Transient Liver Dysfunction Research Articles

Plasma cholesterol-lowering and transient liver dysfunction in mice lacking squalene synthase in the liver

Squalene synthase (SS) catalyzes the biosynthesis of squalene, the first specific intermediate in the cholesterol biosynthetic pathway. To test the feasibility of lowering plasma cholesterol by inhibiting hepatic SS, we generated mice in which SS is specifically knocked out in the liver (L-SSKO) using Cre-loxP technology. Hepatic SS activity of L-SSKO mice was reduced by >90%. In addition, cholesterol biosynthesis in the liver slices was almost eliminated. Although the hepatic squalene contents were markedly reduced in L-SSKO mice, the hepatic contents of cholesterol and its precursors distal to squalene were indistinguishable from those of control mice, indicating the presence of sufficient centripetal flow of cholesterol and/or its precursors from the extrahepatic tissues. L-SSKO mice showed a transient liver dysfunction with moderate hepatomegaly presumably secondary to increased farnesol production. In a fed state, the plasma total cholesterol and triglyceride were significantly reduced in L-SSKO mice, primarily owing to reduced hepatic VLDL secretion. In a fasted state, the hypolipidemic effect was lost. mRNA expression of liver X receptor α target genes was reduced, while that of sterol-regulatory element binding protein 2 target genes was increased. In conclusion, liver-specific ablation of SS inhibits hepatic cholesterol biosynthesis and induces hypolipidemia without increasing significant mortality.

Two patients with HNF4A-related congenital hyperinsulinism and renal tubular dysfunction: A clinical variation which includes transient hepatic dysfunction

The HNF4A p.R76W mutation causes congenital hyperinsulinism with Fanconi syndrome. Here, we report two cases who also presented with increased urinary calcium excretion and one had a transient hepatic dysfunction with hepatomegaly. Clinical variations including transient liver dysfunction is a likely mutation-specific clinical characteristic.

Repeat liver resection for recurrent colorectal metastases: a single‐centre, 13‐year experience

ObjectivesIsolated intrahepatic recurrence is noted in up to 40% of patients following curative liver resection for colorectal liver metastases (CLM). The aims of this study were to analyse the outcomes of repeat hepatectomy for recurrent CLM and to identify factors predicting survival. MethodsData for all liver resections for CLM carried out at one centre between 1998 and 2011 were analysed. ResultsA total of 1027 liver resections were performed for CLM. Of these, 58 were repeat liver resections performed in 53 patients. Median time intervals were 10.5 months between the primary resection and first hepatectomy, and 15.4 months between the first and repeat hepatectomies. The median tumour size was 3.0 cm and the median number of tumours was one. Six patients had a positive margin (R1) resection following first hepatectomy. There were no perioperative deaths. Significant complications included transient liver dysfunction in one and bile leak in two patients. Rates of 1‐, 3‐ and 5‐year overall survival following repeat liver resection were 85%, 61% and 52%, respectively, at a median follow‐up of 23 months. R1 resection at first hepatectomy (P = 0.002), a shorter time interval between the first and second hepatectomies (P = 0.02) and the presence of extrahepatic disease (P = 0.02) were associated with significantly worse overall survival. ConclusionsRepeat resection of CLM is safe and can achieve longterm survival in carefully selected patients. A preoperative knowledge of poor prognostic factors helps to facilitate better patient selection.

α-type-1 polarized dendritic cell-based vaccination in recurrent high-grade glioma: a phase I clinical trial

