[Contribution of synthetic somatostatin analogues to the clinical features of gastroenteropancreatic endocrine tumors].
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Gastrointestinal Neoplasms↗
Biomedical subjects
G Biliotti
Publications and source records attributed to G Biliotti.
[Risk of recurrence following partial thyroidectomy for benign lesions. Report of 58 patients 15-25 years after surgery].
BACKGROUND: Since the 1980's, thanks to the introduction of new techniques and methods for the study of thyroid function, new light has been shed on certain aspects of thyroid disease that constitute the basis for surgical therapy. Multinodular goiter is a disorder affecting the entire gland, even when alterations mostly or exclusively involve a single lobe. The functional deficit resulting from partial or subtotal resection has a hypertophic/hyperplastic effect on the remaining parenchyma. Partial resections often lead to postoperative hypothyroidism, usually of a subclinical nature, which implies difficult management by means of replacement therapy. METHODS: The authors report a series of 58 patients who underwent partial thyroidectomy to treat benign thyroid disease at the 2nd Surgical Department of the University of Florence during the period 1975-1985. RESULTS: Of these patients, operated on more than 15 years ago, 36.2% - the majority of whom (87.5%) have constantly been on substitutive therapy using L-thyroxin - currently shows no alteration of the remaining parenchyma. Conversely, in 60.3% of the patients there was evidence of nodular/pseudonodular alterations; in this group, only 40% of the patients were on substitutive therapy. There seems to be no doubt that, with few exceptions, disease involving an apparently circumscribed area of the thyroid in reality affects the entire parenchyma. CONCLUSIONS: Total thyroidectomy, therefore, represents the most appropriate treatment for multinodular goiter, even when the disease is limited to one lobe, thereby providing a cure for the disease and at the same time a state of euthyroidism easily achieved with the proper therapy.
Adolescent↗
Evaluation of prothrombin F1+2 fragment after videolaparoscopic surgery.
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Adult↗
Structural changes of the exocrine pancreas in a patient with cholecystolithiasis.
The exocrine pancreas has been studied histologically, morphometrically, and ultrastructurally in a patient with cholecystolithiasis in comparison with three control patients free from gastrointestinal or pancreatic diseases. In the gallstone-bearing patient, acinar cells undergo a significant increase in the average cell area and average zymogenic area (i.e., the portion of acinar cell cytoplasm occupied by zymogen granules). In addition, these cells showed cytological signs of enhanced synthesis of secretory proteins and increased formation and release of zymogen granules. The findings concerning centroacinar/ductular cells are consistent with a significant increase in their number and average cell area that is associated with ultrastructural signs of enhanced functional activity.
Adult↗
Are pancreatic VIPomas paraneuron neoplasms? A clue to the neuroectodermal origin of these tumors.
Three pancreatic vasoactive intestinal polypeptide (VIP)-producing tumors associated with the watery diarrhea-hypokalemia-achlorhydria syndrome were studied histologically, ultrastructurally, and immunocytochemically. All the tumors contained varying numbers of cells arranged in pseudoglandular structures. The cells showed a polar organization, with apical tuft of microvilli and basal VIP-containing, synaptic vesicle-like granules. Based on the morphology of the VIPoma cells typical of recepto-secretory cells, together with the ability to synthesize and release a peptide that in normal conditions is expressed exclusively by neurons, and the absence of VIP-producing endocrine cells in normal pancreas and gastrointestinal mucosa, the hypothesis is drawn that the pancreatic VIPomas reported here are paraneuron neoplasms, which possibly originate from neuroectodermal ancestors.
Adult↗
Immunocytochemical and ultrastructural abnormalities of islet tissue in patients with VIP-producing tumors of the pancreas.
Nontumoral endocrine pancreas from three patients with malignant vasoactive intestinal polypeptide (VIP)-omas and the Verner-Morrison (watery diarrhea, hypokalemia, and hypoachlorhydria) syndrome was studied immunocytochemically, ultrastructurally, and morphometrically. Compared with normal islets from control subjects, those of the VIPoma-associated pancreas showed a decrease of immunoreactive insulin in B-cells associated with cytological features indicative of enhanced insulin synthesis and secretion and an increase in the number of immunoreactive somatostatin- and pancreatic polypeptide-containing cells, in the absence of ultrastructural signs of modified secretory activity. No substantial alterations of A-cells were observed. In addition, images of diffuse de novo formation of ducts and islet tissue were often found. Possible mechanisms involved in determining the above changes are discussed.
Adult↗
Morphological changes in the human endocrine pancreas induced by chronic excess of endogenous glucagon.
