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Πέμπτη, 28 Φεβρουαρίου 2019

Extranodal natural killer/T‐cell lymphoma (ENKTL)

Allergy/Rhinology
Prognostic indicators of survival in sinonasal extranodal natural killer/T‐cell lymphoma
Antonios N. Varelas BA  Ashwin Ganti BA  Michael Eggerstedt MD  Bobby A. Tajudeen MD
First published: 23 February 2019 https://doi.org/10.1002/lary.27886
Editor's Note: This Manuscript was accepted for publication on February 5, 2019.

Abstract
Objectives
Extranodal natural killer/T‐cell lymphoma (ENKTL) is a highly aggressive tumor of the sinonasal tract associated with poor overall survival (OS). This study expands upon epidemiologic, prognostic, and treatment factors for OS and disease‐specific survival (DSS), incorporating newly accessible chemotherapy data.

Methods
Retrospective population‐based cohort study performed on cases of sinonasal ENKTL identified through the Surveillance, Epidemiology, and End Results database. Univariate Kaplan‐Meier analysis and subsequent multivariate Cox‐regression analysis were performed to evaluate prognostic and treatment variables for OS and DSS.

Results
Four hundred and sixty cases of sinonasal ENKTL were identified. Five‐year OS and DSS were 46% and 56%, respectively. On multivariate analysis, higher Ann Arbor stage was associated with worse OS (P < 0.001) and DSS (P < 0.001), whereas administration of radiotherapy was associated with improved OS (P < 0.001) and DSS (P = 0.001). Additionally, a higher age at diagnosis was associated with reduced OS (P = 0.024). Chemotherapy was associated with improved OS (P < .01) and DSS (P = .04) for Ann Arbor stage I disease. Surgery was not associated with improved survival.

Conclusion
This represents the first study to investigate the use of chemotherapy for the treatment of sinonasal ENKTL using population‐based analysis. Radiation therapy and chemotherapy significantly improve survival in all Ann Arbor stage patients and early‐stage patients, respectively. Early‐stage disease is significantly associated with improved survival. With no established treatment regimen for sinonasal ENKTL, these findings suggest combination chemoradiation is an effective therapy for prolonged survival, especially in early stages of disease.

Level of Evidence
3.

Laryngoscope, 2019

Submucosal Masses of the Upper Lip

Clinical Challenge 
Pathology
February 28, 2019
Author Affiliations 
  • 1Department of Otolaryngology–Head and Neck Surgery, University of Texas Southwestern Medical Center, Dallas
JAMA Otolaryngol Head Neck Surg. Published online February 28, 2019. doi:10.1001/jamaoto.2018.4363
Case
Awoman in her 60s reported right upper lip submucosal masses that had been present for several weeks. She denied associated pain, bleeding, or recent trauma to the lip. She also denied any other constitutional symptoms. Her social history was significant for a 45–pack-year smoking history and social drinking. On physical examination, the patient had right upper lip submucosal masses without any tenderness or mucosal abnormality. The remainder of the otolaryngic examination was unremarkable. A computed tomographic scan of the neck with contrast demonstrated multiple hyperenhancing nodules; the largest was 3 × 7 × 6 mm, with no local bony erosion or cervical lymphadenopathy (Figure 1).
Figure 1.
Computed tomographic (CT) scans of hyperenhancing nodules of the upper lip (red arrows).
Computed tomographic (CT) scans of hyperenhancing nodules of the upper lip (red arrows).

What Is Your Diagnosis?

