Outcomes and indications for intervention in non-operative management of paediatric liver trauma: a 5 year retrospective study.

AIM: To determine the applicability of accurate computed tomography (CT) evaluation and embolization as non-operative management for liver trauma in a paediatric population. MATERIAL AND METHODS: A retrospective observational study of 37 children (mean age 10.5 years) with hepatic trauma (28 blunt, 9 penetrating) admitted to a trauma referral centre over a 5 year period. All patients were evaluated with CT and scored with an Association for the Surgery of Trauma score. Inpatient information was reviewed for demographics, associated injuries, modes of management, efficacy and complications of management, and outcome.Statistical analysis was performed. RESULTS: There were seven contusions, two grade I, two grade II, nine grade III, and 17 grade IV liver lacerations. Only two patients (grade IV, penetrating) underwent surgery for the management of bowel perforation. All children had non-surgical treatment of their liver trauma: three cases (grade IV) had primary angiography due to CT evidence of active bleeding and embolization was performed in two of these. Seven patients (two grade III, five grade IV)had angiography during the follow-up for evidence of a complicating pseudoaneurysm and embolization was performed in six of them. Embolization was successful in all the children; one minor complication occurred (cholecystitis). Endoscopic retrograde cholangiopancreatography (ERCP) plus stenting was performed in two cases for a bile leak. All 37 children had a positive outcome. CONCLUSION: The present study demonstrates that non-operative management of hepatic trauma is applicable to children and may have a higher success rate than in adults.

Hepatic splenosis presenting as arterialised liver lesion in a patient with NASH.

INTRODUCTION: Splenosis represents the heterotopic autotransplantation of splenic tissue after a traumatic splenic rupture and splenectomy. It is not a rare condition and it is estimated to occur in up to 67% of patients with traumatic splenic rupture. CASE REPORT: We report one case of patient, affected by non alcoholic steatohepatitis (NASH), with a hypervascularised liver lesion, that the final histological examination revealed hepatic splenosis. This is a rare condition that may be misinterpreted as adenoma or hepatocellular carcinoma (HCC). Imaging techniques and features that might contribute to the diagnosis and may avoid invasive treatment are also discussed. Although hepatic splenosis is a rare condition, this diagnosis should be considered in patients with previous history of abdominal trauma and then the diagnosis of splenosis may be confirmed by Tc-99m-DRBC scintigraphy, avoiding biopsy or further surgery.

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.

Predictive value of bile duct dimensions measured by ultrasound in neonates presenting with cholestasis.

OBJECTIVES: : The significance of extrahepatic bile duct dilatation on ultrasound examination in jaundiced infants is often uncertain. We wished to clarify the diagnostic and prognostic significance of the present finding in neonatal conjugated hyperbilirubinaemia. PATIENTS AND METHODS: : We retrospectively enrolled all of the infants younger than 3 months with extrahepatic biliary dilatation > or =1.2 mm (nonfasting ultrasound) who presented during the study period. We reviewed clinical, radiological, and laboratory data to determine mode of presentation, diagnosis, interventions, and long-term outcome. RESULTS: Seventy-six infants (41 male) were identified, all of whom were referred with conjugated hyperbilirubinaemia. Median gestational age was 39 weeks (range 24-42 weeks). Inspissated bile was the most common diagnostic category, whereas congenital choledochal malformation was the diagnosis made in 13% infants. Dilatation was an incidental finding in 9% of the infants. Seventeen percent of infants had required either surgical or radiological intervention by the time of follow-up. Overall, 41% infants had spontaneous resolution of bile duct dilatation, including 8% who had "grown into" an unchanged duct size rather than involution of dilatation. The median size of bile duct at presentation for those who required intervention was 4.7 versus 2 mm for the remainder (P < 0.001). Of those who resolved spontaneously, the median size of duct at presentation was 1.8 mm. CONCLUSIONS: : Bile duct dilatation <3 mm (nonfasting ultrasound) with neonatal cholestasis is unlikely to be of significance whereas >4 mm is likely to be associated with choledochal malformation or need for intervention. The intermediate group is likely to be associated with inspissated bile syndrome following resolution of which innocent biliary dilatation may persist.

Hepatocyte transplantation followed by auxiliary liver transplantation--a novel treatment for ornithine transcarbamylase deficiency.

