Nasal Endoscopy in the Clinical Diagnosis of Hereditary Hemorrhagic Telangiectasia.

OBJECTIVES: To evaluate the role of nasal endoscopy for early clinical diagnosis of hereditary hemorrhagic telangiectasia (HHT) in children and to investigate the characteristics of epistaxis and mucocutaneous telangiectases in our pediatric population. STUDY DESIGN: From May 2016 to December 2019, a cross-sectional observational study was conducted, recruiting children aged 2-18 years with a parent affected by HHT. To identify the Curaçao criteria, all children underwent collection of clinical history, mucocutaneous examination, and nasal endoscopy. The clinical data were then compared with the genetic data acquired subsequently. RESULTS: Seventy children (median age, 10.8 years) were included. All underwent nasal endoscopy without complications. Forty-six children were positive by genetic testing; of these, 26 % had skin and oral telangiectases and 91 % had nasal telangiectases. The diagnostic sensitivity of the Curaçao criteria increased from 28 % (95 % CI, 16%-43 %) to 85 % (95 % CI, 71%-94 %; P < .0001) when the nasal telangiectases were included. CONCLUSIONS: The magnified and complete endoscopic view of the nasal cavities proved useful in increasing the diagnostic sensitivity of the Curaçao criteria. Such an examination turned out to be feasible and safe. For this reason, we believe that nasal endoscopy should be included in the diagnostic assessment of pediatric patients with suspected HHT.

An alternative way to perform diagnostic nasopharyngeal swab for SARS-CoV-2 infection.

On March 11, 2020, WHO has defined the novel coronavirus disease SARS-CoV-2 (COVID-19) outbreak as a pandemic and still today continues to affect much of the world. Among the reasons for the rapid spread of SARS-CoV-2 infection, there is not only the high transmissibility of the virus, but also the role of asymptomatic or minimally symptomatic carriers. Therefore diagnostic testing is central to contain the global pandemic. Up to now real-time reverse transcriptase polymerase chain reaction (RT-PCR)-based molecular assays for detecting SARSCoV-2 in respiratory specimens is the current reference standard for COVID-19 diagnosis. Nasopharyngeal swab is the preferred choice for SARS-CoV-2 testing; however is not always a free of complications procedure. In patients with severe coagulopathies or diseases such as HHT, the risk of nosebleeding may be high. As in all those conditions like advanced stage sinonasal neoplasms or unfavorable anatomical characteristics, the nasopharyngeal swab may not be feasible. This work reports a safe and effective procedure of nasopharyngeal swab collection for COVID-19 testing, through the transoral way, in patients with contraindication to perform it transnasally. The procedure proved feasible and well tolerated. The discomfort for the patient is comparable with the execution of an oropharyngeal swab without exposing him to additional complications. In selected cases, the procedure described represents a valid alternative to nasopharyngeal swab performed transnasally. In particular, it allows reaching the area with the highest diagnostic sensitivity. Moreover it can be performed by Otolaryngology and, with adequate training, also by non-specialist staff.

"TuNa-saving" endoscopic medial maxillectomy: a surgical technique for maxillary inverted papilloma.

The maxillary sinus is the most common site of sinonasal inverted papilloma. Endoscopic sinus surgery, in particular endoscopic medial maxillectomy, is currently the gold standard for treatment of maxillary sinus papilloma. Although a common technique, complications such as stenosis of the lacrimal pathway and consequent development of epiphora are still possible. To avoid these problems, we propose a modification of this surgical technique that preserves the head of the inferior turbinate and the nasolacrimal duct. A retrospective analysis was performed on patients treated for maxillary inverted papilloma in three tertiary medical centres between 2006 and 2014. Pedicle-oriented endoscopic surgery principles were applied and, in select cases where the tumour pedicle was located on the anterior wall, a modified endoscopic medial maxillectomy was carried out as described in this paper. From 2006 to 2014 a total of 84 patients were treated. A standard endoscopic medial maxillectomy was performed in 55 patients (65.4%), while the remaining 29 (34.6%) had a modified technique performed. Three recurrences (3/84; 3.6%) were observed after a minimum follow-up of 24 months. A new surgical approach for select cases of maxillary sinus inverted papilloma is proposed in this paper. In this technique, the endoscopic medial maxillectomy was performed while preserving the head of the inferior turbinate and the nasolacrimal duct ("TuNa-saving"). This technique allowed for good visualization of the maxillary sinus, good oncological control and a reduction in the rate of complications.