BackgroundHigh-grade gliomas including glioblastoma multiforme (GBM) are among the most malignant and aggressive of tumors, and have a very poor prognosis despite a temozolomide-based intensive treatment. Therefore, a novel therapeutic approach to controlling recurrence is needed. In the present study, we investigated the effect of activated dendritic cell (DC) (α-type-1 polarized DC)-based immunotherapy on high-grade glioma patients with the HLA-A2 or A24 genotype.MethodsNine patients with recurrent high-grade gliomas including 7 with GBMs who fulfilled eligibility criteria were enrolled into a phase I study of monocyte-derived DC-based immunotherapy. HLA-genotyping revealed 1 case of HLA-A*0201 and 8 cases of A*2402. Enriched monocytes obtained using OptiPrepTM from leukapheresis products on day1, were incubated with GM-CSF and IL-4 in a closed serum-free system, and activated on day6 with TNF-α, IL-1β, IFN-α, IFN-γ, and poly I/C. After pulsing with a cocktail of 5 synthetic peptides (WT-1, HER2, MAGE-A3, and MAGE-A1 or gp100) restricted to HLA-A2 or A24 and KLH, cells were cryopreserved until used. Thawed DCs were injected intradermally in the posterior neck at a dose per cohort of 1.0, 2.0 and 5.0× 107/body.ResultsThe frequency of CD14+ monocytes increased to 44.6% from 11.9% after gradient centrifugation. After a 7-day-incubation with cytokines, the mean percentage of DCs rated as lin-HLA-DR+ in patients was 56.2 ± 19.1%. Most DCs expressed high levels of maturation markers, co-stimulatory molecules and type-1 phenotype (CD11c+HLA-DR+) with a DC1/2 ratio of 35.6. The amount of IL-12 produced from activated DCs was 1025 ± 443 pg/ml per 105 cells. All 76 DC injections were well tolerated except for transient liver dysfunction with grade II. Six patients showed positive immunological responses to peptides in an ELISPOT assay, and positive skin tests to peptide-pulsed DC and KLH were recognized in 4 cases. The clinical response to DC injections was as follows :1 SD and 8 PD. Interestingly, the SD patient, given 24 DC injections, showed a long-term recurrence-free and immunological positive response period.ConclusionsThese results indicate peptide cocktail-treated activated α-type-1 DC-based immunotherapy to be a potential therapeutic tool against recurrent high-grade glioma with mainly HLA-A*2402.Trial registrationCurrent non-randomized investigational trial UMIN-CTR UMIN ID: 000000914.

Vici syndrome—A rapidly progressive neurodegenerative disorder with hypopigmentation, immunodeficiency and myopathic changes on muscle biopsy

Since its first description by Vici et al. [1988], further reports have continued to broaden the clinical phenotype of this rare multisystem disorder. Main features of agenesis of corpus callosum (ACC), hypopigmentation, immunodeficiency/recurrent infections, cataracts, severe failure to thrive, and profound psychomotor delay have been reported in all cases. An additional feature is the recent evidence for neuromuscular involvement. We describe a female infant with the above core features in whom an initial rapid neurological deterioration and associated transient left ventricular hypertrophy and liver dysfunction was followed by relative clinical stability after ten months of age. This case further underlines the clinical phenotype of Vici syndrome as an early onset neurodegenerative disorder with hypopimentation, recurrent infections and muscle findings indicating myopathic and neurogenic features.

Granulomatous interstitial nephritis associated with atypical drug-induced hypersensitivity syndrome induced by carbamazepine

We report the case of a 70-year-old female patient with granulomatous interstitial nephritis (GIN) induced by carbamazepine (CBZ). The patient had a 22-year history of bipolar disorder. Approximately 50 days before admission to our hospital, she was switched from valproic acid to 200 mg/day CBZ for mood swings. Forty days later, she presented with mild transient platelet depletion and liver dysfunction along with a C-reactive protein (CRP) level of 2.65 mg/dL. At that time, she discontinued CBZ without consulting the doctor. She subsequently developed high fever and a pruritic maculopapular rash. Laboratory tests revealed an elevated CRP level (11.98 mg/dL) and serum creatinine (sCr) of 1.6 mg/dL. Hence, she was admitted to our hospital, where she showed eosinophilia and immunoglobulin suppression. She was diagnosed with atypical drug-induced hypersensitivity syndrome (DIHS). All drugs prescribed by the previous doctor were discontinued. A lymphocyte transformation test showed CBZ positivity; a renal biopsy revealed many granulomatous lesions connected to arterioles, without angionecrotic findings. The patient had no history of allergic disorders or tuberculosis. Because of psychological instability, we treated her conservatively without steroid administration. She had a good recovery except for mild residual renal insufficiency (sCr, 1.0 mg/dL). Although granuloma formation has been observed in kidney biopsy specimens of rare cases with DIHS, no previous studies have reported on the relationship between arterioles and granuloma formation.

