10.14639/0392-100X-N0915
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.
application/xml
1827-675X
915
en
Elina Matti
https://creativecommons.org/licenses/by-nc-nd/4.0
ACTA Otorhinolaryngologica Italica
argon plasma coagulation
Endoscopic surgical treatment of epistaxis in hereditary haemorrhagic telangiectasia: our experience
Text.Serial.Journal
https://www.actaitalica.it/
41
Rhinology
2021-03-19
2020-06-10
2021-03-19
2021-03-24
59-68
1
Elina Matti
2021/03/19
10.14639/0392-100X-N0915
59
Department of Otorhinolaryngology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
1827-675X
argon plasma coagulation
68
Endoscopic surgical treatment of epistaxis in hereditary haemorrhagic telangiectasia: our experience
https://www.actaitalica.it/article/download/915/525
41
ACTA OTORHINOLARYNGOLOGICA ITALICA 2021;41:59-68; doi: 10.14639/0392-100X-N0915




Rhinology


Endoscopic surgical treatment of epistaxis in hereditary
haemorrhagic telangiectasia: our experience
Il trattamento endoscopico dell’epistassi nella teleangectasia emorragica ereditaria:
la nostra esperienza
Fabio Pagella1,2, Alessandro Pusateri1, Eugenia Maiorano1,2, Giuseppe Spinozzi1, Sara Ugolini1,2, Roberta Lizzio1,
Rosolino Mirabella1,2, Carmine Tinelli3, Carla Olivieri2,4, Elina Matti1
1
 Department of Otorhinolaryngology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; 2 University of Pavia, Italy; 3 Clinical
Epidemiology and Biometric Unit, Fondazione I.R.C.C.S. Policlinico San Matteo, Pavia, Italy; 4 General Biology and Medical Genetics,
Department of Molecular Medicine, Pavia, Italy


SUMMARY
Objectives. Hereditary haemorrhagic telangiectasia (HHT) is a rare autosomal dominant
disease characterised by epistaxis. Surgical procedures for epistaxis vary from diathermo-
coagulation 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%) under-
went endoscopic surgery for epistaxis, for a total of 679 procedures. General anaesthesia       Received: June 10, 2020
was used in 77.2% of procedures; argon plasma coagulation was the instrument of choice in       Accepted: October 16, 2020
the majority of patients, followed by lasers and quantum molecular resonance technology.
Conclusions. We report one of the largest cohorts undergoing endoscopic treatment of            Correspondence
epistaxis in HHT patients. This mini-invasive surgical treatment allowed us to control          Eugenia Maiorano
                                                                                                Department of Otorhinolaryngology, Fondazione
epistaxis without major complications and nasal packaging and can be repeated over time.
                                                                                                IRCCS Policlinico San Matteo, piazzale Golgi 19,
For these reasons, we recommend it as first choice in case of epistaxis in HHT patients.        27100 Pavia, Italy
KEY WORDS: hereditary haemorrhagic telangiectasia, Rendu Osler Weber disease,                   E-mail: eugenia_maiorano@libero.it
epistaxis, nosebleeds, endoscopy, argon plasma coagulation
                                                                                                Funding
                                                                                                None.
RIASSUNTO
Obiettivi. L’obiettivo di questo studio è riportare la nostra esperienza nel trattamento en-    Conflict of interest
doscopico dell’epistassi nei pazienti con Teleangectasia Emorragica Ereditaria (HHT).           The Authors declare no conflict of interest.
Metodi. Si tratta di uno studio longitudinale retrospettivo svolto presso l’UOC di Otorino-
laringoiatria della Fondazione IRCCS Policlinico San Matteo di Pavia, centro di riferimen-        How to cite this article: Pagella F, Pusateri A,
to per la diagnosi e la cura dell’HHT. Sono stati valutati i pazienti sottoposti dal 1996 al      Maiorano E, et al. Endoscopic surgical treat-
2015 a trattamento chirurgico delle epistassi ricorrenti, includendo solo quelli trattati con     ment of epistaxis in hereditary haemorrhagic
tecnica endoscopica.                                                                              telangiectasia: our experience. Acta Otorhi-
Risultati. Dei 591 pazienti ricoverati e sottoposti a screening per HHT, 323 (54.7%) sono         nolaryngol Ital 2021;41:59-68. https://doi.
stati sottoposti a trattamento chirurgico endoscopico per epistassi, per un totale di 679         org/10.14639/0392-100X-N0915
procedure. Il 77,2% delle procedure è stato eseguito in anestesia generale; il sistema ad
Argon Plasma è stato lo strumento di scelta nella maggior parte dei pazienti, seguito dai       © Società Italiana di Otorinolaringoiatria
                                                                                                e Chirurgia Cervico-Facciale
laser e dalla quantum molecular resonance.
Conclusioni. Riportiamo una delle più ampie casistiche nel trattamento endoscopico
                                                                                                               OPEN ACCESS
dell’epistassi nei pazienti con HHT. Tale approccio consente di gestire i pazienti senza
necessità di tamponamento nasale, è scevro da complicanze maggiori, ripetibile nel tempo        This is an open access article distributed in accordance with
                                                                                                the CC-BY-NC-ND (Creative Commons Attribution-Non-
e riteniamo che debba essere preso in considerazione come trattamento di prima scelta in        Commercial-NoDerivatives 4.0 International) license. The
caso di epistassi in pazienti con HHT.                                                          article can be used by giving appropriate credit and mentio-
                                                                                                ning the license, but only for non-commercial purposes and
PAROLE CHIAVE: teleangectasia emorragica ereditaria, malattia di Rendu Osler Weber,             only in the original version. For further information: https://
epistassi, endoscopia, argon plasma                                                             creativecommons.org/licenses/by-nc-nd/4.0/deed.en




