Flow Of Pancreatic Juice Research Articles

Dorsal Pancreatic Duct Dominance in Pancreaticobiliary Maljunction

In patients with pancreaticobiliary maljunction (PBM), reflux of pancreatic juice to the bile duct may contribute to carcinogenesis of the biliary tract. This study aimed to investigate the pancreatographic findings in patients with PBM and the relationship to their clinical findings in view of pancreatic juice flow. Seventy-eight cholangiopancreatograms were reviewed. When the maximum diameter of the Santorini duct was almost equal to or greater than that of the ventral pancreatic duct, the relationship between the 2 ducts was defined as dorsal pancreatic duct (DPD) dominance. Pancreatographic findings were divided into 2 groups: a normal duct group (69 patients) and a DPD dominant group (9 patients). Although 40 patients (58%) with biliary carcinoma were identified in the normal duct group of PBM, only 1 gallbladder carcinoma (11%) occurred in DPD-dominant patients (P < 0.01). A large-caliber Santorini duct was noted to flow straight from the upstream DPD in all patients with DPD dominance. Concentration of amylase in the bile of DPD dominance was significantly lower than that of normal pancreatic duct system (P < 0.01). In PMB with DPD dominance, most pancreatic juice in the upper DPD is drained into the duodenum through the minor duodenal papilla, and reflux of pancreatic juice to the biliary tract might be reduced, resulting in reduced frequency of associated biliary carcinogenesis.

Dorsal Pancreatic Duct Dominance in Pancreaticobiliary Maljunction

Background and Aims: In patients with pancreaticobiliary maljunction (PBM), reflux of pancreatic juice to the bile duct may contribute to carcinogenesis of the biliary tract. This study aimed to investigate the pancreatographic findings in patients with PBM, and the relationship to their clinical findings in view of pancreatic juice flow. Materials and Methods: Seventy-eight cholangiopancreatograms of PBM were reviewed. When the maximum diameter of the Santorini's duct was almost equal to or greater than that of the ventral pancreatic duct, the relationship between the two ducts was defined as dorsal pancreatic duct (DPD) dominance. Radiological and clinical findings including the incidence of associated biliary carcinoma were examined. Results: Pancreatographic findings were divided into two groups; a normal duct group (69 patients) and a DPD dominant group (9 patients). There was no significant difference in age and sex between the two groups. Although 40 patients (58%) with biliary carcinoma (gallbladder carcinoma, n=35; bile duct carcinoma, n=5) were identified in the normal duct group of PBM, only one gallbladder carcinoma (11%) occurred in DPD-dominant patients (P<0.01). In DPD-dominant patients, 8 patients underwent prophylactic surgical treatment except for one patient with advanced gallbladder carcinoma. There was no patient in which metachronous biliary carcinoma occurred during follow-up period. Patients with a dominant DPD included 7 patients with PBM with biliary dilatation and 2 with PBM without biliary dilatation. Although there was no difference in the diameter of the ventral pancreatic duct, the maximum diameter of the Santorini's duct in DPD dominance was significantly larger than that of normal pancreatic duct system (mean 2.7 mm vs. 0.9 mm, p<0.01). A large-caliber Santorini's duct was noted to flow straight from the upstream DPD in all patients with DPD dominance. Concentration of amylase in the bile of DPD dominance was significantly lower than that of normal pancreatic duct system (mean 85750 IU/L vs. 420600 IU/L, p<0.01). Conclusions: PBM sometimes exhibits DPD dominance. In PMB with DPD dominance, most pancreatic juice in the upper DPD is drained into the duodenum via the minor duodenal papilla, and reflux of pancreatic juice to the biliary tract might be reduced, resulting in reduced frequency of associated biliary carcinogenesis. Background and Aims: In patients with pancreaticobiliary maljunction (PBM), reflux of pancreatic juice to the bile duct may contribute to carcinogenesis of the biliary tract. This study aimed to investigate the pancreatographic findings in patients with PBM, and the relationship to their clinical findings in view of pancreatic juice flow. Materials and Methods: Seventy-eight cholangiopancreatograms of PBM were reviewed. When the maximum diameter of the Santorini's duct was almost equal to or greater than that of the ventral pancreatic duct, the relationship between the two ducts was defined as dorsal pancreatic duct (DPD) dominance. Radiological and clinical findings including the incidence of associated biliary carcinoma were examined. Results: Pancreatographic findings were divided into two groups; a normal duct group (69 patients) and a DPD dominant group (9 patients). There was no significant difference in age and sex between the two groups. Although 40 patients (58%) with biliary carcinoma (gallbladder carcinoma, n=35; bile duct carcinoma, n=5) were identified in the normal duct group of PBM, only one gallbladder carcinoma (11%) occurred in DPD-dominant patients (P<0.01). In DPD-dominant patients, 8 patients underwent prophylactic surgical treatment except for one patient with advanced gallbladder carcinoma. There was no patient in which metachronous biliary carcinoma occurred during follow-up period. Patients with a dominant DPD included 7 patients with PBM with biliary dilatation and 2 with PBM without biliary dilatation. Although there was no difference in the diameter of the ventral pancreatic duct, the maximum diameter of the Santorini's duct in DPD dominance was significantly larger than that of normal pancreatic duct system (mean 2.7 mm vs. 0.9 mm, p<0.01). A large-caliber Santorini's duct was noted to flow straight from the upstream DPD in all patients with DPD dominance. Concentration of amylase in the bile of DPD dominance was significantly lower than that of normal pancreatic duct system (mean 85750 IU/L vs. 420600 IU/L, p<0.01). Conclusions: PBM sometimes exhibits DPD dominance. In PMB with DPD dominance, most pancreatic juice in the upper DPD is drained into the duodenum via the minor duodenal papilla, and reflux of pancreatic juice to the biliary tract might be reduced, resulting in reduced frequency of associated biliary carcinogenesis.

