Francesco Chu

Efficacy and safety of thalidomide for the treatment of severe recurrent epistaxis in hereditary haemorrhagic telangiectasia: results of a non-randomised, single-centre, phase 2 study.

BACKGROUND Hereditary haemorrhagic telangiectasia is a genetic disease that leads to multiregional angiodysplasia. Severe recurrent epistaxis is the most common presentation, frequently leading to severe anaemia. Several therapeutic approaches have been investigated, but they are mostly palliative and have had variable results. We aimed to assess the efficacy of thalidomide for the reduction of epistaxis in patients with hereditary haemorrhagic telangiectasia that is refractory to standard therapy. METHODS We recruited patients aged 17 years or older with hereditary haemorrhagic telangiectasia who had severe recurrent epistaxis refractory to minimally invasive surgical procedures into an open-label, phase 2, non-randomised, single-centre study at IRCCS Policlinico San Matteo Foundation (Pavia, Italy). We gave patients thalidomide at a starting dose of 50 mg/day orally. If they had no response, we increased the thalidomide dose by 50 mg/day increments every 4 weeks, until a response was seen, up to a maximum dose of 200 mg/day. After patients had achieved a response, they continued treatment for 8-16 additional weeks. The primary endpoint was the efficacy of thalidomide measured as the percentage of patients who had reductions of at least one grade in the frequency, intensity, or duration of epistaxis. We followed up patients each month to assess epistaxis severity score and transfusion need, and any adverse events were reported. We included all patients who received any study drug and who participated in at least one post-baseline assessment in the primary efficacy population. The safety population consisted of all patients who received any dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT01485224. FINDINGS Between Dec 1, 2011, and May 12, 2014, we enrolled 31 patients. Median follow-up was 15·9 months (IQR 10·1-22·3). Three (10%, 95% CI 2-26) patients had a complete response, with bleeding stopped, 28 (90%, 95% CI 74-98) patients had partial responses. Overall, all 31 (100%, 89-100) patients responded to therapy with a significant decrease in all epistaxis parameters (p<0·0001 for frequency, intensity, and duration). A response was achieved by 25 (81%) patients at 50 mg/day of thalidomide, five (16%) patients at 100 mg/day, and one (3%) patient at 150 mg/day. Patients had only non-serious, grade 1 adverse effects, the most common of which were constipation (21 patients), drowsiness (six patients), and peripheral oedema (eight patients). One patient died a month after the end of treatment, but this was not deemed to be related to treatment. INTERPRETATION Low-dose thalidomide seems to be safe and effective for the reduction of epistaxis in patients with hereditary haemorrhagic telangiectasia. Our findings should be validated by further studies with larger patient populations, longer follow-up, and that also assess the benefit for quality of life. FUNDING Telethon Foundation.

Argon plasma coagulation is an effective treatment for hereditary hemorrhagic telangiectasia patients with severe nosebleeds

Abstract Conclusions: In contrast to the current trend according to which the treatment of hereditary hemorrhagic telangiectasia (HHT) epistaxis depends on clinical severity, argon plasma coagulation (APC) has also proven to be effective as a first-line procedure in patients with severe nosebleeds. Furthermore, with this approach patients are free from requirements for blood transfusions for a long time in the vast majority of cases. Objective: The aim of this study was to test the efficacy of APC treatment as a first-line procedure in HHT patients affected by severe epistaxis. Methods: From 1996 until 2011, 252 HHT patients were treated with APC in our clinic. We selected 26 patients with severe epistaxis for whom the need for blood transfusion had been recorded. This group of patients was asked to answer a questionnaire that aimed to evaluate the severity of epistaxis (defined by its intensity, frequency, and duration), to assess the duration of the benefit of treatment and to evaluate the number of blood transfusions required before and after treatment. Results: After APC treatment, a statistically significant decrease in all epistaxis parameters was recorded and most patients did not need blood transfusions for several years after the procedure.

Adenoid assessment in paediatric patients: the role of flexible nasal endoscopy.

