Publications by authors named "Lars-Uwe Scholtz"

8 Publications

  • Page 1 of 1

Chronic inflammation of middle ear cholesteatoma promotes its recurrence via a paracrine mechanism.

Cell Commun Signal 2021 Feb 24;19(1):25. Epub 2021 Feb 24.

Department of Otolaryngology, Head and Neck Surgery, Medical School OWL Campus Klinikum Bielefeld, Bielefeld University, Teutoburger Str. 50, 33604, Bielefeld, Germany.

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-1β 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-1β, 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.
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http://dx.doi.org/10.1186/s12964-020-00690-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903614PMC
February 2021

A novel technique for patulous Eustachian tube augmentation.

Eur Arch Otorhinolaryngol 2020 Aug 14. Epub 2020 Aug 14.

Department of Otorhinolaryngology, Head and Neck Surgery, Medical Faculty OWL, Bielefeld University, Campus Klinikum Bielefeld, Teutoburger Str. 50, 33604, Bielefeld, Germany.

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.
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http://dx.doi.org/10.1007/s00405-020-06277-0DOI Listing
August 2020

[End-to-side venous anastomosis with a coupler device in microvascular free flaps].

Handchir Mikrochir Plast Chir 2020 Aug 18;52(4):325-329. Epub 2019 Sep 18.

Klinikum Bielefeld Mitte, Klinik für Plastische, Wiederherstellungs- und Ästhetische Chirurgie, Handchirurgie.

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.
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http://dx.doi.org/10.1055/a-0942-9780DOI Listing
August 2020

Recurrent respiratory papillomatosis (RRP)-time for a reckoning?

Laryngoscope Investig Otolaryngol 2017 08 28;2(4):184-186. Epub 2017 May 28.

Department of Ear, Nose and Throat Surgery (L.-U.S., H.S.) Bielefeld Germany.

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.
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http://dx.doi.org/10.1002/lio2.80DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5562946PMC
August 2017

Measurement of middle ear pressure changes during balloon eustachian tuboplasty: a pilot study.

Acta Otolaryngol 2017 May 15;137(5):471-475. Epub 2016 Nov 15.

b Department of Otorhinolaryngology, Head and Neck Surgery , Klinikum Bielefeld, Academic Teaching Hospital University of Münster University , Bielefeld , Germany.

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.
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http://dx.doi.org/10.1080/00016489.2016.1253870DOI Listing
May 2017

Molecular analyses of unselected head and neck cancer cases demonstrates that human papillomavirus transcriptional activity is positively associated with survival and prognosis.

BMC Cancer 2016 06 13;16:367. Epub 2016 Jun 13.

Department of Pathology, University of Cambridge, Cambridge, UK.

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.
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http://dx.doi.org/10.1186/s12885-016-2398-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4906991PMC
June 2016

Osteopetrosis of the temporal bone.

Otol Neurotol 2012 Aug;33(6):e45-6

Department of Otorhinolaryngology, Head and Neck Surgery, Klinikum Bielefeld, Academic Teaching Hospital University of Münster University, Bielefeld, Germany.

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http://dx.doi.org/10.1097/MAO.0b013e318248ea6fDOI Listing
August 2012

Validation of the GlideScope video laryngoscope in pediatric patients.

Paediatr Anaesth 2009 Jul;19(7):667-71

Department of Anesthesia and Critical Care, University of Würzburg, Würzburg, Germany.

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.
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http://dx.doi.org/10.1111/j.1460-9592.2009.03046.xDOI Listing
July 2009