Publications by authors named "Enzo Emanuelli"

54 Publications

Bilateral Choanal Atresia and Endoscopic Surgery: A Chance for CHARGE Patients.

J Clin Med 2021 Jun 30;10(13). Epub 2021 Jun 30.

Department of Neurosciences, Section of Otorhinolaryngology, University of Padova, 35128 Padova, Italy.

Bilateral choanal atresia (CA) is a rare congenital malformation frequently associated with other anomalies. CHARGE association is closely linked to bilateral CA. The aim of this study was to describe the outcomes of the endoscopic repair in bilateral CA, and to assess the role of postoperative nasal stenting in two cohorts of CHARGE-associated and non-syndromic CA. Thirty-nine children were retrospectively analyzed (16 patients had CHARGE-associated CA). The rate of postoperative neochoanal restenosis was 31.3% in the CHARGE population, and 47.8% in the non-syndromic CA cohort. Data on postoperative synechiae and granulation tissue formation, need for endonasal toilette and dilation procedures, and number of procedures per patient were presented. Stent positioning led to a higher number of postoperative dilation procedures per patient in the non-syndromic cohort ( = 0.018), and to a higher rate of restenosis both in the CHARGE-associated, and non-syndromic CA populations. Children with CHARGE-associated and non-syndromic bilateral CA benefitted from endonasal endoscopic CA correction. The postoperative application of an endonasal stent should be carefully evaluated.
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http://dx.doi.org/10.3390/jcm10132951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269040PMC
June 2021

Sinonasal Squamous Cell Carcinoma, a Narrative Reappraisal of the Current Evidence.

Cancers (Basel) 2021 Jun 7;13(11). Epub 2021 Jun 7.

Section of Otorhinolaryngology-Head and Neck Surgery, Department of Neurosciences, University of Padua-"Azienda Ospedaliera di Padova", 35128 Padua, Italy.

Sinonasal squamous cell carcinoma is a rare tumor affecting the nasal cavity and paranasal sinuses. Several aspects of this disease, ranging from epidemiology to biology, pathology, diagnosis, staging, treatment, and post-treatment surveillance are controversial, and consensus on how to manage this sinonasal cancer is lacking. A narrative literature review was performed to summarize the current evidence and provide the reader with available data supporting the decision-making process in patients affected by sinonasal squamous cell carcinoma, alongside the authors' personal opinion on the unsolved issues of this tumor. The review has highlighted several advances in molecular definition of epithelial cancers of the sinonasal tract. Surgery represents the pivot of treatment and is performed through an endoscopic transnasal approach whenever feasible. Open surgery is required for a large proportion of cases. Reconstruction of the defect follows principles of skull base and cranio-maxillo-facial reconstruction. Chemotherapy is given as neoadjuvant treatment or concomitantly to radiotherapy. Photon-based radiation therapy has a crucial role in the adjuvant setting. Particle therapy is providing promising results. Management of the neck should be planned based on the presence of clinically appreciable metastases, primary tumor extension, and need for recipient vessels. Biotherapy and immunotherapy are still underexplored therapeutical modalities.
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http://dx.doi.org/10.3390/cancers13112835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201377PMC
June 2021

Sellar and parasellar lesions: multidisciplinary management.

Acta Otorhinolaryngol Ital 2021 Apr;41(Suppl. 1):S30-S41

Department of Neurosciences DNS, Neurosurgery Section, Padua University, Padua, Italy.

Introduction: The endoscopic endonasal transsphenoidal approach to the sella and parasellar regions is now increasingly used for removal of a variety of lesions localized in the ventral skull base. The advantage of the endoscope is enhanced visualization and improved panoramic view that can result in more complete removal of the tumor. An extensive knowledge of the anatomy is mandatory to approach this region.

Materials And Methods: From February 2009 to March 2020, the endoscopic endonasal approach was used in 153 patients with sellar and parasellar lesions, at our Institution: 136 pituitary adenomas, 7 craniopharyngiomas, 3 Rathke's cysts, a tuberculum sellae meningioma, an aneurysm of the internal carotid artery (ICA), a clivus chordoma, a papillary glioneuronal tumor, an histiocytosis, a pituitary metastasis from breast cancer and a chondrosarcoma.

Results: The most common surgical complications were cerebral spinal fluid leak (9), bleeding (2), pituitary abscess (2). Among endocrinological complications, the most important were diabete insipidus (23) and panhypopituitarism (3). Two patients complicated with meningitis. There were no visual worsening and no operative mortality. We had persistence of disease in 20 cases. Twelve patients underwent surgical revision for recurrence of the disease.

Conclusions: Pre-operative planning and collaboration with several specialists are necessary in order to offer the patient the best treatment, minimizing complications.
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http://dx.doi.org/10.14639/0392-100X-suppl.1-41-2021-03DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172107PMC
April 2021

When is a multidisciplinary surgical approach required in sinonasal tumours with cranial involvement?

