Immunohistochemistry (IHC) tests for JNA.
\r\n\t
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Member of IEEE, IET, IEM.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"24699",title:"Dr.",name:"Kim Ho",middleName:null,surname:"Yeap",slug:"kim-ho-yeap",fullName:"Kim Ho Yeap",profilePictureURL:"https://mts.intechopen.com/storage/users/24699/images/system/24699.jpg",biography:"Kim Ho Yeap is an Associate Professor at Universiti Tunku Abdul Rahman, Malaysia. He is an IEEE senior member, a Professional Engineer registered with the Board of Engineers, Malaysia,a Chartered Engineer registered with the UK Engineering Council, and an ASEAN Chartered Professional Engineer (ACPE). He received his BEng (Hons) Electrical and Electronics Engineering from Universiti Teknologi Petronas in 2004, his MSc in microelectronics from Universiti Kebangsaan Malaysia in 2005, and his PhD from Universiti Tunku Abdul Rahman in 2011. In 2008 and 2015, respectively, Dr. Yeap underwent research attachment at the University of Oxford (UK) and Nippon Institute of Technology (Japan). Dr. Yeap is the external examiner and external course assessor of Wawasan Open University. He is also the Editor in Chief of the i-manager’s Journal on Digital Signal Processing. He has also been a guest editor for the Journal of Applied Environmental and Biological Sciences and Journal of Fundamental and Applied Sciences. Dr. Yeap has been given the university teaching excellence award, and 22 research grants. He has published more than 100 research articles (including refereed journal papers, conference proceedings, books, and book chapters). Prior to joining the academic industry, Dr. Yeap worked in Intel corporation in the pre-silicon validation group. He was awarded 4 Kudos awards by Intel for his contributions in the design and verification of the microchip’s design for testability (DFT) features.",institutionString:"Universiti Tunku Abdul Rahman",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"3",institution:{name:"Universiti Tunku Abdul Rahman",institutionURL:null,country:{name:"Malaysia"}}}],coeditorOne:{id:"454196",title:"Dr.",name:"Magdalene",middleName:null,surname:"Goh Wan Ching",slug:"magdalene-goh-wan-ching",fullName:"Magdalene Goh Wan Ching",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:"Dr Magdalene Goh Wan Ching\r\nDesignation: Senior lecturer\r\nQualifications: Diploma in Electrical & Electronics Engineering (Inti College), BEng in Electrical\r\nEngineering & Electronics (University of Liverpool, UK), PhD in Solid State\r\nDevice Physics & RF Transistors Design (University of Liverpool, UK)\r\n\r\nProfessional Body\r\nMemberships:\r\n\r\nInaugural Senior Member, International Engineering & Technology Institute\r\n(IETI), Hong Kong\r\n\r\nBiodata: Dr. Magdalene Goh obtained her Diploma in Electrical & Electronics Engineering\r\nfrom Inti College before leaving for the UK to pursue her BEng in Electrical\r\nEngineering & Electronics and later on, her PhD. Prior to joining the academia,\r\nshe has worked for a few years in the industry in the areas of semiconductor\r\nprocess technology, silicon wafer characterizations, mask layout design,\r\nanalogue circuits design and design for testability (DFT). While in the academic,\r\nshe had served as a judge for Innovate Malaysia undergraduate final year\r\nprojects competition from 2012 - 2015. She had served as an external examiner\r\nfor a PhD candidate from VIT University, India in 2013, and an external examiner\r\nfor SEGi College Penang from 2014 – 2018. She has been actively involved with\r\nthe Penang Science Cluster in their radio telescope team since 2014, where she\r\nworks with a team of volunteers (from both academia and the industry in\r\nPenang) to create curricula in radio astronomy, for the purpose of introducing the\r\nconcepts of radio astronomy and radio telescopes to both school pupils and\r\ncollege students. She has been a member of the Astronomical Society of\r\nPenang since 2016.\r\n\r\nCourse Development\r\nExperience:\r\n\r\nSince joining WOU, Dr. Goh has developed eight courses, namely Control\r\nSystems, Microprocessors, Digital Communications, Microelectronics, VLSI\r\nDesign, Process Control & Instrumentation, Power Electronics & Drives and\r\nElectrical Power & Drives.\r\n\r\nResearch Interest: Dr. Goh’s research interests are in the areas of semiconductor physics and\r\nelectromagnetics. She also has strong interest in the field of astronomy and is\r\nworking with a group of volunteers to promote astronomy education in the\r\nsecondary schools in Penang. She had also worked with some interns on the\r\nradio telescope project at the Penang Science Cluster.\r\n\r\nResearch Projects and\r\nConsultancy Work:\r\nSelected Publications: Design of Radio Frequency Metal-Insulator-Metal (MIM) Capacitors. \r\n\r\nExperimental Investigation on Thermoelectric Generator for Battery - Charger\r\nBased Oven.\r\nAnalyzing the Physics of Radio Telescopes and Radio Astronomy (book\r\nchapters).\r\n\r\nConferences,\r\nSeminars and\r\nWorkshops:\r\n\r\nDr. Goh was appointed as one of the Technical Committee Member for the\r\nVirtual Conference on Electronics and Communication: Loading Intelligence on\r\nFuture Electronics (October 2020).\r\n\r\nHonorary\r\nAppointments and\r\nAwards:\r\n\r\nDr. Goh is a reviewer of the following journals:-\r\n1. Microwave and Optical Technology Letters.\r\n2. Journal of Electrical Engineering.\r\n3. Journal on Digital Signal Processing.\r\n\r\nOfficial\r\n\r\nDr. Magdalene Goh Wan Ching\r\nSenior Lecturer & Programme Coordinator of Bachelor of Technology in\r\n\r\nCorrespondence\r\nAddress:\r\n\r\nElectronics,\r\nSchool of Science & Technology\r\nWawasan Open University\r\n54, Jalan Sultan Ahmad Shah,\r\n10050 Penang\r\n\r\nEmail Address: magdalenegoh@wou.edu.my\r\nPersonal Homepage\r\n(optional):\r\n\r\nBTEL facebook page:\r\nhttps://www.facebook.com/groups/238200129533176/",institutionString:"Technology Wawasan Open University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Wawasan Open University",institutionURL:null,country:{name:"Malaysia"}}},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"11",title:"Engineering",slug:"engineering"}],chapters:[{id:"82415",title:"Power Consumption in CMOS Circuits",slug:"power-consumption-in-cmos-circuits",totalDownloads:15,totalCrossrefCites:0,authors:[null]}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"444312",firstName:"Sara",lastName:"Tikel",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/444312/images/20015_n.jpg",email:"sara.t@intechopen.com",biography:"As an Author Service Manager, my responsibilities include monitoring and facilitating all publishing activities for authors and editors. 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Although JNAs comprise of less than 0.05% of all head and neck tumors, their tendency to bleed torrentially makes them an interesting disease entity to study and treat [1].
Development of other medical fields has been instrumental in studying the origin, growth and other characteristics of this disease entity. Advancements in radiology, histopathology and endoscopic nasal surgeries have been particularly useful. We can now better diagnoses, stage and treat JNA than the previous decade.
Earliest known documentation of juvenile nasopharyngeal angiofibroma is credited to Hippocrates in the 4th century BC [2]. The term “juvenile nasopharyngeal angiofibroma” was coined by Chaveau in 1906 and his works re-sparked the interest in JNA [3]. Shaheen et al. [4] reported the first female case of JNA (1930).
Harma et al. in 1959 gave a detailed clinico-pathological insight into this tumor [5]. Works of Bensch, Ewing, Som, Neffson, Moore, Handousa, Denker etc. have been vital in understanding the natural history of disease and its surgical management [6, 7, 8, 9].
Nasopharynx is a near-cuboidal shaped space with an approximate volume of 30cm3. It is located exactly below the middle cranial fossa.
Boundaries of Nasopharynx:
Posterior to the torus tuboris, lies a deep recess called
Endoscopic anatomy of nasopharynx as seen through right nasal cavity
Pterygopalatine fossa is a bilateral wedge-shaped space located below the orbital apex and behind the posterior wall of maxillary sinus. It communicates with other regions of skull through various canals and foramina.
