The place of total and extended total pancreatectomy in pancreatic cancer.
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Adenocarcinoma↗
Biomedical subjects
A R Moossa
Publications and source records attributed to A R Moossa.
Glucose counterregulation in patients after pancreatectomy. Comparison with other clinical forms of diabetes.
Glucose and counterregulatory hormone responses to a high-dose (1.7 mU/kg/min) insulin infusion were studied in 6 patients who had undergone total pancreatectomy, and the results were compared with those of normal controls and patients with other clinical forms of diabetes. The maximum increase in the plasma glucagon concentration during hypoglycemia in the pancreatectomized patients (5 +/- 5.6 pg/ml) was less than in normals (121 +/- 22 pg/ml). Type I diabetic subjects (28 +/- 14 pg/ml), and insulin-treated diabetic subjects of recent onset (36 +/- 12 pg/ml) also had reduced responses, while responses were normal in type II diabetic subjects (102 +/- 26 pg/ml). The epinephrine response to the hypoglycemic stimulus was reduced after pancreatectomy (278 +/- 81 pg/ml) and in type I diabetic subjects (628 +/- 244 pg/ml), but was not different from control (858 +/- 126 pg/ml) in type II and recent-onset diabetic patients. There was considerable overlap in counterregulatory hormone responses in individual patients with and without autonomic neuropathy and with normal or undetectable fasting C-peptide concentrations. While the control subjects all experienced symptoms of hypoglycemia within a narrow range of plasma glucose concentrations (35-46 mg/dl), five of the diabetic subjects experienced symptoms of hypoglycemia at plasma glucose levels of greater than or equal to 55 mg/dl, and five had no subjective awareness of hypoglycemia despite plasma glucose levels less than 30 mg/dl.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Naloxone decreases centrally induced hyperglycemia in dogs. Evidence for an opioid role in glucose homeostasis.
Intracerebroventricular (ICV) instillation of morphine and beta-endorphin causes centrally induced hyperglycemia. Locally active, endogenous opioids in the central nervous system may, therefore, also be involved in the elevation of blood sugar. This possibility was tested by examining the glucoregulatory response to central glucoprivation induced by ICV administration of 2-deoxy-D-glucose (2DG) in dogs. Administration of 2DG resulted in a rise in plasma glucose and immunoreactive glucagon (IRG) of 108 +/- 19 mg/dl and 70 +/- 20 pg/ml, respectively. These changes were attenuated by the simultaneous central infusion of the opiate antagonist naloxone: plasma glucose levels increased by 77 +/- 14 mg/dl and IRG by 43 +/- 3 pg/ml, both significantly different from the effect of 2DG alone (P less than 0.05-0.01). These findings suggest that opiate receptors participate in the counterregulatory response to central glucoprivation. They also provide a mechanism by which endogenous opioid peptides may play a role in the central regulation of glucose homeostasis.
Animals↗
Pancreatic hormone profiles and metabolism posthepatectomy in the dog. Evidence for a hepatotrophic role of insulin, glucagon, and pancreatic polypeptide.
Gut-related peptide hormones, especially insulin and glucagon, have been implicated in promoting hepatic regeneration. To elucidate the interrelationship between pancreatic peptide hormones and hepatic regenerative activity, we evaluated pancreatic hormone levels and their metabolism before and over a 15-day period after limited (42%) and extended (72%) hepatectomy in the dog. Serum insulin, glucagon, and pancreatic polypeptide levels increased significantly after both limited and extended hepatectomy but not after sham laparotomy. In the case of glucagon only, these increases were related to the extent of liver resection. No significant changes in plasma somatostatin levels were observed posthepatectomy. Plasma glucose levels remained normal throughout the period of study. Metabolic clearance rates and plasma half-lives for insulin, glucagon, and pancreatic polypeptide did not change over the study period. Peripheral C-peptide/insulin molar ratios were unchanged posthepatectomy, indicating no change in hepatic insulin extraction. In the absence of demonstrable changes in hormone metabolism or metabolic stimuli to secretion, these increases in pancreatic hormone levels, coinciding with the period of known maximal hepatic regenerative activity, are compatible with the notion that these are hepatotrophic responses, which could conceivably be mediated by humoral feedback signals from the liver to the endocrine pancreas.
Animals↗
Effects of resection or bypass of the distal ileum on the lithogenicity of bile.
