生长抑素及大黄素对犬急性坏死性胰腺炎Oddi括约肌的作用

目的探讨生长抑素及大黄素对犬急性坏死性胰腺炎Ｏｄｄｉ括约肌压力的影响。方法杂种犬１５条，予胰管内逆行注入５％牛磺酸钠加自身胆汁诱发急性坏死性胰腺炎（ＡＮＰ）模型；随机分为ＡＮＰ非治疗组、生长抑素组和大黄素组；采用低顺应性毛细灌注测压导管及高分辨多通道胃肠动力仪于造模前及给药后测定Ｏｄｄｉ括约肌（ＳＯ）的基础压（ＢＰ）及时相收缩幅度（ＰＣＡ）。结果ＡＮＰ组与造模前正常比较，ＢＰ显著升高；生长抑素能显著降低ＡＮＰ时ＳＯ的ＢＰ及ＰＣＡ，而大黄素则无影响。结论ＳＯ功能异常是ＡＮＰ发展及影响其严重程度的重要因素，生长抑素对ＳＯ具有松弛作用，大黄素虽对ＡＮＰ有治疗作用，但对ＳＯ无松弛作用。     

生长抑素对Oddi括约肌功能的影响

天然生长抑素(somatostatin,SST)是一种胃肠激素及神经肽,主要分布于神经和消化系统中,具有广泛的生物学效应. 消化系SST大多由胰腺和胃肠黏膜中的D细胞分泌,能抑制胃肠运动及多种激素分泌. SST调节作用由G蛋白偶联受体,即生长抑素受体(somatostatin receptor,SSTR)介导. Oddi括约肌(sphincter of Oddi,SO)位于十二指肠乳头周围,是一结构和功能相对独立的器官,其运动主要受神经、激素、Cajal间质细胞的调节. SST对SO的作用尚存在争议,本文就生长抑素对SO功能的影响进行综述.     

Effect of somatostatin analog octreotide on human sphincter of Oddi

The effect of the long-acting somatostatin analog octreotide on the sphincter of Oddi was investigated in seven subjects referred for endoscopic sphincter of Oddi manometry. Six patients had unexplained right upper quadrant pain and one had bile duct dilatation without evidence of fixed obstruction on endoscopic retrograde cholangiopancreatography. A triple-lumen low-compliance system was used to record the sphincter of Oddi basal pressure, phasic contraction frequency, amplitude, duration, and direction of wave propagation before and after intravenous administration of octreotide in a dose of 50 micrograms. After a mean latency period of 1 min, significant changes included increased basal pressure in all seven patients, increased frequency of wave contractions in six patients, and decreased wave amplitude in six patients. The median duration of wave contraction and wave propagation sequence were not significantly influenced. Thus, octreotide has a significant stimulatory affect on the sphincter of Oddi activity, which may impair biliary and pancreatic flow.     

Effect of nalbuphine on the motility of the sphincter of Oddi in patients with suspected sphincter of Oddi dysfunction

BACKGROUND: Nalbuphine is an ideal supplementary analgesic drug for midazolam-induced conscious sedation during operative endoscopy because it has no cardiovascular effect and only a moderate depressive effect on respiration. However, no data are available as to whether nalbuphine is suitable as an analgesic drug during endoscopic sphincter of Oddi manometry. The aim of the present study was to investigate the effect of nalbuphine on the sphincter of Oddi motility in patients with a suspected sphincter of Oddi dysfunction. METHODS: Seventeen patients who were suspected clinically to have SOD after cholecystectomy were prospectively investigated. Five mg of midazolam was administered intravenously before the procedure to induce conscious sedation. After approximately 5 minutes of stationary sphincter of Oddi manometry recording (baseline), either 10 mg of nalbuphine or saline solution (placebo) was administered intravenously in random fashion and pressure was recorded for a further 5 minutes. Maximum sphincter of Oddi basal pressure and average phasic contraction amplitude and frequency were measured before and after the infusion of the drug or saline solution. RESULTS: Nalbuphine administration effectively enhanced the sedation obtained with midazolam without any adverse effect. When the sphincter of Oddi manometric periods before and after the administration of nalbuphine versus placebo were compared, there was a significantly increased basal sphincter of Oddi pressure only in the nalbuphine group: respectively, 49 (18) and 77 (29) mm Hg (p = 0.003) versus 51 (24) and 49 (23) mm Hg (p = 0.9). The phasic contraction amplitude did not change in response to nalbuphine, but the phasic contraction frequency increased significantly, from 5 (3) to 8 (4) per minute (p = 0.04). CONCLUSIONS: Nalbuphine has a stimulatory effect on sphincter of Oddi motility in patients with a suspected sphincter of Oddi dysfunction. Nalbuphine should not be used as premedication before endoscopic ERCP if sphincter of Oddi manometry is to be performed.     

