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1.
Cell Death Dis ; 15(7): 517, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39030166

ABSTRACT

Head and neck squamous cell carcinoma (HNSCC) is a highly malignant disease, and death rates have remained at approximately 50% for decades. New tumor-targeting strategies are desperately needed, and a previous report indicated the triggered differentiation of HPV-negative HNSCC cells to confer therapeutic benefits. Using patient-derived tumor cells, we created a similar HNSCC differentiation model of HPV+ tumor cells from two patients. We observed a loss of malignant characteristics in differentiating cell culture conditions, including irregularly enlarged cell morphology, cell cycle arrest with downregulation of Ki67, and reduced cell viability. RNA-Seq showed myocyte-like differentiation with upregulation of markers of myofibril assembly. Immunofluorescence staining of differentiated and undifferentiated primary HPV+ HNSCC cells confirmed an upregulation of these markers and the formation of parallel actin fibers reminiscent of myoblast-lineage cells. Moreover, immunofluorescence of HPV+ tumor tissue revealed areas of cells co-expressing the identified markers of myofibril assembly, HPV surrogate marker p16, and stress-associated basal keratinocyte marker KRT17, indicating that the observed myocyte-like in vitro differentiation occurs in human tissue. We are the first to report that carcinoma cells can undergo a triggered myocyte-like differentiation, and our study suggests that the targeted differentiation of HPV+ HNSCCs might be therapeutically valuable.


Subject(s)
Cell Differentiation , Cell Survival , Head and Neck Neoplasms , Squamous Cell Carcinoma of Head and Neck , Humans , Squamous Cell Carcinoma of Head and Neck/virology , Squamous Cell Carcinoma of Head and Neck/pathology , Squamous Cell Carcinoma of Head and Neck/metabolism , Head and Neck Neoplasms/virology , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/metabolism , Papillomavirus Infections/virology , Papillomavirus Infections/pathology , Papillomavirus Infections/metabolism , Cell Lineage , Muscle Cells/virology , Muscle Cells/metabolism , Muscle Cells/pathology , Papillomaviridae/physiology , Cell Line, Tumor , Human Papillomavirus Viruses
2.
J Clin Med ; 13(11)2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38893011

ABSTRACT

Background: In most cases, intralabyrinthine schwannoma (ILS) occurs in patients with unilateral hearing deterioration or neurofibromatosis type II (NF II). The pattern of localization of these tumors varies but mostly affects the cochlea. Extirpation of the cochlear schwannoma, if hidden by the cochlea modiolus, is difficult under the aspect of complete removal. Therefore, a tissue removal device (TRD) was designed and tested in temporal bones. The principle of handling the new device is a pushing and pipe cleaner handling inside the cochlea. This present study aimed to describe the first in vivo experience with the newly developed TRD for removing cochlear intralabyrinthine schwannomas. Methods: In three patients, the TRD was used for the tumor removal of cochlear schwannomas. In two patients with a cochlear schwannoma in combination with a cochlea implantation and one patient suffering from NF II, a cochlear schwannoma was removed with the TRD. The access was performed with a posterior tympanotomy, an enlarged round window approach and an additional second turn access. The device was inserted and extracted gradually from the second turn access until the rings were visible in the second turn access. By pushing and pipe cleaner handling, the tumors were removed. An MRI control was performed on the day postoperatively with a T1 GAD sequence. Results: Tumor removal with the TRD was performed in a 15-min procedure without any complications. An MRI control confirmed complete removal on the postoperative day in all cases. Conclusions: In vivo handling of the device confirmed straightforward handling for the tumor removal. MRI scanning showed complete removal of the tumor by the TRD.

