Hemangiomas are the most common benign tumors of the liver. They are generally asymptomatic, but giant hemangiomas can lead to abdominal discomfort, bleeding, or obstructive symptoms. Kasabach-Merritt syndrome is a rare but life-threatening complication of hemangioma, characterized by consumptive coagulopathy with large vascular tumors. More than 80% of Kasabach-Merritt syndrome cases occur within the first year of life. However, there are few reports of Kasabach-Merritt syndrome with giant hepatic hemangioma in adults and, as far as we know, no reports of Kasabach-Merritt syndrome with hepatic hemangioma treated with first line medical treatment only. The most important treatment for this syndrome is removal of the large vascular tumor. However, surgical treatment entails risk of bleeding, and the patient's condition can mitigate against surgery. We herein present a case of unresectable giant hepatic hemangioma with disseminated intravascular coagulopathy. The patient was a 60-year-old woman who complained of hematochezia, ecchymosis, and abdominal distension. She refused all surgical management and was therefore treated with systemic glucocorticoids and beta-blockers. After two weeks of steroid therapy, she responded partially to the treatment. Her laboratory findings and hematochezia improved. She was discharged on hospital day 33 and observed without signs of bleeding for three months.
Abdomen/diagnostic imaging ; Ecchymosis/etiology ; Female ; Gastrointestinal Hemorrhage/etiology ; Hemangioma/complications/*diagnosis ; Humans ; Kasabach-Merritt Syndrome/complications/*diagnosis/drug therapy ; Middle Aged ; Prednisone/therapeutic use ; Propranolol/therapeutic use ; Tomography, X-Ray Computed

OBJECTIVETo investigate the effects of oral administration of low-dose propranolol on heart rate variability (HRV), acceleration capacity (AC), deceleration capacity (DC), and cardiac conduction in the treatment of infantile hemangioma.

METHODSA total of 118 infants with hemangioma (≤1 year) were enrolled, and 24-hour ambulatory electrocardiography was performed before oral administration of low-dose propranolol and after one month of administration. The changes in time-domain indices [standard deviation of all normal sinus RR intervals (SDNN), standard deviation of all mean 5-minute RR intervals (SDANN), root mean squared successive difference (RMSSD), and percentage of successive normal sinus RR intervals >50 ms (PNN50)] and frequency-domain indices [low frequency (LF) and high frequency (HF)] for HRV, AC, and DC were observed, as well as abnormalities in cardiac conduction and other aspects after administration of propranolol.

RESULTSAfter administration of propranolol, the infants had significantly increased SDNN, RMSSD, LF, HF, and PNN50 (P<0.01), and significantly reduced AC, mean heart rate (HR) and minimum HR (P<0.01). The 24-hour ambulatory electrocardiographic findings showed a nonsignificantly higher abnormal rate after administration of propranolol.

CONCLUSIONSIn the treatment of infantile hemangioma, propranolol can inhibit the activity of sympathetic nerve and block cardiac conduction, but without any serious adverse effect.

Administration, Oral ; Electrocardiography ; drug effects ; Female ; Heart Rate ; drug effects ; Hemangioma ; drug therapy ; physiopathology ; Humans ; Infant ; Male ; Propranolol ; pharmacology ; therapeutic use

OBJECTIVETo investigate whether propranolol application as collyrium or intraperitoneal (IP) injection can promote the recovery of oxygen-induced retinopathy (OIR).

METHODThirty-six 7-day-old mice were divided into the following 6 groups: normal control, propranolol eye drops, propranolol IP injection, eye drops negative control, IP injection negative control, and pathological model with 6 mice in each. In a typical model of OIR, litters of mice pups with their nursing mothers were exposed to an infant incubator to high oxygen concentration (75 ± 5)% between postnatal day (PD) 7 and PD12, prior to returning to room air. Two routes of propranolol treatment were assessed from PD12 to PD17: IP injection and eye drop, with doses 2 mg/(kg·time), three times a day. Another three groups were given citric acid buffer eye drops, IP injection of citric acid buffer, and negative control were not treated with any drug. Neonatal mice fed in normal conditions served as normal control. Mice were sacrificed at PD17 to evaluate the morphological changes of retinal vessels by fluorescein isothiocyanate-dextran perfusion and retinal whole mount. The retinal neovascularization was evaluated by counting the number of nuclei of the endothelial cell breaking through the internal limiting membrane (ILM).