Acta Otorhinolaryngol Ital 2021 Apr;41(Suppl. 1):S3-S17

Section of Otorhinolaryngology, Head and Neck Surgery, University of Padua, "Azienda Ospedaliera di Padova", Padua, Italy.

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http://dx.doi.org/10.14639/0392-100X-suppl.1-41-2021-01DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172110PMC
April 2021

Agger nasi mucocele cause nasolacrimal duct obstruction and chronic dacryocystitis: clinical profile, management and outcome.

BMJ Case Rep 2021 May 24;14(5). Epub 2021 May 24.

Department of Neurosciences, Faculty of Medicine and Surgery, University of Padova, Padova, Italy.

Epiphora is the first symptom of acquired nasolacrimal duct obstruction (NLDO), which may be due to various causes, including paranasal sinuses and tumours of the nasal cavity. A 28-year-old male patient presented chronic dacryocystitis with left-sided epiphora. Endoscopically, a bulging of the lateral nasal wall at the left-sided agger nasi area was noted. Imaging studies (CT and MRI) revealed a left-sided giant agger nasi mucocele. An endonasal endoscopic dacryocystorhinostomy (DCR) as well as opening of the agger nasi cell with mucocele removal and anterior ethmoidectomy was performed. Based on the literature, intranasal causes have very often occurred in patients with chronic dacryocystitis, but not reported as the cause of inflammation in the mucocele of agger nasi. Identification and recognition of this endonasal rare cause of NLDO-like agger nasi mucocele entity may facilitate timely intervention and can be treated successfully with a simultaneous endoscopic DCR procedure.
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http://dx.doi.org/10.1136/bcr-2021-242140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154990PMC
May 2021

Orbital metastasis from hepatocellular carcinoma revealed by sudden exophthalmos.

BMJ Case Rep 2021 May 12;14(5). Epub 2021 May 12.

Department of Neuroscience, University of Padova, Padova, Veneto, Italy.

Orbital metastases represent a rare condition and only 33 cases of metastases from hepatocellular carcinoma (HCC), usually revealed by slowly progressive exophthalmos, have been described in the literature. A 62-year-old man affected by HCC reported a sudden left exophthalmos and amaurosis. A cranial CT scan revealed pathological tissue occupying the superior portion of the orbit. During endoscopic decompression of the optic nerve, an active venous intraorbital haemorrhage was noted. Following angiography, permanent occlusion was performed on a neoforming circulus fed by ramification of the anterior deep temporal artery, anterior ramification of the superficial temporal artery and sphenoidal ramification of the medial meningeal artery. A percutaneous incisional orbital biopsy showed features of metastatic foci of HCC. This is the first description of orbital metastasis from HCC revealed by a sudden exophthalmos.
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http://dx.doi.org/10.1136/bcr-2021-242136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8118017PMC
May 2021

Diagnosis and treatment of congenital nasal glioma.

BMJ Case Rep 2021 Apr 13;14(4). Epub 2021 Apr 13.

Department of Neuorosciences, University of Padova Faculty of Medicine and Surgery, Padova, Veneto, Italy.

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http://dx.doi.org/10.1136/bcr-2021-242138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051431PMC
April 2021

TUSC (TUrbinate Surgery Classification): A Novel Classification Proposal for Turbinate Surgery.

Ear Nose Throat J 2020 Dec 11:145561320981448. Epub 2020 Dec 11.

ENT & Audiology Unit, Department of Neuroscience and Rehabilitation, University Hospital of Ferrara, Ferrara, Italy.

Aim of this manuscript is to propose a clear and easily applicable classification for turbinate surgery, based on the use of a numerical model, which could be introduced in the practice of Otolaryngologists and Maxillo-Facial surgeons.Applying this classification, it will be possible to offer an easy format when describing which turbinates are involved in a procedure, and to offer a quick method to record and analyse clinical data, also for scientific purpose.
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http://dx.doi.org/10.1177/0145561320981448DOI Listing
December 2020

Health-Related Quality of Life in Patients With ANCA-Associated Vasculitis and Sinonasal Involvement: A Single-Center Cross-Sectional Study.

J Clin Rheumatol 2020 Oct 30. Epub 2020 Oct 30.

Rheumatology Unit, Department of Medicine DIMED, University of Padua, Padua, Italy.

Background/objective: The aim of this study was to assess the impact of sinonasal morbidity on quality of life (QoL) in antineutrophil cytoplasmic antibody-associated vasculitis (AAV).

Methods: This cross-sectional case-control study enrolled 71 patients-44 AAV cases with (ear, nose, and throat [ENT]-AAV) or without ENT involvement (non-ENT-AAV) undergoing multidisciplinary evaluations and 27 chronic rhinosinusitis (CRS) cases. Three validated QoL questionnaires (Sino-Nasal Outcomes Test-22 [SNOT-22], Nasal Obstruction Symptom Evaluation [NOSE], and Short-Form 36) were administered, and the 3 groups were compared.