3.
Front Surg ; 11: 1341118, 2024.
Article in English | MEDLINE | ID: mdl-38496212

ABSTRACT

Introduction: Otalgia can have multiple causes. Mostly otalgia is caused by a tubal dysfunction or an acute middle ear infection. This case describes a patient with an inflammation of the Jacobson's nerve causing severe persistent otalgia after an acute otitis media. The patients complaints completely disappeared after neurolysis of the Jacobson's nerve. Case presentation: We describe a case of a 21-year-old female caucasian patient with acute otitis media and persistent intractable otalgia. Infection was first successfully controlled by antibiotics. But the patient reported a persistent otalgia not responding to analgetics. We performed a CT scan, which exhibited a regular aerated middle ear finding, and a diagnostic tympanoscopy to examine the middle ear structures particularly the tympanic Jacobson's nerve as a possible cause for persistent pain. The following neurolysis of Jacobson's nerve under general anaesthesia led to a resolution of otalgia. Conclusion: An inflamed tympanic Jacobson's nerve is a rare observation and a persisting otalgia after an acute otitis media not responding to conservative treatment can be treated by a neurolysis.

4.
Brain Sci ; 13(6)2023 May 25.
Article in English | MEDLINE | ID: mdl-37371333

ABSTRACT

INTRODUCTION: Cochlear implantation in patients with Ménière's disease (MD) is the treatment of choice in cases of functional deafness. Additional vertigo control is of central importance in this group of patients. Endolymphatic hydrops (ELH) is the pathophysiological correlate of MD and can be evaluated by magnet resonance imaging (MRI). Bilateral MD occurs in 10-33% and can be the reason for a postoperative persisting or newly occurring vertigo in this group. Recent developments in the field of implant magnets and experience in MRI sequences allow the diagnostic performance of MRI in cochlear implantees to be evaluated. The aim of the present study was to evaluate the possibility of MRI as a visual diagnostic tool for endolymphatic hydrops in cochlear implantees. MATERIAL AND METHODS: This was a retrospective study including three cochlear implantees (age: 61-76 years, one female, two male) suffering from MD who, postoperatively, had a recurrence of vertigo with Ménière's-like symptoms. An MRI was performed for the evaluation of ELH (ELH-MRI). MRI observation was performed by a 4 h iv. delayed Gad 3 D Flair sequence. RESULTS: In all cases, the ipsilateral implant magnet artifact covered the vestibulum, the semicircular canals and the cochlea. The contralateral vestibulum, the semicircular canal and the cochlea were fully observable, and a classification of the ELH-MRI could be performed. CONCLUSION: ELH-MRI scanning allows for the detection of contralateral labyrinthine endolymphatic hydrops and is a tool for the postoperative evaluation of vertigo in cochlear implantees.

5.
Front Surg ; 10: 1195473, 2023.
Article in English | MEDLINE | ID: mdl-37188097

ABSTRACT

[This corrects the article DOI: 10.3389/fsurg.2023.1077407.].

6.
NPJ Vaccines ; 8(1): 49, 2023 Apr 01.
Article in English | MEDLINE | ID: mdl-37005390

ABSTRACT

Recurrent Respiratory Papillomatosis(RRP) is a rare disease with severe morbidity. Treatment is surgical. Prevailing viewpoint is that prophylactic HPV vaccines do not have therapeutic benefit due to their modus operandi. Studies on HPV vaccination alongside surgery were meta-analysed to test effect on burden of disease. Databases were accessed Nov and Dec 2021 [PubMed, Cochrane, Embase and Web of Science]. Main outcome measured was: Mean paired differences in the number of surgeries or recurrences per month. Analyses was performed using: Random effect maximal likelihood estimation model using the Stata module Mataan(StataCorp. 2019. Stata Statistical Software: Release 16. College Station, TX:StataCorp LLC.) Our results found n = 38 patients, suitable for syntheses with one previous meta-analyses (4 published, 2 unpublished studies) n = 63, total of n = 101 patients. Analyses rendered an overall reduction of 0.123 recurrences or surgeries per month (95% confidence interval [0.064, 0.183]). Our meta-analyses concludes that HPV vaccine is a beneficial adjunct therapy alongside surgery.

