Gastrosphincter of Oddi reflex

Gastric distention is known to stimulate gallbladder contraction as well as gastric acid and pancreatic exocrine secretion by way of neural reflexes. Gallbladder distention, in turn, has been shown to affect sphincter of Oddi motility. Since gastric distention may accompany endoscopic or operative biliary manometry, we tested the hypothesis that gastric distention alters sphincter of Oddi motility. In the prairie dog model, gastric distention with acid (0.1 M hydrochloric acid, pH 1.3) and alkaline (10(-5) sodium hydroxide, pH 8.8) isotonic saline solutions both resulted in significant increases in sphincter of Oddi phasic wave frequency, amplitude, and motility index. Similarly, gallbladder pressure increased during both distention periods, thus confirming the previously described pylorocholecystic reflex. These responses were abolished by systemic pretreatment with atropine, suggesting that this reflex is cholinergically mediated. These data suggest the presence of a gastrosphincter of Oddi reflex whereby gastric distention stimulates sphincter of Oddi motility in the prairie dog. We conclude that gastric distention is an important variable to be controlled when performing endoscopic or operative sphincter of Oddi manometry.     

Small Pancreatic and Periampullary Neuroendocrine Tumors: Resect or Enucleate?

Objective  The aim of this study was to compare the outcomes of enucleation versus resection in patients with small pancreatic, ampullary, and duodenal neuroendocrine tumors (NETs). Methods  Multi-institutional retrospective review identified all patients with pancreatic and peri-pancreatic NETs who underwent surgery from January 1990 to October 2008. Patients with tumors ≤3 cm and without nodal or metastatic disease were included. Results  Of the 271 patients identified, 122 (45%) met the inclusion criteria and had either an enucleation (n = 37) and/or a resection (n = 87). Enucleated tumors were more likely to be in the pancreatic head (P = 0.003) or functioning (P < 0.0001) and, when applicable, less likely to result in splenectomy (P = 0.0003). The rate of pancreatic fistula formation was higher after enucleation (P < 0.01), but the fistula severity tended to be worse following resection (P = 0.07). The enucleation and resection patients had similar operative times, blood loss, overall morbidity, mortality, hospital stay, and 5-year survival. However, for pancreatic head tumors, enucleation resulted in decreased blood loss, operative time, and length of stay compared to pancreaticoduodenectomy (P < 0.05). Conclusion  These data suggest that most outcomes of enucleation and resection for small pancreatic and peri-pancreatic NETs are comparable. However, enucleation has better outcomes than pancreaticoduodenectomy for head lesions and the advantage of preserving splenic function for tail lesions. Presented at the 2009 American Hepatopancreaticobiliary Association, March 14, 2009, Miami, FL American College of Surgeons Resident Research Scholarship, NIH Grant T32 CA009614 Physician Scientist Training in Cancer Medicine.     

Duodenal acidification inhibits sphincter of Oddi motility in the prairie dog

Recent studies have explored the influence of various hormones, peptides, and neural innervation on the sphincter of Oddi (SO). However, only older and conflicting data are available on the effect of intraduodenal (ID) perfusion of acid on SO activity. Therefore, we tested the hypothesis that acidification of the proximal small bowel would alter SO motility. In acute terminal experiments, 19 adult male prairie dogs underwent cannulation of the gallbladder (GB) with a pressure-monitored perfusion catheter. The common bile duct was cannulated proximally with a drainage catheter and distally with a triple-lumen, side-hole, closed-tip catheter with one port positioned in the SO. The duodenum was cannulated distal to the SO to allow perfusion of the proximal 30 cm of intestine with saline. SO phasic wave frequency (F), amplitude (A), and baseline pressure as well as GB pressure were measured for 40 min prior to and during ID perfusion of saline at pH 8.8, pH 6.0, or pH 2.0. A SO motility index (MI = F X A) was calculated for each 10-min period of the experiment. Infusion of saline at pH 8.8 had no effect on SO function. ID perfusion of saline at pH 6.0 reduced SO MI to 39% (P less than 0.05) and 34% (P less than 0.05) of control values at 20-30 and 30-40 min, respectively. ID saline at pH 2.0 reduced the SO MI to 51% (P less than 0.01) and 53% of control values during the same periods.(ABSTRACT TRUNCATED AT 250 WORDS)     