Results: The ENT-AAV patients were significantly younger (p = 0.01), with less antineutrophil cytoplasmic antibody positivity frequency (p = 0.035) and lower renal involvement (p = 0.003) than the non-ENT-AAV patients.The SNOT-22 questionnaire demonstrated significantly greater sinonasal morbidity in ENT-AAV patients compared with CRS patients (p < 0.001). The NOSE score of ENT-AAV patients was comparable to those of CRS patients, but higher than that of non-ENT-AAV patients (p < 0.001). The SNOT-22 and NOSE scores positively correlated with disease activity (p = 0.037; p = 0.004, respectively). Short-Form 36 domain-by-domain analysis revealed a significantly poorer QoL in ENT-AAV patients, especially with physical functioning being progressively impaired in CRS, non-ENT-AAV, and ENT-AAV patients (p < 0.001). No significant differences in QoL came to light when AAV patients were stratified according to current systemic o local treatments.

Conclusions: The QoL in AAV patients is significantly reduced, especially in the presence of ENT involvement. The AAV-related nasal morbidity is consistent and comparable to that reported by CRS patients. It significantly affects patients' QoL and in particular social functioning, leading to limitation in daily/work activities. Organ-focused questionnaires and multidisciplinary management are warranted to pursue a treat-to-target approach in these patients.
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http://dx.doi.org/10.1097/RHU.0000000000001630DOI Listing
October 2020

Disorders Involving a Persistent Craniopharyngeal Canal: A Case Series.

J Neurol Surg B Skull Base 2020 Oct 21;81(5):562-566. Epub 2019 Jun 21.

Department of Otorhinolaryngology - Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States.

 A persistent craniopharyngeal canal (CPC) is a rare embryologic remnant that presents as a well-corticated defect of the midline sphenoid body extending from the sellar floor to the nasopharynx. Our case series aims to describe three unique presentations of this congenital anomaly and their subsequent management.  Retrospective review.  Tertiary academic medical center.  Patients who underwent endoscopic transnasal surgical repair of a CPC lesion.  Resolution of symptoms and surgical outcomes.  A total of three patients were identified. The clinical presentation varied, however, all cases prompted further imaging which demonstrated a persistent CPC and associated pathologic lesion. The presentation of a persistent CPC with nasal obstruction and subsequent iatrogenic cerebrospinal fluid leak as in Case 1 demonstrates the importance of imaging in this work-up. Cases 2 and 3 in the series were representative of the larger subset of patients in the literature who present with the defect incidentally but still warrant surgical management. Nonetheless, a standard approach to diagnosis with preoperative imaging and subsequent transnasal endoscopic repair of the skull base defect was undertaken.  The persistent CPC is a rare congenital anomaly associated with diverse pathology and careful review of preoperative radiology is critical to the management. When warranted, subsequent surgical repair and reconstruction is associated with excellent postoperative outcomes.
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http://dx.doi.org/10.1055/s-0039-1692638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591367PMC
October 2020

Endoscopic sinus surgery outcomes in CRS: quality of life and correlations with NOSE scale in a prospective cohort study.

Eur Arch Otorhinolaryngol 2021 Apr 8;278(4):1059-1066. Epub 2020 Sep 8.

Department of Otolaryngology, University Hospital of Larisa, University of Thessaly, Larissa, Greece.

Background: To evaluate the impact of endoscopic sinus surgery (ESS) on clinical outcomes, quality of life (QoL) and Nasal Obstruction and Symptom Evaluation (NOSE) scale in patients with CRSwNP and CRSsNP. An additional question that needs to be investigated is whether there is a correlation between patients at the age of relapse.

Methodology/principal: A prospective cohort study of 150 subjects [96 males, 54 females, mean age: 51.99 ± (15.73)]. The SNOT-22 and NOSE questionnaires were used to measure the patients' QoL and their nasal blockage symptoms, respectively. Endoscopic and computerized tomography (CT) scores depicted the objective findings.

Results: Following ESS, the endoscopic scale showed a significant improvement in 83.85% of patients. QoL measured with SNOT-22 improved by 78.85% and with NOSE scale by 92.10%. Also, a statistically significant correlation was found between NOSE, SNOT-22 and the Lund-Kennedy scale. Recurrence was observed in 13 patients during follow-up. There was no statistically significant correlation between age, gender, smoking and recurrence tendency. Patients with baseline SNOT-22 and NOSE scores lower than 30 typically fail to obtain a clinically meaningful benefit. Patients with a rate greater than or equal to 40 achieved a minimal clinically important difference (MCID) of 83.9% and had an average symptom reduction (RI) rate of 60.3%.

Conclusions: ESS is an important treatment option for symptomatic patients with CRSwNP and CRSsNP. Both objective and subjective measurements including QoL improved significantly, and the results stabilized at 12 to 18 months. The NOSE scale is a sensitive outcome measure in the CRS population, including subjects with and without nasal polyps. In our study, SNOT-22 and NOSE are excellent predictors of postoperative improvement.
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http://dx.doi.org/10.1007/s00405-020-06334-8DOI Listing
April 2021

Correction to: Multiple spontaneous skull base cerebrospinal fluid leaks: some insights from an international retrospective collaborative study.

