Pancreaticobiliary Secretions Research Articles

2149 Successful Stenting of the Common Bile Duct Through an Ectopic Ampulla of Vater in the Pylorus

INTRODUCTION: The ampulla of Vater comprises the choledochopancreatic junction and sphincter of Oddi, traversing the posteromedial wall of the descending duodenum via the major papilla. Ectopic gastric ampullae are rare, and since the 16th century, pyloric ampullae of Vater are only documented in a handful of case reports 1 . We present a case of an extremely rare ectopic ampulla of Vater in the pylorus through which successful stenting of the common bile duct (CBD) was performed during ERCP. CASE DESCRIPTION/METHODS: A 51-year-old man presented with nausea, vomiting, and midepigastric pain radiating to the back. He was tachycardic to 117 bpm with right upper quadrant tenderness on exam. Labs showed WBC 13.5 × 109/L, AST 123 IU/L, ALT 186 IU/L, ALP 722 IU/L, lipase of 195 IU/L, and total bilirubin of 3.1 mg/dL. Contrast CT revealed a distended gallbladder with wall thickening and pericholecystic fluid, intrahepatic and extrahepatic biliary dilatation, and calcified CBD stones with pancreatic duct dilatation. Ultrasound confirmed a sonographic Murphy sign and a 9 mm CBD. After receiving intravenous ciprofloxacin and metronidazole, he underwent ERCP. Initial attempts to locate the ampulla in the duodenum were unsuccessful with a side-viewing scope. Eventual use of a forward-viewing scope identified the ampulla and a clean based ulcer in the pylorus. Purulent drainage was observed following sphincterotomy and balloon extraction. A 7 French x 5 cm stent was carefully deployed in the CBD. Prior to discharge, the patient underwent uncomplicated laparoscopic cholecystectomy. Stent was successfully retrieved 6 weeks later, again using the forward-viewing scope. Biopsies of the ampulla and ulcer confirmed acute and chronic gastritis negative for H. pylori or malignancy. DISCUSSION: As in the present case, literature suggests a recurrent triad of choledocholithiasis, cholangitis, and ulcer disease, perhaps due to reflux of gastric secretions into the hepatobiliary tree and increased mucosal exposure to pancreaticobiliary secretions. To the authors’ knowledge, this case possibly represents the first successful stenting of the CBD through an ectopic ampulla of Vater in the pylorus, proving that this can be a safe and effective option. Gastroenterologists should be aware of ectopic anatomy when the ampulla cannot be located in the duodenum.

Atypical anastomotic malignancies of small bowel after subtotal gastrectomy with Billorth II gastroenterostomy for peptic ulcer: Report of three cases and review of the literature.

AIMTo present patients who developed small-bowel malignancy at the level of the gastrointestinal anastomosis decades after a subtotal gastrectomy for ulcer, to review relevant literature, and to attempt to interpret the reasons those cancers developed to these postsurgical non-gastric sights.METHODSFor the current retrospective study and review of literature, the surgical and histopathological records dated from January 1, 1993 to December 31, 2017 of our department were examined, searching for patients who have undergone surgical treatment of small-bowel malignancy to identify those who have undergone subtotal gastrectomy for benign peptic ulcer. A systematic literature search was also conducted using PubMed, EMBASE, and Cochrane Library to identify similar cases.RESULTSWe identified three patients who had developed small-intestine malignancy at the level of the gastrointestinal anastomosis decades after a subtotal gastrectomy with Billroth II gastroenterostomy for benign peptic ulcer-two patients with adenocarcinoma originated in the Braun anastomosis and one patient with lymphoma of the efferent loop. All three patients were submitted to surgical resection of the tumor with Roux-en-Y reconstruction of the digestive tract. In the literature review, we only found one case of primary small-intestinal cancer that originated in the efferent loop after Billroth II gastrectomy because of duodenal ulcer but none reporting Braun anastomosis adenocarcinoma following partial gastrectomy for benign disease. We also did not find any case of efferent loop lymphoma following gastrectomy.CONCLUSIONAnastomotic gastric cancer following distal gastrectomy for peptic ulcer is a well-established clinical entity. However, malignancies of the afferent or efferent loop of the gastrointestinal anastomosis are extremely uncommon. The substantial diversion of the potent carcinogenic pancreaticobiliary secretions through the Braun anastomosis and the stomach hypochlorhydria, allowing the formation of carcinogenic factors from food, are the two most prominent pathogenetic mechanisms for those tumors.