7.
Front Surg ; 10: 1077407, 2023.
Article in English | MEDLINE | ID: mdl-36816011

ABSTRACT

Background: Intralabyrinthine schwannoma (ILS) is a rare, mostly unilateral disease that causes deafness. Different intralabyrinthine sites of ILS can occur and can be removed by different surgical approaches. Cochlear ILSs are frequently partially hidden by the modiolus and therefore difficult to extirpate. Surgical techniques can be traumatic, offer limited surgical control during removal, and are time-consuming. The aim of this present study was to demonstrate the performance and handling of a newly developed device for the removal of cochlear intralabyrinthine schwannoma in the temporal bone. Methods: In a temporal bone study with a prepared posterior tympanotomy, an enlarged round window approach, and additional second turn access, a stiffened device with silicone rings was inserted and extracted gradually from the second turn access until the rings were visible in the second turn access. Results: Insertion and extraction of the second cochlear access were easily performed. Pulling and pushing the silicone rings through the modiolus and hidden parts of the basal turn was possible and worked like a pipe cleaner. Conclusion: This newly developed tissue removal device in combination with the proposed surgical handling offers a new and less traumatic way to remove cochlear ILS.

8.
BMC Cancer ; 23(1): 47, 2023 Jan 13.
Article in English | MEDLINE | ID: mdl-36639629

ABSTRACT

BACKGROUND: New concepts for a more effective anti-cancer therapy are urgently needed. Experimental flaws represent a major counter player of this development and lead to inaccurate and unreproducible data as well as unsuccessful translation of research approaches into clinics. In a previous study we have created epithelial cell cultures from head and neck squamous cell carcinoma (HNSCC) tissue. METHODS: We characterize primary cell populations isolated from human papillomavirus positive HNSCC tissue for their marker expression by RT-qPCR, flow cytometry, and immunofluorescence staining. Their sensitivity to MDM2-inhibition was measured using cell viability assays. RESULTS: Primary HNSCC cell cultures showed the delayed formation of spheroids at higher passages. These spheroids mimicked the morphology and growth characteristics of other established HNSCC spheroid models. However, expression of epithelial and mesenchymal markers could not be detected in these cells despite the presence of the HNSCC stem cell marker aldehyde dehydrogenase 1 family member A1. Instead, strong expression of B- and T-lymphocytes markers was observed. Flow cytometry analysis revealed a heterogeneous mixture of CD3 + /CD25 + T-lymphocytes and CD19 + B-lymphocytes at a ratio of 4:1 at passage 5 and transformed lymphocytes at late passages (≥ passage 12) with CD45 + CD19 + CD20 + , of which around 10 to 20% were CD3 + CD25 + CD56 + . Interestingly, the whole population was FOXP3-positive indicative of regulatory B-cells (Bregs). Expression of transcripts specific for the Epstein-Barr-virus (EBV) was detected to increase in these spheroid cells along late passages, and this population was vulnerable to MDM2 inhibition. HPV + HNSCC cells but not EBV + lymphocytes were detected to engraft into immunodeficient mice. CONCLUSIONS: In this study we present a primary cell culture of EBV-infected tumor-infiltrating B-lymphocytes, which could be used to study the role of these cells in tumor biology in future research projects. Moreover, by describing the detailed characteristics of these cells, we aim to caution other researchers in the HNSCC field to test for EBV-infected lymphocyte contaminations in primary cell cultures ahead of further experiments. Especially researchers who are interested in TIL-based adopted immunotherapy should exclude these cells in their primary tumor models, e.g. by MDM2-inhibitor treatment. BI-12-derived xenograft tumors represent a suitable model for in vivo targeting studies.


Subject(s)
Epstein-Barr Virus Infections , Head and Neck Neoplasms , Humans , Mice , Animals , Squamous Cell Carcinoma of Head and Neck , Herpesvirus 4, Human , Lymphocytes , Cell Proliferation , Cell Culture Techniques
9.
Brain Sci ; 12(10)2022 Oct 19.
Article in English | MEDLINE | ID: mdl-36291339