Changes in the composition and lithogenicity of gallbladder bile after resection and bypass of the distal ileum were investigated in the prairie dog. In animals fed a trace cholesterol diet, both ileal resection and ileal bypass increased the cholesterol saturation of bile. In animals fed a cholesterol-enriched diet, the cholesterol saturation was increased by ileal resection but not by ileal bypass. In the animals fed the trace cholesterol diet, both ileal resection and ileal bypass induced the formation of bilirubinate gallstones.
Animals↗
Pancreatic biopsy.
The necessity, value, and safety of various techniques of pancreatic biopsy are evaluated. The authors also offer a general policy on pancreatic biopsies.
Biopsy↗
Hormonal control of biliary lipid secretion in dogs.
Five dogs were anesthetized, their cystic ducts were ligated, and their common bile ducts cannulated. The experiments were divided into four 1-hour periods. Taurocholic acid (18 mumol/min) and pipenzolate methylbromide (0.5 mg/kg body weight initially followed by 0.1 mg/kg body weight/20 minutes) were infused during all periods. Somatostatin (800 ng/kg/min) was infused during periods 2, 3, and 4 to suppress the endogenous secretion of peptide hormones. During periods 3 and 4, insulin was infused into a mesenteric vein at rates of 0.2 mU/kg/min and 0.8 mU/kg/min, respectively. These rates have been shown to produce fasting and postprandial portal vein insulin levels. Bile was collected during each period and the volume, bile acid concentration, and biliary lipid content were measured. Another five dogs were studied in a similar way, except that glucagon was infused in place of insulin at rates of 0.6 and 3.0 ng/kg body weight/min to produce fasting and postprandial portal vein levels. The results show that 1) the biliary secretion of cholesterol and phospholipid is increased by pharmacologic doses of somatostatin and 2) physiologic doses of glucagon, but not insulin , suppress the biliary secretion of cholesterol and phospholipid.
Animals↗
Pharmacological and physiological doses of insulin and determinants of bile flow in dogs.
The role of insulin in control of bile secretion is uncertain. To study the mechanism of choleresis produced by large doses of insulin, bile was collected through modified Thomas cannulas from dogs anesthetized with pentobarbital. Animals received pipenzolate methylbromide, sodium taurocholate, and [14C]erythritol. After bile flow had stabilized three animals received infusions of insulin at 2, 4, 13, 26, 35, and 70 mU . kg-1 . min-1 for 40 min each. Bile and [14C]erythritol clearance increased (P less than 0.005), but bile salt output remained constant, suggesting that the choleresis was mainly due to enhanced bile salt-independent canalicular flow. Plasma insulin and glucagon levels also rose when insulin was infused. To exclude the possible effects of glucagon three additional animals received somatostatin (800 ng . kg-1 . min-1) along with infusions of insulin. Bile flow and [14C]erythritol clearance again increased significantly, but glucagon levels remained low, suggesting that the effects on bile flow were due to insulin alone. To determine whether physiological doses of insulin altered bile flow dogs were anesthetized with pentobarbital and received pipenzolate methylbromide, taurocholate, [14C]erythritol, and somatostatin (800 ng . kg-1 . min-1). Insulin (0.2 and 0.8 mU . kg-1 . min-1) was infused through the portal vein for 1 h each. Bile flow and [14C]erythritol clearance increased with insulin (0.8 mU . kg-1 . min-1; P less than 0.02), suggesting that the choleresis may have been due to bile salt-independent canalicular flow. Plasma insulin rose to physiological postprandial levels. These studies demonstrate that pharmacological and physiological levels of insulin administered to dogs produce a significant choleresis. Thus insulin may play an important role in the regulation of bile secretion.
Animals↗
Metabolism of C-peptide in the dog. In vivo demonstration of the absence of hepatic extraction.