Boundaries of Pterygopalatine Fossa:
I
Communications of Pterygopalatine Fossa:
Via
Via
Via
Via
Via
Via
Via
Contents of Pterygopalatine Fossa:
Pterygopalatine ganglion with its branches
Maxillary nerve (V2) and its branches
Vidian Nerve (carrying secretomotor fibers of facial nerve from superior salivatory nucleus and sympathetic fibers from internal carotid artery via deep petrosal nerve)
Third part of maxillary artery
Juvenile Nasopharyngeal Angiofibroma occurs almost exclusively in males and that too in adolescent period. Mean age of presentation is 14 years (range 7 years to 19 years) [10]. Isolated cases of JNAs in females or in younger/ older ages have been reported in literature [4, 11]. Exact etiology, although unknown, evidences point towards a hormonal influence on its occurrence and growth.
Juvenile nasopharyngeal angiofibroma can arise from any one of the following sites:
Scientists are still looking out for exact etiological factors and how these affect the growth of the tumor. Following factors should be considered:
The fibrous stroma has varying amounts of fine and coarse collagen fibers. Plump spindle, angular, or stellate-shaped cells are also seen. Rarely, mast cells may be present. The nuclei of stromal cells generally lack any characteristic features; although, multinucleated pleomorphic cells are not uncommon.
The vascular and fibrous elements vary in proportion within the same tumor and with the tumor age. While the fibrous component is more towards the centre of the tumor, peripheral areas have abundance of vascular elements. Also, newer lesions have predominantly vascular component while long standing tumors are enriched with fibrous tissue.
Embolised specimens show myxoid changes with areas of infarction. Embolic agent can be seen in the tumor vessels. Post flutamide therapy or radiotherapy specimens show a significant increase in fibrous component (Figure 2).
Histopathological section of JNA as seen under a microscope. Multiple blood vessels of varying diameters are seen in a fibrous stroma.
IMMUNOHISTOCHEMISTRY | |||
---|---|---|---|
TEST ANTIBODY | TUMOR COMPONENT | TUMOR CELLS | STAINING PATTERN |
1. Vimentin | Vascular & Fibrous | All tumor cells | Cytoplasmic |
2. Androgen receptor | Vascular & Fibrous | All stromal cells and endothelial cells | Nuclear |
3. VEGF | Vascular & Fibrous | Stromal and vascular cells | Cytoplasmic |
4. PDGF | Vascular & Fibrous | Stromal and vascular cells (+/−) | Cytoplasmic |
5. IGF-2 | Vascular & Fibrous | Stromal and vascular cells (+/−) | Cytoplasmic |
6. TGF- β | Vascular & Fibrous | Stromal and vascular cells (+/−) | Cytoplasmic |
7. SMA (Smooth Muscle Actin) | Vascular | Smooth muscle cells in blood vessels | Cytoplasmic |
8. Desmin | Vascular | Cells in walls of larger blood vessels | Cytoplasmic |
9. FVIIIRAg | Vascular | Endothelial cells | Cytoplasmic |
10. CD31 | Vascular | Endothelial cells | Cytoplasmic |
11. CD34 | Vascular | Endothelial cells | Cytoplasmic |
12. ER | Vascular | Vascular cell nuclei (+/−) | Nuclear |
13. PR | Vascular | Vascular cell nuclei (+/−) | Nuclear |
14. CD117 (c-kit) | Fibrous | Stromal cells | Cytoplasmic |
15. β Catenin | Fibrous | Stromal cells | Nuclear |
Immunohistochemistry (IHC) tests for JNA.
JNA arises at the upper lip of sphenopalatine foramen. As it grows further, it spreads along the path of least resistance to involve many vital structures.
From sphenopalatine foramen, it extends into the nasopharynx and grows submucosally. It can occupy the entire nasopharynx to produce bilateral nasal obstruction and nasal intonation of voice (rhinolalia clausa). Recurrent epistaxis often starts at this stage only. The tumor mass may depress the soft palate or hang in the oropharynx. Blockage of eustachian tube(s) results in conductive hearing loss (otitis media with effusion).
It enters the ipsilateral nasal cavity first to cause unilateral nasal obstruction and epistaxis. Here it may acquire secondary attachments.
As the tumor grows further within the ipsilateral nasal cavity, it pushes the nasal septum towards the opposite side to produce contralateral nasal obstruction as well.
Further tumor growth allows it to involve ethmoidal sinuses. This results in flattening of the nasal bridge and an increase in the intercanthal distance. An associated proptosis gives a classical ‘
The tumor may encroach upon and erode anterior wall of sphenoid sinus. It may further invade the sphenoid sinus.
Lateral growth of the tumor results in the involvement of pterygopalatine fossa. Pterygopalatine fossa is a small wedge-shaped cavity, which can be considered as a cross-section/ junction point of many important ‘highways’.
As the mass lesion fills the pterygopalatine fossa, it causes anterior bowing of the posterior wall of maxillary sinus
From pterygopalatine fossa, it can extend into the orbit via the inferior orbital fissure. This produces proptosis. Further involvement of orbital apex results in loss of vision. Involvement of extraocular muscles produces diplopia.
From pterygopalatine fossa, tumor grows laterally to invade infratemporal fossa via the pterygomaxillary fissure. This causes facial swelling and fullness in the cheek region. Erosion of the anterior face of greater wing of sphenoid causes entry of tumor into the middle cranial fossa.
From pterygopalatine fossa, it can grow along the vidian canal to reach foramen lacerum. Foramen lacerum opens in the middle cranial fossa, providing easy access to the tumor for intra cranial extension.
The tumor can erode the pterygoid process posteriorly and spread downwards into the pterygoid fossa. It can reach as far as the parapharyngeal space.
Tumor growth in the posterolateral part of nasopharynx can cause extension into the fossa of rosenmuller. Further posterolateral growth into the apex of this fossa results in intracranial extension by eroding the carotid canal and petrous apex.
The tumor can involve the orbit through the following routes-
Sphenopalatine foramen ➔ pterygopalatine fossa ➔ via inferior orbital fissure ➔ enters orbit.
Sphenopalatine foramen ➔ nasopharynx and nasal cavity ➔ erodes lamina papyracea ➔enters orbit.
The tumor can have intracranial extension through the following routes:
Sphenopalatine foramen ➔ pterygopalatine fossa ➔ infratemporal fossa ➔ erosion of anterior face of greater wing of sphenoid AND/ OR through foramen ovale causing its widening ➔ middle cranial fossa. The tumor lies lateral to Internal Carotid Artery (ICA) and Cavernous Sinus (CS) in such cases.
Sphenopalatine foramen ➔ pterygopalatine fossa ➔ via inferior orbital fissure ➔ orbit ➔ growth within orbit towards orbital apex and superior orbital fissure ➔ middle cranial fossa. The tumor lies anterolateral to ICA and lateral to CS.
Sphenopalatine foramen ➔ nasopharynx and nasal cavity ➔ erosion of floor and anterior wall of sphenoid sinus to invade sphenoid sinus ➔ erosion of roof of sphenoid sinus ➔ intracranial spread. The tumor lies medial to ICA and lateral to pituitary gland.
Sphenopalatine foramen ➔ pterygopalatine fossa ➔ pterygoid (vidian) canal ➔ foramen lacerum ➔ middle cranial fossa. Encasement of ICA is seen early.
Sphenopalatine foramen ➔ nasopharynx ➔ fossa of rosenmuller ➔ erodes carotid canal and petrous apex ➔ intracranial spread.
Sphenopalatine foramen ➔ nasopharynx ➔ nasal cavity ➔ through cribriform plate ➔ anterior cranial fossa (rare route for intracranial extension).
The patient is almost invariably male in his second decade of life. Mean age of presentation is 14 years (reference).
The patient may have one or more of the following symptoms
Mucopurulent discharge in the involved side is seen. Tumor mass may also be visualized. Septum is often deviated towards contralateral side.
Mass lesion is visualized in the nasopharynx.
Examination with a Hopkin’s rigid rod lens 0o endoscope reveals a fleshy mass lesion. It is usually covered in mucopurulent secretions which require gentle suctioning. Probing is avoided as it can complicate into profuse nasal bleed.
Though for any nasal mass, golden rule is that biopsy is preceded by radiological imaging to ascertain origin, extent, and nature of the disease; in vascular tumors such as JNAs, biopsy is contraindicated. Risk of bleeding during and/ or after the procedure outweighs any added advantage we may get out of preoperative biopsy.
Water’s view (Occipitomental view)/ Peer’s view (Occipitomental view with open mouth) shows haziness of the involved sinus. Lateral view shows anterior bowing of posterior wall of maxillary antrum (
Contrast enhanced computed tomographic imaging is the investigation of choice for JNA. Infact, the diagnosis of JNA is confirmed by presence of a mass in nasopharynx and pterygopalatine fossa that enhances after contrast administration on CECT. CECT is a non-invasive procedure that forms the basis for JNA diagnosis and staging.
mass lesion in the nasopharynx/ nasal cavity and pterygopalatine fossa
erosion of posterior bony margin of sphenopalatine foramen with extension to the upper medial pterygoid plate.
