Acute endotoxemia following transjugular intrahepatic stent-shunt insertion is associated with systemic and cerebral vasodilatation with increased whole body nitric oxide production in critically ill cirrhotic patients.

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.

Bleeding ectopic varices in cirrhosis: the role of transjugular intrahepatic portosystemic stent shunts.

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.

Palliation for suspected unresectable hilar cholangiocarcinoma.

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.

Follow-up and outcomes for resection of colorectal liver metastases in Edinburgh.

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.

Transjugular intrahepatic portosystemic stent shunt (TIPSS) modification in the management of post-TIPSS refractory hepatic encephalopathy.

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.

Refining the role of laparoscopy and laparoscopic ultrasound in the staging of presumed pancreatic head and ampullary tumours.

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.

The value of residual liver volume as a predictor of hepatic dysfunction and infection after major liver resection.

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.

Randomised controlled trial of long term portographic follow up versus variceal band ligation following transjugular intrahepatic portosystemic stent shunt for preventing oesophageal variceal rebleeding.

BACKGROUND/AIMS: Transjugular intrahepatic portosystemic stent shunt (TIPSS) is effective in the prevention of variceal rebleeding but requires invasive portographic follow up. This randomised controlled trial aims to test the hypothesis that combining variceal band ligation (VBL) with TIPSS can obviate the need for long term TIPSS surveillance without compromising clinical efficacy, and can reduce the incidence of hepatic encephalopathy. PATIENTS/METHODS: Patients who required TIPSS for the prevention of oesophageal variceal rebleeding were randomised to either TIPSS alone (n = 39, group 1) or TIPSS plus VBL (n = 40, group 2). In group 1, patients underwent long term TIPSS angiographic surveillance. In group 2, patients entered a banding programme with TIPSS surveillance only continued for up to one year. RESULTS: There was a tendency to higher variceal rebleeding in group 2 although this did not reach statistical significance (8% v 15%; relative hazard 0.58; 95% confidence interval (CI) 0.15-2.33; p = 0.440). Mortality (47% v 40%; relative hazard 1.31; 95% CI 0.66-2.61; p = 0.434) was similar in the two groups. Hepatic encephalopathy was significantly less in group 2 (20% v 39%; relative hazard 2.63; 95% CI 1.11-6.25; p = 0.023). Hepatic encephalopathy was not statistically different after correcting for sex and portal pressure gradient (p = 0.136). CONCLUSIONS: TIPSS plus VBL without long term surveillance is effective in preventing oesophageal variceal rebleeding, and has the potential for low rates of encephalopathy. Therefore, VBL with short term TIPSS surveillance is a suitable alternative to long term TIPSS surveillance in the prevention of oesophageal variceal rebleeding.

Predicting survival in patients with liver cancer considered for transarterial chemoembolization.

INTRODUCTION: Transarterial chemoembolization (TACE) has been used extensively to treat tumours confined to the liver in patients unsuitable for surgical resection. This study attempts to identify patients with liver cancer most likely to benefit from this type of treatment. PATIENTS AND METHODS: All patients undergoing TACE for liver cancer between 1989 and 2001 were included in the study. RESULTS: In a group of 137 consecutive patients undergoing TACE, univariate analysis identified a number of pre-treatment factors that were associated with poor prognosis. Multivariate analysis of these factors subsequently identified three pre-treatment factors; age greater than 60, serum alkaline phosphatase concentration >120U/l and albumin less than 35 g/l; that were independently and significantly associated with reduced survival duration. A scoring system was devised with one point allocated for each adverse factor which produced median survivals related to points scored as follows, 0 points-20 months, 1 point-12 months, 2 points-7 months and 3 points-4 months. To validate this scoring system the next 40 consecutive patients undergoing TACE were studied prospectively. These patients had median survival durations related to points scored as follows 0 points not calculable, 1 point-10 months, 2 points-7 months, 3 points-4 months. CONCLUSION: This simple scoring system can be used to predict prognosis in patients with liver cancer and may assist in clinical decision making in the selection of patients likely to benefit from TACE.

Postchemoembolisation syndrome--tumour necrosis or hepatocyte injury?