  1. Multifocal basal cell adenoma
  2. Basal cell adenocarcinoma
  3. Multifocal canalicular adenoma
  4. Adenoid cystic carcinoma
Discussion
Diagnosis
C. Multifocal canalicular adenoma
Canalicular adenoma is an uncommon salivary gland tumor arising almost exclusively from the minor salivary glands of the oral cavity. It is usually asymptomatic and slow growing, and accounts for less than 1% to 3% of all salivary neoplasms.1,2 Canalicular adenoma is most commonly diagnosed as an upper lip nodule found in women in their seventh decade of life, as exemplified by our patient.1 Other locations in which canalicular adenoma can be found include the hard palate and buccal mucosa.1 It is the third most common benign salivary gland tumor, with a recurrence rate of approximately 5%.1,2 Canalicular adenoma was previously thought to be a variant of basal cell adenoma; however, its unique clinical and pathologic features warrant defining it as its own entity.3 For example, while canalicular adenoma is seen almost exclusively in the oral cavity, basal cell adenoma has a predilection for the major salivary glands, especially the parotid gland.2-4 This locational difference is the first hint in differentiating between these 2 entities.
Histologically, canalicular adenoma tends to be a well-circumscribed solitary nodule consisting of anastomosing cords formed by columnar cells arranged in a loose connective tissue stroma.1,2 As seen in this patient, however, approximately 15% of canalicular adenomas are multifocal, a feature that must not be misinterpreted as invasive growth, a defining feature of salivary gland carcinomas such as adenoid cystic carcinoma or basal cell adenocarcinoma. By immunohistochemistry, canalicular adenoma is consistently positive for S100 and SOX10, variably positive for p63, and negative for p40.1,2 Although basal cell adenoma is also composed of basaloid cells growing as nests and cords, it exhibits a more cellular stroma and has 2 cell populations: basaloid myoepithelial cells and ductal cells; the myoepithelial cells can by highlighted by immunohistochemistry for smooth muscle actin, calponin, glial fibrillary acidic protein, and others.5 More important, canalicular adenoma is composed of 1 population of ductal cells, and does not stain for myoepithelial elements that are found in basal cell adenoma, basal cell adenocarcinoma, and adenoid cystic carcinoma.4 Surgical resection is the treatment of choice for canalicular adenoma.1 In contrast, malignant neoplasms such as adenoid cystic carcinoma may need further management with radiotherapy and frequent monitoring, making differentiation imperative.6
Clinically, canalicular adenoma may mimic a mucocele, which is a collection of mucus in the soft tissue after rupture of a salivary gland duct.4,7 Both can present as well-demarcated blue-tinted masses or even match the color of normal oral mucosa.7 Unlike canalicular adenoma, mucoceles are often associated with a history of trauma, which our patient denied.7 In addition, mucoceles are often diagnosed earlier in life, around the second decade, and are found equally in males and females.7 Mucoceles are found predominately in the lower labial mucosa with virtually no presentation in the upper labial mucosa, making this diagnosis unlikely for our patient.7 Histologically, the differentiation is simple, with mucocele histologic characteristic showing mucin in a subepithelial vesicle.7
In summary, histologic characteristics and immunohistochemistry are crucial for distinguishing canalicular adenoma from other diagnoses. Canalicular adenoma is occasionally multifocal, a feature that must be distinguished from the truly invasive growth that characterizes similar-appearing malignant neoplasms. Although surgical resection is the mainstay of treatment for upper lip masses, differentiation is necessary in cases in which the diagnosis of adenoid cystic carcinoma necessitates concurrent use of radiotherapy. Other factors such as patient sex, decade of life, and location of mass are also helpful in the initial formation of a differential diagnosis.
Patient Outcome
After surgical excision, pathologic examination revealed a nodular proliferation of basaloid cells (Figure 2A) made up of nodules ranging from less than 1 to 7 mm. In the background minor salivary tissue, there were several additional microscopic, incipient nodules with an identical appearance (Figure 2B). The nodules were composed of nests and interconnecting cords of uniform cells with bland, elongated nuclei with vesicular chromatin and delicate nucleoli. The tumor cells were set in a loose myxoid stroma (Figure 2C). Although the tumor was multinodular, no convincing invasive growth was seen. By immunohistochemistry the tumor was diffusely positive for S100 and SOX10, focally positive for p63, and negative for p40.
Figure 2.
Staining of excised mass reveals nodular proliferation of basaloid cells (hematoxylin-eosin, original magnification x40) (A); microscopic, incipient nodules (black arrowheads) in the background minor salivary gland tissue (hematoxylin-eosin, original magnification x100) (B); and tumor cells in loose myxoid stroma (hematoxylin-eosin, original magnification x200) (C).
Staining of excised mass reveals nodular proliferation of basaloid cells (hematoxylin-eosin, original magnification x40) (A); microscopic, incipient nodules (black arrowheads) in the background minor salivary gland tissue (hematoxylin-eosin, original magnification x100) (B); and tumor cells in loose myxoid stroma (hematoxylin-eosin, original magnification x200) (C).
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Article Information
Corresponding Author: Larry L. Myers, MD, Department of Otolaryngology–Head and Neck Surgery, University of Texas Southwestern Medical Center, 2001 Inwood Rd, Dallas, TX 75390 (larry.myers@utsw.edu).
Published Online: February 28, 2019. doi:10.1001/jamaoto.2018.4363
Conflict of Interest Disclosures: None reported.
Additional Contributions: We thank the patient for granting permission to publish this information.
References
1.
Peraza  AJ, Wright  J, Gómez  R.  Canalicular adenoma.  J Craniomaxillofac Surg. 2017;45(10):1754-1758.PubMedGoogle ScholarCrossref
2.
Thompson  LDR, Bauer  JL, Chiosea  S,  et al.  Canalicular adenoma.  Head Neck Pathol. 2015;9(2):181-195.PubMedGoogle ScholarCrossref
3.
Daley  TD, Gardner  DG, Smout  MS.  Canalicular adenoma.  Oral Surg Oral Med Oral Pathol. 1984;57(2):181-188.PubMedGoogle ScholarCrossref
4.
Samar  ME, Avila  RE, Fonseca  IB, Anderson  W, Fonseca  GM, Cantín  M.  Multifocal canalicular adenoma of the minor labial salivary glands.  Int J Clin Exp Pathol. 2014;7(11):8205-8210.PubMedGoogle Scholar
5.
Machado de Sousa  SO, Soares de Araújo  N, Corrêa  L, Pires Soubhia  AM, Cavalcanti de Araújo  V.  Immunohistochemical aspects of basal cell adenoma and canalicular adenoma of salivary glands.  Oral Oncol. 2001;37(4):365-368.PubMedGoogle ScholarCrossref
6.
Bradley  PJ.  Adenoid cystic carcinoma of the head and neck.  Curr Opin Otolaryngol Head Neck Surg. 2004;12(2):127-132.PubMedGoogle ScholarCrossref
7.
Chi  AC, Lambert  PR  III, Richardson  MS, Neville  BW.  Oral mucoceles.  J Oral Maxillofac Surg. 2011;69(4):1086-1093.PubMedGoogle ScholarCrossref

Hearing Preservation Surgery via Retrosigmoid Approach with Retrolabyrinthine Meatotomy in Small Vestibular Schwannoma

10-1055-s-0039-1677847_180168ov-1.jpg

J Neurol Surg B
DOI: 10.1055/s-0039-1677847

Objectives Vestibular schwannomas (VS) extending into the internal auditory canal (IAC) are currently considered as an unfavorable condition for hearing preservation surgery (HPS) via retrosigmoid (RS) approach due to the poor direct visualization of the facial and cochlear nerves course through the IAC and the fundus during microsurgery. Design The operative steps are described in a surgical instructional video. Setting The surgery took place at a tertiary-care center. Participants Patient is a 45-year-old man who was incidentally diagnosed with an extrameatal VS extending for 9 mm into the left cerebellopontine angle (CPA). Hearing function at diagnoses was excellent, with pure tone average (PTA) = 15 dB and speech discrimination score (SDS) = 100% (class A according to the Tokyo classification) and minimal impairments on auditory brainstem response (ABR). Given these preoperative features in small VS, hearing was the main function to look into in the treatment planning. Initial observation or HPS were proposed. Results The patient underwent surgical excision for HPS via RS approach combined with retrolabyrinthine meatotomy (RLM). RLM enables the complete exposure of the IAC to the fundus, after drilling the bony surface of the posterior IAC wall, under guidance of the anatomical landmarks, namely, the endolymphatic duct, the blue lines of the posterior, and superior semicircular canals, and common crus. Nor intra-, neither postoperative complications occurred. Histologic examination confirmed the diagnosis of VS. A 3-month short-term follow-up revealed a class B hearing function with PTA = 30 dB, SDS = 100%, and normal facial nerve status. Conclusions RLM via RS approach proved to be effective for HPS, enabling the full course of the facial and cochlear nerves through the IAC to be directly exposed.The link to the video can be found at: https://youtu.be/KC1S4pxpLCk.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  open access Full text