                                                                                                                                                          59
F. Pagella et al.




Introduction                                                    scribe our experience in the endoscopic management of
                                                                epistaxis in HHT patients, focusing on mini-invasive surgi-
Hereditary haemorrhagic telangiectasia (HHT) is an auto-
                                                                cal procedures.
somal dominant disorder characterised by multiorgan sys-
temic vascular dysplasia. The prevalence of the disease is
estimated to be between 1:5000 and 1:8000 in the Europe-        Materials and methods
an population 1. HHT is characterised by a highly variable      The Department of Otorhinolaryngology of I.R.C.C.S.
phenotype and complete penetrance by the age of 40 years;       Policlinico San Matteo in Pavia is a national reference cen-
vascular dysplasia leads to visceral arteriovenous malfor-      tre for diagnosis and treatment of HHT. After Local Ethics
mations (AVMs) and mucosal and skin telangiectasias. Re-        Committee approval (Comitato Etico di Pavia, reference
current epistaxis from telangiectasias of the nasal mucosa is   number 1-29/1/14), we retrospectively reviewed data of
the most frequent symptom, which is present in more than        HHT patients treated from 1996 until 2015 for nosebleeds,
95% of HHT patients 1. AVMs are frequently found in the         including demographics, surgical technique, number of
lungs (15-50% of patients), liver (32-78%) and brain (23%)      procedures carried out on each patient, time between each
and should be recognised in these patients since they may       procedure, characteristics of nasal telangiectasias, pres-
cause severe life-threatening complications 1. The clinical     ence of septal perforation and intraoperative bleeding.
diagnosis of HHT is confirmed if three of the four diag-
                                                                Patient records were stored in a Filemaker Pro Advance
nostic Curacao criteria (positive family history, recurrent
                                                                database (version 14.0.1, Filemaker Inc.) and extracted for
epistaxis, mucocutaneous telangiectasias, visceral AVMs)
                                                                this study. Molecular analyses on peripheral blood DNA
are met. Two major genes are involved in HHT: ENG
                                                                were performed as described in a previous paper: 100 ng of
(OMIM #187300) and ACVRL1 (OMIM #600376), coding
                                                                genomic DNA was amplified in the coding regions of both
for proteins involved in the TGF-β/BMP pathway 1,2.
                                                                ENG and ACVRL1 2.
In HHT patients, the clinical manifestations of epistaxis are
                                                                The endoscopic endonasal mini-invasive surgical proce-
variable, from rare blood spots to patients in whom nose-
                                                                dure was performed in the operating theatre under local or
bleed severity can require frequent blood transfusions, with
                                                                general anaesthesia. During surgery, patients were placed
a substantial worsening in quality of life. Over the years,
                                                                in a reverse Trendelenburg position. Careful preparation
different grading scale systems have been proposed to
quantify the severity of epistaxis related to HHT. Moreo-       of the nasal cavities was undertaken: cottons soaked with
ver, in recent years, to enhance the visualisation of nasal     xylometazoline chlorohydrate 0.1% and oxybuprocaine
vascular structures, our group developed new methods of         chlorohydrate 0.01% were placed in the nasal fossa and left
intraoperative endoscopy based on narrow-band imaging           in place for 5-10 min to decongest and clean the nasal mu-
and fluorescein-guided endoscopy 3,4. However, epistaxis        cosa. Surgery was performed under endoscopic endonasal
in HHT remains a clinically unsolved problem; current           control with a 0° rigid 4 mm optic (Karl Storz and Co.,
therapies do not lead to a definitive resolution but only to    Germany) to selectively treat involved mucosa and telan-
temporary control of the condition. Multiple therapeutic        giectasias located along the nasal fossae. After surgery, an
approaches have been proposed in the literature and can be      antibiotic ointment was placed in the nasal cavities and no
schematically classified into the destruction of telangiecta-   nasal packing was necessary. In some patients whose intra-
sia, reduction of blood flow, reduction of trauma, improve-     operative bleeding was more severe than expected and not
ment of protection and control of fibrinolytic activity.        managed elsewhere, we applied selective bipolar cauteri-
Regarding medical therapy, different approaches have been       sation or an intranasal haemostatic matrix such as Floseal
proposed and described with variable results 5-8. From a        (Baxter, U.S.), Surgiflo (Ethicon, U.S.), Perclot (Cryolife,
surgical perspective, the management of epistaxis depends       U.S.), or Haemocer (BioCer GmbH, Germany) as an ad-
on clinical severity. In patients with mild nosebleeds, vari-   junct to local coagulation control of haemostasis. In the
ous forms of mini-invasive surgical techniques including        postoperative period, patients were periodically evaluated
bipolar cautery, argon plasma coagulation (APC), lasers         (every 6–12 months) for epistaxis with medical evaluation
and Diego-PK Shaver treatment can be indicated, while           and/or follow-up phone call. In cases in which good control
more invasive procedures, such as modified Young’s proce-       of epistaxis was obtained, follow-up was continued as de-
dure, are reserved for cases of severe epistaxis 9,10.          scribed; in cases of worsening of symptoms, a new surgical
Various therapeutic approaches for epistaxis in HHT have        procedure was performed. Non-responders (31 patients)
been described, but there still is no general agreement on      were given medical therapy with oral thalidomide and ex-
the best treatment. The purpose of this study was to de-        cluded from the present analysis 5.