Contrast enhanced MRI (CE-MRI) is the investigation of choice for advanced JNA tumors, particularly those with intracranial, intra-orbital, or parapharyngeal space involvement. It can accurately determine the extent of the tumor. ‘Salt and pepper’ appearance on contrast MRI is characteristic to any vascular tumor, resulting due to flow-void areas (T2WI and contrast enhanced T1WI) [22, 34].
MRI is also the preferred modality for post-operative long-term surveillance because of its superior soft tissue differentiation quality without any radiation exposure.
CT angiography is useful to identify the feeder vessel(s) to the tumor. Internal maxillary artery is the most common feeder vessel for JNA. JNA may additionally acquire blood supply from ascending pharyngeal artery, contralateral external carotid artery branches, ipsilateral or contralateral internal carotid artery and its branches (ophthalmic, meningohypophyseal, vidian artery).
Knowledge about the feeding vessel and its site of entry into the tumor is absolutely critical to decide the surgical approach for JNA excision. For example, where feeder vessels are located posterior to the main tumor mass without direct access, open approach is preferred to endoscopic approach.
DSA is used in preoperative phase to identify the feeder vessel and its preoperative embolization. Selective vessel angiography in DSA allows to determine the exact branch(es) supplying the tumor and its selective embolization. JNA shows a characteristic
Various staging systems have been proposed over the years, each with its own merits and demerits.
SESSION’S STAGING SYSTEM | |
---|---|
STAGE | TUMOR EXTENSION |
IA | Involvement of the nose or nasopharyngeal vault |
IB | Extension into one or more sinuses |
IIA | Minimal extension into the pterygopalatine fossa |
IIB | Full occupation of the pterygopalatine fossa |
IIC | Infratemporal extension (± involvement of the cheek) |
III | Intracranial extension |
JNA staging system by Sessions, 1981 [36].
CHANDLER’S STAGING SYSTEM | |
---|---|
STAGE | TUMOR EXTENSION |
I | Involvement of the nasopharyngeal vault |
II | Extension into nasal cavity or sphenoid sinus |
III | Extension into maxillary sinus, ethmoid sinus, pterygopalatine fossa, infratemporal fossa, cheek, palate |
IV | Intracranial extension |
JNA staging system by Chandler, 1984 [37].
ANDREWS-FISCH’S STAGING SYSTEM | |
---|---|
STAGE | TUMOR EXTENSION |
I | Confined to nose or nasopharyngeal vault |
II | Invasion of the pterygopalatine fossa or maxillary/ ethmoid/ sphenoid sinuses with bone destruction |
IIIA | Extension into the infra- temporal fossa or orbit |
IIIB | Intracranial but extradural extension (parasellar area) |
IVA | Intracranial intradural extension |
IVB | Intracranial intradural extension involving |
JNA staging system by Andrew- Fisch, 1989 [38].
RADKOWSKI’S STAGING SYSTEM | |
---|---|
STAGE | TUMOR EXTENSION |
IA | Involvement of the nose or nasopharyngeal vault |
IB | Extension into one or more sinuses |
IIA | Minimal extension into pterygopalatine fossa |
IIB | Complete extension into pterygopalatine fossa |
IIC | Extension into infratemporal fossa/ posterior to pterygoid plates |
IIIA | Minimal skull base involvement (middle cranial fossa/ base of pterygoid plates) |
IIIB | Extensive intracranial involvement ± involvement of cavernous sinus |
JNA staging system by radkowski, 1996 [39].
Only valid for tumors which are preoperatively embolised (Table 6).
UPMC/ SNYDERMAN’S STAGING SYSTEM | |
---|---|
STAGE | TUMOR EXTENSION |
I | Nasal cavity, medial pterygopalatine fossa |
II | Paranasal sinuses and lateral pterygopalatine fossa, no residual vascularity |
III | Skull base erosion, orbit, infratemporal fossa, no residual vascularity |
IV | Skull base erosion, orbit, infratemporal fossa, with residual vascularity from ICA |
V | Intracranial extension with residual vascularity from ICA |
VM | Medial cavernous sinus |
VL | Middle cranial fossa |
JNA staging system by Snyderman/ UPMC, 2010 [40].
Choice of treatment depends on the size and extent of the tumor. Treatment modalities include surgical excision (open v/s endoscopic approach) and non-surgical adjuvant therapy (embolization/hormonal/ radiotherapy) or their combination(s).
Complete excision of the entire tumor mass should be the aim of any surgical procedure and the approach selected accordingly. Though the advancements in endoscopic surgery have minimized the need for open approaches, the surgeon should be well versed with all the techniques.
In general, open approaches have the advantage of providing a wide exposure. But this comes at the cost of higher morbidity, increased hospital stay, and some degree of cosmetic deformity.
This is the shortest and most direct approach for tumors limited to nasopharynx with/ without minimal extension into sphenoid sinus/ choana [41, 42].
A U-shaped incision (Wilson’s incision) is made 2.5 cm anterior to the junction of hard and soft palate. Submucoperiosteal flap is elevated posteriorly till the soft palate to bare the underlying horizontal plate of palatine bone. Soft palate and hard palate are separated. Bone is removed from the posterior part of hard palate to visualize the entire nasopharynx along with the tumor.
This approach has the advantage of good post-operative healing with no visible scar.
Lateral rhinotomy was first described by Irwin Moore in 1917 [43].
The incision is started 5 mm anterior and superior to the medial canthus and continued inferiorly along the deepest portion of the nasomaxillary groove. At its inferior end, it is curved medially in the crease beneath the ala. Skin flaps are elevated over the maxilla and nasal bones. Medial wall of maxillary antrum is removed.
This provides adequate exposure for tumors extending into the nasal cavity and/ or sinuses with minimal extension into the pterygopalatine fossa.
Adequate healing allows for an inconspicuous scar mark, well hidden within the facial creases.
The lateral rhinotomy incision is further extended inferiorly along the ipsilateral ridge of the philtrum and continued to split the upper lip in paramedian position. After dividing the upper lip, incision is continued laterally along the gingivobuccal sulcus upto the first molar. This approach is required in cases needing exposure beyond the infraorbital neurovascular bundle.
The main objective of this approach is to expose the maxillary antrum and remove its medial, anterior and posterolateral walls along with perpendicular plate of palatine bone. Orbital floor and alveolar arch are left intact. This converts the maxillary sinus, nasal cavity, nasopharynx, pterygopalatine fossa and infratemporal fossa into a single large accessible cavity.
This wide exposure is required for large tumors spilling in the infratemporal fossa. Lateral most aspect of these tumors is identified. Feeder vessel in the form of internal maxillary artery (most common feeder vessel) is identified as it enters the lateral aspect of the tumor in the infratemporal fossa and ligated before starting with the tumor dissection. Ascending pharyngeal artery maybe seen entering and supplying the tumor at its posterior aspect. It is also identified and ligated. This allows for minimal blood loss during the tumor dissection and delivery. Tumor delivery is done in-toto through transnasal/ transoral route or in a piecemeal fashion.
Two pathways for this approach have been described:
An incision is made in the gingivobuccal sulcus between the two upper second molars. Periosteum is elevated to expose maxilla in its anterior and lateral aspect. Horizontal osteotomies from pyriform aperture to pterygomaxillary fissure and from pyriform aperture to palatine canals are made. Nasal septum is freed from anterior nasal spine and maxillary crest. Pterygoid dysjuctioning allows easy down fracturing of maxilla to achieve a wide exposure of the tumor extending into multiple paranasal sinuses, infratemporal fossa or intracranial space. After tumor excision, fixation of mid facial skeleton is achieved using titanium plates. This approach provides the widest possible exposure without any external scar [44].
A Weber-Ferguson incision is combined with the splitting of the hard palate [45, 46]. Multiple osteotomies are done and maxilla is disarticulated. Overlying skin and muscles are NOT dissected. Rather they are raised as a single flap along with underlying maxillary and zygomatic bone (
This approach provides accessibility to nasopharynx, paranasal sinuses, infratemporal fossa, parapharyngeal space and intracranial space. Malocclusion of upper jaw and palatal fistula are some uncommon but difficult to manage complications associated with this procedure [47].
MRR starts as a midfacial degloving approach through a sublabial incision [48]. Partial osteotomy at nasofrontal angle allows extended degloving of midface. Multiple osteotomies are made to resect and remove the maxillary bone. Tumor is resected. Maxilla is repositioned at its original anatomical position and secured with titanium plates/ absorbable plates.