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Retrosigmoid Craniotomy for Cerebellopontine Epidermoid Cyst

10-1055-s-0039-1677844_180155ov-1.jpg

J Neurol Surg B
DOI: 10.1055/s-0039-1677844

Epidermoid cysts are benign lesions. The goal of this surgery is complete removal while preserving cranial nerves. Here, we illustrate the case of a 31-year-old male who presented with persistent headache following a short period of impaired consciousness. Imaging revealed a mass at the cerebellopontine angle (CPA) which at surgery proved to be an epidermoid cyst. In this video, we present the key steps of surgery. The postoperative course was uneventful and the patient was symptom-free at the 3 months of follow-up.The link to the video can be found at: https://youtu.be/0xwpkKwQoLI.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  open access Full text



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Staged Approach for Petroclival Meningioma Resection

10-1055-s-0039-1677849_180249ov-1.jpg

J Neurol Surg B
DOI: 10.1055/s-0039-1677849

Introduction Petroclival meningiomas represent very uncommon and challenging tumors. Surgical morbidity is high due to the difficult and complex approaches to this area. In the present video presentation, we demonstrate a staged-approach surgical resection for petroclival meningioma. Patient and Methods A 47-year- old female was incidentally diagnosed with right sizable petroclival meningioma (Fig. 1). The decision to proceed with a staged approach was made based on size and extension of the tumor to both the middle and posterior fossa. At the first stage we performed a right anterior petrosectomy with the patient in the supine position and the head turned 45 degrees to the left. Residual tumor was left behind along its inferior pole. At the second stage, 2 weeks after the 1st surgery, a right retrosigmoid craniotomy was performed with the patient placed on left park-bench position and the residual tumor was removed. The patient tolerated both stages very well without significant neurological deficits except a transient diplopia after the first stge. Postoperative magnetic resonance imaging (MRI) revealed gross total resection of the tumor. Conclusion Staged approach for petroclival meningiomas represents a safe and effective surgical management, tolerable for the patient and more comfortable for the neurosurgeon.The link to the video can be found at: https://youtu.be/QJJchjAwD5c.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  open access Full text



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Transcanal Microscopic Transpromontorial Approach for Vestibular Schwannoma

J Neurol Surg B
DOI: 10.1055/s-0039-1677843

Objectives This video demonstrates the transcanal transpromontorial approach for resection of vestibular schwannoma. Design/Setting/Participants Present study is based on a video of a single patient undergoing the above approach at a tertiary care skull base surgery program. Results This video demonstrates a transcanal microscopic transpromontorial approach for resection of an enlarging intracanalicular vestibular schwannoma in a young patient with nonserviceable hearing. The video highlights the pertinent surgical anatomy and outlines, in a step-by-step fashion, the approach to the internal auditory canal via this minimally invasive approach. The surgical indications and reconstructive techniques are also discussed (Fig. 1). Conclusions A transcanal microscopic transpromontorial approach for vestibular schwannoma is feasible and offers a minimally invasive option for patients electing for microsurgical resection.The link to the video can be found at: https://youtu.be/-oKkRooytws.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  open access Full text



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Impact of Multilayer Vascularized Reconstruction after Skull Base Endoscopic Endonasal Approaches

10-1055-s-0039-1677705_180251-1.jpg

J Neurol Surg B
DOI: 10.1055/s-0039-1677705

Background The use of vascularized flap to reconstruct the skull base defects has dramatically changed the postoperative cerebrospinal fluid (CSF) leak rates allowing the expansion of endoscopic skull base procedures. At present, there is insufficient scientific evidence to permit identification of the optimal reconstruction technique after the endoscopic endonasal approach (EEA). Objective The main purpose of this article is to establish the risk factors for failure in the reconstruction after EEA and whether the use of a surgical reconstruction protocol can improve the surgical results. Material and Methods A retrospective cohort study was conducted in our institution, selecting patients that underwent EEA with intraoperative CSF leak. Two reconstructive protocols were defined based on different reconstructive techniques; both were vascularized but one monolayer and the other multilayer. A multivariate analysis was performed with outcome variable presentation of postoperative leak. Results One hundred one patients were included in the study. Patients reconstructed with protocol 1, with the diagnosis different to the pituitary adenoma and older than 45 years old had higher risk of presenting postoperative leak, and with statistically significant differences when we adjusted for the remaining variables Conclusion The vascularized reconstructions after endoscopic endonasal skull base approaches have demonstrated to be able to obtain a low rate of postoperative CSF leak. The multilayer vascularized technique may provide a more evolved technique, even reducing the postoperative leak rates comparing with the monolayer vascularized one. The reconstructive protocol employed in each case, as well as age and histological diagnosis, is independent risk factor for presenting postoperative leak.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text



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Making Decisions Together

decisions-banner.jpgI love working with kids. It's one of the reasons I got into this gig, and it makes the day...

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The Whole Ball of Wax: A Longer Than Normal Post About Your Cerumen

EarFBbanner.jpg"But what do I do with my ear wax?" says the man in my chair, a fully grown man who...

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Analysis of Venture Capital Investment in Therapeutic Otolaryngologic Devices

This cross-sectional analysis characterizes venture capital investments in otolaryngologic devices by therapeutic area using data from a private capital market data provider from 2008 through 2017.

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Chondrosarcoma in the Mastoid Involving the Intratemporal Facial Nerve

This case study describes a man in his 60s who presented with a 2-year history of gradual-onset right facial weakness leading to paralysis.

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Association of Head and Neck Cancer With Mental Health Disorders in a Large Insurance Claims Database

This cohort study assesses the prevalence of mental health disorders and their associations with survival and recurrence among patients with head and neck cancer in a large insurance claims database.

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Failure to Report Related Studies

To the Editor On behalf of my coauthors, I write to report our failure to include discussion of and reference to previously published, related articles in our Original Investigation titled, "Risk Factors Associated With Postoperative Delirium in Patients Undergoing Head and Neck Free Flap Reconstruction," which was published online in the January 3, 2019, issue of JAMA Otolaryngology–Head & Neck Surgery. In this study, we analyzed a cohort of 515 patients who had undergone free flap reconstruction at The Ohio State University Comprehensive Care Center (2006-2012) to assess risk factors associated with development of postoperative delirium after surgery. We identified a number of risk factors, including preoperative alcohol abstinence as predictor associated with a reduced risk of postoperative delirium.