60
                                                                             Endoscopic surgical treatment of epistaxis in HHT: our experience




Statistical analysis                                               Table I. Number of epistaxis-related surgical procedures performed in HHT
Descriptive statistics were used for demographic character-        patients.
istics for this sample of patients. The Shapiro-Wilk test was       Number of surgeries           No. of patients                 %
used to test the normal distribution of quantitative variables.     1 procedure                          175                    54.18%
When quantitative variables were normally distributed, the          2 procedures                          56                    17.34%
results were expressed as mean value and standard devia-            3 procedures                          43                    13.31%
tion (SD), otherwise median and interquartile range (IQR;           4 procedures                          19                     5.88%
25th -75th percentile) were reported. Qualitative variables         5 procedures                          14                     4.33%
were summarised as counts and percentages. The compari-             6 procedures                          5                      1.55%
sons between gender or patients with one procedure versus
                                                                    7 procedures                          7                      2.16%
patients with more than one procedure were performed with
                                                                    8 procedures                          2                      0.62%
chi-square test for categorical variables and Student’s t test
(or Kruskall-Wallis test if data are skewed) for continuous         9 procedures                          1                      0.31%
variables. All tests were two-sided and p values < 0.05 were        10 procedures                         1                      0.31%
considered statistically significant. The data analysis was         Total                                323                     100%
performed with the STATA statistical package (release 14.0,
2015, Stata Corporation, College Station, Texas, USA).
                                                                   tasias were analysed before the first surgery and this data
Results                                                            was available for 160/323 patients (49.5%): according to the
                                                                   description performed by Pagella et al. in 2009 6, the most
Five hundred and ninety-one HHT patients, diagnosed                common pattern was “mixed” (90 patients, 56.3%), followed
according to the Curacao criteria, were hospitalised and           by the “large” (56 patients, 35%) and “punctate” pattern (14
screened at our department. Of these, 323 patients (54.7%)         patients, 8.7%) (Fig. 2). The nasal septum and lateral nasal
underwent endoscopic surgery for epistaxis, for a total of         walls were involved, respectively, in 91.9% and 91.3% of
679 procedures. Concerning mutational screening, analy-            patients, and the nasal floor in 43.7% and nasal valve in 31%.
ses were completed on 207 patients: 152 patients (73.4%)           Interestingly, a significant difference (p = 0.033) between
carried a mutation in ACVRL1, while 55 (26.6%) carried a           males and females was found in the pattern of telangiecta-
mutation in ENG.                                                   sias: the punctate pattern was more common in females (11
The group consisted of 182 men (56.3%) and 141 women               vs 3), while mixed and large patterns were more common in
(43.6%), with a mean age of 56 years at first surgery (range       males (respectively 51 vs 39 and 33 vs 23).
5–86 years); interestingly, we found a significant difference      In our sample of HHT patients treated with endoscopic
between males (mean 53 years, SD 14 years) and females             endonasal mini-invasive technique, APC (Fig. 3) was the
(mean 57 years, SD 15 years) regarding mean age at first
surgery (p = 0.0158).
General anaesthesia was used in 524 procedures (77.2%),
while local anaesthesia was used in 155 (22.8%). In 175
patients (54.2%), a single surgical procedure was effective
to obtain acceptable control of epistaxis (median follow-up
in this group was 48 months), while 148 patients (45.8%)
required more than one procedure over time, for a total num-
ber of 679 procedures (Tab. I). During the follow-up period,
25 patients (7.7%) were lost and 31 patients (9.6%) died.
The mean number of surgical procedures in our group was
1.9 in females (SD 1.4), 2.3 in males (SD 1.8) and 2.1 (SD
1.6) overall. No significant difference was noted between
ACVRL1 and ENG patients regarding the number of surgi-
cal procedures (one surgery vs two or more; p = 0.1389). In
patients with more than one surgery, the time between pro-
cedures was analysed (Tab. II; Fig. 1). Preoperative epistaxis
                                                                   Figure 1. Plot showing the time between surgical procedures (in days) in
severity was scored according to Pagella et al. and was mod-       HHT patients with more than one surgery. Columns: medians; lines: interquar-
erate or severe in all patients 6. Characteristics of telangiec-   tile ranges. Females represented in white and males in black.



                                                                                                                                           61
F. Pagella et al.




Table II. Time between surgical procedures in patients with more than one surgery. Results are reported in days, with the median of days between surgeries in
each subgroup.
                                      No. of patients                  Median                    IQR (25th- 75th)                Min             Max
 First – Second                                 150                          612                  299               1225                23                 4979
 Second – Third                                 92                           447                  205               769                 17                 3810
 Third – Fourth                                 50                           540                  267               917                 14                 2175
 Fourth – Fifth                                 30                           420                  279               762                 55                 1820
 Fifth – Sixth                                  16                           583                  278               848                 19                 1211
 Sixth – Seventh                                11                           224                   42               697                 21                 1468
 Seventh – Eighth                                4                           322                  207               647                133                 930
 Eighth – Ninth                                  2                           345                  311               379                311                 379
 Ninth – Tenth                                   1                           261                  261               261                261                 261




Figure 2. Nasal endoscopies in HHT patients, different patterns are shown. In (A), “large” pattern. In (B), “mixed” pattern. In (C), “punctate” pattern.


instrument of choice (661 procedures, 97.3%), while lasers                           visualisation of the intraoperative field. In our experience,
(diode, thulium) and quantum molecular resonance tech-                               we successfully used these devices during surgery in 83
nology (Figs. 4, 5) were used in 15 procedures (2.2%).                               procedures (12.2%).
Since 2004, intranasal haemostatic matrices such as Floseal                          Septal perforation was observed in 75 patients (23.2%).
(Baxter, U.S.), Surgiflo (Ethicon, U.S.), Perclot (Cryolife,                         Among these, 31 patients (41.3%) had a septal perforation
U.S.), or Haemocer (BioCer GmbH, Germany) were intro-                                before our first surgery, so in these patients the complica-
duced in our clinical practice in order to permit adequate                           tion was not related to our treatment. On the other hand,
management of severe intraoperative bleeding and better                              44 patients (58.7%) developed a septal perforation during




Figure 3. Intraoperative endoscopic sequence showing an APC procedure on left-side telangiectasias located on the lateral nasal wall.