Polyester Preserves the Highest Breaking Point After Prolonged Incubation in Pancreatic Juice

BackgroundThe impact of suture materials on the development of pancreatic fistula after pancreaticoduodenectomy remains unclear. Thus, their choice among pancreatic surgeons is still mostly experience-based. Aim of the present study is to assess what is the best suture material to be used for pancreaticojejunostomy. Materials and MethodsThe force needed to reach the breaking point of five widely used suture materials (polypropylene, polyester, polydioxanone, silk, and polyglactin 910) has been determined through a digital precision dynamometer at baseline and after 5 and 20 days of incubation in pancreatic juice, bile, or a mixture of both. ResultsRegardless of the condition, polyglactin 910 has retained only 10% of its baseline force. Silk has maintained almost 90% of its initial force showing a very low baseline value of force. In pancreatic juice, polypropylene has lost less force compared to polyester (0.25 vs. 0.93 N; p = 0.03) and polydioxanone (0.25 vs. 3.67 N; p = 0.04). Polyester and polydioxanone have showed similar values of force. However, polydioxanone has lost a significant amount of force in pancreatic juice when compared to polyester (0.93 vs. 3.67 N; p = 0.03). Polyester has showed the highest value of force needed to reach the breaking point after 20 days of incubation in pancreatic juice. ConclusionsAfter incubation in pancreaticobiliary secretions, polyglactin 910 loses almost all its force. Polypropylene preserves its characteristic, but polydioxanone and polyester show absolute higher breaking points, with polyester retaining the highest value of force needed to reach its breaking point after incubation in pancreatic juice.

Give 'em 3 liters of hyperal.

Give 'em 3 liters of hyperal.

Prospective Markers for Early Diagnosis and Prognosis of Sporadic Pancreatic Ductal Adenocarcinoma

Sporadic pancreatic ductal adenocarcinoma (PDA) is a highly lethal cancer. No proven screening strategies are available and frequent cross-sectional imaging studies (CT/MRI) are impractical even in patients thought to be at higher risk than the general population. Few PDA biomarkers have been studied prospectively for screening. Here, we prospectively evaluated the Adnab-9 monoclonal antibody in stool, pancreaticobiliary secretions, and tissue for screening and prognostic value in sporadic PDA. We also evaluated the prognostic value of characterized early biomarkers in pancreaticobiliary secretions. Adnab-9 diagnostic ability was tested in stool in 249 and 1,132 patients from China and the US, respectively. Immunohistochemistry was performed in 22 tissue samples with Adnab-9 antibody and anti-Defensin 5, a constituent of Paneth cells. Pancreatobiliary secretions were collected from 12 PDA patients and 9 controls. The enriched PCR method was performed to detect K-ras mutations. ELISA was performed with Adnab-9, anti-Her-2/neu, and monoclonal antibody D4 (anti-Reg I). Adnab-9 alone was diagnostic and prognostic when measured in pancreatic secretions, feces, and tissues of PDA patients compared to controls (p<0.05). Significantly, Adnab-9 fecal binding can precede the clinical diagnosis by 2.3years, potentially allowing earlier clinical intervention. In pancreatic secretions, a combination of K-ras and Her-2/neu when appropriately standardized can be diagnostic in 75% of PDA. Our study suggests that Adnab-9 may be an effective marker for diagnosis and prognosis of PDA. Adnab-9 may be reflective of the presence of Paneth cells confirmed by Defensin-5 staining. These cells may modulate the biological activity of the cancer and confer a better prognosis.

Bacteriologic Culture During ERCP: Technique, Results and Clinical Impact

Background: Sampling for bacteriologic culture has rarely been reported at ERCP. In the era of increasing antibiotic resistance to common organisms and the increasing complexity of ERCP procedures, a technique to reliably sample pancreaticobiliary secretions is needed. We report our initial experience with a new technique. Patients and Methods: 20 pts with symptoms of biliary (n = 16) or pancreatic infection (n = 4) underwent 23 indicated ERCPs. Pts were aged 35 to 90+. Biliary indications for ERCP: cholangitis, sclerosing cholangitis and biliary fistula.

