Secondary prophylaxis of hepatocellular carcinoma: the comparison of direct-acting antivirals with pegylated interferon and untreated cohort.

During the past two decades, several studies showed reduced rates of hepatocellular carcinoma recurrence in patients with HCV-related cirrhosis after interferon-based antiviral therapies respect to untreated controls, even without reaching viral clearance. The recent development of new all-oral regimens with direct-acting antivirals has radically improved the therapeutic management of hepatitis C. Nevertheless, paradoxical, or at least unexpected, high rates of both occurrence and recurrence of hepatocellular carcinoma after a treatment with direct-acting antivirals, have been reported in the recent literature. These findings generated a strong rebound in the hepatology community and are at present still controversial. We sought to compare the hepatocellular carcinoma recurrence-free survival of a historical cohort treated with pegylated interferon/ribavirin and an untreated cohort with a cohort treated with direct-acting antivirals.

Accuracy of VirtualTouch Acoustic Radiation Force Impulse (ARFI) imaging for the diagnosis of cirrhosis during liver ultrasonography.

PURPOSE: VirtualTouch is a new technique recently proposed to evaluate liver stiffness during B-mode ultrasonography. The goal of the present study was to analyze the diagnostic accuracy of VirtualTouch in the diagnosis of cirrhosis and its correlation with transient elastography (Fibroscan). MATERIALS AND METHODS: A total of 133 patients with chronic liver disease were enrolled. 90 of 133 underwent VirtualTouch and transient elastography and 70 patients assessed with VirtualTouch were submitted to liver biopsy. Stiffness was assessed by both techniques in the right liver lobe. The diagnostic accuracy for cirrhosis was first assessed in the 90 patients submitted to transient elastography with > 13 kPa (47 % of patients) as diagnostic for cirrhosis values. The best cut-off for cirrhosis with VirtualTouch was then tested in the 70 patients with biopsy (cirrhosis in 38 % of patients). 41 patients were assessed by VirtualTouch by two different operators. RESULTS: The VirtualTouch values in controls, chronic hepatitis and cirrhosis were respectively 113, 147 and 255 cm/sec. The AUROC of liver VirtualTouch for the diagnosis of cirrhosis (reference Fibroscan) was 0.941 with 175 cm/sec as the best cut-off (sensitivity 93.0 %; specificity 85.1 %). VirtualTouch confirmed good performance also in patients with bioptic diagnosis of cirrhosis (AUROC 0.908, sensitivity 81.5 %, specificity 88.4 %,). The correlation of VirtualTouch with transient elastography was strict (r = 0.891) and the correlation in VirtualTouch measurements between two operators was also good (r = 0.874). CONCLUSION: VirtualTouch is able to identify the presence of cirrhosis with good accuracy, shows good interobserver reproducibility and the correlation of its values with those obtained by transient elastography with Fibroscan is good.

Palliation of complex cardiac anomalies with subaortic obstruction: new operative approach.

The modified Fontan operation for complex cardiac anomalies associated with subaortic obstruction entails a high surgical risk. It is likely that ventricular hypertrophy secondary to chronic pressure overload plays a significant role. This problem was approached with a new type of palliative operation comprising both a proximal pulmonary artery to ascending aorta anastomosis and a bidirectional cavopulmonary anastomosis. This operation was performed in six children ranging in age from 26 to 63 months. There was one intraoperative death due to hemorrhage. In one patient, a pulmonary to aorta conduit caused compression of the right coronary artery; the problem was solved by lengthening the conduit with a second period of cardiopulmonary bypass. The five survivors experienced an uneventful postoperative course. Repeat cardiac catheterization in these five patients showed low pressure in the cavopulmonary system (mean 10 mm Hg), absence of a gradient at rest between the systemic ventricle and aorta and fair arterial oxygenation (mean 82%). A technetium-99m perfusion lung scan visualized a slight prevalence of pulmonary blood flow ipsilateral to the shunt in three cases, whereas in one case preferential flow to the right lung was associated with a narrowing at the site of the cavopulmonary anastomosis. Mild hypoperfusion of the anterior pulmonary segments was observed in two cases. Both pressure and volume overload are abolished with this procedure and a satisfactory oxygenation is provided. Low venous pressure in the coronary, hepatic and renal areas as well as the short bypass time may explain the smoothness of the postoperative course in our patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Minimally invasive or interventional repair of atrial septal defects in children: experience in 171 cases and comparison with conventional strategies.