A novel device for intraoperative cauterization of bleeding points in endoscopic sinus surgery.

Hemostasis is a critical point in endoscopic sinus and skull base surgery. A variety of techniques are presently available for reducing intraoperative bleeding; however, several limitations of the classical instruments should be stated. For example, reaching bleeding points in an anatomically angled site with straightforward bipolar devices could be quite difficult. With the aim of solving this problem, we developed a simple system using a standard curved suction tube, a rubber catheter and a monopolar system. This device provides an integrated suction function and is able to reach all paranasal and skull base areas, making it extremely useful in gaining precise access to the site of bleeding while providing excellent endoscopic vision. The described monopolar suction tube has proven to be a valid instrument for intraoperative hemostasis in endoscopic procedures; moreover, it does not add any further cost, making it applicable in particular healthcare settings, such as those in developing countries.

Endoscopic evaluation of gastrointestinal tract in patients with hereditary hemorrhagic telangiectasia and correlation with their genotypes.

PURPOSE: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal-dominant vascular dysplasia characterized by telangiectases and arteriovenous malformations. Three causative genes are known: ENG (HHT-1), ACVRL1 (HHT-2), and SMAD4 (mutated in HHT in association with juvenile polyposis). Gastrointestinal bleeding is the most common symptom after epistaxis. The stomach and the duodenum are the main gastrointestinal sites of telangiectases. Our aim was to explore gastrointestinal tract of consecutive HHT patients to assess distribution, number, size, and type of telangiectases in relation to genotype. METHODS: HHT patients underwent gastroduodenoscopy, video capsule endoscopy, and colonoscopy. Molecular analysis of ENG and ACVRL1 was performed to identify the disease-causing mutation. RESULTS: Twenty-two patients (13 men; mean age: 59 ± 9 years) were analyzed: 7 with HHT-1, 13 with HHT-2, and 2 undefined. Gastrointestinal telangiectases were identified as follows: at gastroduodenoscopy in 86% of HHT-1 patients and in 77% of HHT-2 patients, at video capsule endoscopy in all HHT-1 patients and in 84% of HHT-2 patients, and at colonoscopy in 1 patient for each group. HHT-1 showed multiple telangiectases with a higher prevalence, more relevant in the duodenum. CONCLUSION: Our data demonstrate extensive involvement of the gastrointestinal tract with a more severe association in HHT-1. Gastroduodenoscopy provides significant information on gastrointestinal involvement, and video capsule endoscopy may be added in selected patients. Colonic polyps/adenomas were identified as occasional findings.

CD64 expression on monocytes in children with adenoid hypertrophy.

OBJECTIVE: Adenoids with obstructive hypertrophy (AH) are considered to be one of the most ancient and common problems in Paediatrics. This study aimed at investigating the expression of CD 64 on monocytes in children who had to undergo adenoidectomy. METHODS: Therefore, 66 children (24 females, 42 males, mean age 4.9 years), affected by AH and requiring adenoidectomy (54%) or adeno-tonsillectomy (46%) were consecutively enrolled into the study. Moreover, 30 healthy children (11 females, 19 males, mean age 11.2 years) were enrolled in this study as controls. CD64 expression on monocytes was measured. RESULTS: Children with severe AH had higher CD64 values than children with AH size 3 and controls. CONCLUSIONS: This preliminary study shows that CD64 expression on monocytes may be associated with severe AH, suggesting a more intense immune activation in these subjects.

Silicone septal splint for recurrent epistaxis in HHT patients: experience of a national referral centre.