Development of a new method for small bowel transit study

Currently, most studies combine the small bowel transit examination with gastric emptying time examination. There are significant drawbacks to this method. The radiotracer does not enter the small intestine in a bolus and the starting time for transit in the duodenum is difficult to define. This makes the result unreliable. In this study, we used a commercial enteric capsule containing radioactive charcoal to solve these problems. Activated charcoal powder was mixed with Tc-99m pertechnetate and loaded to the enteric capsule which can resist gastric acid and dissolve only in the small intestine. In-vitro stability experiment was performed by immersing these capsules in a colorless phosphate buffer of variable pH which mimicked the condition in stomach and small intestine. In addition, ten healthy Chinese volunteers were included for in-vivo experiment. Anterior and posterior views of abdomen were obtained at regular 30-minute intervals until the eighth hour after administration of the radioactive enteric capsule. Small bowel transit time was calculated. The enteric capsule remained intact for at least 480 minutes in the solution mimicking gastric content (pH = 3.0) and disrupted at a mean duration of 227.2 minutes at a pH of 6.8 and at a mean duration of 212.4 minutes at a pH of 7.4 in the solution mimicking pancreaticobiliary secretions. In nine of ten volunteers, the small bowel transit time was between 30 to 270 minutes with a mean transit time of 140 min. In one volunteer, we failed to detect the exact time of small bowel transit because the capsule remained in the stomach throughout the study for up to 8 hours. We consider activated charcoal labeled with Tc-99m pertechnetate using an enteric capsule as the carrier to be a potential radioactive marker for small bowel transit study.

Mechanisms of Enteral Nutrient-Enhanced Intestinal Adaptation

The role of enteral nutrients in maintaining small intestinal structure and function is well established. Evidence that enteral nutrients induce intestinal adaptation include the structural and functional gradient along the length of the healthy intestine, the atrophy and functional compromise induced by fasting and parenteral nutrition, and the enhanced adaptive capacity of the distal intestine following partial enterectomy. Key mechanisms contributing to enteral nutrient-induced intestinal adaptation include nonspecific luminal stimulation and that provided by specific nutrients, "functional workload" induced by polymeric nutrients, potential stimulation of pancreaticobiliary secretions, secretion of humoral mediators, and induction of intestinal hyperemia.

The role of pancreatico-biliary secretions in intestinal adaptation after resection, and its relationship to plasma enteroglucagon.

Two groups, each containing 16 male Wistar rats, had either 75 per cent small bowel resection or jejunal transection; 8 animals from each group; had previously been subjected to pancreatico-biliary diversion. All animals were killed 12 days after the operation, plasma enteroglucagon levels were measured and crypt cell production rate (CCPR) at different sites of the remaining small intestine was measured using a metaphase arrest technique with vincristine. In each of the resected groups there was a significant increase in the CCPR and enteroglucagon levels compared with the transected groups. Furthermore it was found that the CCPR and enteroglucagon levels were higher in the resected group without the pancreatico-biliary diversion compared with the resected group with the diversion. This study, although it confirms the importance of pancreatico-biliary secretions in intestinal adaptation, could also indicate that a humoral factor may be important in the control of intestinal cell proliferation. Our findings do not exclude the possibility that enteroglucagon could be a candidate for such a role.

High-fat nutrition for short gut syndrome: Another indication for the Atkin’s diet?

High-fat nutrition for short gut syndrome: Another indication for the Atkin’s diet?

Glucagon-Like Peptide-2 and Intestinal Adaptation: An Historical and Clinical Perspective

Of the many models of intestinal adaptation, the structural and functional changes seen in the residual small bowel following jejunectomy or ileectomy are the most predictable and best studied. There are three major mechanisms for these adaptive phenomena: changes in i) luminal nutrition, ii) pancreatico-biliary secretions and iii) hormonal factors. Observations in a unique patient with an "enteroglucagon"-secreting tumor of the kidney associated with massive small bowel enlargement, provided the strongest evidence, at that time (>30 y ago), in favor of hormonal factors. When the patient's renal tumor was removed, the markedly increased circulating concentrations of the glucagon-like peptide (now presumed to be GLP-2) returned to normal-as did her intestinal anatomy. Subsequent studies showed that there are increased tissue and plasma enteroglucagon (and recently GLP-2) levels in many animal models of intestinal adaptation. This, and anecdotal evidence from three other case reports, coupled with contemporary studies of GLP-2, strongly suggest that this glucagon-like peptide is a potent, but not the sole, enterotrophin.

