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Unusual clinical courses of gastrinoma
76
Abstracts from the l l th h~ternational Symposium on Regulatory Peptides
EFFECT OF NONPEPTIDE NEUROTENSIN RECEPTOR ANTAGONIST (SR48692) ON GROWTH OF MOUSE SMALL INTESTINE. Kazuhiro Iwase, M.D., B. Mark Evers, M.D., Shunichi Higashide, Ph.D., M.D., Mark R. Hellmich, Ph.D., and Courtney M. Townsend, Jr., M.D. Department of Surgery, The University of Texas Medical Branch, Galveston, Texas, U.S.A. Neurotensin (NT), a gut tridecapeptide, stimulates growth of normal gut mucosa and certain human colon and pancreatic cancers; administration of NT also stimulates the growth of the small intestine in nude mice. Recently, SR48692 (SR), a nonpeptide NT receptor antagonist, has been developed which blocks the high-affinity, biologically-active NT receptor and the trophic effect of NT on the human pancreatic cancer cell line MIA-PaCa-2; the effect of SR on normal gut growth is not known. The purpose of our study was to determine the effect of SR on NT-mediated growth of small intestine in nude mice. Methods. Athymic nude mice (n = 28) were randomized into four groups to receive either vehicle (Control), NT (600 p.g/kg), SR (2 mg/kg), or NT + SR administered s.c., tid, for 30 days; body weight was measured weekly. Weight, protein, and DNA content of jejunum and ileum were measured at sacrifice (day 30). (Data are expressed as mean+SEM; * = p < 0 . 0 5 vs. Control; t = p < O . 0 5 vs. NT alone). Results. NT significantly increased weight, protein and DNA contents of the jejunum and protein content of the ileum; SR significantly blocked the trophic effects of NT on the small bowel; SR alone did not significantly decrease any parameter of 4of t growth in the jejunum or ileum. Con,oo ~ ~= N I t _ clusions. Administration of NT stimulates growth of the small bowel in a 20~~ 0 0 differential fashion with a more draJejunum Ileum Jejunum Ileum Jejunum Ileum matic effect on jejunal mucosa. SR competively antagonized the trophic effect of exogenous NT on the small bowel whereas SR alone did not affect gut growth suggesting that endogenous NT may not be required to maintain normal gut growth. Our study is the first to demonstrate that the NT receptor antagonist SR can block the trophic effects of NT on normal gut in vivo.
UNUSUAL
CLINICAL
COURSES
OF
GASTRINOMA
M. JABLONSK~ , R. Hyrdel IVth Med~!'ical Clinlc,Charles U n l v e r s i t y , P r a g u e , C z e c h Med~ical Clinic, Martin, Slovakia .
Republic and IInd
Gastrinomas may present with unusual features w h i ~ do not rise any suspicion of the disease . This may be particularly important in regions where a complex diagnosis of gastrinoma is not a common p r o c e d u r e . Here we report four such cases with delay in the diagnosis . I/ a male /43/ with an 8 year history of intermittent diarrhoe developed acute diffuse peritonitis due to Jejunal perforation . A year later a new perforation ocoured in the same l o c a t i o n ~ a peptic ulcer was diagnosed in the resected specimen ; serum gastri~ testing and imaging confirmed a gastrlnoma - 2/ a female /46/ with an 11 year history of recurring uncomplicated duodenal ulcer developed severe upper gastrointestinal bleeding ; after a s e c o n d attack a pancreatic g~strlnoma was diagnosed - 3/ a female /53/ with a 14 year mild to moderate course of recurring duodenal ulcer and chronic viral hepatitis B developed space occurylng lesions in the right liver lobe ; primary liver cancer was suspected but not confirmed by US gulded biopsy ; autopsy revealed surprisingly a pancreatic gastriaoma - 4/ in a male /41/ 9 years after partial gastrectomy for peptic ulcer and some upper gastrointestinal symptoms urgent endoscopy perf-ormed for acute uppe gastrointestinal bleeding revealed a deep anastomotlc ulcer ; after re-operatlon a pancreatic gastrlnoma was diagnosed . - Conclusions : Gastrinoma should be suspected more frequently not only in recurring duodenal ulcer , but also in some less characteristic clinical pictures . Patients referral in due time to a special unit to achieve an early diagnosis appears to be vitally important .