Eur Arch Otorhinolaryngol 2020 Dec;277(12):3365

ENT Department, Ospedale Bellaria, Bologna, Italy.

In the original publication of the article, the following affiliation "Medical school, University of Nicosia, Nicosia, Cyprus" of the author "Christos Georgalas" was missed and included in this correction.
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http://dx.doi.org/10.1007/s00405-020-06283-2DOI Listing
December 2020

Multiple spontaneous skull base cerebrospinal fluid leaks: some insights from an international retrospective collaborative study.

Eur Arch Otorhinolaryngol 2020 Dec 28;277(12):3357-3363. Epub 2020 Jul 28.

ENT Department, Ospedale Bellaria, Bologna, Italy.

Purpose: Spontaneous skull base cerebrospinal fluid leaks occurring without any apparent cause are rare. But those patients that present such leaks simultaneously, or successively, in multiple locations are even rarer. Given the rarity of this condition, we collected data from other groups in a multicentre study to reach an adequate number of patients and draw some preliminary considerations.

Methods: We carried out a multicentre retrospective study on a cohort of patients treated at third level hospitals in Italy, Spain, United Kingdom and Greece for multiple spontaneous-CSF leaks and we compared them with a control group of patients treated for recurrent spontaneous-CSF leaks. Data regarding clinical aspects, radiological findings, surgical techniques and outcome were collected and preliminary considerations on the results were discussed.

Results: A total of 25 patients presented multiple simultaneous spontaneous CSF leaks while 18 patients fit with the criteria of recurrent spontaneous CSF leaks. Data analysis was conducted separately.

Conclusions: Our understanding of the pathogenesis of this condition is currently very limited. A causative role of IIH may be present but the differences that emerged from the comparison with patients with recurrent fistulas seem to promote the possible role of other cofactors. A longer follow-up period is needed, and, in our opinion, prospective and multicentre studies are the only solution to seriously deal with such a complex topic.
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http://dx.doi.org/10.1007/s00405-020-06227-wDOI Listing
December 2020

Ectopic lacrimal gland in the lacrimal sac mimicking tumour: literature review.

BMJ Case Rep 2020 Jul 22;13(7). Epub 2020 Jul 22.

Otolaryngology and Otologic Surgery, University of Padova, Padova, Veneto, Italy.

An 80-year-old man referred with repeated episode of dacryocystitis from the left lacrimal drainage system and palpable swelling. For many years, he has being presented with epiphora unilaterally with chronic dacryocystitis. Investigations with dye-test revealed subocclusion of the natural passage of the tears, and CT and MRI scans revealed solid mass in the lacrimal sac. The lacrimal sac was opened by endonasal endoscopic approach, the sacral mass was identified and completely removed. The histopathological examination showed lacrimal gland in ectopic position. Patient followed for 18 months with complete recovery of symptoms. In our differential diagnosis, the ectopic lacrimal gland is also identified, when a mass in the lacrimal sac and duct is present. Successful surgical excision required considerable multidisciplinary teamwork between ophtalmologist-ENT (Otolaryngologist) and radiologist. Endonasal endoscopic approach is perfectly safe with direct control and ensures a smooth postoperative recovery.
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http://dx.doi.org/10.1136/bcr-2020-235187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380840PMC
July 2020

18F-FDG PET/MRI of Rhinosporidiosis of the Upper Airways.

Clin Nucl Med 2020 Oct;45(10):e461-e462

From the Unit of Otorhinolaryngology, Department of Neurosciences.

A 41-year-old man from South Asia presented with a several months' history of unilateral nasal obstruction and bleeding. At nasal endoscopy, two strawberry-like, friable, polypoid masses in the upper airways were detected. The patient's clinical trait was compatible with an infectious disease. F-FDG PET/MRI was performed to evaluate the disease extension. Two lesions occupying the nasal cavity and the nasopharynx, slightly hyperintense in T2-weighted sequences, with intense radiopharmaceutical uptake were evidenced. Endoscopic resection was performed with histopathologic diagnosis of rhinosporidiosis, a chronic granulomatous disease caused by Rhinosporidium seeberi. Although rare, rhinosporidiosis should be considered in the differential diagnoses of sinonasal hypermetabolic lesions.
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http://dx.doi.org/10.1097/RLU.0000000000003138DOI Listing
October 2020

Benralizumab as a glucocorticoid-sparing treatment option for severe asthma in eosinophilic granulomatosis with polyangiitis.

J Allergy Clin Immunol Pract 2020 10 4;8(9):3225-3227.e2. Epub 2020 Jun 4.

Rheumatology Unit, Department of Medicine DIMED, University of Padova, Padova, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.jaip.2020.05.033DOI Listing
October 2020

High prevalence of human papillomavirus infection in sinonasal inverted papilloma: a single-institution cohort of patients.