ABSTRACT

INTRODUCTION: The approval process for MRI safety of implants includes physical observations and an experimental evaluation in artificial settings to simulate the in vivo effect. This contains the observation of temperature changes and artificial current generation by the magnetic field. From these findings, the safety of an implant and its effect on the patient can be estimated. MRI safety is based on an in vivo evaluation of adverse events after the approval process, but an actual analysis of the effect on different tissues is not followed. The effect of MRI scanning in cochlea implantees on their residual hearing as the correlate of the hair cell function is so far unknown, therefore the aim of the present study was to observe the effect of 3 T MRI on the residual hearing of cochlea implantees. MATERIAL AND METHODS: In this prospective study, we performed a 3 T MRI T2 2D MS Drive sequence in eight cochlea-implanted ears. Before and after the MRI scan, a bone conduction pure tone audiogram (BC PTA) was performed. All cochlea implantees had a pre-scanning threshold of low frequency residual hearing between 20 dB and 65 dB. RESULTS: Low frequency mean residual hearing was not affected by the 3 T T2 2D MS Drive sequence. We observed a pre-scanning threshold at 250 Hz of 42.9 (SD 3.9) dB and for 500 Hz 57.1 (SD 6.4) dB. Post-scanning BC PTA was for 250 Hz 42.1 (SD 3.9) dB and for 500 Hz 57.1 (SD 5.7) dB. CONCLUSION: 3 T MRI scanning has no significant functional effect on the hair cells in cochlea implantees in low frequencies with a T2 2D MS Drive sequence.

10.
Curr Oncol Rep ; 24(7): 929-942, 2022 07.
Article in English | MEDLINE | ID: mdl-35347592

ABSTRACT

PURPOSE OF REVIEW: This study assesses the current state of knowledge of head and neck squamous cell carcinomas (HNSCC), which are malignancies arising from the orifices and adjacent mucosae of the aerodigestive tracts. These contiguous anatomical areas are unique in that 2 important human oncoviruses, Epstein-Barr virus (EBV) and human papillomavirus (HPV), are causally associated with nasopharyngeal and oropharyngeal cancers, respectively. Mortality rates have remained high over the last 4 decades, and insufficient attention paid to the unique viral and clinical oncology of the different subgroups of HNSCC. RECENT FINDINGS: We have compared and contrasted the 2 double-stranded DNA viruses and the relevant molecular oncogenesis of their respective cancers against other head and neck cancers. Tobacco and alcohol ingestion are also reviewed, as regard the genetic progression/mutation accumulation model of carcinogenesis. The importance of stringent stratification when searching for cancer mutations and biomarkers is discussed. Evidence is presented for a dysplastic/pre-invasive cancerous phase for HPV+ oropharyngeal cancers, and analogous with other HPV+ cancers. This raises the possibility of strategies for cancer screening as early diagnosis will undoubtedly save lives. Staging and prognostication have changed to take into account the distinct biological and prognostic pathways for viral+ and viral- cancers. Diagnosis of pre-cancers and early stage cancers will reduce mortality rates. Multi-modal treatment options for HNSCC are reviewed, especially recent developments with immunotherapies and precision medicine strategies. Knowledge integration of the viral and molecular oncogenic pathways with sound planning, hypothesis generation, and clinical trials will continue to provide therapeutic options in the future.


Subject(s)
Carcinoma, Squamous Cell , Epstein-Barr Virus Infections , Head and Neck Neoplasms , Oropharyngeal Neoplasms , Papillomavirus Infections , Carcinoma, Squamous Cell/pathology , Epstein-Barr Virus Infections/complications , Head and Neck Neoplasms/complications , Head and Neck Neoplasms/therapy , Herpesvirus 4, Human , Humans , Medical Oncology , Papillomaviridae/genetics , Papillomavirus Infections/complications , Papillomavirus Infections/genetics , Squamous Cell Carcinoma of Head and Neck
11.
Brain Sci ; 11(9)2021 Sep 16.
Article in English | MEDLINE | ID: mdl-34573240

