Background
Hepatic hemangiomas are the most common benign liver tumors of infancy. They are termed congenital if fully developed at birth or infantile if they appear in the first weeks of life. ...Previous studies suggested that most focal hepatic hemangiomas are congenital in nature, exhibit no postnatal growth and have an evolution that parallels their cutaneous counterparts. They are subdivided by pattern of involution, whether rapidly involuting (RICH), partially involuting (PICH) or non-involuting (NICH) congenital hemangiomas. In our experience, some focal hepatic hemangiomas show postnatal growth, behaving like infantile forms.
Objectives
To analyze the spontaneous evolution of focal congenital hepatic hemangiomas with quantification of tumor volume changes over time and to identify initial postnatal ultrasound (US) imaging biomarkers predictive of their evolution pattern.
Materials and methods
A retrospective review of clinical, imaging and pathology data of children diagnosed with focal congenital hepatic hemangioma (prenatal diagnosis or age at diagnosis <7 days and/or glucose transporter protein 1 GLUT1-negative tumor) diagnosed between 2000 and 2018 was performed with analysis of tumor volume changes over time. Exclusion criteria were treatment inducing a tumor volume change (hepatic artery embolization, propranolol, or corticosteroids), imaging follow-up less than 1 month or fewer than two US examinations. Volumetric analysis was based on US and cross-sectional imaging. Lesion volumes were estimated using the standard ellipsoid formula. A 35% margin of error was assumed for tumor volume variation to account for variability in measurements. Imaging studies, including US, computed tomography, and magnetic resonance imaging, were reviewed and initial postnatal US features were correlated with evolution pattern.
Results
Twenty-five patients with focal congenital hepatic hemangiomas were included. The median follow-up time was 46.5 months (range: 4–144 months). Eight (32%) lesions showed postnatal growth before involuting, without signs of intralesional hemorrhage, as do cutaneous infantile hemangiomas. The other 17 (68%) lesions exhibited a strict decrease in volume with age, of which 15 underwent complete involution (8 before age 18 months and 7 after age 18 months) and 2 underwent partial involution. The different evolution patterns of focal congenital hepatic hemangiomas showed overlapping imaging features and we found no initial US feature to be significantly associated with postnatal growth. However, large vascular spaces with marked vascularity at US were noted in three of the eight rapidly involuting lesions.
Conclusion
Focal congenital hepatic hemangiomas are not the equivalent of cutaneous RICH, as some may increase in size and tumor regression may be rapid or slow. The different evolution patterns of focal congenital hepatic hemangiomas show overlapping US features.
Castleman disease (CD) is a rare non-malignant lymphoproliferation of undetermined origin. Two major disease phenotypes can be distinguished: unicentric CD (UCD) and multicentric CD (MCD). Diagnosis ...confirmation is based on histopathological findings in a lymph node. We attempted to survey all cases of paediatric CD identified to date in France to set up a national registry aiming to improve CD early recognition, treatment and follow-up, within the context of a new national reference center (http://www.castleman.fr).
In 2016, we e-mailed a questionnaire to members of the French paediatric immunohaematology society, the paediatric rheumatology society and the Reference Centre for Castleman Disease to retrospectively collect cases of paediatric CD (first symptoms before age 18 years). Anatomopathological confirmation was mandatory.
We identified 23 patients (12 girls) with a diagnosis of UCD (n = 17) and MCD (n = 6) between 1994 and 2018. The mean age at first symptoms was 11.47 ± 4.23 years for UCD and 8.3 ± 3.4 years for MCD. The mean diagnosis delay was 8.16 ± 10.32 months for UCD and 5.16 ± 5.81 years for MCD. In UCD, the initial symptoms were isolated lymph nodes (n = 10) or lymph node associated with other symptoms (n = 7); fever was present in 3 patients. Five patients with MCD presented fever. No patients had HIV or human herpesvirus 8 infection. Autoinflammatory gene mutations were investigated in five patients. One patient with MCD carried a K695R heterozygous mutation in MEFV, another patient with MCD and Duchenne myopathy carried two variants in TNFRSF1A and one patient with UCD and fever episodes carried two heterozygous mutations, in IL10RA and IL36RN, respectively. Treatment of UCD was mainly surgical resection, steroids, and radiotherapy. Treatment of MCD included tocilizumab, rituximab, anakinra, steroids, chemotherapy, and splenectomy. Overall survival after a mean of 6.1 ± 6.4 years of follow-up, was 100% for both forms.
