Embolization, Therapeutic ; Hepatic Encephalopathy/therapy* ; Humans ; Telangiectasia, Hereditary Hemorrhagic/therapy*

Hereditary hemorrhagic telangiectasia (HHT, also called Osler-Weber-Rendu Disease) is a rare systemic fibrovascular dysplasia characterized by recurrent epistaxis, cutaneous telangiectasia, and visceral arteriovenous malformations (AVMs). HHT is an autosomal dominant disease with a prevalence of 1 in 5,000~8,000. Recurrent epistaxis is often the first and most common manifestation, and about 30% of patients reveal pulmonary AVM. Presently, we report a familial case of HHT. A 61-year-old male with asymptomatic multiple pulmonary AVMs was successfully treated with embolization. His older brother who presented with recurrent epistaxis and multiple telangiectasias was treated with laser ablation. Their pedigree revealed a family history of recurrent epistaxis.
Arteriovenous Malformations ; Epistaxis ; Humans ; Laser Therapy ; Male ; Middle Aged ; Pedigree ; Prevalence ; Siblings ; Telangiectasia, Hereditary Hemorrhagic ; Telangiectasis

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder that leads to mucocutaneous telangiectasias, epistaxis, and gastrointestinal bleeding. Depending on the severity and manifestation of the disease, various therapeutic modalities have been used, from local bleeding control to surgery or concomitant drug therapy. Several articles under review have presented guidelines for treatment of HHT with bevacizumab as a direct anti-angiogenesis strategy. Still, neither the exact optimal dose nor the minimum effective dose of intravenous bevacizumab in patients with severe HHT has been reported. A 55-year-old man presented with long-standing epistaxis, recent melena, dizziness, and a three-generation family history of chronic epistaxis, anemia, and regular blood transfusions. Treatment with argon plasma coagulation (APC) for the gastrointestinal bleeding failed to raise hemoglobin levels, we considered using the bevacizumab. We report a patient with severe HHT, who was treated with low-dose bevacizumab (2 mg/kg) and improved substantially.
Anemia ; Argon Plasma Coagulation ; Blood Transfusion ; Dizziness ; Drug Therapy ; Epistaxis ; Hemorrhage ; Humans ; Melena ; Middle Aged ; Telangiectasia, Hereditary Hemorrhagic* ; Telangiectasis ; Bevacizumab

OBJECTIVES: Hereditary hemorrhagic telangiectasia (HHT) is characterized by the presence of vascular malformations with an absence of capillaries between arteries and veins. One major manifestation site is the nasal mucous membrane where recurrent nosebleeds occur. Our clinical strategy to treat patients with HHT has the aim to reduce nasal bleeding long-term with minimal local and general side effects. METHODS: We describe staged diagnosis and therapy including individual medical treatments of 97 patients with HHT. The success of treatment is monitored with a systematic questionnaire. RESULTS: The neodymium-doped yttrium aluminium garnet (Nd:YAG) laser therapy remains standard treatment of choice with no major side effects despite the need for repeated treatment. In addition new treatment strategies like nasal occlusion, local drug therapy, and nasal septal splinting show initial success. CONCLUSION: Improvement of the quality of life of HHT patients can be achieved by a multimodal concept. Several new treatment strategies like nasal septal splinting and nasal occlusion successfully expand the range of established methods. Further studies have to prove the safety and long-term effectiveness of the described individual medical treatments.
Arteries ; Arteriovenous Malformations ; Bevacizumab ; Capillaries ; Diagnosis ; Drug Therapy ; Epistaxis ; Humans ; Laser Therapy ; Mucous Membrane ; Quality of Life ; Splints ; Telangiectasia, Hereditary Hemorrhagic* ; Vascular Malformations ; Veins ; Yttrium

Antibodies, Monoclonal, Humanized ; therapeutic use ; Bevacizumab ; Electrocoagulation ; methods ; Endoscopy ; Epistaxis ; therapy ; Hemostatic Techniques ; Humans ; Male ; Middle Aged ; Telangiectasia, Hereditary Hemorrhagic ; therapy