The changes of Oddi sphincter motility after canine pancreas transplantation with bladder drainage

To study the changes of canine Oddi sphincter (SO) function after pancreas transplantation with bladder drainage and the effect on the graft function. Normal canine SO, transplant canine SO and canine SO in vitro manometry were performed by triple lumen catheter. At the same time, pancreas endocrine and exocrine function after transplantation were determined. After transplantation, anti-reflux function of graft SO was also measured. Endocrine and exocrine function of all the transplanted dogs showed that pancreas graft function was good. Basal pressure of SO in control group was (18.5 +/- 2.8) mm Hg (1 mm Hg = 0.133 kPa). The contraction frequency was (9.7 +/- 1.5) per min, the contraction amplitude was (47.1 +/- 5.5) mm Hg, the motility index was (236 +/- 56). After transplantation, basal pressure increased to (27.8 +/- 2.8) mm Hg, frequency increased to (13.1 +/- 1.9) per min, amplitude decreased significantly to (8.3 +/- 1.8) mm Hg. There was no significant difference of motility index. Basal pressure of SO in vitro increased significantly to (37.2 +/- 5.1) mm Hg. Phasic contraction was not absent. After transplantation, the pressure in the bile duct residual did not increase in accordance with the increase of bladder pressure. After pancreas transplantation with bladder drainage, Basal pressure and frequency of canine SO could increase while amplitude could decrease, which provide the anti-reflux function of graft SO and may serve as an obstacle to pancreatic juice flow.

Distended glands or overreplacement of ampullary mucosa at the papilla of Vater.

The role of the ampullary mucosa, especially its distended glands at the papilla of Vater, has not been fully explored. Twenty-nine pancreatoduodenectomized specimens from pancreatobiliary diseases and 44 autopsied cases, as controls, were studied histopathologically and immunohistochemically. In 12 out of the 29 pancreatoduodenectomized cases the ampullary mucosa was in contact with the duodenal mucosa just at the outlet of the ampulla. In the remaining 17 cases, the ampullary mucosa overgrew beyond the ostium, replacing a portion of the surrounding duodenal mucosa, termed "distended glands," which measured an average of 1532 microm in length. The muscularis mucosae of the duodenum and the Oddi's sphincter muscle merged in an "end-to-end, sharp-angled" manner at the ostium in the former, whereas this occurred in an "end-to-side, less sharp, rather right-angled" manner in the latter. Immunohistochemically, the distended glands in some cases showed negative/weakly positive staining for anti-carbohydrate antigen (CA) 19-9 and a high proliferation index evaluated using Ki67. In the autopsied materials, distended glands were found in 24 out of the 44 cases. Distended glands of the ampullary mucosa were frequently found and only grew on the Oddi's sphincter muscle extension. They may represent not only malignant change but also an adaptive phenomenon for bile and pancreatic juice flow.

Clinical significance of the minor duodenal papilla and accessory pancreatic duct.