The non-tumoral endocrine pancreas from a patient with elevated plasma levels of glucagon due to a malignant glucagonoma was studied immunocytochemically, ultrastructurally and morphometrically. Compared with normal pancreatic islets from control subjects, those of the pancreas from the patient with a glucagonoma showed an almost complete disappearance of A cells, a decrease in immunoreactive insulin in B cells associated with cytological features indicating enhanced synthesis and secretion of this hormone, and an increase in immunoreactive somatostatin and pancreatic polypeptide (PP) accompanied by unusually high numbers of D and PP cells. In addition, numerous B cells were found outside the islets, either forming micro-islets or scattered in the exocrine tissue (nesidioblastosis). The possible mechanisms involved in determining the changes in the secretory activity of B cells and the alterations in the cell composition of the islets are discussed.
Adolescent↗
Effect of octreotide (SMS 201-995) on meal-stimulated pancreatic secretion in three patients with external pancreatic fistula.
Octreotide (SMS 201-995) is a long-acting somatostatin analogue that inhibits both basal and secretin-cholecystokinin-stimulated pancreatic secretion. This study assesses the effect of this compound on pancreatic secretion induced by ordinary meals. Three patients with stable secretion of pure pancreatic juice from high output pancreatic fistula were studied. In all three, meal ingestion caused a marked and prolonged increase in pancreatic juice flow, and in bicarbonate and protein output. The subcutaneous injection of 50 micrograms octreotide before meals almost totally prevented (by about 90%) this increase. The inhibitory effect of octreotide on postprandial pancreatic secretion appeared soon, and persisted for the duration of the study period (8 h).
Food↗
Intramural distribution of immunoreactive vasoactive intestinal polypeptide (VIP), substance P, somatostatin and mammalian bombesin in the oesophago-gastro-pyloric region of the human gut.
The intramural distribution of vasoactive intestinal polypeptide (VIP), substance P, somatostatin and mammalian bombesin was studied in the oesophago-gastro-pyloric region of the human gut. At each of 21 sampling sites encompassing this entire area, the gut wall was separated into mucosa, submucosa and muscularis externa, and extracted for radioimmunoassay. VIP levels in the mucosa were very high in the proximal oesophagus (1231 +/- 174 pmol/g, mean +/- SEM) and showed varied, but generally decreasing concentrations towards the stomach, followed by a clear-cut increase across the pyloric canal (distal antrum: 73 +/- 16 pmol/g, proximal duodenum: 366 +/- 62 pmol/g); consistent levels were found in submucosa and muscle (200-400 pmol/g) at most sites, the stomach again showing lower concentrations. By contrast, substance P was present in small amounts as far as the proximal stomach, but sharply increased across the pyloric canal, especially in mucosa and submucosa (distal antrum: 20 +/- 6.5 and 5.5 +/- 1.3 pmol/g; proximal duodenum: 62 +/- 8.5 and 34 +/- 11 pmol/g, respectively). Somatostatin concentrations were very low in the mucosa of the oesophagus and stepwise increased in the cardiac, mid-gastric and pyloric mucosa (cardia: 224 +/- 72 pmol/g; distal antrum: 513 +/- 152 pmol/g; proximal duodenum: 1013 +/- 113 pmol/g); concentrations in the submucosa and muscularis were generally low, with the exception of antrum and duodenum. Mammalian bombesin was comparatively well represented throughout the oesophageal muscularis (5-8 pmol/g), but most abundant in the stomach in all layers (oxyntic mucosa: 24 +/- 2.7 pmol/g; submucosa: 20 +/- 5.7 pmol/g; muscle: 28 +/- 5.0 pmol/g).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
The exocrine pancreas in patients with hyperinsulinemic hypoglycemia. A morphometrical and ultrastructural study.
The exocrine pancreas has been studied morphometrically and ultrastructurally in 12 patients with insulin-producing tumors in comparison with control patients free from gastrointestinal or pancreatic diseases and with normal glucose homeostasis. Light microscopical examination and morphometrical data revealed that in the insulinoma-bearing patients acinar cells undergo a marked and significant decrease in zymogen granule content, together with a slight reduction in the mean cell area. Such changes were accompanied by ultrastructural features indicating increased production and exocytosis of zymogen granules. The findings concerning centroacinar/ductular cells are consistent with an increase in their number and mean cell area, and an enhancement of their functional activity. In synthesis, both the enzyme- and bicarbonate-secreting cells appear to be greatly stimulated in conditions of chronic hyperinsulinemic hypoglycemia owing to the presence of insulinomas.
Adenoma, Islet Cell↗
A malignant tumor of the pancreas producing glucagonoma syndrome: immunocytochemistry and ultrastructure of liver metastases and comparison with the primary tumor.