Hydrolysis of dietary fat by pancreatic lipase stimulates cholecystokinin release

Background & Aims: The hypothesis that cholecystokinin release requires adequate dietary fat digestion in the small intestine was investigated in 10 healthy volunteers, and the consequences of reduced fat hydrolysis on pancreaticobiliary secretions were assessed. Methods: Fat hydrolysis was inhibited by intraduodenal perfusion of tetrahydrolipstatin, an irreversible lipase inhibitor. An oil emulsion containing 0, 30, 60, or 120 mg tetrahydrolipstatin was perfused. After a 40-minute basal period, a test meal was eaten to stimulate cholecystokinin release and pancreaticobiliary responses. Results: In the control without tetrahydrolipstatin, lipase output increased threefold with meal ingestion and remained doubled for 4 hours. At the ligament of Treitz, free fatty acid concentration averaged 60% of total fatty acids. Increasing doses of tetrahydrolipstatin induced a dose-dependent inhibition of duodenal lipase activity ( P < 0.01); 120 mg tetrahydrolipstatin eliminated the postprandial lipase peak activity, free fatty acid levels decreased to <5% of total fatty acids, and plasma cholecystokinin levels were suppressed by 77% ( P < 0.01). Amylase and trypsin outputs were reduced by 77% and 59%, respectively, and bilirubin secretion was virtually abolished ( P < 0.01). Conclusions: These findings show that tetrahydrolipstatin prevents triglyceride hydrolysis and that plasma cholecystokinin release, gallbladder emptying, and pancreatic enzyme secretion require adequate triglyceride digestion. These data also support the concept of negative feedback regulation of cholecystokinin secretion. GASTROENTEROLOGY 1998;114:123-129

Solid-phase extraction and determination of ranitidine in human plasma by a high-performance liquid chromatographic method utilizing midbore chromatography.

An improved high-performance liquid chromatographic (HPLC) method utilizing solid-phase extraction (SPE) and midbore chromatography was developed for the determination of ranitidine in human plasma. A mobile phase of 20 mM K2HPO4-acetonitrile-triethylamine (87.9:12.0:0.1, v/v) pH 6.0 was used with a phenyl analytical column and ultraviolet detection (UV). The method demonstrated linearity from 25 to 1000 ng/ml in 500 microliters of plasma with a detection limit of 10 ng/ml. The method was utilized in a pharmacokinetic study evaluating the effects of pancreatico-biliary secretions on ranitidine absorption.

Character of a wheat amylase inhibitor preparation and effects on fasting human pancreaticobiliary secretions and hormones

BACKGROUND & AIMS: Amylase inhibition induces carbohydrate tolerance, satiety, and weight loss and prolongs gastric emptying, effects that may be useful in the treatment of obesity and non-insulin-dependent diabetes mellitus. The aim of this study was to determine (1) purity of a wheat amylase inhibitor preparation, (2) intraduodenal concentration of the wheat amylase inhibitor preparation that inhibits > 90% amylase activity (which causes carbohydrate malabsorption), and (3) if the inhibitor alters pancreaticobiliary secretions or intraluminal pH. METHODS: High-performance liquid chromatography followed by electrophoresis and sodium dodecyl sulfate-polyacrylamide gel electrophoresis were used for characterization. Groups of 3 subjects received intraduodenal infusions of 3.0, 4.5, or 6.0 mg/mL of the inhibitor for 90 minutes during the middle of a 270-minute essential amino acid solution infusion (which stimulates 50% maximal pancreatic enzyme secretion). Pancreatic enzyme and bile acid delivery to the duodenum were measured for a 270-minute period. RESULTS: The inhibitor is 96% protein, 59% containing 0.19, 0.28, 0.38, and 0.53 inhibitors. The 0.38 inhibitor has the most antipancreatic alpha-amylase activity. The inhibitor reduced amylase activity in the duodenum dose dependently (r = 0.7; P = 0.04); > 4 mg/mL inhibited > 90% amylase activity but did not affect delivery of other enzymes or bile acids to the duodenum or gastric or duodenal pH. CONCLUSIONS: The preparation has a high protein purity and a high specific activity against alpha-amylase activity and effectively inhibits human pancreatic amylase activity secreted into the duodenum. (Gastroenterology 1996 Nov;111(5):1313-20)

Imaging of patients with pancreaticobiliary diversion for obesity: post-operative anatomy and findings in small bowel obstruction.