Paediatric CD still seems underdiagnosed, with a significant diagnosis delay, especially for MCD, but new international criteria will help in the future. Unlike adult CD, which is strongly associated with HIV and human herpesvirus 8 infection, paediatric CD could be favored by primary activation of innate immunity and may affect life expectancy less.
Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a rare liver disease caused by biallelic variations in ABCB4. Data reporting on the impact of genotype and of response to UDCA therapy ...on long-term outcome are scarce.
We describe retrospectively a cohort of 38 PFIC3 patients with a median age at last follow-up of 19.5 years (3.8-53.8).
Twenty patients presented with symptoms before 1 year of age. Thirty-one patients received ursodeoxycholic acid (UDCA) therapy resulting in serum liver test improvement in 20. Twenty-seven patients had cirrhosis at a median age of 8.1 years of whom 18 received a liver transplantation (LT) at a median age of 8.5 years. Patients carrying at least one missense variation were more likely to present with a positive (normal or decreased) MDR3 canalicular expression in native liver and had a prolonged native liver survival (NLS; median: 12.4 years (3.8-53.8)). In contrast, patients with severe genotypes (no missense variation) had no detectable MDR3 canalicular expression, earlier symptom onset and age at cirrhosis and all underwent LT at a median age of 6.7 years (range: 2.3-10.3). The former group was refractory to UDCA treatment, whereas 87% of patients with at least one missense variation displayed a liver biochemistry improvement. Biliary phospholipid level over 6.9% of total biliary lipids predicted response to UDCA therapy. Response to UDCA predicted NLS.
Patients carrying at least one missense variation, with a positive MDR3 canalicular expression, and a biliary phospholipid level over 6.9% were more likely to respond to UDCA therapy and to exhibit prolonged NLS.
In this study, data show that genotype and response to UDCA therapy predicted nature liver survival of PFIC3 patients. Patients carrying at least one missense variation, with a positive (decreased or normal) MDR3 canalicular immuno-staining, and a biliary phospholipid level over 6.9% of total biliary lipids were more likely to respond to UDCA therapy and to exhibit prolonged native liver survival.
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•71% of patients had cirrhosis at a median age of 8.1 years of whom 66% received a liver transplant at a median age of 8.5 years.•Patients with severe genotype (no missense variation) did not response to UDCA treatment.•87% of patients with at least one missense variation responded partially or fully to UDCA treatment.•Biliary phospholipid level over 6.9% of total biliary lipids predicted response to UDCA therapy.•Severity of gentotypes and response to UDCA treatment predicted native liver survival.
Widening spectrum of liver angiosarcoma in children Ackermann, Oanez; Fabre, Monique; Franchi, Stephanie ...
Journal of pediatric gastroenterology and nutrition,
2011-December, Letnik:
53, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Liver hemangiomas are vascular tumors, which occur in the first months of life and carry risks of initial complications, but are considered to be benign histologically and to regress with time. ...Histologic studies suggest that a subtype, type 2 hemangioendothelioma, is akin to angiosarcoma and may have a severe long-term prognosis. We report 5 girls with type 2 hemangioendothelioma of the liver.
Three children initially presented with classical infantile multinodular hemangioma, including cardiac and pulmonary complications and regression of tumors at age 1½ to 2½ years. All 3 experienced tumor relapse at ages 2½ to 3, leading to death at ages 2½ to 5. Tumor histology showed type 2 hemangioendothelioma. The other 2 children presented with liver tumors at ages 2 and 3 years. In 1, initial biopsy of a single tumor showed benign type 1 hemangioendothelioma, but surgical resection was followed by relapse in the remaining liver, lung metastases, and death. Whole tumor histology showed both type 1 and 2 lesions. In the other child, tumor biopsy showed type 2 lesions. She underwent liver transplantation and is alive without tumor recurrence 3 years later.
