Diagnosis of Alagille syndrome-25 years of experience at King's College Hospital.

OBJECTIVE: The aim of the study was to study the clinical and histological features of Alagille syndrome (AGS) at presentation comparing the value of the various modalities before the implementation of genetic diagnosis. PATIENTS AND METHODS: We performed a retrospective analysis of the records of 117 children diagnosed as having AGS after referral to King's College Hospital between 1980 and 2005. RESULTS: Cholestasis was seen in 104 of 117 (89%), characteristic facies in 91 of 117 (77%), posterior embryotoxon in 72 of 117 (61%), butterfly vertebrae in 44 of 117 (39%), heart disease (most often peripheral pulmonary stenosis) in 107 of 117 (91%), and renal disease in 27 of 117 (23%). Serum cholesterol levels of >5 mmol/L were seen in 52 of 86 (60.4%). Liver biopsy showed characteristic features of paucity of interlobular bile ducts in 59 of 77 (76.6%) children younger than 16 weeks of age, in 10 of 14 (71.4%) between 16 weeks and 1 year of age, and in 8 of 12 (66.66%) older than 1 year of age. Other biopsy findings were those of nonspecific hepatitis and biliary features. Iminodiacetic acid scans showed no excretion of isotope into the bowel after 24 hours in 21 of 35 (60%), and small/no gallbladder on ultrasound was seen in 29 of 104 (27.8%). Eleven of 117 (9.4%) had a diagnostic laparotomy and operative cholangiography, 2 proceeding to Kasai portoenterostomy before referral to our unit. CONCLUSIONS: Clinical features of AGS are not as consistently informative as suggested in the literature. Hypercholesterolaemia is nonspecific but may be a helpful pointer. Histology is not characteristic in 25%; hepatobiliary iminodiacetic acid scan and ultrasound may suggest a false diagnosis of biliary atresia in 60% and 28%, respectively, supporting the concept that infants with liver disease warrant early referral to a specialist centre. The advent of genetic diagnosis will redefine the syndrome with likely effects on the prognosis of the defined group.

Manganese-enhanced MRI predicts the histological grade of hepatocellular carcinoma in potential surgical candidates.

AIM: To evaluate the role of manganese-enhanced magnetic resonance (Mn-MRI) in predicting tumour differentiation prior to liver transplant or resection for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: The inclusion criteria were patients with HCC who underwent Mn-MRI prior to transplantation or resection from 2001-2008. T1-weighted MRI images were acquired at 0 and 24h after manganese dipyridoxal diphosphate (MnDPDP) intravenous contrast medium and reviewed prospectively. Manganese retention at 24h was correlated with tumour differentiation and disease-free survival. RESULTS: Eighty-six patients underwent Mn-MRI (transplantation 60, resection 26); 114/125 lesions (91%) that were arterialised as evidenced at computed tomography (CT) and had manganese uptake on MRI were HCC. There were 11 false positives (9%) that were regenerative nodules. Ten of fourteen non-manganese-retaining HCC (71%) were poorly differentiated, compared with only 13/114 manganese-retaining HCC (11%) (p<0.0001). Sensitivity, specificity, positive and negative predictive values of non-retention of MnDPDP in predicting poorly differentiated tumours were 0.43, 0.96, 0.71 and 0.88. Median disease-free survival of patients with non-manganese-retaining HCC was less than for patients with manganese-retaining HCC (14±5 months versus 39±3 months, log rank p=0.025). CONCLUSION: Non-manganese-retaining HCCs are likely to be poorly differentiated and have a poor prognosis. Manganese-enhanced MRI appears to have a role in preoperative assessment of HCC and warrants further evaluation.

Comparison of the hepatic perfusion index measured with gadolinium-enhanced volumetric MRI in controls and in patients with colorectal cancer.