OBJECTIVES: The goal of this study was to evaluate percutaneous interventional and minimally invasive surgical closure of secundum atrial septal defect (ASD) in children. BACKGROUND: Concern has surrounded abandoning conventional midline sternotomy in favor of the less invasive approaches pursuing a better cosmetic result and a more rational resource utilization. METHODS: A retrospective analysis was performed on the patients treated from June 1996 to December 1998. RESULTS: One hundred seventy-one children (median age 5.8 years, median weight 22.1 kg) underwent 52 device implants, 72 minimally invasive surgical operations and 50 conventional sternotomy operations. There were no deaths and no residual left to right shunt in any of the groups. The overall complication rate causing delayed discharge was 12.6% for minimally invasive surgery, 12.0% for midline sternotomy and 3.8% for transcatheter device closure (p < 0.01). The mean hospital stay was 2.8 +/- 1.0 days, 6.5 +/- 2.1 days and 2.1 +/- 0.5 days (p < 0.01); the skin-to-skin time was 196 +/- 43 min, 163 +/- 46 min and 118 +/- 58 min, respectively (p < 0.001). Extracorporeal circulation time was 49.9 +/- 10.1 min in the minithoracotomy group versus 37.2 +/- 13.8 min in the sternotomy group (p < 0.01) but without differences in aortic cross-clamping time. Sternotomy was the most expensive procedure (15,000 EUR +/- 1,050 EUR vs. 12,250 EUR +/- 472 EUR for minithoracotomy and 13,000 EUR +/- 300 EUR for percutaneous devices). CONCLUSIONS: While equally effective compared with sternotomy, the cosmetic and financial appeal of the percutaneous and minimally invasive approaches must be weighed against their greater exposure to technical pitfalls. Adequate training is needed if a strategy of surgical or percutaneous minimally invasive closure of ASD in children is planned in place of conventional surgery.

Truncus arteriosus with single pulmonary artery: influence of pulmonary vascular obstructive disease on early and late operative results.

Nineteen patients with truncus arteriosus and single pulmonary artery had corrective operations at the Mayo Clinic from 1969 to 1983. At operation, their ages ranged from 4 months to 20 years (mean 8.1 years). The preoperative pulmonary resistance divided by 2 was used to predict the degree of pulmonary vascular obstructive disease at operation. The influence of elevated pulmonary resistance and the intraoperative postrepair ratio of pulmonary artery to left ventricular pressure on operative and late mortality were examined. The outcome of patients with single pulmonary artery was compared with the outcome of 148 patients with truncus arteriosus and two pulmonary arteries operated on during the same period. Patients with a single pulmonary artery had an operative mortality similar to that of patients with two pulmonary arteries (32 versus 28%, p greater than 0.05). Late mortality was, however, significantly greater (p less than 0.001) for patients with a single pulmonary artery. Elevated ratios of intraoperative postrepair pulmonary artery to left ventricular pressure were associated with significantly higher (p less than 0.02) operative and late mortality, but elevated preoperative pulmonary resistance was not (p greater than 0.10). Truncus arteriosus with single pulmonary artery is associated with poor postoperative survival, and although elevated pulmonary resistances preoperatively did not predict outcome, elevated intraoperative postrepair pulmonary artery to left ventricular pressure ratios were associated with increased operative and late survival, suggesting a deleterious role of pulmonary hypertension.

Deletion 22q11 in patients with interrupted aortic arch.

In our series of 27 children with various types of interruption of the aortic arch (IAA), deletion 22q11 is prevalent in patients with simple IAA type B, and is absent in patients with IAA type A and in those with associated additional major cardiac defects. Anomalies of the infundibular septum should be considered a characteristic aspect of children with IAA and deletion 22q11.

Heterotaxy with left atrial isomerism in a patient with deletion 18p.