RESULTCompared with the oxygen-exposed group, the branches of retinal vessels went normal with a less un-perfused area in the propranolol eye drops and propranolol IP injection groups [(38.9 ± 9.9)% and (5.6 ± 2.3)% vs. (16.2 ± 10.0)% and (2.2 ± 0.8)%, (25.9 ± 5.0)% and (2.1 ± 2.7)%, F=36.12 and 14.55, P both<0.001]. The number of nuclei of endothelial cells breaking through the ILM on the retinal cross-section in the propranolol eye drops group decreased (14.2 ± 5.1) per slide, which was less than that in the oxygen-exposed group (49.1 ± 8.9) per slide and the propranolol IP injection group (18.0 ± 5.9) per slide; it was also less than that in the eye drops negative control group (47.4 ± 8.1) per slide (F=187.60, P<0.05). Moreover, the number of nuclei of endothelial cells breaking through the ILM on the retinal cross-section in the propranolol IP injection group was less than that in the IP injection negative control group (49.9 ± 7.1) per slide (P<0.05).

CONCLUSIONPropranolol could effectively inhibit the formation of retinal neovascularization in mice; the eye drops was more effective than the IP injection.

Animals ; Dextrans ; Disease Models, Animal ; Endothelial Cells ; Fluorescein-5-isothiocyanate ; analogs & derivatives ; Injections, Intraperitoneal ; Mice ; Ophthalmic Solutions ; Oxygen ; adverse effects ; Propranolol ; therapeutic use ; Retina ; drug effects ; Retinal Neovascularization ; chemically induced ; drug therapy ; prevention & control ; Retinal Vessels ; drug effects

The effect of topical propranolol gel on the levels of plasma renin, angiotensin II (ATII) and vascular endothelial growth factor (VEGF) in superficial infantile hemangiomas (IHs) was investigated. Thirty-three consecutive children with superficial IHs were observed pre-treatment, 1 and 3 months after application of topical propranolol gel for the levels of plasma renin, ATII and VEGF in Department of General Surgery of Dongfang Hospital from February 2013 to February 2014. The plasma results of IHs were compared with those of 30 healthy infants of the same age from out-patient department. The clinical efficiency of topical propranolol gel at 1st, and 3rd month after application was 45%, and 82% respectively. The levels of plasma renin, ATII and VEGF in patients pre-treatment were higher than those in healthy infants (565.86 ± 49.66 vs. 18.19 ± 3.56, 3.20 ± 0.39 vs 0.30 ± 0.03, and 362.16 ± 27.29 vs. 85.63 ± 8.14, P < 0.05). The concentrations of VEGF and renin at 1st and 3rd month after treatment were decreased obviously as compared with those pre-treatment (271.51 ± 18.59 vs. 362.16 ± 27.29, and 405.18 ± 42.52 vs. 565.86 ± 49.66 P < 0.05; 240.80 ± 19.89 vs. 362.16 ± 27.29, and 325.90 ± 35.78 vs. 565.86 ± 49.66, P < 0.05, respectively), but the levels of plasma ATII declined slightly (2.96 ± 0.37 vs. 3.20 ± 0.39, and 2.47 ± 0.27 vs. 3.20 ± 0.39, P > 0.05). It was indicated that the increased renin, ATII and VEGF might play a role in the onset or development of IHs. Propranolol gel may suppress the proliferation of IHs by reducing VEGF.
Administration, Cutaneous ; Adrenergic beta-Antagonists ; therapeutic use ; Angiotensin II ; blood ; Case-Control Studies ; Female ; Gels ; Hemangioma, Capillary ; blood ; blood supply ; drug therapy ; pathology ; Humans ; Infant ; Infant, Newborn ; Male ; Propranolol ; therapeutic use ; Renin ; blood ; Skin Neoplasms ; blood ; blood supply ; drug therapy ; pathology ; Treatment Outcome ; Vascular Endothelial Growth Factor A ; blood

Humans ; Infant, Newborn ; Infant, Premature ; Propranolol ; therapeutic use ; Retinopathy of Prematurity ; drug therapy