The aim of the study was to adapt the methodology established for dynamic CT measurements of the hepatic perfusion index (HPI) to MRI, and to assess the potential role of MRI measurements of the HPI in detecting regional alterations in liver perfusion between patients with colorectal liver metastases and normal controls. The HPI was evaluated from serial T(1) volume acquisitions acquired over the course of a Gd-DTPA bolus injection. Time-course data from regions of interest in the liver, spleen and aorta were used to calculate the HPI; and HPI data from control subjects were compared with data from patients with known colorectal metastases. Significant differences were found between the relative portal perfusion and hepatic perfusion indices calculated for the patient and control groups (p<0.005). These results suggest that hepatic perfusion indices can be derived using MRI-based methods, and that these perfusion indices are sensitive to differences in liver perfusion associated with established metastatic liver disease on imaging. This technique may contribute to the early detection of liver metastases, allowing early surgical intervention and improved patient survival.

The use of percutaneous transluminal angioplasty in hepatic artery stenosis after transplantation.

Graft ischemia following liver transplantation is associated with a high incidence of morbidity and mortality. The present report concerns a group of seven patients in whom an anastomotic stenosis of the hepatic artery was identified. Three patients had unexplained allograft dysfunction at a median time of 28 days (range 13-64 days), and 3 had a biliary leak at a median time of 42 days after liver transplantation (range 35-270 days). In one patient the stenosis was diagnosed by routine Doppler ultrasound one week after transplant. Management was by percutaneous transluminal angioplasty at a median time of 35 days (range 13-270 days) after transplantation. After angioplasty there was a marked improvement in clinical appearance, liver function, and liver histology in 5 of the 7 patients. Those patients who had a biliary leak subsequently developed strictures that eventually required biliary tract reconstruction (hepaticojejunostomy) in two and retransplantation in one. Percutaneous transluminal angioplasty is an effective way of improving arterial blood flow in cases of anastomotic stenosis, reducing the likelihood of complete occlusion by thrombosis. If recognized early and treated promptly ischemic changes in the graft can resolve and the development of biliary strictures may be avoided.

Interventional radiology of the biliary tract. Intraductal radiation.

One palliative method of treating patients with a high duct cholangiocarcinoma is the use of 192Ir wire. This is placed through the tumor, which has been previously intubated, and delivers a high local dose of radiation. The mean survival time in 30 patients treated with intraductal radiation was 16.8 months, an improvement compared to surgical bypass or endoscopic and radiologic drainage procedures.

Survival and outcome after hepatic artery thrombosis complicating pediatric liver transplantation.

BACKGROUND/PURPOSE: Hepatic artery thrombosis (HAT) represents a significant cause of graft loss and mortality after pediatric orthotopic liver transplantation (OLT). The incidence and etiology of this complication have been investigated in detail but relatively little is known about outcome. METHODS: A review was conducted of all children with confirmed HAT complicating OLT during a 10-year period (1990 through 1999) in a single center. HAT was established by angiography or at operation in all cases. RESULTS: From a consecutive series of 400 pediatric OLTs, there were 31 (7.8%) instances of HAT in 29 children of median age 3.8 years (range, 8 days to 16 years). Twenty-four (83%) are alive after a median follow-up of 3.6 years. Fourteen cases occurred after transplantation of whole grafts and 17 after reduced or split livers. Of the 18 episodes resulting in retransplantation, there were 5 deaths and 2 second episodes of HAT; surviving children are alive with good graft function. Of the 13 episodes managed without retransplantation, 4 patients underwent attempted early revascularisation of the graft, which was successful in 2, and the remainder initially were treated conservatively. All 13 children are alive after a median follow-up of 4.1 years (range, 0.6 to 5.8), but 5 required radiologic or surgical intervention for biliary or septic complications; biochemical liver function is normal in 8, mildly abnormal in 3, and poor in 2. Retransplantation was less likely in those who had received reduced or split grafts (7 of 17) compared with those who had received whole grafts (11 of 14), but this difference just failed to reach statistical significance (chi(2) = 3.01, 0.1 > P > .05). CONCLUSIONS: Using a selective policy of retransplantation, revascularisation, and conservative treatment, 83% of children survived HAT complicating OLT. Approximately 40% of children with HAT survived without retransplantation. J Pediatr Surg 36:888-891.