62
                                                                                          Endoscopic surgical treatment of epistaxis in HHT: our experience




Figure 4. Intraoperative endoscopic sequence showing a thulium laser procedure on a right-side telangiectasia located on the nasal septum.


our treatment: 18 patients (40.9%) after one procedure, 8                       bidity, reduced trauma of nasal mucosa, low risk of septal
patients (18.2%) after two procedures, 12 patients (27.3%)                      perforation, treatment repeatability, no need for post-surgical
after three procedures, and 6 patients (13.6%) after four or                    nasal packing, the possibility of local anaesthesia and short
more procedures. In most of these patients, previous surgery                    time of hospitalisation. A review of the literature suggests
in another hospital was performed, which could explain the                      that the choice of treatment should be based on the severity
relatively high rate of septal perforations in our group.                       of nosebleeds: in cases of bleeding of mild entity, a mini-
                                                                                invasive technique can be proposed; on the other hand, in
Discussion                                                                      patients with severe epistaxis more invasive surgeries should
                                                                                be chosen (e.g. septodermoplasty, septectomy, closure of the
Epistaxis in HHT remains a problem with regards to defini-                      nostrils) 10. However, in 2013, our group demonstrated the
tive treatment: current therapies permit control of nosebleeds,                 efficacy and long-term benefit of a mini-invasive approach
but not complete resolution. As stated by Silva et al., first-                  (APC) in a group of HHT patients affected by severe epistax-
line treatment of HHT-related nosebleeds includes hygiene                       is with a history of blood transfusion 16.
of the nasal cavities and avoidance of triggering factors 7.                    In this paper, we report our 20-year experience in the sur-
Different therapies, both medical and surgical, have been                       gical management of epistaxis in HHT, focusing on endo-
proposed in the literature 5,8-45. In our opinion, endoscopic                   scopic mini-invasive techniques. The Department of Oto-
endonasal mini-invasive techniques have several advantages                      rhinolaryngology at I.R.C.C.S. Policlinico San Matteo in
over other techniques, and these are represented by less mor-                   Pavia is a reference centre for diagnosis and treatment of




Figure 5. Intraoperative endoscopic sequence showing the quantum molecular resonance technology procedure on a left-side telangiectasia located on the
inferior turbinate/nasal valve.



                                                                                                                                                       63
F. Pagella et al.




HHT in Italy, and, over the period analysed (1996-2015),          patterns. We also observed a higher incidence of mixed and
591 patients with a diagnosis of HHT (according to Cura-          large patterns in surgical candidates; this is in accordance
cao criteria) were referred to our centre. The first concept      with a previous paper in which we observed a significantly
that should be stressed is that only 54.7% of these patients      higher frequency of nosebleeds in patients presenting the
required surgery for control of epistaxis. This is, to the best   large pattern 6.
of our knowledge, one of the most extensive reported case         Regarding surgical technique applied, APC was the instru-
series on epistaxis surgical treatment in HHT. For the re-        ment of choice in most of our patients (661 procedures,
maining 268 patients, although epistaxis was still present        97.3%), while lasers and quantum molecular resonance tech-
(in fact, it is usually the most common symptom that leads        nology were used only in 2.7% of cases. Indeed, APC is our
to diagnostic suspicion), quality of life-related to this prob-   instrument of choice in the treatment of epistaxis in HHT pa-
lem was deemed acceptable and did not require further in-         tients independently of preoperative epistaxis severity, which
terventions. Another interesting piece of data is that in 175     was moderate or severe before surgery in all patients 14,16.
patients (54.2%), a single surgical procedure was effective       Bergler first described APC treatment of nosebleeds in 1999
to obtain acceptable control of epistaxis (median follow-         on 12 HHT patients 17. From a technical point of view, APC is
up: 48 months), while 148 patients (45.8%) required more          based on high-frequency electric energy transmitted through
than one procedure over time; even if not objective, this         ionised argon gas. The generator is set at 40–60 W and the
is a good outcome measure of patient satisfaction with            argon gas flow at 1.2 L/min. Endoscopic endonasal visuali-
epistaxis control. In our opinion, in fact, it is essential to    sation permits selective treatment in a noncontact mode of
take into consideration the personal satisfaction of each pa-     telangiectasias located along all the nasal fossae (also in their
tient, given that each treatment used for epistaxis in HHT is     posterior portion) and in the nasopharynx. Coagulation of
symptomatic. According to this management strategy, Sau-          tissue is limited to a 1-2 mm depth. This permits low risk of
tter and Smith also stated in 2016 that, regardless of treat-     local tissue damage because the temperature is rarely over
ment modality, HHT-related epistaxis would continue 10.           100°C. Finally, the applicator tips can be sterilised, and the
The mean number of surgical procedures in our group was           cost of argon gas is very low.
2.1 (1.9 in females and 2.3 in males, no significant dif-         In the literature, multiple techniques have been described
ference). No significant difference was reported between          for endoscopic surgical treatment of nasal telangiectasias
ACVRL1 and ENG patients regarding the number of pro-              (Tab. III). Ablative therapies, such as sclerotherapy, electro-
cedures. Repetition of a mini-invasive surgical procedure,        surgery and laser treatment, show good outcomes in reduc-
given its low risk of short-term and long-term complica-          ing epistaxis in HHT patients. Sclerotherapy with foamed
tions (44/323 patients developed a septal perforation dur-        sodium tetradecyl sulfate has been shown to be effective
ing treatment, most underwent previous repeated cauteri-          and safe in four studies, including one randomised clinical
sations in other hospitals) is possible when nasal bleeding       trial 20-23. The potential side effects are tissue necrosis, cel-
returns and has a negative impact on the quality of life. A       lulitis at the site of injection and, more rarely, anaphylaxis,
“staged” procedure should be performed when telangiecta-          pulmonary embolus and permanent blindness due to cen-
sias are present on opposing sides of the anterior nasal sep-     tral retinal artery or ophthalmic artery occlusion 24.
tum in order to avoid septal perforation. Moreover, some          Bipolar electrosurgery is preferable to monopolar elec-
authors report that submucosal injections of bevacizumab          trosurgery due to the lower risk of septal perforation, and
associated with surgical treatment may increase the risk of       Ghaheri et al. reported on the efficacy of bipolar cautery for
perforation 10.                                                   epistaxis treatment in HHT 25.
Regarding the characteristics of nasal telangiectasias, data      Laser photocoagulation is also a viable option, and many
was available for 160 of 323 patients (49.5%): the most           different types of laser exist 18,26,29. Lasers with higher tis-
common pattern was mixed (90 patients, 56.3%), followed           sue penetration that use haemoglobin as a chromophore,
by the large (56 patients, 35%), and punctate patterns (14        such as the Nd:YAG laser, are preferred over lasers with
patients, 8.7%). The nasal septum and lateral nasal walls         less penetration. The problem with laser use is that not all
were involved, respectively, in 91.9% and 91.3% of pa-            devices can be used with flexible fibres, and the manoeu-
tients, nasal floor in 43.7% and nasal valve in 31%. Wide         verability inside nasal cavities can be limited. Moreover,
variability can be found not only in the nasal pattern of         increased thermal damage to surrounding tissue is a con-
telangiectasias, but also in the number of nasal subsites         cern when using lasers.
involved, even in patients with the same pattern. Further-        Multiple uncontrolled series demonstrated that laser treat-
more, we confirmed that different subsites in nasal fossae,       ments are efficient in reducing epistaxis duration, frequen-
and even the same subsite, can present similar or different       cy and severity in HHT patients 14,16-18,27-31.