We report on a female infant with partial deletion of the short arm of chromosome 18 (del 18p) and heterotaxy with left atrial isomerism. Congenital heart defect (CHD) is found in 10% of the literature reports. Interestingly, situs abnormalities have been diagnosed in four patients with del 18p, including ours. This finding could imply that a locus or loci involved in the development of normal body situs lies within this chromosomal region. Del 18p must be consid- ered when evaluating a patient with phenotypic anomalies and CHD in lateralization defects.

Balloon dilation of postsurgical subaortic obstruction.

Two children aged 10 and 5.5 years underwent balloon dilation for postsurgical subaortic obstruction. The outcome and the role of this procedure are discussed.

Surgical bypass of the systemic atrioventricular valve in children by means of a valved conduit.

The surgical approach to relief of mitral stenosis in children is still a controversial problem. We describe our experience with four severely symptomatic children in whom a valved conduit from the left atrium to the left ventricle was successfully used to bypass a hypoplastic systemic atrioventricular valve. A left atrial-left ventricular extracardiac conduit was implanted in these patients with a hypoplastic mitral anulus and an adequate left ventricular chamber. There were no early or late deaths. Postoperative cardiac catheterization performed in all patients 1 month after the operation showed reduced size of the left atrium, a reduction of the left atrial-left ventricular gradient from a mean of 14 mm Hg to a mean of 5 mm Hg, and an increase of the left atrial outlet from a mean diameter of 10.7 mm to 28.7 mm (including the diameter of the native mitral valve plus the internal diameter of the valved conduit). The application of this unconventional operation in children with congenital or acquired stenosis of the systemic atrioventricular valve should be considered when the mitral valve obstruction cannot be relieved by conventional valve repair or replacement. Furthermore, the left atrial-left ventricular conduit does not preclude future alternative surgical options.

Age-dependent ventricular response to pressure overload. Considerations for the arterial switch operation.

Success with the arterial switch operation for D-transposition of the great arteries and the concept of left ventricular suitability for systemic work stimulated this literature review of the age-dependent mechanisms in normal cardiac growth and pressure-induced left ventricular hypertrophy. Normal postnatal myocardial growth is markedly influenced by hemodynamic factors. It consists of an early hyperplastic phase of both myocytes and capillaries that is followed by a myocyte hypertrophic phase. Similarly, imposition of a pressure overload induces both myocyte hyperplasia/hypertrophy and increased angiogenesis in neonates, but only myocyte hypertrophy at a later age. The functional consequences of ventricular hypertrophy are the result of adaptive and nonadaptive changes resulting from the overload stimulus, for example, induction of protooncogene expression, myosin isoenzyme shifts, degree of coronary perfusion, responsiveness to beta-adrenergic stimulation, and myocyte capacity to re-accumulate or sequester cytosolic calcium. Strikingly, both the capacity and the rapidity of left ventricular hypertrophy decrease with increasing age. This experimental information supports the current use of primary arterial switching for neonates with D-transposition of the great arteries and the use of "rapid" two-stage arterial switching in infants more than 3 to 4 weeks of age; it raises some concern about the practice of late retraining of the left ventricle in cases of failed atrial inversion operation.

Total repair of pulmonary atresia with ventricular septal defect and major aortopulmonary collaterals: an integrated approach.

