Reconstructive surgery for ischemic-type lesions at the bile duct bifurcation after liver transplantation

Cholestatic liver injury appears to result from the induction of hepatocyte apoptosis by toxic bile salts such as glycochenodeoxycholate (GCDC). Previous studies from this laboratory indicate that cathepsin B is a downstream effector protease during the hepatocyte apoptotic process. Because caspases can initiate apoptosis, the present studies were undertaken to determine the role of caspases in cathepsin B activation. Immunoblotting of GCDC-treated McNtcp.24 hepatoma cells demonstrated cleavage of poly(ADP-ribose) polymerase and lamin B1 to fragments that indicate activation of effector caspases. Transfection with CrmA, an inhibitor of caspase 8, prevented GCDC-induced cathepsin B activation and apoptosis. Consistent with these results, an increase in caspase 8-like activity was observed in GCDC-treated cells. Examination of the mechanism of GCDC-induced caspase 8 activation revealed that dominant-negative FADD inhibited apoptosis and that hepatocytes isolated from Fas-deficient lymphoproliferative mice were resistant to GCDC-induced apoptosis. After GCDC treatment, immunoprecipitation experiments demonstrated Fas oligomerization, and confocal microscopy demonstrated DeltaFADD-GFP (Fas-associated death domain-green fluorescent protein, aggregation in the absence of detectable Fas ligand mRNA. Collectively, these data suggest that GCDC-induced hepatocyte apoptosis involves ligand-independent oligomerization of Fas, recruitment of FADD, activation of caspase 8, and subsequent activation of effector proteases, including downstream caspases and cathepsin B.     

Traumatic neuroma with biliary duct obstruction after orthotopic liver transplantation

BACKGROUND: Traumatic neuromas may develop after injury to nerve fibers encased in Schwann cells. The incidence of symptomatic neural tumors appears to be low after orthotopic liver transplantation (OLT). Only two cases of biliary stricture caused by infiltrating traumatic neuroma have been described previously. METHODS: We report two new cases of biliary tract obstruction after OLT that failed to respond to percutaneous balloon dilatation and were corrected by a resection of the bile duct stricture followed by biliary reconstruction with a Roux-en-Y jejunal loop. RESULTS: The first patient (17 months after OLT) had a traumatic neuroma appearing as a distinct mass with nerve bundles confirmed histologically; the traumatic neuroma in the second patient (5 months after OLT) was a nerve stump with infiltration of nervous elements in the bile duct. Both patients recovered without complications. CONCLUSIONS: Traumatic neuromas should be considered in the differential diagnosis of late biliary stricture after OLT, in particular when not responding to percutaneous dilatation or stenting.     

Intrahepatic bile duct injury and nodular regenerative hyperplasia of the liver in a patient with polyarteritis nodosa

Although involvement of the hepatic vasculature in patients with polyarteritis nodosa is not unusual, biliary manifestations are very rare. We describe a patient with polyarteritis nodosa presenting with a febrile cholestatic anicteric syndrome. Histological examination of the liver revealed necrotizing arteritis of small hepatic arteries associated with significant lesions of intrahepatic bile ducts of the sclerosing cholangitis type, i.e. fibrous collar around the ducts, periductal inflammation and ductal proliferation. Concomitant nodular regenerative hyperplasia was found, a condition which has rarely been described in association with polyarteritis nodosa. We think that hepatic arteritis compromising arterial blood flow to the liver was responsible for the most likely ischemic nature of the bile duct injury and the nodular regenerative hyperplasia seen in our patient.     

Protein energy malnutrition, vitamin A deficiency and night blindness in Bangladeshi children

The occurrence of night blindness and serum vitamin A concentrations among children in rural Bangladesh were studied in relation to protein energy malnutrition, dietary habits and intake of vitamin A capsules. In 1992, 124 night-blind children were registered in a cross-sectional survey in the northern part of Bangladesh, and age-, sex- and neighbourhood-matched controls were selected. Of these, the first reported night-blind child from a household (n = 105) and their controls were included in the analyses. Our results showed that night blindness was associated with protein energy malnutrition when using the mid-upper arm circumference (MUAC) as a measure of nutritional status. The odds ratio for a confirmed diagnosis of night blindness among children with a MUAC < 80% of the reference versus normal children was 5.4 (CI 1.9-15.5). Low MUAC was associated with low intake of beta-carotene-rich and vitamin A-containing foods as well as with low serum vitamin A in the total series of cases and controls. This may indicate that night blindness is only one aspect of the general protein energy malnutrition problems in this population. We therefore suggest that measures to prevent vitamin A-related morbidity and mortality should include improvement of the general diet with increased consumption of dietary vitamin A.     

Long-term survival of a patient with bile duct carcinoma by endoscopic biliary drainage

An 80-yr-old female presented with obstructive jaundice. Endoscopic retrograde cholangiopancreatography showed a carcinoma in the middle extrahepatic bile duct, and a biliary endoprosthesis was inserted. Exfoliative cytology of the bile and forceps biopsy of the tumor revealed a papillary adenocarcinoma. Surgical resection could not be done because of her cardiovascular complications, and neither chemotherapy nor radiotherapy was administered. Stents were exchanged and cleaned 21 times because of occlusion and cholangitis. Subsequent serial cholangiogram showed a slow growth of the papillary tumor, but local invasion to the adjacent organs or distant metastasis was not observed. The patient survived for 7 yr and 6 months after insertion of the biliary endoprosthesis.     

