Exocrine pancreatic enzyme and calcium secretion in health and pancreatitis.

Calcium, enzyme, and total protein secretion were measured in secretin stimulated pancreatic juice in health, "early" chronic pancreatitis, and in chronic calcific pancreatitis. Increased concentrations of trypsin, total protein, and calcium, and increased outputs of calcium and protein were shown to be present in the "early" stages of the disease, indicating that an environment conducive to the formation of protein plugs and possibly later calcification already exists.     

The production of calcium and magnesium during pancreatic function tests in health and disease

Duodenal calcium and magnesium concentrations after pancreatic stimulation were measured in 25 patients with and without pancreatic disease. The concentration of both ions was higher in those with pancreatic disease, and furthermore these patients showed a different secretory pattern. These findings may be relevant to the aetiology of pancreatitis and to pancreatic calcification, and might be of diagnostic value.     

Secretin dose-response in health and chronic pancreatic inflammatory disease.

Stepwise increasing doses of secretin (0.078, 0.233, 0.7, and 2.1 U/kg-h) were given to 12 healthy volunteers (HV) and to patients with a history of chronic pancreatic inflammatory disease of more than five years (CP5, 12 patients) and two years or less (CP2, 9 patients). The maximal bicarbonate response (Vmax) and the half maximal dose of secretin (Km) were calculated for each individual. Bicarbonate responses below that in HV were found in the majority of CP5 and in one-third of CP2. Vmax showed no superiority to the responses to the three largest doses of secretin in the diagnosis of bicarbonate secretory deficiency. In CP2 bicarbonate responses above that in HV were frequently found with the small doses of secretin. No evidence of hypersecretion was found. The findings suggested, however, that the early stage of chronic pancreatic inflammatory disease may be associated with an increased sensitivity to secretin. Km was poorly reproducible and showed no diagnostic ability. Large doses of secretin stimulated the secretion of proteolytic enzymes, but the diagnostic efficiency was less than for bicarbonate. The output of calcium varied markedly in CP2 and CP5. The bicarbonate/calcium ratio, however, was almost invariably lowered in these patients and showed diagnostic superiority to bicarbonate secretion.     

Effect of bovine pancreatic polypeptide on basal pancreatic and biliary outputs in man

Basal pancreatic and biliary outputs were examined in seven healthy volunteers during intravenous infusion of bovine pancreatic polypeptide (BPP) at a mean dose of 320 pmoll kg/hr. BPP significantly (P<0.02) inhibited outputs of trypsin and bilirubin, without affecting bicarbonate. These studies suggest the possibility that pancreatic polypeptide may have a role in the regulation of biliary and pancreatic enzyme secretion in man.A preliminary report of this work has been published as an abstract (1).     

Duodenal endocrine cells in adult coeliac disease.

Using immunohistochemical techniques we studied duodenal biopsies from 18 patients with coeliac disease and 24 patients with normal duodenal morphology. We had access to antisera against the following gastrointestinal peptides: cholecystokinin (CCK), gastric inhibitory peptide (GIP), gastrin-17, glucagon-enteroglucagon, motilin, neurotensin, pancreatic peptide (PP), secretin, somatostatin, substance P and vasoactive intestinal peptide (VIP). The somatostatin, GIP, CCK, and glucagon cells were increased in number in coeliac disease. The number of motilin cells was slightly increased, while secretin cells were reduced. Cells storing gastrin-17, substance P, or neurotensin were rare in all patients regardless of diagnosis. No PP immunoreactive cells were found and VIP was localised to neurons only. In biopsies from patients having a mucosa with ridging of villi the number of the various endocrine cell types did not differ from that in the control group.     

Duodenal Hodgkin's disease

An unusual case of primary extranodal Hodgkin's disease, localized to the duodenum is reported and illustrated. A review of the literature stressing the incidence, clinical presentation, radiographic appearance and prognosis of primary gastrointestinal Hodgkin's disease is presented. It is pointed out that although the majority of the lesions are infiltrating in type, intestinal Hodgkin's may present as a solitary ulceration or as a polypoid lesion indistinguishable from other forms lymphoma.     

Duodenal Crohn's disease

Duodenal Crohn's disease is a rare condition not frequently encountered by the general or colo-rectal surgeon. Manifestations of Crohn's disease may appear in the duodenum as result of primary involvement, or secondary to complications of more distal gastrointestinal disease. Symptoms of duodenal Crohn's are often non-specific, and diagnosis can be difficult. This paper presents a summary of the published literature on duodenal Crohn's disease, including a review of the surgical approaches to this uncommon problem. Received: 6 November 2000 / Accepted: 16 January 2001     

Serum pancreatic isoamylase activity in pancreatic disease.