Objective: To observe the clinical effects of bevacizumab in the treatment of familial epistaxis caused by hereditary hemorrhagic telangiectasia (HHT). Methods: The data of 27 patients with familial epistaxis caused by HHT who were treated with bevacizumab intravenously from Beijing Anzhen Hospital, the First Clinical Center of Chinese People's Liberation Army General Hospital and Binzhou Central Hospital between December 2016 and December 2019 were retrospectively analyzed. There were 14 males and 13 females, aged (55.3±11.2) years. The dose of bevacizumab was calculated according to the body weight of 5 mg/kg. The curative effect was observed one month after the first treatment. Visual analogue scale (VAS) was used to compare patients' self-scores of systemic symptoms before and after treatment. Epistaxis severity score (ESS) was used to compare and analyze the six problems (including the frequency, duration, intensity, treatment demand, anemia and blood transfusion) of the patients before and after treatment. The changes of hemoglobin levels before and after treatment were compared. SPSS 20.0 statistical software was used to process the data. Results: Among the 27 patients at one month after the first bevacizumab treatment, 22 cases reported that the severity of epistaxis was improved significantly, and 5 cases reported that the treatment effect was not significant. The effective rate was 81.5% (22/27). The significant effect in 22 patients lasted for 5-24 months, with a median duration of 11.23 months. The VAS score of systemic symptoms decreased significantly compared with that before treatment (2.41±2.55 vs 8.19±1.47, t=9.708, P<0.01). The scores of six aspects and standardized scores of ESS were significantly decreased after treatment (epistaxis frequency: 1.78±1.22 vs 3.44±0.80, t=6.814, P<0.01; epistaxis duration: 0.85±0.91 vs 3.00±0.73, t=8.845, P<0.01; epistaxis intensity: 0.19±0.40 vs 1.00±0.00, t=10.696, P<0.01; treatment demand: 0.22 ± 0.42 vs 1.00±0.00, t=9.539, P<0.01; anemia: 0.41±0.50 vs 0.89±0.32, t=4.914, P<0.01; blood transfusion: 0.11±0.32 vs 0.41±0.50, t=3.309, P<0.01; ESS standardized score: 2.50±2.45 vs 7.60±1.30, t=9.344, P<0.01). The hemoglobin level after treatment was significantly higher than that before treatment ((105.48±24.31) g/L vs (73.07±23.71) g/L, t=6.864, P<0.01). Among the 27 patients, there were 8 cases of HHT1 (ENG gene) and 19 cases of HHT2 (ACVRL1 gene). The improvement duration of epistaxis in group HHT1 and group HHT2 was (4.76±5.12) months and (7.60±10.84) months, respectively, which was in group HHT2 longer than that of group HHT1, but there was no significant difference between the two groups (P>0.05). There was no significant difference in ESS scores between the two groups before and after treatment (P>0.05). Two female patients had amenorrhea after the first medication. All patients had no other adverse reactions and complications. Conclusion: Intravenous bevacizumab is significantly effective and safe in the treatment of familial epistaxis caused by HHT.
Activin Receptors, Type II ; Adult ; Aged ; Bevacizumab/therapeutic use* ; Epistaxis/etiology* ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Telangiectasia, Hereditary Hemorrhagic/drug therapy*

Adolescent ; Adult ; Arteriovenous Fistula ; surgery ; therapy ; Child ; Child, Preschool ; Female ; Heart Defects, Congenital ; surgery ; therapy ; Heparin ; therapeutic use ; Humans ; Infant ; Male ; Middle Aged ; Pulmonary Artery ; abnormalities ; surgery ; Pulmonary Veins ; abnormalities ; surgery ; Retrospective Studies ; Telangiectasia, Hereditary Hemorrhagic ; surgery ; therapy ; Young Adult

This is a case report of a 68-year-old man with hepatocellular carcinoma (HCC) accompanied by hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu disease, and hepatic vascular malformation. HHT is an autosomal dominant disorder of the fibrovascular tissue that is characterized by recurrent epistaxis, mucocutaneous telangiectasias, and visceral arteriovenous malformations. HHT is caused by mutation of the genes involved in the signaling pathway of transforming growth factor-beta, which plays an important role in the formation of vascular endothelia1. Hepatic involvement has been reported as occurring in 30-73% of patients with HHT. However, symptomatic liver involvement is quite rare, and the representative clinical presentations of HHT in hepatic involvement are high-output heart failure, portal hypertension, nodular regenerative hyperplasia, and symptoms of biliary ischemia. Some cases of HCC in association with HHT have been reported, but are very rare. We present herein the characteristic radiologic and genetic findings of HHT that was diagnosed during the evaluation and treatment of HCC.
Activin Receptors, Type II/genetics ; Aged ; Angiography ; Carcinoma, Hepatocellular/*complications/*therapy ; Chemoembolization, Therapeutic ; Exons ; Gene Deletion ; Humans ; Liver Neoplasms/*complications/*therapy ; Male ; Mutation ; *Telangiectasia, Hereditary Hemorrhagic/complications/genetics/pathology/radiography ; Tomography, X-Ray Computed