ABSTRACT

BACKGROUND: The combination of intralabyrinthine schwannoma (ILS) removal and cochlear implantation is the standard of care after surgical resection for audiological rehabilitation. Intracochlear ILS is not only the most frequent tumor in this group of schwannomas, but it is also, to some degree, surgically the most challenging because of its position behind the modiolus. Recent developments in the knowledge of implant position, implant magnet choice, and magnetic resonance imaging (MRI) sequences make an MRI follow-up after surgical removal possible. Thus far, no results are known about the surgical success and residual rate of these kind of tumors. The aim of the present study was to perform an early MRI follow-up for the evaluation of residual or recurrent intracochlear ILS after surgical removal and cochlear implantation. METHODS: In a retrospective study, we evaluated seven patients after an intracochlear ILS removal and single-stage cochlear implantation with a mean period of 13.4 months post surgery with a 3T T1 GAD 2 mm sequence for a residual ILS. Patients were operated on using an individualized technique concept. RESULTS: In six out of seven cases, 3 T T1 GAD 2 mm MRI follow-up showed no residual or recurrent tumor. In one case, a T1 signal indicated a tumor of the upper inner auditory canal (IAC) at the MRI follow up. CONCLUSION: MRI follow-up as a quality control tool after ILS removal and cochlear implantation is highly important to exclude residual tumors. Long-term MRI evaluation results are needed and can be obtained under consideration of implant position, implant magnet, and MRI sequence choice. A preoperative MRI slice thickness less than 2 mm can be recommended to visualize possible modiolar and IAC expansion.

12.
Case Rep Otolaryngol ; 2021: 5541703, 2021.
Article in English | MEDLINE | ID: mdl-34234970

ABSTRACT

OBJECTIVE: To introduce a novel surgical approach to petrous apex lesion (PA) with superior semicircular canal plugging for hearing preservation. Patient. A 63-year-old patient presented with a recurrent cholesteatoma of the left petrous apex. The patient had a long-term history of cholesteatoma and MRI with diffusion-weighted imaging (DWI) detected a suspicious lesion in the left petrous apex on follow-up. Intervention. The cholesteatoma could be completely removed from the petrous apex with partial superior semicircular canal plugging and removal with hearing preservation. Outcomes. Cholesteatomas of the temporal bone are managed by surgery with complete excision of the lesion. RESULTS: The translabyrinthine approach, generally useful in nonhearing ears, could be utilized with the additional technique of superior semicircular canal plugging to preserve hearing in this patient. CONCLUSIONS: This case highlights the possibility of a hearing preservation strategy for PA cholesteatomas using a translabyrithine approach.

13.
Cell Commun Signal ; 19(1): 25, 2021 02 24.
Article in English | MEDLINE | ID: mdl-33627146

ABSTRACT

BACKGROUND: Cholesteatoma disease is an expanding lesion in the middle ear. Hearing loss and facial paralysis alongside with other intracranial complications are found. No pharmaceutical treatment is available today and recurrence after surgical extraction occurs. We investigated possible TLR4-based mechanisms promoting recurrence and explore possible treatments strategies. METHODS: We isolated fibroblasts and epidermal stem cells from cholesteatoma tissue and healthy auditory canal skin. Subsequently, their expression under standard culture conditions and after stimulation with LPS was investigated by RT-qPCR. Cell metabolism and proliferation were analysed upon LPS treatment, with and without TLR4 antagonist. An indirect co-culture of fibroblasts and epidermal stem cells isolated from cholesteatoma tissue was utilized to monitor epidermal differentiation upon LPS treatment by RT-qPCR and immunocytochemistry. RESULTS: Under standard culture conditions, we detected a tissue-independent higher expression of IL-1ß and IL-8 in stem cells, an upregulation of KGF and IGF-2 in both cell types derived from cholesteatoma and higher expression of TLR4 in stem cells derived from cholesteatoma tissue. Upon LPS challenge, we could detect a significantly higher expression of IL-1α, IL-1ß, IL-6 and IL-8 in stem cells and of TNF-a, GM-CSF and CXCL-5 in stem cells and fibroblasts derived from cholesteatoma. The expression of the growth factors KGF, EGF, EREG, IGF-2 and HGF was significantly higher in fibroblasts, particularly when derived from cholesteatoma. Upon treatment with LPS the metabolism was elevated in stem cells and fibroblasts, proliferation was only enhanced in fibroblasts derived from cholesteatoma. This could be reversed by the treatment with a TLR4 antagonist. The cholesteatoma fibroblasts could be triggered by LPS to promote the epidermal differentiation of the stem cells, while no LPS treatment or LPS treatment without the presence of fibroblasts did not result in such a differentiation. CONCLUSION: We propose that cholesteatoma recurrence is based on TLR4 signalling imprinted in the cholesteatoma cells. It induces excessive inflammation of stem cells and fibroblasts, proliferation of perimatrix fibroblasts and the generation of epidermal cells from stem cells thru paracrine signalling by fibroblasts. Treatment of the operation site with a TLR4 antagonist might reduce the chance of cholesteatoma recurrence. Video Abstract.