The diagnostic value of serum amylase determination for pancreatic disease has been questioned due to its lack of specificity. Several methods have been developed to separate the tissue-unspecific salivary fractions from the tissue-specific pancreatic fractions. Agarose or cellulose acetate gel electrophoresis are most suitable for clinical practice. The isoamylase patterns were studied by agarose electrophoresis in 55 patients with known pancreatic diseases (acute pancreatitis, pancreatic pseudocysts, exocrine pancreatic insufficiency and pancreatic carcinoma). Increased P-type isoamylase seems to be more sensitive than total amylase in diagnosing acute pancreatitis, while identification of the minor isoamylase P3 is more specific and could have a prognostic value. Detection of low P-type isoamylase levels is an easy method to diagnose exocrine pancreatic insufficiency. Furthermore, a group of patients with pancreatic disease (Pa), was compared with a group of patients with biliary disease without clinical evidence of pancreatic involvement (Bi), and patients with abdominal pain, without evidence of biliary or pancreatic disease (Ab). More than half of the Bi patients presented with abnormal P isoenzyme patterns, whereas 72% of the Ab patients had a normal pattern. Only P3 could distinguish between the Bi and Ab group. This might point to pancreatic involvement in patients presenting with biliary disease, only detected by isoamylase analysis.     

Duodenal somatostatin in coeliac disease

The frequency of duodenal somatostatin cells was assessed and correlated to the number of enterocytes in patients with coeliac disease and in patients with a normal duodenal mucosa. The concentration of somatostatin in the duodenal mucosa was also determined. The number of duodenal somatostatin cells was increased in coeliac disease, whereas the somatostatin concentration did not differ significantly from that of the control patients.     

Duodenal fistulas in Crohn's disease

Of 1,480 patients with Crohn's disease admitted to The Mount Sinai Hospital between 1960 and 1983, eight (0.5%) had duodenal fistulas (DF), all originating from diseased small or large bowel and not from primary disease of the duodenum. The extent, duration, and major clinical features of Crohn's disease did not differ between patients with DF and those with other fistulas. Six of the patients underwent surgery for refractory disease or abscess formation and two patients were treated medically. All improved and were able to maintain an adequate oral intake after treatment. At follow-up 3-10 years later, the surgically treated patients were well but both medically treated patients had died, one from a probably unrelated brain tumor 7 years after discharge and one from necrotizing pancreatitis 10 years later. Our experience suggests that the presence of a DF is not an absolute indication for early surgery. The initial therapeutic management of such patients should be determined by the nature and severity of the underlying Crohn's disease rather than the presence of a DF. The late pancreatic complication in a patient with a chronic DF, however, raises the question of an association between the two.     

Duodenal mucosa and extracellular cyclic nucleotide pattern in coeliac disease.

This study measured the values of cyclic nucleotides and adenylate and guanylate cyclase activities in duodenal mucosa homogenates to verify if they played a part in coeliac disease. Nine controls, 13 patients who did not receive treatment and nine patients who received treatment were studied. Cyclase activity assays were performed under basal conditions and in the presence of gliadin derived peptides. Duodenal mucosa cyclic nucleotide values and adenylate cyclase activity were significantly higher in patients who did not receive treatment than in those who did and in controls, whereas guanylate cyclase activity was similar in all groups. Gliadin derived peptides did not affect guanylate cyclase activity, but significantly increased adenylate cyclase activity in homogenates from patients who did not receive treatment. As extracellular cyclic nucleotide concentrations could reflect changes in their intracellular metabolism, plasma and urine cyclic nucleotide values were also measured in 25 controls and in 55 patients studied at different stages of their disease. Extracellular cyclic nucleotides were considerably high in patients who were not healed and became normal after about one year of treatment. These data suggest that cyclic nucleotides may participate in the pathophysiological processes of coeliac disease.     

Duodenal ulcer and pancreatitis associated with pancreatic arteriovenous malformation

Arteriovenous malformation (AVM) of the pancreas is a rare condition that may cause severe gastrointestinal bleeding. We describe a 54-year-old man with a 7-year history of recurrent duodenal ulcer due to AVM in the pancreatic head. We recommended pancreatoduodenectomy because of recurrent haemorrhage from the duodenal ulcer, but the patient refused surgery on several occasions. He was admitted to our hospital complaining of severe upper abdominal pain radiating to the back and was diagnosed with acute pancreatitis. He agreed at that stage to the surgical treatment. The resected specimen contained a highly vascular malformation in the pancreatic head and ulceration in the adjacent descending duodenum. Histopathological examination revealed numerous vascular structures with dilated and tortuous vessels in the pancreatic head, confirming the presence of AVM. Moreover, oedema, inflammatory cell infiltration, haemorrhage and necrosis were evident, confirming the presence of acute pancreatitis.     

Duodenal mucosa synthesis of prostaglandins in duodenal ulcer disease.