OBJECTIVE: To evaluate the clinical and radiological outcomes of transcatheter embolotherapy for treating sporadic pulmonary arteriovenous malformations (PAVMs) that were not associated with hereditary hemorrhagic telangiectasia. MATERIALS AND METHODS: Between January 2001 and June 2008, thirty-five sporadic PAVMs were detected in 23 patients. The clinical follow up consisted of assessing the changes of the signs and symptoms of the PAVMs, and radiological evaluation with chest radiographs or chest CT scans. RESULTS: The lower lung regions (63%) and peripheral locations (86%) were the common locations of the PAVMs. Thirty-four PAVMs (97%) had simple architecture (one arterial feeder within a single pulmonary segment). Technical success was achieved in 33 PAVMs (94%); two cases of technical failure were due to catheterization failure (n = 1) and too large a feeding artery (17 mm) that disabled embolotherapy (n = 1). Coils and Amplatz vascular plugs were used in 30 and three PAVMs, respectively. Inadvertent placement of one coil (n = 1) and pulmonary infarction (n = 1) occurred, but no relevant symptoms developed. For the 13 patients with available data, the mean arterial O2 saturation changed significantly from 92% to 98%. Complete or near-complete involution of the sac was observed in 30 of the 33 embolized PAVMs (91%). In these 33 embolized PAVMs, the mean sac diameter significantly decreased from 17.83 mm to 0.68 mm. CONCLUSION: Sporadic PAVMs are mostly the simple type with predominance in the lower lobe and peripheral locations. Transcatheter embolotherapy with coils or Amplatz vascular plugs is a safe and effective treatment for sporadic PAVMs and this provides excellent functional and radiological improvement.
Adolescent ; Adult ; Aged ; Arteriovenous Malformations/radiography/*therapy ; Child ; Cohort Studies ; Embolization, Therapeutic/*methods ; Female ; Humans ; Male ; Middle Aged ; Pulmonary Artery/*radiography ; Pulmonary Veins/*radiography ; *Telangiectasia, Hereditary Hemorrhagic ; Tomography, X-Ray Computed/methods ; Treatment Outcome ; Young Adult

BACKGROUNDHereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease characterized by recurrent epistaxis, mucocutaneous telangiectasia, and arteriovenous malformations. The efficacy of traditional treatments for HHT is very limited. The aim of this study was to investigate the therapeutic role of thalidomide in HHT patients and the effect in FLI-EGFP transgenic zebrafish model.

METHODSHHT was diagnosed according to Shovlin criteria. Five HHT patients were treated with thalidomide (100 mg/d). The Epistaxis Severity Score (ESS), telangiectasia spots, and hepatic computed tomography angiography (CTA) were used to assess the clinical efficacy of thalidomide. The Fli-EGFP zebrafish model was investigated for the effect of thalidomide on angiogenesis. Dynamic real-time polymerase chain reaction assay, ELISA and Western blotting from patient's peripheral blood mononuclear cells and plasma were used to detect the expression of transforming growth factor beta 3 (TGF-β3) messenger RNA (mRNA) and vascular endothelial growth factor (VEGF) protein before and after 6 months of thalidomide treatment.

RESULTSThe average ESS before and after thalidomide were 6.966 ± 3.093 and 1.799 ± 0.627, respectively (P = 0.009). The "telangiectatic spot" on the tongue almost vanished; CTA examination of case 2 indicated a smaller proximal hepatic artery and decreased or ceased hepatic artery collateral circulation. The Fli-EGFP zebrafish model manifested discontinuous vessel development and vascular occlusion (7 of 10 fishes), and the TGF-β3 mRNA expression of five patients was lower after thalidomide therapy. The plasma VEGF protein expression was down-regulated in HHT patients.

CONCLUSIONSThalidomide reverses telangiectasia and controls nosebleeds by down-regulating the expression of TGF-β3 and VEGF in HHT patients. It also leads to vascular remodeling in the zebrafish model.

Animals ; Animals, Genetically Modified ; Female ; Green Fluorescent Proteins ; genetics ; metabolism ; Humans ; Middle Aged ; Telangiectasia, Hereditary Hemorrhagic ; drug therapy ; metabolism ; Thalidomide ; therapeutic use ; Transforming Growth Factor beta3 ; genetics ; Vascular Endothelial Growth Factor A ; metabolism ; Zebrafish