Not only an antihypertensive Not only an antihypertensive but also …!!but also …!!

Department of Pediatrics and Department of Pediatrics and Haemato Oncology Haemato Oncology

SRMC UNIT IV SRMC UNIT IV

HISTORYHISTORY

Preterm (36 weeks)/LSCS/ Girl babyPreterm (36 weeks)/LSCS/ Girl baby Referred on first day of life Referred on first day of life

Antenatal USG(mediscans) at 35 weeksAntenatal USG(mediscans) at 35 weeks

(6.4 x 4.9 x 4.8cm) - hypoechoeic (6.4 x 4.9 x 4.8cm) - hypoechoeic

multiloculated cystic mass with increased multiloculated cystic mass with increased

vascularityvascularity in liver - Hepatic vascular mass in liver - Hepatic vascular mass

Examination on 1Examination on 1stst day of life day of life

Wt- 2.25kg, Length 46cm, HC 33 cmWt- 2.25kg, Length 46cm, HC 33 cm

Liver 2cm below RCM Liver 2cm below RCM

No pallor/petechiae/cutaneous haemangiomaNo pallor/petechiae/cutaneous haemangioma

No features of respiratory distress/ CCFNo features of respiratory distress/ CCF

Imaging on 1Imaging on 1stst day of life day of life

USG abdomen USG abdomen

Large multiloculated mixed echoic lesion (5.5 X Large multiloculated mixed echoic lesion (5.5 X 3cms) in the left lobe of liver3cms) in the left lobe of liver

Colour DopplerColour Doppler

continuous flow with dilated vesselscontinuous flow with dilated vessels,, suggestive suggestive of of hemangiomahemangioma of liverof liver. .

OTHER INVESTIGATIONSOTHER INVESTIGATIONS

D Dimer NormalD Dimer Normal Fibrinogen 119 mg/dl Fibrinogen 119 mg/dl

(175-300) (175-300) LFT normalLFT normal T4 TSH normalT4 TSH normal

HBHB 17.417.4

TCTC 99509950

DCDC P46 L46P46 L46PLATELETPLATELET 90,00090,000

PTPT 24.3(14.3)24.3(14.3)

PTTPTT 54.9(29.9)54.9(29.9)

INRINR 1.871.87

TREATMENTTREATMENT

Prednisolone started at Prednisolone started at 3mg/kg/day3mg/kg/day

11stst month of age month of age

Platelet count- 2.72 lakhs/cumm Platelet count- 2.72 lakhs/cumm

USG abdomen USG abdomen 3.3 x 2.7cm size 3.3 x 2.7cm size reduction in size of tumor reduction in size of tumor when compared to previous scanwhen compared to previous scan

Steroid continued at same dose Steroid continued at same dose

2nd month of age2nd month of age

USG abdomen USG abdomen

- 4.6 x 3.2 cm size - 4.6 x 3.2 cm size

- Mild increase in size of tumor- Mild increase in size of tumor

compared to USG at one month.compared to USG at one month.

Prednisolone continued at same dosePrednisolone continued at same dose

2nd month of age2nd month of age

Leaute – Labreze C et al* study on effect of Leaute – Labreze C et al* study on effect of propanolol in 11 children with cutaneous propanolol in 11 children with cutaneous hemangioma.hemangioma.

Oral Propranolol started at 1mg/kg/day increased to 2 Oral Propranolol started at 1mg/kg/day increased to 2 mg /Kg/day in addition to steroid.mg /Kg/day in addition to steroid.

Monitored for 48 hours for hypoglycemia, Monitored for 48 hours for hypoglycemia, bradycardia and hypotension. bradycardia and hypotension.

**Leaute – Labreze C, Dumas dela Roque E, Hubiche T, et al Propranolol Leaute – Labreze C, Dumas dela Roque E, Hubiche T, et al Propranolol for severe hemangiomas of infancy. N Engl J Med 2008; 358:2649-2651for severe hemangiomas of infancy. N Engl J Med 2008; 358:2649-2651

3rd Month of age3rd Month of age

USG abdomen USG abdomen

- 4.1 x 2.7cm size - 4.1 x 2.7cm size

- Slight reduction in size, - Slight reduction in size,

- More cystic areas seen.- More cystic areas seen.

Both drugs continued at same doseBoth drugs continued at same dose

Imaging at 3Imaging at 3rdrd month of age month of age

4th Month of age4th Month of age

Platelet count - 3.82 Lakhs/cumm Platelet count - 3.82 Lakhs/cumm

USG abdomen- USG abdomen- DID NOT REVEAL ANY LESIONDID NOT REVEAL ANY LESION

Prednisolone tapered to 1mg/kg/day Prednisolone tapered to 1mg/kg/day Propranolol continued at 2mg/kg/dayPropranolol continued at 2mg/kg/day

On follow upOn follow up

Imaging at 4 months of ageImaging at 4 months of age

SUM UPSUM UPAGEAGE Platelet Platelet

Lakths/cummLakths/cumm

USG abd size of USG abd size of mass CMSmass CMS

MANAGEMENTMANAGEMENT

newbornnewborn 90,00090,000 5.5 x 35.5 x 3 predinisolonepredinisolone 3mg/kg/day3mg/kg/day

11stst month month 2.722.72 3.3 x 2.73.3 x 2.7 steroids at same steroids at same dosedose

22ndnd month month __ 4.6 x 3.24.6 x 3.2 Propranolol added Propranolol added 2mg/kg/day2mg/kg/day

33rdrd month month __ 4.1 x 2.74.1 x 2.7 Continued both drugs Continued both drugs at same doseat same dose

44thth month month 3.823.82 No lesionNo lesion Prednisolone Prednisolone 1mg/kg/day1mg/kg/day propranolol propranolol 2mg/kg/day2mg/kg/day

Infantile Hepatic HemangiomasInfantile Hepatic Hemangiomas

Third most common tumor of the liver in Third most common tumor of the liver in childhood childhood

Exhibits rapid post natal growth followed by Exhibits rapid post natal growth followed by slow involutionslow involution

Female predilection 2:1Female predilection 2:1 Most are asymptomatic - incidentally Most are asymptomatic - incidentally

discovered on imaging studies. discovered on imaging studies.