OBJECTIVE: Predicting postrepair right ventricular/left ventricular pressure ratio has prognostic relevance for patients undergoing total repair of pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries. To this purpose, we currently rely on 2 novel parameters: (1) preoperative total neopulmonary arterial index and (2) mean pulmonary artery pressure changes during an intraoperative flow study. METHODS: Since January 1994, 15 consecutive patients (aged 64 +/- 54 months) with pulmonary atresia, ventricular septal defect, and major aortopulmonary collaterals were managed according to total neopulmonary arterial index. Seven patients with hypoplastic pulmonary arteries and a total neopulmonary arterial index less than 150 mm(2)/m(2) underwent palliative right ventricular outflow tract reconstruction followed by secondary 1-stage unifocalization and ventricular septal defect closure. The other 8 patients with a preoperative index of more than 150 mm(2)/m(2) underwent primary single-stage unifocalization and repair. The ventricular septal defect was closed in all cases (reopened in 1). In 9, such decision was based on an intraoperative flow study. RESULTS: Patients treated by right ventricular outflow tract reconstruction had a significant increase of pulmonary artery index (P=.006) within 22 +/- 6 months. Repair was successful in 14 cases (postrepair right ventricular/left ventricular pressure ratio = 0.47 +/- 0.1). One hospital death occurred as a result of pulmonary vascular obstructive disease, despite a reassuring intraoperative flow study. Accuracy of this test in predicting the postrepair mean pulmonary artery pressure was 89% (95% CI: 51%-99%). At follow-up (18 +/- 12 months), all patients are free of symptoms, requiring no medications. CONCLUSIONS: The integrated approach to total repair of pulmonary atresia, ventricular septal defect, and major aortopulmonary collaterals by preoperative calculation of total neopulmonary arterial index, right ventricular outflow tract reconstruction (when required), and intraoperative flow study may lead to optimal intermediate results.

Staged Fontan operation for complex cardiac anomalies with subaortic obstruction.

Ventricular hypertrophy is a recognized risk factor for the Fontan operation in cases of complex cardiac anomalies with unrestricted pulmonary blood flow and subaortic obstruction. Between 1986 and 1991 we have treated 23 such patients with a new type of palliation combining a main pulmonary artery-ascending aorta anastomosis with a bidirectional cavopulmonary anastomosis. Their ages averaged 57 +/- 36 months (7 to 155 months). Nine patients had (S,L,L) single ventricule with transposition and the other 14 had more complex cardiac anomalies unsuitable for biventricular repair. Subaortic obstruction was defined by a hemodynamic criterion (n = 6) or by a morphologic criterion (n = 17). There were five hospital deaths (21.7%): All three patients older than 7 years of age died (p = not significant). Follow-up averaged 28 +/- 21 months (range 1 to 58 months). Among the 18 hospital survivors, the proportions surviving 1 and 5 years after the operation were 78% and 63%, respectively. Control cardiac catheterization in 11 patients showed no or trivial subaortic gradient, a mean cavopulmonary pressure of 10 +/- 3 mm Hg, and a mean arterial oxygen saturation of 83%. Nine patients underwent secondary Fontan repair in our institution 21 +/- 4 months after palliation, without deaths. Another patient died elsewhere, 3.7 years after palliation, as a result of hemorrhage at sternal reentry during attempted Fontan operation (overall mortality at repair, 10%). The other eight patients are awaiting Fontan operation. This staged approach reduces both pressure and volume ventricular load and provides adequate oxygenation before the Fontan operation. In our experience, it resulted in reduced mortality at definitive repair.

Neonatal repair of tetralogy of Fallot with and without pulmonary atresia.

Our experience with the arterial switch operation for transposition of the great arteries has confirmed the attainability of excellent results with elective neonatal surgery. Up to this time, we have repaired tetralogy of Fallot during the neonatal period only when symptoms, either severe persistent cyanosis or cyanotic spells, have been present. This review assesses the results of such nonelective neonatal correction of tetralogy between 1973 and 1988. Twenty-seven neonates with either symptomatic tetralogy of Fallot or symptomatic tetralogy of Fallot with valvar pulmonary atresia underwent repair. Mean age at repair was 8 +/- 8.4 days and mean weight was 3.0 +/- 0.7 kg. Unsatisfactory palliative shunts had previously been placed elsewhere in four patients. Twenty-five transannular patches and two conduits were used for reconstruction of the right ventricular outflow tract. There were five deaths in the hospital, three of which were due to avoidable technical problems. All deaths occurred in patients with pulmonary artery (Nakata) index less than 150 mm2/m2. One premature child weighing 2.3 kg displayed an absent pulmonary valve-like syndrome after repair and died late of respiratory complications caused by aneurysmal branch pulmonary arteries. Actuarial survival at 5 years was 74%. There was a single rapidly declining hazard phase for death, with the hazard approaching zero at 1 1/2 years after repair. Actuarial freedom from need for reoperation was 76% at 5 years. Postoperative catheterization of 15 long-term survivors showed right ventricular pressure less than 70% systemic in 13 cases. All patients are symptomatically well and functioning in sinus rhythm 1 to 15 years after repair (mean, 5 +/- 4 years). This experience with neonates with symptoms suggests that, if mortality is lower in the absence of symptoms, elective repair of tetralogy of Fallot could be reasonably undertaken during the first months of life.