Effect of native somatostatin on Sphincter of Oddi motility in patients with acute recurrent pancreatitis: A pilot study with Ultrasound-Secretin test

BACKGROUND: The effect of native somatostatin on Sphincter of Oddi motility still remains controversial. Sphincter of Oddi inhibition was demonstrated at manometry in patients in the acute phase of alcoholic pancreatitis. Other investigators showed marked somatostatin-induced impairment of bile flow by hepato-biliary scintigraphy. AIM: Aim of the study was to determine the effects of therapeutical doses of exogenous somatostatin on Sphincter of Oddi motility. PATIENTS AND METHODS: We studied eight patients (two men, six women, age 18-42), in the quiescent phase of idiopathic recurrent pancreatitis. We directly studied Sphincter of Oddi motility by perendoscopic manometry and, indirectly, secretin-stimulated pancreatic juice outflow by Ultrasound-Secretin test. The two tests were repeated before and after somatostatin infusion. RESULTS: Manometry was performed in two patients. After 250 microg somatostatin bolus the sphincter showed an increase of motor activity. At Ultrasound-Secretin test mean diameters were significantly larger at 40-60 min evaluation intervals during 250 microg/h somatostatin infusion as compared to saline infusion, showing a delayed pancreatic duct emptying. CONCLUSIONS: Acute administration of somatostatin seems to induce an excitatory effect on Sphincter of Oddi motility, with impaired pancreatic outflow in patients in the quiescent phase of recurrent pancreatitis.     

The sphincter of Oddi and pancreatitis

A review of three widely studied mechanisms by which pancreatitis is produced—biliary-pancreatic reflux, obstruction of the pancreatic duct and duodenopancreatic reflux—shows serious objections to each when they are considered individually. The possibility is considered that all three may contribute, each acting at different times. It is likely that the pathogenesis of pancreatitis will remain obscure until methods for studying the sphincter of Oddi are improved and biochemical changes in pancreatic disease are better understood.     

奥曲肽对犬急性重症胰腺炎Oddi括约肌的影响

目的 观察急性重症胰腺炎Ｏｄｄｉ括约肌（ＳＯ）的压力变化及奥曲肽对之影响,方法 １５只犬分为２组,急性重症胰腺炎非治疗组（５只）,奥曲肽组（１０只）;制备犬急性急症胰腺炎模型,于制备前,后及给药后各时间点分别测定ＳＯ的基础压和时相收缩幅度。结果 急性重症胰腺炎时ＳＯ压力显著升高（Ｐ＝０．０００１）;奥曲肽能显著降低重症胰腺炎时ＳＯ的基础压（Ｐ＝０．０００３）;但对时相收缩幅度无影响（Ｐ＝０．２３０     

Effect of somatostatin on immune inflammatory response in patients with severe acute pancreatitis

