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Introduction Biliary obstruction is associated with impaired intestinal barrier function and translocation of enteric bacteria to the systemic circulation. Traditional live culture techniques may overlook translocation of dead bacterial fragments that stimulate the inflammatory response. The aim of this study was to estimate the extent and pattern of bacterial translocation in experimental biliary obstruction. Materials and methods Thirty 9-week-old male Wistar rats were randomized to undergo bile duct ligation (BDL, n = 20) or sham operation ( n = 10). Seven days after operation, each animal received 1 ml of 111 indium-oxyquinolone-labeled Escherichia coli p.o. Samples of liver, spleen, mesenteric lymph nodes, and lung were harvested 4 h later and analyzed for live bacteria and 111 indium activity. Results There was significantly more live bacterial translocation detected in BDL animals than in sham-operated animals ( P = 0.00008, χ 2 ). Labeled bacterial fragments were detected in all locations sampled in all animals. Sham-operated animals had significantly more labeled bacterial fragments detected in the liver ( P = 0.0001) and the spleen ( P = 0.03) than the BDL animals. The mean total bacterial survival in the BDL group was 30 ± 13% and 0% in the sham operated group. Conclusion These results demonstrate that non-viable bacterial fragments are present in sterile extra-intestinal sites in normal animals and that translocation of live bacteria is markedly increased in experimental biliary obstruction. These results also suggest that failure of bacterial killing is an important factor facilitating bacterial translocation in the presence of established biliary obstruction.

Background Gram-negative sepsis and its sequelae frequently complicate invasive procedures in patients with obstructive jaundice. In response to endotoxin, Kupffer cells secrete tumour necrosis factor (TNF), a pivotal early mediator of sepsis. An investigation was carried out into the specific role of Kupffer cell TNF secretion following endotoxin challenge in obstructive jaundice. Methods Survival following intraperitoneal administration of endotoxin (2·0, 0·02 and 0·0002 mg per 100 g) was determined in rats following bile duct ligation (BDL) or sham operation. Plasma TNF concentration was quantified following endotoxin administration (0·0002 mg per 100 g) at 1, 2 and 6 h. Subsequently, the effect of Kupffer cell blockade by gadolinium chloride on survival and plasma TNF concentration was assessed. Results Jaundiced animals showed a significantly increased mortality rate following intraperitoneal injection of endotoxin 2·0 mg per 100 g (BDL 100 per cent versus sham 0 per cent) and 0·02 mg per 100 g (BDL 70 per cent versus sham 0 per cent; P = 0·002, Fisher's exact test). Median plasma TNF concentration was significantly greater in jaundiced animals 1 h after endotoxin administration (BDL 943 (interquartile range (i.q.r.) 211–3900) pg/ml versus sham 64 (i.q.r. 47–127) pg/ml; P = 0·002, Mann–Whitney U test). Kupffer cell blockade with gadolinium chloride increased the survival rate following endotoxin administration in BDL animals (BDL-GdCl3 100 per cent versus BDL-saline 40 per cent; P = 0·0003, Fisher's exact test) and decreased median plasma levels of TNF (BDL-GdCl3 88 (i.q.r. 0–1065) pg/ml versus BDL-saline 16 550 (1255–29 360) pg/ml; P = 0·002, Mann–Whitney U test). Conclusion Kupffer cell blockade improved survival and suppressed systemic TNF activity after endotoxin challenge. In obstructive jaundice, hypersecretion of TNF by Kupffer cells may supplement systemic cytokine production and be responsible for significant complications.