We report the first successful use of hepatocyte transplantation as a bridge to subsequent auxiliary partial orthotopic liver transplantation (APOLT) in a child antenatally diagnosed with severe ornithine transcarbamylase (OTC) deficiency. A total of 1.74 x 10(9) fresh and cryopreserved hepatocytes were administered intraportally into the liver over a period of 6 months. Immunosuppression was with tacrolimus and prednisolone. A sustained decrease in ammonia levels and a gradual increase in serum urea were observed except during episodes of sepsis in the first 6 months of life. The patient was able to tolerate a normal protein intake and presented a normal growth and neurological development. APOLT was successfully performed at 7 months of age. We conclude that hepatocyte transplantation can be used in conjunction with APOLT as an effective treatment for severe OTC-deficient patients, improving neurodevelopmental outcomes.

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.

Peribiliary cysts can mimic Caroli's disease: a case report.

Peribiliary cysts, otherwise known as cystic dilatation of the peribiliary glands, are uncommon, and are usually discovered incidentally at autopsy, or in explants following liver transplantation. Preoperative diagnosis is often difficult owing to their asymptomatic nature and small size. Exclusion of a premalignant or malignant cystic condition is mandatory. We report a case of peribiliary cysts, initially thought to represent Caroli's disease, and briefly discuss the management of this condition.

Adoptive immunotherapy administered via the hepatic artery and intralesional interleukin-2 in hepatocellular carcinoma.

We assessed the feasibility of using lymphokine-activated killer cells (adoptive immunotherapy) with infusions of interleukin-2 when given regionally in three patients with unresectable primary hepatocellular carcinoma (PHC). In 2 patients, 2 cycles, which included a bolus of LAK (10(7) to 10(8) cells followed by a 4-hourly infusion of IL-2 were administered via selective arterial catheterization of the hepatic artery. One further patient received 3 cycles of IL-2 alone by direct intralesional and perilesional injections. Minimal toxicity was observed and side effects such as fever were comparable to those observed with systemic infusions of IL-2 alone. Serial alpha-fetoprotein (AFP) levels initially fell but subsequently rose within 2 to 4 weeks of therapy. AFP levels had not reached pre-treatment values at 4 months in 2 patients, 1 of whom was alive and well at 15 months follow-up.

Accessory right hepatic artery arising from the left: implications for split liver transplantation.

BACKGROUND: Variant arterial anatomy must be recognized and appropriately managed during split liver transplantation to ensure complete vascular supply to both grafts. We describe an accessory posterior right hepatic artery, arising from the left and passing behind the portal vein bifurcation. METHODS: Thirty-seven consecutive livers were examined during ex vivo liver-splitting procedures. An abnormal right accessory artery arising from the left hepatic artery was identified high in the porta hepatis. The anatomical variant is described and illustrated by methylene blue injection and arteriography. RESULTS: The anomaly was encountered in 2 of 37 split liver procedures. The two right lobes with the abnormal artery were discarded. CONCLUSION: Care should be taken during dissection behind the portal vein bifurcation to exclude an accessory segmental right hepatic artery. If present, the liver may not be suitable for splitting without compromising the right lobe, unless the left hepatic artery can be divided distal to the origin of the accessory vessel.

Hepatic artery thrombosis after liver transplantation in children under 5 years of age.

The incidence of hepatic artery thrombosis (HAT) following orthotopic liver transplantation in children varies from 4% to 26% and represents a significant cause of graft loss. The purpose of this study was to analyze the risk factors for HAT following liver transplantation in children less than 5 years old. Seventy-three transplants were performed in 62 children under 5 years of age, including 16 for acute hepatic failure, 46 for chronic liver disease, and 11 retransplants. Twenty-four whole liver grafts (WLG) and 49 reduced size grafts (3 right lobes, 16 left lobes, and 30 left lateral segments) were transplanted. The recipient common hepatic artery was used to provide arterial inflow in 22 transplants and an infrarenal iliac conduit in 51 transplants. The overall incidence of HAT was 8 out of 73 transplants (11%). The cold ischemia time (14.3 +/- 3.03 hr) in this group was significantly longer than the cold ischemia time for those without HAT (11.7 +/- 3.94 hr) (P = 0.049). The incidence of HAT for whole and reduced grafts was 25% (6/24) and 4% (2/49), respectively (P = 0.01). HAT occurred in 6 of 22 grafts (27.3%) revascularized from the recipient common hepatic artery, compared with 2 of 51 grafts (3.9%) using an infrarenal arterial conduit (P = 0.008). The combination of recipient hepatic arterial inflow to a WLG resulted in HAT in 50% (6/12), whereas there were no cases of HAT with an iliac conduit to a WLG (P = 0.01). Of the eight patients with HAT, five are alive (median follow-up, 20 months; range, 7-27 months). Five patients were retransplanted, three within the first 2 weeks and two at 4 and 5 months for abnormal liver function in association with clinical and histological features of chronic rejection. Prolonged cold ischemia time and use of a whole graft with recipient hepatic arterial inflow are risk factors for developing HAT. The use of reduced size grafts and infrarenal iliac arterial conduits are associated with a low incidence of HAT.