The accessory pancreatic duct (APD) is the main drainage duct of the dorsal pancreatic bud in the embryo, entering the duodenum at the minor duodenal papilla (MIP). As development progresses, the duct of the dorsal bud undergoes varying degrees of atrophy at the duodenal end. In cases of patent APD, smooth-muscle fiber bundles derived from the duodenal proper muscular tunics surround the APD. The APD shows long and short patterns on pancreatography, and ductal fusion in the two types appears to differ embryologically. Patency of the APD in control cases, as determined by dye-injection endoscopic retrograde pancreatography, was 43%. Patency of the APD may depend on duct caliber, course, and terminal shape of the APD. A patent APD may prevent acute pancreatitis by reducing the pressure in the main pancreatic duct. Pancreas divisum is a common anatomical anomaly in which the ventral and dorsal pancreatic ducts do not unite embryologically. As the majority of exocrine flow is routed through the MIP in individuals with pancreas divisum, interrelationships between poor function of the MIP and increased flow of pancreatic juice caused by alcohol or diet may increase dorsal pancreatic duct pressure and lead to the development of pancreatitis. Wire-guided minor sphincterotomy, followed by dorsal duct stenting, is recommended for acute recurrent pancreatitis associated with pancreas divisum.

Mechanism of exocrine pancreatic insufficiency in streptozotocin-induced diabetes mellitus in rat: effect of cholecystokinin-octapeptide.

This study investigated the effects of cholecystokinin-octapeptide (CCK-8) on pancreatic juice flow and its contents, and on cytosolic calcium (Ca2+) and magnesium (Mg2+) levels in streptozotocin (STZ)-induced diabetic rats compared to healthy age-matched controls. Animals were rendered diabetic by a single injection of STZ (60 mg kg(-1), I.P.). Age-matched control rats obtained an equivalent volume of citrate buffer. Seven weeks later, animals were either anaesthetised (1 g kg(-1) urethane; IP) for the measurement of pancreatic juice flow or humanely killed and the pancreas isolated for the measurements of cytosolic Ca2+ and Mg2+ levels. Non-fasting blood glucose levels in control and diabetic rats were 92.40 +/- 2.42 mg dl(-1) (n = 44) and >500 mg dl(-1) (n = 27), respectively. Resting (basal) pancreatic juice flow in control and diabetic anaesthetised rats was 0.56 +/- 0.05 ul min(-1) (n = 10) and 1.28 +/- 0.16 ul min(-1) (n = 8). CCK-8 infusion resulted in a significant (p < 0.05) increase in pancreatic juice flow in control animals compared to a much larger increase in diabetic rats. In contrast, CCK-8 evoked significant (p < 0.05) increases in protein output and amylase secretion in control rats compared to much reduced responses in diabetic animals. Basal [Ca2+]i in control and diabetic fura-2-loaded acinar cells was 109.40 +/- 15.41 nM (n = 15) and 130.62 +/- 17.66 nM (n = 8), respectively. CCK-8 (10(-8)M) induced a peak response of 436.55 +/- 36.54 nM (n = 15) and 409.31 +/- 34.64 nM (n = 8) in control and diabetic cells, respectively. Basal [Mg2+]i in control and diabetic magfura-2-loaded acinar cells was 0.96 +/- 0.06 nM (n = 18) and 0.86 +/- 0.04 nM (n = 10). In the presence of CCK-8 (10(-8)) [Mg2+]i in control and diabetic cells was 0.80 +/- 0.05 nM (n = 18) and 0.60 +/- 0.02 nM (n = 10), respectively. The results indicate that diabetes-induced pancreatic insufficiency may be associated with derangements in cellular Ca2+ and Mg2+ homeostasis.

Effect of insulin on exocrine pancreatic secretion in healthy and diabetic anaesthetised rats

