Background & Aims: Transjugular intrahepatic stent-shunt (TIPSS) insertion, in patients with uncontrolled gastro-intestinal bleeding, often results in worsening of the systemic hemodynamics which can be associated with intracranial hypertension but the underlying mechanisms are unclear. This study explored the hypothesis that TIPSS insertion results in acute endotoxemia which is associated with increased nitric oxide production resulting in systemic and cerebral vasodilatation.Methods: Twelve patients with cirrhosis who were undergoing TIPSS for uncontrolled variceal bleeding were studied prior to and 1-h after TIPSS insertion. Changes in cardiac output (CO) and cerebral blood flow (CBF) were measured. NO production was measured using stable isotopes using L[guanidino-(15)N(2)] arginine and L-[ureido-(13)C;5,5-(2)H(2)] citrulline infusion. The effect of pre- and post-TIPSS plasma on nitric oxide synthase (NOS) activity on human endothelial cell-line (HUVEC) was measured.Results: TIPSS insertion resulted in a significant increase in CO and CBF. Endotoxin and induced neutrophil oxidative burst increased significantly without any significant changes in cytokines. Whole body NO production increased significantly and this was associated with increased iNOS activity in the HUVEC lines. The change in NO production correlated with the changes in CO and CBF. Brain flux of ammonia increased without significant changes in arterial ammonia.Conclusions: In conclusion, the insertion of TIPSS results in acute endotoxemia which is associated with increased nitric oxide production possibly through an iNOS dependent mechanism which may have important pathophysiological and therapeutic relevance to understanding the basis of circulatory failure in the critically ill cirrhotic patient. (C) 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

OBJECTIVE—11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates cortisol from cortisone. 11β-HSD1 mRNA and activity are increased in vitro in subcutaneous adipose tissue from obese patients. Inhibition of 11β-HSD1 is a promising therapeutic approach in type 2 diabetes. However, release of cortisol by 11β-HSD1 from adipose tissue and its effect on portal vein cortisol concentrations have not been quantified in vivo. RESEARCH DESIGN AND METHODS—Six healthy men underwent 9,11,12,12-[2H]4-cortisol infusions with simultaneous sampling of arterialized and superficial epigastric vein blood sampling. Four men with stable chronic liver disease and a transjugular intrahepatic porto-systemic shunt in situ underwent tracer infusion with simultaneous sampling from the portal vein, hepatic vein, and an arterialized peripheral vein. RESULTS—Significant cortisol and 9,12,12-[2H]3-cortisol release were observed from subcutaneous adipose tissue (15.0 [95% CI 0.4–29.5] and 8.7 [0.2–17.2] pmol · min−1 · 100 g−1 adipose tissue, respectively). Splanchnic release of cortisol and 9,12,12-[2H]3-cortisol (13.5 [3.6–23.5] and 8.0 [2.6–13.5] nmol/min, respectively) was accounted for entirely by the liver; release of cortisol from visceral tissues into portal vein was not detected. CONCLUSIONS—Cortisol is released from subcutaneous adipose tissue by 11β-HSD1 in humans, and increased enzyme expression in obesity is likely to increase local glucocorticoid signaling and contribute to whole-body cortisol regeneration. However, visceral adipose 11β-HSD1 activity is insufficient to increase portal vein cortisol concentrations and hence to influence intrahepatic glucocorticoid signaling.

BACKGROUND:Bleeding from ectopic varices is uncommon but can be difficult to manage.AIM:To report our experience of the use of transjugular intrahepatic portosystemic stent shunts (TIPSS) in the management of uncontrolled bleeding from ectopic varices.METHODS:A retrospective study of patients who had TIPSS for bleeding ectopic varices. Patients were selected from a dedicated data base.RESULTS:Over 14 years, of 750 TIPSS insertions, 28 patients had TIPSS for bleeding ectopic varices (Child-Pugh score: 8.8 +/- 1.8). Varices were rectal (12), stomal (8), duodenal (4) and at other sites (4). Concomitant variceal embolization was performed in five. Portal pressure gradient fell from 18.2 +/- 6.4 to 7.2 +/- 3.5 mmHg. TIPSS achieved haemostasis in six of nine patients who presented with active bleeding. Five patients rebled from ectopic varices. This was related to shunt dysfunction in two and responded to shunt interventions. Three patients rebled despite a functional shunt. Of these, thrombin controlled bleeding in one. Eight patients developed hepatic encephalopathy post-TIPSS.CONCLUSIONS:Transjugular intrahepatic portosystemic stent shunt is a safe and effective treatment for bleeding ectopic varices. Rebleeding from ectopic varices related to shunt dysfunction responds to shunt intervention. A significant proportion of patients have rebleeding despite a patent shunt, when other adjunctive measures like thrombin injection may be tried.