Int Forum Allergy Rhinol 2020 05 27;10(5):629-635. Epub 2020 Feb 27.

Department of Medicine, Surgical Pathology and Cytopathology Section, University of Padova, Padova, Italy.

Background: Both the prevalence of sinonasal inverted papilloma (IP) and the causal association with alpha-human papillomaviruses (alpha-HPVs) are controversial. In this study we aimed to determine HPV status in histologically selected, microdissected, formalin-fixed, and paraffin-embedded tissue samples of IP.

Methods: HPV status was assessed retrospectively by polymerase chain reaction (PCR)-bead-based multiplex genotyping on tissue samples of patients diagnosed with IP and consecutively treated with endoscopic resection. Forty-one HPV genotypes were considered, distinguishing between high risk and low risk. HPV status was correlated with demographics and clinical variables. Sixty sinonasal IP tissue samples were initially considered. After exclusion of 5 cases due to insufficient quality/quantity of the samples, 55 patients were included for analysis.

Results: HPV-DNA sequences were identified in 34 of 55 (61.8%) IPs, with a higher prevalence of high-risk than low-risk HPV genotypes (19 [55.9%] and 15 cases [44.1%], respectively). HPV16 strongly prevailed among the high-risk HPV cases (84.2%), and HPV54 prevailed among the low-risk HPV cases (53.3%). IPs with origin within the maxillary sinus were significantly associated with high-risk HPV (p = 0.019). No significant associations emerged between HPV status and demographics or clinical variables.

Conclusion: In a series of 55 IP tissue samples, HPV-DNA sequences were identified in 61.8% of cases, which differs from the data of previous investigations. Further case-control studies are advocated to confirm this prevalence in the Italian population addressed, and also to clarify any pathogenic involvement of HPV in the natural history of IPs.
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http://dx.doi.org/10.1002/alr.22539DOI Listing
May 2020

Deep Neck Abscesses in Children: An Italian Retrospective Study.

Pediatr Emerg Care 2020 Feb 24. Epub 2020 Feb 24.

Department for Woman and Child Health-Pediatric Emergency Department, University of Padua, Padua.

Background: Retropharyngeal and parapharyngeal abscesses (RPAs, PPAs) usually affect young children. Surgical drainage and/or antibiotic therapy are treatment of choice, but no specific guidelines exist. In order to reduce the risk of severe complications, appropriate diagnosis and therapy are necessary. The aims of the study were to review diagnosis and management of children with RPAs/PPAs and to compare surgical versus medical approach.

Methods: This is a multicenter retrospective study including all patients younger than 15 years admitted at 4 Italian pediatric hospitals of Florence, Padua, Rome, and Treviso, with International Classification of Diseases, Ninth Revision discharge diagnosis code of RPAs and PPAs, from January 1, 2008, to December 31, 2016.

Results: One hundred fifty-three children were included. The median age was 4.4 years, with overall male predominance. Heterogeneous signs and symptoms (fever, neck cervical, lymphadenopathy, pain, and stiff neck most frequently) and a large mixture of bacteria from pus cultures were detected. Computer tomography (66.7%) and magnetic resonance imaging (27.5%) were performed to confirm the presence of abscess. Fifty-one percent of abscesses were greater than 3 cm. Eighty-seven patients (56.9%) underwent surgery, and 66 (43.1%) were treated with antibiotics alone (mostly ceftriaxone, metronidazole, amikacin, and clindamycin) with median days of therapy of 26.5 days and length of therapy of 16.0 days of median. Median length of stay was 11 days. None had severe complications. Multivariate analysis indicated as independent predictive factors of surgery abscess of 3 cm or greater, high white blood cell count, and-most of all-the hospital of admission.

Conclusions: Deep neck abscesses mostly affect patients in early childhood, with a combination of nonspecific signs and symptoms, and it still emerges as a heterogeneous approach in diagnosis and management of these infections. Thus, common shared protocols represent an essential tool in order to standardize care and improve patients' outcomes.
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http://dx.doi.org/10.1097/PEC.0000000000002037DOI Listing
February 2020

Tumor budding is an adverse prognostic marker in intestinal-type sinonasal adenocarcinoma and seems to be unrelated to epithelial-mesenchymal transition.

Virchows Arch 2020 Aug 24;477(2):241-248. Epub 2020 Jan 24.

Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padova, Via Aristide Gabelli, 61, 35121, Padua, Italy.