Selective arterial embolisation for hepatic trauma.

The technique of selective arterial embolisation for patients presenting with major hepatic trauma is described. We have used this technique successfully in four patients, three of whom had continued bleeding after emergency laparotomy. It can abolish localised intrahepatic arterial haemorrhage and arteriovenous shunting. Selective embolisation may prove to be a useful technique in reducing the mortality of major hepatic trauma.

Role of imaging in the management of pancreatic mass.

Pancreatic cancer is the second commonest malignant gastrointestinal neoplasm. Modern imaging techniques have greatly increased sensitivity in diagnosing and staging pancreatic cancers. Multidetector CT in particular, plays a critical role in local staging and determining the resectability of pancreatic tumours. MR and endoscopic ultrasound are valuable in those groups of patients in whom CT findings alone are inconclusive in tumour characterisation and local staging, particularly vascular involvement. In this article we review the current established concepts and the role of imaging in the multidisciplinary management of pancreatic tumours together with a comprehensive review of the literature.

Cerebral manifestations in liver disease and transplantation.

Patients with liver disease frequently develop cerebral complications. The brain may be affected directly by the pathological process or agent responsible for the liver disease, as a consequence of the metabolic and haemodynamic derangement caused by hepatic dysfunction, or as a complication of the treatment of liver disease. Computed tomography (CT) and magnetic resonance imaging (MRI) can be helpful in the diagnosis and management of these complications, and advanced techniques such as diffusion weighted imaging (DWI) and magnetic resonance spectroscopy (MRS) are providing new insights into the underlying pathophysiological processes. We present a radiological overview of the cerebral manifestations of liver disease, categorized as acute presentations, chronic presentations, and conditions occurring in the context of liver transplantation.

Vanishing liver tumours.

Spontaneous resolution of liver tumours is a rare, but recognized entity that has been reported to occur within the spectrum of benign and malignant liver tumours occurring in both adult and paediatric population. The aetiology of this unusual phenomenon is not clearly understood. In this article we present case examples of various benign and malignant liver tumours that have regressed spontaneously without treatment together with a review of the literature, and a summary of the current understanding of the pathogenesis of these tumours.

Colocutaneous fistula complicating therapeutic mesenteric embolisation.

Percutaneous embolotherapy has now assumed an important role in the management of massive colonic haemorrhage. However, this therapeutic option is associated with a significant risk of irreversible segmental colonic ischaemia. We present a case where distal segmental ischaemia led to a colocutaneous fistula, a complication not reported so far in the literature.

Parametric mapping of the hepatic perfusion index with gadolinium-enhanced volumetric MRI.

The purpose of this study was to adapt the hepatic perfusion index (HPI) methodology previously developed for MRI to derive 3D parametric maps of HPI, and to investigate apparent differences in HPI maps between a group of colorectal cancer patients and controls. To achieve this, a new and simpler approach to HPI calculation which does not require measurements from the aorta or portal vein is introduced, and assessed with large liver regions of interest (ROIs) in patients and controls. Several example HPI maps showing localized variation are then presented. The subject group consisted of 12 patients with known colorectal metastases, and 13 control subjects referred for routine contrast-enhanced spine imaging with no history of neoplastic disease. HPI was evaluated from serial T1 volume acquisitions acquired over the course of a Gd-DTPA bolus injection. Regions of abnormal perfusion were visible on the HPI maps derived for the patient group, manifested as areas of locally increased HPI extending around the visible margins of known metastases evident on the conventional contrast-enhanced images. This method for MR voxel-based parametric mapping of HPI has the potential to demonstrate regional variations in perfusion at the segmental and subsegmental level.

Rib abnormalities arising before and after birth.