Wide exposure for tumor resection from infratemporal fossa, parapharyngeal space, and middle and anterior cranial fossa is achieved. Such extensive resections can cause malocclusions, visual disturbances and disruption of growth centres in the maxillary bone, resulting in future cosmetic deformities.
A combination of infratemporal fossa approach and transfacial approach is required in certain cases with advanced stage angiofibromas [52]. This approach allows access to the infratemporal fossa, middle and anterior cranial fossa, and entire cavernous sinus (both medial and lateral aspects). An added enhanced exposure to the nasopharynx, paranasal sinuses and pterygopalatine fossa facilitates complete tumor excision. Facial skeletal growth retardations and facial asymmetry is rare [53].
Large primary tumors or recurrent tumors may necessitate the need for using more than one open approach in the same sitting. These combinations can be tailor –made depending on size of the tumor, involvement of vital structures, and surgeon’s expertise in one or more approaches. Some commonly used combined approaches are-
Last decade has seen a paradigm shift from open approach to transnasal endoscopic approach. In today’s time, endoscopic surgery can be regarded as the most rapidly advancing surgical field. As the surgeon’s familiarity with the endoscopes is increasing, hard to reach anatomical regions are also becoming more accessible, thereby, widening the horizon for this approach. Tumors, which were earlier labeled as operable via an open approach only, can now be easily and completely resected using endoscopic approach.
Endoscopic surgery has the advantage of better illumination and magnification, lower morbidity, and shorter duration of hospital stay which ultimately leads to cost saving. Advantage of no visible facial scar adds to the cosmetic viability of this approach.
Tumor size and extent decides the exact endoscopic approach required. While smaller tumors are managed via an endonasal approach; medium to large sized tumors require an endoscopic Denker’s / Sturman- Canfield or a more extensive transpterygoid approach [57, 58].
Extended anterior skull base approaches are recommended for intracranial lesions [59].
Exposure is the key to a successful surgery. Adequate exposure allows identification of tumor limits, delineation of feeder vessels, and assessment of tumor’s relation with vital structures. Most of the surgical time is spent in achieving this exposure before starting off with the tumor resection.
It is always advisable to identify and ligate the feeding artery first (usually internal maxillary artery), before starting with tumor dissection.
Posterior septectomy, wherever required, is recommended. This greatly increases the access to the tumor.
Dissection is carried along the tumor pseudocapsule from lateral to medial direction. Any injury to tumor surface can provoke massive bleeding.
For larger tumors, a four-handed technique is recommended [22]. For large tumors with extensive lateral extension into infratemporal fossa/ parapharyngeal space, the four-port Bradoo’s technique is a worthy option [60].
Drilling of pterygoid base at the end of the procedure should be a routine practice, so as to minimize the recurrence rates (Figures 3–8).
The operative room should have the availability of hemostatic materials like SURGICEL, FLOSEAL, TIS SEEL and a functioning bipolar cautery. Access to a blood bank is recommended.
Coblation is a plasma based device that can be used for surface coagulation of the tumor without causing any collateral thermal damage. This shrinks the tumor and also greatly reduces intra-op bleeding.
During preoperative planning stage, it is imperative to discuss with the patient, the possibility to convert an endoscopic approach into an open approach at any given time during the surgery.
CE-MRI showing hyperintense tumor (*) with massive lateral extension into infratemporal fossa.
CE-MRI showing hyperintense tumor (*) in the infratemporal fossa.
CECT showing JNA occupying nasopharynx (1), pterygoid wedge (2), infratemporal fossa (3) and intracranial space (4). Notice the widening of left pterygoid wedge (red arrow) as compared to the right normal pterygoid wedge (green arrow)-
CT angiography showing a vascular tumor (*). Notice the internal maxillary artery supplying this tumor (orange arrow).
Endoscopic view through left nasal cavity: Medial and posterior walls of left maxillary sinus and left inferior turbinate have been removed. 1-nasopharyngeal component of JNA; 2- pterygopalatine fossa + infratemporal fossa component of JNA; 3- remnants of left inferior turbinate; R- right, L- left, S- superior, I- inferior.
Coblation wand being used in juvenile nasopharyngeal angiofibroma endoscopic surgery. 1- coblation wand, 2- tumor, R- right, L- left, S- superior, I- inferior.
Broad skull base infiltration
extensive blood supply from ICA
encasement of ICA
brain infiltration
Considering the pace of progress in endoscopic techniques, it would not be surprising if some more indications are added by the time this chapter reaches the readers.
Though Juvenile angiofibroma is now an established surgical entity, there has been an era when medical management alone was the rule for extensive tumors especially those with intracranial extension. With paradigm shift towards more aggressive surgical procedures for all stages of the tumor, other treatment modalities are now valued as adjuvant therapy only.
The procedure is usually done 24 to 48 hours before the scheduled surgery. Further surgical delay is not appreciated/recommended as tumor gains collateral blood supply through neoangiogenesis. A wide variety of materials are available as embolic agents: microspheres, gelatin sponge, Teflon particles, gel foam, poly-vinyl alcohol, polystyrene, silicone particles, silk, cyanoacrylate, sodium tetradacyl sulphate, autogenous clot, duramater, muscle fragments, etc. 300–500 micrometer spheres are preferred owing to greater blocking capacity of vascular lumen [62].
The procedure is not without complications. Cerebral ischemia and vision loss are known complications following embolic agent migrating to ICA system. Rare complications like cerebral edema, hemiplegia and aphasia have also been reported [63].
This results in almost complete filling of tumor microvasculature with irreversible occlusion of embolized vessels. Tumor gains a dark color (due to tungsten powder with blue dye) which helps to better distinguish it from surrounding normal tissue. Direct cytotoxicity of absolute ethanol has shown good therapeutic effects.
DPTE alone or in combination with TAE has shown to have better devascularisation effects than TAE alone [65, 66].
Hormonal influence on growth of JNA has been speculated since long. An interplay between estrogens and androgens has been associated with tumor proliferation and its spontaneous involution. Various hormonal therapies are recommended based on these concepts.
Flutamide therapy is recommended as a six week preoperative adjuvant therapy for intracranial and intraorbital lesions, recurrent lesions and those with their blood supply primarily from ICA.
Low dose radiotherapy is used for angiofibromas extending intracranially, not amenable to primary surgery. Typically, total radiation dose of 3,500 cGy is given over 3 weeks. A successful response in terms of decreased tumor size and vascularity is seen over several months in 80% of the patients [67, 68]. Those showing no response/incomplete response by 2 years post radiotherapy are deemed as failures and taken up for salvage surgery.
There are numerous side effects to use of radiotherapy at a young age. Posterior capsular opacities, glaucoma, optic nerve atrophy, xerostomia, hypopituitarism, cerebral necrosis, osteoradionecrosis of mandible, skull base osteomyelitis, risk of developing new head–neck tumors later in life, potential malignant transformation of angiofibromas are few of the complications associated with the use of radiotherapy in head and neck region.
Juvenile nasopharyngeal angiofibroma, although an old disease entity, is still fascinating medical experts all over the world. Although still largely unknown, with advanced genetic and molecular studies, we have moved a step closer to find the origin and etiology of this disease. At present, surgery is the mainstay of treatment with endoscopic approach replacing the conventional open approach. Future considerations can be focused on therapeutic embolisation, stereotactic radiotherapy and targeted molecular therapy for a non-surgical cure.
I wish to express my sincere gratitude towards Dr. Anupama Mahajan, Dr. Stuti Mahajan and Dr. Anugeet Sethi for their constant moral support. I am fortunate to have worked with Dr. Rajesh Choudhary and Dr. Bikramjeet Singh on numerous juvenile nasopharyngeal angiofibroma cases. A special vote of thanks to Dr. Rohan Sardana and Dr. Karamjeet Singh Gill for providing valuable insight into the pathology of this disease. I shall always be indebted to ENT Department of my alma mater VMMC & Safdarjung Hospital, New Delhi.
The authors declare no conflict of interest.
Larynx plays role in phonation, respiration, airway protection, prevention of aspiration, and swallowing. The extrinsic muscles are associated with swallowing, while the prime function of intrinsic muscles is respiration and phonation.
Vocal cord refers to the immobility of vocal cord. It can be unilateral or bilateral. Both can be due to diseases affecting the vocal cord itself such as tumor or scarring; or due to paralysis of recurrent laryngeal nerve or superior laryngeal nerve.