Size reduction of small bowels from adult cadaveric donors to alleviate the scarcity of pediatric size-matched organs: an anatomical and feasibility study.

BACKGROUND: Small bowel transplantation in children weighing less than 10 kg is hindered by the lack of size-matched donors. The ability to create reduced size small bowel grafts from adult cadaveric donors suitable for use in young children has been studied. METHODS: Volumetric assessment of computed tomography scans were used to evaluate abdominal cavity and small bowel volumes in children. Small bowels were retrieved from adult cadaveric donors and reduced in size. RESULTS: Computed tomography studies of the abdominal cavity showed that the mean volume available for a small bowel graft was 260 ml in children less than 5 kg (n = 5) and 460 ml in children weighing 5-10 kg (n = 5). Fifteen small bowels were successfully reduced to provide an ileal graft of one meter while keeping the whole length of the superior mesenteric artery and vein after their dissection in the proximal part of the mesentery. The mean volume of the grafts created was 270 ml in seven thin patients (body mass index [BMI] <25), 390 ml in five preobese patients (25< BMI<30), and 490 ml in three obese patients (BMI>30). Mesenteric transillumination in thin donors allowed safe dissection and complete hemostasis. No diameter reduction was required. Technical modifications permitted the creation of two grafts, one ileal and the other jejunal from a single donor. Volumetric and surgical data show that implantation of up to two meters of ileum from a thin adult weighing up to 80 kg is feasible in children weighing less than 10 kg. CONCLUSION: Size reduction of adult cadaveric small bowels can provide suitable grafts for children of less than 10 kg and could expand the potential pool of donors for these patients.

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.

Therapy for hepatocellular-carcinoma (review).

Hepatocellular carcinoma remains one of the commonest malignant tumours in the world. It usually arises on a background of hepatic cirrhosis which limits the possibility of resection or transplantation. The literature contains few good randomised trials of therapy for this common tumour. This review discusses the role of surgery and liver transplantation together with recent developments in medical therapy, namely chemoembolisation, percutaneous ethanol injection and hormonal treatment, and arrives at a consensus as to the place of these treatments in the current management of hepatoma.

Living related adult-to-adult liver transplantation: meeting the donor shortage.

Experience in the Cromwell Hospital London, Adult-to-Adult Living Donor Liver Transplantation programme is described with particular reference to the results obtained in the first five recipients. The first two of these received a left lobe graft and the remaining three a right lobe graft. Three sons/daughters, and two siblings were the donors. Four of the five recipients survived and did well. The one recipient who died was a complicated retransplant procedure. The donors showed rapid recovery of liver function with normal tests by the 10th day and with evidence of regeneration on follow-up CT volume evaluation. The value of the procedure for patients who have little chance of obtaining a cadaver organ is undoubted, but critical assessment of the recipient's clinical state is essential if success is to be obtained with a small graft and at all times the safety of the donor must remain of paramount concern, as reports to date indicate instances of donor death in adult programme.

Congenital hepatoportal arteriovenous fistula.

BACKGROUND: Two children with congenital hepatoportal arteriovenous fistulas have been investigated and treated surgically. These cases have been reviewed with five cases previously reported. METHODS: Two children, 5 months and 14 months of age, presenting with failure to thrive, hepatosplenomegaly, ascites, and recurrent gastrointestinal bleeding with evidence of portal hypertension, were found to have congenital hepatoportal arteriovenous fistulas. RESULTS: Doppler ultrasonographic examination was important in identifying abnormal portal venous flow. Angiogram identified the fistulas, confirming the diagnosis. Both patients had significant portal hypertension (pressure more than 30 mm Hg). Surgical resection in one child was unsuccessful, but surgical ligation of the hepatic artery controlled the symptoms in both patients. CONCLUSIONS: Rapid collateralization of the hepatic arterial blood supply made embolization a short-term therapeutic measure, and surgical ligation of the hepatic artery is the treatment of choice for congenital hepatoportal arteriovenous fistulas.