Subject(s)
Cholesteatoma, Middle Ear , Toll-Like Receptor 4/genetics , Cell Differentiation , Cell Proliferation/drug effects , Cells, Cultured , Cholesteatoma, Middle Ear/genetics , Cholesteatoma, Middle Ear/metabolism , Cytokines/genetics , Ear Canal , Fibroblasts/drug effects , Fibroblasts/metabolism , Humans , Inflammation/genetics , Inflammation/metabolism , Intercellular Signaling Peptides and Proteins/genetics , Keratins, Type II/metabolism , Lipopolysaccharides , Recurrence , Skin/cytology , Stem Cells/drug effects , Stem Cells/metabolism
14.
Eur Arch Otorhinolaryngol ; 278(7): 2219-2224, 2021 Jul.
Article in English | MEDLINE | ID: mdl-32797273

ABSTRACT

OBJECTIVE: To determine the effectiveness of a soft-tissue bulking agent comparing novel approaches of Eustachian tube (ET) augmentation procedures: transpalatinatal Eustachian tube augmentation in local and general anesthesia versus an augmentation with velotraction under general anesthesia. The clinical endpoint was the resolution of symptoms related to unilateral patulous Eustachian tube dysfunction (PETD) requiring no additional revision augmentations. STUDY DESIGN: Combined retrospective clinical chart review. SETTING: Tertiary referral center. METHODS: Patients suffering from PETD underwent one of the following procedures: Group (A) transpalatinatal soft-tissue bulking agent with infiltration/augmentation under local anesthesia in a sitting position, group (B) transpalatinatal soft-tissue bulking agent infiltration/augmentation under general anesthesia in the flat position or group (C) infiltration/transoral augmentation of the ET with velotraction under general anesthesia in a flat position. The requirement to repeat the procedure due to recurrence of any PETD-related symptoms was recorded and retrospectively analyzed. RESULTS: A total of 50 procedures were executed in 50 patients with unilateral PETD. The necessity to perform a second procedure has analyzed a mean of 6 months postoperatively (range: 6-17 months). Compared to the transpalatinatal augmentation in local anesthesia (group A) (100% success rate), the 6-month failure rate was significantly higher for transpalatinatal augmentation under general anesthesia (group B) (80% success rate) and velotraction augmentation under general anesthesia (group C) (67% success rate). Patient cohort with transpalatinatal augmentation under general anesthesia required 20% and augmentation with velotraction under general anesthesia in 33% revision augmentation procedures reviewed at 6 months follow-up (mean follow-up 11.2 months). CONCLUSIONS: Although all different approaches resulted in a reduction of PETD related symptoms, the transpalatinatal ET augmentation in local anesthesia achieved a statistically significant superior clinical improvement. A complete resolution of PETD related symptoms was obtained and required additional procedures. This improvement may be related to the intraoperative "feedback" by the patients in local anesthesia in the sitting position eliminating the necessity for repeated procedures.


Subject(s)
Ear Diseases , Eustachian Tube , Otitis Media , Otologic Surgical Procedures , Ear Diseases/diagnosis , Ear Diseases/surgery , Eustachian Tube/surgery , Humans , Retrospective Studies
15.
Handchir Mikrochir Plast Chir ; 52(4): 325-329, 2020 Aug.
Article in German | MEDLINE | ID: mdl-31533154

ABSTRACT

The aim of this study was to describe our results and experience with end-to-side venous anastomosis using a coupler device in microvascular free flaps.