64
                                                                                                Endoscopic surgical treatment of epistaxis in HHT: our experience




Table III. Surgical techniques for epistaxis treatment in HHT patients.
 Study                                 Study design          No. of            Treatment              Outcome of interest                   Results
                                                            patients
 Boyer H. et al., 2011 20               Retrospective           7            Sclerotherapy           Epistaxis frequency and            100% improved
                                                                                                             severity
 Morais D. et al., 2012 21              Retrospective          45            Sclerotherapy           Epistaxis frequency and             95% Improved
                                                                                                             severity
 Boyer H. et al., 2015 22               Randomised             17            Sclerotherapy                      ESS                        Improved
                                       controlled trial
 Esteban-Casado S. et al.,             Cross-sectional         38            Sclerotherapy              ESS, VAS, EQ-5D                    Improved
 2019 23                                                                    and topical nasal
                                                                               propranolol
 Ghaheri B. et al., 2006 25             Retrospective          18            Bipolar cautery           Need for recurrent        Recurrent intervention in 50%
                                                                                                          intervention            at a mean follow-up of 2.3
                                                                                                                                             years
 Bergler W. et al., 1999 17              Prospective           12                 APC                Epistaxis frequency and               Improved
                                                                                                             intensity
 Pagella F. et al., 2006 14              Prospective           36                 APC                  Reported bleeding         100% reduction at 6 months
 Pagella F. et al., 2013 16             Retrospective          26                 APC                     Epistaxis score           Improved at 12 months
 Jørgensen G. et al., 2011 28            Prospective           30                Laser                  Epistaxis duration       Reduced at 1.5 and 6 months
 Kuan E.C. et al., 2017 31              Retrospective          20                Laser                       SNOT-22               Improved at 1.5 months
 Fiorella M.L. et al., 2012 18          Retrospective          24             Diode laser            Epistaxis frequency and              Improved
                                                                                                              severity
 Poje G. et al., 2017 32                Retrospective          17             Diode laser            Epistaxis frequency and               Improved
                                                                                                              severity
 Papaspyrou G. et al., 2016 29          Retrospective          38             Nd:YAG laser             Need for recurrent       18% recurrent intervention at a
                                                                                                           intervention            mean follow-up of 3 years
 Papaspyrou G. et al., 2017 30           Prospective           45         Nd:YAG laser +/- APC         Need for recurrent        20-33% recurrent intervention
                                                                                                           intervention                 at 3-10 years
 Joshi H. et al., 2011 36                Case series            5              Coblation                 Epistaxis control             80% of patients
 Mortuaire G. et al., 2013 34            Prospective           16              Coblation             Epistaxis frequency and    Reduced frequency at 6 months
                                                                                                             duration
 Rotenberg B. et al., 2015 35           Retrospective          37              Coblation                        ESS                  Improved at 6 months
 Luk L. et al., 2014 27                  Prospective           11          Coblation vs KTP                     ESS                No difference in mean ESS
                                                                                  laser
 Ishibashi T. et al., 2003 33            Case report            2              Harmonic              Frequency of epistaxis                Improved
                                                                                 Scalpel
                                                                           Harmonic scalpel
 Ichimura K. et al., 2006 38            Retrospective          15          Septodermoplasty            Patient satisfaction                100% satisfied
 Lesnik G.T. et al., 2007 15            Retrospective           9          Septodermoplasty         Epistaxis frequency, QoL,      100% improved QoL, blood
                                                                            with septectomy            blood transfusions               transfusion reduced
 Levine C.G. et al., 2008 39            Retrospective         106          Septodermoplasty                     QoL                 62% responded and 86%
                                                                                                                                             improved
 Harvey R. et al., 2008 37              Retrospective          33          Septodermoplasty          Frequency of KTP laser           Frequency of KTP laser
                                                                                                                                    treatment decreased (p =
                                                                                                                                               0.012)
 Rimmer J. et al., 2014 40               Prospective            7          Septodermoplasty         Epistaxis frequency and             100% improvement
                                                                                                             severity
 Lee J.M. et al., 2019 44                Prospective            7           Temporary nasal       ESS and clinical assessment            No significant ESS
                                                                             occlusion with              of nasal cavity            improvement(p = 0.179);
                                                                                Floseal®                                           clinical assessment of nasal
                                                                                                                                  cavity improved (p = 0.0088)
                                                                                                                                             at 1 month
 Hosni A.A. et al., 1994 13              Case series            2            Nasal closure             Epistaxis frequency                    Improved

                                                                                                                                                               u


                                                                                                                                                               65
F. Pagella et al.




Table III. (follows).
 Study                                     Study design            No. of            Treatment                Outcome of interest                        Results
                                                                  patients
 Ichimura K. et al., 2012 41                 Prospective              7             Nasal closure              Epistaxis cessation                    57% success
 Richer S. et al., 2012 42                  Retrospective             43            Nasal closure              Epistaxis cessation             84% responded and 83%
                                                                                                                                                        success
 Lund V. et al., 2017 12                    Retrospective            100            Nasal closure              Epistaxis cessation             50% responded and 94%
                                                                                                                                                        success
 Andersen J.H. et al., 2020 43              Retrospective             10            Nasal closure                       GBI                    Overall GBI score of 38.05
                                                                                                                                              with an average follow-up 66
                                                                                                                                                         months
ESS: Epistaxis Severiry Score; VAS: visual analoge scale; EQ-5D: EuroQol-5D scale; APC: Argon plasma coagulation; SNOT-22: Sinonasal outcome test-22; QoL: Quality of life; KTP:
Potassium-titanyl-phosphate; GBI: Glasgow benefit inventory.



