Risk factors for mortality in patients with multifocal and diffuse hepatic hemangiomas

doi:10.1016/j.jpedsurg.2014.09.056

Journal of Pediatric Surgery

Volume 50, Issue 5, May 2015, Pages 837-841

https://doi.org/10.1016/j.jpedsurg.2014.09.056 Get rights and content

Abstract

Purpose

Multifocal and diffuse hepatic hemangiomas are true infantile hemangiomas, which likely exist in a continuum. We reviewed our hepatic hemangioma registry to identify prognostic indicators for mortality.

Methods

Registry records entered between 1995 and 2012 were reviewed. Clinical characteristics were evaluated for prognostic significance using the multivariable Cox proportional hazards model. Survival data were analyzed using the Kaplan–Meier product–limit method.

Results

We identified 123 patients with multifocal (n = 91) and diffuse (n = 32) hepatic hemangiomas. Mortality was 16% (n = 20); 40% (n = 8) had multifocal and 60% (n = 12) had diffuse lesions. A diagnosis of diffuse disease (hazard ratio: 9.9, 95% CI: 2.0–50.8, P = .002) and congestive heart failure (CHF) (hazard ratio: 3.9, 95% CI: 1.3–14.2, P = .031) were significant risk factors for mortality across the continuum; age at presentation, cardiomegaly, presence of shunts, and hypothyroidism were not statistically significant independent risk factors. Among patients with diffuse lesions, eight (67%) who died had abdominal compartment syndrome, which was also associated with mortality (P = .002).

Conclusions

Hepatic hemangioma patients with CHF or diffuse disease are at higher risk for mortality. Patients with multifocal lesions without CHF may go undetected until lesions become diffuse. Aggressive treatment of symptomatic patients and close follow-up of asymptomatic patients may improve mortality.

Section snippets

Study population

With approval of the Committee on Clinical Investigation, our Vascular Anomalies Center database and online registry (www.liverhemangioma.org) were reviewed for all patients with HH entered from 1995 to 2012. All patients with clinical history and radiographic imaging consistent with multifocal and diffuse HH were included. Multifocal HH were characterized as multiple lesions with intervening segments of normal hepatic parenchyma, while diffuse HH were characterized as extensive hepatic

Results

A total of 205 patients with hepatic hemangioma were identified. Of these, 123 patients had multifocal (n = 91) or diffuse (n = 32) hepatic hemangiomas. Fifty-two patients (42%) were evaluated at our institution. The majority (65%) were female. The median age of presentation was 49 days (interquartile range (IQR) 14–98 days). Cutaneous lesions were present in 74% of patients for which these data were available (n = 90/121). Anemia and thrombocytopenia were present in 40% (n = 34/86) and 18% (n = 15/84),

Discussion

Hepatic hemangiomas are benign vascular neoplasms that often resolve without sequelae. We have previously described a classification scheme and treatment algorithm involving three categories of lesions: focal, multifocal, and diffuse [1]. This classification system was validated by an interim analysis of our database and online registry [3]. Multifocal and diffuse HH are usually not detectable at birth. Patients typically present within the first few weeks of life as lesions proliferate.

Acknowledgments

Dr. Rialon is supported by the Stuart and Jane Weitzman Fellowship in Vascular Anomalies.

References (29)

R.L. Meyers
Tumors of the liver in children
Surg Oncol
(2007)
A.M. Kulungowski et al.
Lessons from a liver hemangioma registry: subtype classification
J Pediatr Surg
(2012)
M. Davenport et al.
Hemangioendothelioma of the liver in infants
J Pediatr Surg
(1995)
L.M. Boon et al.
Hepatic vascular anomalies in infancy: a twenty-seven-year experience
J Pediatr
(1996)
R.C. Cohen et al.
Diagnosis and management of massive hepatic hemangiomas in childhood
J Pediatr Surg
(1986)
J. Mazereeuw-Hautier et al.
Efficacy of propranolol in hepatic infantile hemangiomas with diffuse neonatal hemangiomatosis
J Pediatr
(2010)
S. Warmann et al.
Interventional treatment of infantile hepatic hemangioendothelioma
J Pediatr Surg
(2003)
J.A. Hughes et al.
Cutaneous haemangioma: prevalence and sonographic characteristics of associated hepatic haemangioma
Clin Radiol
(2004)
B. Dickie et al.
Spectrum of hepatic hemangiomas: management and outcome
J Pediatr Surg
(2009)
E.R. Christison-Lagay et al.
Hepatic hemangiomas: subtype classification and development of a clinical practice algorithm and registry
J Pediatr Surg
(2007)

J.A. Daller et al.

Hepatic hemangioendothelioma: clinical experience and management strategy

J Pediatr Surg

(1999)

W. Zenzen et al.

Hepatic failure in a rapidly involuting congenital hemangioma of the liver: failure of embolotherapy

Pediatr Radiol

(2009)

E. Grabhorn et al.

Neonates with severe infantile hepatic hemangioendothelioma: limitations of liver transplantation

Pediatr Transplant

(2009)

A. Kassarjian et al.

Angiographic classification of hepatic hemangiomas in infants

Radiology

(2002)

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Independent ArticleRisk factors for mortality in patients with multifocal and diffuse hepatic hemangiomas

Abstract

Purpose

Methods

Results

Conclusions

Section snippets

Study population

Results

Discussion

Acknowledgments

Surg Oncol

J Pediatr Surg

J Pediatr Surg

J Pediatr

J Pediatr Surg

J Pediatr

J Pediatr Surg

Clin Radiol

J Pediatr Surg

Hepatic hemangiomas: subtype classification and development of a clinical practice algorithm and registry

J Pediatr Surg

Hepatic hemangioendothelioma: clinical experience and management strategy

J Pediatr Surg

Hepatic failure in a rapidly involuting congenital hemangioma of the liver: failure of embolotherapy

Pediatr Radiol

Neonates with severe infantile hepatic hemangioendothelioma: limitations of liver transplantation

Pediatr Transplant

Angiographic classification of hepatic hemangiomas in infants

Radiology

Independent Article
Risk factors for mortality in patients with multifocal and diffuse hepatic hemangiomas