UK guidelines for management of acute pancreatitis: is it time to change?
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Acute Disease↗
Biomedical subjects
M Farouk
Publications and source records attributed to M Farouk.
Prospective randomized trial of end-to-end versus side-to-side biliary reconstruction after orthotopic liver transplantation.
BACKGROUND: Biliary reconstruction is the Achilles heel of liver transplantation. Side-to-side anastomosis of donor and recipient bile duct has been claimed to be superior to end-to-end anastomosis in uncontrolled studies. METHODS: A total of 100 consecutive patients undergoing orthotopic liver transplantation were randomized after commencement of the transplant procedure to end-to-end or side-to-side anastomosis. No T tube drainage was employed. Endoscopic retrograde cholangiography was performed 2 weeks after transplantation and findings were reported by an experienced endoscopist as normal, leak or stricture. Median follow-up was 53 (range 35-63) months. RESULTS: Patient age, sex, the graft preservation time and indication for transplantation were similar in both groups. Sixty patients received end-to-end and 40 side-to-side anastomosis. Ten patients randomized to side-to-side anastomosis had an end-to-end procedure. The total number of biliary complications was similar in both groups (end-to-end 32 per cent versus side-to-side 30 per cent) as were the number of leaks (17 versus 18 per cent) and biliary strictures (15 versus 12 per cent). There was no difference in the number of biliary complications that required interventional treatment (22 per cent in both groups). CONCLUSION: Side-to-side and end-to-end biliary anastomosis at liver transplantation are equally effective.
Adolescent↗
Prospective study of hepatobiliary scintigraphy and endoscopic cholangiography for the detection of early biliary complications after orthotopic liver transplantation.
BACKGROUND: Biliary complications are a significant cause of morbidity and death after orthotopic liver transplantation (OLT). This study was a prospective evaluation of endoscopic retrograde cholangiography (ERC) and hepatobiliary scintigraphy (HBS), using 99mTc Mebrofenin, to detect early biliary complications following OLT. METHODS: One hundred consecutive patients who had OLT with a biliary duct-to-duct anastomosis were studied. Of these, 67 had both ERC and HBS performed within 30 days of OLT. Sensitivity, specificity and diagnostic accuracy of HBS in identifying biliary leak or stricture was calculated. RESULTS: Of the 67 cholangiographies performed 45 were normal. In 22 patients there was radiological evidence of a leak (n = 14) or stricture (n = 8) which required further intervention in nine and four patients respectively. The sensitivity and specificity of scintigraphy for the detection of biliary leak after transplantation was 50 and 79 per cent and for biliary stricture 62 and 64 per cent respectively. No patient with normal scintigraphy required biliary intervention. Only six of 14 patients with biliary leaks and two of 20 with strictures suggested by scintigraphy required intervention. If both ERC and HBS reported leak or stricture, the intervention rate was considerably higher at five of seven leaks and two of five strictures. CONCLUSION: This study suggests that scintigraphy is a useful screening test for biliary complications after OLT, ERC is only necessary if HBS is abnormal.
Adolescent↗
Duct-to-duct biliary reconstruction following liver transplantation for primary sclerosing cholangitis.
The biliary complications in patients undergoing biliary reconstruction by duct-to-duct (D-D) anastomosis or with a Roux-en-Y loop (RL) at the time of liver transplantation for primary sclerosing cholangitis (PSC, 16 D-D, 10RL) or primary biliary cirrhosis (PBC, 31 D-D, 1 RL) were reviewed and compared. Patients were followed up for a mean period of 32 months. Extrahepatic biliary strictures occurred in 18.7%, 10% and 9.7% of DD-PSC, RL-PSC and DD-PBC patients, respectively, leaks in 6.2%, 20% and 6.4% DD-PSC, RL-PSC and DD-PBC patients, respectively (P = NS). Four intrahepatic biliary abnormalities developed in the PSC group. Duct-to-duct anastomosis did not significantly increase the risk of stricture formation or bile leaks in PSC patients compared to PBC patients. We conclude that duct-to-duct biliary reconstruction following liver transplantation for PSC is satisfactory unless the distal common bile duct is strictured.
Adolescent↗
Insulin and counterregulatory hormones influence acute-phase protein production in human hepatocytes.
