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Treatment of malignant endocrine pancreatic tumors with a new long-acting somatostatin analogue, SMS 201–995
39s
A-073
CHROMOGRANIN IN ENDOCRINE CELLS AND CARCINOIDS OF SMALL INTESTINE Lundqvist M.‘, Wilander E.*, Malmgren M.*, Eriksson B.’ and Oberg K.i Ludwig Institute for Cancer Research’, Uppsala Branch, Clinical Group and Department of Pathology*, Academic Hospital, S-751 8.9Uppsala,Sweden. Silver stains and immunocytochemistry with hormone antisera are current methods for identification and characterization of and/or biogenic amine-producing endocrine peptide cells and tumors in histological sections. It is sometimes desired to visualize two antigens in the same section in such tissues. Several techniques with combinations of different immunotechniques have been reported. However, aviablelightmicroscopicaltechniques for
double immunocytochemicaldetectionof two antigensin the same sectionare allassociated with certainproblems,when two antigens are in the same compartment. For evaluation of endocrine cell and tumor properties we developed novel sequential staining and have restaining techniques for visualization of hormone content and silver staining properties and for demonstrating two antigens in the same compartment. The immunocytochemical staining with chromogranin antibodies and the restaining with either the argentaffin or the argyrophil silver stains revealed that all argentaffin and all argyrophil cells of the small intestinal mucosa were chromogranin immunoreactive. Small intestinal carcinoids were immunoreactive to chromogranin, argyrophil and argentaffin. However, sequential staining showed that the tumor cells varied in their staining properties that some cells were varied in and tumor their staining properties and that some tumor cells were chromogranin positive but silver negative and vice versa. A-074
HISTOPATHOGENESIS Lundqvist M.‘, Ludwig Institute for Academic Pathology2,
OF MID-GUT CARCINOIDS Wilander E.* and Oberg K.’ Uppsala Branch, Clinical Cancer Research’, Hospital, S-751 8S Uppsala, Sweden.
Group and Department
of
Immunocytochemical study was performed on subepithelial neuroendocrine cells of the small of these sites, using antisera to serotonin, nerone-specific intestine, appendix and carcinoids appendix carcinoid were cut serenolase and S-100 protein. One small intestine and one Subepithelial neuroendocrine cells were identified in ially and stained with silver technique. appendix. These cells displayed serotonin and NSE immunoreactivity lamina propria of the surrounded by S-100 protein immunoreactive cells. Appendiceal carcinoids displayed and were component while small intermingled S- 100 protein immunoreactive cells as an integral intestinal S-100 protein immunoreactive cells. There was no apparent carcinoids lacked and the carcinoid tumor of the appendix. connection between the The serial mucosal crypts small intestine showed proliferating aggregates of endocrine cells inside the crypts section from and later on infiltration through the basement membrane into the lamina propria of the mucosa. of appendiceal and small intestinal carcinoids The results indicate that the histopathogenesis are not identical. It is conceivable that appendiceal carcinoids mainly develop from the subepithelial neuroendocrine the periferal nervous system, in cells and are related to opposite to the small intestinal carcinoids, from the intra epithelial endocrine which arise cells derived from the entoderm. A-075
TREATMENT OF MALIGNANT ENDOCRINE PANCREATIC TUMORS WITH A NEW LONG-ACTING SOMATOSTATIN Eriksson ~.+NA~~~~~'K?S ~~e~~~on T.2, Lundqvist G.3, Wide L.3 and Wilander E. Ludwig Institute for Cancer Resfarch, Uppsalg Branch, Clinical Group and Department of Internal Medicine , Radiology , Clinical Chemistry and Pathology , University Hospital, Uppsala, Sweden Nine patients with malignant endocrine pancreatic tumors were treated with a new long-acting somatostatin analogue, SMS 201-995 at doses of 50 pg twice daily, administered subcutaneously. Four out of nine patients syndrome and 3/S with the (44%), one patient with the Zollinger-Ellison WDHA syndrome, responded objectively with more than 50% reduction of peptide levels, median duration 9.5 months. All four patients improved symptomatically. Two additional patients had a clear relief of symptoms without an effect on tumor secreted peptides. Three patients progressed during treatment, one of whom produced excessive amounts of endogenous somatostatln and the therapy resistance presumably depended on down regulation of somatostatin receptors. No reduction of tumor mass was seen in any of the patients, however tumor s=e remained unchanged on CT in all patients during the observation time (mean 6 months). The only main side effect was a slight but maintained increase in fasting blood glucose in four patients. In conclusion, SMS 201-995 had a beneficial effect in more than half of the patients and it seems to be a valuable adjunct to other causal therapy in this patient category.
