MRI-based deep learning model for differentiation of hepatic hemangioma and hepatoblastoma in early infancy.

Hepatic hemangioma (HH) and hepatoblastoma (HBL) are common pediatric liver tumors and present with similar clinical manifestations with limited distinguishing value of serum AFP in early infancy. An accurate differentiation diagnostic tool is warranted for optimizing treatments and improving prognosis. The present study aimed to develop an innovative and cost-effective diagnostic tool to differentiate HH and HBL in early infancy using advanced deep learning (DL) techniques. One hundred forty patients ≤4 months old diagnosed as HH or HBL with histological specimens were recruited from two institutions assigned into a training set with cross-validation and a testing set for external validation, respectively. Based on MRI images, imaging diagnoses were interpreted by two radiologists, and imaging-derived radiomic features were extracted by pretrained convolutional neural networks (CNNs)-Xception extractor via DL analysis. A nomogram model was constructed integrating predictive clinical variables, radiologist-based interpretation, and DL features, evaluated comprehensively on diagnostic and calibration accuracy. The DL-based model performed an area under the receiver operating characteristic curve (AUC) of 0.966 for the training cohort and 0.864 for the testing cohort. The radiologist-interpreted differentiation model showed an AUC of 0.837 in the testing cohort. The integrated nomogram model represented an increasing performance with an AUC of 0.887, accuracy of 78.57%, sensitivity of 76.19%, and specificity of 80.95% in the testing cohort. CONCLUSION:  The MRI-based integrated model, a noninvasive preoperative diagnostic tool, yielded favorable efficacy for differentiating HH and HBL in early infancy, which might reduce the patients' costs of repetitive and unnecessary examinations or over-treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05170282. WHAT IS KNOWN: • Hepatic hemangioma (HH) and hepatoblastoma (HBL) are common pediatric liver tumors and present with similar clinical manifestations with limited distinguishing value of serum AFP in early infancy. • Considering the rare incidence of infantile hepatic tumors, the distinguishing accuracy between HBL and HH for cases in early infancy is unsatisfactory for radiologists' recognition solely. WHAT IS NEW: • The MRI-based integrated model, a noninvasive preoperative diagnostic tool yielded favorable efficacy for differentiating HH and HBL in early infancy, which might reduce the patients' costs of repetitive and unnecessary examinations or over-treatment.

Clinical evaluation of transcatheter arterial embolization combined with propranolol orally treatment of infantile hepatic hemangioma.

PURPOSE: To assess the efficacy of transcatheter arterial embolization (TAE) plus propranolol treatment for infantile hepatic hemangioma (IHH). METHODS: A retrospective study of symptomatic IHH and hemodynamic changes in IHH was conducted between 2016 and 2019. RESULTS: There were five boys and seven girls with diffuse lesions (n = 7) and multifocal lesions (n = 5). Hepatomegaly and abdominal distension (n = 6) were the predominant clinical presentations. Seven patients (58.3%) had multiple cutaneous hemangiomas. Pulmonary arterial hypertension, heart failure (n = 4), and hypothyroidism (n = 4) were observed. A total of 17 TAE procedures were performed in 12 IHH cases, with a technical success rate of 100%. All patients received standard propranolol orally, and one patient was orally administered metacortandracin. Two patients died of heart failure and multiple organ dysfunction caused by an enlarged liver. In addition, one patient was not reexamined after discharge. Of the remaining nine children, the average follow-up time was 10.78 months (range 2-28 months), and they all responded well to TAE combined with oral propranolol. CONCLUSION: TAE combined with propranolol is safe and effective for the treatment of IHH, demonstrating low complication rates.

Screening for infantile hepatic hemangioma in patients with cutaneous infantile hemangioma: A multicenter prospective study.

BACKGROUND: Abdominal ultrasonography has been proposed to screen for infantile hepatic hemangioma (IHH) in patients with multiple cutaneous infantile hemangiomas (IHs). OBJECTIVES: The aim of this study was to establish the optimal cutoff point for the number of cutaneous IHs needed to screen for IHH. METHODS: We performed a prospective, multicenter study to screen for IHH in patients younger than 9 months who had multiple cutaneous IHs (n ≥ 3) on ultrasonography. For comparison, a group of patients with 1 or 2 focal cutaneous IHs was also recruited. RESULTS: In total, 676 patients with at least 3 cutaneous IHs and 980 patients with 1 or 2 focal cutaneous IHs were enrolled. Thirty-one patients were found to have IHH. A higher number of cutaneous IHs was associated with an increased risk of IHH (R = 0.973; P < .001). Receiver operating characteristic curve analysis showed that 5 cutaneous IHs was the optimal cutoff point to screen for IHH, with an area under the curve of 0.872 (P < .001; 95% confidence interval, 0.789-0.955). LIMITATIONS: This was an uncontrolled study. CONCLUSIONS: Screening for IHH is recommended in patients younger than 9 months who present with 5 or more cutaneous IHs.