Transarterial chemoembolisation of liver tumours is typically followed by elevated body temperature and liver transaminase enzymes. This has often been considered to indicate successful embolisation. The present study questions whether this syndrome reflects damage to tumour cells or to the normal hepatic tissue. The responses to 256 embolisations undertaken in 145 patients subdivided into those with hepatocyte-derived (primary hepatocellular carcinoma) and nonhepatocyte-derived tumours (secondary metastases) were analysed to assess the relative effects of tumour necrosis and damage to normal hepatocytes in each group. Cytolysis, measured by elevated alanine aminotransferase, was detected in 85% of patients, and there was no difference in the abnormalities in liver function tests measured between the two groups. Furthermore, cytolysis was associated with a higher rate of postprocedure symptoms and side effects, and elevated temperature was associated with a worse survival on univariate analysis. Multivariate analysis demonstrated that there was no benefit in terms of survival from having elevated temperature or cytolysis following embolisation. Cytolysis after chemoembolisation is probably due to damage to normal hepatocytes. Temperature changes may reflect tumour necrosis or necrosis of the healthy tissue. There is no evidence that either a postchemoembolisation fever or cytolysis is associated with an enhanced tumour response or improved long-term survival in patients with primary or secondary liver cancer.

The role of the transjugular intrahepatic portosystemic stent shunt (TIPSS) in the management of bleeding gastric varices: clinical and haemodynamic correlations.

BACKGROUND: The transjugular intrahepatic portosystemic stent shunt (TIPSS) is effective in the management of both oesophageal and gastric variceal bleeding. Although it has been reported that gastric varices can bleed at pressures of < or = 12 mm Hg, this phenomenon has been little studied in the clinical setting. AIMS: To assess the efficacy of TIPSS on rebleeding and mortality following gastric and oesophageal variceal bleeding, and the importance of portal pressure in both groups. METHODS: Forty eligible patients who had bled from gastric varices and 232 from oesophageal varices were studied. Patients were also subdivided into those whose portal pressure gradients (PPG) prior to TIPSS were < or = 12 mm Hg (group 1) and >12 mm Hg (group 2). RESULTS: There was no difference in Child-Pugh score, age, sex, or alcohol related disease between patients bleeding from gastric or oesophageal varices. Patients who bled from gastric varices had a lower PPG pre-TIPSS (15.8 (0.8) v 21.44 (0.4) mm Hg; p<0.001). There was no difference in the rebleeding rate (20.0% v 14.7%; NS). There was a significant difference (p<0.05) in favour of the gastric varices group in the one year mortality (30.7% v 38.7%) and five year mortality (49.5% v 74.9%), particularly in those patients in group 2. Gastric variceal bleeding accounted for significantly more cases in group 1 than in group 2 (36.8% v 10.2%; p<0.001). Most patients in group 2 who rebled had a PPG post-TIPSS of >7 mm Hg. CONCLUSIONS: TIPSS is equally effective in the prevention of rebleeding following gastric and oesophageal variceal bleeding. A significant proportion of gastric varices bleed at a PPG < or = 12 mm Hg. The improved mortality in patients with gastric variceal bleeding is seen only in those that bleed at a PPG >12 mm Hg, and warrants further study.

Treatment of hepatic metastases of neuroendocrine malignancies: a 10-year experience.

BACKGROUND: Liver metastases from neuroendocrine tumours may give rise to symptoms due to hormone production or mass effect. Accepted management options include administration of somatostatin-analogues, selective chemoembolisation or hepatic resection. The aim of this study was to review the management of hepatic neuroendocrine metastases in our unit. METHODS: Patients with neuroendocrine tumours presenting between 1989 and 1999 were identified from pathology, radiology and surgical databases. Case notes were retrospectively reviewed for demographic data, treatment modality and outcome. Response to treatment was based on biochemistry, radiology or symptoms, and response rates were defined accordingly. RESULTS: Thirty patients with a mean age of 55 years presented with, or later developed liver metastases. The most frequent presenting symptoms were abdominal pain (63%), diarrhoea (40%), weight loss (33%) and flushing (13%). Five patients underwent liver resection with complete symptomatic response, nine underwent chemoembolisation with a 75% response rate (either biochemically, radiologically or symptomatic) and fifteen were treated with a somatostatin-analogue, with a response rate of 86%. Median survival from detection of metastases was 45 months. CONCLUSIONS: Liver resection provides good symptomatic relief, but it is only indicated in a small proportion of patients with metastatic neuroendocrine tumours. Both chemoembolisation and somatostatin-analogues offer useful symptomatic control for these patients with good survival prospects.

Transjugular intrahepatic portosystemic stent-shunt insufficiency and the role of diabetes mellitus.