This investigation characterised the effects of exogenous insulin on exocrine pancreatic secretion in anaesthetised healthy and diabetic rats. Animals were rendered diabetic by a single injection of streptozotocin (STZ, 60 mg kg(-1) I.P.). Age-matched controls were injected citrate buffer. Rats were tested for hyperglycaemia 4 days after STZ injection and 7-8 weeks later when they were used for the experiments. Following anaesthesia (1 g kg(-1) urethane I.P.), laparotomy was performed and the pancreatic duct cannulated for collection of pure pancreatic juice. Basal pancreatic juice flow rate in diabetic rats was significantly (p < 0.001) increased whereas protein and amylase outputs were significantly (p < 0.001) decreased compared to control rats. Insulin (1 IU, I.P.) produced in healthy rats significant increases in pancreatic flow rate, amylase secretion and protein output compared to basal (p < 0.05). Insulin action also included a reduction in blood glucose (152.7 +/- 16.9 mg dl(-1), n = 6, prior to insulin and 42.0 +/- 8.4 mg dl(-1), n = 4, 100 min later). In fact, flow rate and glycaemia showed a strong negative correlation (p < 0.01, Pearson). Pretreatment with atropine (0.2 mg kg(-1), I.V.) abolished the effects of insulin on secretory parameters despite a similar reduction in glycaemia; in this series of experiments the correlation between flow rate and blood glucose was lost. In diabetic rats, insulin (4 IU, I.P.) did not modify exocrine pancreatic secretion. There was a fall in blood glucose (467.6 +/- 14.0 mg dl(-1), n = 10, prior to insulin and 386.6 +/- 43.6 mg dl(-1), n = 7, 120 min later). Rats, however, did not become hypoglycaemic. Similar results were observed in diabetic atropinized rats. The results of this study indicate that the effects of insulin on exocrine pancreatic secretion in anaesthetised healthy rats are mediated by hypoglycaemia-evoked vagal cholinergic activation.

The Efficacy of Pancreatic Stenting for Management of Pancreatic Stones

Background and Aim: Pancreatic duct stones are a common finding in obstructive chronic pancreatitis and often firmly impacted proximal to a stricture. The stones and strictures may impair the pancreatic juice flow to the duodenum, inducing ductal hypertension, which is a major cause of pain. More recently, therapeutic endoscopy and stone fragmentation by extracorporeal shockwave lithotripsy (ESWL) have been used to perform pancreatic duct drainage and clearance. Pancreatic stenting is effective for the ductal decompression, but is still controversial because of the stent occulusion or the stent-related ductal changes. Therefore, we analyzed the efficacy of pancreatic stenting after stone extraction. Patients and Methods: Thirty-one patients with symptomatic pancreatic stones have been treated with endoscopy in combination with ESWL between January 1998 and September 2003. If there were one or more severe strictures in main pancreatic duct (MPD) on endoscopic retrograde pancreatography at the end of the complete stone clearance of MPD, a 7Fr, 8.5Fr or 10Fr polyethylene stent was inserted immediately after balloon dilatation of the stricture and the papilla of Vater so that all strictures were bypassed. The inserted stent was exchanged every three months or soon after any symptoms due to occulusion, and removed after one year. On the other hand, those who had mild or no stricture in MPD were observed without stenting until any symptoms related to pancreatitis were seen. Recurrent rates of pancreatic symptoms in severe and mild/no stricture group were evaluated. Results: Twenty of 31 patients had severe stricture and stenting was successful in 19 of them. The stent had been removed in 13 of 19 patients after one year's stenting period. Recurrent pancreatic pains were seen only in 3 (23%) of 13 patients in the severe stricture group by stenting, compared with 8 (73%) of 11 patients in the mild/no stricture group (p<0.01) in the mean follow up periods of 18 months. Seven of 8 patients with recurrent pancreatic pain in mild stricture group were received stenting at the recurrence, all of whom were improved. Conclusion: Additional stenting for MPD to stone extraction is effective for the management of the pancreatic stone.

Patent Accessory Pancreatic Duct Prevent Post-ERCP pancreatitis

Background/Aims: Pancreatitis is the most important complication of ERCP. Moreover, efforts to understand its pathogenesis and to identify ways to reduce the frequency and severity of this complication have shown no convincing benefit to date. Although very complex factors are involved in the development of post-ERCP pancreatitis, mechanical injury to the papilla causing papillary edema and restriction of pancreatic juice flow, and hydrostatic injury from over-injection are the most common causes. We have prospectively examined patency of the accessory pancreatic duct (APD) by dye-injection ERP. We examined the role of the APD in vivo, and proposed a new way to prevent post-ERCP pancreatitis. Methods: During ERP, 2 or 3 ml of contrast medium containing indigo carmine was injected through a catheter in the main pancreatic duct (MPD) with usual pressure in 443 cases. Dye excretion from the minor papilla was then observed endoscopically. Results: Of 312 controls, patency of the APD was observed in 43%, whereas in 51 patients with acute pancreatitis, only 8 (16%) had a patent APD (p<0.01). In particular, patency of the APD was seen in only one of 17 patients with acute biliary pancreatitis. Patency of the APD showed a close relationship to the course and terminal shape of the APD. The long-type APD, which joined the MPD at its neck portion and ran straight from the upper dorsal pancreatic duct, was more frequently patent than the short-type APD which joined the MPD near its first inferior branch and followed a descending course (75.5% patency vs. 36.0%, p<0.01). Regarding terminal shape of the APD, patency of the cudgel (89.2%) and spindle type (92.0%) was more frequent than of the branch type (5.9%) or saccular type (16.7%) (p<0.01). According to the above findings, we retrospectively examined patency of the APD in 25 patients with acute pancreatitis after diagnostic ERP (6500 cases). Patency of the APD was estimated at only 8% (2/25). Furthermore, 3 cases showing acute pancreatitis after stone extraction with endoscopic balloon dilatation, exhibited nonpatent APD. Conclusions: A patent APD may prevent acute pancreatitis by lowering the pressure in the MPD. During ERCP, in cases with short type APD or APD with branch or saccular terminal shape, endoscopists should be more cautious and never persist when selective cannulation is difficult, or alternatively consider prophylactic pancreatic stenting.

