Perioperative management of patients on new oral anticoagulants.

BACKGROUND: New oral anticoagulants (NOACs) offer an alternative to warfarin for preventing stroke in patients with atrial fibrillation. NOACs are expected to replace warfarin and other vitamin K antagonists for most of their indications in the future. Knowledge of the use of NOACs in the perioperative period is important for optimal care. METHODS: Studies that reported on the use of NOACs were identified, focusing on evidence-based guidance relating to the perioperative period. PubMed was searched for relevant articles published between January 2000 and January 2014. RESULTS: The anticipated expanded clinical use of NOACs such as rivaroxaban (Xarelto™), apixaban (Eliquis™) and dabigatran (Pradaxa™) has the potential to simplify perioperative anticoagulant management because of fewer drug-drug interactions, rapid onset of action, predictable pharmacokinetics and relatively short half-lives. However, coagulation status cannot be monitored by international normalized ratio and no antidotes are currently available. In elective surgery, it is important to discontinue the use of NOACs, with special consideration of renal function as route of elimination. Guidelines for the management of bleeding complications in patients on NOACs are provided, and may be considered for trauma and emergency surgery. Haemodialysis could be considered for bleeding with use of dabigatran. Better options for reversal of the effects of NOACs when bleeding occurs may follow with novel drugs. CONCLUSION: Management of NOACs in elective and emergency conditions requires knowledge of time of last intake of drug, current renal function and the planned procedure in order to assess the overall risk of bleeding. Currently no antidote exists to reverse the effects of these drugs.

Laparoscopic gastric resection for bleeding metastatic choriocarcinoma.

Although intestinal metastases from extraabdominal malignancies are an infrequent occurrence, they may cause obstruction, visceral perforation, or gastrointestinal bleeding. We report a case of upper gastrointestinal bleeding from a metastasis in the body of the stomach in a 69-year-old man with advanced malignant disease treated by laparoscopic wedge resection. Laparoscopic exploration was undertaken under general anesthesia, confirming the position of the tumor on the greater curve of stomach adjacent to the lower pole of the spleen. The greater curve of the stomach was mobilized with the harmonic scalpel. The gastroepiploic arcade was divided below the tumor, and local resection of the tumor was performed. The specimen was removed in a bag. Postoperatively, the patient made an uneventful recovery and was discharged on the 3rd postoperative day. Histological examination of the specimen indicated choriocarcinoma. We conclude that in selected patients with good functional status, resection of bleeding metastatic lesions of the gastrointestinal tract is a useful palliative procedure. Laparoscopic resection is especially advantageous in patients with a limited prognosis because it shortens postoperative stay and enables early resumption of daily activities.

Transhepatic balloon sphincteroplasty for bile duct stones after total gastrectomy.

Previous upper gastrointestinal surgery with the construction of a Roux-en-Y jejunal loop may prevent endoscopic access to the second part of the duodenum. We report a technique of percutaneous transhepatic balloon sphincteroplasty to facilitate the removal of common bile duct (CBD) stones. A 67-year-old woman presented with a 1-week history of right upper quadrant abdominal pain and fever, deranged liver function tests, and dilated intrahepatic ducts. The patient had previously had a total gastrectomy with Roux-en-Y reconstruction for a high-grade B-cell lymphoma of the stomach. Peroral endoscopic access to the biliary tree was unsuccessful. Percutaneous transhepatic cholangiography confirmed the presence of CBD stones. Over a period of 8 weeks, sequential dilatation of the percutaneous tract was undertaken. After a further 2 weeks, percutaneous choledochoscopy was performed. Several large stones were visualized and then fragmented. The choledochoscope would not pass through to the duodenum due to postinflammatory stenosis of the papilla, so the papilla was dilated with an endoscopic balloon. The remaining fragments were pushed through, and the duct was thoroughly irrigated with saline. Repeat cholangiography confirmed a clear CBD. Balloon catheter sphincteroplasty and biliary stone extrusion into the duodenum is a novel technique that enabled clearance of the CBD in an elderly patient who may otherwise have required open surgical exploration.

Lung injury in the microembolic model of acute pancreatitis and amelioration by lexipafant (BB-882), a platelet-activating factor antagonist.

Acute pancreatitis is associated with the development of pulmonary dysfunction in a number of patients. The aim of this study was to determine whether acute lung injury was a feature of the microembolic model of pancreatitis in rats and to assess the therapeutic effect of lexipafant (BB-882), a potent platelet-activating factor antagonist, on the lung injury. Acute pancreatitis was induced by microembolisation of the pancreas with 20-microns polystyrene microspheres. After 12 h tissue capillary permeability was assessed by an Evans blue dye (EBD) extravasation technique and compared with that in control animals. A further group of animals received an intraperitoneal injection of BB-882 (5 mg/kg) 30 min after the induction of pancreatitis. There was a significantly increased tissue content of EBD in the pancreas and lungs of the group of animals with acute pancreatitis (p < 0.05). BB-882 ameliorated the pulmonary changes when administered after the induction of pancreatitis, as demonstrated by a significant reduction in the EBD content of the lungs (p < 0.01). Increased pulmonary vascular permeability is an early feature of the microembolic model of acute pancreatitis and these changes appear to be modified by the administration of BB-882, providing further evidence for the potential role of platelet-activating factor antagonists in the treatment of acute pancreatitis and its complications.

Selective cholangiography with laparoscopic cholecystectomy: review of a protocol.