Aim: The aim of this study was to evaluate the outcome of different techniques of palliation for patients with hilar cholangiocarcinoma.Method: All patients treated with palliative intent between 1988 and 2004 at the Royal Infirmary of Edinburgh were reviewed. Patients were analysed on an intention to treat basis. Demographics, procedure and outcome (including re-admissions) were recorded.Results: Two hundred and thirty-three patients underwent palliative treatment for suspected hilar cholangiocarcinoma. The diagnosis was confirmed histologically in 109 patients. The procedure related morbidity and mortality was 54/225 and 18/207 respectively. Seventy-one patients required re-admission. Twenty patients underwent surgical biliary bypass for jaundice. Those undergoing surgical palliation had a longer median (95% CI) time to re-admission (16 (0-36) vs.7 (2-12) weeks, p = 0.001). Endoscopic retrograde cholangio-pancreatography (ERCP) and stenting was only successful in 28 patients and was associated with a significantly higher re-admission rate compared to patients in whom ERCP was not performed (60/179 vs. 4/27, p = 0.050). The overall median (95% CI) survival was 145 (124-185) days.Conclusion: Current options for palliation of hilar cholangiocarcinoma provide good short term success but are all associated with significant early and late morbidity. Due to its low success and association with an increased re-admission rate, ERCP for definitive palliation should not be used in the first line staging and management of these patients. (c) 2006 Elsevier Ltd. All rights reserved.

BACKGROUND:Post-transjugular intrahepatic portosystemic stent shunt (TIPSS) hepatic encephalopathy (HE) can occur in up to one third of patients. In 5%, this can be refractory to optimal medical treatment and may require shunt modification. The efficacy of shunt modification has been poorly studied.AIMS:To evaluate the efficacy of and natural history following TIPSS modification for treatment of refractory HE.METHODS:From a dedicated database, we selected and further studied patients who had TIPSS modification for refractory HE.RESULTS:Over a 14 year period, of 733 TIPSS insertions, 211(29%) patients developed HE post-TIPSS. In 38 patients, shunt modification (reduction (n = 9) and occlusion (n = 29)) was performed for refractory HE. Indications for TIPSS were: variceal bleeding (n = 32), refractory ascites (n = 5), and other (n = 1). Child's grades A, B, and C were noted in 11%, 47%, and 42% of cases, respectively. HE improved in 58% of patients and remained unchanged or worsened in 42%, with similar results for occlusions and reductions. Following shunt modification, variceal bleeding recurred in three patients and ascites in three. Twenty five patients have died (liver related in 15) at a median duration of 10.2 months. Three patients died due to procedure related complications following shunt occlusions (mesenteric infarction (n = 2) and septicaemia (n = 1)). Median survival of patients whose HE did not improve following shunt modification was 79 days compared with 278 days in patients whose did (p<0.05). No variables independently predicted response to shunt modification.CONCLUSIONS:TIPSS modification is a useful option for patients with refractory HE following TIPSS insertion. Due to the significant risk of iatrogenic complications with shunt occlusions, shunt reduction is a safer and preferred option.