Background Sepsis and endotoxaemia occur frequently in biliary obstruction. Impaired Kupffer cell endocytosis is implicated in these events. Tumour necrosis factor and interleukin 6, secreted by Kupffer cells, are important mediators of sepsis. Kupffer cell clearance of endotoxin and secretion of cytokines in experimental obstructive jaundice were investigated. Methods Wistar rats were randomized to bile duct ligation, sham operation or control. Groups (n = 8) were studied 1 and 3 weeks after operation. Kupffer cell function was assessed using in situ hepatic perfusion. Results Clearance of endotoxin was significantly depressed 1 week (median (interquartile range) 20·3 (10·5–27·1) per cent) and 3 weeks (22·1 (20·2–23·2) per cent) after bile duct ligation compared with that in respective sham animals (35·5 (29·9–41·6) and 40·9 (37·7–47·0) per cent) and controls (39·5 (37·3–46·8) per cent). Secretion of tumour necrosis factor was significantly greater 1 week (1113·7 (706·5–1436·8) pg/ml) and 3 weeks (1118·2 (775·7–1484·1) pg/ml) following bile duct ligation compared with that in respective sham animals (114·3 (0–178·5) and 107·6 (63·7–166·4) pg/ml) and controls (0 (0–20·7) pg/ml). Interleukin 6 was not secreted by sham or control animals but was present in the perfusate from jaundiced animals at 1 and 3 weeks (52·5 (9·9–89·5) and 66·2 (60·2–193·1) pg/ml). Conclusion These data demonstrate simultaneous impairment of Kupffer cell clearance of endotoxin and increased secretion of proinflammatory cytokines in experimental obstructive jaundice. These diverse responses may contribute to the development of sepsis-related complications in biliary obstruction.

BACKGROUND: Gram negative septic events are the commonest source of morbidity and mortality as a result of surgery in jaundiced patients. The large intestine provides the major source of Gram negative bacteria in mammals and is implicated in the pathogenesis of systemic endotoxaemia in obstructive jaundice. Bile salts have an important part in maintaining indigenous microecological homeostasis through their emulsifying properties. AIMS: The aim was to investigate the effects of biliary obstruction and isolated external biliary diversion on gastro-intestinal structure and caecal bacterial flora in relation to bacterial translocation. METHOD: Six groups of adult male Wistar rats were studied (no operation, sham operated, and bile duct ligated (BDL) for one and three weeks and a choledocho-vesical fistula (CDVF) for one week). At the end of the study period plasma was assayed for evidence of endotoxaemia and the animals were tested for bacterial translocation to the mesenteric lymph node complex (MLNC), liver, lungs, and spleen. Quantitative and qualitative bacteriological studies were performed on the caecal contents and segments of colon and terminal ileum were washed and prepared for histological assessment. RESULTS: Bacterial translocation was significantly increased in the BDL1 (68.8%) and BDL3 (60%) groups compared with the sham1 (6.3%), sham3 (9.1%), No operation (0%), and CDVF1 (16.7%) groups. Although translocation was more pronounced in the BDL1 group, this was almost exclusively to the MLNC compared with the more widespread translocation to other organs in the BDL3 group. The BDL3 group was the only group with significantly raised concentrations of endotoxin and anticore glycolipid. The caecal Gram negative aerobic counts were significantly increased in the BDL1 and CDVF1 groups compared with all other groups. There was evidence of structural abnormalities in the terminal ileum of rats jaundiced for three weeks, but not in the other groups. CONCLUSIONS: Biliary obstruction for one and three weeks promotes bacterial translocation although the mechanisms may be different. Absence of intralumenal bile results in a significant but self limiting increase in the Gram negative aerobic population, which may account for translocation in the early stages of biliary obstruction. As the duration of biliary obstruction increases systemic endotoxaemia is a consistent feature which, combined with factors such as immunological depression and physical disruption of gut barrier function, may promote bacterial translocation perpetuating systemic sepsis.

Summary— A novel repair of the distal urethra with glanular and preputial reconstruction is described for distal penile hypospadias; 52 consecutive patients underwent this procedure without catheter splintage or urinary diversion. All voided without problems on the day of operation; 44 (85%) were treated as day cases, while the remaining 8 boys stayed in hospital for at least 1 night post-operatively for reasons not associated with the operation. Follow-up was complete and ranged from 15 to 30 months (mean 18). There was no evidence of meatal stenosis, phimosis or urethral stricture; 26 boys (50%) had associated chordee pre-operatively which was incompletely corrected in 2 (8%). These have a minor degree of chordee of glans on penile shaft and neither has required further treatment. Four boys (8%) developed partial wound breakdown which necessitated reconstruction in 2 and both of these have now been treated successfully. Functional and cosmetic results are excellent.