In this study, liver metastases from a patient with a pancreatic glucagonoma producing the syndrome have been investigated histologically, ultrastructurally, and immunocytochemically. A comparison has also been made between the metastases and the primary pancreatic tumor investigated in a parallel study. In the metastatic tissue, glucagon-, pancreatic polypeptide (PP)-, and somatostatin-containing cells were found together with a majority of cells without any immunoreactivity. Glucagon-positive cells were much more numerous than PP- and somatostatin-immunoreactive cells. As in the primary tumor, double immunogold staining of ultrathin sections demonstrated the co-existence of glucagon and PP immunoreactivities in most of the granulated cells, but PP immunolabeling was often faint, so that it probably could not be revealed by the PAP method in light microscopical sections. Such a finding, together with the histological and ultrastructural features, is consistent with an ontogenic and phylogenetic primitiveness of the metastatic cell population.
Adenoma, Islet Cell↗
A malignant tumor of the pancreas producing glucagonoma syndrome: coexistence of glucagon and pancreatic polypeptide (PP) in the tumor cells.
A malignant tumor of the pancreas producing the glucagonoma syndrome and associated with high plasma levels of glucagon and pancreatic polypeptide was studied histologically, ultrastructurally, and immunocytochemically. The histologic and ultrastructural features were closely similar to those of previously reported malignant glucagonomas. However, immunolabeling with specific antisera revealed that, in addition to cells having only glucagon- or only pancreatic polypeptide-immunoreactivity, other cells were also present, showing a co-existence of both peptides. These findings indicate that the tumor contains a cell population with a phenotype similar to that of intestinal L-cells rather than to pancreatic A-cells.
Adenoma, Islet Cell↗
The endocrine pancreas in patients with insulinomas. An immunocytochemical and ultrastructural study of the nontumoral tissue with morphometrical evaluations.
The nontumoral endocrine pancreas was studied immunocytochemically and ultrastructurally in 12 patients with isolated insulinomas. Changes affecting hormone content and secretion of B-, A-, and D-cells were found in the islets of insulinoma-bearing patients when compared with controls, in terms of a significant decrease of the insulin-immunoreactive tissue areas and an increase in the glucagon- and somatostatin-immunoreactive ones. Conversely, only in two of the patients examined were PP-immunoreactive tissue areas augmented. Diffuse ducto-endocrine proliferation (nesidioblastosis) was also a common feature in the tumor-associated pancreas. Both morphometry and qualitative features revealed that islet cell hyperplasia occurs in the presence of insulinoma. Ultrastructural examination revealed that the functional activity of B-cells is substantially depressed in the insulinoma-bearing patients, whereas it is maintained or even enhanced in the other cell types. The islet content in immunoreactive insulin decreases along with duration of hypoglycemic symptoms. The present findings indicate that, in the presence of an insulinoma, the endocrine pancreas undergoes changes that can be regarded as an adaptive response to the chronic excess of insulin and are possibly responsible for the patients' postoperative clinical course.
Adenoma, Islet Cell↗
Pancreatic secretory response to ordinary meals: studies with pure pancreatic juice.
We have studied the pancreatic secretory response to a normal meal in 5 subjects with an external drainage of the main pancreatic duct carried out after biliary tract surgery. Pancreatic juice was collected at 60-min intervals from 10 AM to 7 PM, starting 2 h before and ending 7 h after lunch, and was analyzed for volume, bicarbonate content, and protein content. Large doses of pancreatic extract were given between and during meals. Both bicarbonate and protein output increased rapidly after the beginning of the meal and the increase persisted, with minor fluctuations, for the entire 7-h study period between lunch and dinner. The peak postprandial bicarbonate and protein outputs were higher (on average by 20% and 26%, respectively) than bicarbonate and protein outputs induced by exogenous infusion of submaximal doses of secretin and cerulein. The profile and magnitude of the bicarbonate secretory pattern elicited by food were not substantially different from those of protein secretion. In an additional patient who had undergone a duodenocephalopancreatectomy plus two-thirds distal gastrectomy before the study, the pancreatic response to meals showed an initial phase characterized by an increase in pancreatic secretion during the first postprandial hour followed by a tendency to decrease in the subsequent 2 h, and a later phase (from the fourth postprandial hour to the end of the study) characterized by a more marked and more persistent increase in pancreatic secretion than occurred in the initial 3 h. These data indicate that (a) the pancreatic secretory response to ordinary meals is much more prolonged than is generally believed. The late phase of the response is not dependent on gastric emptying of food into the duodenum, but is probably related to the arrival of chyme in the distal ileum. (b) The pancreatic secretory response to a normal meal is quantitatively slightly higher than that produced by exogenous pancreatic stimulation with submaximal doses of secretin and cerulein. (c) The pattern of postprandial bicarbonate secretion is similar to that for protein.
Adult↗
Intramural distribution of Met5-enkephalin-Arg6-Gly7-Leu8 in sphincter regions of the human gut.