Symptomatic HemangiomasSymptomatic Hemangiomas

Abdominal distensionAbdominal distension Cutaneous hemangiomasCutaneous hemangiomas High output cardiac failureHigh output cardiac failure Thrombocytopenia (Thrombocytopenia (Kasabach Merritt Kasabach Merritt

syndrome) syndrome) Consumptive coagulopathyConsumptive coagulopathy Hypothyroidism Hypothyroidism Fulminant hepatic failureFulminant hepatic failure

Management of hepatic Management of hepatic Hemangiomas Hemangiomas

High dose corticosteroids (3 to 5mg/kg/day) are still first High dose corticosteroids (3 to 5mg/kg/day) are still first line of therapy.line of therapy.

Anti neoplastic drugs-Vincristine,Cyclophosphamide. Anti neoplastic drugs-Vincristine,Cyclophosphamide.

Alpha interferon - 50% regression of lesion but 20% Alpha interferon - 50% regression of lesion but 20% incidence of spastic diplegia.incidence of spastic diplegia.

Surgical excision or selective hepatic artery Surgical excision or selective hepatic artery embolization . embolization .

Propranolol - newer promising Propranolol - newer promising therapy therapy

Le’aute’ – Labre’ze et al* studyLe’aute’ – Labre’ze et al* study Effect of propranolol in 11 children with Effect of propranolol in 11 children with

cutaneous capillary hemangioma. cutaneous capillary hemangioma.

Significant reduction in the size of Significant reduction in the size of hemangiomashemangiomas

No regrowth even after stopping prednisoloneNo regrowth even after stopping prednisolone

* * Leaute – Labreze C, Dumas dela Roque E, Hubiche T, et al. Propranolol for Leaute – Labreze C, Dumas dela Roque E, Hubiche T, et al. Propranolol for

severe hemangiomas of infancysevere hemangiomas of infancy N Engl J Med 2008; 358:2649-2651 N Engl J Med 2008; 358:2649-2651

How Propanolol works in How Propanolol works in Hemangiomas?Hemangiomas?

Vasoconstriction.Vasoconstriction.

*Decreased expression of pro-angiogenic factors basic *Decreased expression of pro-angiogenic factors basic Fibroblast growth factor(bFGF) & vascular Fibroblast growth factor(bFGF) & vascular endothelial growth factor(vEGF) -stimulants endothelial growth factor(vEGF) -stimulants for the proliferation and division of endothelial and for the proliferation and division of endothelial and interstitial cells.interstitial cells.

**Triggering of apoptosis of capillary endothelium.**Triggering of apoptosis of capillary endothelium.

*D’Angelo G, Lee H, Weiner RI., J Cell Biochem 1997; 67:353-366.*D’Angelo G, Lee H, Weiner RI., J Cell Biochem 1997; 67:353-366.

**Sommers Smith SK, Smith DM. In Vitro Cell Dev Biol Anim 2002; 38:298-**Sommers Smith SK, Smith DM. In Vitro Cell Dev Biol Anim 2002; 38:298-

304304..

Side Effects of PropanololSide Effects of Propanolol

Bradycardia,Hypotension,Blunting the clinical signs Bradycardia,Hypotension,Blunting the clinical signs of cardiac failure and hypoglycemiaof cardiac failure and hypoglycemia

*Can be avoided by monitoring sugar levels and *Can be avoided by monitoring sugar levels and vitals / increasing the propranolol dose in increments vitals / increasing the propranolol dose in increments

**Siefgried EC, Siefgried EC,

Keenan WJ, Al-Jureidini S, Propranolol for severe hemangiomas of infancyKeenan WJ, Al-Jureidini S, Propranolol for severe hemangiomas of infancy N N Engl J Med 2008; 359:2847Engl J Med 2008; 359:2847

Propranolol inPropranolol in Hepatic HemangiomaHepatic Hemangioma

Alberto Mansciani et al* studied effect of Propanolol in Alberto Mansciani et al* studied effect of Propanolol in an Infant with massive hepatic hemangiomaan Infant with massive hepatic hemangioma

Started on high dose steroid ,vincristine and Started on high dose steroid ,vincristine and cyclophosphamide- No responsecyclophosphamide- No response

Marked reduction of hepatic lesions following starting Marked reduction of hepatic lesions following starting propranololpropranolol

**Alberto Marciani, Roberta Pericoli Rita – Alaggio et al, - Paediatric Blood Cancer Alberto Marciani, Roberta Pericoli Rita – Alaggio et al, - Paediatric Blood Cancer

2010; 54:1762010; 54:176

CONCLUSIONCONCLUSION

Our case, showed a similar dramatic response Our case, showed a similar dramatic response disappearance of the hepatic lesion after disappearance of the hepatic lesion after starting propranolol therapy.starting propranolol therapy.

Reinforces the promising therapeutic option of Reinforces the promising therapeutic option of propranolol in the treatment of infantile propranolol in the treatment of infantile hepatic hemangioma. hepatic hemangioma.

ACKNOWLEDGEMENTSACKNOWLEDGEMENTS

Dr VENKATASAIDr VENKATASAI

Prof of RadiologyProf of Radiology

Dr Binu NinanDr Binu Ninan

Prof of neonatology Prof of neonatology

SRMCSRMC

THANK YOU