Pancreaticobiliary diversion is a surgical procedure undertaken for obesity. It consists of a distal gastrectomy with a long Roux-en-Y reconstruction, the enteroenterostomy being placed 200 cm distal to the gastroenterostomy and 50 cm proximal to the ileocaecal valve. Three intestinal limbs are recognized: (a) the alimentary loop from the gastroenterostomy to the enteroenterostomy; (b) common loop from the enteroenterostomy to the ileocaecal valve and (c) pancreaticobiliary loop from the duodenum to the enteroenterostomy. The radiological findings in 15 pancreaticobiliary diversion patients with small bowel obstruction were reviewed (15 plain abdominal radiographs, 13 ultrasound (US), 8 CT) and compared with 20 plain abdominal radiographs, 10 US, and 10 CT studies performed for other causes in patients with pancreaticobiliary diversion and 15 CT scans from non-operated patients. After pancreaticobiliary diversion the pancreaticobiliary loop was completely air-free. In the patients operated on more than 1 year previously, alimentary and common loops were significantly larger than the pancreaticobiliary loop and small bowel loops of non-operated subjects. Obstruction of the pancreaticobiliary loop arrests only the flow of pancreaticobiliary secretions with non-specific clinical findings. Plain abdominal radiographs were not diagnostic in all but two cases with radiographically detectable dilated fluid filled loops. Air-fluid levels were never apparent. US and CT showed markedly dilatated intestinal loops and duodenum. Obstruction of the alimentary and common loops presented with symptoms, clinical signs, and radiological findings more typical for bowel obstruction in intact subjects.

Elimination of the Roux stasis syndrome using a new type of “uncut Roux” limb

Background: The Roux stasis syndrome, a syndrome of nausea, vomiting, abdominal pain, and postprandial fullness that follows Roux-en-Y gastrojejunostomy, is thought to result from the jejunal transection performed during the construction of a conventional Roux limb. The purpose of this study was to test a new type of “uncut” Roux limb construction, in which a neuromuscular bridge maintains neuromuscular continuity between the proximal jejunum and the Roux limb, while a jejunojejunostomy provides distal diversion of pancreaticobiliary secretions. Methods: After a distal hemigastrectomy, 5 dogs underwent the uncut Roux operation, while 5 others had a Billroth II reconstruction (controls). Three weeks later, recordings of jejunal myoelectrical activity and assessment of gastric emptying and bile reflux were performed in fully conscious dogs. Results: In the dogs with uncut Roux limbs, jejunal pacesetter potentials propagated aborally across the neuromuscular bridge, although their frequency was slightly slower distal to the bridge (proximal 19.5 ± 0.7 cpm versus distal 18.8 ± 1.1 cpm; P<0.05). No frequency change occurred across the comparable area of jejunum of the controls. Both groups had similar rates of gastric emptying. Only small amounts of bile acids were found in gastric aspirates from dogs with uncut Roux limbs. Conclusions: A new uncut Roux operation eliminated the Roux stasis syndrome by preserving neuromuscular continuity between the proximal jejunum and the Roux limb, and yet provided near-total diversion of bile from the gastric remnant.

Mechanisms of small intestinal adaptation.

Luminal nutrition, hormonal factors and pancreaticobiliary secretions are probably the major mediators of small intestinal adaptation. Their actions, as discussed in this paper, are likely to be interrelated. Direct local enterotrophic effects cannot account for all the actions of luminal nutrients. Additionally, hormonal factors have been shown to contribute to indirect effects of luminal nutrients and enteroglucagon is a likely mediator of adaptive responses. Furthermore, epidermal growth factor is a peptide for which there is convincing evidence of an enterotrophic action. Attention is drawn to the fact that pancreaticobiliary secretions may have a physiological role in stimulating small intestinal mucosal proliferation. Other factors may also influence small intestinal mucosal proliferation (e.g. prostaglandins, neurovascular mechanisms, bacteria). Additionally, polyamines are crucial in initiating cell division in the small intestine, but the detailed mechanisms of their action require further clarification. Finally, a number of therapeutic applications of small intestinal epithelial cell proliferation are discussed.