Partial hepatectomy aggravates cyclosporin A-induced neurotoxicity by lowering the function of the blood–brain barrier in mice

Aims Cyclosporin A, a calcineurin inhibitor, produces neurotoxicity with relatively high frequency in organ-transplanted patients. The aim of the present study was to clarify whether acute liver failure (ALF) simulated to the transient liver dysfunction at an early phase after liver transplantation increases the susceptibility to cyclosporin A-induced neurotoxicity through the blood–brain barrier (BBB) dysfunction. Main methods The right internal, left lateral and left internal lobes in male ddy mice were surgically excised under sodium pentobarbital anesthesia. Effect of cyclosporin A on harmine-induced tremors was examined and BBB permeability to 3[H]cyclosporin A was assessed in partially (70%) hepatectomized mice at postoperative days 1, 3 and 7. Key findings Patrial hepatectomy aggravated harmine-induced tremors. Cyclosporin A (50 mg/kg, i.p.) markedly augmented harmine-induced tremors in partially hepatectomized mice at postoperative day 1. Consistent with these behavioral findings, the brain uptake of 3[H]cyclosporin A in mice injected with 3[H]cyclosporin A into the jugular vein at postoperative day 1 was significantly increased by partial hepatectomy compared with sham operation. Significance Our results indicate that ALF increases BBB permeability to cyclosporin A by lowering the function of P-glycoprotein and tight junctions, consequently leading to augmentation of cyclosporin A-induced neurotoxicity. The possibility that cyclosporin A increases the risk of neurotoxicity including tremors at an early phase of liver transplantation must be considered.

Portal vein resection and reconstruction combined with left trisectionectomy for advanced hilar cholangiocarcinoma

The clinical value of applying portal vein resection and reconstruction in left trisectionectomy for treating advanced hilar cholangiocarcinoma is approved, while it is still a big challenge for clinicians. One female patient suffering from abdominal pain and jaundice received treatment in the General Hospital of PLA in July, 2009. She was prelimiarily diagnosed with Bismuth type Ⅲ a hilar cholangiocarcinoma. A tube was inserted in the left lateral inferior bile duct to carry out percutaneous transhepatic biliary drainage (PTBD). After the anatomic variation of the left bile duct was found, the diagnosis was revised as Bismuth type Ⅳ. A left trisectionectomy was proposed, and another PTBD tube was inserted in the right posterior bile duct.Combined portal vein resection and reconstruction and left trisectionectomy was successfully performed. The postoperation course was uneventful, except for the transient liver dysfunction and biliary-enteric anastomotic leakage. Key words: Biliary neoplasms,portal; Portal vein; Left trisectionectomy

A Protective Technique for Retraction of the Liver During Laparoscopic Gastrectomy for Gastric Adenocarcinoma: Using a Penrose Drain

BackgroundRetraction of the liver is necessary to ensure an adequate working space in laparoscopic surgery, but the retraction force applied may cause transient liver dysfunction. We have introduced the technique using a Penrose drain to suspend the liver with the performance of laparoscopic gastrectomy for gastric adenocarcinoma. Methods111 patients with gastric adenocarcinoma underwent laparoscopic gastrectomy using either a Penrose drain (n = 47) or a Nathanson’s retractor (n = 64) for displacement of the liver. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, alkaline phoshatase (ALP) and albumin were compared among the groups at baseline, immediately after operation, and on postoperative days (POD) 1, 2, 3, 5, and 7. ResultsThe levels of ALT on POD 2, 3, and 5 were significant higher in the Nathanson’s retractor group than in the Penrose drain group. Levels of AST on POD 2 and 3 were also higher in the Nathanson’s retractor group than in the Penrose drain group. There was no significant difference in total bilirubin, ALP, and serum albumin levels between groups. ConclusionsThe use of the Penrose drain for retraction of the liver appears to attenuate postoperative liver dysfunction during laparoscopic gastrectomy for gastric adenocarcinoma.