Ishibashi and Takamatsu described the intraoperative appli-                                intraoperative field: we successfully used these devices in 83
cation of the harmonic scalpel (an ultrasonic system) in two                               procedures (12.2%). To the best of our knowledge, only one
HHT patients; highlighting the lack of damage to the sur-                                  description of the intranasal use of a haemostatic matrix in
rounding mucosa, but long-term results were not reported 33.                               HHT has been reported 44.
Some authors described coblation in the treatment of HHT-                                  Possible drawbacks of this study include the lack of objec-
related nosebleeds; this method has been shown to be a use-                                tive outcome measures, its retrospective nature and the lack
ful alternative to other surgical devices, improving nose-                                 of a control group treated with different procedures (e.g.
bleed severity 33-35.                                                                      APC vs other techniques).
Septodermoplasty and nasal closure are considered useful
in patients whose epistaxis fails to respond sufficiently to                               Conclusions
ablative therapies 35. According to several authors, septoder-
moplasty improves both quality of life and epistaxis sever-                                Recurrent epistaxis from telangiectasias of the nasal mucosa
ity 37-40. This surgical technique permits an adequate treat-                              is a common manifestation present in more than 95% of HHT
ment of septal lesions, while it does not allow for epistaxis                              patients. Current therapies cannot permit a definitive resolu-
control in situations where bleeding originates in the lateral                             tion of the symptom, but only temporary control of nose-
wall, which was involved in more than 90% of patients in                                   bleeds and improvement in the quality of life. Herein, we
our group. Worsening sinus infections, decreased sense of                                  describe our 20-year experience in the endoscopic surgical
smell and crusting are the major complications 36.                                         treatment of epistaxis in a large group of 323 HHT patients.
Only a few studies have investigated nasal closure out-                                    Endoscopic endonasal mini-invasive surgical options, and in
comes, but there is general agreement on the efficacy in                                   particular APC, allowed good control of epistaxis without
controlling nose bleeds, with an epistaxis cessation rate                                  major complication and nasal packaging. These treatment
ranging from 57 to 94% 41-43.                                                              modalities are repeatable, non-invasive and can be used as
The major limit in comparing different surgical techniques                                 a first step even in patients with severe epistaxis. In conclu-
in HHT is that there is no homogeneity among outcomes                                      sion, since no treatment could be considered definitive and
defining surgical success: some authors used epistaxis se-                                 the natural history of HHT-related nosebleeds is unknown, in
verity score as the primary outcome, while others report                                   our opinion the application of mini-invasive treatment mo-
only patient satisfaction or quality of life (Tab. III).                                   dalities that permit preservation of nasal anatomy and physi-
A fundamental preoperative step is careful preparation of the                              ology should be the approach of choice.
nasal cavities before surgery with local decongestion and me-
ticulous cleaning of crusting and blood clots. In case of pro-                             References
fuse and uncontrollable intraoperative bleeding, we suggest                                1
                                                                                               Faughnan ME, Palda VA, Garcia-Tsao G, et al. International guide-
a “three-hands” or even a “four-hands” procedure: two sur-                                     lines for the diagnosis and management of hereditary haemorrhagic
geons in the operative room, one holding the endoscope and                                     telangiectasia. J Med Genet 2011;48:73-87. https://doi.org/10.1136/
the APC and the other holding the suction tube (one or two if                                  jmg.2009.069013
necessary). Moreover, an intranasal haemostatic matrix can
                                                                                           2
                                                                                               Olivieri C, Pagella F, Semino L, et al. Analysis of ENG and ACVRL1
                                                                                               genes in 137 HHT Italian families identifies 76 different mutations
be applied during surgery to permit adequate management of                                     (24 novel). Comparison with other European studies. J Hum Genet
severe intraoperative bleeding and better visualisation of the                                 2007;52:820-9. https://doi.org/10.1007/s10038-007-0187-5




66
                                                                                           Endoscopic surgical treatment of epistaxis in HHT: our experience




