Hemodynamic failure as an indication to urgent liver transplantation in infants with giant hepatic hemangiomas or vascular malformations--report of four cases

Abstract:  The aim of this study was to present acute hemodynamic failure as a rare indication for liver transplantation in neonates and infants with liver hemangiomatosis. We report four patients aged one to six months with giant liver hemangiomas, with huge arterio-venous shunting within these malformations. In three, many skin hemangiomas were found. All children developed right ventricular failure. In two, a trial of pharmacological reduction was attempted with corticosteroids and cyclophosphamide. In one patient, the arterio-venous fistulas were embolized without any improvement in hemodynamic status. Two children underwent rescue hepatic artery surgical ligation, which did not prevent heart and then multiorgan failure including liver failure. After unsuccessful conventional therapy, all infants were considered for urgent liver transplantation; in three cases, it was performed with a living-related donor, and in one case with a deceased donor. All patients are alive and well with the follow-up between nine and 37 months after transplantation. Liver transplantation should be considered as a rescue treatment in children with hepatic vascular malformations leading to hemodynamic insufficiency when conventional therapy is unsuccessful and multiorgan failure develops.     

Unusual presentation of infantile hemangioendothelioma

Infantile hemangioendothelioma is a rare benign hepatic tumor arising from mesenchymal tissue. Most of the cases present with congestive heart failure and asymptomatic abdominal mass were before 6 months of age. We described a patient with projectile vomiting, which is quite an unusual presentation. Following surgical resection, neither recurrence nor symptoms were seen in 2 years of follow-up.     

Selective hepatic artery ligation for hepatic haemangioendothelioma: case report and review of the literature.

Although benign, hepatic haemangioendotheliomas (HHE) are rare vascular tumours of the infant which have a high mortality rate secondary to high output congestive heart failure. The management of these tumours is still controversial and none of the different medical or surgical options has been unanimously accepted. We report the case of a neonate with congestive heart failure (CHF) due to a localized HHE, treated successfully by selective ligation of the left hepatic artery branch irrigating the tumour, under perioperative ultrasound Doppler control. A review of the literature showed 35 cases of HHE treated by hepatic artery ligation (HAL) with a survival rate of 80 %.     

Severe valvular toxicity and pericarditis early after radiation therapy in a patient treated for Hodgkin's lymphoma

Hodgkin's disease can be cured in most cases by radiotherapy. However, it can increase the risk of cardiotoxicity. Here, we report a patient with Hodgkin's disease and superior vena cava syndrome who was treated with chemotherapy in combination with radiotherapy. Four months after the initiation of this therapy, she developed progressive dyspnea. Pleural and pericardial effusion, severe mitral regurgitation, moderate aortic insufficiency, and mild tricuspid regurgitation were detected in echocardiography, which suggested heart failure. The patient was then treated with intrapericardial drainage and received dopamine and diuretics for congestive heart failure; she responded well to this treatment and was discharged in good condition. After high-dose mediastinal radiation, cardiologic screening is recommended in order to identify patients with radiation-induced heart disease and to assess their need for treatment and follow-up.     

Cornstarch therapy in a patient with type III glycogen storage disease

A child with type III glycogen storage disease is described. The patient presented with growth failure and hepatic dysfunction, and no clinical or biochemical evidence of myopathy. Institution of high protein nocturnal intragastric feedings was associated with improved growth and less hepatic dysfunction. Compliance with tube feedings was sporadic necessitating another approach to the patient's management. The use of oral cornstarch supplements enabled the child to maintain normoglycemia and was associated with clinical and biochemical improvement. Our experience with this child suggests cornstarch therapy may be useful in those patients with type III glycogen storage disease who suffer primarily from hepatic dysfunction and growth failure.     

Cardiac Relapses in Myeloid Leukemia: Case Report and Review of the Literature

Granulocytic sarcoma (GS) is a localized destructive tumor mass composed of immature cells of the granulocytic series, occurring before, concomitantly, or after the overt development of acute or chronic myelogenous leukemia. Although this tumor is known to occur in almost every site of the body, cardiac involvement is rare. We report a case of a 12-year-old female previously treated for 28 months with chemotherapy for acute promyelocytic leukemia, who presented with GS in the left mastoid 3 months after discontinuing treatment. The patient was treated with local radiotherapy only. Thirty months later she presented with heart failure, the result of a right-sided intracardiac mass, while in continuous hematological remission of the primary disease and off therapy. The cardiovascular, hematological, and postmortem findings are described and the literature is reviewed. This is the first clinicopathologic report of GS involving the heart in which the echocardiographic and pathologic findings are detailed.     