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Addition of 2 References and Discussion of These Studies

In the article titled "Risk Factors Associated With Postoperative Delirium in Patients Undergoing Head and Neck Free Flap Reconstruction," 2 references and a brief discussion of these references were added to help contextualize the cohort of patients examined in the study. A letter of explanation describes these changes in more detail. This article was corrected online.

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Submucosal Masses of the Right Upper Lip

A woman in her 60s reported a several-week history of right upper lip submucosal masses with no tenderness, mucosal abnormality, or recent trauma to the lip. What is your diagnosis?

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Checkpoint inhibitor treatment induces an increase in HbA1c in nondiabetic patients

Immunotherapy greatly improves clinical outcomes in treated patients with cancer. However, the long-lasting immune response and long duration of therapy could induce long-term adverse effects owing to the chronic inflammation induced. Type 2 diabetes is now recognized as an inflammatory disease. In addition, immunotherapy is concerned with increase in the production of tumor necrosis factor-α, interleukin-2, and interferon-γ, which are involved in the inflammatory process. Based on these observations, we hypothesized that anti-programmed cell death-1 (anti-PD-1) and/or anticytotoxic T-lymphocyte-associated protein-4 therapy could contribute to type 2 diabetes genesis in treated patients. Therefore, to evaluate this hypothesis, we studied HbA1c levels during follow-up in patients treated with anti-PD-1 and/or anticytotoxic T-lymphocyte-associated protein-4 therapy. A prospective and observational study was performed in an oncodermatology department (Saint-Louis Hospital, Paris, France) from March 2015 to February 2017. Sixty-two patients meeting the inclusion criteria were enrolled. Forty-three patients had paired HbA1c measurements during their follow-up period and were analyzed. The median follow-up was 3 months. We noted an increase in HbA1c levels from 5.3% [interquartile range (IQR): 5.1–5.5; range: 4.5–6.2) to 5.45% (IQR: 5.2–5.7; range: 4.7–6.2; P=0.037). This observation was confirmed in the subgroup of patients who did not receive concomitant glucocorticoids; their median HbA1c levels increased from 5.3% (IQR: 5.1–5.5; range: 4.7–6.2) to 5.5% (IQR: 5.2–5.7; range: 4.7–6.3; P=0.025). Variables such as age, BMI, and sex were not associated with the HbA1c level increase, but a tendency toward rising HbA1c levels was observed in treatments longer than 12 months. This study demonstrates that treatment with anti-PD-1 antibodies may impair glucose metabolism, as measured by increasing HbA1c levels. Correspondence to Marie-Léa Gauci, MD, Saint-Louis Hospital, 1, Avenue Claude Vellefaux, 75010 Paris, France Tel:+33 786 851 900; fax:+33 142 494 465; e-mail: marie-lea.gauci@hotmail.fr Received November 8, 2018 Accepted January 18, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

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A Rare Case of Vocal Cord Aspergillosis

Abstract

Primary aspergillosis of larynx is very rare. Till now only 28 cases of isolated laryngeal aspergillosis are documented in the English literature. In the field of otorhinolaryngology, aspergillosis most frequently affects external auditory canal or nasal sinuses and larynx is usually secondarily involved. It usually affects the patients with immunocompromised state and usually presents with hoarseness of voice. Laryngeal lesions usually mimics malignancy, so accurate diagnosis with direct laryngoscopy and biopsy is needed for further management. As these lesions responds very well to antifungal therapy, early diagnosis and starting antifungal therapy is important. Here we are presenting a case report of 67 years old male with aspergillosis of vocal folds without any immunodeficiency.



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A Prospective Study of Apatinib Plus Concurrent Neoadjuvant Chemoradiotherapy in Patients With Esophageal Squamous Cell Carcinoma

Condition:   Esophageal Squamous Cell Carcinoma
Intervention:   Combination Product: Apatinib,Paclitaxel,Cisplatin,RT
Sponsor:   Hebei Medical University Fourth Hospital
Not yet recruiting

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Laryngo-pharyngeal reflux in clinical practice: The relevance of age

Publication date: Available online 27 February 2019

Source: Acta Otorrinolaringológica Española

Author(s): Giorgio Ciprandi, Matteo Gelardi



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Geriatric assessment and 1‐year mortality in older patients with cancer in the head and neck region: A cohort study

Abstract

Background

The aim is to describe the association of functional capacity and cognitive functioning with 1‐year mortality in older patients with cancer in the head and neck region.

Methods

We performed a cohort study in which all patients aged 70 years and older received a geriatric screening before treatment. Main outcome was 1‐year mortality.

Results

A total of 102 patients were included. Median age was 78.7 years (interquartile range [IQR], 72.3‐84.5), 25% were cognitive impaired, 40% were malnourished, and 28.4% used a walking device. Overall, 1‐year mortality was 42.3%. Male sex (hazard ratio [HR], 4.30; 95% confidence interval [CI], 1.35‐13.67), malnutrition (HR, 2.55; 95% CI, 1.19‐5.16), and using a walking device (HR, 2.80; 95% CI 1.13‐6.93) were associated with higher mortality risk, independent of stage and comorbidities.

Conclusion

In older patients with head and neck cancer, the mortality rates are high. Nutritional status and mobility are determinants of 1‐year mortality, independent of tumor stage, age, and comorbidity.



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Quality of life and voice outcome of patients treated with transoral CO2 laser microsurgery for early glottic carcinoma (T1-T2): a 2-year follow-up study.

Quality of life and voice outcome of patients treated with transoral CO2 laser microsurgery for early glottic carcinoma (T1-T2): a 2-year follow-up study.