3
     Pagella F, Pusateri A, Chu F, et al. Narrow-band imaging in the endo-      19
                                                                                     Chin CJ, Rotenberg BW, Witterick IJ. Epistaxis in hereditary hem-
     scopic evaluation of hereditary hemorrhagic telangiectasia patients. La-        orrhagic telangiectasia: an evidence based review of surgical man-
     ryngoscope 2013;123:2967-8. https://doi.org/10.1002/lary.24338                  agement. J Otolaryngol Head Neck Surg 2016;45:3. https://doi.
4
     Pagella F, Pusateri A, Zaccari D, et al. Fluorescein-guided intraopera-         org/10.1186/s40463-016-0116-8.
     tive endoscopy in patients with hereditary hemorrhagic telangiectasia:     20
                                                                                     Boyer H, Fernandes P, Duran O, et al. Office-based sclerotherapy
     first impressions. Int Forum Allergy Rhinol 2017;7:300-3. https://doi.          for recurrent epistaxis due to hereditary hemorrhagic telangiectasia:
     org/10.1002/alr.21880                                                           a pilot study. Int Forum Allergy Rhinol 2011;1:319-23. https://doi.
5
     Invernizzi R, Quaglia F, Klersy C, et al. Efficacy and safety of tha-           org/10.1002/alr.20053
     lidomide for the treatment of severe recurrent epistaxis in hereditary     21
                                                                                     Morais D, Millás T, Zarrabeitia R, et al. Local sclerotherapy with
     haemorrhagic telangiectasia: results of a non-randomised, single-               polydocanol (Aethoxysklerol®) for the treatment of epistaxis in rendu-
     centre, phase 2 study. Lancet Haematol 2015;2:e465-e73. https://doi.            osler-weber or hereditary hemorrhagic telangiectasia (HHT): 15 years
     org/10.1016/S2352-3026(15)00195-7                                               of experience. Rhinology 2012;50:80-6. https://doi.org/10.4193/Rhi-
6
     Pagella F, Colombo A, Matti E, et al. Correlation of severity of                no11.211
     epistaxis with nasal telangiectasias in hereditary hemorrhagic telan-      22
                                                                                     Boyer H, Fernandes P, Le C, et al. Prospective randomized trial of
     giectasia (HHT) patients. Am J Rhinol Allergy 2009;23:52-8. https://            sclerotherapy vs standard treatment for epistaxis due to hereditary
     doi.org/10.2500/ajra.2009.23.3263                                               hemorrhagic telangiectasia. Int Forum Allergy Rhinol 2015;5:435-40.
7
     Silva BM, Hosman AE, Devlin HL, et al. Lifestyle and dietary in-                https://doi.org/10.1002/alr.21484
     fluences on nosebleed severity in hereditary hemorrhagic telangi-          23
                                                                                     Esteban-Casado S, Martín de Rosales Cabrera AM, Usarralde Pérez
     ectasia. Laryngoscope 2013;123:1092-9. https://doi.org/10.1002/                 A, et al. Sclerotherapy and topical nasal propranolol: an effective and
     lary.23893                                                                      safe therapy for HHT-epistaxis. Laryngoscope 2019;129:221623.
8
     Gaillard S, Dupuis-Girod S, Boutitie F, et al. Tranexamic acid for              https://doi.org/10.1002/lary.27930
     epistaxis in hereditary hemorrhagic telangiectasia patients: a Euro-       24
                                                                                     Hanks JE, Hunter D, Goding GS Jr, et al. Complications from of-
     pean cross-over controlled trial in a rare disease. J Thromb Haemost            fice sclerotherapy for epistaxis due to hereditary hemorrhagic telan-
     2014;12:1494-502. https://doi.org/10.1111/jth.12654                             giectasia (HHT or Osler-Weber-Rendu). Int Forum Allergy Rhinol
9
     Dupuis-Girod S, Ambrun A, Decullier E, et al. ELLIPSE Study: a                  2014;4:422-7. https://doi.org/10.1002/alr.2128
     Phase 1 study evaluating the tolerance of bevacizumab nasal spray          25
                                                                                     Ghaheri BA, Fong KJ, Hwang PH. The utility of bipolar electrocau-
     in the treatment of epistaxis in hereditary hemorrhagic telangiecta-            tery in hereditary hemorrhagic telangiectasia. Otolaryngol Head Neck
     sia. mAbs 2014;6:793-8. https://doi.org/10.4161/mabs.28025                      Surg 2006;134:1006-9. https://doi.org/10.1016/j.otohns.2005.12.019
10
     Sautter NB, Smith TL. Treatment of hereditary hemorrhagic telan-           26
                                                                                     Abiri A, Goshtasbi K, Maducdoc M, et al. Laser-assisted control of
     giectasia-related epistaxis. Otolaryngol Clin North Am 2016;49:639-             epistaxis in hereditary hemorrhagic telangiectasia: a systematic re-
     54. https://doi.org/10.1016/j.otc.2016.02.010                                   view. Lasers Surg Med 2020;52:293-300. https://doi.org/10.1002/
11
     Faughnan ME, Mager JJ, Hetts SW, et al. Second International Guide-             lsm.23147
     lines for the diagnosis and management of hereditary hemorrhagic           27
                                                                                     Luk L, Mace JC, Bhandarkar ND, et al. Comparison of electrosurgi-
     telangiectasia. Ann Intern Med 2020;173:989-1001. https://doi.                  cal plasma coagulation and potassium-titanyl-phosphate laser photo-
     org/10.7326/M20-1443                                                            coagulation for treatment of hereditary hemorrhagic telangiectasia-
12
     Lund VJ, Darby Y, Rimmer J, et al. Nasal closure for severe heredi-             related epistaxis. Int Forum Allergy Rhinol 2014;4:640-5. https://doi.
     tary haemorrhagic telangiectasia in 100 patients. The Lund modifi-              org/10.1002/alr.21328
     cation of the Young’s procedure: a 22-year experience. Rhinology           28
                                                                                     Jørgensen G, Lange B, Wanscher JH, et al. Efficiency of laser treat-
     2017;55:135-41. https://doi.org/10.4193/Rhin16.315                              ment in patients with hereditary hemorrhagic telangiectasia. Eur Arch
13
     Hosni AA, Innes AJ. Hereditary haemorrhagic telangiectasia:                     Otorhinolaryngol 2011;268:1765-70. https://doi.org/10.1007/s00405-
     Young’s procedure in the management of epistaxis. J Laryngol Otol               011-1677-9
     1994;108:754-7. https://doi.org/10.1017/s0022215100128026                  29
                                                                                     Papaspyrou G, Schick B, Al Kadah B. Nd:YAG laser treatment for
14
     Pagella F, Semino L, Olivieri C, et al. Treatment of epistaxis in he-           extranasal telangiectasias: a retrospective analysis of 38 patients
     reditary hemorrhagic telangiectasia patients by argon plasma coagu-             with hereditary hemorrhagic telangiectasia and review of the litera-
     lation with local anesthesia. Am J Rhinol 2006;20:421-5. https://doi.           ture. ORL J Otorhinolaryngol Relat Spec 2016;78:245-51. https://doi.
     org/10.2500/ajr.2006.20.2886                                                    org/10.1159/000447949
15
     Lesnik GT, Ross DA, Henderson KJ, et al. Septectomy and septal der-
                                                                                30
                                                                                     Papaspyrou G, Hecker D, Linxweiler M, et al. Combined therapy for
     moplasty for the treatment of severe transfusion-dependent epistaxis            epistaxis by hereditary hemorrhagic teleangiectasia: a 3-year follow
     in patients with hereditary hemorrhagic telangiectasia and septal               up study on 45 patients. J Craniomaxillofac Surg 2017;45:1179-82.
     perforation. Am J Rhinol 2007;21:312-5. https://doi.org/10.2500/                https://doi.org/10.1016/j.jcms.2017.05.018
     ajr.2007.21.3017                                                           31
                                                                                     Kuan EC, Peng KA, Thompson CF, et al. Sinonasal quality of life
16
     Pagella F, Matti E, Chu F, et al. Argon plasma coagulation is an effec-         outcomes following laser treatment of epistaxis related to hereditary
     tive treatment for hereditary hemorrhagic telangiectasia patients with          hemorrhagic telangiectasia. Lasers Med Sci 2017;32:527-31. https://
     severe nosebleeds. Acta Otolaryngol 2013;133:174-80. https://doi.or             doi.org/10.1007/s10103-017-2144-7
     g/10.3109/00016489.2012.718097                                             32
                                                                                     Poje G, Kavanagh MM. Hereditary hemorrhagic telangiectasia-laser
17
     Bergler W, Riedel F, Baker-Schreyer A, et al. Argon plasma coagula-             treatment of epistaxis. Ear Nose Throat J 2017;96:E10-E4.
     tion for the treatment of hereditary hemorrhagic telangiectasia. La-       33
                                                                                     Ishibashi T, Takamatsu S. Hereditary hemorrhagic telangiectasis
     ryngoscope 1999;109:15-20. https://doi.org/10.1097/00005537-                    treated by the harmonic scalpel. Head Neck 2003;25:333-6. https://
     199901000-00004                                                                 doi.org/10.1002/hed.10201
18
     Fiorella ML, Lillo L, Fiorella R. Diode laser in the treatment of          34
                                                                                     Mortuaire G, Boute O, Hatron PY, et al. Pilot study of submucosal
     epistaxis in patients with hereditary haemorrhagic telangiectasia. Ac-          radiofrequency for epistaxis in hereditary hemorrhagic telangiecta-
     ta Otorhinolaryngol Ital 2012;32:164-9.                                         sia. Rhinology 2013;51:355-60. https://doi.org/10.4193/Rhin13.027