Understanding chronic heart failure

The key principles of chronic heart failure and the development of clinical management strategies are described. The physiological changes in chronic heart failure and the clinical management of children with heart failure are considered, but the treatment of heart failure related to congenital heart disease or the intensive care management of heart failure are not mentioned as both topics require consideration in their own right. A greater understanding of the maladaptive responses to chronic heart failure has enabled targeted therapy to be introduced with consequent improvement in symptoms, reduction in hospitalisation and lower mortality.     

Understanding chronic heart failure.

The key principles of chronic heart failure and the development of clinical management strategies are described. The physiological changes in chronic heart failure and the clinical management of children with heart failure are considered, but the treatment of heart failure related to congenital heart disease or the intensive care management of heart failure are not mentioned as both topics require consideration in their own right. A greater understanding of the maladaptive responses to chronic heart failure has enabled targeted therapy to be introduced with consequent improvement in symptoms, reduction in hospitalisation and lower mortality.     

Neonatal Hypertension and Cardiomegaly Associated with a Congenital Neuroblastoma

A neonate who died 12 days after birth from complications related to a congenital neuroblastoma is described. Hypertension and congestive heart failure occurred soon after birth. Hospital course was marked by a consumptive coagulopathy and the development of acute renal and hepatic failure. At autopsy the heart was hypertrophied but normally formed. Although there was elevated urinary excretion of vanilmandelic acid and homovanillic acid, levels of epinephrine, norepinephrine, metanephrine, and normetanephrine were not documented. This case shows that a congenital neuroblastoma may be associated with hypertension and cardiomegaly in the neonatal period.     

Congestive heart failure, hypertension, and hyperreninemia in bilateral Wilms' tumor: successful medical management

Congestive heart failure is an unusual complication of the hyperreninemia of Wilms' tumors. Cases with bilateral tumors present a difficult management problem. This is a report of the successful medical management of a child with congestive heart failure secondary to hyperreninemia from bilateral Wilms' tumor. Hypertension and hyperreninemia were extensively documented. Their etiologic relation to the congestive heart failure was supported by the patient's improved cardiac function following specific renin-angiotensin blockade. With unilateral tumors, surgical excision corrects the hypertension; however, with large bilateral tumors, excision is out of the question. A unique feature of this case is the ability to control the blood pressure with saralasin. With subsequent antitumor therapy, renin concentrations decreased proportional to tumor size, and renin angiotensin blocking therapy could be discontinued.     

Cavernous hemangioma and disseminated intravascular coagulation (Kasabach-Merritt syndrome) in a newborn infant with a large ventricular septal defect

In a 3170 g newborn with a large cavernous hemangioma at the left thigh, heart failure was evident. Echo- and angiographically a large perimembranous ventricular septal defect was found. An important a-v shunt within the hemangioma could be excluded by hemodynamic investigation and selective arteriographic examination of the vascular tumor. Thrombocytopenia present from the first day of life was only temporarily overcome by corticosteroid therapy but nevertheless consumption coagulopathy (Kasabach-Merritt-Syndrome) developed and additional therapy with heparin was necessary in order to normalize the coagulation factors. However, no regression in size of the tumor occurred over the first 8 weeks of life and a total exstirpation of the hemangioma was performed. Postoperatively no further cortison or heparin therapy was necessary. Despite vigorous medical treatment the congestive heart failure persisted. After surgical closure of the ventricular septal defect at the age of three months the infant thrived and could be discharged without pathological symptoms.     

Two-dimensional echocardiographic assessment of infective endocarditis in children

We examined 11 children with infective endocarditis initially and serially by two-dimensional echocardiography. Nine (82%) of the 11 patients had echocardiographic findings at initial examination compatible with infective endocarditis. These results provided strong evidence in support of the diagnosis before bacteriologic confirmation was available. Congestive heart failure, major emboli, and/or the need for surgical intervention occurred in seven of the nine patients with positive two-dimensional echocardiograms. Echocardiographic evidence of vegetations persisted during antibiotic therapy and resolved slowly during many months. Serial echocardiograms were useful in cases in which obvious valve destruction or marked increase in vegetation size imaged echocardiographically could be combined with clinical evidence of progressive heart failure to support a decision for early surgical intervention. Two-dimensional echocardiography can make important contributions to the diagnosis and management of children with infective endocarditis.     