The intramural distribution of Met5-enkephalin-Arg6-Gly7-Leu8 (MERGL) was studied in the oesophago-cardiac, pyloric, ileo-caecal and sigmoid-recto-anal regions of the human digestive tract. Serial samples encompassing each area were separated into mucosa, submucosa and muscularis externa and extracted for radioimmunoassay. Comparatively low levels of MERGL immunoreactivity were measured throughout the cardiac junction. Conversely, a remarkable peak of MERGL concentration was detected at the pyloric junction, in both submucosa and muscularis. A progressive decrease in tissue levels of the same peptide, most evident in the submucosa, was detected on the proximal side of the ileo-caecal region. In the distal sigmoid colon and rectum MERGL concentrations showed a rapid decline, down to very low levels in the anal canal. The results may suggest the involvement of an enkephalinergic mechanism in the control of the human pylorus.
Cardia↗
Intramural distribution of regulatory peptides in the human stomach and duodenum.
The distribution of regulatory peptides was studied by radioimmunoassay in the separated mucosa, submucosa and muscularis externa of the human oxyntic stomach, antrum and duodenum. Immunoreactive gastrin, secretin, gastric inhibitory polypeptide and motilin were virtually confined to the mucosa and duodenal submucosa, where endocrine cells are present. Only minor amounts of motilin and gastrin (3.2 +/- 0.5% and 4.3 +/- 0.8% of their total content, means + SEM, respectively) were found in the separated duodenal muscle. Somatostatin-, vasoactive intestinal polypeptide-, substance P-, and mammalian bombesin-like peptides showed distinct differential distributions in all layers. Substance P was low in the stomach and markedly increased in the duodenum, especially in the mucosa (fundus 0.8 +/- 0.2 pmol/g, duodenum 66 +/- 12). Vasoactive intestinal polypeptide and somatostatin, although well represented in the stomach, also increased in the duodenum in all layers of the wall (whole fundus 281 +/- 33 and 334 +/- 46 pmol/g, antrum 124 +/- 18 and 426 +/- 59, duodenum 507 +/- 99 and 1816 +/- 149, respectively). Mammalian bombesin immunoreactivity was comparatively abundant in the oxyntic stomach (mucosa 34 +/- 4.5 pmol/g, muscularis externa 29 +/- 4.8), less so in the antrum (6.3 +/- 1.5 and 11 +/- 3.2 pmol/g, respectively). Low concentrations of this peptide were measured in the duodenum, practically confined to the muscle (this layer 5.1 +/- 1.5 pmol/g, or 83 +/- 5.6% of the total content).
Aged↗
A multihormonal tumor of the pancreas producing neurotensin associated with the WDHA syndrome. Histology, histochemistry and origin.
A pancreatic tumor associated with severe WDHA syndrome has been studied histologically and immunohistochemically. Light microscopy revealed that the growth pattern of the tumor varied greatly from zone to zone but with prevailing solid arrangement of the tumoral cells. The majority of the endocrine cells showed numerous eosinophilic, PTAH-positive, and argyrophilic secretory granules, that were ultrastructurally similar to those of normal and tumoral neurotensin-containing cells. A minority of the endocrine cells had secretory granules ultrastructurally different from the aforementioned ones, but these were not diagnostic on purely morphological grounds. Inside the tumor, immunohistochemistry demonstrated a majority of neurotensin-immunoreactive cells, sparse and small clusters of VIP-immunoreactive cells and few, dispersed pancreatic polypeptide-immunoreactive cells. Some structural and ultrastructural aspects of the tumoral stroma have also been reported. Ducts and solid masses of duct-like cells were also found, and small clusters and singly dispersed duct-like cells were seen invading the endocrine tissue and undergoing mitoses. Such features suggest that the tumor originated from precursors located in the medium-sized and small pancreatic ducts. Because of the multihormonal nature of the tumor, the role of neurotensin and VIP in producing the patient's symptoms is discussed and a synergistic action of the two hormones is suggested in causing the particularly severe WDHA syndrome.
Adult↗
Nesidioblastosis and intermediate cells in the pancreas of patients with hyperinsulinemic hypoglycemia.
The pancreases of three patients with hyperinsulinemic hypoglycemia were studied: one of these patients was a child born to a diabetic mother, the other two were adults with insulinomas. All the patients had nesidioblastosis, namely the presence of a number of pancreatic endocrine cells spread throughout the exocrine tissue singly or clustered in small groups. In the hypoglycemic child the endocrine cells scattered in the acinar tissue were mostly A cells, whereas in the patients with insulinomas both A and B cells were found with a similar frequency. Intermediate cells (acinar-islet cells) were found in all the cases. These findings suggest that nesidioblastosis and the de novo formation of intermediate cells are associated phenomena. Possible mechanisms for the genesis of the islet cell types spread throughout the exocrine parenchyma and of the intermediate cells are discussed and their possible clinical implications are suggested.
Adenoma, Islet Cell↗