UNLABELLED: Rib abnormalities detected in the neonatal period are usually thought to be part of a skeletal disorder. There are, however, many causes which include metabolic bone disease, infection and trauma. Rib abnormalities are also found in general disorders such as chromosomal abnormalities or hypothyroidism. CONCLUSION: A thorough examination of the neonatal chest radiograph must include the review of the skeletal parts, which can often be revealing.

Retroperitoneal collections--aetiology and radiological implications.

PURPOSE: Retroperitoneal collections related to the psoas, in the absence of pancreatitis, are uncommon. This study reviews the imaging, pathogenesis and management of retroperitoneal collections with particular emphasis on distinguishing imaging features and the role of percutaneous drainage. MATERIALS AND METHODS: Twenty-three retroperitoneal collections in 22 patients were reviewed in a 2-year period. Twenty-one patients underwent computed tomography (CT), with ultrasound (US) conducted in 14 and magnetic resonance imaging (MRI) in four. The clinical history and associated aetiological factors were noted. Methods of drainage were compared, pathological/microbiological results were recorded and the clinical outcome noted. RESULTS: The mean age of presentation was 46.9 years (range 18-85 years). There was a male to female preponderance (17 to 6). Eighteen collections proved to be abscesses with five haematomas confirmed. Of the abscesses, three were primary and 15 were secondary to spinal, gastrointestinal or renal disease. Escherichia coli was the commonest isolated organism followed by Mycobacterium tuberculosis. No haematomas were drained. Twelve abscesses were drained successfully by percutaneous methods; three were managed with antibiotics alone; three were managed surgically. CONCLUSION: Secondary abscesses predominate and investigation should be directed at excluding a gastrointestinal or renal source. Tuberculous disease remains a significant problem. Percutaneous drainage allows effective management, even in the presence of a secondary abscess.

Hepatic artery stenosis following liver transplantation: significance of the tardus parvus waveform and the role of microbubble contrast media in the detection of a focal stenosis.

PURPOSE: To evaluate the role of microbubble ultrasound contrast media in detecting stenosis of the post-liver transplant extrahepatic hepatic artery (HA) in the presence of the tardus parvus spectral Doppler waveform of the intrahepatic HA. MATERIALS AND METHODS: All post-liver transplant patients with a prolonged systolic acceleration time (SAT>0.08s) and/or a reduced resistant index (RI<0.50) of the HA (the tardus parvus waveform) on colour Doppler ultrasound (CDUS), were assessed with microbubble contrast medium for a focal arterial stenosis. Following microbubble contrast-enhanced CDUS, patients underwent arteriography or follow-up CDUS. RESULTS: A total of 2038 examinations were performed in 529 liver transplant recipients; 16 (3.02%) tardus parvus waveforms were identified. The median SAT of the intrahepatic HA was 0.18s (range 0.11-0.38s) and the RI 0.47 (range 0.22-0.58). No extrahepatic elevated peak systolic velocity (PSV), defined as above 1.00m/s, was detected on the baseline examinations. Following the administration of microbubble contrast, medium, PSV in the extrahepatic HA was elevated in 14 of 16 patients, (median=2.15m/s, range=1.44-3.10m/s); flow was not identified in two patients. Arteriography was performed in 10 patients and confirmed stenosis in eight (median grade of stenosis 93%, range 60-99%) and occlusion in two. The measured median PSV at contrast-enhanced CDUS in the stenosis group was 2.03m/sec (range 1.44-2.71m/sec). Repeat CDUS in six patients not undergoing arteriography showed resolution in four; one underwent re-transplantation before arteriography and one patient maintains a tardus parvus waveform. In transplant recipients undergoing arteriography during the study period (n=55), no hepatic artery stenosis without a tardus parvus waveform was seen. CONCLUSION: The tardus parvus waveform pattern is an excellent screening test for the presence of post-liver transplantation hepatic artery stenosis. There is only a limited role for microbubble ultrasound contrast agent in the presence of a tardus parvus waveform. It could be used following equivocal colour Doppler ultrasound, but arteriography will still be necessary.

Pseudotumours of hepatic imaging.