Palisaded neutrophilic granulomatous dermatitis with leukocytoclastic vasculitis in a patient without any underlying systemic disease detected to date

Palisaded neutrophilic granulomatous dermatitis (PNGD) is a rare dermatologic condition which shows various clinical and histopathological features. Although the PNGD lesions have been suggested to begin as leukocytoclastic vasculitis (LCV), there is still insufficient clinicopathological information in the reported cases of PNGD in acute stage with LCV. The relationship between PNGD and interstitial granumatous dermatis (IGD) also remains unclear. This report presents the case of a 60-year-old female patient with multiple erythematous nodules on the extremities. She had no underlying systemic disease detected to date, although transient, abnormal liver function tests were seen. The histopathological examination of an erythematous nodule revealed the features of PNGD in the acute stage. The patient presented the characteristic features of LCV including palisaded granulomatous pattern, and the interstitial granulomatous pattern was seen together, suggesting that PNGD with LCV can show an interstitial granulomatous pattern. The present case also suggested that PNGD in the acute stage with LCV tends to clinically manifest as erythematous nodules on the extremities and histopathologically shows a remarkable papillary edema and an extensive fibrin deposition in and around the vessel wall. PNGD may be associated with transient liver dysfunction.

Congestion of the donor remnant right liver after extended left lobe donation

The clinical importance of congestion of the remnant right lobe has not yet been fully elucidated in donors who donate their left lobe with the middle hepatic vein. The impact of congestion on clinical course and liver regeneration in 52 donor remnant livers were evaluated. The donors were divided into three groups according to the degree of the congestion: the mild [congestion ratio (CR) < 10%], moderate (CR ranged from 10% to 25%) and severe congestion groups (CR > 25%). The regeneration ratio of the graft at postoperative day 7 (7 POD) was 22.0 +/- 14.3% and inversely correlated with the CR in the remnant right lobe (P = 0.003). Aspartate aminotransferase and alanine aminotransferase at 7 POD were significantly higher in the severe CR group in comparison to the mild CR group (P = 0.003 and 0.019, respectively), but those of the three groups were comparable at 30 POD. The hospital stays were significantly longer in the severe CR group (P = 0.010). In conclusion, the congestion of the donors' remnant right liver can lead the transient liver dysfunction and poor regeneration. Therefore, the conversion of the graft from the left to right lobe might be appropriate according to the degree of the congestion.

A Phase I Study of Hyperthermic Isolated Hepatic Perfusion with Oxaliplatin in the Treatment of Unresectable Liver Metastases from Colorectal Cancer

Isolated hepatic perfusion (IHP) is a proven approach for regional delivery of chemotherapy in patients with unresectable primary and metastatic tumors of the liver. Most trials of IHP have utilized melphalan as the active drug in the perfusate. We performed a phase I trial to evaluate the efficacy, safety, and maximum tolerated dose (MTD) of oxaliplatin delivered by hyperthermic isolated hepatic perfusion. A phase I dose-escalation trial of hyperthermic IHP with oxaliplatin in patients with unresectable metastatic colorectal cancer scheduled to undergo placement of a hepatic arterial infusion (HAI) pump was carried out. Thirteen patients were enrolled between November 2003 and September 2006. Dose-limiting veno-occlusive disease was observed at 60 mg/m(2). At the MTD of 40 mg/m(2) only minor transient liver dysfunction was observed. Ultrafilterable platinum area under the curve and maximum concentration delivered by IHP increased nonlinearly with dose as did platinum concentrations in liver biopsies obtained at the end of the 60 min IHP. Seventy-seven percent of patients had a >50% decrease in serum carcinoembryonic antigen (CEA) after IHP. The overall response rate to the combined IHP and HAI therapy was 66%. One patient had a durable complete response (>4 years). We conclude that hyperthermic IHP with oxaliplatin was safe and feasible at a dose of 40 mg/m(2). The ability to obtain complete vascular isolation with open IHP was confirmed. The response rate in this small phase I study was encouraging.