Eur Arch Otorhinolaryngol. 2019 Feb 27;:

Authors: Hendriksma M, van Loon Y, Klop WMC, Hakkesteegt MM, Heijnen BJ, El Hasnaoui I, de Jong M, Langeveld TPM, van Benthem PPG, Baatenburg de Jong RJ, Sjögren EV

Abstract
PURPOSE: Longitudinal studies in laryngeal cancer can provide clinicians information about short-term and long-term functional outcomes, like quality of life (QoL) and voice outcome. This information is important when counseling patients or choosing a primary treatment modality. The present study assessed long-term (2 years) QoL and voice outcome in patients with extended T1 and limited T2 glottic carcinoma treated with transoral CO2 laser microsurgery (TLM) (unilateral type III or bilateral type II resections).
METHODS: Three questionnaires were administered: the Voice Handicap Index (VHI), the European Organization for Research and Treatment of Cancer (EORTC) QoL questionnaire (QLQ)-C30, the EORTC QLQ-HN35. A perceptual voice evaluation at six different time points was conducted: preoperatively, and postoperatively at 6 weeks, 3 months, 6 months, 1 year, and 2 years. Fluctuations over time were investigated.
RESULTS: Sixty-one patients were included in the analysis. Patients reported high-level functioning and low symptom scores 2 years postoperatively. Gender significantly affected the VHI scores at 2 years (mean VHI scores: female 8.7 vs. male, 23.9; p = 0.023). The major improvement in VHI scores was observed within the first 6 months. The tumor stage (T1a, T1b, and T2) significantly impacted the grade (mean scores at 2 years: 1.0, 1.9, and 1.7; p = 0.001). These scores stabilized at 6 months.
CONCLUSIONS: Patients show good long-term QoL with low symptom scores, a low voice handicap, and mild to moderate dysphonia, 2 years postoperatively. Scores stabilize at 6 months and provide a clear indication of status at 1 and 2 years.

PMID: 30810819 [PubMed - as supplied by publisher]



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Expanding unilateral cochlear implantation criteria for adults with bilateral acquired severe sensorineural hearing loss.

Expanding unilateral cochlear implantation criteria for adults with bilateral acquired severe sensorineural hearing loss.

Eur Arch Otorhinolaryngol. 2019 Feb 27;:

Authors: Huinck WJ, Mylanus EAM, Snik AFM

Abstract
OBJECTIVES: To report on a retrospective cohort study on the effects of expanding inclusion criteria for application of cochlear implants (CIs) on the performance 1-year post-implantation.
METHODS: Based on pre-implantation audiometric thresholds and aided speech recognition scores, the data of 164 CI recipients were divided into a group of patients that fulfilled conservative criteria (mean hearing loss at 0.5, 1 and 2 kHz > 85 dB HL and phoneme scores with hearing aids < 30%), and the remaining group of patients that felt outside this conservative criterion. Speech recognition scores (in quiet) and quality of life (using the NCIQ) of both groups, measured at 1-year post-implantation, were compared.
RESULTS: The group that felt outside the conservative criterion showed a higher phoneme score at 1-year post-implantation compared to the conservative group, suggesting that relaxed criteria have a positive influence on the speech recognition results with CI. With respect to quality of life, both groups significantly improved 1-year post-implantation. The conservative group showed a higher benefit on the advanced perception domain of the NCIQ. Based on their worse pre-implantation hearing, this was expected.
CONCLUSIONS: The data suggest that relaxation of CI indication positively affects the speech recognition performance of patients with severe hearing loss. Both groups of patients showed a positive effect of CI on the quality of life. This benefit relates to communication skills and the subjective day-to-day functioning in society.

PMID: 30810818 [PubMed - as supplied by publisher]



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Positive pressure device treatment for Menière's disease: an overview of the current evidence and a meta-analysis.

Related Articles

Positive pressure device treatment for Menière's disease: an overview of the current evidence and a meta-analysis.

Eur Arch Otorhinolaryngol. 2019 Feb 27;:

Authors: Devantier L, Guldfred FL, Djurhuus BD, Händel MN, Schmidt JH, Hougaard DD, Edemann-Callesen H

Abstract
OBJECTIVE: The objective was to critically assess the current evidence investigating the efficacy of using a positive pressure device in patients with definite or probable Menière's disease.
METHODS: We performed a systematic literature search in MEDLINE, EMBASE and PsycINFO up to February 2018. We included both systematic reviews and primary literature [randomized controlled trials (RCTs)] investigating positive pressure treatment, in patients (≥ 18 years of age), with Menière's disease. We assessed the internal validity of systematic reviews using the AMSTAR tool and risk of bias of primary studies using the Cochrane Risk of bias tool. We performed a meta-analysis for each outcome based on the identified studies. The overall certainty of evidence for the outcomes was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE).
RESULTS: The search for systematic reviews identified four relevant reviews. These all included the same four RCTs. An updated search identified one additional RCT. In total, five RCTs were included in the data synthesis. Our data synthesis showed no effect of positive pressure treatment on primary nor secondary outcomes. No serious adverse events were reported. The overall certainty of evidence ranged from very low to low, due to the serious risk of bias and imprecision.
CONCLUSION: The current available evidence does not support positive pressure device treatment in patients with Menière's disease. However, the limitations of the current literature hinder the possibility of any solid conclusion. There remains a need for randomized controlled trials of high quality to fully access the utility of this treatment.

PMID: 30809697 [PubMed - as supplied by publisher]



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Subglottic Stenosis in Children: Our Experience at a Pediatric Tertiary Center for 8 Years in South Korea

Publication date: Available online 27 February 2019

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Jin-Choon Lee, Min-Sik Kim, Dong-Jo Kim, Da-Hee Park, IL-Woo Lee, Hwan-Jung Roh, Byung-Joo Lee, Young-A. Kim, Sunghwa Ko, Eui-Suk Sung

Abstract
Objective

The incidence of SGS has been reported to be less than 8% after endotracheal intubation. Therefore there is an increasing trend in the number of patients with acute acquired SGS due to mechanical ventilation in the intensive care unit. However, there have been no reports describing the treatment of SGS in children in South Korea. The objective of this study was to evaluate the management and outcomes of children with SGS at a pediatric tertiary center in South Korea over an 8-year period.

Methods

All patients underwent microlaryngobronchoscopy (MLB) with bougination, incision using cold knife or laser and balloon dilatation. Data on age, sex, grade of SGS, number of management interventions, tracheostomy, comorbidities, mean follow-up period, complications, and outcome were reviewed from patient medical charts.