AIM:The aim of this study was to assess the value of a defined follow-up protocol for patients undergoing potentially curative hepatic resection for colorectal hepatic metastases. METHODS:A standard protocol for the duration of the study consisted of clinical assessment, serum carcinoembryonic antigen (CEA) and computed tomography. Patterns of recurrence, method and timing of diagnosis and outcome were recorded. RESULTS:One hundred and ninety-one patients underwent potentially curative resection from 1989 to 2004 of whom 103 developed recurrence. The median (inter-quartile range) follow-up was 24.4 (6.5-42.3) months. The median (IQR) time to recurrence and overall survival was 25.0 (10 -not yet reached) and 45.2 (21-123) months, respectively. Seventeen patients (8.9%) underwent further surgery with curative intent. Fifty-five patients (57.9%) had recurrence diagnosed at routine follow-up with 71% (44/62) being diagnosed by CEA and CT. The CEA was elevated in 85.7% (72/84 patients) at the time of diagnosis of recurrence. CONCLUSION:Although the detection of recurrent disease is common during follow-up after hepatic resection for colorectal metastases, few patients will be suitable for further intervention with curative intent. The exact nature of the follow-up protocol remains to be determined but if it is going to be performed it should be most intensive within the first 3 years.

Laparoscopy and laparoscopic ultrasound have been validated previously as staging tools for pancreatic cancer. The aim of this study was to identify if assessment of vascular involvement with abdominal computed tomography (CT) would allow refinement of the selection criteria for laparoscopy and laparoscopic ultrasound (LUS). The details of patients staged with LUS and abdominal CT were obtained from the unit's pancreatic cancer database. A CT grade (O, A-F) of vascular involvement was recorded by a single radiologist. Of 152 patients, who underwent a LUS, 56 (37%) had unresectable disease. Three of 26 (12%) patients with CT grade O, 27 of 88 (31%) patients with CT grade A to D, 17 of 29 (59%) patients with CT grade E and all nine patients with CT grade F were found to have unresectable disease. In all, 24% of patients with tumours <3 cm were found to have unresectable disease. In those patients with tumours considered unresectable, local vascular involvement was found in 56% of patients and vascular involvement with metastatic disease in 17%, while 20% of patients had liver metastases alone and 5% had isolated peritoneal metastases. The remaining patient was deemed unfit for resection. Selective use of laparoscopic ultrasound is indicated in the staging of periampullary tumours with CT grades A to D.

POSTERSsystem.Hence, low levels of actin-free Gc-globulin (AfGc) may serve as a prognostic marker of survival in acute liver failure (ALF).Aim: To evaluate the prognostic value of AfGc in paediatric ALE Patients and Methods: Serum AfGc levels were measured using a rapid ELISA kit (Antibody Shop, Gentofte, Denmark) at admission in 115 children (60 male, median age 5.05 years, range 0 17.4) with ALF (INR>2 unresponsive to vitamin K and abnormal liver enzymes).Causes of ALF were: autoimmune hepatitis (10), drug-induced ( 16), haemophagocytic lymphohistiocytosis (5), hypoxia (4), viral hepatitis (10), metabolic ( 14), neonatal haemochromatosis (7), veno-occlusive disease (2), Wilson disease (6), idiopathic (41).Fifty-eight patients survived with medical treatment only (Group 1); 20 died (Group 2); 37 were transplanted, of whom 26 survived (Group 3) and 11 died (Group 4).Results: AfGc levels (gg/ml) were: Group 1: median 255 (range 0.2 525); Group 2:105 (0.1 365); Group 3:95 (0.1 355); Group 4:85 (0.1~70), values being significantly higher in Group 1 when compared to Group 2 (p 0.002) and to all the children who died or required transplantation taken together (p 0.00001).At a cut-off level of 190 gg/ml (obtained by plotting a receiver operative characteristic curve; the value of the area under the curve being 0.79), sensitivity and specificity for predicting survival with native liver were 85% and 62% respectively.Conclusions: These results show that AfGc levels on admission are of prognostic importance in children with ALE Prospective studies with serial measurements are necessary to further elucidate the accuracy and practical value of this test.