Percutaneous repair of a traumatic bile duct laceration in a liver transplant allograft

BACKGROUND: Phrenic nerve palsy in infants and young children usually results from birth injury or iatrogenic damage. The newborn almost invariably presents with severe respiratory distress, diaphragmatic elevation, and paradoxical movement at the affected side. METHODS/RESULTS: In this retrospective analysis a group of 23 patients below the age of 1 year with an obstetric or postoperative phrenic nerve injury was studied and compared with cases in the literature. All patients were admitted between 1986 and 1997 to the Pediatric Surgical Center, Amsterdam. Thirteen of 18 patients with an obstetric phrenic nerve injury underwent plication of the diaphragm after an average observation period of 100 days. In the remaining five children with an obstetric phrenic nerve injury, spontaneous recovery appeared within 1 month. Only one of five patients with a phrenic nerve palsy after a cardiac surgical procedure underwent plication of the diaphragm. Fifteen of the 34 patients described in the literature underwent plication of the diaphragm after an average of 54 days. CONCLUSIONS: If after 1 month no spontaneous recovery of the diaphragmatic paralysis caused by a phrenic nerve injury occurs, plication of the diaphragm is indicated. This operation proved to be successful for relief of symptomatic phrenic nerve injury in all cases. If the condition of the patient clinically deteriorates during this first month of life, the patient should be operated on immediately.     

Friedreich''s ataxia with isolated vitamin E deficiency: a neuropathological study of a Tunisian patient

PURPOSE: Percutaneous radiofrequency interstitial thermal ablation is a new method in local tumour therapy. The aim of this study was to define the relations between the variable parameters and local efficacy in vitro and to evaluate optimal parameter combinations for this system. Furthermore, we studied the feasibility of increasing the volume of destroyed tissue using perfusion electrodes. MATERIAL AND METHODS: Thermal lesions were produced with radiofrequency in ex vivo pig livers. In separate experiments the parameters wattage (5-30 watts), exposure time (1-15 minutes) and tip exposure were varied. The resulting areas of tissue necrosis coagulation were measured; in 30 of 90 cases the macroscopic findings were compared to the histological findings. RESULTS: Lesion size correlated with tip exposure, wattage and procedure duration up to 10 minutes. For a tip exposure of 2 cm (3 cm) the maximal lesion volume was 18.8 cm3 (33.2 cm3) at a wattage of 20 watts (30 watts) and a procedure duration of 10 minutes. The maximal cross- (length-) diameter of these lesions was 3 cm (4 cm) for 2 cm tip exposure and 3.6 cm (4.9 cm) for 3 cm tip exposure. CONCLUSION: The parameters wattage, procedure duration and tip exposure affect the size of lesions created with radiofrequency under ex vivo conditions. Perfusion electrodes make it possible to produce larger lesions than described for non-perfused electrodes. The ablation of hepatic neoplasms up to a size of 3 cm seems to be possible with a single electrode.     

Detection of hepatitis G virus from serum and liver of a patient with long-term liver dysfunction after autologous bone marrow transplantation

Long-term effects after blood or bone marrow transplantation (BMT) are emerging as an important issue, as more patients are included in BMT programmes and as this procedure becomes more successful. Long-term liver dysfunction, mainly due to chronic graft-versus-host disease or hepatitis C virus infection, is a well-known complication. Nevertheless, the diagnosis of liver disease in this patient group is sometimes difficult and, despite adequate studies, it may remain undetected. A novel hepatitis-associated virus, hepatitis G virus (HGV), has recently been identified. The virus belongs to the Flaviviridae family and is known to be parenterally transmitted, although there is no clear evidence to implicate this agent in causing acute or chronic hepatitis. We report a patient who developed mild, but persistent, abnormalities in transaminases for 2 years after an autologous BMT. HGV RNA was detected in both serum and liver. HGV RNA persisted in serum for at least 8 months. No other known hepatitis virus was found. This report provides the first direct evidence of a patient with long-term liver abnormalities after a BMT in whom the only known hepatitis virus isolated was the HGV.     

Spontaneous pneumomediastinum in a patient with bronchiolitis obliterans after bone marrow transplantation

After allogeneic bone marrow transplantation for chronic myelogenous leukemia, spontaneous pneumomediastinum and subcutaneous emphysema developed in a patient with bronchiolitis obliterans. Computed tomography scanning of the chest failed to reveal the cause. There was no evidence of a pulmonary process, pneumothorax, or pharyngeal or upper airway leak. Despite the alarming appearance of the patient, conservative management, including high-flow oxygen, resulted in resolution of the pneumomediastinum and subcutaneous emphysema. The cause of pneumomediastinum and subcutaneous emphysema in bone marrow transplant recipients is discussed.     