Synthesis of prostaglandins (PGE2, PGI2 and PGF2 alpha) and thromboxane A2 was investigated in short term incubates of duodenal mucosa biopsies. Mucosa close to the ulcer site synthesised significantly less PGF2 alpha (p less than 0.001) and PGI2 (p less than 0.002) measured as its stable metabolite 6-oxo-PGF1 alpha than healthy mucosa from non-ulcer patients. In paired biopsies taken from the ulcer site and opposite the ulcer in the same patient PGF2 alpha and PGI2 syntheses were both significantly and similarly depressed when compared with normal mucosa. Synthesis of PGE2 and TxA2 (as its stable metabolite TxB2) was not different in any tissue. There is a defect in the ability of the human duodenal mucosa in duodenal ulcer disease to synthesise PGF2 alpha and PGI2; the defect is not limited to the ulcer site.     

Serum and pancreatic juice carcinoembryonic antigen in pancreatic and biliary disease.

Serum and pancreatic juice carcinoembryonic antigen (CEA) concentrations were studied in a group of 144 patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) with a variety of benign and malignant pancreatic and biliary diseases. Serum CEA was found to be a poor diagnostic and discriminating marker for pancreatic disorders and was raised in obstructive jaundice from various causes correlating with serum alkaline phosphatase. A pancreatic juice CEA concentration of greater than 106 mcg/l was associated with pancreatic disease but did not distinguish benign from malignant lesions. Criteria derived from pancreatic juice volumes and bicarbonate responses provided additional diagnostic differentiation of normal from pancreatic disease but not cancer from pancreatitis. Pancreatic juice CEA may have a limited application where imaging techniques have failed or are not available and additional study of pancreatic juice biochemistry is required before adequate diagnostic criteria can be established.     

Duodenal volume and osmoreceptors in the stimulation of human pancreatic secretion

It is generally accepted that the intestinal phase of pancreatic secretion is initiated by the stimulation of chemoreceptors sensitive to fat and protein degradation products and hydrogen ions. The effect of the volume and osmolality of food emptied by the stomach into the duodenum has received less attention. We investigated the effects of these factors on the stimulation of pancreatic secretion by studying 8 healthy male volunteers (ages 23-69 yr), in random order on 3 separate days. On day 1, an amino acid mixture (L-phenylalanine, L-tryptophan) was infused intraduodenally at increasing rates, 0.2, 0.8, and 3.2 ml X min-1. On day 2, normal saline was infused into the intestine at the same increasing rates. On day 3, mannitol solutions of increasing osmolality 370, 520, and 700 mosmol X kg-1 were infused into the duodenum at 0.2 ml X min-1. Duodenal contents were continuously aspirated via a double-lumen tube and PEG 4000 was used as a recovery marker. All studies were repeated 90 min later during i.v. infusion of atropine (20 micrograms X kg-1 X h-1). Increasing volumes of amino acids significantly increase amylase and bicarbonate output (p less than 0.05) in a stepwise fashion. Increasing volumes of saline also caused a similar stepwise increase in amylase and bicarbonate output. Furthermore, increasing osmolality caused an increase in enzyme output up to 520 mosmol X kg-1 and no increase was seen thereafter. The responses seen with volume and osmolality were approximately 40% of that obtained with the amino acids. All responses were significantly reduced (p less than 0.05) during atropine infusion. We conclude that the human duodenum contains receptors for volume and osmolality that stimulate both pancreatic enzyme and bicarbonate secretion. Both mechanisms are atropine sensitive, suggesting they are mainly neurally mediated.     

Ultrasonic scanning in pancreatic disease.

We have analysed retrospectively the pancreatic ultrasound scans (using a bistable machine) in 138 consecutive patients, and have related the results to the clinical status and the final diagnosis in each case. The scans were read without knowledge of the patient's clinical state. When technically unsatisfactory scans were excluded from consideration, the overall diagnostic accuracy of ultrasonography proved to be 82%, with a false positive rate of 8%. The scan was abnormal in all 10 patients with cancer of the pancreas: a positive diagnosis of cancer was made in six. All patients with chronic pancreatitis in relapse had abnormal scans, but in 53% the scans were normal in patients in whom the disease was in clinical remission. In seven patients with chronic pancreatitis who suffered relentless pain, the head of the pancreas was swollen and contained cystic areas or emitted abnormal echoes. In acute pancreatitis ultrasonic scanning proved useful in following the progression of the disease to final resolution, or to development of complicating pseudocyst, abscess, or ascites. Random echoes in the early stages of acute pancreatitis are features of haemorrhagic necrosis. In alcoholic relapsing pancreatitis the persistence of abnormal echoes, disposed linearly along the axis of major ducts, suggests the presence of chronic pancreatitis.