Relief of membranous obstruction of the inferior vena cava in a 5-year-old child.

Membranous obstruction of the inferior vena cava is a rare congenital anomaly that may present clinical features of Budd-Chiari syndrome caused by chronic obstruction of the hepatic drainage. We report membranous obstruction of the inferior vena cava in a 5-year-old boy. Surgical repair was prompted by signs and symptoms of hepatic venous obstruction. To our knowledge, this is the youngest patient successfully operated on for this anomaly.

Bidirectional cavopulmonary anastomosis in patients under two years of age.

Between December 1986 and December 1990, a bidirectional cavopulmonary anastomosis was performed in 27 patients younger than 2 years of age, including 12 with heterotaxia syndrome. Age and weight of patients averaged 14.2 +/- 6.6 months and 8.1 +/- 2.2 kg, respectively. Eleven had pulmonary atresia and 16 had pulmonary stenosis. The main pulmonary artery was ligated in seven patients in the latter group (subsequently reopened in one) and left open in nine (subsequently ligated in two). There were four hospital deaths (15%). All patients were discharged with anticoagulant/antithrombotic therapy to be continued for 6 months. There were two late deaths before further operations (8.7%). Two patients, one with acquired massive pulmonary arteriovenous fistulas and one with progressive common atrioventricular valve regurgitation, subsequently underwent definitive repair (biventricular in one), and both died. Heterotaxia syndrome (p = 0.087) and preoperative mean pulmonary artery pressure higher than 15 mm Hg (p = 0.09) were the only risk factors for overall mortality.

Combined mustard and Rastelli operations. An alternative approach for repair of associated anomalies in congenitally corrected transposition in situs inversus [I,D,D].

We report on two patients with congenitally corrected transposition of the great arteries in situs inversus who underwent successful anatomic repair of associated cardiac anomalies--ventricular septal defect and pulmonary outflow tract obstruction. Surgical intervention was influenced by the recently introduced technique of Ilbawi and colleagues in cases of congenitally corrected transposition in situs solitus. Principles of the correction are as follows: (1) patch redirection of venous flows at the atrial level through an incision in the left-sided right atrium; (2) patch closure of the ventricular septal defect through a right ventriculotomy, baffling the left ventricle to the aorta; and (3) valved conduit interposition between the right ventricle and the pulmonary artery. If the ventricular septal defect is restrictive, it can be safely enlarged by extensive resection of the anterosuperior border, because of the posteroinferior location of the bundle of His in this anomaly. With this technique, the left ventricle and the native mitral and aortic valves are recruited for systemic work, with intrinsic long-term advantages. It is, however, a complex procedure involving substantial use of prosthetic material. More experience is necessary to establish whether this approach is superior to currently available physiologic repairs.

Fifteen-year experience with surgical repair of truncus arteriosus.

From 1965 until March, 1982, 167 patients underwent surgical repair of truncus arteriosus. The age at operation ranged from 18 days to 33 years (mean 6 years). There were 48 hospital deaths (28.7%). The following factors had a positive correlation with the possibility of a surgical death: age at operation less than 2 years (p less than 0.001), a postrepair pulmonary arterial/left ventricular pressure ratio greater than 0.5 for patients with two pulmonary arteries (p less than 0.001) and greater than 0.6 for patients with unilateral absence of a pulmonary artery (p less than 0.02), and a postrepair right ventricular/left ventricular pressure ratio greater than 0.8 (p less than 0.008). The 119 hospital survivors were followed up for a total of 829 person-years. Late survival rate at 5 years was 84.4% and at 10 years, 68.8%. Preoperative factors that correlated with a reduced long-term survival rate were as follows: increasing age at operation (p = 0.004), the presence of moderate or severe truncal valve insufficiency (p = 0.008), lower pulmonary/systemic flow ratio (p = 0.04), and unilateral absence of a pulmonary artery (p less than 0.001). Thirty-six patients required reoperation during the follow-up period (30%) primarily for replacement of the right ventricular-pulmonary arterial conduit and/or for truncal valve replacement. The long-term results obtained in these patients support the need for early repair of the anomaly, improvement in the methods for control or repair of the truncal valve insufficiency, and the continued search for better extracardiac valved conduits.