Clinical Efficacy of ATRA for Adult T-Cell Leukemia

We previously reported that all-trans retinoic acid (ATRA) inhibited growth in HTLV-I- positive T-cell lines and fresh cells from patients with adult T-cell leukemia. We here confirmed the clinical effects of ATRA in 20 patients with ATL. Twenty patients (n=20) with median age of 56 years (range 35–68 years) diagnosed with ATL received ATRA orally. ATRA was administered for a median of 25.7 days (range 14–56 days). Efficacy was described below; no CR case, PR case was 55%, NR case was 45%. In 7 acute cases, PR case was 4 (20%) and NR case was 3 (15%). In 3 lymphoma cases, no NR case and 3 PR cases (15%) was found. In 4 chronic cases, PR case was 1 (4%) and NR case was 3 (15%). In 6 skin type. PR case was 3 (15 %) and NR case was 3 (15%). Major side effects were headache (n=5), transient liver dysfunction (n=2), hyperlipidemia (n=2) and anorexia (n=1). No major toxicity was observed. These results indicated that ATRA might be a useful agent for skin involvement of ATL with safety.

Clinical efficacy of all-trans retinoic acid for treating adult T cell leukemia

We previously reported that all-trans retinoic acid (ATRA) inhibited growth in human T-cell leukemia virus type I (HTLV-I)-positive T-cell lines and in fresh cells from patients with adult T cell leukemia (ATL). Here, we confirmed the clinical effects of ATRA in 20 patients with ATL. The 20 patients (n = 20) with a median age of 56 (range 35-73) years who were diagnosed with ATL received ATRA orally. The efficacy of treatment was as follows: no complete response (CR), a partial response (PR) in 40% of the patients, no change (NC) in 45% of the patients, and a progressive disease (PD) in 15% of the patients. In seven acute-type ATL patients, a PR was achieved in two (28.5%), NC was observed in two (28.5%), and a PD was observed in three (42.8%). In three lymphoma-type ATL patients, a PR (100%) was achieved. Among four chronic-type ATL patients, a PR was achieved in one (25%) and NC was observed in the remaining three (75%). In six smoldering-type ATL patients, a PR was achieved in two (33.3%) and NC was observed in four (66.6%). The major side effects were headache (n = 5), transient liver dysfunction (n = 2), hyperlipidemia (n = 2), and anorexia (n = 1). These results indicated that ATRA might be a useful agent for the safe treatment of ATL.

Transient Liver Dysfunction after Laparoscopic Gastrectomy for Gastric Cancer Patients

The effect of laparoscopic surgery under CO2 pneumoperitoneum on liver function is not clear. The aim of this study was to clarify whether laparoscopy-assisted distal gastrectomy (LADG) is associated with changes in liver function compared with open distal gastrectomy (ODG). A total of 205 patients who underwent LADG (n = 147) or ODG (n = 58) between January 1994 and April 2004 were included in this study. Liver function tests-aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, total bilirubin-were examined before surgery and at 1, 3, and 7 days after surgery. The postoperative clinical course was compared between the two groups. AST levels on day 1 and ALT levels on days 1 and 3 were significantly higher in the LADG group. Albumin levels showed a marked decrease after operation in both groups, but the level recovered more rapidly in the LADG group than in the ODG group, showing significant differences on days 3 and 7. The total bilirubin levels remained unchanged from baseline. The postoperative complication rate was similar in the two groups, although 3 LADG patients among the 27 patients with liver disease suffered severe enteritis. Transient liver dysfunction was documented in patients after laparoscopic gastrectomy under CO2 pneumoperitoneum.