Objective: To report our experience in the use of silicone septal splint for recurrent severe epistaxis in hereditary haemorrhagic telangiectasia patients (HHT). Methods: This is a descriptive analysis carried out at the Otorhinolaryngology Department of Fondazione IRCCS Policlinico San Matteo in Pavia, a reference centre for the treatment and diagnosis of HHT. We retrospectively evaluated HHT patients who underwent silicone septal splint positioning after the endoscopic surgical treatment of epistaxis from 2000 to 2022. Results: Of the 506 patients surgically treated in the period of analysis, 74 patients underwent silicone septal splint positioning and 37 were post-operatively interviewed. With a mean of 2.4 previous surgical treatments and a mean epistaxis severity of 7.38, the majority of patients presented with septal perforation (71.6%). On average, patients maintained the splint in place for 54.5 months, with a good tolerability and a significant reduction in epistaxis severity, need for blood transfusion and improvement of haemoglobin levels. Conclusions: In HHT patients with recurrent severe epistaxis and with septal perforation, the placement of septal splints offers a useful additional strategy in the management of nosebleeds.

Impact of SARS-CoV-2 infection in patients with hereditary hemorrhagic telangiectasia: epidemiological and clinical data from the comprehensive Italian retrospective multicenter study.

Rare Disease patients manifested high concern regarding the possible increased risk of severe outcomes and worsening of disease-specific clinical manifestation due to the impact of COVID-19. Our aim was to assess the prevalence, outcomes, and impact of COVID-19 in patients with a rare disease such as Hereditary Hemorrhagic Telangiectasia (HHT) in Italian population. A nationwide, multicentric, cross-sectional observational study was conducted on patients with HHT from five Italian HHT centers by online survey. The association between COVID-19-related signs and symptoms and nosebleeds worsening, the impact of personal protective equipment on nosebleeds pattern, and the relationship between the presence of visceral AVMs and severe outcomes were analyzed. Out of 605 total survey responses and eligible for analysis, 107 cases of COVID-19 were reported. A mild-course COVID-19 disease, not requiring hospitalization, was observed in 90.7% of patients, while the remaining eight cases needed hospitalization, two of them requiring intensive-care access. No fatal outcome was recorded and 79.3% of patients reported a complete recovery. No difference in infection risk and outcome between HHT patients and general population was evidenced. No significative interference of COVID-19 on HHT-related bleeding was found. The majority of patients received COVID-19 vaccination, with relevant impact on symptoms and need for hospitalization in case of infection. COVID-19 in HHT patients had an infection profile similar to the general population. COVID-19 course and outcome were independent from any specific HHT-related clinical features. Moreover, COVID-19 and anti-SARS-CoV-2 measures did not seem to affect significantly HHT-related bleeding profile.

Hereditary hemorrhagic telangiectasia: First demonstration of a founder effect in Italy; the ACVRL1 c.289_294del variant originated in the country of Bergamo 200 years ago.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder, affecting 1:5000 individuals worldwide. All the genes associated to the disease (ENG, ACVRL1, SMAD4, GDF2) belong to the TGF-ß/BMPs signaling pathway. We found 19 HHT unrelated families, coming from a Northern Italy region and sharing the ACVRL1 in-frame deletion c.289_294del (p.H97_N98). METHODS: To test the hypothesis of a founder effect, we analyzed 88 subjects from 19 families (66 variant carriers, showing clinical signs of HHT, and 22 non-carriers, unaffected) using eight microsatellite markers within 3.7 Mb around the ACVRL1 locus. After the haplotype reconstruction, age estimation of the variant was carried out. RESULTS: We observed a common disease haplotype in 16/19 families, while three families showed evidence of recombination around the ACVRL1 locus. The subsequent age estimation analyses suggested that the mutation occurred about 8 generations ago, corresponding to about 200 years ago. We also present novel in silico and modeling data supporting the variant pathogenicity: the deletion alters the protein stability and removes the unique extracellular glycosylation site. CONCLUSION: We have demonstrated, for the first time, a "founder effect" for a HHT pathogenic variant in Italy.

Endoscopic surgical treatment of epistaxis in hereditary haemorrhagic telangiectasia: our experience.