After trauma or sepsis, the liver undergoes a reprioritization of export protein synthesis with elevated production of some acute-phase reactants and reduced production of others. We have examined the effects of combinations of insulin and the counterregulatory hormones (dexamethasone, glucagon, and epinephrine), in the presence or absence of interleukin (IL)-6, on the production by isolated hepatocytes of the positive acute-phase proteins C-reactive protein, alpha 1-antichymotrypsin, alpha 1-acid glycoprotein, and haptoglobin, and the negative acute-phase proteins prealbumin and transferrin. The effect of IL-6 on the production of the above proteins was influenced significantly by insulin and all of the counterregulatory hormones. Significant three-way interactions as well as higher order interactions between the stress hormones and insulin were seen in the case of C-reactive protein. The results indicate that both positive and negative acute-phase proteins respond differently to insulin and the counterregulatory hormones and that the potential exists for the regulation of synthesis of individual acute-phase reactants by interaction between the cytokine network and the classical endocrine hormones.
Acute-Phase Proteins↗
Transforming growth factor-beta 1 and mannose 6-phosphate/insulin-like growth factor-II receptor expression during intrahepatic bile duct hyperplasia and biliary fibrosis in the rat.
These studies investigate the role of transforming growth factor-beta 1, a potent inhibitor of epithelial cell proliferation and stimulator of extracellular matrix biosynthesis, during intrahepatic bile duct hyperplasia and biliary fibrosis. These pathogenic responses were induced in rats by common bile duct ligation. Bile duct cell replication, measured by the bromodeoxyuridine labeling index, was significantly increased 24 hr after common bile duct ligation. This response diminished to baseline by 1 wk. Liver collagen content, determined by quantification of hydroxyproline, was increased significantly after 1 wk of common bile duct ligation, and by 4 wk was increased by a factor of 4. Immunohistochemistry revealed low levels of TGF-beta 1 in normal intrahepatic bile duct epithelium. In contrast, the bile duct epithelium in bile duct-ligated rats stained strongly positive for transforming growth factor-beta 1 at 1 and 4 wk after ligation. These results suggest that transforming growth factor-beta 1 may play a role in both the termination of the bile duct epithelial cell proliferative response and the induction of fibrogenesis after common bile duct ligation. In addition, the mannose 6-phosphate/insulin-like growth factor II receptor was up-regulated in hyperplastic bile duct epithelium 1 and 4 wk after ligation. Because the mannose 6-phosphate/insulin-like growth factor-II receptor has been shown to facilitate the proteolytic activation of transforming growth factor-beta 1, these results suggest that the bile duct epithelium may also be involved in the activation of transforming growth factor-beta 1.
Animals↗
Colonic obstruction in acute myeloid leukaemia.
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Acute Disease↗
Secretin receptors in a new preparation of plasma membranes from intrahepatic biliary epithelium.
Secretin is thought to cause choleresis by acting on a receptor expressed by bile duct epithelial cells. In this study, the receptor was characterized using a new preparation of intrahepatic bile duct plasma membranes. Hyperplastic biliary trees were obtained from 3-week bile duct-ligated rats. The biliary trees were homogenized, filtered, and subjected to an aqueous two-phase partition technique to yield highly purified plasma membranes (confirmed by a 14-fold enrichment in gamma-glutamyl transpeptidase activity and a 10-fold enrichment in 125I-secretin binding). 125I-secretin bound saturably with high affinity and in a dose-dependent fashion (Kd = 1.3 +/- 0.1 nM, Bmax = 273 +/- 23 fmole/mg) to purified plasma membranes. The binding characteristics of secretin were most consistent with a single site receptor model. Competitive binding studies indicated that the secretin-related peptides glucagon, peptide histidine isoleucine, gastric inhibitory peptide, and growth hormone releasing factor did not inhibit binding. Vasoactive intestinal peptide (1 microM) reduced maximal binding by 19 +/- 1%. The GTP analogs guanylylimidodiphosphate and guanosine 5'-O-[3-thiotriphosphate] (1 microM) inhibited binding by 16 +/- 2 and 13 +/- 1%, respectively. In conclusion, secretin binds to a specific, high-affinity receptor in intrahepatic bile duct epithelium that is coupled to a G-protein-linked signal transduction system.
Animals↗
Technique of intraluminal biliary ultrasonography during laparoscopic cholecystectomy.