Intestinal-type adenocarcinoma (ITAC) of sinonasal tract is a rare malignant tumor with strong morphological, immunophenotypical, and molecular similarities to colorectal adenocarcinoma (CRC). Tumor budding (TB) is a well-established adverse prognostic marker in CRC and some head and neck tumors, with features of epithelial-mesenchymal transition (EMT). The aim of this study was to assess TB in ITAC and to evaluate its possible association with EMT markers in this setting. We selected 32 surgically resected specimens of non-mucinous/non-signet ring ITAC and evaluated them for TB according to the international recommendations developed for CRC. The expression of the EMT markers E-cadherin, ZEB1, ZEB2, SLUG, and SNAIL was evaluated by immunohistochemistry (IHC). Results were stratified using clinical and follow-up data (2/32 patients had metastatic disease and 4/32 died of disease). We observed TB in 13/32 (40.6%) ITAC cases including the 7 patients with relapse (p = 0.0005) and the 4 patients dead of disease (p = 0.02). Lymphovascular invasion was associated with TB (p = 0.008). Absence of TB was associated with low ZEB2 expression (p = 0.003). No other association with EMT markers emerged. Occupational exposure to wood and leather dust was not related to the presence of TB. TB interobserver concordance was substantial (proportion of agreement = 87%; Cohen's kappa = 0.73). This work suggests that TB is associated with a worse prognosis in ITAC, but our findings do not seem to support the involvement of EMT in this specific setting. Further larger studies are needed to address this point.
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http://dx.doi.org/10.1007/s00428-020-02748-1DOI Listing
August 2020

Comments on "Nasolacrimal Duct Management During Endoscopic Sinus and Skull Base Surgery".

Ann Otol Rhinol Laryngol 2020 01 5;129(1):93-94. Epub 2019 Sep 5.

Department of Neuroscience, Unit of Otorhinolaryngology, University of Padova, Padova, Italy.

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http://dx.doi.org/10.1177/0003489419873353DOI Listing
January 2020

The diagnostic value of cytology in parotid Warthin's tumors: international multicenter series.

Head Neck 2020 03 24;42(3):522-529. Epub 2019 Nov 24.

Department of ENT/Head and Neck Surgery, Queen Elizabeth University Hospital Birmingham, Birmingham, UK.

Introduction: Warthin's tumor (WT) is a common benign salivary gland neoplasm with a negligible risk of malignant transformation. However, there is a risk of malignant tumors being misdiagnosed as WT on cytology and inappropriately managed conservatively.

Methods: Patients from nine centers in Italy and the United Kingdom undergoing parotid surgery for cytologically diagnosed WT were included in this multicenter retrospective series. Definitive histology was compared with preoperative cytological diagnoses. Surgical complications were recorded.

Results: A total of 496 tumors were identified. In 88.9%, the final histological diagnosis was WT. In 21 cases (4.2%) a malignant neoplasm was diagnosed, which had been incorrectly labeled as WT on cytology.

Conclusions: The risk of undiagnosed malignancy should be balanced against surgical risks when considering the management of WT. Although nonsurgical management remains an appropriate option, there may be a rationale for serial clinical or radiological evaluation if surgical excision is not performed.
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http://dx.doi.org/10.1002/hed.26032DOI Listing
March 2020

Rapid disease progression in patient with mismatch-repair deficiency pituitary ACTH-secreting adenoma treated with checkpoint inhibitor pembrolizumab.

Anticancer Drugs 2020 02;31(2):199-204

Department of Oncology, Medical Oncology 1, Veneto Institute of Oncology IOV-IRCCS.

Secreting pituitary adenomas are tumors for which few treatment options are available, including surgical treatment and management of hormonal imbalance due to altered pituitary secretion. In case of inoperable relapse, radiotherapy or chemotherapeutic treatment can be considered; the effectiveness of these treatments, however, remains limited. In the immunotherapy era, it is necessary to select patients who can benefit from immunotherapeutic treatment. Mismatch repair deficiency is strongly associated with responsiveness to anti-PD-1 in other cancers and can be detected using immunohistochemistry for MLH1, MSH2, MHS6, and PMS2. In this case report, we report a case of rapid disease progression to pembrolizumab in a patient with a MMRd pituitary adrenocorticotropic hormone (ACTH)-secreting adenoma. For the best of our knowledge, we described for the first time, a poor efficacy of pembrolizumab in a patient with ACTH-secreting pituitary adenoma having mismatch repair deficiency probably caused by high levels of cortisol in this patient. Prospective study should be performed to assess the activity of immune checkpoint inhibitor alone or in association with temozolomide in this subsetting of pituitary adenomas.
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http://dx.doi.org/10.1097/CAD.0000000000000856DOI Listing
February 2020

Fungus ball of the maxillary sinus: Retrospective study of 48 patients and review of the literature.

Am J Otolaryngol 2019 Sep - Oct;40(5):700-704. Epub 2019 Jun 15.

Azienda Ospedaliero Universitaria of Udine, Department of Medical and Biological Science, University of Udine, Udine, Italy.

Background: Maxillary fungus ball (FB) is the most frequent paranasal localization.

Objective: To review clinical presentation, surgery and results of treatment in our series of patients with maxillary FB. To review the literature concerning treatment of maxillary FB.