A congenital diaphragmatic hernia (Bochdalek’s hernia) rarely presents in adulthood. We present the case of a 21-year-old woman with thrombocytopenia secondary to hypersplenism due to left-sided (sinistral) portal hypertension. This portal hypertension was caused by strangulation of the spleen within a Bochdalek’s hernia. Subacute gastric volvulus compounded by portal hypertensive gastropathy resulted in her presentation with acute haematemesis. Congenital diaphragmatic hernias may present in the adult. Their presentation is variable, and they may produce life-threatening complications.

Objective: To determine the effects of enteral administration of glutamine on intestinal barrier function in experimental biliary obstruction. Background: Extrahepatic biliary obstruction is associated with the failure of intestinal barrier function, allowing bacteria and other substances from the intestine to enter the circulation and initiate a systemic inflammatory response, causing impairment of multiple organs. The amino acid glutamine has been shown to improve intestinal barrier function in other conditions, but its effects in biliary obstruction have not been fully examined. Methods: This study examined the effects of enteral administration of glutamine on intestinal permeability and on bacterial translocation from the intestine in a rodent model of biliary obstruction. Results: Glutamine was shown to reduce intestinal permeability measured as percentage excretion of 14C 7 days after biliary obstruction (0.35 ± 0.03 vs. 0.56 ± 0.085% in controls, p = 0.028), and glutamine administration was also associated with a decreased incidence of bacterial translocation to extra-intestinal sites (p = 0.03). Radiolabelled bacterial studies also demonstrated reduced translocation of bacterial fragments to extra-intestinal sites in glutamine-treated animals (p = 0.01). There was also some evidence of decreased exposure to endotoxin, reduced systemic inflammation and increased bacterial killing by the immune system in glutamine-treated animals. Conclusions: Glutamine modulates intestinal permeability and reduces bacterial translocation in an animal model of experimental biliary obstruction and may increase bacterial killing by the immune system.

Self-expanding metallic stents have been employed successfully for vascular, urethral, and biliary strictures. In a prospective study we examined the efficacy of the 16 mm Wallstent for palliation of malignant dysphagia.Eight patients with severe dysphagia due to advanced primary (four) or secondary (four) oesophageal malignant disease were recruited and nine Wallstents were inserted (one patient required two). Dysphagia was reduced in all but one patient, who died after oesophageal perforation; a second patient had a self-limiting bout of haematemesis. Two patients required subsequent treatment for tumour ingrowth but five had no further palliative therapy from stent insertion to time of death.With careful patient selection and skilful application, a 16 mm self-expanding metal endoprosthesis affords effective palliation in malignant oesophageal obstruction.

We report a case of malignant fibrosarcoma involving the brachial plexus presenting in childhood. Primary malignant tumours of the brachial plexus are rare entities. In particular, fibrosarcoma of the brachial plexus occurring in a child has not been previously reported. Dilemmas in resolving the management and long-term consequences of this condition are discussed.

Achalasia is an incurable neuromuscular disorder of the esophagus, resulting from destruction of the esophageal myenteric plexus. This leads to aperistalsis and failure of the lower esophageal sphincter to relax after swallowing. Symptoms of achalasia are gradual in onset and include dysphagia, regurgitation, and weight loss. Severe malnutrition can ensue. Wernicke's encephalopathy (WE) is a serious, potentially fatal, neurologic disorder caused by thiamine deficiency (vitamin B(1)), classically described as presenting with a triad of ocular abnormalities, ataxia, and confusion. The incidence is uncertain, and many cases likely go unrecognized. It is usually diagnosed in the alcoholic population. We describe its onset after the successful surgical treatment of achalasia.

