Background: Mechanistic target of rapamycin (mTOR) inhibitors are being used off-label showing promising results in patients with vascular anomalies. Children with lymphatic malformations (LMs) involving the airway benefit from sirolimus therapy soon after birth, reducing the need of tracheostomy. Available information about efficacy and side effects in neonates remains poor. We present seven newborns with severe head and neck LM showing response to sirolimus with no significant toxicity. Methods and Results: We performed a retrospective review of neonates with head and neck LM who received sirolimus between January 2014 and May 2018 with upper airway involvement needing ventilatory support. We analyzed type of LM, involved anatomical area, symptoms and response to sirolimus, including dosage, blood levels, response, side effects, and complications. Seven neonates received primary treatment with sirolimus in the context of cervical LM. Sirolimus was started at the recommended dose of 0.8 mg/m ² /12 h and adjusted to maintain blood levels between 4 and 12 ng/mL. Median follow-up was 32 months (4–43) with a median treatment duration of 12 months (3–43). One patient had complete resolution of the malformation, one had complete resolution of symptoms, and five had partial resolution of the malformation with significant improvement in their respiratory conditions. Two patients required additional subtotal surgical resection and one tracheostomy. Four patients remain under treatment. Toxicity was not observed. Conclusions: Sirolimus is a safe drug in neonates and can be considered the first therapeutical option in newborns at high risk of respiratory failure before sclerosis or surgery. Close follow-up is mandatory to identify side effects at long-term use.

Aim Hepatoblastoma is the most frequent hepatic tumor in children, and its initial presentation will affect treatment and prognosis. The aim of this study is to evaluate long-term results of liver transplantation in children with unresectable hepatoblastoma. Patients and Methods This is a retrospective review of patients with hepatoblastoma who underwent liver transplantation, analyzing risk factors, tumor presentation, treatment, and long-term survival to identify prognostic factors. Results Thirty-one patients underwent liver transplantation in the context of unresectable hepatoblastoma, mainly males (67%) and with risk factors such as prematurity (12.9%), maternal smoking (6.5%), and familial adenomatous polyposis (3.2%). Most frequent presentation was multifocal PRETEXT III (51.6%) and PRETEXT IV (45.2%), with metastasis at diagnosis in 12.9% and vascular involvement in 54.8%.Twenty-one patients received a living-donor (67.7%) and 10 a cadaveric graft (32.2%), at 31.7 months of age (5–125). Most transplants were primary, and only two were performed as rescue therapy after an attempt of surgical resection of the tumor.Overall survival 1 and 5 years after transplantation were 93.3% ± 4.6% and 86.4% ± 6.3%, respectively. We could not find any statistically significant differences between risk factors, tumor presentation, type of graft, or type of transplant. Conclusion Liver transplantation has increased hepatoblastoma survival in unresectable tumors. Probably due to these good results, we have not been able to find significant prognostic factors in this cohort.

Background Kaposiform hemangioendothelioma (KHE) is a vascular tumor frequently associated with Kasabach–Merritt phenomenon (KMP), characterized by severe thrombocytopenia and consumptive coagulopathy. Visceral involvement in KHE is rare. In our recent experience, sirolimus has shown to be an effective treatment in cutaneous KHE, becoming indeed the treatment of choice in KMP. We report a case of pancreatic KHE associated with KMP and refractory to sirolimus. Case Report A 4-month-old infant is referred for obstructive jaundice (10 mg/dL conjugated bilirubin) secondary to vascular pancreatic tumor. Magnetic resonance (MR) and immunohistochemistry were compatible with KHE, but the tumor was considered unresectable. We initiated sirolimus (0.8 mg/m²/12 h) to treat KMP, and interventional radiology was performed for percutaneous biliary diversion. This procedure prompted KMP (platelets: 51,000/µL). Sirolimus treatment for 7 days showed no effect; therefore, we started our VAT protocol (vincristine/aspirine/ticlopidin) with great response after 10 days (platelets: 3,70,000/µL). Three months later, percutaneous biliary diversion was replaced by a biliary stent. The tumor disappeared leaving fibrosis and dilatation of biliary tract needing hepaticojejunostomy 6 months later. Discussion It is difficult to establish protocols for an unusual presentation of a tumor with different targets. This is a reason collaborative multicenter studies should be performed. Management of obstructive jaundice secondary to a tumor that usually regresses in 10 years is an added challenge; therefore, the management should be led by a multidisciplinary team. Sirolimus treatment in cutaneous KHE has been described as successful in the literature, as well as in our own experience; however, it failed in our first patient with visceral KHE. We need to investigate the different response to pharmacological agents in tumors with similar histopathology, but with visceral involvement.