Hodgkin''s disease occurring in a child after liver transplantation

Broiler chicks were treated by oral gavage on the day of hatch with a continuous-flow competitive exclusion culture (PREEMPT). At 4 h, 1 day, or 2 days posttreatment, chicks were challenged by oral gavage with 10(2) or 10(4) Salmonella CFU to determine the effects of challenge time on Salmonella cecal colonization. Cecal propionic acid concentrations in two trials increased (P < or = 0.001) within 1 day posttreatment in chicks given PREEMPT, and the increases were indicative of the establishment of the PREEMPT bacteria. Salmonella cecal populations decreased (P < or = 0.001) on average 6 log10 units in these two trials in chicks challenged 4 h posttreatment with 10(4) Salmonella CFU. In a third trial propionic acid did not increase significantly until 2 days after treatment, and there was no decrease in Salmonella colonization when chicks were challenged at 4 h after treatment. However, there were decreases in that same trial when chicks were challenged at 1 and 2 days after treatment. The early establishment of PREEMPT followed by challenges with 10(2) and 10(4) Salmonella CFU resulted in 3% and 3%, respectively, of the ceca testing Salmonella-culture-positive, compared to 28% and 95%, respectively, culture-positive ceca in untreated chicks. The results from this study indicated that in most instances young broiler chicks can be protected against cecal colonization when challenged with 10(2) and 10(4) Salmonella CFU as early as 4 h posttreatment on the day of hatch with the PREEMPT bacteria.     

Noninvasive mechanical ventilation in a patient with respiratory failure after hematopoietic progenitor transplantation

Respiratory failure requiring orotracheal intubation (OTI) and mechanical ventilation (MV) is almost always a fatal complication in patients who undergo hematopoietic progenitor transplantation (HPT). We present the case of a woman who suffered respiratory failure with bilateral infiltrates on a chest X-ray taken on day +14 following autologous bone marrow transplantation. We managed the patient satisfactorily with noninvasive ventilation, avoiding OTI. We believe that patients with non-progressive pulmonary lesions and without multiple system organ failure, may be correctly managed with noninvasive positive-pressure ventilation (NPPV).     

Domino hepatic transplantation using the liver from a patient with familial amyloid polyneuropathy

BACKGROUND: In transplantation, novel methods are required to augment the supply of donor organs. We report the first domino liver transplant in which a patient with familial amyloid polyneuropathy (FAP) received an orthotopic split liver graft, and her explanted liver was donated to another patient. Three successful liver transplants were thus achieved from the one cadaver liver. PATIENTS AND METHODS: A cadaveric donor liver was split and the left lobe was grafted into a child with biliary atresia. The right lobe was transplanted into a woman with FAP associated with the transthyretin Met30 variant. Her own otherwise healthy liver was donated to a patient with cirrhosis and hepatocellular carcinoma. RESULTS: Fifteen months after transplantation, all three recipients are well with normal liver function. The domino recipient developed inferior vena cava stricturing at the level of anastomosis after surgery with resultant ascites, requiring dilatation and LeVeen shunt insertion. Serum amyloid P component scintigraphy showed amyloid regression in the domino donor and to date has not identified any amyloid deposits in the recipient, who also remains free of tumor recurrence. CONCLUSIONS: Domino transplantation using the livers from patients with FAP may be justified for patients whose disease condition precludes a long spell on the waiting list, including those with hepatic malignancies and those for whom palliation rather than long-term cure is the aim.     

Sudden cardiac tamponade due to hemorrhagic myocarditis after preconditioning marrow transplantation with cyclophosphamide in a patient with aplastic anemia

Matrix metalloproteinases have been shown to be important in tumour invasion and metastasis, and the use of matrix metalloproteinase inhibitors in animal models has suggested that these agents may be useful in the control of malignant disease. This article reports the results of an early clinical trial of batimastat, one of the first generation of metalloproteinase inhibitors, in patients with malignant ascites. The drug was well absorbed via the intraperitoneal route and associated with few side-effects. Furthermore, a response to treatment was seen in about half the evaluable patients with advanced malignant disease. The results suggest that further research on the use of matrix metalloproteinase inhibitors in patients with malignant disease is worthwhile.     

Complete neurological recovery of an adult patient with type II citrullinemia after living related partial liver transplantation

Type II citrullinemia is an adult-onset hepatocerebral disease caused by a deficiency of argininosuccinate synthetase in liver. A 25-year-old Japanese man suddenly developed encephalopathy, showing disorientation and flapping tremor. Plasma concentrations of ammonia and citrulline were extremely high, and hepatic argininosuccinate synthetase activity was deficient. The patient's condition deteriorated rapidly in spite of intensive medications. Therefore, we performed a partial liver transplantation using a graft obtained from his healthy 61-year-old father. After surgery, his neurological symptoms soon disappeared and plasma levels of ammonia and citrulline were normalized within 3 months after operation. Type II citrullinemia is one fulminant form of various liver-based metabolic diseases, and immediate liver transplantation is necessary to rescue patients with this disease. As liver transplantation from cadaveric donor is still not possible in Japan, it seems justifiable to use living related partial liver transplantation for our patient.