Abstracts from the l l th h~ternational Symposium on Regulatory Peptides
EFFECT OF NONPEPTIDE NEUROTENSIN RECEPTOR ANTAGONIST (SR48692) ON GROWTH OF MOUSE SMALL INTESTINE. Kazuhiro Iwase, M.D., B. Mark Evers, M.D., Shunichi Higashide, Ph.D., M.D., Mark R. Hellmich, Ph.D., and Courtney M. Townsend, Jr., M.D. Department of Surgery, The University of Texas Medical Branch, Galveston, Texas, U.S.A. Neurotensin (NT), a gut tridecapeptide, stimulates growth of normal gut mucosa and certain human colon and pancreatic cancers; administration of NT also stimulates the growth of the small intestine in nude mice. Recently, SR48692 (SR), a nonpeptide NT receptor antagonist, has been developed which blocks the high-affinity, biologically-active NT receptor and the trophic effect of NT on the human pancreatic cancer cell line MIA-PaCa-2; the effect of SR on normal gut growth is not known. The purpose of our study was to determine the effect of SR on NT-mediated growth of small intestine in nude mice. Methods. Athymic nude mice (n = 28) were randomized into four groups to receive either vehicle (Control), NT (600 p.g/kg), SR (2 mg/kg), or NT + SR administered s.c., tid, for 30 days; body weight was measured weekly. Weight, protein, and DNA content of jejunum and ileum were measured at sacrifice (day 30). (Data are expressed as mean+SEM; * = p < 0 . 0 5 vs. Control; t = p < O . 0 5 vs. NT alone). Results. NT significantly increased weight, protein and DNA contents of the jejunum and protein content of the ileum; SR significantly blocked the trophic effects of NT on the small bowel; SR alone did not significantly decrease any parameter of 4of t growth in the jejunum or ileum. Con,oo ~ ~= N I t _ clusions. Administration of NT stimulates growth of the small bowel in a 20~~ 0 0 differential fashion with a more draJejunum Ileum Jejunum Ileum Jejunum Ileum matic effect on jejunal mucosa. SR competively antagonized the trophic effect of exogenous NT on the small bowel whereas SR alone did not affect gut growth suggesting that endogenous NT may not be required to maintain normal gut growth. Our study is the first to demonstrate that the NT receptor antagonist SR can block the trophic effects of NT on normal gut in vivo.
UNUSUAL
CLINICAL
COURSES
OF
GASTRINOMA
M. JABLONSK~ , R. Hyrdel IVth Med~!'ical Clinlc,Charles U n l v e r s i t y , P r a g u e , C z e c h Med~ical Clinic, Martin, Slovakia .
Republic and IInd
Gastrinomas may present with unusual features w h i ~ do not rise any suspicion of the disease . This may be particularly important in regions where a complex diagnosis of gastrinoma is not a common p r o c e d u r e . Here we report four such cases with delay in the diagnosis . I/ a male /43/ with an 8 year history of intermittent diarrhoe developed acute diffuse peritonitis due to Jejunal perforation . A year later a new perforation ocoured in the same l o c a t i o n ~ a peptic ulcer was diagnosed in the resected specimen ; serum gastri~ testing and imaging confirmed a gastrlnoma - 2/ a female /46/ with an 11 year history of recurring uncomplicated duodenal ulcer developed severe upper gastrointestinal bleeding ; after a s e c o n d attack a pancreatic g~strlnoma was diagnosed - 3/ a female /53/ with a 14 year mild to moderate course of recurring duodenal ulcer and chronic viral hepatitis B developed space occurylng lesions in the right liver lobe ; primary liver cancer was suspected but not confirmed by US gulded biopsy ; autopsy revealed surprisingly a pancreatic gastriaoma - 4/ in a male /41/ 9 years after partial gastrectomy for peptic ulcer and some upper gastrointestinal symptoms urgent endoscopy perf-ormed for acute uppe gastrointestinal bleeding revealed a deep anastomotlc ulcer ; after re-operatlon a pancreatic gastrlnoma was diagnosed . - Conclusions : Gastrinoma should be suspected more frequently not only in recurring duodenal ulcer , but also in some less characteristic clinical pictures . Patients referral in due time to a special unit to achieve an early diagnosis appears to be vitally important .