Results

Twenty patients (13 [65%] males, 7 [35%] females; mean [±SD] age at the diagnostic procedure 15.26±22.54 months) underwent MLB between March 2009 and December 2017. According to the Myer-Cotton scale, twelve of the 20 (60%) patients had grade III SGS, 7 (35%) had grade II and 1 (5%) had grade 1; there were no patients with grade IV SGS. Nine (45%) patients were diagnosed with acute SGS, and 11 (55%) with chronic SGS. Patients with SGS underwent MLB with interventions (mean 2.41±2.23 per patient). Tracheostomy was performed in 13 of 20 (65%) patients, 2 of 9 (22.2%) with acute SGS, and 11 of 11 (100%) with chronic SGS. Two of 13 (15.3%) patients underwent successful decannulation. One of 2 (50%) patients with acute SGS underwent successful decannulation. Seven of 9 (77.7%) patients with acute SGS underwent MLB only without tracheostomy.

Conclusions

In patients with acute acquired SGS, the outcome was good due to the lower rate of tracheostomy and higher decannulation rate. Therefore, it is recommended that MLB with balloon laryngoplasty be performed at the earliest in patients with acute acquired SGS.



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Comparison of distortion product otoacoustic emission (DPOAE) and automated auditory brainstem response (AABR) for neonatal hearing screening in a hospital with high delivery rate

Publication date: Available online 27 February 2019

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Ling Xiu Ngui, Ing Ping Tang, Narayanan Prepageran, Zhun Wieng Lai

Abstract
Introduction

Congenital hearing loss is one of the commonest congenital anomalies. Neonatal hearing screening aims to detect congenital hearing loss early and provide prompt intervention for better speech and language development. The two recommended methods for neonatal hearing screening are otoacoustic emission (OAE) and automated auditory brainstem response (AABR).

Objective

To study the effectiveness of distortion product otoacoustic emission (DPOAE) and automated auditory brainstem response (AABR) as first screening tool among non-risk newborns in a hospital with high delivery rate.

Method

A total of 722 non-risk newborns (1444 ears) were screened with both DPOAE and AABR prior to discharge within one month. Babies who failed AABR were rescreened with AABR ± diagnostic auditory brainstem response tests within one month of age.

Results

The pass rate for AABR (67.9%) was higher than DPOAE (50.1%). Both DPOAE and AABR pass rates improved significantly with increasing age (p-value<0.001). The highest pass rate for both DPOAE and AABR were between the age of 36-48 hours, 73.1% and 84.2% respectively. The mean testing time for AABR (13.54 mins +/-7.47) was significantly longer than DPOAE (3.52 mins +/-1.87), with a p-value of <0.001.

Conclusions

OAE test is faster and easier than AABR, but with higher false positive rate. The most ideal hearing screening protocol should be tailored according to different centre.



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The histological properties and possible origin of cervical thymus with cysts – a case report and hypotheses about its development

Publication date: Available online 27 February 2019

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Ivan Varga, Lenka Fedorová, Martin Klein, Jozef Babala, René Jáger, Ildikó Bódi, Lukáš Plank

Abstract

Ectopic accessory thymic tissue usually presents as an asymptomatic neck mass found at any level corresponding to the embryonic descent of the thymus. This tissue may contain smaller or larger cysts. However, the exact pathogenesis of "enigmatic" cervical thymic cysts remains controversial. A 7-year-old boy was referred to our workplace for the evaluation of a cervical mass. An ultrasound suggested a multi-loculated cystic mass, while CT and MRI indicated a left-sided, anteriorly located cervical mass beneath the sternocleidomastoid muscle. Following the radiological findings, surgical excision revealed a cystic mass. The mass of tissue was covered by a capsule. In H&E staining, the cervical mass had the same structure as normal thymus. Additionally, immunohistochemical findings suggest that the cellular microenvironment of cervical thymus also displays a place for development of T-lymphocytes. Within the parenchyma multiple cysts lined with cytokeratin-positive thymic epithelial cells were found. Inside the cysts, there were CD68-positive multinucleated giant cells and cholesterol clefts. A tendency to cystic degeneration inside the thymic tissue occurs more often in cervical thymuses than in normally located ones. The reason for the formation of cysts is unknown. We summarized seven possible histological, embryological and evolutional backgrounds for the development of these thymic cysts.



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Binaural Hearing Advantages for Children with Bimodal Fitting

Publication date: Available online 27 February 2019

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Younes Lotfi, Mahdieh Hasanalifard, Abdollah Moossavi, Enayatollah Bakhshi, Mohammad Ajaloueyan

Abstract
Objectives

Bimodal fitting (BF) allows children with cochlear implant to benefit from binaural hearing advantages. Three major binaural hearing advantages, which enhance hearing function of people with normal hearing, are head shadow effect (HSE), binaural squelch effect (BSQ) and binaural summation effect (BSU). This study in pediatric patients attempting to measure the auditory benefits of bimodal stimulation in children with long-standing use of a cochlear implant (CI), and residual hearing on the contralateral side.

Methods

This cross-sectional study investigated binaural advantages in 24 children of 8-12 years who had undergone cochlear implantation in a cochlear implant center in Tehran and continuously used BF. Improved score of speech perception in noise (SPiN) under BF condition, as compared to the application of cochlear implant alone, was a binaural advantage found in this study. Each binaural advantage was measured by obtaining the SPiN score under different listening and noise conditions, using relevant formulas. The measured value of each advantage reflects the improved score of SPiN, caused by that certain advantage.

Results

In this study, improved mean SPiN score caused by the HSE, BSQ and BSU was, respectively, 3.13, 1.42 and 2.04dB, indicating greater binaural advantages and hence improved SPiN, under BF condition in comparison with cochlear implant alone.

Conclusion

Children with unilateral cochlear implant and measurable residual hearing in non-implanted ear can benefit from binaural advantages and better SPiN when hearing aid is used in the unaided ear.



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Obstructive sleep apnea (OSA) with persistent daytime hypoxemia,Arteriovenous (AV) malformations in the lower lobe of the lung

Uncommon cause of persistent hypoxia in a patient with obstructive sleep apnea p. 763
Subodh Kumar Mahto, Pankaj Kumar Gupta, Pritam Majumdar, Gwenette Andrea War, Vishakha Mittal, Atul Goel
DOI:10.4103/jfmpc.jfmpc_3_19 
We report a case of hypothyroidism, obstructive sleep apnea (OSA) with persistent daytime hypoxemia. Cause of hypoxemia was two arteriovenous (AV) malformations in the lower lobe of the lung. We must be alert to other causes of hypoxemia in patients of OSA with persistent daytime hypoxemia.