A new synthetic porcine secretin for facilitation of cannulation of the dorsal pancreatic duct at ERCP in patients with pancreas divisum: A multicenter, randomized, double-blind comparative study

Background: Secretin, a 27 amino acid polypeptide released in response to duodenal luminal acidification, stimulates secretion of water and bicarbonate from pancreatic ductal cells. To date the only secretin available for clinical use has been a biologically derived compound extracted from porcine duodenums. Although used to facilitate pancreatic duct cannulation, secretin has not been approved for this indication. In this study, a new synthetic porcine secretin with an identical amino acid composition was compared with saline solution for the facilitation of minor papilla cannulation in patients with pancreas divisum. Methods: A multicenter, prospective, randomized, placebo-controlled, double-blind, comparative trial was conducted at 4 centers with expertise in pancreaticobiliary endoscopy. Patients with pancreas divisum in whom minor papilla cannulation initially was unsuccessful were enrolled. Either saline solution (placebo) or synthetic porcine secretin was administered. If the minor papilla orifice and/or pancreatic juice flow was noted, cannulation was attempted and success or failure was documented (phase 1), as well as the time taken for successful cannulation. If cannulation was unsuccessful, no juice flow was noted, or the orifice was not seen, the alternate agent was administered (phase 2). Results: Twenty-nine patients (7 men, 22 women; mean age 51 years, range 21-76 years) were enrolled. In phase 1, cannulation was achieved in 1 of 13 patients (7.7%) after the placebo was given and in 13 of 16 patients (81.3%) after synthetic porcine secretin was given (p < 0.0001). In phase 2, cannulation was achieved in 12 of 12 patients (100%) after synthetic porcine secretin was given and in 0 of 3 patients (0%) after the placebo was given (p = 0.0022). Overall, cannulation was successful in 25 of 28 patients (89.3%) who received synthetic porcine secretin and in 1 of 16 (6.3%) who received the placebo (p < 0.0001). Mean time to cannulation was significantly greater for the placebo than for the synthetic porcine secretin (4.75 min vs. 2.63 min; p = 0.0001). No adverse events directly attributable to synthetic porcine secretin administration were documented. Conclusions: This study confirmed the use and safety of synthetic porcine secretin in facilitating cannulation of the minor papilla in patients with pancreas divisum in whom cannulation was difficult. Use of this agent has the potential to further increase the cannulation success rate in this group of patients. (Gastrointest Endosc 2003;57:643-7.)

Oddi sphincter function after canine auto-pancreas transplantation with bladder drainage.

Several neural and hormonal factors are known to affect motility of sphincter of Oddi (SO). The major roles of SO are to regulate the flow of bile and pancreatic juice into the duodenum and to prevent the reflux of duodenal contents into the biliary and pancreatic duct. After pancreas transplantation, graft SO was denervated and graft pancreatitis might have relations to SO motility. The motility of SO after canine pancreas transplantation with bladder drainage was investigated. Normal canine SO manometry and pancreas graft SO manometry after pancreas transplantation with bladder drainage were performed in seven dogs respectively before and after cholecystokinin (CCK) administration. Data of SO basal pressure, contraction frequency, amplitude and motility index after transplantation and CCK administration were compared with that in controls and before CCK administration. SO showed regular contractions with a certain basal pressure in control dogs. After transplantation, the graft SO basal pressure and contraction frequency were higher than that in controls, but the amplitude decreased (P<0.01). There was no great difference in SO motility index. CCK administration could relax normal SO but stimulate graft SO after pancreas transplantation with bladder drainage. After CCK administration, SO basal pressure, frequency and motility index were increased significantly (P<0.05), in comparison with that before administration. The amplitude remained unchanged (P>0.05), in comparison with that before CCK administration. After auto-pancreas transplantation with bladder drainage, canine SO motility was inhibited. Basal pressure and frequency increased but amplitude decreased. CCK administration after transplantation had an inhibitory effect on canine SO instead of a relaxation effect observed in normal canine SO. This will increase the resistance of SO to the pancreatic juice flow and induce pancreatic juice stagnation and can not prevent reflux of urine and duodenal contents when the bladder pressure is increased to a certain extent, which may cause graft pancreatitis.