Patients And Methods: 48 patients with a diagnosis of maxillary FB were treated with endoscopic sinus surgery (ESS) alone or in association with external approaches. Before surgery all patients received computed tomography (CT), nasal endoscopy and dental examination. All the patients were followed for 1 year after surgery. Studies concerning surgical treatment of maxillary FB from 2006 were reviewed.

Results: The mean age of patients was 53.6 ± 11.9 years. 20 patients (41.6%) did not present any symptom, 19 patients (39.7%) had nasal symptoms, 3 patients (6.2%) had facial pain, 6 patients (12.5%) had a combination of both. Endoscopic examination was positive in 31 patients (64.6%), 17 patients (35.4%) showed negative findings. Logit regression model demonstrated that clinical symptoms contribute to the prediction of a positive endoscopic examination. 25 patients (52.1%) presented odontogenic factors. Complete clinical and radiological resolution of FB was observed in 46 patients (95.8%).

Conclusions: Comparing our sample to the studies reviewed we may concluded that odontogenic factors were frequently reported and should be treated at the same time of maxillary FB. ESS alone or in association with external approaches is an effective treatment for patients with maxillary FB.
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http://dx.doi.org/10.1016/j.amjoto.2019.06.006DOI Listing
February 2020

Single-step surgical treatment of odontogenic maxillary sinusitis: A retrospective study of 98 cases.

J Craniomaxillofac Surg 2019 Aug 4;47(8):1249-1254. Epub 2019 May 4.

Maxillofacial Surgery, Chief of Maxillofacial Surgery Unit, Azienda Ospedaliero Universitaria of Udine, Department of Medical and Biological Science, University of Udine, Udine, Italy.

Purpose: The aim of this study was to review clinical and radiological presentation, surgery, and results of treatment in patients with chronic odontogenic maxillary sinusitis (OMS) treated with a single surgical procedure, including endoscopic sinus surgery (ESS) and oral surgical approaches to treat the odontogenic source of infection.

Materials And Methods: A retrospective case series analysis of 98 patients was performed. All the patients received ESS. 88 patients required oral surgical approaches.

Results: Nasal symptoms were present in 58 patients (59.2%). Nasal endoscopy was positive in 65 patients (66.3%). A positive nasal endoscopy was significantly associated with nasal symptoms (p < 0.05). 60 patients (61.2%) had OMS of iatrogenic origin. Total opacification of the maxillary sinus was the most common radiological presentation (74.5%) and was significantly associated with nasal symptoms (p < 0.05). 91 patients (92.9%) had complete clinical and radiological resolution of the OMS.

Conclusions: Iatrogenic origin, sinonasal symptoms and positive clinical endoscopy are common in patients with OMS. Nasal symptoms were significantly associated with total maxillary sinus opacification and positive endoscopic clinical examination. Combining treatment of the odontogenic source of infection via an oral surgical approach and of the sinus inflammation by ESS appears to be sufficient for successfully treating patients with OMS.
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http://dx.doi.org/10.1016/j.jcms.2019.04.012DOI Listing
August 2019

HER2 status in sinonasal intestinal-type adenocarcinoma.

Pathol Res Pract 2019 Jun 28;215(6):152432. Epub 2019 Apr 28.

Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padova, Padova, Italy. Electronic address:

Given that the prognosis of patients with sinonasal intestinal-type adenocarcinoma (ITAC) has not significantly changed recently, there is a desire for new therapeutic approaches to improve clinical management. HER2-targeted therapy has remarkably improved the overall survival of patients with HER2 amplified tumors. To date, HER2 assessment has produced contradictory results in ITAC. The aim of this study was to assess HER2 status at both protein and DNA levels in a large series of ITAC. HER2 status was assessed by immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH) in forty-three patients that underwent surgical resection for ITAC at the Otorhinolaryngology Section, Padua University Hospital, between 2007 and 2016. IHC was evaluated using the four-tier score developed for gastroesophageal cancer. As for IHC, 83.7% (36/43) of ITAC were scored 0, 14% (6/43) 1+, and 2.3% (1/43) 2+. No HER2 amplification was detected by CISH. The present is the largest study of sinonasal ITAC tested with both IHC and CISH confirmation for HER2 status. No HER2 overexpression/amplification was detected. Contrary to previous studies, our findings seem to rule out any oncogenetic role of HER2 in ITAC pathogenesis.
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http://dx.doi.org/10.1016/j.prp.2019.04.024DOI Listing
June 2019

Malignant Versus Benign Tumors of the Sinonasal Cavity: A Case-Control Study on Occupational Etiology.

Int J Environ Res Public Health 2018 12 17;15(12). Epub 2018 Dec 17.

Department of Cardiac Thoracic Vascular Sciences and Public Health, Preventive Medicine and Risk Assessment Unit, University of Padova, Via Giustiniani 2, 35128 Padova, Italy.