OBJECTIVES: Hereditary haemorrhagic telangiectasia (HHT) is a rare autosomal dominant disease characterised by epistaxis. Surgical procedures for epistaxis vary from diathermocoagulation to nasal closure. The aim of this paper is to report our experience in endoscopic surgical management of epistaxis in HHT patients. METHODS: This is a descriptive, longitudinal study carried out at the Otorhinolaryngology Department of IRCCS Policlinico San Matteo in Pavia, a reference centre for the treatment and diagnosis of HHT. We retrospectively evaluated HHT patients who underwent surgery for epistaxis from 1996 to 2015, including only those treated with endoscopic surgery. RESULTS: Among the 591 patients hospitalised and screened for HHT, 323 (54.7%) underwent endoscopic surgery for epistaxis, for a total of 679 procedures. General anaesthesia was used in 77.2% of procedures; argon plasma coagulation was the instrument of choice in the majority of patients, followed by lasers and quantum molecular resonance technology. CONCLUSIONS: We report one of the largest cohorts undergoing endoscopic treatment of epistaxis in HHT patients. This mini-invasive surgical treatment allowed us to control epistaxis without major complications and nasal packaging and can be repeated over time. For these reasons, we recommend it as first choice in case of epistaxis in HHT patients.

Adenoidectomy: Anatomical variables as predictive factors of intraoperative adenoid residues.

OBJECTIVES: Adenoid hypertrophy is a common cause of upper airway obstruction in children. However, after adenoidectomy, nasal obstructive symptoms may persist or recur, requiring surgical revision. The aim of this study is to evaluate if individual patient features can influence the efficacy of the traditional technique. METHODS: A retrospective observational study was conducted by recruiting patients from candidates for adenoidectomy. All children underwent conventional transoral curettage adenoidectomy with endoscopic control at the end of procedure, and in presence of adenoid residues, a concomitant revision adenoidectomy was performed. For each patient, the following data were collected: age, sex, weight, height, length of the soft palate and surgical technique used. RESULTS: In 18% of patients (113/612), the most critical areas of the nasopharynx were not reached by standard surgery, making a complete adenoidectomy difficult. In this group, the average length of the soft palate was 3.1 cm, 5 mm more than the average of the sample, and 6 mm more than the average length of patients undergoing standard surgery alone (p < 0.001). CONCLUSION: Our study confirms the hypothesis that a greater length of the soft palate conditions the results of the intervention. The length of the soft palate can be considered an intraoperative criterion to select the cases in which perform endoscopic control after the standard procedure.

Characterization of epidemiological distribution and outcome of COVID-19 in patients with hereditary hemorrhagic telangiectasia: a nationwide retrospective multi-centre study during first wave in Italy.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) continues to have a devastating impact across the world. A number of pre-existing common clinical conditions were reported to represent risk factors for more severe COVID-19 outcomes. Hereditary Hemorrhagic Telangiectasia (HHT) is a rare vascular heritable disorders, characterized by complications secondary to visceral Arterio-Venous Malformations. The impact of HHT, as well as for many Rare Diseases (RDs) on infection susceptibility profile and clinical adverse outcome risk is an unresolved issue. OBJECTIVES: The main objectives were: to assess the clinical features and outcomes of HHT patients infected with COVID-19; to compare the relative infection risk in these patients with the Italian general population throughout the first pandemic wave; to investigate the factors potentially associated with severe COVID-19 outcome in HHT patients, and the possible impact of COVID-19 infection on HHT-related symptoms/complications. Finally, we aimed to estimate how the lockdown-associated wearing of personal protective equipment/individual protection devices could affect HHT-related telangiectasia bleeding frequency. METHODS: The study is a nation-wide questionnaire-based survey, with a multi-Center retrospective cross-sectional design, addressed to the whole Italian HHT population. COVID-19 cases, occurring throughout the first pandemic wave, were collected by a questionnaire-based semi-structured interview. Only the cases ascertained by laboratory confirmation (molecular/serological) were included for epidemiological estimates. Information concerning eventual SarS-Cov-2 infection, as well as regarding HHT-related manifestations and HHT-unrelated co-morbidities were collected by the questionnaire. Prevalence data were compared to Italian general population in the same period. RESULTS: The survey disclosed 9/296 (3.04%) COVID-19 cases, 8/9 of them being resident in Lombardy, the main epidemic epicenter. Pneumonia was reported by 4/9 patients, which prompted hospital admission and intensive care management in 2 cases. No fatal outcome was recorded. After careful refinement of epidemiological analysis, the survey evidenced overlapping infection risk in HHT compared to general population. CONCLUSIONS: COVID-19 infection profile parallels geographical distribution of epidemic foci. COVID-19 in HHT patients can lead to highly variable clinical profile, likely overlapping with that of general population. The HHT disease does not seem to involve a different approach in terms of hospital admission and access to intensive care with respect to general population.