Symptomatic liver involvement in neonatal hereditary hemorrhagic telangiectasia

High-flow hepatic vascular anomalies with arteriovenous shunting commonly manifest during the neonatal period with signs and symptoms of congestive heart failure, but to our knowledge, they have never been described in patients with hereditary hemorrhagic telangiectasia (HHT). We report here our experience with 3 patients with hepatic arteriovenous malformations (AVMs) who presented with symptoms of high-output congestive heart failure during the neonatal period and were subsequently diagnosed with HHT. Imaging showed large hypervascular lesions and multiple hepatic arteriovenous shunts that differentiated these lesions from liver hemangiomas. Transcatheter embolization was performed in all cases. One infant died of sepsis shortly after embolization; follow-up at the age of 2.5 years of the surviving infants revealed involution of the vascular lesions and no evidence of symptom recurrence. We conclude that severe symptoms related to hepatic AVMs in HHT can occur in the neonatal period and that HHT should therefore be included in the differential diagnosis of symptomatic neonatal hepatic vascular malformations. Imaging plays a key role in differentiating hepatic AVMs from hemangiomas, because the latter require additional pharmacologic treatments. Early transcatheter embolization seems to be effective, but long-term outcomes still need to be assessed.     

Diuretic therapy of heart failure in infants and children

Diuretics are the mainstay of traditional therapy for congestive heart failure. The syndrome of heart failure is now understood to involve complex interactions of neurohumoral substances released in response to poor cardiac function. Developmental changes during infancy and childhood will affect both the activation of systemic neurohumoral responses and the pharmacokinetic and pharmacodynamic actions of diuretics. Few human studies directly evaluate the efficacy of diuretic therapy in heart failure in adults. The pharmacodevelopmental aspects of diuretic therapy in infants and children are also incompletely studied. This review will describe the kidney's role in the pathogenesis of sodium and water retention in heart failure and the developmental changes in the kidney related to fluid retention. Known principles of diuretic therapy in congestive heart failure will be described. All these factors can then be used by the reader to evaluate the role of diuretic therapy in the complex syndrome of heart failure in infants and children.     

Supplemental Nitrogen Inhalation Therapy in Very Low-Birth-Weight Infants with Patent Ductus Arteriosus

Very low-birth weight infants with patent ductus arteriosus (PDA) accompanied by severe heart failure do not respond to indomethacine therapy. It is essential to stabilize the general condition of these infants until surgical intervention. We tried to regulate the pulmonary blood flow to control congestive heart failure by administering supplemental nitrogen inhalation therapy to six very low-birth-weight infants with PDA. After the inhalation of supplemental nitrogen gas was begun, the arterial oxygen saturation and partial oxygen pressure immediately decreased. Furthermore, the blood pH, systolic pressure, and urine output significantly increased. The infants were well stabilized. Furthermore, there were no complications related to nitrogen gas inhalation. Supplemental nitrogen inhalation therapy is an effective and feasible therapy for severe congestive heart failure in very low-birth-weight infants with PDA.     

A RARE CASE OF ADENOVIRAL FULMINANT HEPATIC NECROSIS AFTER CHEMOTHERAPY

The authors report a rare case of fulminant adenoviral hepatic necrosis occurring after chemotherapy in a patient with a second relapse of acute myeloid leukemia. The literature is reviewed and the a role of rapid viral diagnosis in the clinical management of this complication is discussed. A 10-year-old girl with relapsed acute myeloid leukemia after allogeneic bone marrow transplant underwent re-induction chemotherapy with high-dose cytosine arabinoside and amsacrine. During induction she developed diarrhea and a marked coagulopathy, followed by fulminant hepatic failure and acute pre-renal failure. She rapidly deteriorated and died. A limited autopsy was performed. Adenovirus type 5 was cultured from ante mortem clinical samples and detected by polymerase chain reaction in postmortem samples of heart blood, lung, trachea, spleen, and liver. At autopsy, the liver demonstrated massive hepatic necrosis with positive immunofluorescence for adenovirus. Electron microscopy demonstrated intranuclear inclusions, typical of adenovirus. There was no evidence of pneumonia. Adenovirus can cause fulminant hepatic necrosis following chemotherapy in a nontransplant setting. If adenoviral disease is suspected, appropriate rapid viral studies should be undertaken, because early intervention with ribavirin or cidofovir may prevent rapid fulminant progression. Further studies on the role of antiviral therapy in this setting are warranted.     