OBJECTIVE: In this study, there was an investigation as to whether there is a functional difference in essential tremor (ET), according to responses to beta-blockers, by evaluating regional changes in cerebral glucose metabolism. MATERIALS AND METHODS: Seventeen male patients with ET were recruited and categorized into two groups: 8 that responded to medical therapy (group A); and 9 that did not respond to medical therapy (group B). Eleven age-sex matched healthy control male subjects were also included in this study. All subjects underwent F-18 fluorodeoxyglucose (FDG)-PET, and evaluated for their severity of tremor symptoms, which were measured as a score on the Fahn-Tolosa-Marin tremor rating scale (FTM). The FDG-PET images were analyzed using a statistical parametric mapping program. RESULTS: The mean FTM score 6 months after the initiation of propranolol therapy was significantly lower in group A (18.13 > 8.13), compared with group B (14.67 = 14.67). The glucose metabolism in group A in the left basal ganglia was seen to be decreased, compared with group B. The ET showed a more significantly decreased glucose metabolism in both the fronto-temporo-occipital lobes, precuneus of right parietal lobe, and both cerebellums compared with the healthy controls. CONCLUSION: Essential tremor is caused by electrophysiological disturbances within the cortical-cerebellar networks and degenerative process of the cerebellum. Furthermore, ET may have different pathophysiologies in terms of the origin of disease according to the response to first-line therapy.
Adrenergic beta-Antagonists/*pharmacology/therapeutic use ; Aged ; Brain/*drug effects/metabolism/radiography ; Brain Mapping ; Essential Tremor/*diagnosis/drug therapy/radiography ; Fluorodeoxyglucose F18/*chemistry ; Glucose/*metabolism ; Humans ; Male ; Middle Aged ; *Positron-Emission Tomography ; Propranolol/pharmacology/therapeutic use ; Radiopharmaceuticals/*chemistry

BACKGROUND/AIMS: Angiotensin receptor blockers (ARBs) inhibit activated hepatic stellate cell contraction and are thought to reduce the dynamic portion of intrahepatic resistance. This study compared the effects of combined treatment using the ARB candesartan and propranolol versus propranolol monotherapy on portal pressure in patients with cirrhosis in a prospective, randomized controlled trial. METHODS: Between January 2008 and July 2009, 53 cirrhotic patients with clinically significant portal hypertension were randomized to receive either candesartan and propranolol combination therapy (26 patients) or propranolol monotherapy (27 patients). Before and 3 months after the administration of the planned medication, the hepatic venous pressure gradient (HVPG) was assessed in both groups. The dose of propranolol was subsequently increased from 20 mg bid until the target heart rate was reached, and the candesartan dose was fixed at 8 mg qd. The primary endpoint was the HVPG response rate; patients with an HVPG reduction of >20% of the baseline value or to <12 mmHg were defined as responders. RESULTS: The mean portal pressure declined significantly in both groups, from 16 mmHg (range, 12-28 mmHg) to 13.5 mmHg (range, 6-20 mmHg) in the combination group (P<0.05), and from 17 mmHg (range, 12-27 mmHg) to 14 mmHg (range, 7-25 mmHg) in the propranolol monotherapy group (P<0.05). However, the medication-induced pressure reduction did not differ significantly between the two groups [3.5 mmHg (range, -3-11 mmHg) vs. 3 mmHg (range, -8-10 mmHg), P=0.674]. The response rate (55.6% vs. 61.5%, P=0.435) and the reductions in mean blood pressure or heart rate also did not differ significantly between the combination and monotherapy groups. CONCLUSIONS: The addition of candesartan (an ARB) to propranolol confers no benefit relative to classical propranolol monotherapy for the treatment of portal hypertension, and is thus not recommended.
Adolescent ; Adult ; Aged ; Antihypertensive Agents/*therapeutic use ; Benzimidazoles/*therapeutic use ; Blood Pressure ; Drug Therapy, Combination ; Female ; Humans ; Hypertension, Portal/complications/*drug therapy ; Liver Cirrhosis/complications/diagnosis ; Male ; Middle Aged ; Propranolol/*therapeutic use ; Prospective Studies ; Tetrazoles/*therapeutic use ; Treatment Outcome ; Young Adult