Intraluminal ultrasonography of the common duct was performed in nine patients undergoing laparoscopic cholecystectomy, using a system comprising a 20-MHz crystal in a 95-cm, blunt-tipped 6F sheath, mechanically rotated at 1,800 rpm. The probe was introduced through an incision in the cystic duct and passed into the duodenum. When the catheter was withdrawn, excellent visualization of the common and cystic ducts and lower end of the common hepatic duct was achieved. In seven patients, the biliary tree was normal. A small calculus was discovered in the common duct in one patient. This stone was not seen on a subsequent cholangiogram and was subsequently retrieved. An additional patient had mucus or sludge noted in the duct, which cast no acoustic shadow and thus was distinguished from calculi. The technique was fast, efficient, and easy to perform in this small group of patients and holds promise for screening the common duct pathology during laparoscopic cholecystectomy.
Adult↗
Exogenous neuropeptide Y blocks myoelectric activity in the upper gastrointestinal tract of starved dogs. Brain neuropeptide Y converts a fasting pattern of myoelectric activity to a fed pattern.
The effect of intracerebroventricular (ICV) neuropeptide Y (NPY) on the migrating motor complex (MMC) was examined in five starved dogs. Myoelectric activity was recorded using gastric, duodenal, and jejunal electrodes. Intragastric pressure was monitored via a gastric fistula, and ICV injections were given through a cerebroventricular guide. Recordings were made with no ICV injection and before and after 250-microliters bolus injections of vehicle as control (0.1% dog serum albumin in saline) or 500 pmol/kg NPY. The mean interval between MMCs was 98 +/- 10 min without ICV injection and 96 +/- 7 min after control solution. After ICV injection of NPY no further MMCs were recorded in any dog, even though the study was continued for a minimum of 3.5 h. Instead, the myoelectric pattern became indistinguishable from that in fed dogs. We conclude that central NPY plays a role in modulation of upper gastrointestinal myoelectric activity. This may reflect a central regulatory role for NPY in the coordination of feeding.
Animals↗
The effect of octreotide on hepatic regeneration in rats.
The effect of the long-acting somatostatin analog octreotide on liver regeneration was studied in rats in vitro and in vivo. The effect of continuous subcutaneous octreotide infusion on regenerative liver weight and relative DNA synthesis was examined in rats that had undergone 70% hepatectomy. Administration of octreotide resulted in a 33% reduction of regenerating liver weight at 72 hours and a 67% reduction of regenerative hepatocellular hyperplasia at 24 hours. This effect was reversed within 12 hours after withdrawal of the drug. The mechanism for the inhibitory effect of octreotide appears to be indirect, because experiments in hepatocyte cultures did not demonstrate a direct inhibitory effect on serum-free or epidermal growth factor-induced regenerative hepatocyte proliferation. Because insulin levels were suppressed by octreotide in the in vivo experiments, suppression of hepatotrophs may be the mechanism by which octreotide inhibits liver regeneration.
Animals↗
Localization and characterization of secretin binding sites expressed by rat bile duct epithelium.
The goal of the present studies was to identify and characterize the site of secretin action in the liver. Sections of normal and bile duct-ligated rat livers were used for in vitro 125I-secretin receptor autoradiography. Saturable binding was observed in both normal and bile duct-ligated livers but was much greater in the bile duct-ligated preparations. Binding was limited to biliary epithelium and the increased secretin binding observed in the ligated livers correlated with the increase in ductular tissue. Saturable binding was inhibited in a dose-dependent fashion by increasing concentrations of nonradioactive secretin. Analysis of saturation binding showed that 125I-secretin binding was best fit by a one-site receptor model with a Kd of 5.3 +/- 1.1 nmol/L. Glucagon, vasoactive intestinal polypeptide, gastric inhibitory polypeptide, growth hormone-releasing hormone, and cholecystokinin did not inhibit saturable 125I-secretin binding at concentrations of 1 pmol/L to 1 mumol/L. The authors conclude that high-affinity, specific secretin binding sites are present in rat intrahepatic biliary epithelium. When bile ducts are stimulated to proliferate by bile duct ligation, secretin binding is also increased.
Animals↗
The effects of liver denervation on the regulation of hepatic biliary secretion.