Infantile hepatic hemangioma: current state of the art, controversies, and perspectives.

Infantile hepatic hemangioma (IHH) is a common vascular tumor, distinctive for its perinatal presentation, rapid growth during the first year of life, and subsequent involution. Although they generally follow a benign course, some tumors have been reported to undergo malignant transformation. The diagnosis of IHH is based on patient's medical history, physical examination, and imaging. Moreover, the management of this vascular tumor is based on clinical presentation and includes observational, medical, surgical, and radiological interventional treatment options. The present review presents the currently available data in the literature on the diverse aspects of the terminology, epidemiology, clinical presentation, pathogenesis, diagnosis, indications for surgery, malignant potential, and long-term outcomes of these tumors.Conclusion: No formal guidelines have yet been established for the treatment of these hepatic lesions, and the therapeutic strategies implemented vary widely from simple observation to medical, radiological, and surgical interventions in the prism of multidisciplinary teams.What is Known:• Infantile hepatic hemangioma is the most common benign tumor of the liver in infancy, but despite its benign nature, it can present with life-threatening complications.• The treatment strategies range from simple observation to a series of medical, surgical, and radiological interventions.What is New:• This review gives an overview of the developments and current status about the management of IHH.• The aim of this study is to clear up the confusion and controversy that exists about terminology, diagnosis, and treatment of IHH.

A Case of Consumptive Hypothyroidism in a 1-Month-Old Boy with Diffuse Infantile Hepatic Hemangiomas.

Consumptive hypothyroidism is a rare paraneoplastic syndrome characterized by excessive inactivation of the thyroid hormones due to increased type 3 iodothyronine deiodinase activity of tumors. We report the case of severe consumptive hypothyroidism in a 1-month-old boy with infantile hepatic hemangiomas who presented with cardiac failure and cholestasis. Diffuse infiltration of hepatic hemangiomas was detected on abdominal imaging studies, and thyroid function screening test revealed severe hypothyroidism, which necessitated the administration of higher-than-usual doses of levothyroxine for the normalization of thyroid function. The patient was successfully treated with propranolol, prednisolone, and levothyroxine, and he showed normal thyroid function at 3 months of age and normal neurodevelopment at 9 months of age. This case highlights the importance of early recognition and prompt management of consumptive hypothyroidism in patients with infantile hepatic hemangiomas.

Infantile hepatic hemangiomas associated with high-output cardiac failure and pulmonary hypertension.

BACKGROUND: Infantile hepatic hemangioma (IHH) is a rare endothelial cell neoplasm, which may be concurrent with severe complications and result in poor outcomes. Moreover, the coexistence of IHH and congenial heart disease is even rarer. CASE PRESENTATION: We present a 10-day-old male born with IHH associated with patent ductus arteriosus (PDA), atrial septal defect (ASD) and pulmonary hypertension. Moreover, we reviewed a series of studies of IHH-associated high-output cardiac failure between 1974 and 2018, and summarized the treatment outcomes. CONCLUSIONS: Infantile hepatic hemangioma (IHH) has been known to induce high-output heart failure. There is no literature to summarize the severity of its impact on heart, which can lead to a high mortality rate. When IHH is detected by ultrasound, the heart should be evaluated to facilitate treatment. The outcomes of IHH associated with heart failure are good.

Infantile Hepatic Hemangioma.

Infantile hepatic hemangioma (IHH) historically called "hemangiomaendothelioma" refers to visceral manifestation of infantile hemangioma. The diagnosis of infantile hepatic hemangioma is primarily based on the radiological features. We present a case of 4 month old infant who presented with abdominal distention. Contrast enhanced CT demonstrated typical features of diffuse infantile hepatic hemangiomas.

Critical hepatic hemangioma in infants: recent nationwide survey in Japan.