Diagnostic laparoscopy or thoracoscopy can improve diagnosis of occult injuries to the diaphragm and reduce the risk of serious late morbidity

Background—Endotoxaemia is implicated in the pathophysiology of obstructive jaundice. The EndoCab enzyme linked immunosorbent assay (ELISA) is a novel assay which measures endogenous antibody (IgG) to the inner core region of circulating endotoxins (ACGA).Aims—To investigate the significance of endotoxaemia in biliary obstruction using the EndoCab assay and assess the specificity of the humoral response to endotoxin compared with an exogenous antigenic challenge (tetanus toxoid, TT).Methods—Three groups of adult male Wistar rats were studied: no operation, sham operation, and bile duct ligation for 21 days (BDL). In the second study, rats rats received prior immunisation with TT.Results—In the preliminary experiment, plasma ACGA was significantly increased in the BDL group (306.6 (18.3)% versus 119.9 (6.7)% and 105.2 (4.6)% in the sham and no operation groups, respectively; pConclusions—The specific rise in ACGA supports the hypothesis that endotoxin has an integral role in the pathophysiology of obstructive jaundice. The production of anticore glycolipid antibodies specifically reflects systemic endotoxaemia in this model. The EndoCab assay provides a novel, sensitive, and specific method for endotoxin detection.

Introduction Bariatric surgery has increased by 530% in the UK in the past 6 years. Benefits include weight reduction, improvement in weight related co-morbidities and cost-effectiveness compared to conventional weight reduction programmes. Aims/Background NICE clinical guidance 43 recommends that bariatric surgery be considered for patients with a BMI >40 or >35 with other co-morbidities. There are over 25,000 with a BMI >40 in Northern Ireland (NI). Bariatric surgery is not commissioned on the NHS in NI. Despite this, clinicians in NI increasingly have to treat its complications. This study was undertaken in order to review the complications of bariatric surgery that have presented to our hospital in the past 6 years. Method The hospital PAS system was interrogated for codes relating to emergency admissions due to complications following bariatric surgery between 2007 and 2012. Results There were 38 admissions across 32 female patients. Thirty had a gastric band, 1 bypass and 1 gastric balloon. Only one of the procedures was performed in NI. The mean length of stay was 6 days (range 1–20). The mean time since the procedure was 32 months (range 0–120). Complications included abdominal pain, vomiting, infected ports, internal hernia, infected bands, band erosion and gastric/oesophageal perforation. Twenty-five bands and 2 ports were removed. Conclusion It is anticipated that healthcare professionals in NI will continue to see increasing numbers of patients admitted with complications from bariatric procedures. Regardless of the current lack of commissioning for bariatric services, significant expertise and resources will continue to be required in order to manage these patients.

BACKGROUND: Jaundiced patients undergoing surgical procedures have an increased risk of Gram negative sepsis with potential morbidity and mortality. Depressed Kupffer cell clearance capacity (KCCC) predisposes jaundiced patients to endotoxaemia and its sequelae. Biliary decompression remains the main therapeutic strategy in obstructive jaundice. AIMS: This study investigates the efficacy of internal (ID) and external biliary drainage (ED) on KCCC in an experimental model of extrahepatic biliary obstruction. METHODS: Adult male Wistar rats (250-300 g) were assigned to one of six groups: sham operated, where the bile duct was mobilised but not divided; bile duct ligation (BDL) for three weeks, and sham operated or BDL for three weeks followed by a second laparotomy and further 21 days of ID or ED, by way of choledochoduodenostomy or choledochovesical fistula respectively. KCCC was measured using an isolated hepatic perfusion technique with FITC labelled latex particles (0.75 mu) as the test probe. Plasma was assayed for bilirubin, endotoxin, and anticore glycolipid antibody (ACGA) concentrations. RESULTS: Jaundiced rats had reduced KCCC (p < 0.001), increased concentrations of ACGA (p < 0.001), and endotoxin (p < 0.001) compared with controls. Biliary drainage for three weeks produced a recovery in KCCC and normalisation of endotoxin and ACGA concentrations, however, external drainage was less effective than ID (p < 0.01). CONCLUSIONS: These data support the hypothesis that endotoxaemia and its mediated effects are integral in the pathophysiology of jaundice. Furthermore, a short period of internal biliary drainage is a useful therapeutic strategy in restoring Kupffer cell function and negating systemic endotoxaemia and consequent complications in biliary obstruction.