                                                                                                                                                        67
F. Pagella et al.




35
     Rotenberg B, Noyek S, Chin CJ. Radiofrequency ablation for treat-           hereditary hemorrhagic telangiectasia. Laryngoscope 2014;124:67-9.
     ment of hereditary hemorrhagic telangiectasia lesions: “How I do            https://doi.org/10.1002/lary.24303
     it”. Am J Rhinol Allergy 2015;29:226-7. https://doi.org/10.2500/       41
                                                                                 Ichimura K, Kikuchi H, Imayoshi S, et al. Are patients with severe
     ajra.2015.29.4163                                                           epistaxis caused by hereditary hemorrhagic telangiectasia satisfied
36
     Joshi H, Woodworth BA, Carney AS. Coblation for epistaxis manage-           with nostril closure surgery? Auris Nasus Larynx 2012;39:59-64.
     ment in patients with hereditary haemorrhagic telangiectasia: a mul-        https://doi.org/10.1016/j.anl.2011.03.003
     ticentre case series. J Laryngol Otol 2011;125:1176-80. https://doi.   42
                                                                                 Richer SL, Geisthoff UW, Livada N, et al. The Young’s proce-
     org/10.1017/S0022215111001733                                               dure for severe epistaxis from hereditary hemorrhagic telangiecta-
37
     Harvey RJ, Kanagalingam J, Lund VJ. The impact of septoder-                 sia. Am J Rhinol Allergy 2012;26:401-4. https://doi.org/10.2500/
     moplasty and potassium-titanyl-phosphate (KTP) laser therapy                ajra.2012.26.3809
     in the treatment of hereditary hemorrhagic telangiectasia-related      43
                                                                                 Andersen JH, Kjeldsen AD. Patient-recorded benefit from nasal clo-
     epistaxis. Am J Rhinol 2008;22:182-7. https://doi.org/10.2500/              sure in a Danish cohort of patients with hereditary haemorrhagic tel-
     ajr.2008.22.3145                                                            angiectasia. Eur Arch Otorhinolaryngol 2020;277:791-800. https://
38
     Ichimura K, Tanaka H, Yamamoto Y, et al. Nasal dermoplasty for              doi.org/10.1007/s00405-019-05758-1
     Japanese hereditary hemorrhagic telangiectasia. Auris Nasus Larynx     44
                                                                                 Lee JM, Wu V, Faughnan ME, et al. Prospective pilot study of Flo-
     2006;33:423-8. https://doi.org/10.1016/j.anl.2006.03.001                    seal® for the treatment of anterior epistaxis in patients with hereditary
39
     Levine CG, Ross DA, Henderson KJ, et al. Long-term complications            hemorrhagic telangiectasia (HHT). J Otolaryngol Head Neck Surg
     of septal dermoplasty in patients with hereditary hemorrhagic telan-        2019;48:48. https://doi.org/10.1186/s40463-019-0379-y
     giectasia. Otolaryngol Head Neck Surg 2008;138:721-4. https://doi.     45
                                                                                 Meccariello G, Georgalas C, Montevecchi F, et al. Management of
     org/10.1016/j.otohns.2008.01.005                                            idiopathic epistaxis in adults: what’s new? Acta Otorhinolaryngol Ital
40
     Rimmer J, Lund VJ. A modified technique for septodermoplasty in             2019;39:211-9. https://doi.org/10.14639/0392-100X-2155




68