Diagnostic testing for SARS-CoV-2 infection in HHT patients: nasopharyngeal versus oropharyngeal swab.

On March 11, 2020, WHO has defined the novel coronavirus disease SARS-CoV-2 (COVID-19) outbreak as a pandemic that still today continues to affect much of the world. Among the reasons for the rapid spread of SARS-CoV-2 infection, there is the role of asymptomatic or minimally symptomatic carriers. Therefore diagnostic testing is central to contain the global pandemic. Up to now real-time reverse transcriptase polymerase chain reaction-based molecular assays for detecting SARS-CoV-2 in respiratory specimens is the current reference standard for COVID-19 diagnosis. Based on current knowledge regarding the sensitivity of the molecular test, the highest positive detection rate is from lower respiratory tract specimens; alternatively it is possible to perform a nasopharyngeal or oropharyngeal swab. Nasopharyngeal swab is the preferred choice for SARS-CoV-2 testing since it seems to have a greater sensitivity; however the procedure is not always free of complications and an epistaxis can occur. Among patients with greatest risk of massive nosebleed there are HHT patients. Hereditary hemorrhagic telangiectasia is an autosomal dominant disease that leads to multiregional mucocutanous telangiectases and visceral arteriovenous malformations. Clinically, the presence of telangiectases in nasal mucosa is the cause of recurrent epistaxis. In HHT patients the execution of the nasopharyngeal swab can determine from little or no consequences to a massive epistaxis leading to the necessity of nasal packing generally followed by hospital admission. In HHT patients undergoing a diagnostic test to evaluate the SARS-CoV-2 infection status, especially in those patients with frequent epistaxis with a history of anemia and repeated hospitalizations, it is therefore advisable to perform an oropharyngeal swab. This, compared to the nasopharyngeal swab, exposes to a lower risk of severe nosebleeds related treatments, such as blood transfusions or invasive procedures. According to the risk-benefit assessment and based on our experience, we consider that, despite a lower diagnostic sensitivity, oropharyngeal swab is preferable to nasopharyngeal swab for the diagnosis of SARS CoV-2 infection in patients with HHT.

Endoscopic removal of a nasal foreign body with the "hook-scope" technique.

We present a case of a pediatric nasal foreign body removal with a new technique, the "hook-scope" technique, in which the flexible scope is used both as an endoscope and as a hook and permits a safe and rapid extraction of the object. This is the first report where such technique is presented with an image-documentation of a real case.

Is canine fossa access necessary for successful maxillary fungus ball treatment?

BACKGROUND: Sinus fungus ball (FB) is a non-invasive mycosis that affects immunocompetent hosts, most frequently localized in the maxillary sinus. The current golden standard treatment is surgical removal. OBJECTIVE: To evaluate the effectiveness of an endonasal endoscopically assisted approach to remove a maxillary FB combined or not with a transoral approach (sinusoscopy via canine fossa). METHODS: A retrospective evaluation of paranasal FB treated by functional endoscopic sinus surgery (FESS) + transoral approach, compared to those treated by a sole FESS procedure. RESULTS: In total, 65 out of 90 patients presented with a maxillary localization and were treated by FESS. Thirthy-three patients received a combined FESS + transoral approach and 32 received solely a FESS procedure. Antimycotic medical therapy was not used in any case. With a mean follow-up of 93 months, the treatment was successful in 62 patients (95,4%) without significant differences between the two groups. CONCLUSIONS: Our data confirm the efficacy of FESS in the treatment of maxillary FB. A similarity in long-term results in both groups demonstrated that transoral sinusoscopy can be avoided. With the assistance of lateral-view and flexible endoscopes, angled surgical equipment and maxillary saline solution irrigations, complete removal of the diseased material and sinus clearance can be achieved by a sole middle meatotomy, reducing both morbidity and operating time.

Removal of a fronto-ethmoidal osteoma using the sonopet omni ultrasonic bone curette: first impressions.