Scedosporium apiospermum

Scedosporium apiospermum as a rare cause of fungal rhinosinusitis
Ankita Baidya, Nitin Gupta, Ayan Basu, Parul Kodan, Karan Aggarwal, Chirom A Singh, Gagandeep Singh, Manish Soneja, Immaculata Xess
DOI:10.4103/jfmpc.jfmpc_434_18
Fungal rhinosinusitis is not very uncommon in diabetic patients, but Scedosporium apiospermum as a cause of this infection is rare. We report a case of fungal rhinosinusitis by Scedosporium spp. in a diabetic male along with literature review. The patient is on voriconazole, with adequate therapeutic response after 6 months of follow up.


. 2016 Mar; 11: 40–43.
Published online 2016 Apr 26. doi: 10.1016/j.mmcr.2016.04.005
PMCID: PMC4857212
PMID: 27182483

Scedosporium apiospermum infections and the role of combination antifungal therapy and GM-CSF: A case report and review of the literature

1. Introduction

Scedosporium apiospermum, once considered the asexual form of Pseudoallescheria boydii, is a filamentous fungus found worldwide in soil, sewage, and polluted waters . Previously considered exceedingly rare, S. apiospermum is increasingly reported as a cause of opportunistic infection, as use of corticosteroids, immunosuppressants, antineoplastics, and broad-spectrum antibiotics have become more widespread . Furthermore, it is thought that increased use of antifungals in immunocompromised patients with agents that have activity against Candida spp. and Aspergillus fumigatus but only modest or no activity against Scedosporium (e.g. amphotericin B and echinocandins), may exert a selective pressure and contribute to the increased incidence of Scedosporium infections .
S. apiospermum infections most commonly occur in the paranasal sinuses, lungs, skin, soft tissue, central nervous system, and bones, but disseminated disease is also common and often fatal . Herein we report a case of disseminated infection from a cutaneous source in a patient exposed to steroids in which progression of disease was observed despite adequate treatment with voriconazole, the current drug of choice. S. apiospermum poses a therapeutic challenge due to its intrinsic resistance to commonly used antifungal agents and its ability to recur even when susceptibility to these medications is demonstrated. In our case, the addition of echinocandins and granulocyte macrophage colony-stimulating factor (GM-CSF) to the patient's treatment regimen provided partial recovery. This case demonstrates a potential synergistic role for dual-antifungal treatment with adjunctive immunotherapeutic agents in the treatment of S. apiospermum infections. As S. apiospsermum infections become increasingly prevalent, further consideration and investigation of this combination therapy is necessary to combat this highly fatal and aggressive organism.

2. Case

A 77-year-old man on high dose steroids for presumed temporal arteritis presented on day 0 with a 10 day history of progressive swelling, erythema, and pain of the left leg. He denied fever, chills, nausea, vomiting or diarrhea and denied any history of trauma or travel inside or outside the United States. The patient's past medical history included hypercholesterolemia, hypertension, congestive heart failure, coronary artery disease, chronic obstructive pulmonary disease, benign prostatic hypertrophy and sphenoid sinusitis. He was admitted to the hospital on day 0 for treatment of leg cellulitis. Physical exam revealed diffuse, circumferential, macular erythema and warmth extending from the left ankle to the popliteal fossa. There were three, 5 mm pink papules with fine scale at the superior-most aspect of the erythema. On the anterior tibia there were two 1 cm flaccid bullae. The leg was non-tender. The patient received vancomycin and cefepime and after 7 days of therapy there was partial improvement of the erythema; however, on day +7, new diffuse, non-tender, 0.5–1.5 cm subcutaneous nodules emerged (Fig. 1A). Histopathologic examination revealed a dermal nodular infiltrate of neutrophils with surrounding histiocytes, some of which were multinucleated. A periodic acid-Schiff-diastase (PAS-D) stain revealed small, narrow angled, branching hyphae. Wound cultures were positive for mold, subsequently identified as S. apiospermum.Identification was based on phenotypic characteristics and sequencing of the intertranscribed spacer (ITS) region, which was compared to reference data available at GenBank using the basic local alignment search tool (BLAST) . The isolate was susceptible to voriconazole and posaconazole, but resistant to amphotericin B, 5-fluorocytosine, itraconazole, and caspofungin using the Sensititre YeastOne kit , as shown in Table 1. Other cultures for bacteria and acid-fast bacilli were negative. On day +10, the patient was started on intravenous (IV) voriconazole 6 mg/kg for 1 day followed by 4 mg/kg for 4 days, and he continued on oral voriconazole 200 mg q12 hours as an outpatient. Therapeutic trough levels were measured and maintained in a range of 4–6 mg/L. The prednisone, which had been started on day −60 at a dose of 60 mg, had been tapered to 40 mg at day 0 and was tapered off completely by day +84.

A. Left shin on initial presentation after treatment with antibiotic therapy. B. Left shin lesion after addition of micafungin and GM-CSF. (For interpretation of the references to color in this figure, the reader is referred to the web version of this article.)