Thymoglobuline use in pediatric heart transplantation.

The literature has few data regarding the use of polyclonal anti-thymocyte globulin in pediatric cardiac transplantation. We describe our single-center, retrospective study of the use of Thymoglobuline in a pediatric population. We included in the study 31 consecutive heart transplant recipients (mean age, 7.8 years; median age, 9 years; range, 4 months-17 years), who all survived surgery. To induce immunosuppression, all patients received Thymoglobuline therapy at age-dependent doses (1-1.5 mg/kg/day between 0 and 1 year; 1.5-2 mg/kg/day from 1 year to 8 years; and 2.5 mg/kg/day >8 years). Duration of treatment was 1 to 7 days. In patients <1 year, the total number of lymphocytes was maintained at >500/mm(3). Thirty of 31 patients are alive at the end of follow-up. During the first 3 months, 3 Grade 3A and 10 Grade 1A (Working Formulation grading system) rejection episodes occurred. All reversed after steroid treatment. Eleven viral infections, 2 bacterial infections, and 1 fungal infection occurred. Not all patients with infection were symptomatic but all responded successfully to treatment. One episode of post-transplantation lymphoproliferative disease regressed after decreasing immunosuppression therapy and after acyclovir therapy. At the end of follow-up, 19 patients are without steroids. Immunosuppression therapy with Thymoglobuline is safe in the pediatric age group if the number of lymphocytes is monitored strictly.

Evaluation of the Damus-Kaye-Stansel operation in infancy.

Thirteen patients, 12 of whom younger than 2 years, underwent a Damus-Kaye-Stansel procedure for complete transposition of the great arteries, ventricular septal defect, or double-outlet right ventricle and subpulmonary ventricular septal defect. In 6 patients, associated cardiac anomalies caused systemic flow obstruction. There were six hospital deaths (mortality rate, 42%). In a mean follow-up period of 57 months, 5 of 7 survivors required relief of right ventricular hypertension through conduit replacement or enlargement (4 patients) or conduit valve balloon dilation (1 patient). The aortic valve became regurgitant in 2 patients in whom it had been left in potential connection with the right ventricle. One patient has moderate pulmonary valve regurgitation. The main advantage of the Damus-Kaye-Stansel procedure is that it avoids coronary relocation; also, the spatial relationship of the great arteries and the coronary anatomy do not affect its feasibility. One drawback is the need for a conduit in infancy. Our present indication for Damus-Kaye-Stansel procedure is confined to double-outlet right ventricle with subpulmonary ventricular septal defect; 5 of 6 patients survived repair in this series. Possible indications are for patients with associated subaortic obstruction or unusual coronary arrangements. Fresh or cryopreserved homografts as extracardiac conduits and primary closure of the subaortic area may reduce the need for reoperation after Damus-Kaye-Stansel procedure.

Bidirectional cavopulmonary shunts: clinical applications as staged or definitive palliation.

A standard Glenn anastomosis between the superior vena cava and the right pulmonary artery has been the accepted mode of treatment for patients with complex cyanotic congenital heart disease. We report our experience in 18 patients with such disease who underwent a bidirectional cavopulmonary shunt because of increasing cyanosis and growth cessation. All patients were considered less than "ideal" candidates for a Fontan procedure. We divided the patients into two groups: group 1 had azygos continuation and group 2 did not. Fourteen patients required hypothermic cardiopulmonary bypass. Bidirectional pulmonary blood flow was achieved in all patients. Only 1 death occurred (group 2). The improvement in oxygen saturation and overall clinical condition of these patients, together with the low mortality and morbidity, is encouraging. However, long-term follow-up is mandatory for a comprehensive evaluation of this surgical approach as definitive palliation or as a first stage for a Fontan operation.