The most common causes include laryngeal or extralaryngeal cancers, iatrogenic trauma during neck, thyroid gland, or chest surgery, and various neurogenic conditions (e.g., amyotrophic lateral sclerosis and closed head injury) [1, 2, 3, 4].
Vocal cord paralysis is most commonly unilateral. The affected vocal cords do not adduct or abduct properly causing voice disorder. Along with that there might be difficulty in swallowing. As for bilateral paralysis, breathing difficulty, choking, and aspiration are there along with voice change. The incidence of the bilateral vocal cords paralysis comprises around one-third of all vocal cord paralysis cases [2].
It requires interprofessional team of otolaryngologists, radiologists, and speech therapists in the evaluation and management of vocal cord paralysis.
Five positions of vocal cords are described traditionally (Table 1; Figure 1). The position of the vocal cords may not correlate with the severity and site of the lesion and, thus, is not a reliable indicator. As re-innervation occurs the position of the vocal cord often changes.
Position of vocal cords | Location of the cord from midline | Healthy | Diseased |
---|---|---|---|
Median | Midline | Phonation | RLN paralysis |
Paramedian | 1.5 mm | Strong whisper | RLN paralysis |
Intermediate(cadaveric) | 3 mm, this is the neutral position of vocal cords. | Paralysis of both RLN & SLN | |
Gentle abduction | 7 mm | Quite respiration | Paralysis of adductors |
Full abduction | 9 mm | Deep respiration | — |
Position of vocal cords from midline in healthy and diseased individuals.
Diagram showing different positions of vocal cords (FA—full abduction, SA—slight abduction, C—cadaveric, PM—paramedian, M—median).
Causes of vocal cord paralysis include
Supranuclear-stroke, tumor, meningitis, or head injury. Diffuse emboli in cerebral cortex may cause sustained abduction(aphonia) or inappropriate adduction(inspiratory stridor).
Nuclear-lesions of Nucleus ambigus in medulla, usually associated with other lower cranial N. paralysis, stroke, tumors, motor neuron disease, poliomyelitis, syringobulbia.
High vagal lesions—Intracranial: Tumors of posterior fossa, Basal meningitis(tubercular).
Jugular foramen (skull base): Fractures, nasopharyngeal cancer, Glomus tumor, skull base osteomyeltis.
Parapharyngeal space: Penetrating injury, parapharyngeal tumor, metastatic nodes, lymphoma.
Low vagal lesions or RLN: Most common cause, referTable 2.
Systemic causes: Diabetes mellitus, diphtheria, typhoid, lead poisoning, amyotrophic lateral sclerosis (ALS), Guillain-Barre syndrome(GBS).
Idiopathic—In around 30% of cases.
Right | Left | Both |
---|---|---|
Neck trauma | 1. Neck Accidental trauma | |
Benign or malignant thyroid disease | Benign or malignant thyroid disease | |
Thyroid surgery | Thyroid surgery | |
Carcinoma cervical esophagus | Carcinoma cervical esophagus | Thyroid surgery |
Cervical lymphadenopathy | Cervical lymphadenopathy | Carcinoma thyroid |
Subclavian artery aneurysm | 2. Mediastinum | Carcinoma cervical esophagus |
Carcinoma apex right lung | Bronchogenic carcinoma | Cervical lymphadenopathy |
Tuberculosis of cervical pleura | Carcinoma thoracic esophagus | |
Idiopathic | Aortic aneurysm | |
Mediastinal lymphadenopathy | ||
Enlarged left auricle | ||
Intrathoracic surgery | ||
Idiopathic |
Causes of recurrent laryngeal nerve paralysis (low vagal trunk or RLN).
Studies on comparison of patient demographics show no statistically significant difference in age, gender, or duration of symptoms. About one-third of UVCP cases are neoplastic in origin, one-third are post traumatic and one-third are idiopathic. Viral neuronitis probably accounts for most idiopathic cases. Paralysis of the left vocal cord is reported to be 1.4–2.5 times more than right [5].
RLN damage is the most common cause of vocal cord paralysis. Combined paralysis of RLN and SLN is also possible and is seen post-thyroidectomy surgeries due to iatrogenic trauma.
To understand the pathophysiology of vocal cord paralysis, it is of importance to know the origin and course of vagus nerve and its branches as they give rise to laryngeal sensory and motor supply.
Vagus nerve has two nuclei—nucleus ambiguous and dorsal nucleus of vagus. Nucleus ambiguous is situated in medulla and gives origin to motor efferent fibers to soft palate, pharynx, and larynx. Dorsal nucleus of vagus is an autonomic nucleus, which gives general efferent visceral fibers that supply smooth muscles and glands of trachea and bronchi, heart, and abdominal viscera.
The superior laryngeal nerve arises from inferior ganglion of vagus and descends behind internal carotid artery, and at the level of greater cornua of hyoid, it divides into internal and external branches. The internal branch travels medially along superior laryngeal branch of superior thyroid artery and pierces the thyrohyoid membrane about 1 cm anterior to greater cornu and about 1 cm above ala of thyroid cartilage. The nerve then runs submucosally in the lateral wall of pyriform fossa. It provides sensory innervation to the mucosa above the true vocal cords. The external branch runs along the posterior aspect of superior thyroid artery and proceeds inferiorly along oblique line of thyroid. As it reaches inferior constrictor muscle, it sends a branch and then passes deep to sternothyroid muscle to reach the cricothyroid muscle. It innervates the cricothyroid muscle (essential in changing the pitch of the voice). Isolated superior laryngeal nerve lesions are rare and it is usually part of combined paralysis. It results in loss of sensation above the level of true vocal cords and a husky voice.
On the right side, RLN arises from vagus in front of subclavian artery in lower part of neck, and it traversus below the subclavian artery after emerging from vagus nerve. RLN is derived from sixth arch and is displaced by arteries of previous arch, which necessitates change in direction and course of recurrent laryngeal nerve. The right recurrent laryngeal nerve stays lateral to the trachea-esophageal groove in the fat plane and comes closure to the groove as it crosses inferior thyroid artery. The left RLN has longer course and from its origin at the anterior surface of arch of aorta to the interspace between origin of left common carotid artery and subclavian artery. The nerve loops around arch of aorta distal to ligamentum arteriosum and then enters the neck, and lies deeper in the trachea-esophageal groove. Rest of the course is in similar on both sides, as RLN reaches the suspensory ligament of thyroid gland and lies on either medial or lateral from within. Then, it divides to supply the intrinsic muscles of larynx. Left RLN is more prone for injury as it has a longer course and injury most commonly occurs in the region of trachea-esophageal groove during thyroid or any other neck surgery.
There are two theories to explain the position of vocal cord in cases of cord paralysis. Semon’s law states that in the sequence of position of the vocal cords in slowly progressive organic central lesions, motor nerve fibers supplying the abductors of vocal cords become involved much earlier than adductors. Wegner and Grossman hypothesis explains the median and paramedian position of cords after RLN palsy, on the basis that cricothyroid muscle that receives supply from superior laryngeal nerve takes over & it has adductor and tensor function.
Patients with unilateral cord paralysis present with a sudden onset of change in voice, that is, dysphonia and/or transient aphonia. In addition to dysphonia, a significant proportion of patients present with swallowing difficulties, weak cough reflex, and regurgitation. Poor exercise tolerance with shortness of breath on minimal exertion is observed in many patients with UVCP in spite of normal lung function.
It is important to obtain elaborate history including the symptoms and signs pertaining to head and neck cancer. History of pain during swallowing, hemoptysis, neck nodes, referred ear pain, and significant weight loss should be asked. Past medical history including heart or lung disease, smoking, tobacco chewing, and alcohol consumption status are all important indicators of potential malignant disease. Clinical evaluation of the patient should include a complete otolaryngological examination, with particular attention to inspection and palpation of the neck. Flexible nasal endoscopy of the oropharynx and glottis helps forming the diagnosis. Assessment of voice quality can be graded with GRBAS scale (Grade, Roughness, Breathlessness, Aesthenia, Strain) [6], which has frequently shown the voice to be worse in such patients.
Flexible laryngoscopy of the glottis is the most useful method of evaluating appearance and movement of vocal cords. It is easily performed in the outpatient setting and can be combined with videostroboscopy to obtain a detailed overview of vocal cord movements (Figure 2).
Videolaryngoscopy showing left vocal cord paralysis post left hemithyroidectomy (a)abduction (b) adduction.
Videostrobscopy uses the same equipment as videolaryngoscopy combined with a microphone and flashing strobe light. During speech production, our vocal cords move at a very high speed, too fast to be perceived by naked human eyes. Stroboscopy is used to “slow down” the movement to study the detailed vocal cord movements such as amplitude, mucosal wave, vibratory pattern. It is a gold standard test in cases of voice disorders (Figure 3).