Iron deficiency transiently suppresses biliary neuronal nitric oxide synthase

BACKGROUND: Iron deficiency results in altered gallbladder and sphincter of Oddi (SO) motility and cholesterol crystal formation. In addition, gallbladder neuronal nitric oxide synthase (nNOS) has been shown to be markedly reduced after 8 weeks on an iron-deficient diet. However, the effects of prolonged iron deficiency on gallbladder and SO nNOS as well as crystal formation have not been determined. Therefore, we tested the hypothesis that iron deficiency would downregulate both gallbladder and SO nNOS expression and that nNOS downregulation and cholesterol crystal formation would progress over time. MATERIALS AND METHODS: Thirty-eight adult female prairie dogs were fed either an ironsupplemented (Fe+) (200 ppm) or an iron-deficient (Fe-) (8 ppm) diet for 8 weeks (Fe+ n = 9, Fe- n = 10) or 16 weeks (Fe+ n = 9, Fe- n = 10). Blood hemoglobin (HbG) was measured; gallbladder cholesterol crystals were counted; and cholesterol saturation indices (CSI) were calculated. Gallbladder and SO nNOS levels were measured by Western blot. RESULTS: The Fe+ prairie dogs had significantly higher HbG than the Fe- animals (16.9 +/- 0.6 g/dl vs 15.2 +/- 0.5 g/dl, respectively, P < 0.05) after 8 weeks. This difference was even greater after 16 weeks (16.1 +/- 0.4 g/dl vs 14.0 +/- 0.5 g/dl, P < 0.01). At 8 weeks, more cholesterol crystals per 10 HPF were observed in the Fe- animals (0.4 +/- 0.3 vs 1.6 +/- 0.4 per 10 HPF, P < 0.05). This difference was even greater after 16 weeks (0.0 +/- 0.0 vs 52.6 +/- 25.3 per 10 HPF, P < 0.01). No difference in the CSI was observed in the four groups. Iron deficiency decreased the nNOS/beta-actin protein levels in the gallbladder and SO at 8 weeks (57.0 +/- 29.6 vs 7.4 +/- 2.6, gallbladder, P < 0.05) (98.4 +/- 39.7 vs 29.9 +/- 11.0, SO, P = 0.09), but these levels returned to baseline at 16 weeks. CONCLUSIONS: We conclude that iron deficiency acutely suppresses gallbladder and SO nNOS, and that compensatory mechanisms return nNOS to baseline levels while cholesterol crystal formation increases over time.     

Flowcharts for the diagnosis and treatment of acute cholangitis and cholecystitis: Tokyo Guidelines

Diagnostic and therapeutic strategies for acute biliary inflammation/infection (acute cholangitis and acute cholecystitis), according to severity grade, have not yet been established in the world. Therefore we formulated flowcharts for the management of acute biliary inflammation/infection in accordance with severity grade. For mild (grade I) acute cholangitis, medical treatment may be sufficient/appropriate. For moderate (grade II) acute cholangitis, early biliary drainage should be performed. For severe (grade III) acute cholangitis, appropriate organ support such as ventilatory/circulatory management is required. After hemodynamic stabilization is achieved, urgent endoscopic or percutaneous transhepatic biliary drainage should be performed. For patients with acute cholangitis of any grade of severity, treatment for the underlying etiology, including endoscopic, percutaneous, or surgical treatment should be performed after the patient's general condition has improved. For patients with mild (grade I) cholecystitis, early laparoscopic cholecystectomy is the preferred treatment. For patients with moderate (grade II) acute cholecystitis, early laparoscopic or open cholecystectomy is preferred. In patients with extensive local inflammation, elective cholecystectomy is recommended after initial management with percutaneous gallbladder drainage and/or cholecystostomy. For the patient with severe (grade III) acute cholecystitis, multiorgan support is a critical part of management. Biliary peritonitis due to perforation of the gallbladder is an indication for urgent cholecystectomy and/or drainage. Delayed elective cholecystectomy may be performed after initial treatment with gallbladder drainage and improvement of the patient's general medical condition.     