The International Society for the Study of Vascular Anomalies (ISSVA) classification divides vascular lesions into two major entities: neoplasms originating from the vascular endothelium and vascular malformations. Although this concept has been widely accepted, little has been established regarding vascular lesions in deep organs, such as infantile hepatic hemangioma (IHH). The current nationwide survey identified 19 critical infantile hemangiomas during the most recent 5 years. On histopathology all the lesions examined were neoplastic, but portovenos shunt was found histologically or clinically in some cases. High-output cardiac failure, consumption coagulopathy, and respiratory distress were the major symptoms, and treatment-resistant coagulopathy seemed to be the most reliable predictor of fatal outcome. Although steroid has been the gold standard treatment for these lesions, 25% of the patients were totally insensitive to steroids, whereas propranolol had a prompt effect in one case. For critical IHH with steroid-insensitive thrombocytopenia and prothrombin time prolongation, novel therapeutic options including beta-blocker therapy, surgery, and liver transplantation should be urgently considered as alterative treatment. The present review summarizes the results of the survey.

Diffuse infantile hepatic hemangioma successfully treated with propranolol orally: a case report and literature review.

Background: Infantile hepatic hemangioma (IHH) is a common vascular, fast-growing hepatic tumor that is usually accompanied by multiple cutaneous hemangiomas. Diffuse IHH (DIHH) is a rare type of IHH that exhibits many tumors with nearly complete hepatic parenchymal replacement. At present, there is no specific standardized treatment plan for DIHH. Herein, we present the case of a 2-month-old girl with DIHH and without cutaneous hemangioma who achieved complete remission after undergoing propranolol monotherapy. Case presentation: The infant with low birth weight was presented to the pediatric department with a 2-month history of persistent vomiting and feeding difficulty. Ultrasonography and abdominal magnetic resonance imaging revealed hepatomegaly and diffused intrahepatic lesions. A computed tomography-guided percutaneous liver biopsy was performed, and the pathological examination suggested the diagnosis was DIHH. The patient exhibited remarkably response to an increasing dose of oral propranolol, from 0.5 mg/kg to 2 mg/kg every day. The intrahepatic lesions were almost completely regressed after one year of treatment and no distinct adverse reaction was observed. Conclusion: DIHH can induce life-threatening complications that require prompt interventions. Propranolol monotherapy can be an effective and safe first-line treatment strategy for DIHH.

Clinical features of cutaneous infantile hemangioma combined with asymptomatic infantile hepatic hemangioma and efficacy of propranolol treatment.

INTRODUCTION: Infantile hepatic hemangioma (IHH) is a common liver tumor in infants and shares the same characteristics as cutaneous infantile hemangioma (IH). Propranolol is effective for symptomatic IHH. The clinical features between cutaneous IH and IHH, and treatment efficacy of IHH (smaller than 4 cm) is unclear. To evaluate the correlation of clinical features between cutaneous IH and IHH, as well as efficacy of systemic propranolol in the treatment of cutaneous IH combined with IHH. MATERIALS AND METHODS: The clinical data of infants with complicated cutaneous IH combined with IHH treated with systemic propranolol (1.5 ~ 2 mg/(kg d)) from January 2011 to October 2020 were retrospectively analyzed. RESULTS: Forty-five cases with IHH combined with complicated cutaneous IH were reviewed. Single cutaneous IH is more likely to be combined with focal IHH, cutaneous IH greater than 5, more likely to be combined with multiple IHH (Pearson = 0.546, p < 0.01). The mean age of focal and multiple IHH regression was 11.93 ± 14.42 months and 10.20 ± 9.15 months, respectively. CONCLUSIONS: The number of cutaneous IH were correlated with the number of IHH. There was no difference in the age of complete remission for focal and multiple IHH.

Propranolol Monotherapy in Multifocal/Diffuse Infantile Hepatic Hemangiomas in Indian Children: A Case Series.