OBJECTIVE: Somatostatin regulates immune inflammatory response via apoptosis and adhesion of leukocytes in many diseases. This article reported a study that aimed to observe the mechanism and effect of somatostatin on the immune inflammatory response through apoptosis and adhesion of leukocytes in severe acute pancreatitis. METHODS: Thirty‐eight patients with severe acute pancreatitis, that fulfilled the guidelines for the treatment of severe acute pancreatitis of China and Balthazar computed tomography severity index (≥5) were enrolled consecutively. Nineteen of these patients received our routine treatment and 19 received additional somatostatin. In all patients the expressions of CD₄, CD₈, CD₉₅/CD₉₅ ligand and CD₁₈/CD₆₂ ligand on leukocytes were determined by flow cytometry, both upon admission and on the fourth day. Thirty healthy volunteers constituted the normal healthy group. RESULTS: In the treatment group, CD₄, CD₄ : CD₈ ratio and CD₆₂ ligand on leukocytes increased from 11.4 ± 8.2, 0.47 ± 0.10 and 25.5 ± 9.2 to 22.1 ± 9.7, 0.68 ± 0.11 and 36.2 ± 11.7 (P < 0.05) respectively, while CD₉₅ ligand on both lymphocyte and polymorphonuclear cells increased from 0.65 ± 0.21 and 0.76 ± 0.29 to 1.18 ± 0.32 and 1.58 ± 0.43 after treatment with somatostatin (P < 0.05). Furthermore, lactate dehydrogenase, aspartate aminotransferase, amylase, C reactive protein and acute physiology and chronic healthy evaluation (APACHE II) score in the treatment group reduced faster than those in the control group (P < 0.05), though there was no difference in mortality (15.7%vs 5.3%) between the two patient groups (P > 0.05). CONCLUSION: Somatostatin can modulate the immune inflammatory response and the severity of severe acute pancreatitis through apoptosis and adhesion of leukocytes, but this modulatory effect by itself is not strong enough to improve the final.     

Endoscopic manometry of the sphincter of Oddi and pancreatic duct in patients with chronic pancreatitis

Summary Conclusion Endoscopic manometry in patients with chronic pancreatitis has demonstrated some manometric abnormalities in the sphincter of Oddi, but these abnormalities have no significant role in the pathogenesis of chronic pancreatitis. Background The study was undertaken to determine whether the sphincter of Oddi dysfunction plays a significant role in the pathogenesis of chronic pancreatitis. Methods Manometric investigation was performed in 32 patients with chronic pancreatitis. Twenty-three of them had alcohol-induced chronic pancreatitis, seven had biliary pancreatitis, and two patients had annular pancreas with chronic pancreatitis. Fifteen of them had dilated main pancreatic duct. Twenty-one cholecystectomized patients with no abnormality of the pancreas and biliary system served as controls. Results This study showed no significant difference in the mean pressures in the pancreatic duct, sphincter of Oddi (basal and phasic), and frequency of the sphincter of Oddi phasic contractions when comparing patients and controls. Sphincter of Oddi basal pressure (26–44 mmHg) was markedly increased in seven patients, whereas three patients (two of them had increased sphincter of Oddi basal pressure) had increased pancreatic duct pressure (20–24 mmHg). Increased numbers of retrograde contractions were found in seven patients.     

Complications of sphincter of Oddi manometry: biliary-like pain versus acute pancreatitis

OBJECTIVE: Although acute pancreatitis is the most significant complication of sphincter of Oddi manometry (SOM), acute biliary-like abdominal pain--similar or identical to the patient's usual recurrent acute episodes of pain and not fulfilling clinical criteria for acute pancreatitis--can also be provoked by SOM. The aim of the article is to determine and compare the relative frequency of occurrence of, and risk factors for, post-manometry biliary-like abdominal pain and post-manometry pancreatitis. MATERIAL AND METHODS: The clinical and laboratory features, the manometric recordings from the sphincter of Oddi, and the immediate post-manometry outcomes, were examined in 234 consecutive patients undergoing sphincter of Oddi manometry at our Unit. RESULTS: Post-manometry pancreatitis occurred in 9% of patients, and was associated with two risk factors on multivariate analysis: a history of post-ERCP pancreatitis (odds ratio [OR] 5.9) and a raised basal sphincter pressure (> or =40 mmHg) at SOM (OR 3.5). An increased sphincter phasic wave frequency (> or =7/min) at SOM was identified as a significant (p<0.05) risk factor on univariate testing only. Post-manometry biliary-like pain occurred in 12% of patients, and was associated with 3 different risk factors on multivariate analysis: age below 50 years (OR 4.6); less than a 2-year history of recurrent abdominal pain (OR 3.0); and ERCP and/or ES carried out during the SOM procedure (OR 9.3). CONCLUSIONS: Provocation of biliary-like pain following SOM, without clinical evidence of pancreatitis, occurs at least as frequently as post-manometry acute pancreatitis. In contrast to post-manometry pancreatitis, post-manometry biliary-like pain occurs more often in younger patients with a shorter duration of symptoms and does not appear related to the manometric features of the sphincter documented at SOM; we propose that this clinical entity may reflect the presence of bile duct or duodenal hypersensitivity/hyperalgesia.     