The first case is that of a 60−year−old man with alcoholic liver disease who present− ed with refractory esophageal variceal bleeding. A TIPSS procedure was success− fully performed followed by coil emboli− zation of the left gastric vein. A subse− quent surveillance TIPSS check revealed that the shunt was occluded, and the pa− tient was entered into a variceal banding programme as patency of the TIPSS could not be restored. At endoscopy, two embo− lization coils were seen emerging from gastric fundal varices, with no stigmata of recent haemorrhage (Figure 1). The coils were left in situ, and the patient was discharged without complication.

OBJECTIVE:To evaluate the contribution of the liver to total circulatory reticuloendothelial system (RES) phagocytosis capacity in patients undergoing liver resection and to compare it with values in end-stage chronic liver disease. SUMMARY BACKGROUND DATA:The mechanism whereby major liver resection is associated with a high incidence of infection is unknown. Significant impairment of RES phagocytosis has been described in liver failure, rendering such patients susceptible to infection; and we hypothesized that similar impairment might occur following major liver resection. METHODS:A prospective study was conducted in which Tc-albumin microspheres blood clearance served as a parameter for RES phagocytosis and was studied together with indocyanine green blood clearance, actual liver volume measured by three-dimensional image analysis, and a clinical score of hepatic dysfunction in 17 patients undergoing liver resection and in 8 patients with end-stage chronic liver disease assessed for liver transplantation. RESULTS:When expressed relative to volume unit of residual liver, microspheres clearance increased significantly in the immediate postoperative period (day 1) following major (0.009% versus 0.022% min(-1) mL(-1), P < 0.001), but not minor liver resection. In contrast, the absolute rate of microsphere clearance decreased following major resection (15% min(-1) versus 10% min(-1), P < 0.001) and was comparable with the rate observed in end-stage chronic liver disease (9% min(-1)). This decrease in circulatory microspheres clearance after resection paralleled a decrease in indocyanine green clearance (R2 = 0.511, P = 0.006), and there was a trend for those with moderate liver dysfunction to have lower microspheres clearance rates (P = 0.068). CONCLUSION:Preservation of a minimum volume of functioning liver is a prerequisite for adequate RES phagocytosis capacity, and failure of this system may predispose patients undergoing major liver resection to infection as observed in clinical studies.

Introduction:Bleeding from ectopic varices is uncommon but can be difficult to manage.We report our experience of uncontrolled bleeding from ectopic varices managed by insertion of TIPSS.Methods: Patients in whom TIPSS was inserted for ectopic varices were selected from a TIPSS dedicated data-base.Results: Over 14 years, 732 TIPSS have been inserted.TIPSS was inserted for bleeding ectopic varices in 24 (males 11) patients.Mean age (SD) at TIPSS insertion was 56.6(10.6)years.Mean (SD) Child Pugh score was 7.6(1.84);A/B/C (%): 9/59/32.Aetiology of liver disease: alcoholic 15, cryptogenic 3, viral 2, others 4. Site of bleeding was rectal 11, stomal 7, duodenal 3, caput medusae 1, falciform ligament varix 1 and intraperitoneal varix 1. TIPSS was successful in 23/24 (96%).Complete data available on 20 patients.Portal pressure gradient (PPG) fell from 19(6.34) to 7.47(3.84)mmHg.Covered stents were used in 4 patients.Embolisation of varices was performed in 4 at the initial procedure.TIPSS insertion was initially effective in controlling bleeding in 18 (90%) patients.In four (covered stents 2, uncovered stents 2) of these patients bleeding recurred at 13 to 202 days after TIPSS insertion.This necessitated parallel shunt insertion for occluded shunts in 2, shunt extension for shunt insufficiency in 1, thrombin injection into the stomal varix in 2 patients and embolisation of varices in 1.These measures effectively controlled rebleeding in 3 patients and the fourth patient continues to have intermittent bleeding despite patent TIPSS.TIPSS was unsuccessful in controlling bleeding in 2 patients and one of these died due to liver failure 8 days post TIPSS.14 patients died (7 liver related, 1 due to G.I. bleed) since the TIPSS insertion and 6 patients had liver transplant at a median duration of 248 (5 1869) days.Conclusions: TIPSS is effective in the management of bleeding ectopic varices.Variceal rebleeding is frequently related to shunt insufficiency.Additional therapies such as thrombin and embolisation may be effective in difficult cases and may have a role in index therapy as an adjunct to TIPSS.