A-073
CHROMOGRANIN IN ENDOCRINE CELLS AND CARCINOIDS OF SMALL INTESTINE Lundqvist M.‘, Wilander E.*, Malmgren M.*, Eriksson B.’ and Oberg K.i Ludwig Institute for Cancer Research’, Uppsala Branch, Clinical Group and Department of Pathology*, Academic Hospital, S-751 8.9Uppsala,Sweden. Silver stains and immunocytochemistry with hormone antisera are current methods for identification and characterization of and/or biogenic amine-producing endocrine peptide cells and tumors in histological sections. It is sometimes desired to visualize two antigens in the same section in such tissues. Several techniques with combinations of different immunotechniques have been reported. However, aviablelightmicroscopicaltechniques for
double immunocytochemicaldetectionof two antigensin the same sectionare allassociated with certainproblems,when two antigens are in the same compartment. For evaluation of endocrine cell and tumor properties we developed novel sequential staining and have restaining techniques for visualization of hormone content and silver staining properties and for demonstrating two antigens in the same compartment. The immunocytochemical staining with chromogranin antibodies and the restaining with either the argentaffin or the argyrophil silver stains revealed that all argentaffin and all argyrophil cells of the small intestinal mucosa were chromogranin immunoreactive. Small intestinal carcinoids were immunoreactive to chromogranin, argyrophil and argentaffin. However, sequential staining showed that the tumor cells varied in their staining properties that some cells were varied in and tumor their staining properties and that some tumor cells were chromogranin positive but silver negative and vice versa. A-074
HISTOPATHOGENESIS Lundqvist M.‘, Ludwig Institute for Academic Pathology2,
OF MID-GUT CARCINOIDS Wilander E.* and Oberg K.’ Uppsala Branch, Clinical Cancer Research’, Hospital, S-751 8S Uppsala, Sweden.
Group and Department
of
Immunocytochemical study was performed on subepithelial neuroendocrine cells of the small of these sites, using antisera to serotonin, nerone-specific intestine, appendix and carcinoids appendix carcinoid were cut serenolase and S-100 protein. One small intestine and one Subepithelial neuroendocrine cells were identified in ially and stained with silver technique. appendix. These cells displayed serotonin and NSE immunoreactivity lamina propria of the surrounded by S-100 protein immunoreactive cells. Appendiceal carcinoids displayed and were component while small intermingled S- 100 protein immunoreactive cells as an integral intestinal S-100 protein immunoreactive cells. There was no apparent carcinoids lacked and the carcinoid tumor of the appendix. connection between the The serial mucosal crypts small intestine showed proliferating aggregates of endocrine cells inside the crypts section from and later on infiltration through the basement membrane into the lamina propria of the mucosa. of appendiceal and small intestinal carcinoids The results indicate that the histopathogenesis are not identical. It is conceivable that appendiceal carcinoids mainly develop from the subepithelial neuroendocrine the periferal nervous system, in cells and are related to opposite to the small intestinal carcinoids, from the intra epithelial endocrine which arise cells derived from the entoderm. A-075
TREATMENT OF MALIGNANT ENDOCRINE PANCREATIC TUMORS WITH A NEW LONG-ACTING SOMATOSTATIN Eriksson ~.+NA~~~~~'K?S ~~e~~~on T.2, Lundqvist G.3, Wide L.3 and Wilander E. Ludwig Institute for Cancer Resfarch, Uppsalg Branch, Clinical Group and Department of Internal Medicine , Radiology , Clinical Chemistry and Pathology , University Hospital, Uppsala, Sweden Nine patients with malignant endocrine pancreatic tumors were treated with a new long-acting somatostatin analogue, SMS 201-995 at doses of 50 pg twice daily, administered subcutaneously. Four out of nine patients syndrome and 3/S with the (44%), one patient with the Zollinger-Ellison WDHA syndrome, responded objectively with more than 50% reduction of peptide levels, median duration 9.5 months. All four patients improved symptomatically. Two additional patients had a clear relief of symptoms without an effect on tumor secreted peptides. Three patients progressed during treatment, one of whom produced excessive amounts of endogenous somatostatln and the therapy resistance presumably depended on down regulation of somatostatin receptors. No reduction of tumor mass was seen in any of the patients, however tumor s=e remained unchanged on CT in all patients during the observation time (mean 6 months). The only main side effect was a slight but maintained increase in fasting blood glucose in four patients. In conclusion, SMS 201-995 had a beneficial effect in more than half of the patients and it seems to be a valuable adjunct to other causal therapy in this patient category.