BACKGROUND/AIMS: Maintenance of long-term patency of transjugular intrahepatic portosystemic stent-shunts (TIPSS) has proved problematic. Various prognostic variables have been assessed as predictors, but the role of diabetes mellitus, which induces vascular endothelial cell dysfunction, has not been assessed. METHODS: We analysed the records of 248 patients who underwent TIPSS between July 1991 and July 1997, followed-up through to August 1998. Patients with at least one shunt assessment by portography and available blood glucose levels were eligible (177 patients; median follow-up, 15.0 months). Fourteen patients had a pre-procedural diagnosis of diabetes (one insulin dependent, seven oral hypoglycaemic treated and six diet controlled). In another 14 patients, diabetes was diagnosed at TIPSS insertion, giving a 28/177 (15.8%) prevalence of diabetes in our patients. Fifty-nine patients were excluded from the final analysis (including five diabetics), as they either died or had early shunt insufficiency (within 1 month of stent placement), leaving 118 patients (including 23 diabetics) to be included in the final analysis. RESULTS: Mean age, sex distribution, median follow-up (months) and pre-shunt portal pressure gradient were comparable in the two groups (diabetics versus non-diabetics). Child-Pugh classes A and B were more common in the diabetic group (P < 0.01), and the mean inserted stent diameter was larger in the diabetic group (P < 0.05). The presence of diabetes was associated with a higher incidence of delayed shunt insufficiency (P = 0.02), but there was no evidence of an association between presence of diabetes and variceal haemorrhage post TIPSS. Kaplan-Meier analyses revealed earlier insufficiency in diabetic patients compared with those without diabetes (P = 0.04). Age, gender and presence of diabetes are included in the final logistic regression model. Individuals who have diabetes are more likely to experience shunt insufficiency independent of age and gender. CONCLUSIONS: Diabetes mellitus is common in patients undergoing TIPSS and is associated independently with increased incidence of primary delayed shunt insufficiency.

Acute changes in cerebral blood flow and metabolism during portasystemic shunting.

This report describes the instantaneous changes in cerebral blood flow (CBF), determined by intravascular ultrasound and Doppler, in a patient with cirrhosis undergoing placement of a transjugular intrahepatic stent-shunt for uncontrolled variceal bleeding. Acute changes in CBF were observed during and after portasystemic shunting, which culminated in cerebral edema and cerebral herniation.

Virtual hepatic resection using three-dimensional reconstruction of helical computed tomography angioportograms.

OBJECTIVE: To establish the accuracy of virtual hepatic resection using three-dimensional (3D) models constructed from computed tomography angioportography (CTAP) images in determining the liver volume (LV) resected during resectional liver surgery. SUMMARY BACKGROUND DATA: The ability to measure LV before surgery could be useful in determining the extent and nature of hepatic resection. Accurate assessment of LV and an estimate of liver function may also allow prediction of postoperative liver failure in patients undergoing resection, assist in volume-enhancing embolization procedures, help with the planning of staged hepatic resection for bilobar disease, and aid in selection of living-related liver donors. METHODS: A retrospective study was conducted involving 27 patients scheduled for liver resection. Using mapping technology, 3D models were constructed from helical CTAP images. From these 3D models, tumor volume, total LV, and functional LV were calculated and were compared with body weight. The 3D liver models were subjected to a virtual hepatectomy along established anatomical planes, and the resected LV was calculated. The resected volume predicted by radiologists (unaware of the actual weight) was compared with the specimen weight measured after actual surgical resection. RESULTS: A significant correlation was found between body weight and functional LV but not total LV. The computer prediction of resected LV after virtual hepatectomy of 3D models compared well with resected liver weight. CONCLUSION: Virtual hepatectomy of 3D CTAP reconstructed images provides an accurate prediction of liver mass removed during subsequent hepatic resection. The authors intend to combine this technology with an assessment of liver function to attempt to predict patients at risk for liver failure after hepatic resection.

Distribution of colorectal liver metastases in patients referred for hepatic resection.

BACKGROUND: There is a perception that streamline flow of blood in the portal vein may influence the anatomic distribution of liver metastases, depending on the site of the primary tumor. It has previously been reported that cancers arising in the right colon are distributed to the right lobe of the liver 10 times more commonly than to the left lobe, whereas liver metastases from tumors arising from the left colon and rectum are believed to be distributed homogenously. METHODS: Data were collected prospectively on the anatomic site of hepatic metastases in 207 patients with colorectal metastases referred for consideration for surgery. Anatomic site was established by a combination of computed tomography scanning and either laparoscopic or intraoperative ultrasonography. The site of the primary tumor was known in all cases. RESULTS: A total of 708 metastases were identified, of which 67% were in the right hemiliver and 33% were in the left. The ratio of involvement of the right and left hemilivers by metastases arising from right colon tumors was 2. 02:1 and for left colon tumors 2.1:1. When patients with unilobar disease only were considered, the ratio of involvement of the right and left hemilivers increased to 2.9:1, but again no difference was evident that depended on the site of the primary tumor. CONCLUSIONS: This study could not find any evidence to support a differential pattern of metastasis within the liver dependent on the location of the primary colorectal carcinoma.