The diagnosis of liver tumours with CT depends on differential attenuation coefficients and enhancement patterns. The sensitivity of CT in defining tumours is well established but there remain a variety of conditions that mimic these patterns, presenting a 'pseudotumour' appearance. A common illustrative example is hepatic steatosis, but less well recorded are the sphingolipidoses and intrahepatic arterioportal shunts, either post-traumatic or related to venous outflow block. Alpha-1-antitrypsin deficiency and hereditary tyrosinaemia provide examples in childhood.

Segmental portal hypertension due to splenic vein obstruction: imaging findings and diagnostic pitfalls in four cases.

Segmental portal hypertension due to isolated splenic vein obstruction is a rare but important entity as it is the only curable cause of portal hypertension by splenectomy. Four cases are presented illustrating the radiological features of splenic vein obstruction, and the diagnostic pitfalls that arose in patients with complicated clinical presentations.

MnDPDP-enhanced MR imaging of the liver. Correlation with surgical findings.

PURPOSE: To compare lesion detection and characterisation predicted by MnDPDP-enhanced MR imaging with surgical excision and pathological examination. MATERIAL AND METHODS: Ninety patients were intravenously infused at a rate of 2 to 3 ml/min with 5 mumol/kg mangafodipir trisodium (MnDPDP, Teslascan). The patients were examined with spin-echo and gradient-echo T1-weighted MR imaging at 1 h and 24 h after the end of infusion. The results were compared with identical pre-contrast sequences. In 20 of these patients, the pre-operative MR findings were compared with intra-operative ultrasonography and histology of the resected liver specimens. RESULTS: In those with liver metastases, there was a good correlation between MR and the hepatic disease in 11 out of 14 cases. In the group with primary liver tumours, MR findings correlated with hepatic disease in 5 out of 6 cases. CONCLUSION: Liver lesion characterisation is possible with MnDPDP, and MR contrast enhancement with this agent is considered to be an important adjunct to the radiological assessment of patients with neoplastic liver disease where accurate decisions for surgical planning are imperative.

Developmental intrahepatic shunts of childhood: radiological features and management.

The purpose of this study was to evaluate the role of radiological techniques in the diagnosis and management of developmental intrahepatic shunts. Hepatic vascular fistulae are recognised sequelae of liver trauma and intrahepatic tumours. However, there are rare developmental malformations which may present in childhood or later life and which may carry life-threatening complications. Retrospective analysis of clinical and radiological data was carried out in 24 patients. Anomalies evaluated were: (a) direct communication between hepatic artery and hepatic veins; (b) congenital hepatoportal arteriovenous malformations; and (c) congenital portocaval anastomosis with persistent flow through the ductus venosus. Although rare, the prompt recognition of these vascular anomalies allows early surgical or radiological intervention and reversal of the haemodynamic complications.

Biliary complications following orthotopic liver transplantation.

The gall-bladder conduit anastomosis (choledocho-cholecysto-choledochostomy) has been the most frequently used technique for the biliary tract anastomosis in the Cambridge/King's College Hospital joint liver transplantation programme since 1976. Cholangiograms and interventional biliary procedures performed over a 3 year period were reviewed retrospectively. Seventy-six of 148 patients managed post-operatively at King's College Hospital were studied (79 transplants). Cholangiograms were abnormal in 63 (80%) transplants with biliary strictures; inspissated bile formation, bile leak and T-tube malposition occurring in 50, 23, 14 and three transplants respectively. Anastomotic strictures occurred most frequently, predominantly at the proximal anastomosis, and the presence of inspissated bile and the T-tube in relation to these contributed towards subsequent biliary obstruction. Non-anastomotic strictures in the donor biliary tract were associated with a high position of the T-tube tip at or above the liver hilum. Saline irrigation of the bile ducts for inspissated bile or its removal via the endoscope were effective measures in the management of biliary obstruction but percutaneous balloon dilatation and endoscopic stent insertion for biliary strictures were found to have a limited role.