Case-control studies on malignant sinonasal tumors and occupational risk factors are generally weakened by non-occupational confounders and the selection of suitable controls. This study aimed to confirm the association between sinonasal malignant tumors and patients' occupations with consideration for sinonasal inverted papillomas (SNIPs) as a control group. Thirty-two patients affected by adenocarcinoma (ADC) and 21 non-adenocarcinoma epithelial tumors (NAETs) were compared to 65 patients diagnosed with SNIPs. All patients were recruited in the same clinical setting between 2004 and 2016. A questionnaire was used to collect information on non-occupational factors (age, sex, smoking, allergies, and chronic sinusitis) and occupations (wood- and leather-related occupations, textile industry, metal working). Odds ratios (OR) with 95% confidence intervals (CI) associated with selected occupations were obtained by a multinomial and exact logistic regression. Between the three groups of patients, SNIP patients were significantly younger than ADC patients ( = 0.026). The risk of NAET increased in woodworkers (OR = 9.42; CI = 1.94⁻45.6) and metal workers (OR = 5.65; CI = 1.12⁻28.6). The risk of ADC increased in wood (OR = 86.3; CI = 15.2⁻488) and leather workers (OR = 119.4; CI = 11.3⁻1258). On the exact logistic regression, the OR associated to the textile industry was 9.32 (95%CI = 1.10⁻Inf) for ADC, and 7.21 (95%CI = 0.55⁻Inf) for NAET. Comparing sinonasal malignant tumors with controls recruited from the same clinical setting allowed demonstrating an increased risk associated with multiple occupations. Well-matched samples of cases and controls reduced the confounding bias and increased the strength of the association.
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http://dx.doi.org/10.3390/ijerph15122887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6313789PMC
December 2018

Clinical features and management of antrochoanal polyps in children: Cues from a clinical series of 58 patients.

Int J Pediatr Otorhinolaryngol 2018 Nov 29;114:87-91. Epub 2018 Aug 29.

ENT Department, University Hospital of Ferrara, Italy.

Objective: To review the clinical features of pediatric patients affected by antrochoanal polyps (ACPs) and surgically treated at three University settings.

Methods: Retrospective study. The present research includes the clinical data of subjects affected by ACPs, aged <18 years and referred to three ENT Departments, between January 1st 2003 and September 30th 2016. All patients underwent nasal endoscopy and sinonasal imaging; all subjects have been treated surgically.

Results: Fifty-eight patients underwent functional endoscopic sinus surgery (FESS) for ACPs removal, under general anesthesia. There were no major intraoperative complications. Recurrence occurred in 12 cases (20.5%).

Conclusions: FESS was the first-choice treatment for APCs in the present series; our recurrence rate was similar to that of other reports available in literature. Recurrences of ACPs in children still represent a clinical challenge; it is likely that an improved comprehension of ACPs biology could help in better understanding the pathophysiology of this disease.
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http://dx.doi.org/10.1016/j.ijporl.2018.08.033DOI Listing
November 2018

Endoscopic Transsphenoidal Salvage Surgery for Symptomatic Residual Cystic Craniopharyngioma after Radiotherapy.

J Neurol Surg B Skull Base 2018 Apr 8;79(Suppl 3):S256-S258. Epub 2018 Feb 8.

Department of Neurosciences, Neurosurgery Section, University of Padua, Padua, Italy.

 Ideal treatment of craniopharyngiomas is still controversial. Radiotherapy (RT) is considered effective for recurrences or after subtotal tumor removal (STR). About 40 to 50% of patients may experience tumor cyst expansion soon after RT; in these cases, the role of salvage surgery is debated.  Operative video.  Tertiary care center.  An 11-year-old boy diagnosed with persistent craniopharyngioma. In 2015, the patient underwent right frontotemporal craniotomy for STR at another center, complicated by panhypopituitarism. Two years later, fractionated 54-Gy RT was performed on growing residual tumor. After 3 months, he was admitted to our hospital due to persistent malaise, vomiting, pulsating headache, and epistaxis. Ophthalmologic evaluation evidenced left homonymous hemianopsia.  A contrast-enhanced magnetic resonance imaging (MRI) showed a 27-mm cystic component enlarging from the cranial end of the persistent craniopharyngioma lesion, extending into the third ventricle. Biventricular hydrocephalus and brain midline shift to the right were present. Compared with the early post-RT MRI, the cystic component of the tumor demonstrated growth. The patient underwent external ventricular drainage placement for emergent treatment of hydrocephalus and endoscopic transsphenoidal surgery. After cystic content drainage, the lesion was completely removed with its capsule. A "gasket seal" technique was performed for skull base reconstruction, with autologous fascia lata, septal bone, and mucoperiosteum from inferior turbinate. Histologic examination confirmed the craniopharyngioma diagnosis. Postoperative MRI showed resolution of the hydrocephalus and complete tumor removal.  Although shrinkage of cystic components of craniopharyngioma residuals may occur within 5 to 6 months after RT, salvage surgery is indicated in symptomatic patients. The link to the video can be found at https://youtu.be/4x6Qe76bf60 .
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http://dx.doi.org/10.1055/s-0038-1636504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5868918PMC
April 2018
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