The data suggest that, although Kupffer cells appear to initiate the inflammatory response to endotoxin in obstructive jaundice, other hepatic cells release proinflammatory cytokines subsequently.

Jaundiced patients undergoing invasive diagnostic and therapeutic procedures are at increased risk of complications and death. Despite the large number of clinical and experimental investigations carried out to identify relevant risk factors, no single parameter has been found to be consistently useful in predicting morbidity or mortality. Biliary decompression was initially employed by surgeons and subsequently by interventional radiologists. More recently, endoscopic retrograde cholangiopancreatography has provided an alternative route for decompression of the biliary tree and preliminary data using this method are encouraging. Although there are enthusiastic proponents of various therapeutic techniques, controlled trials have not been convincing in highlighting the benefits of biliary drainage or in determining the best approach. This article reviews the literature pertaining to this complex surgical problem; an attempt has been made to balance the advantages and disadvantages of biliary decompression as palliation and/or preliminary treatment for extrahepatic biliary obstruction.

Early is better and less costly

Obstructive jaundice is often a clinical manifestation of diseases of the extrahepatic biliary system and pancreas. Surgical procedures in these patients are associated with significant mortality and morbidity due mainly to the development of postoperative complications such as sepsis, bleeding disorders and renal failure (Armstrong et al. 1984; Pain et al. 1985). Therapeutic endoscopic and radiological procedures carry similar risks although their frequency is less well documented. Clinical and experimental studies have identified several aetiological factors including hypotension, impaired nutritional status, impaired immune function, hepatic dysfunction and the presence of toxic substances (bilirubin, bile salts) in the circulation. Wardle and Wright (1970) reported an association between renal insufficiency and endotoxaemia in obstructive jaundice and since that time there has been increasing recognition of the role of circulating endotoxins in the development of many of the complications of obstructive jaundice (Wilkinson et al. 1976; Hunt 1980). This has led to the investigation of factors that result in the development of endotoxaemia, including the absence of intraluminal bile salts and impairment of immunological function. These in turn initiated studies on therapeutic measures to reduce endotoxaemia, such as oral replacement of bile salts, percutaneous and endoscopic decompression of the biliary tract, stimulation of immune function and the use of antibiotics and antiendotoxin agents (Diamond and Rowlands 1991). This chapter will concentrate on the critical evaluation of the effects of biliary drainage in obstructive jaundice in animal and clinical studies, and their implications for current therapeutic strategies.

Jaundiced patients experience intense pruritus, the pathophysiology of which is unclear. In this study, blood histamine concentrations, skin mast cell counts and intracellular histamine concentrations in peritoneal mast cells were examined in an experimental model of biliary obstruction. Three weeks after bile duct ligation (BDL), total blood histamine concentrations were significantly elevated compared with those from control animals (p

This study demonstrated laparoscopy to be an important adjunct in the staging of upper gastrointestinal malignancy as it identified advanced disease that CT failed to demonstrate, hence altering stage assignment and management. Positive peritoneal washout cytology did not contribute significantly in the pre-operative staging.

Both pro- and anti-inflammatory cytokines are elevated in this model of obstructive jaundice. The global effect of the increased inflammatory response is a down-regulation of neutrophil respiratory burst activity. This may result in subsequent immunological dysfunction and anergy, as a result of a prominent anti-inflammatory response, increasing the susceptibility to septic complications. The use of the neutrophil chemiluminescence assay may be a more reliable assessment of the effects of the inflammatory balance in obstructive jaundice rather than measurement of individual cytokines.