Effects of liver denervation on bile formation were studied in eight dogs prepared with chronic biliary fistulas. The animals were studied in the basal state, after feeding, and during infusion of glucagon 50 ng/kg/min, secretin 2 U/kg/hr, or somatostatin 200 ng/kg/min. After this first set of experiments the animals underwent a total hepatic denervation that consisted of section of the hepatic ligaments and a careful dissection of the portal vein, hepatic artery, and common duct with stripping of all the surrounding connective tissue and topical application of phenol. The above experiments were then repeated. Denervation did not modify bile flow, or bile salts, cholesterol, or phospholipid concentration or output. Biliary response to glucagon and secretin was similar before and after denervation. Somatostatin had an anticholerectic effect in both intact and denervated animals, but significantly reduced bile salt output only in the intact dogs. Feeding had a choleretic effect pre- and postdenervation, and the infusion of somatostatin following feeding decreased bile flow to the same degree before and after denervation. In the intact animals the output of all three biliary lipids was reduced by somatostatin after feeding but they were unaffected by somatostatin after denervation. Moreover, cholesterol and phospholipid outputs were stable after feeding in intact animals, but significantly decreased after denervation. 14C-erythritol clearance studies indicated no change in the canalicular component of bile flow with denervation, except again during somatostatin suppression of feeding. These data indicate that basal bile flow is normal after denervation but that innervation may play an important role in the modulation of responses to somatostatin and more complex stimuli such as feeding.
Animals↗
Intracerebroventricular neuropeptide Y stimulates bile secretion via a vagal mechanism.
UNLABELLED: The effect of intracerebroventricular injection of neuropeptide Y on biliary secretion was studied in conscious dogs, prepared with gastric and duodenal fistulas and cerebroventricular guides. Bile secretion was increased in a dose-dependent fashion by intracerebroventricular neuropeptide Y. The peak increase was seen after 500 pM/kg of neuropeptide Y which resulted in a 30 x 2% increase in bile flow over the period 30-150 minutes after injection. ( CONTROL: 23 x 2 (1 x 2) ml/2 hours; neuropeptide Y 500 pM/kg: 30 x 5 (1 x 1) ml/2 hours). Biliary lipid composition was not altered significantly but bicarbonate output was increased at all doses tested. Intravenous infusion of neuropeptide Y (1000 pM) for 1 hour had no significant effect. Intracerebroventricular neuropeptide Y (1000 pM/250-300 mg body weight) also increased bile flow in urethane-anaesthetised rats. This effect was abolished by cervical vagotomy. The demonstration of a central stimulation of alkaline bile flow suggests that bile secretion may be subject to central modulation.
Animals↗
Indications for and the technique of local resection of tumors of the papilla of Vater.
Local resection of tumors of the papilla of Vater was performed in six cases (three benign adenomas and three adenocarcinomas). Pathology was suggested in all cases by endoscopic biopsy and confirmed by operative excision. A method of excision of the tumor and reconstruction of the pancreaticobiliary apparatus was used that eliminated all gross and microscopic disease. Only one of the patients with benign disease (familial polyposis) suffered from local recurrence. All three patients with malignant tumors developed local recurrences within 2 years of resection. Local resection seems to be a viable alternative to Whipple's resection in patients with benign tumors. In malignant cases, local resection should be considered only a palliative procedure and confined to elderly patients with severe concomitant disease and patients in whom a more radical procedure would incur an undue surgical risk.
Adenocarcinoma↗
Biliary response to glucagon in humans.
Glucagon has been demonstrated to have profound effect on biliary secretion in several species. Glucagon's biliary effects were studied in humans following biliary tract surgery. Nine patients underwent common bile duct exploration and insertion of a balloon-occludable t tube. An aliquot of the collected sample was kept and the enterohepatic circulation was maintained by reinfusion of the collected bile via the distal t-tube port. Glucagon increased bile flow and decreased cholesterol and phospholipid output during stable bile acid output. Furthermore high-performance liquid chromatographic analysis of bile acid profiles revealed no significant changes in bile salt species or conjugation after glucagon infusion. Glucagon is probably important in the physiologic regulation of biliary secretion in humans.
Bile↗
Bile compositional changes and cholesterol stone formation following orthotopic liver transplantation.
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Adult↗
Postlaminectomy arteriovenous fistula formation: a continuing problem.
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Adult↗