Development of a bent-type tube stent for simultaneous drainage of bile and pancreatic juice.

Endoscopic lithotomy is a useful medical procedure for treating choledocholithiasis. Although this procedure is commonly performed, complications such as pancreatitis and cholangitis are recognized as major and serious problems. The obstruction of bile and pancreatic juice flow caused by papillary edema or spasm is thought to be responsible for such complications. We have developed a new bent-type tube stent that can drain bile and pancreatic juice simultaneously. From June to November 2001, temporary implantation of the new bent-type tube stent was performed in four patients (two women, two men; mean age, 73.3 years) with choledocholithiasis, for the drainage of bile and pancreatic juice simultaneously after endoscopic lithotomy by endoscopic sphincterotomy or endoscopic balloon sphincter dilatation. Immediately after the implantation of the new type of tube stent, bile and pancreatic juice flow from the respective ducts was recognized under endoscopic observation. Neither pancreatitis nor cholangitis occurred after these procedures. This procedure may be a helpful means to prevent pancreatitis and cholangitis after endoscopic lithotomy.

A brief commentary: electroacupuncture may relax the contraction of sphincter of Oddi.

Animal studies have shown that acupuncture can affect the function of the sphincter of Oddi, a smooth muscle encircling major papilla located at the second portion of the duodenum that regulates the flow of bile and pancreatic juice. This study of thirteen patients was the first to observe the effects of acupuncture on sphincter of Oddi motility in humans. Stimulation of the acupuncture point GB-34, which is known to Oriental medicine as an acupoint with effect on the biliary system, showed reversible inhibition of sphincter of Oddi contractions. In contrast, stimulation of a nonspecific control acupoint did not induce significant change. This study suggests that acupuncture may be one alternative treatment for patients with sphincter of Oddi dysfunction.

Pancreatic exocrine responses to parasympathetic stimulation in anaesthetized pigs

Pancreatic exocrine responses to stimulation of the peripheral ends of the vagus nerves intermittently have been investigated in anaesthetized pigs and compared with the effects of continuous stimulation at corresponding frequencies. At relatively low frequencies (≤20 Hz in bursts or 2 Hz continuously) both the flow of pancreatic juice and the output of protein therein were potentiated by stimulating in bursts. Thus stimulation at 20 Hz in bursts produced a significantly greater flow of pancreatic juice than stimulation at 2 Hz continuously (10.9±0.9 compared to 4.8±0.7 μl min −1 (g gland) −1, respectively; P<0.01). Likewise the output of protein during intermittent stimulation at 20 Hz (144±23 μg min −1 (g gland) −1) far exceeded that produced during continuous stimulation at 2 Hz (49±9 μg min −1 (g gland) −1; P<0.01). Both differences were abolished by atropine (0.5 mg kg −1 i.v.), which augmented the flow during continuous stimulation (to 8.7±1.5 μl min −1 (g gland) −1; P<0.05 at 2 Hz) and substantially reduced the output of protein during intermittent stimulation (to 27±7 ng min −1 (g gland) −1; P<0.01 at 20 Hz in bursts). These results show that a variety of pancreatic exocrine responses can be enhanced by stimulating the parasympathetic innervation in bursts. They are also consistent with the contention that the secretion of protein from the gland, in response to parasympathetic stimulation, is dependent mainly on activation of muscarinic receptors. They confirm that the flow of pancreatic juice is due mainly to the release of VIP and show that, in the absence of atropine, this is restricted by muscarinic inhibition which may be presynaptic as elsewhere.

Sphincterotomy for biliary sphincter of Oddi dysfunction.