Table 1

Sensitivities of Scedosporium apiospermum isolate.
AntifungalFirst admission MICa(μg/ml)Second admissions MICb(μg/ml)SynergybMICb(μg/ml)Interpretation
AMB2>2AMB+CAS>2+>4Indifferent
MON0.5AMB+MICA>2+>4Indifferent
ITC>16
VRC0.121AMB+POS2+4Indifferent
POS0.5>4AMB+VRC2+0.5Indifferent
MICA0.5MICA+TRB0.5+<0.015Indifferent
CAS>81
ANID4
KTC1
TRB>2
5FC>64
AMB, amphotericin B; MON, miconazole; ITC, itraconazole; 5FC, flucytosine; VRC, voriconazole; TRB, terbinafine; CAS, caspofungin; MICA, micafungin; POS, posaconazole; ANID, anidulafungin; KTC, ketoconazole
aObtained by CLSI adapted method based on breakpoints available for pathogenic yeasts, Wadsworth Center Laboratories, Albany NY.
bObtained by M38-A2 CLSI broth dilution antifungal susceptibility testing, University of Texas Health Science Center at San Antonio, South Texas reference laboratories.
On day +99, the patient was admitted for acute decompensated heart failure. At that time, voriconazole was discontinued given improvement of his left lower extremity lesion. By day +114 (15 days since discontinuing therapy), recurrence of disease was observed with new metastatic nodules in the upper extremities, one of which was incised and drained and again grew S. apiospermum with sensitivities and synergy studies shown in Table 1. IV voriconazole was restarted at 6 mg/kg for 1 day followed by 4 mg/kg for 5 days and was continued orally at 200 mg q12 hours as an outpatient. The patient was subsequently re-admitted on day +155 with septic shock thought to be due to bacterial superinfection of the left leg lesions given an increased area of ulceration, oozing and eschar formation. New metastatic lesions in his upper extremities were also observed at that time. Computed tomography scans of the left leg throughout all three admissions were consistent with progressing cellulitis without evidence of osteomyelitis. The margin of the left leg ulcer was biopsied and a PAS-D stain revealed fungal elements. Wound culture again grew S. apiospermum. In addition to IV voriconazole 4 mg/kg, Micafungin 100 mg and GM-CSF 250 μg IV daily were started as salvage therapy. An improvement in the left leg lesion was noted (Fig. 1B), no new nodules emerged, and the existing nodules regressed. He remained stable and was discharged to physical rehabilitation on oral voriconazole 200 mg q12 hours and micafungin 100 mg daily for an indefinite period of time. The patient remained on dual-antifungal suppressive therapy until he presented on day +256 with sepsis secondary to pneumonia from which he was not able to recover with antibiotic therapy, and he expired on day +266.

3. Discussion

This case report draws attention to the importance of having increased awareness of S. apiospermum, particularly in immunocompromised patients. However, it is unlikely for patients to provide a history that raises suspicion for this organism in particular. For example, while most cases of cutaneous S. apiospermum infection follow surgery or trauma, particularly when there is contact with soil where this organism is ubiquitious, most patients will specifically deny any history of trauma . However, even minor lesions on extremities that go unnoticed can provide a portal of entry for this organism, as suggested by Uenotsuchi et al.’s review of 20 cases of cutaneous S. apiospermum infection that all happened to have occurred on extremities . In line with this, our patient's lesion was located on the left leg and he did not report any history of trauma. Interestingly, he was a resident of the Rockaway Peninsula of New York City, which was severely affected by Hurricane Sandy approximately 6 months prior to his initial presentation. We hypothesize that environmental destruction may have led to increased epidemiologic risk in this immunosuppressed host after he returned to his home in the aftermath of the hurricane.
Accurate and prompt diagnosis of S. apiospermum is essential, as this organism can be often misidentified as other molds with different resistance profiles, such as Aspergillus spp. and Fusarium spp . These three species are angioinvasive and have non-pigmented, slender, septate hyphae 2–4 µm in width. Scedosporium spp. can be differentiated by their more irregular branching pattern compared to the orderly dichotomous 45-° angle branching observed in Aspergillus and by their production of ovoid conidia with truncated bases, which can be confused with yeast . These distinguishing features, however, are often absent from histological specimens , rendering a diagnosis by histopathological means alone unreliable. Shah et al. found that the diagnosis of Aspergillus by histopathologic and cytopathalogic examination was only 78% accurate . The erroneous diagnosis of Aspergillus was often favored over both common (ScedosporiumFusarium, and Paecilomyces spp.) and uncommon mimickers (Trichosporon loubieri). Culture is routinely used for diagnosis and speciation but even its utility is limited by slow growth, false-negatives, and contaminations with other organisms . In our case, the early detection of fungal elements in the dermis, phenotypic characteristics on culture, and sequencing of the ITS region were all necessary to make a timely and accurate diagnosis.
Treatment of Scedosporium spp. is often difficult, particularly when numerous small abscesses are not amenable to surgical intervention, as inadequate debridement impedes the penetration of systemic antifungals. Scedosporium spp. are inherently resistant to amphotericin B and frequently, though unpredictably, resistant to azoles . The broad-spectrum azole voriconazole is the drug of choice for S. apiospermum infections. It has demonstrated fungicidal activity against S. apiospermum in vitro, and it has been shown to be effective in mouse and guinea pig models  as well as in case reports in humans . Duration and efficacy of therapy is not widely known due to a lack of large studies. However, in one of the largest studies on the treatment of scedosporiosis with voriconazole, 57% of patients achieved response at a median of 103 days . Recurrences are common, as seen in our patient, and might happen even without interruption of therapy or development of resistance to voriconazole.
A marked clinical response was observed when micafungin and GM-CSF were started and no further metastatic nodules were observed. The combination of micafungin and voriconazole has been demonstrated to have a synergistic effect against several fungi in vitro including Scedosporium spp . The underlying mechanism is thought to involve cell wall reorganization and exposure of β-glucan, resulting in enhanced immune recognition . In clinical practice, combination antifungal therapy is more often necessary with the highly resistant S. prolificans, and treatment response has been demonstrated in several cases  as well as for other invasive filamentous fungal infections . While antifungal therapy is important as an adjuvant, the containment and ultimate clearance of Scedosporium infections is dependent on innate host defense, particularly the numeric and functional activity of polymorphonuclear cells (PMNs). The addition of GM-CSF and interferon-gamma (IFN-γ) have been shown to increase antifungal activity of PMNs in vitro , which is thought to be due to enhancement of phagocytosis and oxidative burst leading to increased hyphal damage . There has been one reported case of GM-CSF and IFN-γ used in concert with several antifungals, including itraconazole and amphotericin B, as salvage therapy, which ultimately resulted in clinical cure in a 10-year-old HIV-positive patient who presented with S. apiospermum otomastoiditis . However, to our knowledge, this is the first reported case of dual-antifungal therapy with adjunctive cytokine therapy in the treatment of refractory S. apiospermum in the non-pediatric literature.
Although the cause of this patient's death was not suspected to be due to scedosporiosis, a clear clinical cure was not achieved. Therapeutic considerations may have included more prolonged treatment with GM-CSF or the addition of IFN-γ, however no standardized regimens for dual-antifungal or cytokine therapies currently exist. Given the importance of this emerging area and a paucity of guidelines to guide management, more studies are needed to outline appropriate administration of combination antifungals and cytokines as salvage therapies for the management of refractory scedosporiosis.

Conflict of interest

There are none.

Acknowledgements

There are none.

References

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