BACKGROUND/AIMS: To investigate the efficacy and longterm outcome of esophageal variceal ligation (EVL) plus propranolol in comparison with propranolol alone for the primary prophylaxis of esophageal variceal bleeding. METHODS: A total of 504 patients were retrospectively enrolled in this study. 330 patients were in propranolol group (Gr1) and 174 patients were in EVL plus propranolol group (Gr2). The endpoints of this study were esophageal variceal bleeding and mortality. Association analyses were performed to evaluate bleeding and mortality between Gr1 and Gr2. RESULTS: EVL was more applied in patients with high risk, such as large-sized varices (F2 or F3) or positive red color signs. Total 38 patients had bleeds, 32 in Gr1 and 6 in Gr2. The cumulative probability of bleeding at 120 months was 13% in Gr1 versus 4% in Gr2 (P=0.04). The predictive factors of variceal bleeding were red color signs (OR 2.962, P=0.007) and the method of propranolol plus EVL (OR 0.160, P=0.000). 20 patients died in Gr1 and 12 in Gr2. Mortality rates are similar in the two groups compared, 6.7% in Gr1 and 6.9% in Gr2. The cumulative probability of mortality at 120 months was not significantly different in the two groups (7% in Gr1, 12% in Gr2, P=0.798). The prognostic factors for mortality were age over 50 (OR 5.496, P=0.002), Child-Pugh class B (OR 3.979, P=0.001), and Child-Pugh class C (OR 10.861, P=0.000). CONCLUSIONS: EVL plus propranolol is more effective than propranolol alone in the prevention of the first variceal bleeding in patients with liver cirrhosis.
Adrenergic beta-Antagonists/*therapeutic use ; Adult ; Aged ; Esophageal and Gastric Varices/*pathology ; Female ; Follow-Up Studies ; Gastrointestinal Hemorrhage/*drug therapy/mortality/surgery ; Humans ; Ligation ; Liver Cirrhosis/etiology ; Logistic Models ; Male ; Middle Aged ; Odds Ratio ; Proportional Hazards Models ; Propranolol/*therapeutic use ; Retrospective Studies ; Severity of Illness Index ; Survival Rate

BACKGROUND/AIMS: The most appropriate treatment for acute gastric variceal bleeding (GVB) is currently endoscopic gastric variceal obturation (GVO) using Histoacryl(R). However, the secondary prophylactic efficacy of beta-blocker (BB) after GVO for the first acute episode of GVB has not yet been established. The secondary prophylactic efficacy of BB after GVO for the first acute episode of GVB was evaluated in this study. METHODS: Ninety-three patients at Soonchunhyang University Hospital with acute GVB who received GVO using Histoacryl(R) were enrolled between June 2001 and March 2010. Among these, 42 patients underwent GVO alone (GVO group) and 51 patients underwent GVO with adjuvant BB therapy (GVO+BB group). This study was intended for patients in whom a desired heart rate was reached. The rates of rebleeding-free survival and overall survival were calculated for the two study groups using Kaplan-Meyer analysis and Cox's proportional-hazards model. RESULTS: The follow-up period after the initial eradication of gastric varices was 18.14+/-25.22 months (mean+/-SD). During the follow-up period, rebleeding occurred in 10 (23.8%) and 21 (41.2%) GVO and GVO+BB patients, respectively, and 39 patients died [23 (54.8%) in the GVO group and 16 (31.4%) in the GVO+BB group]. The mean rebleeding-free survival time did not differ significantly between the GVO and GVO+BB groups (65.40 and 37.40 months, respectively; P=0.774), whereas the mean overall survival time did differ (52.54 and 72.65 months, respectively; P=0.036). CONCLUSIONS: Adjuvant BB therapy after GVO using Histoacryl(R) for the first acute episode of GVB could decrease the mortality rate relative to GVO alone. However, adjuvant BB therapy afforded no benefit for the secondary prevention of rebleeding in GV.
Adrenergic beta-Antagonists/*therapeutic use ; Adult ; Aged ; Enbucrilate/therapeutic use ; Endoscopy, Digestive System ; Esophageal and Gastric Varices/*drug therapy ; Female ; Follow-Up Studies ; Gastrointestinal Hemorrhage/mortality/*therapy ; Heart Rate ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Proportional Hazards Models ; Propranolol/therapeutic use ; Risk Factors ; Severity of Illness Index

Antineoplastic Agents ; therapeutic use ; Child, Preschool ; Facial Neoplasms ; drug therapy ; Female ; Follow-Up Studies ; Forearm ; pathology ; Hand ; pathology ; Hemangioma ; drug therapy ; Humans ; Infant ; Male ; Propranolol ; therapeutic use ; Skin Neoplasms ; drug therapy ; Wrist ; pathology