The sphincter of Oddi regulates both bile and pancreatic juice flow into the duodenum. When dysfunction occurs it leads to problems relating to either the bile or pancreatic ducts. On the biliary side, the most common problem is recurrent biliary type pain following cholecystectomy. Is sphincterotomy effective treatment for biliary sphincter of Oddi dysfunction patients? Electronic data bases, including the Collaborative Review Group trial registers, MEDLINE, and EMBASE, as well as checking reference lists in as many languages as possible that had the titles: sphincter of Oddi dysfunction, biliary dyskinesia, papillary stenosis, biliary dyssynergia, odditis, papillitis, post-cholecystectomy pain, right upper quadrant pain, or unexplained right upper quadrant pain were included. These titles were matched with sphincterotomy. Randomised placebo-controlled trials performing sphincterotomy in patients with suspected biliary sphincter of Oddi dysfunction using manometry as part of the patient evaluation. A basal pressure > 40 mmHg was defined as abnormal. The primary outcome measure were symptomatic response (defined either as cure/improvement or not improved) to sphincterotomy. Electronic data bases were used to search for the studies. Studies were attempted to be stratified as randomised clinical trials, controlled clinical trials (i.e., quasi-randomised clinical trials), well designed observational studies using a well matched control group, or other. These groupings were then entered into a meta-analysis. Only two randomised clinical trials met the inclusion criteria. In 49 patients studied, sphincterotomy was more effective than placebo in treating patients with an elevated basal pressure (Peto odds ratio 9.08, 95% confidence interval 2.97-277.77). In 77 patients studied, sphincterotomy was no better than placebo in treating patients with a normal normal basal pressure (Peto odds ratio 1.28, 95% confidence interval 0.52-3.13). There was no data on quality of life or health economics. These results suggest that sphincterotomy for biliary sphincter of Oddi dysfunction appears effective in those patients with an elevated sphincter of Oddi basal pressure (>40 mmHg), but is no better than placebo in those patients with a normal basal pressure. The results reported in this review must be interpreted with caution as there are only two studies and one of the reviewers (Toouli) has been an author in both studies. Further trials by independent groups are recommended.

Effects of M1 and CCK antagonists on latency of pancreatic amylase response to intestinal stimulants

In six conscious dogs with gastric and duodenal cannulas, secretin (164 pmol. kg(-1). h(-1) iv) was given to provide a flow of pancreatic juice of approximately 1 drop/s. Amylase activity was measured in each drop before and after rapid intravenous injection of caerulein (7.4 pmol/kg) or intraduodenal injection of L-tryptophan (1 mmol), sodium oleate (3 mmol), and HCl (3 mmol). All experiments were repeated in the presence of the M1 receptor antagonist telenzepine (81 nmol. kg(-1). h(-) iv) and the cholecystokinin (CCK) receptor antagonist L-364718 (0.1 mg/kg iv). Latency of amylase response (time between injection of stimulant and sustained increase in amylase activity greater than mean + 3 SD of prestimulatory activity) to tryptophan (17 +/- 7 s; n = 6) and oleate (16 +/- 5 s) was significantly (P < 0.05) shorter than to caerulein (28 +/- 4 s) and HCl (120 +/- 47 s). Telenzepine significantly increased the latency of amylase response to tryptophan and oleate by >10-fold but not the latency to caerulein or HCl. L-364718 abolished the amylase response to all stimulants. These findings indicate that the early amylase response to intraduodenal tryptophan and oleate is mediated by a neural enteropancreatic reflex ending on M1 receptors rather than by hormone release. However, the activation of (possibly vagal) CCK receptors is essential to run the reflex. The early amylase response to intraduodenal HCl is probably mediated by the release of CCK into the blood circulation.

A secretin releasing peptide exists in dog pancreatic juice

Canine pancreatic juice has been shown to stimulate exocrine pancreatic secretion in the dog. In the present study we investigated whether there is a secretin-releasing peptide in canine pancreatic juice. Pancreatic juice was collected from the dogs with Thomas gastric and duodenal cannulas while pancreatic secretion was stimulated by intravenous administration of secretin at 0.5 μ/gk/gh and CCK-8 at 0.2 μg/kg/h, respectively. The pancreatic juice was separated into three different molecular weight (MW) fractions (Fr) by ultrafiltration (Fr 1; MW > 10,000, Fr 2; MW = 10,000 − 4,000 and Fr 3; MW < 4,000), respectively. All the fractions were bioassayed in anesthetized rats. Fraction 3 dose-dependently and significantly stimulated pancreatic juice flow volume from 78.0% to 99.4% (p < 0.05) and bicarbonate output from 128.9% to 202.1% (p < 0.01), respectively. Plasma secretin concentration also increased from 1.2 ± 0.5 pM to 5.0 ± 0.8 pM and 6.0 ± 1.0 pM (p < 0.05). None of these fractions increased pancreatic protein secretion or plasma CCK level. The stimulatory effect of Fraction 3 on pancreatic secretion and the release of secretin was completely abolished by treatment with trypsin (1 mg ml for 60 min at 37 ° C) but not by heating (100 ° C, 10 min). Intravenous injection of a rabbit anti-secretin serum, which rendered plasma secretin almost undetectable in rat plasma, also abolished Fr 3-stimulated pancreatic secretion of fluid and bicarbonate secretion. These observations suggest that a secretin-releasing peptide exists in the canine pancreatic juice. It is trypsin-sensitive and heat-resistant. This peptide may play a significant physiological role on the release of secretin and regulation of exocrine pancreatic secretion.