OBJECTIVE: To report the results of a protocol for the preoperative diagnosis of stones in the common bile duct in patients with symptomatic cholelithiasis. DESIGN: Prospective open study. SETTING: District general hospital, United Kingdom. INTERVENTIONS: Ultrasonography and liver function tests, and in selected patients preoperative cholangiography. MAIN OUTCOME MEASURES: The ability of the investigations to diagnose stones in the common bile duct preoperatively. RESULTS: Ultrasonography or liver function tests, or both indicated that 53 patients were at low risk of having stones in the common duct, and they underwent laparoscopic cholecystectomy without further investigation. A further 38 patients had minor abnormalities on the first two investigations and underwent intravenous cholangiography; ductal stones were identified in 6. Nine patients were thought to be at high risk and so underwent endoscopic retrograde cholangiopancreatography (ERCP) or open exploration of the common bile duct, and stones were found in 5. No further stones have been identified after a minimum follow up of 12 months. CONCLUSION: Selective preoperative cholangiography is a reliable way of detecting stones in the common bile duct before laparoscopic cholecystectomy.

Randomized, double-blind phase II trial of Lexipafant, a platelet-activating factor antagonist, in human acute pancreatitis.

The aims of the study were to determine whether the platelet-activating factor antagonist Lexipafant could alter the clinical course and suppress the inflammatory response of human acute pancreatitis. In a double-blind, placebo-controlled study 83 patients were randomized to receive Lexipafant 60 mg intravenously for 3 days, or placebo. Clinical progression was assessed by daily Acute Physiology And Chronic Health Evaluation (APACHE) II score and organ failure score (OFS). The magnitude of the inflammatory response on days 1-5 was assessed by serial measurement of interleukin (IL) 8, IL-6, E-selectin, polymorphonuclear elastase-alpha1-antitrypsin (PMNE-alpha 1-AT), and C-reactive protein (CRP). At entry, patients receiving Lexipafant (n = 42) or placebo (n = 41) were matched for age and sex, aetiology, APACHE II score and OFS. The disease was classified as severe in 29 patients (APACHE II score eight or more). There was a significant reduction in the incidence of organ failure (P = 0.041) and in total OFS (P = 0.048) at the end of medication (72 h). During this time seven of 12 patients with severe acute pancreatitis who had Lexipafant recovered from an organ failure; only two of 11 with severe acute pancreatitis who had placebo recovered from an organ failure and two others developed new organ failure. Lexipafant treatment significantly reduced serum IL-8 (P = 0.038), and IL-6 declined on day 1. Plasma PMNE-alpha 1-AT complexes peaked on day 1; the gradual fall to baseline over 5 days observed in controls did not occur in patients given Lexipafant. No effect was observed on serum CRP. This study provides a rationale for further clinical trials with the potent PAF antagonist Lexipafant in human acute pancreatitis.

Inflammatory mediators in acute pancreatitis.

The cellular events leading to acute pancreatitis are not well defined and the mechanism by which known aetiological factors initiate the disease process remains to be established. Inflammatory mediators have recently been implicated as potential early markers of disease severity and may help elucidate the pathophysiology of the disease. Oxidative stress is emerging as a common effector of the acinar cell injury in experimental acute pancreatitis and clinical findings indicate that neutrophil activation is a significant early event. In common with neutrophil-mediated tissue damage in states of tissue hypoperfusion, acute pancreatitis shows many features of an ischaemia-reperfusion injury. Increased levels of phospholipase A2 have been demonstrated; this enzyme induces synthesis of prostaglandins and platelet-activating factor, a potent inflammatory mediator. New therapeutic approaches to the complications of acute pancreatitis may be through manipulation of such mediators of inflammation.

Experimental models of acute pancreatitis.

Various models of experimental acute pancreatitis are described. An ideal model would be reproducible, have a similar natural history to that of the human disease and a similar response to treatment. Furthermore, it should be relatively cheap and simple. Few, if any, of the available experimental models completely satisfy these criteria. The appropriate choice of model is discussed, as are possible future developments in this field.

Familial abdominal aortic aneurysm: prevalence and implications for screening.

The high prevalence of abdominal aortic aneurysm (AAA) in men over the age of 65 has led to the establishment of ultrasound screening programmes for this group. The apparent familial tendency towards AAA formation suggests that relatives of aneurysm patients may form another subpopulation in whom screening is appropriate. The first degree relatives of 100 consecutive aneurysm patients were identified. Of 110 relatives over 50 years of age, two were known to have had AAA and ultrasound scans were performed on 74, providing information on aortic size for 76 relatives (69%). No further aortic aneurysms (antero-posterior diameter > or = 4.0 cm) were found on scanning. However, nine relatives were demonstrated to have aortic dilatation (2.5-3.9 cm). Aortic dilatation was observed in 21% of male first degree relatives over 50 years of age, affecting 27% of sons and 17% of brothers. Only 4% of the sisters and none of the daughters were found to have aortic dilatation. The prevalence of aortic enlargement seems to be sufficiently high amongst male first degree relatives of AAA patients over 50 years of age to justify aortic screening.

A laparoscopic technique for full thickness intestinal biopsy and feeding jejunostomy.

A laparoscopic technique is described, suitable for both full thickness intestinal biopsy and placement of a feeding jejunostomy tube. Its application in three cases is reported. The method is simple, permits full laparoscopic examination of the abdominal contents and being minimally invasive, facilitates early patients recovery.

Papillary cystic neoplasm of the pancreas: presentation and natural history in two cases.

Two young women, one white and one Chinese, with the rare but increasingly recognised papillary and cystic neoplasm of the pancreas are reported. The initial symptom in both was non-specific abdominal pain which, after investigation, was found to be caused by a pancreatic tumour. One patient did not come to surgery until five years after the initial diagnosis when she developed jaundice. In the five year interval between diagnosis and the development of jaundice computed tomography showed no change in the size (20 cm) of the pancreatic mass. Histology after resection, however, showed signs of lymphatic invasion. Cystic neoplasm of the pancreas can thus be regarded as an indolent, very slow growing tumour with potential for local invasion and hence metastatic spread.