Tumour ablation and hepatic decompensation rates in multi-agent chemoembolization of hepatocellular carcinoma.

Thirty-seven cirrhotic patients with 62 hepatocellular carcinoma (HCC) foci--most Child-Pugh class B or C and/or with large, inoperable tumours--underwent 148 sessions of transcatheter arterial chemoembolization (TACE) using lipiodol, doxorubicin and cisplatin. Treatment efficacy was assessed by serial hepatic arteriography in 34/37 (91.9%) patients and abdominal CT scanning in 3/37 (8.1%) patients. Child-Pugh status was determined prior to each treatment session. Varying degrees of control of tumour neovascularity occurred for a median 390 days (range 90 to > 1680 days) in 33/34 (97.1%) patients in whom progress hepatic arteriography was performed. Ablation of tumour neovascularity occurred in 6/6 (100%), 4/12 (33.3%) and 6/16 (37.5%) patients with HCC diameters < 4 cm, 4-7 cm and > 8 cm, respectively (p < 0.02). Significantly more sessions were required for ablation of larger tumours (p < 0.05). Recurrent HCC was detected in 50% of patients after a median 240 days (range 60-1120 days). Deterioration in Child-Pugh status followed a session of TACE on 19/148 (12.8%) occasions but resulted in unscheduled hospitalization on only 4/148 (2.7%) occasions, the highest incidence (8.3%) in Child-Pugh C patients. Actuarial survival was 27/36 (75.0%) at 6 months, 17/34 (50.0%) at 12 months, 14/34 (41.2%) at 18 months, 9/31 (29.0%) at 24 months and 4/27 (14.8%) at 36 months. Multi-agent TACE with lipiodol, doxorubicin and cisplatin provides a useful anti-tumour effect, even in cirrhotic patients with large HCCs. The incidence of clinically significant deterioration in hepatic function due to ischaemia of non-tumorous liver is acceptably low, even in Child-Pugh C patients.

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.

Chest radiograph appearance at 24 h of age--prediction of chronic oxygen dependency.

Chronic oxygen dependence is associated with immaturity, male sex and low birthweight, but amongst that high risk group further criteria are necessary to predict those most at risk. We previously developed a chest radiograph scoring system which, when used at 1 month of age, proved useful in predicting chronic oxygen dependency at 36 weeks post-conceptional age (PCA). We have now assessed whether the scoring system, if applied at 24 h of age, added predictive value to readily available demographic and ventilatory data. 50 infants, birthweight less than 1200 g and ventilated from birth, were examined. They had a median gestational age of 27 weeks (range 23-34), birthweight of 886 g (range 470-1172) and chest radiograph score of 7 (range 2-13). Univariate analysis revealed that oxygen dependency at 28 days and 36 weeks PCA was significantly associated with low gestational age, male sex and high ventilatory requirements, in addition to a high chest radiograph score. Stepwise regression analysis, however, demonstrated that a high chest radiograph score predicted oxygen dependence at 28 days, independent of immaturity, low birthweight, male sex and high ventilatory requirements. A chest radiograph score of more than 5 rendered an infant four times more likely to be oxygen dependent at 28 days than those with lower scores. We conclude the chest radiograph appearance at 24 h of age could be used as a criterion to institute interventional strategies aimed at reducing chronic oxygen dependence.

Comparison of a subjective and a quantitative assessment of the neonatal chest radiograph.

The aim of this study was to assess if quantitative classification of the chest radiograph appearance at 7 days predicted chronic oxygen dependency (oxygen dependency beyond 8 weeks of age) more accurately than did subjective classification at 28 days of age. Thirty preterm infants, median gestational age 27 weeks, who had chest radiographs taken for clinical purposes at 7 and 28 days of age, were recruited into the study. The 7-day chest radiograph was scored according to the lung volume, presence of opacification, interstitial changes, pulmonary interstitial emphysema and cystic elements. The range of chest radiograph scores was from 0-18, a score of 18 indicating the most abnormal appearance. The 28-day chest radiograph was classified as Type I or Type II chronic lung disease (CLD), according to the presence or absence, respectively, of coarse reticulation. The median chest radiograph score at 7 days of the 30 infants was 5 (range 2-14). In predicting chronic oxygen dependency, a chest radiograph score of 5 at 7 days had 83% sensitivity and 75% specificity, but a diagnosis of Type II CLD at 28 days of age had only 67% sensitivity and 67% specificity. We conclude that a quantitative assessment of the chest radiograph appearance at 7 days is more useful than a subjective assessment at 28 days of age.