Videostroboscopy pictures showing right vocal cord paralysis.
A
Neck and laryngeal ultrasound can be used to assess vocal cord movement and investigate surrounding pathologies. However, ultrasound does not yield the same anatomical definition as CT requires an experienced ultrasonographer and is less reliable in obese patients.
Routine serological testing only aids in the diagnosis of a particular etiology. There is no strong evidence of them in helping form a diagnosis. Serum tests can be used in suspected inflammatory or infectious UVCP, with common tests including rheumatoid factor, antinuclear antibodies, serum ACE, lyme titer, and erythrocyte sedimentation rate (ESR).
Laryngeal electromyography can be used as a prognostic tool. It is an office-based procedure. A percutaneous EMG needle is inserted through the anterior part of neck to the muscles of the larynx and their electrophysiological evaluation is done. Although growing in popularity, the test is not widely available.
Patients with UVCP are initially treated with speech therapy. A “watchful waiting” period of 6 to 9 months is observed for spontaneous motion recovery by the opposite healthy vocal cord, as there is no definitive guidelines on how long a clinician should wait before surgical intervention.
The aim of surgery in cases of unilateral cord paralysis is cord medialization. The different surgical options are as follows:
Around one-third of patients of UVCP will experience motion recovery, due to the compensatory action of the opposite vocal cord [10]. Laryngeal electromyography is an useful tool to track prognosis in patients with persistent dysphonia [11].
The adverse effect on voice and swallowing can have a significant detrimental impact on the patient’s quality of life. Incomplete closure of the glottis can also lead to a risk of aspiration, and despite being rare, this can lead to life-threatening aspiration pneumonia. In particular, patients who rely on their voice for a living (teachers, singers, secretaries) may suffer significant psychological and financial difficulty as a result of UVCP.
The interprofessional team approach is better in diagnosing and managing cases of UVCP. Otolaryngologists can diagnose it with elaborate history, clinical examination, and flexible video laryngoscopy. Radiologists can aid in diagnosis through the study of the course of nerve involved or mediastinal lesion through CT /MRI imaging. Management can be done with speech therapy with the support of speech and language therapists and surgical treatment for those patients by otolaryngologists who do not respond to initial therapy.
The most common presentation of bilateral vocal cord paralysis is stridor [12]. These patients typically present with respiratory distress. In addition to considerable airway obstruction, bilateral vocal cord paralysis presents with symptoms common in unilateral vocal cord immobility such as ineffective cough, aspiration, recurrent pneumonia, reactive airway disease, and feeding difficulties [13, 14]. Voice and cry may be fairly normal in children with bilateral vocal cord paralysis [15].
As bilateral vocal cord paralysis occurs most commonly after iatrogenic trauma to recurrent laryngeal nerve, there is history of recent thyroid surgery in these patients. The incidence of the bilateral vocal cords paralysis comprises around one-third of all vocal cord paralysis cases. Bilateral cord paralysis is slightly more common in females, and it is attributed to the fact that thyroid diseases are more common in them as compared to males. Idiopathic bilateral paralysis cases show no gender preponderance and incidence is equal in both males and females.
RLN damage is the most common cause of bilateral vocal cord paralysis. Combined paralysis of RLN and SLN is also possible and is seen post-thyroidectomy surgeries due to iatrogenic trauma.
Bilateral vocal cord paralysis can be caused by injury to the vagus nerve near its origin or anywhere along its course or injury to its branches RLN and SLN through neck, thorax, and abdomen. Injury to the RLN is most common, classically leaving the vocal cords in a median position in case of bilateral vocal cord paralysis. Injury to the SLN will lower the pitch of the voice and can lead to a bowing deformity of the vocal cords due to a loss of tone from the dennervated cricothyroid muscles. A high vagal injury can leave the cord in a nearly fully abducted position.
A bilateral vocal cord paralysis patient most commonly presents with breathing difficulties such as stridor, increased work of breathing, and aspiration. It can be life-threatening and immediate measures that have to be taken to secure the airway. Voice in bilateral paralysis is usually of good quality but of limited intensity, changed pitch, and with voice fatigue. Any recent history of URI, any neck or mediastinal surgery or trauma, malignancy, radiation therapy, and a thorough past medical history should be obtained. A thorough physical examination is done, with an emphasis on the head and neck and lung examination.
Clinical diagnosis can be made based on flexible fiber-optic laryngoscopy, where the vocal cord position can be noted and are observed to be immobile. If the diagnosis is still uncertain, video stroboscopy and bronchoscopy can provide additional information about motion wave of the vocal cord vibrations and rule out subglottic and tracheal pathology, such as subglottic stenosis or tracheomalacia.
The investigations that aid in diagnosis are as follows:
Videolaryngoscopy pictures showing bilateral vocal cord paralysis.
In bilateral cord paralysis, patient adequate airway must be re-established. Common surgical options for management include tracheostomy, arytenoidectomy, and cordotomy. Laryngeal re-innervation techniques and botulinum toxin (Botox) injections into the vocal fold adductors have also been used with varying success rates. More recently, there has been research on neuromodulation, laryngeal pacing, gene therapy, and stem cell therapy. These newer approaches have the potential to recover the vocal cord movement without any anatomical destruction. However, clinical data are limited for these new treatment options, and more interventional studies are needed. These areas of research are expected to provide dramatic improvements in the treatment of bilateral cord paralysis in future.
Botulinum toxin injection to adductor muscles provides transient improvement in symptoms for approximately three to 6 months at a time, requiring repeated injections for longer-lasting relief.
Reinnervation techniques are technically challenging and require experienced surgeons in its use for the procedure to be a success. The goal here is to establish vocal cord abduction through the restoration of the activity of the posterior cricoarytenoid (PCA) muscle. While it enables the return of spontaneous vocal cord abduction, it does not affect adduction. Gene therapy and stem cell therapy are in preclinical stage but hold promising for treatment in future.
In adults, spontaneous recovery of idiopathic vocal cord paralysis can occur as early as 12 months following the onset. It is expected in 55% of patients, but full recovery can be very protracted. The prognosis for complete spontaneous recovery is far worse in bilateral vocal cord paralysis than unilateral. Recovery depends upon the underlying etiology.
Bilateral cord paralysis can lead to the following complications: Stridor, airway obstruction, dyspnea, poor cough reflex, aspiration, bronchopneumonia due to aspiration, difficulty in swallowing, feeding difficulties, and failure to thrive in children & voice fatigue. In addition to this, in the long-run arytenoid granuloma formation and chondritis may occur.
Bilateral vocal cord paralysis is a challenging and troublesome entity. Tracheostomy, cordotomy, and arytenoidectomy all have been applied with positive outcomes in bilateral cord paralysis cases. Management should be individualized based on the patient’s clinical presentation and the surgeon’s expertise.
Vocal cord fixation is immobility of vocal cords due to scarring or due to mass effect, involvement of muscles, and joints or the nerve as in case of malignancy. Cord fixation can also be due to rheumatoid arthritis. There may be obvious swelling around cricoarytenoid joint, cord is immobile and fixed, its position does not correspond to any of the described anatomical positions of vocal cords, and aryepiglottic folds are normal. There is no change in position on applying pressure passively on arytenoids, which is in contrast to vocal cord paralysis. Also, in cases of fixation there is absence of any neurological symptoms and signs. In cases of vocal cord paralysis, aryepiglottic folds are paralyzed and pushed aside, cord is fixed to median or paramedian position, but there is no fixation of the joint and it is mobile on manipulating passively. Also, cord paralysis is purely a neurological condition in contrast to cord fixation.
Vocal cord paralysis presents more commonly as stridor in neonates and children. It can be unilateral or bilateral in children, unilateral being more common. Vocal cord paralysis is the second most common cause of stridor in pediatric population following laryngomalacia and accounts for 10% of all congenital anomalies of larynx. Murty et al. estimate the incidence of bilateral vocal cord paralysis to be 0.75 cases per million births per year. Congenital vocal cord paralysis should be part of the differential diagnosis for an infant with respiratory distress. In up to 48–62% of neonates and children with bilateral vocal cord paralysis, spontaneous recovery of vocal cord function can occur, but the prognosis rests with the overall health of the child and any concomitant medical problems [19].
Birth trauma due to vertex or breech delivery and the use of forceps can also lead to RLN injury, though less commonly a bilateral injury [20]. In infants, cardiovascular surgery, including patent ductus arteriosus ligation, and repair of a tracheoesophageal fistula are the common causes of bilateral vocal cord paralysis [21]. Table 3 summarizes causes of congenital vocal cord paralysis.