Introduction: Infantile hepatic hemangioma (IHH) is the most common benign liver tumor in children, and multifocal and diffuse tumors often become life-threatening, necessitating therapy. Propranolol is now considered the first choice of therapy with ample data in Caucasian children. We present a series of nine Indian children with multifocal (n = 5) and diffuse (n = 4) IHH treated with propranolol monotherapy. Methods: This was a retrospective clinical data-based single-center study. Propranolol was used at a median dose of 3.2 mg/kg/day (range 3-3.3 mg/kg/day) for a median duration of 12 months (range 6-32 months). Results: The presentations of IHH (either in isolation or combination) were hypothyroidism in six patients (diagnosed by elevated serum TSH levels), heart failure in three (diagnosed based on clinical and echocardiographic features), and imaging evidence of macrovascular shunting in two patients. A good response to propranolol monotherapy (with a median dose of 3.2 mg/kg/day for a median duration of 12 months) was observed in eight patients, with a poor response in one. One patient experienced recurrence but responded adequately to propranolol retreatment. Conclusions: Our data reiterate the excellent response (88.9% responded) and safety profile with propranolol monotherapy in complicated IHH and strengthen the data in Asian (Indian) children. It includes the maximum proportion of complicated IHH treated with propranolol in East and South Asia, and the largest series from India.

Coexisting Infantile Hepatic Hemangioma and Hepatoblastoma in a Neonate: A Case Report.

Infantile hepatic hemangioma and hepatoblastoma are the most common benign and malignant tumors of the liver in the neonatal and early childhood periods, respectively. However, the simultaneous occurrence of these 2 tumors in the same liver lesion is very rare. We report a case of a newborn infant diagnosed with a liver mass by ultrasound examination 4 days after birth. Serum alpha-fetoprotein (AFP) was elevated for his age (32,881.7 ng/mL). The liver mass was resected. Macroscopically, an externally protruding mass measuring 6 × 4 × 3.5 cm was identified. Microscopically, we observed the coexistence of infantile hepatic hemangioma and epithelial hepatoblastoma components within the tumor. The infantile hepatic hemangioma component was composed of multiple small vascular channels lined by endothelial cells. In the hepatoblastoma component, tumor cells were arranged in a 2- to 3-cell-thick trabecular formation. Immunohistochemistry indicated that the tumor cells in the infantile hepatic hemangioma component expressed CD34, CD31, FLI1, and ERG, and those in the hepatoblastoma component expressed hepatocyte, keratin AE1/AE3 and keratin 8, glypican 3, glutamine synthetase, and AFP. Pathological examination confirmed the presence of an infantile hepatic hemangioma combined with epithelial hepatoblastoma (fetal type). The boy did not undergo chemotherapy after the operation. Regular follow-up through serum AFP levels and liver ultrasound for 16 months to date show that the serum AFP levels decreased continuously to normal levels, with no signs of tumor recurrence or metastasis. The coexistence of infantile hepatic hemangioma and hepatoblastoma is rare. Hepatoblastoma should be considered in neonates with liver tumors and elevated AFP.

Infantile hepatic hemangiomas: looking backwards and forwards.

Infantile hepatic hemangiomas (IHHs) are common benign tumors seen in the liver of infants. IHHs are true infantile hemangiomas (IHs) and have phases of proliferation and involution parallel to those of cutaneous IHs. The definition and classification of IHH are still confusing in the literature. The mechanisms during the pathogenesis of IHH have yet to be discovered. The clinical manifestations of IHH are heterogeneous. Although most IHH lesions are asymptomatic, some lesions can lead to severe complications, such as hypothyroidism, consumptive coagulopathy, and high-output congestive cardiac failure. Consequently, some patients can possibly encounter a fatal clinical condition. The heterogeneity of the lesions and the occurrence of disease-related comorbidities can make the treatment of IHH challenging. Oral propranolol is emerging as an effective systemic approach to IHH with obvious responses in tumor remission and symptom regression. However, the precise clinical characteristics and treatment strategies for patients with severe IHH have not yet been well established. Here, we summarize the epidemiology, pathogenic mechanism, clinical manifestations, diagnosis, and treatment of IHH. Recent updates and future perspectives for IHH will also be elaborated.

Contrast-Enhanced Ultrasound as a Main Radiological Diagnostic Method for Primary Liver Neoplasms and Hemangiomas.

Contrast-enhanced ultrasound (CEUS) is a relatively new approach for the definitive diagnosis of focal liver lesions (FLL). The essential advantages of CEUS are affordability, absence of radiation, and negligible nephrotoxicity-making this diagnostic approach more preferable. This review includes data from 39 different research studies published during the last 10 years, selected through the MeSH strategy in PubMed. We conclude that CEUS is a promising approach for diagnosing primary liver neoplasms and it is an excellent radiological approach for children and pregnant women because of the absence of radiation and nephrotoxicity. Studies showed that CEUS is a very good approach for the differentiation of a variety of hemangiomas and for a detailed description of those findings. Therefore, CEUS is an important and progressive method for the diagnosis of liver neoplasms. The regular use of CEUS will facilitate the diagnosis of primary liver lesions.