Erythromycin-Associated Cholestatic Hepatitis and Liver Dysfunction in Children: The British Experience

Journal of Clinical Gastroenterology: September 2005 - Volume 39 - Issue 8 - p 743-744 doi: 10.1097/01.mcg.0000173931.67739.41

Irinotecan plus Cisplatin Combination Against Metastatic Gastric Cancer: Phase II Study

In this phase II study, we aimed to detect efficacy and toxicity of the combination of CPT-11 and cisplatin administered to patients with metastatic gastric carcinoma. On d 1, CPT-11, 100 mg/m2, was administered by intravenous infusion for 90 min, followed by a 2 h infusion of cisplatin, at 70 mg/m2 every 3 wk. Forty-one patients were enrolled into the study. Twenty-eight patients were chemotherapy naive. The total number of chemotherapy cycles administered was 165, and the median number of cycles received was 4 (range, 1-8 cycles). The median follow-up time was 12 mo (range, 4-34 mo). There were 4 complete responses (9.7%) and 14 partial responses (34.2%), which result in a response rate of 43.9% (18 of 41 patients). The median time to progression was 8.0 +/- 0.8 mo with 56% and 13% of patients progression free at 6 and 12 mo, respectively. The median overall survival was 9.0 +/- 1.1 mo, with 68 % and 32% of patients alive at 6 and 12 mo, respectively. Grade 3-4 nausea and vomiting was observed in five patients (12%) and grade 3-4 neutropenia in five patients (12%). Grade 3 infection was observed in only one patient (2%). Grade 2 transient liver dysfunction related to chemotherapy was observed in one patient (2%). Chemotherapy was stopped due to nephrotoxicity in one patient (2%). There was no treatment-related death. In conclusion, administration of CPT-11 and cisplatin in this particular dose every 3 wk is effective and well-tolerated treatment regimen.

Clinical response in Japanese metastatic melanoma patients treated with peptide cocktail-pulsed dendritic cells

BackgroundMetastatic, chemotherapy-resistant melanoma is an intractable cancer with a very poor prognosis. As to immunotherapy targeting metastatic melanoma, HLA-A2+ patients were mainly enrolled in the study in Western countries. However, HLA-A24+ melanoma patients-oriented immunotherapy has not been fully investigated. In the present study, we investigated the effect of dendritic cell (DC)-based immunotherapy on metastatic melanoma patients with HLA-A2 or A24 genotype.MethodsNine cases of metastatic melanoma were enrolled into a phase I study of monocyte-derived dendritic cell (DC)-based immunotherapy. HLA-genotype analysis revealed 4 cases of HLA-A*0201, 1 of A*0206 and 4 of A*2402. Enriched monocytes were obtained using OptiPrep™ from leukapheresis products, and then incubated with GM-CSF and IL-4 in a closed serum-free system. After pulsing with a cocktail of 5 melanoma-associated synthetic peptides (gp100, tyrosinase, MAGE-2, MAGE-3 and MART-1 or MAGE-1) restricted to HLA-A2 or A24 and KLH, cells were cryopreserved until used. Finally, thawed DCs were washed and injected subcutaneously (s.c.) into the inguinal region in a dose-escalation manner.ResultsThe mean percentage of DCs rated as lin-HLA-DR+ in melanoma patients was 46.4 ± 15.6 %. Most of DCs expressed high level of co-stimulatory molecules and type1 phenotype (CD11c+HLA-DR+), while a moderate number of mature DCs with CD83 and CCR7 positive were contained in DC products. DC injections were well tolerated except for transient liver dysfunction (elevation of transaminases, Grade I-II). All 6 evaluable cases except for early PD showed positive immunological responses to more than 2 melanoma peptides in an ELISPOT assay. Two representative responders demonstrated strong HLA-class I protein expression in the tumor and very high scores of ELISPOT that might correlate to the regression of metastatic tumors. Clinical response through DC injections was as follows : 1CR, 1 PR, 1SD and 6 PD. All 59 DC injections in the phase I study were tolerable in terms of safety, however, the maximal tolerable dose of DCs was not determined.ConclusionsThese results suggested that peptide cocktail-treated DC-based immunotherapy had the potential for utilizing as one of therapeutic tools against metastatic melanoma in Japan.