A rare case of adenoviral fulminant hepatic necrosis after chemotherapy

The authors report a rare case of fulminant adenoviral hepatic necrosis occurring after chemotherapy in a patient with a second relapse of acute myeloid leukemia. The literature is reviewed and the a role of rapid viral diagnosis in the clinical management of this complication is discussed. A 10-year-old girl with relapsed acute myeloid leukemia after allogeneic bone marrow transplant underwent re-induction chemotherapy with high-dose cytosine arabinoside and amsacrine. During induction she developed diarrhea and a marked coagulopathy, followed by fulminant hepatic failure and acute pre-renal failure. She rapidly deteriorated and died. A limited autopsy was performed. Adenovirus type 5 was cultured from ante mortem clinical samples and detected by polymerase chain reaction in postmortem samples of heart blood, lung, trachea, spleen, and liver. At autopsy, the liver demonstrated massive hepatic necrosis with positive immunofluorescence for adenovirus. Electron microscopy demonstrated intranuclear inclusions, typical of adenovirus. There was no evidence of pneumonia. Adenovirus can cause fulminant hepatic necrosis following chemotherapy in a nontransplant setting. If adenoviral disease is suspected, appropriate rapid viral studies should be undertaken, because early intervention with ribavirin or cidofovir may prevent rapid fulminant progression. Further studies on the role of antiviral therapy in this setting are warranted.     

Surgical treatment of congenital heart malformations. Indications and surgical management (author's transl)]

Congenital malformations of the heart have to be expected in approximately 0,8% of all newborns. The majority of them needs surgical treatment and can be corrected anatomically with a low operative risk (atrial and ventricular septal defects, patent ductus arteriosus, coarctation, valvular aortic and pulmonary stenosis etc.). Surgical repair of complex anomalies includes either palliative or functionally corrective procedures and has a much higher operative and early postoperative mortality (transposition of the great arteries, tetralogy of Fallot, tricuspid atresia etc.). Surgery becomes urgent in babies suffering from congestive heart failure and/or progressive severe hypoxia during the first months of life. Early total surgical repair or primary palliation and two-stage correction depends on the kind of anomaly and has to be selected individually. Hemodynamical classification, general distribution and surgical considerations of the most common congenital malformations of the heart are described.     

Adriamycin: a new effective agent in the therapy of disseminated sarcomas.

Thirty-six patients with disseminated sarcomas were treated with adriamycin according to an intermittent single high-dose schedule based on our prior pharmacologic observations. The dose of 60 mg/M2 IV q 3 weeks was reduced 50-75% in the presence of liver disease. Complete remission occurred in 9%, parital remission in 32%, and improvement in 21% for median durations of 37, 18, and 15 weeks, respectively. Survival was prolonged in responding patients. Hematologic suppression was mild in the absence of liver disease or prior extensive radiotherapy. Congestive heart failure, a well-known long-term complication of therapy with anthracycline drugs, occurred in two out of four patients who had cumulative doses of 600 mg/M2 or more. Mucous membrane toxicity was not observed. Adriamycin is an effective new agent in the therapy of disseminated sarcomas and can be used with relative safety by following pharmacologic principles.     

Use of interferon in a case of hepatic hemangioma]

Hepatic hemangioendothelioma can have a fatal outcome. After failure of classic therapies, and when surgery or arterial embolization are not possible, those benign tumours may benefit from interferon alpha treatment. CASE REPORT: We report a case of a 14-month-old infant who presented with hepatic hemangiomatosis and cardiac failure. The disease can neither be controlled by steroids nor by radiotherapy associated with digitalo-diuretic treatment. Due to the important vascular volume of the tumour, neither surgical care nor arterial embolization were possible. Thus this infant was treated for ten months by interferon alpha. The evolution was favourable: cardiac failure, calcifications and volume of the angiomatosis were regressive. CONCLUSION: Interferon alpha treatment helps to control cardiac failure and the course of hepatic hemangioma in childhood.