The cholecysto-sphincter of Oddi reflex

Multiple factors including hormonal and neural influences as well as intravascular volume, body temperature, and pharmacologic agents have been shown to influence sphincter of Oddi function. Recent studies have also suggested that mechanical or electrical stimulation of the gallbladder and the degree of gallbladder filling may affect the frequency and amplitude of sphincter of Oddi phasic contractions. However, the effect of gallbladder filling on sphincter of Oddi phasic wave direction has not previously been studied. In acute terminal experiments, eight adult male prairie dogs underwent cannulation of the gallbladder with a pressure-monitored perfusion catheter. The common bile duct was cannulated proximally with a drainage catheter and distally with a triple-lumen, side-hole, closed-tipped catheter. The distal port of this catheter was positioned in the sphincter of Oddi (SO) while the proximal port was in the distal common bile duct (CBD). Distal CBD and SO phasic wave activity was recorded first with the gallbladder perfused with lactated Ringer's solution at 0.1 ml/min (mean intragallbladder pressure 8.1 ± 0.3 mm Hg) and then with the gallbladder (GB) empty. Sphincter of Oddi phasic wave frequency was 6.7 ± 0.9/min with the GB full and 5.4 ± 0.6/min with the GB empty (P < 0.02). Phasic wave amplitude was also greater with the GB full versus empty in both the distal CBD (6.4 ± 0.6 vs 4.3 ± 0.5 mm Hg, P < 0.05) and the SO (9.5 ± 1.5 vs 6.4 ± 0.8, P = 0.075). Baseline pressures and the direction of phasic waves were unaffected by the degree of gallbladder filling. It is concluded that the degree of gallbladder filling reflexly influences sphincter of Oddi phasic wave activity and should be considered in future studies of the choledochoduodenal junction.     

Adipokines and Cytokines in Human Pancreatic Juice: Unraveling the Local Pancreatic Inflammatory Milieu

Background  

Differential adipokine expression in obesity influences the inflammatory milieu, and may explain in part obesity’s negative impact on pancreatic disease. Pancreatic juice analysis may provide a good means to evaluate the local pancreatic inflammatory milieu. The presence of adipokines in pancreatic juice is unknown.     

Molecular phylogeny of Burkholderia pseudomallei

In terms of population structure, the species Burkholderia pseudomallei contains both clonal and non-clonal elements. By indexing variation in rRNA loci using the restriction endonuclease BamHI, we found that two ribotypes (types 1 and 3) are predominant in nature. Ribotype 3 is prevalent in Asian countries while ribotype 1 is more widespread. Some disease association was suggested for 4 ribotypes and strains of ribotype 4 were markedly associated with a fatal outcome. DNA macrorestriction (XbaI) profiles resolved by pulsed-field gel electrophoresis revealed great heterogeneity within the prevalent ribotypes and these profiles appeared to be reliable strain markers. Arabinose environmental strains were characterised by BamHI ribotypes that were markedly distinct form clinical and environmental isolates of the arabinose negative phenotype.     

Meta-analysis of observed mortality data from all-controlled, double-blind, multiple-dose studies of losartan in heart failure. Losartan Heart Failure Mortality Meta-analysis Study Group

Clinical studies of heart failure utilizing losartan, an angiotensin-II receptor antagonist, found that this drug is well tolerated and demonstrates hemodynamic, neurohormonal, and symptomatic improvement. To assess all-cause mortality in heart failure patients treated with losartan, a meta-analysis including 1,896 patients was performed on 6 controlled, double-blind, multiple-dose studies, regardless of sample size or duration of follow-up. A combination of logarithmic (log) odds ratios with a continuity correction was utilized for the meta-analysis. Treatment groups were comparable with regard to demographic characteristics, heart failure characteristics, and concomitant cardiovascular therapies. Concomitant use of open-label angiotensin-converting enzyme (ACE) inhibitors was not allowed in any study. The mean left ventricular ejection fraction obtained in individual studies ranged from 23% to 31%. Seven hundred forty patients were randomized to control therapy and 1,154 patients were randomized to losartan therapy. There were 36 deaths (3.12%) in the losartan groups compared with 47 in the control groups (6.35%) during the double-blind periods. The odds of dying in the losartan groups were 0.51 times (0.31 to 0.81) that of dying in the control groups (p = 0.004). In this analysis, treatment with losartan provided a beneficial effect upon survival. However, because the number of deaths in these studies is relatively small and the follow-up relatively short, a large confirmatory study is needed to assess the mortality benefit of losartan compared with an ACE inhibitor.