Outcome of right hepatectomies in patients older than 70 years.

The increasing number of elderly patients undergoing liver resections mandates updating of clinical outcomes on this specific population. Case series. A tertiary care teaching hospital. Twenty-three patients older than 70 years who underwent right hepatectomies (including 7 extended right hepatectomies) between January 1, 1995, and October 31, 2001 (group 1) and 99 patients younger than 70 years who underwent 64 right hepatectomies and 35 extended right hepatectomies during the same period (group 2) were included for a total sample population of 122. Preoperative clinicopathological features, intraoperative factors, in-hospital mortality, postoperative complications, intensive care unit requirement, hospital stay, and course of main biochemical liver function test results of groups 1 and 2 were analyzed and compared. The 2 groups were similar for indications for surgery and the presence of underlying liver disease. Group 1 had a higher incidence of associated pulmonary diseases (21.7% vs 5%, P =.02) and patients with an American Society of Anesthesiologists score of III (ie, a patient with severe systemic disease limiting activity, but not incapacitating) (56.5% vs 26.3% of cases, P =.01). There were no differences in intraoperative requirement of packed red blood cells and in operation time. There were no in-hospital deaths in group 1; there were 2 deaths (2%) in group 2. Nine patients (39.1%) in group 1 and 32 patients (32.3%) in group 2 experienced postoperative complications (P =.53), of whom, respectively, 5 (21.7%) and 17 (17.2%) developed transient liver dysfunction (P =.56), and 4 (17.4%) and 5 (5.1%) required a supplementary intesive care unit stay (P =.06). The postoperative stay (mean [SD], 16 [14] days vs 13 [9] days, P =.88) and peak values of the aminotransferase level, total serum bilirubin level, and prothrombin time were similar in the 2 groups. The timing of the peak value of the total serum bilirubin level (mean [SD], 4.1 [4.8] days vs 2.5 [2.5] days, P =.28) and its period of normalization (mean [SD], 9.4 [10.8] days vs 6.7 [5.1] days, P =.67) were also similar for both groups. For patients with malignancies, the 3-year survival rate was 64.2% in group 1 and 53.9% in group 2 (P =.53). Being older than 70 years should not be a contraindication for major hepatectomies, provided that liver cirrhosis and severe associated medical conditions are ruled out during the preoperative evaluation.

Veno-occlusive disease with multi-organ involvement following actinomycin-D

Actinomycin-D (Act-D) is a rare cause of veno-occlusive disease (VOD). Between 1993 and 1998, we managed 6 patients, all male, median age 19 months (range 6–48 months) who received Act-D for Wilms' tumour (n=4), clear cell sarcoma (n=1) or rhabdomyosarcoma (n=1). VOD presented with a median platelet count of 12×109/l, INR 3.8, fibrinogen 16 mg/l, fibrinogen degradation products (FDPs) ⩾80 μg/l, aspartate aminotransferase (AST) 6922 IU/l, bilirubin 47 μmol/l. In 3 cases, transient liver dysfunction and thrombocytopenia without neutropenia had been observed after a previous course of Act-D. All six children developed encephalopathy, hepatomegaly, ascites, reversed portal flow and renal impairment. All received mechanical ventilation and two required haemofiltration. The treatment was supportive. Severe Adult Respiratory Distress Syndrome developed in 3 patients, all of whom died. 3 patients recovered. The outcome of VOD with multi-organ failure is poor. Intravascular coagulopathy precedes and characterises severe VOD during Act-D treatment.