Subject(s)
Free Tissue Flaps , Anastomosis, Surgical , Microsurgery , Retrospective Studies , Veins/surgery
16.
Laryngoscope Investig Otolaryngol ; 2(4): 184-186, 2017 08.
Article in English | MEDLINE | ID: mdl-28894838

ABSTRACT

OBJECTIVES: Recurrent respiratory papillomatosis (RRP) is a rare disease, but one with severe morbidity and occasional mortality. The aetiological agent is human papillomavirus (HPV), and HPV types 6 and 11 account for over 90% of all cases. In the active phase of the disease, patients require multiple hospital admissions for surgical removal or ablation of these benign tumors, which are likely to obstruct the airways if left unchecked. Long-term sequelae include scarring of the vocal cords, change in voice timbre, or even muteness if a tracheostomy is required. The aim of this study was to determine if adjuvant vaccination with the quadrivalent HPV L1 vaccine (Gardasil™) would decrease numbers of surgical treatments post-vaccination. METHODS: A prospective pilot study following a cohort of 12 RRP patients, all of whom gave fully informed consent to participate. All patients had their papillomas typed and if they were found to have types 6 or 11, were vaccinated at the time of first surgical treatment in the hospital, according to the manufacturer's protocols. Patients were followed up closely with 3 or 6 month follow-up visits. Standard surgical treatments were given and were not affected by whether they participated in the study. RESULTS: We found a >7-fold decrease in the incidence rates of papillomatosis requiring surgical intervention from the pre-vaccination period (47.44/1000 patient-months) compared to the post-vaccination period (6.71/1000 patient-months). DISCUSSION: Surgical treatments for RRP are robust markers for papillomata which require treatment because of the dangers of obstruction of the airway. Despite the small size of this cohort (due to the rarity of this disease), the data suggests that adjuvant use of quadrivalent HPV L1 vaccine imparts significant benefit to this group of patients. A large multi-center randomized placebo controlled trial is required to definitively establish whether this hypothesis is true and can become the new standard of therapy. LEVEL OF EVIDENCE: 3b.

17.
Acta Otolaryngol ; 137(5): 471-475, 2017 May.
Article in English | MEDLINE | ID: mdl-27844486

ABSTRACT

CONCLUSION: The middle ear pressure changes detected during BET can be directly attributed to the balloon inflation and may represent a second, immediate, mechanism of action of BET. BET seems to be safe with respect to the risk of a barotrauma. Further human studies are now necessary to confirm the results and gain more insight into the mechanism of action of BET. OBJECTIVE: Since the introduction of Balloon Eustachian Tuboplasty (BET) as a treatment of chronic Eustachian tube dysfunction, the precise mechanism of action is unknown. Long-term effects of BET may be related to observed microfractures of the Eustachian tube cartilage. However, clinical observations indicate a second, immediate mode of action. Therefore, this study investigated and characterized middle ear pressure changes occurring directly during BET procedure. METHODS: Using a micro-optical pressure sensor, pressure changes during BET were monitored transtympanically in a cadaveric animal study using heathland sheep. RESULTS: Middle ear pressure amplitudes during BET are dependent on the speed of balloon inflation as well as the maximum inflation pressure. A 10-bar inflation pressure yielded a mean middle ear pressure of 5.34 mmHg (71.0 daPA). Negative pressure amplitudes occurring on withdrawal of the balloon catheter are influenced by the speed of withdrawal. No pressure amplitudes capable of causing barotrauma to membranous ear structures could be detected.