Endoscopic botulinum toxin injection into the minor papilla for treatment of idiopathic recurrent pancreatitis in patients with pancreas divisum

Background: In some patients with pancreas divisum, obstruction to the flow of pancreatic juice into the duodenum is the presumptive cause of acute recurrent pancreatitis. However, identification of those patients who may benefit from minor papilla sphincterotomy or stent placement is difficult. Methods: Five patients with acute recurrent pancreatitis and pancreas divisum were therefore treated by endoscopic injection of 50 units of botulinum toxin into the minor papilla in an outpatient setting. Results: Botulinum toxin injection was successfully performed on six occasions in 5 patients and no adverse effects were noted. Two patients relapsed after 9 and 10 months, respectively, but had definite relief of symptoms after needle-knife sphincterotomy. One patient relapsed 7 months after botulinum toxin injection but became symptom free again after a second botulinum toxin injection. Another patient is still in clinical remission 4 months after botulinum toxin administration, and 1 patient did not respond to either botulinum toxin administration or to sphincterotomy and stent placement. Conclusions: Endoscopic injection of botulinum toxin into the minor papilla in patients with pancreas divisum and acute recurrent pancreatitis is a safe procedure that is easy to perform and provides short-term relief in some patients. Response to botulinum toxin injection may predict whether patients with pancreas divisum and acute recurrent pancreatitis will benefit from other forms of endoscopic therapy.

Substance P inhibits pancreatic exocrine secretion via a neural mechanism.

We investigated the effects of the sensory neuropeptide substance P (SP) on amylase and fluid secretion in the isolated vascularly perfused rat pancreas. SP inhibited CCK-induced amylase release and secretin-induced juice flow via the pancreatic duct in a dose-related fashion. Threshold inhibition occurred following addition of 10(-10) M SP to the perfusate, and maximal inhibition was seen with 10(-8) M SP. The effects of SP were partially blocked by both the neurokinin-1 (NK1) and neurokinin-2 (NK2) receptor antagonists. Atropine and TTX blocked SP-induced effects on both amylase secretion (26 and 63% blockade, respectively) and pancreatic juice flow (21 and 79% blockade, respectively). Excitation of pancreatic sensory nerves using capsaicin (in the absence of SP) inhibited both amylase and pancreatic juice flow via activation of the NK1 receptor. We conclude that SP inhibits exocrine secretion via an indirect neural mechanism.

Exogenous CCK and gastrin stimulate pancreatic exocrine secretion via CCK-A but also via CCK-B/gastrin receptors in the calf.

A predominance of the pancreatic cholecystokinin (CCK) receptor of the B/gastrin subtype (CCK-B/G) was reported in calves older than 1 month. Specific CCK-A and CCK-B/G receptor antagonists (SR 27897 and PD 135158, respectively) were used to identify the CCK receptor subtype involved in exogenous CCK- and gastrin-induced exocrine pancreatic responses. Conscious calves (2 months old) with catheterized pancreas, jugular vein and duodenum were used; the pancreatic juice was continuously reinfused. CCK (30 pmol kg-1 min-1, 40 min) evoked an increase in pancreatic juice flow and enzyme secretion, while the same dose of gastrin increased enzyme secretion alone. CCK-induced pancreatic secretion was abolished by SR 27897 (15 nmol kg-1 min-1, 55 min) and reduced by PD 135158 (0.15 nmol kg-1 min-1, 55 min). Gastrin-induced enzyme secretion was reduced by PD 135158 (50% to 90%) and to a lesser extent by SR 27897 (50% to 60%). These results demonstrate that CCK and gastrin in the physiological range stimulate pancreatic exocrine secretion in calves and that these effects are partly mediated by CCK-B/G receptors. Although CCK-A receptors are not predominantly expressed, they seem to play a major role in the response of pancreatic exocrine secretion to CCK.