7 Humoral regulation of intestinal adaptation

After the loss of small bowel through disease or surgery the residual bowel adapts by increasing its functional capacity. This process of adaptation involves dilatation, hypertrophy and mucosal hyperplasia, particularly distal to the area of bowel loss or disease. The response of the residual bowel is mediated by a complex interplay of factors including luminal nutrition, pancreaticobiliary secretions, luminal or local growth factors and also humoral or endocrine factors. The experimental model commonly used to characterize the adaptive response, massive small bowel resection (MSBR), involves 80% resection of the small bowel in the rat. Of the various putative humoral factors, most work has focused on the products of the ileal L cells: enteroglucagon and peptide YY. Plasma levels of both hormones are increased after MSBR and indeed their mRNA levels are also increased as a result of an increase in the amount of message per L cell. Whilst PYY probably serves as an 'ileal brake' to slow the movement of the luminal contents and hence increase their mucosal contact time, the role of the enteroglucagon is unresolved. The molecular cloning of the proglucagon gene has revealed, firstly, that there are a number of biologically active peptides which derive from the propeptide and, secondly, that tissue-specific differential processing occurs. Most studies do not clearly define which of these products of proglucagon is being measured and is termed as glucagon-like or enteroglucagon immunoreactivity. The insulin-like growth factors (IGF) have a potent mitogenic action on the bowel. Their role after MSBR is likely to be largely paracrine. Though IGF-I mRNA levels do not increase after MSBR, the precipitous and early fall in ileal IGF-binding protein-3 (IGFBP-3) mRNA levels suggests a fall in IGFBP-3 levels may increase local IGF-I bioactivity. Polyamine synthesis is a critical component of the adaptive response, although the stimulus to their dramatic increase in synthesis after MSBR remains to be elucidated. Other humoral factors such as cholecystokinin, neurotensin and bombesin probably have minor indirect roles in the adaptive response. Components of the epidermal growth factor/transforming growth factor alpha response pathway family of growth factors may be involved as paracrine regulators. There is thus strong evidence that humoral factors play an important role in intestinal adaptation; characterization of the nature of the humoral factors and their relationship with other influences such as luminal nutrition and pancreatic biliary secretions may facilitate the development of new therapeutic strategies for the short bowel syndromes.

Intestinal absorptive function.

The normal gut is adapted to intermittent feeding with complex macromolecular substrates of low sodium content. The high permeability of the upper small intestine to sodium, together with sodium rich saliva and pancreaticobiliary secretions results in large sodium fluxes into the lumen. These substantial sodium influxes are matched by equally large effluxes from the ileum and proximal colon, which are comparatively impermeable to sodium and capable of active sodium absorption. Resection of these distal, sodium absorbing regions of the intestine, lead to problems with sodium depletion. Controlled transit of chyme is essential to permit time for optimum digestion and absorption and a range of feedback control mechanisms exist. Partially digested nutrients, both in the duodenum and ileum, exert inhibitory feedback to delay delivery of further nutrients and here again surgery may compromise these reflexes. Brush border hydrolase values are strongly influenced by luminal nutrient concentrations, being impaired by malnutrition and total parenteral nutrition, but restored by enteral feeding. Viscous fibre slows absorption and may delay transit through mechanisms that are as yet uncertain. Whether and how novel substrates activate normal control mechanisms will be important factors determining their effectiveness and patient acceptability.

Theophylline and prostaglandin E2 on duodenal bicarbonate secretion: Role for 5′-cyclic adenosine monophosphate

Cyclic adenosine monophosphate (cAMP) has been implicated as an intracellular “second” messenger in duodenal mucosal bicarbonate secretion in animals. The purpose of this study was to determine whether cAMP may mediate duodenal mucosal bicarbonate secretion in humans. In healthy volunteers, a 4-cm segment of proximal duodenum was isolated from gastric and pancreaticobiliary secretions. Either the phosphodiesterase inhibitor theophylline, prostaglandin (PG) E2, or a combination thereof was administered topically to the isolated duodenal mucosa. Theophylline (10−2 mol/L) and PGE2 (10−5–10−4 mol/L) each significantly increased bicarbonate secretion and transmucosal potential difference. Moreover, when theophylline and PGE2 were administered in combination, the duodenal bicarbonate output was additive compared to either agent alone. When theophylline was infused with increasing doses of PGE2, the dose-response curve was shifted to the left. Furthermore, increases in bicarbonate secretion and transmucosal potential difference were correlated significantly. These results suggest that cAMP may act as an intracellular mediator of human duodenal mucosal bicarbonate secretion.