Unilateral | Bilateral |
---|---|
More common | Causes |
Causes | Hydrocephalus |
Birth trauma | Arnold-chiari malformation |
Congenital anomaly of | Intracerebral hemmorrhage |
Great vessels of heart | Myelomeningocele |
Cerebral agenesis |
Causes of congenital vocal cord paralysis.
A detailed family and perinatal histories, including prolonged or protracted or forceps-assisted delivery, concurrent congenital conditions and length of any NICU stay, should be inquired. Presenting symptoms in children include stridor, a weak cry, feeding difficulties, failure to thrive, and aspiration. Neonates and children with bilateral cord paralysis are likely to exhibit severe manifestation such as cyanosis and apnea. Bilateral cases usually have good voice because vocal cords are in median or paramedian position with abductor paralysis but can have marked inspiratory stridor and accessory muscles of respiration working.
Diagnosis can be made by awake fiber-optic laryngoscopy and careful evaluation of the larynx by an experienced pediatric otolaryngologist. Laryngomalacia should be considered as differential diagnosis and ruled out during laryngoscopy, which is far more common than bilateral vocal cord paralysis but can have similar presenting symptoms.
If the diagnosis is still uncertain, direct laryngoscopy and bronchoscopy can be performed under general anesthesia. This is done with the patient spontaneously breathing so the motion of the vocal cords can be assessed intraoperatively. This also allows lower airway examination to rule out concurrent or alternate pathology such as subglottic stenosis and trachea- or bronchomalacia.
Before surgical treatment is considered, parents are advised to position the child so that he or she is sitting up and to thicken the food in order to manage feeding difficulties and milk regurgitation. If gastroesophageal reflux is suspected, then this should also be treated. In addition, all children with vocal cord paralysis should be seen by a speech pathologist. Greater than 50% of children will undergo spontaneous symptom resolution in the first 12 months of life, though the prognosis is much more guarded for bilateral vocal cord paralysis cases when compared with unilateral [22].
There are no definite guidelines on when to perform surgery and the decision is difficult since in children spontaneous recovery may occur anytime over the years. It should be guided according to the individual case. In general, for cases of bilateral palsy destructive procedures such as cordotomy or arytenoidectomy are advised to be deferred till adolescence.
Tracheostomy is needed and should be performed to improve the airway in bilateral vord paralysis cases, even if spontaneous recovery is expected. Patient can be decanulated once vocal cord recovery occurs.
An integrated diagnostic and treatment program is necessary for patients with vocal cord paralysis. Otolaryngologists, speech therapist, and radiologists all play important role in evaluation and management. Treatment strategies should be individualized based on the patient’s clinical presentation and the surgeon’s expertise.
I would like to express my gratitude to the faculty members of the department and the management for giving their valuable suggestions and inputs. Special mention and thanks to Dr. Hukam singh and Dr. Avinash goswami for their encouragement and support in making this chapter possible.
The author declares no conflict of interest.
recurrent laryngeal nerve
superior laryngeal nerve
unilateral vocal cord paralysis
computer tomographic imaging
magnetic resonance imaging
electromyography
amyotropic lateral sclerosis
Guillain-Barre syndrome
Grade, Roughness, Breathlessness, Aesthenia, Strain
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All published Book Chapters are licensed under a Creative Commons Attribution 3.0 Unported License. Monographs are licensed under the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) license granted to all others. Our Copyright Policy aims to guarantee that original material is published while at the same time giving significant freedom to our Authors. IntechOpen upholds a flexible Copyright Policy meaning that there is no copyright transfer to the publisher and Authors hold exclusive copyright to their work.
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Naughton M.",authors:null},{id:"63898",doi:"10.5772/intechopen.81478",title:"Indoor Air Quality Monitoring for Enhanced Healthy Buildings",slug:"indoor-air-quality-monitoring-for-enhanced-healthy-buildings",totalDownloads:1637,totalCrossrefCites:8,totalDimensionsCites:12,abstract:"Since most people spend 90% of their time indoors, the indoor environment has a determining influence on human health. In many instances, the air quality parameters are very different from those defined as healthy values. Using real-time monitoring, occupants or the building manager can decide and control behaviors and interventions to improve indoor air quality. The historical database is also useful for assisting doctors to support the medical diagnosis. The continuous technological advancements notably, as regards, networking, sensors, and embedded devices have made it possible to monitor and provide assistance to people in their homes. Smart objects with great capabilities for sensing and connecting could revolutionize the way we are monitoring our environment. This chapter consists of a general overview of several real-time monitoring systems developed and published by the authors. In this chapter, the authors present several new open-source and cost-effective systems that had been developed for monitoring environmental parameters, always with the aim of improving indoor air quality for enhanced healthy buildings.",book:{id:"7473",slug:"indoor-environmental-quality",title:"Indoor Environmental Quality",fullTitle:"Indoor Environmental Quality"},signatures:"Gonçalo Marques and Rui Pitarma",authors:[{id:"202912",title:"Prof.",name:"Rui",middleName:null,surname:"Pitarma",slug:"rui-pitarma",fullName:"Rui Pitarma"},{id:"250831",title:"Dr.",name:"Gonçalo",middleName:"Miguel Santos",surname:"Marques",slug:"goncalo-marques",fullName:"Gonçalo Marques"}]},{id:"66693",doi:"10.5772/intechopen.85808",title:"Lumber-Based Mass Timber Products in Construction",slug:"lumber-based-mass-timber-products-in-construction",totalDownloads:1870,totalCrossrefCites:8,totalDimensionsCites:12,abstract:"This chapter provides information related to commonly used wood construction methods (i.e., light-frame, post-and-beam, and mass timber) and mass timber products. It briefly discusses the manufacturing of four major lumber-based mass timber products (i.e., glue-laminated timber, nail-laminated timber, dowel-laminated timber, and cross-laminated timber), and their available dimensions and typical applications. The discussion also addresses primary lumber products, such as dimension lumber, machine stress-rated lumber, and finger-joined lumber, which are the building blocks from which mass timber products are manufactured. Advantages of using wood in construction are illustrated by examples largely from North American practices. The life cycle assessment concept is also introduced.",book:{id:"8299",slug:"timber-buildings-and-sustainability",title:"Timber Buildings and Sustainability",fullTitle:"Timber Buildings and Sustainability"},signatures:"Meng Gong",authors:[{id:"274242",title:"Dr.",name:"Meng",middleName:null,surname:"Gong",slug:"meng-gong",fullName:"Meng Gong"}]},{id:"9627",doi:"10.5772/8410",title:"Aging in Place: Self-Care in Smart Home Environments",slug:"aging-in-place-self-care-in-smart-home-environments",totalDownloads:3408,totalCrossrefCites:9,totalDimensionsCites:10,abstract:null,book:{id:"3631",slug:"smart-home-systems",title:"Smart Home Systems",fullTitle:"Smart Home Systems"},signatures:"Blanson Henkemans, Olivier A., Alpay, Laurence, L., and Dumay Adrie, C.M.",authors:null},{id:"62021",doi:"10.5772/intechopen.78576",title:"Urbanization and Meeting the Need for Affordable Housing in Nigeria",slug:"urbanization-and-meeting-the-need-for-affordable-housing-in-nigeria",totalDownloads:2681,totalCrossrefCites:5,totalDimensionsCites:10,abstract:"Urbanization is an ongoing trend in developed and developing countries. With particular reference to Nigeria, studies have shown that many urban centres have been experiencing rapid and continuous growth over the years, as people tend to migrate from rural areas to urban centres in order to better their living conditions. However, there has been an inadequacy of the necessary infrastructures to meet the needs of the increasing urban populace. Empirical studies have also shown that about 75% of the urban settlers live in slums and improper housing, which is antithetical to human dignity. Therefore, this study aims at exploring the causes, advantages, and disadvantages of urban slum dwelling in Nigeria, and similarly proper possible solutions to the prevailing urbanization challenges in the country. The authors agree that the policy can bring about an effective provision of affordable housing, thereby meeting the needs of housing and helping to solve most of the problems of urbanization in Nigeria. It is recommended that each element of an effective housing policy, as entrenched in the National Housing Policy 2012, should be critically explored towards the delivery of affordable housing, which would in turn go a long way in solving urbanization problems in Nigeria.",book:{id:"7205",slug:"housing",title:"Housing",fullTitle:"Housing"},signatures:"Temi Oni-Jimoh and Champika Liyanage",authors:[{id:"245547",title:"Mrs.",name:"Temi",middleName:null,surname:"Oni-Jimoh",slug:"temi-oni-jimoh",fullName:"Temi Oni-Jimoh"},{id:"245550",title:"Dr.",name:"Champika",middleName:null,surname:"Liyanage",slug:"champika-liyanage",fullName:"Champika Liyanage"}]}],mostDownloadedChaptersLast30Days:[{id:"67068",title:"Structural Design of a Typical American Wood-Framed Single-Family