Endoscopic exeresis of sinonasal osteomas usually implicates the use of surgical drills with some disadvantages, as underlined by many authors. A new device that performs an ultrasound bone emulsification has been proposed in recent years for bone removal in various surgical disciplines. In this case report, we present the first clinical ENT experience with this device in removing a fronto-ethmoidal osteoma, and we briefly discuss our impressions.

Hyoidthyroidpexia as a treatment in multilevel surgery for obstructive sleep apnea.

CONCLUSION: This type of surgery is effective in patients with obstructive sleep apnea syndrome (OSAS), but may not be effective in obese patients or those with a preoperative apnea hypopnea index (AHI)>35. For these reasons, the careful study and selection of patients is fundamental in the surgical treatment of OSAS. OBJECTIVES: Evaluation of the efficacy of hyoid surgery combined with oropharynx and nose surgery in the treatment of OSAS. SUBJECTS AND METHODS: A total of 109 OSAS patients underwent hyoidthyroidpexia as a treatment in multilevel surgery. Before surgery all patients were treated with continuous positive airway pressure (CPAP) therapy for at least 6 months and underwent preoperative and postoperative polysomnography. The preoperative examination was composed of upper airways endoscopy, lateral cephalometric radiograph, calculation of body mass index (BMI), and subjective analysis of daytime sleepiness. RESULTS: In all, 67/109 patients (61.5%) with postoperative AHI<20 were defined as 'responders', while the other 42 patients (38.5%) were defined as 'non-responders'. The correlation between preoperative BMI and postoperative AHI revealed that non-responders had a much higher average BMI compared with responders. Moreover, when analyzing median preoperative and postoperative AHI, it emerged that non-responders had a much higher preoperative AHI compared with responders.

Fluorescein-guided intraoperative endoscopy in patients with hereditary hemorrhagic telangiectasia: first impressions.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is a rare genetic disease that results in mucocutaneous telangiectasias and arteriovenous visceral malformations. Nasal telangiectasias lead to recurrent epistaxis, which affects up to 96% of patients. Different morphologic classifications and methods of visualization of nasal lesions have been described in the literature. We developed a new method of intraoperative endoscopy based on the intravenous administration of fluorescein. Preliminary data of this technique are reported. METHODS: After the intravenous administration of sodium fluorescein, an intraoperative fluorescein-guided endoscopy was carried out using photographic customized yellow filters on top of a 0-degree, 4-mm endoscope. RESULTS: In 2015, 65 HHT patients underwent surgery for their epistaxis in our institution, and in 7 patients (3 males, 4 females; mean age, 54 years) an intraoperative fluorescein-guided intraoperative nasal endoscopy was performed. No adverse events or complications were observed. CONCLUSION: First impressions regarding the usage of this technique in HHT patients seem to be promising and positive in terms of efficacy and safety. However, further studies with larger cohorts of patients should be performed in order to better investigate the use of this method for diagnostic and surgical purposes in HHT.

An easy method for intraoperative confirmation of lacrimal sac patency in endoscopic dacryocystorhinostomy.

PURPOSE: Few studies have focused on the intranasal localization of the lacrimal sac during endoscopic dacryocystorhinostomy: landmarks in order to find the medial wall of the lacrimal sac have been described, but there is a lack of description of methods for the verification of the complete marsupialization of the lacrimal sac during surgery. In this report, we propose an easy and effective method for certain intraoperative identification of lacrimal sac. METHODS: A method in order to verify the effective marsupialization of the lacrimal sac is applied and described: to ensure that the opening of the sac in the nasal cavity is complete, the surgeon should identify the Rosenmuller valve, which is the end of the common canaliculus in the lacrimal sac. Continuous irrigation with saline solution through the inferior canaliculus can be useful to obtain a clean surgical area and to permit easy intraoperative identification of the valve. RESULTS: Between 2007 and 2015, 193 endoscopic dacryocystorhinostomies were performed in our institutions. Postoperative surgical success at last follow-up (minimum 12 months) was 93.8% (181 out of 193 of cases). No major complications were observed. CONCLUSIONS: Correct and complete exposure of the lacrimal sac during surgery is crucial for a good outcome: when the opening of the common canaliculus is identified, the surgeon is assured that the sac has been correctly and completely marsupialized inside the nasal cavity.