The in vivo hepatic metabolism of connecting peptide (C-peptide) in relation to that of insulin has not been adequately characterized. A radioimmunoassay for dog C-peptide was therefore developed and its metabolism studied in conscious mongrel dogs, with sampling catheters chronically implanted in their portal and hepatic veins and femoral artery. The hepatic extraction of endogenous C-peptide under basal conditions was negligible (4.3 +/- 4.5%) and was similar to the hepatic extraction of C-peptide measured during the constant exogenous infusion of C-peptide isolated from dog pancreas. Simultaneously measured hepatic extraction of endogenous and exogenously infused insulin were 43.8 +/- 7.6 and 47.5 +/- 4.4%, respectively. The metabolic clearance rate of infused C-peptide was 11.5 +/- 0.8 ml/kg per min and was constant over the concentration range usually encountered under physiological conditions. In additional experiments, the effect of parenteral glucose administration on the hepatic extraction of C-peptide and insulin was investigated. The hepatic extraction of C-peptide (6.2 +/- 4.0%) was again negligible in comparison with that of insulin (46.7 +/- 3.4%). Parenteral glucose administration did not affect the hepatic extraction of either peptide irrespective of whether it was infused peripherally, intraportally, or together with an intraportal infusion of gastrointestinal inhibitory polypeptide. The fasting C-peptide insulin molar ratio in both the portal vein (1.2 +/- 0.1) and femoral artery (2.1 +/- 0.3) was also unaffected by the glucose stimulus. These results therefore indicate that, since the hepatic extraction of C-peptide is negligible and its clearance kinetics linear, the peripheral C-peptide concentration should accurately reflect the rate of insulin secretion. New approaches to the quantitation of hepatic extraction and secretion of insulin by noninvasive techniques are now feasible.
Animals↗
Differences in the hepatic and renal extraction of insulin and glucagon in the dog: evidence for saturability of insulin metabolism.
The metabolism of exogenously infused porcine insulin and glucagon was assessed concurrently in normal fasted dogs under anaesthesia. Hepatic and renal extraction of glucagon were 25.6 +/- 2.3 and 43.7 +/- 3.9%, respectively, and its metabolic clearance 16.5 +/- 0.8 ml/kg/min. Hepatic and renal extraction accounted for 28.5 +/- 4.2 and 28.7 +/- 3.7% of total glucagon clearance, respectively. Insulin MCR was 18.3 +/- 1.5 ml/kg/min and its hepatic and renal extraction were 49.6 +/- 3.4 and 41.7 +/- 4.4% accounting for 51.9 +/- 4.4 and 27.3 +/- 3.9% of total insulin clearance, respectively. Neither total glucagon metabolic clearance nor its hepatic or renal components saturated even in the face of circulating glucagon levels extending into the pharmacologic range up to 14 ng/ml. In contrast however, with increasing arterial concentrations of insulin, saturability of metabolism was apparent as evidenced by significant reductions in MCR as well as hepatic and renal extraction. This demonstration of saturability of hepatic insulin metabolism occurred at levels encountered in the portal vein after meals and is compatible with the concept that the hepatic capacity for extraction of this hormone may be an important site of control of the proportion of secreted insulin reaching the periphery. The metabolic handling of each hormone was shown to be independent of the other. Despite similarities in the interaction of insulin and glucagon with the target cell, there are important differences in the mechanisms of metabolism of these peptides as the major degradative sites.
Animals↗
Pregnancy complicated by extrahepatic biliary tract carcinoma. A case report.
Carcinoma of the extrahepatic biliary tract rarely coexists with pregnancy. Survival of both mother and infant beyond the early puerperium has not been reported previously in such instances. We treated a patient for pregnancy complicated by cholangiocarcinoma, with a successful maternal and fetal outcome.
Adenoma, Bile Duct↗
Management of pancreatic trauma.
Twenty patients who sustained pancreatic trauma are reviewed. Eighteen of the patients underwent emergency laparotomy and there were 53 major associated injuries. Three patients died, giving an operative mortality of 17%. All deaths could be directly attributed to the severity and extent of the associated injuries. Eleven of the 15 survivors following emergency operation developed serious postoperative complications which, in 6 instances, were directly related to the pancreatic injury. Two patients were initially treated conservatively because the isolated pancreatic injuries were missed. Both developed complications requiring operation.
Adolescent↗
Pancreatic cancer: approach to diagnosis, selection for surgery and choice of operation.
The physician must suspect pancreatic cancer in patients older than age 40 years who present with minimal vague symptoms. The presence of common disorders such as gallstones, hiatal hernia and diverticulosis coli, does not exclude pancreatic cancer. Ultrasonography, computed tomography, ERCP and cytology are the essential diagnostic tools. Angiography delineates anatomic variations of the foregut vasculature and detects nonresectability of some tumors. Percutaneous fine needle aspiration of pancreatic masses for cytologic examination is recommended for lesions of the body and tail. Percutaneous transhepatic biliary drainage is advised preoperatively in patients whose serum bilirubin exceeds 20 mg/dl. Total pancreatoduodenectomy is recommended for all resectable pancreatic cancers. Surgical palliative procedures include biliary bypass, duodenal bypass and celiac plexus nerve block. Currently, only 30% of all pancreatic cancers seen are resectable and they are confined to the head of the pancreas. About 10% of all pancreatic cancers are potentially curable at the time of presentation. The operative mortality should be under 10%.