Home",slug:"structural-design-of-a-typical-american-wood-framed-single-family-home",totalDownloads:2697,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Light-wood framing construction techniques have been traditionally used in America for the construction of single-family residences. Dimensional wood lumber is readily available and due to its convenient unit dimension can be packaged neatly and transported to work sites by either commercial transport or personal vehicle. The unit pieces of dimensional lumber are light and easily handled once on the work site. Design of light-framed single-family homes is typically conducted by an architect or construction contractor using prescriptive building codes. A structural engineer can assist, if needed, with design items not within the scope of the building code or if alternative design approaches are required. An owner may choose to involve the engineer to improve quality or economy of the home design. Engineers typically become involved with design items such as foundation design, steel framing design, or engineered product specification. In this chapter, the design of a typical light-framed home is discussed. The main structural assemblies are described and subsequently designed using a combination of prescriptive guidance and engineering design.",book:{id:"8299",slug:"timber-buildings-and-sustainability",title:"Timber Buildings and Sustainability",fullTitle:"Timber Buildings and Sustainability"},signatures:"Anthony C. Jellen and Ali M. Memari",authors:[{id:"252670",title:"Prof.",name:"Ali",middleName:null,surname:"M. Memari",slug:"ali-m.-memari",fullName:"Ali M. Memari"},{id:"276003",title:"Mr.",name:"Anthony",middleName:null,surname:"Jellen",slug:"anthony-jellen",fullName:"Anthony Jellen"}]},{id:"60236",title:"The Feasibility of Constructing Super-Long-Span Bridges with New Materials in 2050",slug:"the-feasibility-of-constructing-super-long-span-bridges-with-new-materials-in-2050",totalDownloads:1875,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"This chapter explores the possibility of designing and constructing a super-long-span bridge with new materials in 2050. The proposed bridge design has a total span of 4440 m with two 330-m end spans and a central span of 3780 m. The height of the two pylons is 702 m, and the deck width is 40 m. The features of this structure include the combination of a suspension bridge and cable-stayed bridge, application of carbon fibre materials, extension of deck width and pretension techniques. Linear static analysis, dynamic analysis and theoretical analysis are conducted under different loading cases. In linear static analysis, the stresses under critical load combinations are smaller than the ultimate strength of the materials. However, the maximum deflection under the dead and wind load combination exceeds the specified serviceability limit.",book:{id:"6395",slug:"bridge-engineering",title:"Bridge Engineering",fullTitle:"Bridge Engineering"},signatures:"Faham Tahmasebinia, Samad Mohammad Ebrahimzadeh\nSepasgozar, Hannah Blum, Kakarla Raghava Reddy, Fernando\nAlonso-Marroquin, Qile Gao, Yang Hu, Xu Wang and Zhongzheng\nWang",authors:[{id:"211659",title:"Dr.",name:"Faham",middleName:null,surname:"Tahmasebinia",slug:"faham-tahmasebinia",fullName:"Faham Tahmasebinia"},{id:"221172",title:"Dr.",name:"Samad M.E.",middleName:null,surname:"Sepasgozar",slug:"samad-m.e.-sepasgozar",fullName:"Samad M.E. 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Today, the social structure of mass housing estates becomes more heterogeneous, what puts new requirements on the design of open public spaces and, as well as, on the regeneration and design of children’s playgrounds, to serve the rising demands of the inhabitants and to enhance the livability of the housing estates. The study examines the current examples of the children’s playgrounds from Slovak mass housing estates, which show that nowadays the typified design of the standardized catalog type elements is used and preferred.",book:{id:"7205",slug:"housing",title:"Housing",fullTitle:"Housing"},signatures:"Katarína Kristiánová",authors:[{id:"224853",title:"Dr.",name:"Katarina",middleName:null,surname:"Kristianova",slug:"katarina-kristianova",fullName:"Katarina Kristianova"}]},{id:"62555",title:"Risk Management in Indonesia Construction Project: A Case Study of a Toll Road Project",slug:"risk-management-in-indonesia-construction-project-a-case-study-of-a-toll-road-project",totalDownloads:2917,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"While project risks are generally acknowledged merely from owner and contractor perspectives, other parties also play important roles in the project. 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Radiotherapy and Nuclear Medicine Technology has always been my aspiration and my life. As years passed I accumulated a tremendous amount of skills and knowledge in Radiotherapy and Nuclear Medicine, Conventional Radiology, Radiation Protection, Bioinformatics Technology, PACS, Image processing, clinically and lecturing that will enable me to provide a valuable service to the community as a Researcher and Consultant in this field. My method of translating this into day to day in clinical practice is non-exhaustible and my habit of exchanging knowledge and expertise with others in those fields is the code and secret of success.",institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"313277",title:"Dr.",name:"Bartłomiej",middleName:null,surname:"Płaczek",slug:"bartlomiej-placzek",fullName:"Bartłomiej Płaczek",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/313277/images/system/313277.jpg",biography:"Bartłomiej Płaczek, MSc (2002), Ph.D. (2005), Habilitation (2016), is a professor at the University of Silesia, Institute of Computer Science, Poland, and an expert from the National Centre for Research and Development. His research interests include sensor networks, smart sensors, intelligent systems, and image processing with applications in healthcare and medicine. 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Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University. 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Prof. Sarfraz is also an editor-in-chief and editor of various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/267434/images/system/267434.jpg",biography:"Dr. Rohit Raja received Ph.D. in Computer Science and Engineering from Dr. CVRAMAN University in 2016. His main research interest includes Face recognition and Identification, Digital Image Processing, Signal Processing, and Networking. Presently he is working as Associate Professor in IT Department, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (CG), India. He has authored several Journal and Conference Papers. He has good Academics & Research experience in various areas of CSE and IT. He has filed and successfully published 27 Patents. He has received many time invitations to be a Guest at IEEE Conferences. He has published 100 research papers in various International/National Journals (including IEEE, Springer, etc.) and Proceedings of the reputed International/ National Conferences (including Springer and IEEE). He has been nominated to the board of editors/reviewers of many peer-reviewed and refereed Journals (including IEEE, Springer).",institutionString:"Guru Ghasidas Vishwavidyalaya",institution:{name:"Guru Ghasidas Vishwavidyalaya",country:{name:"India"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:{name:"Medical University Plovdiv",country:{name:"Bulgaria"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Igor Victorovich Lakhno was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPh.D. – 1999, Kharkiv National Medical Univesity.\nDSC – 2019, PL Shupik National Academy of Postgraduate Education \nProfessor – 2021, Department of Obstetrics and Gynecology of VN Karazin Kharkiv National University\nHead of Department – 2021, Department of Perinatology, Obstetrics and gynecology of Kharkiv Medical Academy of Postgraduate Education\nIgor Lakhno has been graduated from international training courses on reproductive medicine and family planning held at Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor in the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics, and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s been a professor in the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics, and gynecology department. He’s affiliated with Kharkiv Medical Academy of Postgraduate Education as a Head of Department from November 2021. Igor Lakhno has participated in several international projects on fetal non-invasive electrocardiography (with Dr. J. A. Behar (Technion), Prof. D. Hoyer (Jena University), and José Alejandro Díaz Méndez (National Institute of Astrophysics, Optics, and Electronics, Mexico). He’s an author of about 200 printed works and there are 31 of them in Scopus or Web of Science databases. Igor Lakhno is a member of the Editorial Board of Reproductive Health of Woman, Emergency Medicine, and Technology Transfer Innovative Solutions in Medicine (Estonia). He is a medical Editor of “Z turbotoyu pro zhinku”. Igor Lakhno is a reviewer of the Journal of Obstetrics and Gynaecology (Taylor and Francis), British Journal of Obstetrics and Gynecology (Wiley), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for a DSc degree “Pre-eclampsia: prediction, prevention, and treatment”. Three years ago Igor Lakhno has participated in a training course on innovative technologies in medical education at Lublin Medical University (Poland). Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: are obstetrics, women’s health, fetal medicine, and cardiovascular medicine. \nIgor Lakhno is a consultant at Kharkiv municipal perinatal center. He’s graduated from training courses on endoscopy in gynecology. He has 28 years of practical experience in the field.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. 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