Pediatric Primary Hepatic Tumors: Diagnostic Considerations.

The liver is the third most common site of abdominal tumors in children. This review article aims to summarize current evidence surrounding identification and diagnosis of primary hepatic tumors in the pediatric population based upon clinical presentation, epidemiology, and risk factors as well as classical imaging, histopathological, and molecular diagnostic findings. Readers will be able to recognize the features and distinguish between benign and malignant hepatic tumors within different age groups.

Contrast-Enhanced Ultrasound for the Characterization of Infantile Hepatic Hemangioma in Premature Neonate.

Contrast-enhanced ultrasonography (CEUS) is a relatively new imaging method for use in children. It is recognized as a safe and easily performed problem-solving method. A premature 10-day-old female infant experienced unusual persistent anemia. The diagnostic workup for the anemia included an abdominal ultrasound examination, which showed pathological formation in the left middle quadrant. MRI was used to further asses the lesion and showed a hypervascular lesion with necrotic areas rising from the left hepatic lobe, mainly showing the pattern that indicates an infantile hepatic hemangioma. Main differential diagnosis, hepatoblastoma, could not be excluded. The crucial examination used to differentiate was CEUS.

Combination therapy of propranolol, levothyroxine, and liothyronine was effective in a case of severe consumptive hypothyroidism associated with infantile hepatic hemangioma.

Infantile hepatic hemangioma (IHH) can be accompanied by consumptive hypothyroidism. We report the case of a 4-mo-old boy who showed massive hepatomegaly, peripheral coldness, lethargy, and failure to thrive. An enhanced computed tomography scans demonstrated multiple hemangiomas in both lobes of the liver, and a thyroid function tests showed severe hypothyroidism: TSH 561.5 µIU/mL, free triiodothyronine (fT3) 1.0 pg/mL, and free thyroxine (fT4) < 0.7 ng/dL. IHH gradually regressed following propranolol treatment and fT4 increased to a low normal level (1.0 ng/dL) by high dose replacement of levothyroxine, while fT3 remained very low (< 1.0 pg/mL), even following high doses of levothyroxine; fT3 eventually normalized following the administration of liothyronine. We suggest that treatment strategies should be individualized based on thyroid function, and that the combination therapy of propranolol for anti-tumor treatment and levothyroxine and liothyronine for respective thyroid hormone replacement is effective, particularly in cases of severe consumptive hypothyroidism due to multiple IHHs.

The value of clinical and ultrasound features for the diagnosis of infantile hepatic hemangioma: Comparison with contrast-enhanced CT/MRI.

OBJECTIVES: To investigate the combined use of ultrasound together with clinical features to differentiate infantile hepatic hemangioma (IHH) from other focal liver lesions (FLLs) in children and to compare the efficacy of the combined method to that of CECT/MRI. METHODS: The location, number, size and appearance of the tumors were evaluated in 45 children with IHH. Another 45 children with FLL were randomly selected as a control group. Independent factors for predicting IHH versus FLLs were evaluated. The diagnostic performance of the clinical and ultrasound features was compared with CECT/MRI. RESULTS: Compared with the control FLL group, the IHH group had a younger age at diagnosis (P = 0.008), lower alpha-fetoprotein (AFP) levels (P = 0.000), smaller lesion sizes (P = 0.000), and a higher tumor proportion with a resistance index (RI) of <0.7. Multiple logistic regression analysis showed that age, size, RI and AFP were independent factors for predicting IHH. Receiver operating characteristic (ROC) curve analysis showed that the AUC (area under the curve) of the four combined independent factors was 0.881 (95% CI: 0.744-0.960), while the AUC for the CECT/MRI method was 0.905 (95% CI: 0.774-0.973), and the combined AUC for the independent factors and CECT/MRI was 0.929 (95% CI: 0.805-0.985). There were not statistically significant among the three AUCs (P > 0.05). CONCLUSIONS: CECT/MRI was the effective diagnostic indicator for IHH. However, the combined clinical and ultrasound diagnoses, including age at diagnosis, lesion size, RI and AFP, can achieve the same effectiveness as CECT/MRI.