Biopsy↗
Secretin enhances [14C]erythritol clearance in unanesthetized dogs.
To determine the effect of secretin infusion on clearance of inert markers into bile, unanesthetized dogs fitted with Thomas cannulas received continuous infusions of [14C]erythritol and [3H]inulin throughout study. Taurocholic acid administered sequentially at 9.0, 20.0, and 40.0 mumol/min enhanced [14C]erythritol clearance, and GIH secretin (3 units/min) administered along with TCA (40.0 mumol/min) increased [14C]erythritol clearance from 4.9 +/- 1.2 ml/10 min to 6.8 +/- 1.3 ml/10 min (P less than 0.001), but simultaneously measured [3H]inulin clearance was unaltered. Secretin alone also increased [14C]erythritol clearance but did not alter [3H]inulin clearance. The increase in [14C]erythritol clearance per unit increase in bile flow was less during secretin infusion than TCA. Thus, secretin increases [14C]erythritol transport through restricted channels, probably distal to the canaliculi. [14C]Erythritol may not be an accurate marker for canalicular bile flow in dogs during secretin infusion.
Animals↗
Is glucagon a choleretic hormone at physiologic blood levels?
The mechanism of action and possible physiologic implications of glucagon-induced choleresis were investigated in two groups of dogs. Group I demonstrated, in chronic animal models, that glucagon-induced choleresis was not associated with increased bile acid output and was not blocked by somatostatin or Piptal, suggesting a direct stimulatory effect on bile acid-independent canalicular flow. In acute animal models (group II), glucagon infusion at rates which produced postprandial levels in the portal vein induced significant choleresis, implying that glucagon may have a physiologic role in the regulation of bile secretion. No consistent relation between bile secretion and portal venous blood flow could be demonstrated.
Alkaline Phosphatase↗
Effect of somatostatin on determinants of bile flow in unanesthetized dogs.
Seven dogs each underwent cholecystectomy, ligation of the accessory pancreatic duct, and insertion of a Thomas duodenal cannula opposite the ampulla of Vater. After full recovery, bile secretions were studied in the unanesthetized dogs by opening the cannula and placing a ureteric catheter through the papilla into the common bile duct. All animals received, throughout study, constant infusions of taurocholic acid to replace losses caused by interruption of the enterohepatic circulation and 14 C-erythritol for measurement of erythritol clearance. After bile flow stabilized somatostatin 800 ng/kg/minute was infused for 100 minutes and bile flow declined from 3.0 +/- 0.7 ml/10 minutes (SD) to 1.19 +/- 0.47 ml/10 minutes (p less than 0.001) and 14C-erythritol clearance fell from 3.6 +/- 1.14 to 1.77 +/- 0.43 ml/10 minutes (p less than 0.001). Bile salt output was unchanged, indicating that somatostatin inhibited bile salt-independent canalicular flow (BSICF). In other experiments animals underwent intraduodenal acidification which resulted in a marked increase in bile flow. Somatostatin infusion again causes a sharp fall in bile flow (p less than 0.05) suggesting that somatostatin also inhibited ductular flow. Infusion of somatostatin did not inhibit choleresis produced by exogenous secretin administration. Thus, somatostatin inhibits 1) ductular flow by inhibiting secretin release and 2) BSICF by a direct effect or by decreasing the release of hormones which induce canalicular flow.
Animals↗
The effect of somatostatin on postresectional ileal hyperplasia.
After somatostatin infusion in rats, the proliferative activity in ileal crypts was examined under a variety of circumstances known to influence mucosal behaviour. The anticipated hyperplastic response to resection was inhibited by somatostatin treatment, not only under conditions of intestinal continuity but also in isolated segments of ileum. These results suggest that postresectional ileal hyperplasia is humorally mediated and is explicable on the basis of somatostatin suppression of trophic gut hormones. However, a direct effect of somatostatin and other secondary effects cannot be excluded.
Animals↗
Effects of an enkephalin analog on pancreatic endocrine function and glucose homeostasis in normal and diabetic dogs.
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Animals↗