Our sample confirmed that, although much progress in the knowledge of GC pathogenesis has been achieved in the last few years, an effective early diagnosis of the disease is still remote. We took into consideration 258 cases, with fully available clinical data, out of 300 cases of GC diagnosed for the first time by biopsy (65.5%) or at autopsy (34.5%) in the years 1986/88, when ~pylori infection was not treated. If we consider that in the Province about 70% of all deaths undergo autopsy and that all biopsies are centralized in the same Institute, the sample has to be Considered highly represantativc of GC epidcmiology in the geographic area. in all cases the gastric biopsies performed before the diagnosis of GC were obtained from the Pathology Department files; if they were negative for malignancy they were reconsidered with special regard to the presence of H.pylort and other lesions such as inflammation, atrophy, ulcer, intestinal mctaplasia, and dysplasia. Surprisingly, although the Gastroenterology Dopartmcnt is very active in our Province, especially as regards prevention, out of 258 patients only 27 had undergone a gastric biopsy before the positive one for GC; H. pylori was present in 12 cases, inflammation in 16 cases, atrophy in 7 cases, ulcer in 13 cases, intestinal mctaplasia in 9 cases, and dysplasia in 10 cases. On the basis of our data, which relate to an European area with an effective Health System, we may state that in the Trieste Province only 10.5% of all the patients who developed GC in the years 1986/88, had previously undergone endoscopy with biopsy in the presumably long period when they were candidate to, but not affected by, GC. in our opinion, this is explained by the absence of early symptoms in most patients. In conclusion, in our Province, but also in Europe, where an effective prevention of GC is still more a speculative maUer than a real strategy, an effort is needed to identify at least suitable criteria for an earlier diagnosis of this very aggressive disease.
GASTROINTESTINAL ENDOSCOPY
AB87