Pancreatic stenting prevents pancreatitis after biliary sphincterotomy in patients with sphincter of Oddi dysfunction

Background & Aims: Patients with sphincter of Oddi dysfunction are at high risk of developing pancreatitis after endoscopic biliary sphincterotomy. Impaired pancreatic drainage caused by pancreatic sphincter hypertension is the likely explanation for this increased risk. A prospective, randomized controlled trial was conducted to determine if ductal drainage with pancreatic stenting protects against pancreatitis after biliary sphincterotomy in patients with pancreatic sphincter hypertension. Methods: Eligible patients with pancreatic sphincter hypertension were randomized to groups with pancreatic duct stents (n = 41) or no stents (n = 39) after biliary sphincterotomy. The primary measured outcome was pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). Results: Pancreatic stenting significantly decreased the risk of pancreatitis from 26% to 7% (10 of 39 in the no stent group and 3 of 41 in the stent group; P = 0.03). Only 1 patient in the stent group developed pancreatitis after sphincterotomy, and 2 others developed pancreatitis at the time of stent extraction. Patients in the no stent group were 10 times more likely to develop pancreatitis immediately after sphincterotomy than those in the stent group (relative risk, 10.5; 95% confidence interval, 1.4–78.3). Conclusions: Pancreatic duct stenting protects significantly against post-ERCP pancreatitis in patients with pancreatic sphincter hypertension undergoing biliary sphincterotomy. Stenting of the pancreatic duct should be strongly considered after biliary sphincterotomy for sphincter of Oddi dysfunction; pancreatic sphincter of Oddi manometry identifies which high-risk patients may benefit from pancreatic stenting.GASTROENTEROLOGY 1998;115:1518-1524     

Effect of octreotide on sphincter of oddi motility in patients with acute recurrent pancreatitis

Sphincter of Oddi dysfunction has been reported as a cause of acute idiopathic recurrent pancreatitis (IRP). Octreotide, a long-acting somatostatin analogue, is an antisecretory drug used in the treatment and prevention of acute pancreatitis. Its action on sphincter of Oddi motility is controversial and no data are available for IRP patients. The aim of this study was to assess sphincter of Oddi motor response to acute administration of octreotide in patients with past attacks of acute pancreatitis without identification of any evident aetiological factor. Six patients (four male, two female; mean age ± SD, 38.8 ± 9 years) suffering from acute pancreatitis for at least 3 months before the examination were submitted to sphincter of Oddi manometry. After a basal recording lasting at least 2 min, octreotide, 0.05 mg i.v., was administered and the recording repeated. Intraduodenal pressure was taken as the zero reference and the basal sphincter of Oddi pressure and amplitude and frequency of phasic contractions were calculated before and after octreotide administration. No significant pre- vs post-octreotide differences were observed in basal pressure (41.9 ± 24 vs 47.5 ± 33 mm Hg, respectively) or in amplitude of phasic contractions (164.6 ± 33 vs 170.8 ± 18 mm Hg). With a latency of about 1 min, octreotide administration caused a high-frequency phasic activity in all cases (mean frequency, 5.5 ± 2.2 contractions/min before and 9.8 ± 2 after octreotide; P < 0.04). After the procedure acute pancreatitis (prolonged abdominal pain and serum amylase levels more than three-fold the normal values) developed in five patients. In conclusion, our data suggest that acute administration of octreotide may induce tachyoddia and thus a rise in sphincter of Oddi pressure, with possible impairment of biliary-pancreatic outflow.     

Management of patients with biliary sphincter of Oddi disorder without sphincter of Oddi manometry

Background  

The paucity of controlled data for the treatment of most biliary sphincter of Oddi disorder (SOD) types and the incomplete response to therapy seen in clinical practice and several trials has generated controversy as to the best course of management of these patients. In this observational study we aimed to assess the outcome of patients with biliary SOD managed without sphincter of Oddi manometry.