Careful follow-up is necessary to detect late recurrence in infants with multinodular liver hemangiomas. Vascular liver tumors occurring after infancy are likely to be malignant. The high risk of relapse in the remaining liver suggests that if no metastases are detected, liver transplantation is preferable to surgical tumor resection in both situations.
Combined respiratory chain defect is a common feature in mitochondrial liver disease during early infancy. Mitochondrial DNA depletions, induced by mutations of the nuclear genes POLG, DGUOK, and ...MPV17, are the major causes of these combined deficiencies. More recently, mutations in TRMU gene encoding the mitochondrial tRNA-specific 2-thiouridylase were found in infantile hepatopathy related to mitochondrial translation defect. It is characterized by a combined defect of respiratory chain complexes without mitochondrial DNA depletion.
We report here clinical, biochemical, and genetic findings from three unrelated children presenting with hepatopathy associated with hyperlactatemia and respiratory chain defect due to bi-allelic mutations in TRMU gene. Two patients recovered spontaneously in a few months, whereas the other one died of acute liver failure. Spontaneous remission is a rare feature in mitochondrial liver diseases, and early identification of TRMU mutations could impact on clinical management. Our results extend the small number of TRMU mutations reported in mitochondrial liver disorders and allowed accumulating data for genotype–phenotype correlation.
Abstract Background and aims Primary prophylaxis of bleeding is debated for children with portal hypertension because of the limited number of studies on its safety and efficacy, the lack of a known ...endoscopic pattern carrying a high risk of bleeding for all causes, and the assumption that the mortality of a first bleed is low. We report our experience with these issues. Methods From 1989 to 2014, we managed 1300 children with portal hypertension. Endoscopic features were recorded; high-risk varices were defined as: grade 3 esophageal varices, grade 2 varices with red wale markings, or gastric varices. Two hundred forty-six children bled spontaneously and 182 underwent primary prophylaxis. The results of primary prophylaxis were reviewed as well as bleeding-free survival, overall survival and life-threatening complications of bleeding. Results High-risk varices were found in 96% of children who bled spontaneously and in 11% of children who did not bleed without primary prophylaxis ( P<0.001 ), regardless of the cause of portal hypertension. Life-threatening complications of bleeding were recorded in 19% of children with cirrhosis and high-risk varices who bled spontaneously. Ten-year probabilities of bleeding-free survival after primary prophylaxis in children with high-risk varices were 96% and 72% for noncirrhotic causes and cirrhosis respectively. Ten-year probabilities of overall survival after primary prophylaxis were 100% and 93% in children with noncirrhotic causes and cirrhosis respectively. Conclusion In children with portal hypertension, bleeding is linked to the high-risk endoscopic pattern reported here. Primary prophylaxis of bleeding based on this pattern is fairly effective and safe. Lay summary In children with liver disease, the risk of bleeding from varices in the esophagus is linked to their large size, the presence of congestion on their surface and their expansion into the stomach but not to the child’s age nor to the cause of portal hypertension. Prevention of the first bleed in children with high-risk varices can be achieved by surgery or endoscopic treatment and decreases mortality and morbidity.
Congenital portosystemic shunts (CPSS) are rare vascular malformations that create an abnormal connection between portal and systemic veins resulting in complete or partial diversion of the portal ...flow away from the liver to the systemic venous system. Different anatomic types exist and several classifications have been proposed. They can be associated with other malformations especially cardiac and heterotaxia. The main complications include hepatic encephalopathy, liver tumors, portopulmonary hypertension, and pulmonary arteriovenous shunts. Diagnosis relies on imaging, and prenatal diagnosis is possible. Spontaneous closure of the CPSS is possible in some anatomic forms during the first year of life. When the CPSS remains patent, radiologic or surgical closure of the CPSS may prevent, resolve, or stabilize complications. Interventional radiology plays a key role for both the preoperative evaluation with occlusion test to assess the exact anatomy and to measure portal pressure after occlusion of the CPSS. Endovascular closure is the first option for treatment when possible.
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