Subject(s)
Ear, Middle/physiology , Eustachian Tube/surgery , Otologic Surgical Procedures , Animals , Pilot Projects , Pressure , Sheep
18.
BMC Cancer ; 16: 367, 2016 06 13.
Article in English | MEDLINE | ID: mdl-27296171

ABSTRACT

BACKGROUND: Human papillomavirus DNA detection in head and neck squamous cell carcinoma has been linked to improved patient prognosis. The main aims of the study was to test the hypotheses that HPV16 E6/E7 oncogene and p53 function within tumours were associated with the widely reported improved patient survival and prognosis in head and neck cancer. METHODS: HPV16 DNA, mRNA and p53 mRNA presence were analysed in a prospective study of 42 unselected HNSCC patients; correlating the data with patient age, tumour staging/grade, treatment response, disease recurrence and survival. RESULTS: HPV16 DNA and HPV16 mRNA were present in 45.2 % and 21.4 % of patients, respectively. There was a significant positive association between the detection of HPV16 E6/E7 mRNA and p53 mRNA (p = 0.032), but this was not replicated for HPV16 DNA. Five-year disease free survival for the whole cohort was 63 % (CI 52.5-73.5 %). Multivariable analysis revealed only HPV16 E6/E7 mRNA expression to have significant prognostic influence (p = 0.04). CONCLUSIONS: Our study suggests that HPV16 oncogenic transcriptional activity within HNSCC tumours is associated with improved patient survival and better prognosis in a German population. Simple HPV DNA detection alone did not demonstrate this association. The significant association of full-length (wild-type) p53 with HPV16 E6/E7 mRNA is further evidence for a functional relationship, which could contribute to the widely reported improved survival and prognosis. Larger studies are required to validate the frequency of HPV16 mRNA expression in HNSCC.


Subject(s)
Carcinoma, Squamous Cell/virology , Head and Neck Neoplasms/virology , Human papillomavirus 16/metabolism , Papillomavirus Infections/virology , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/mortality , Disease-Free Survival , Female , Head and Neck Neoplasms/diagnosis , Head and Neck Neoplasms/metabolism , Head and Neck Neoplasms/mortality , Human papillomavirus 16/genetics , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Molecular Diagnostic Techniques , Neoplasm Recurrence, Local/metabolism , Neoplasm Recurrence, Local/virology , Oncogene Proteins, Viral/genetics , Oncogene Proteins, Viral/metabolism , Papillomavirus E7 Proteins/genetics , Papillomavirus E7 Proteins/metabolism , Papillomavirus Infections/diagnosis , Papillomavirus Infections/metabolism , Papillomavirus Infections/mortality , Polymerase Chain Reaction , Proportional Hazards Models , Prospective Studies , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA, Viral/genetics , RNA, Viral/metabolism , Repressor Proteins/genetics , Repressor Proteins/metabolism , Transcription, Genetic , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism
20.
Paediatr Anaesth ; 19(7): 667-71, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19638111

ABSTRACT

BACKGROUND: GlideScope laryngoscopy provides a glottic view equal or superior compared to Macintosh laryngoscopy for endotracheal intubation in adult patients. Data evaluating GlideScope laryngoscopy in pediatric patients are lacking. This study compared intubation times of GlideScope laryngoscopy vs Macintosh laryngoscopy in pediatric patients. METHODS: Sixty ASA I-III patients, aged 10 years or less, were included in this study. Prior to intubation, airway characteristics were measured, and all patients were given an airway class by a separate anesthesiologist using a Macintosh laryngoscope. Patients were then randomly assigned for endotracheal intubation using a Macintosh laryngoscope or the GlideScope, and intubation time was measured. All blades were investigated for blood traces as a surrogate of laryngeal injury. RESULTS: Demographic data and airway characteristics were not statistically significant different between groups. GlideScope intubation time (14 +/- 5 s) was not different from Macintosh intubation time (13 +/- 5 s). Blood traces were not observed on Macintosh or GlideScope blades. CONCLUSION: The GlideScope video laryngoscope is equally suitable to facilitate orotracheal intubation in pediatric patients compared to the Macintosh laryngoscope with respect to intubation time and laryngeal trauma.


Subject(s)
Laryngoscopes , Laryngoscopy , Anesthesia , Child , Child, Preschool , Female , Humans , Infant , Intubation, Intratracheal , Laryngoscopes/adverse effects , Laryngoscopy/adverse effects , Larynx/injuries , Male , Otorhinolaryngologic Surgical Procedures , Preanesthetic Medication , Treatment Outcome
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