A 36-year-old man with alcohol/hepatitis C induced cirrhosis (Childs C) was admitted with oesophageal variceal bleeding. Variceal band ligation failed to control the haemorrhage and he therefore underwent a transjugular intrahepatic portosystemic stent-shunt (TIPSS) procedure utilising a polytetrafluoroethylene (PTFE) covered stent. The portal pressure gradient was reduced from 29 to 9 mmHg. The patient did not experience any post procedure pain or rise in transaminases. Routine Doppler ultrasonography 3 days post TIPSS insertion demonstrated adequate flow and a heterogenous area in the right lobe of the liver. A subsequent CT scan revealed a low attenuation perfusion defect in the right hemi liver in keeping with liver ischaemia (left panel). This was found to be a transient phenomenon as the follow up CT scan, 6 months later, showed resolution of these changes (right panel). Early studies have suggested that covered stents may improve shunt patency [1Hulek P. Fejfar T. Vanasek T. Karjina A. Lojik M. Zizka J. et al.Covered stents significantly reduce the incidence of in stent stenosis of TIPS: results of RCT in humans.J Hepatol. 2001; 34: A1034Google Scholar, 2Angermayr B. Cejna M. Koenig F. Karnel F. Hackl F. Gangl A. et al.Survival in patients undergoing transjugular intrahepatic portosystemic shunt: ePTFE-covered stentgrafts versus bare stents.Hepatology. 2003; 38: 1043-1050Crossref PubMed Scopus (167) Google Scholar]. In this case, a (PTFE) shunt (Viatorr; W.L.Gore Flagstaff, AZ) was used which has a 2 cm uncovered section to preserve portal vein and a variable length PTFE covered section for lining the parenchymal tract. The shunt was fashioned from the right branch of the portal vein to the inferior vena cava (IVC). The PTFE covering extended to the IVC, therefore blocking outflow of the right hepatic vein and inducing hepatic vein thrombosis. In this case, the effect was transient presumably due to the development of collaterals allowing the right hepatic vein to drain into the left and middle hepatic veins. There has been some concern that this liver injury might lead to deterioration in liver function with liver necrosis and atrophy in the affected area. However, no significant functional or clinical result ensued in this case. There is, however, a potential problem, which should be borne in mind when using these devices. In summary PTFE shunts, which occlude the hepatic vein, may improve patency but the risk of hepatic venous outflow obstruction is yet to be fully described.

Background and aims: Major liver resection incurs a risk of postoperative liver dysfunction and infection and there is a lack of objective evidence relating residual liver volume to these complications.Patients and methods: Liver volumetry was performed on computer models derived from computed tomography (CT) angioportograms of 104 patients with normal synthetic liver function scheduled for liver resection. Relative residual liver volume (% RLV) was calculated as the relation of residual to total functional liver volume and related to postoperative hepatic dysfunction and infection. Receiver operator characteristic curve analysis was undertaken to determine the critical % RLV predicting severe hepatic dysfunction and infection. Univariate analysis and multivariate logistic regression analysis were performed to delineate perioperative predictors of severe hepatic dysfunction and infection.Results: The incidence of severe hepatic dysfunction and infection following liver resection increased significantly with smaller % RLV. A critical % RLV of 26.6% was identified as associated with severe hepatic dysfunction ( p< 0.0001). Additionally, body mass index (BMI), operating time, and intraoperative blood loss were significant prognostic indicators for severe hepatic dysfunction. It was not possible to predict the individual risk of postoperative infection precisely by % RLV. However, in patients undergoing major liver resection, infection was significantly more common in those who developed postoperative severe hepatic dysfunction compared with those who did not ( p = 0.030).Conclusions: The likelihood of severe hepatic dysfunction following liver resection can be predicted by a small % RLV and a high BMI whereas postoperative infection is more related to liver dysfunction than precise residual liver volume. Understanding the relationship between liver volume and synthetic and immune function is the key to improving the safety of major liver resection.