Adenoid hypertrophy is the most common cause of nasal obstruction in paediatric patients. Over the years, various methods to assess the adenoid size were proposed such as the posterior rhinoscopy and the radiological examination of the nasopharynx. Nasal endoscopy was introduced for children in the 80s, and nowadays this is a known and diffuse method in routine practice. The purpose of this article is to describe the personal experience in the assessment of the adenoid size in children, with a particular regard to the flexible nasal endoscopy, and to analyse the literature reports. The personal technique is described in performing nasal endoscopy in paediatric patients, reporting advantages and possible disadvantages of the procedure. A retrospective analysis was conducted on 6036 children since 1999 to 2010. In most cases children fully collaborated to complete the exam. No major or minor complications (such as nose bleedings or other traumatic injuries) were observed. No topical intranasal decongestant, local or general anaesthesia were used in our series. In our opinion, nasal endoscopy in children is a reliable, safe, accurate, easily tolerated and dynamic diagnostic method to assess the adenoid size.

Narrow-band imaging in the endoscopic evaluation of hereditary hemorrhagic telangiectasia patients

Laryngoscope, 123:2967–2968, 2013

Hereditary haemorrhagic telangiectasia in North African and sub-Saharan patients

Hereditary haemorrhagic telangiectasia (HHT) or Osler-Weber-Rendu disease is an autosomal-dominant inherited vascular disease, characterised by the presence of mucocutaneous telangiectasia and visceral arteriovenous malformations (AVMs). Three main causative genes are known: ENG, ACVRL1 and SMAD4. BMP9 has also been shown to be involved in a small number of cases. We report two cases of HHT in North African and sub-Saharan patients.

An Unusual Localization of a Pleomorphic Adenoma in the Rhinopharynx

Pleomorphic adenoma is the most common benign tumor of the parotid glands. Rarely it may arise from minor salivary glands of the upper aerodigestive tract. A 57-year-old woman was admitted at our institution presenting with nasal obstruction. Endoscopic evaluation revealed a pedicled mass in the rhinopharynx. After radiological examination, we opted for a transnasal endoscopic-assisted excision of the mass under general anaesthesia. Histological evaluation deponed for pleomorphic adenoma with clear surgical margins. No endoscopic evidence of local recurrence has been shown after 48 months of followup. In the literature, few cases of pleomorphic adenoma arising in the rhinopharynx have been reported. The introduction of endoscopy, as shown by our experience, leads to important benefits in the identification, treatment, and followup of such rhinopharyngeal benign tumors.

La micosi acuta invasiva rinosinusale in età pediatrica

La micosi acuta invasiva rinosinusale e un’infezione caratterizzata da infiltrazione micotica della mucosa della cavita nasale e dei seni paranasali, osservata in soggetti immunocompromessi. Abbiamo analizzato retrospettivamente i dati di laboratorio, segni e sintomi all’esordio, reperti fibroendoscopici e radiologici relativi a 12 pazienti pediatrici affetti da micosi acuta invasiva e sottoposti ad intervento di chirurgia endoscopica funzionale rinosinusale presso la nostra clinica dal 1996 al 2009. Abbiamo, inoltre, valutato anche i risultati dell’esame colturale ed anatomopatologico eseguiti sul materiale asportato durante l’intervento. Tali dati sono coerenti con quanto descritto nelle diverse casistiche presenti in letteratura. La valutazione endoscopica rinosinusale e sicuramente l’esame fondamentale per la diagnosi di infezione micotica ed il trattamento unisce terapia farmacologica con antimicotici e l’intervento di chirurgia endoscopica. La prognosi e legata a diversi fattori come la rapidita nella diagnosi e nel trattamento, il tipo di infezione micotica, la disseminazione e, soprattutto, la ripresa della funzionalita immunitaria.

Management del paziente pediatrico con patologia della coagulazione sottoposto ad adenotonsillectomia

Adenotonsillectomy is the most common surgical procedure in pediatric patients. We retrospectively reviewed the clinical datas of 2730 pediatric patients who underwent adenotonsillectomy in our Institution between 2003 and 2008. After preoperative coagulation tests we found in 30 patients a bleeding disorder (von Willebrand Disease, Lupus Anticoagulans, factors IX, X, XI deficit and Vitamin K-dependent coagulation factors deficiency); after adequate informations only 24 patients accepted the surgical procedure. We used a hemostatic-support therapy as a preparation for the adenotonsillectomy. The incidence of postoperative hemorrhage in the population with bleeding disorders who had a correct diagnosis and management is 9% (all secondary hemorrhages). These results appear to be in accord with datas described in the scientific literature on a non-pathological population; however, they remain in an high range of the several described bleeding incidence casistics. In conclusion, we found the pediatric patients with bleeding disorder a high-risk population for post-adenotonsillectomy hemorrhage.