Lymphatic drainage of sinonasal malignancies and the role of sentinel node biopsies.

BACKGROUND: Locoregional recurrence is a critical factor in the prognosis of sinonasal malignancies. Due to the rarity of these tumours, as well as the heterogeneity of histologies and anatomical subsites, there is little evidence regarding the rate and location of regional metastases in sinonasal malignancies. Elective regional lymph node dissection in the therapy of sinonasal malignancies has become controversial. On the one hand, elective regional lymph node dissection is considered to be an overtreatment in the cN0 cases. On the other hand, undetected occult lymphatic metastases are associated with a poor prognosis. In this study, we discuss the role of sentinel lymph node biopsy as a minimally invasive procedure in the treatment of sinonasal malignancies based on our two years of practical experience and the currently available data. RESULTS: This is a descriptive, monocentric, retrospective study, including 20 cases of cN0 malignant sinonasal neoplasm, that underwent a surgical therapy between 2020 and 2022. The following aspects were investigated: tumour entity, localisation of the primary tumour, tumoral stage, localisation of the sentinel lymph nodes, and postoperative complications. Squamous cell carcinoma was the most frequently diagnosed tumour entity (50%), followed by adenocarcinoma (20%) and malignant melanoma (15%), adenoid cystic carcinoma and mucoepidermoid carcinoma. Sentinel lymph nodes were most frequently found in the ipsilateral neck region I (45%), followed by the ipsilateral neck region II (40%). In all cases, the removed lymph nodes were free of malignancy. There were no postoperative complications due to lymph node biopsy. There were no recurrences during the study period. CONCLUSION: Sentinel node biopsy could add more safety to the management of cN0 sinonasal malignancies due to its low morbidity. Whether SNB could provide an alternative to elective neck dissection in the management of SNM should be investigated in further studies.

Classification of endonasal HHT lesions using digital microscopy.

BACKGROUND: Recurrent spontaneous epistaxis is the most common clinical manifestation and the most debilitating symptom in hereditary haemorrhagic telangiectasia (HHT) patients. To this date, there exist only a classification of HHT patients by different genetic mutations. There is no standard classification for the mucocutaneous endonasal manifestations of HHT. The aim of the present study was to document the variety of endonasal HHT lesions using digital microscopy and to propose a clinical classification. METHODS: We recorded the endonasal HHT lesions of 28 patients using a digital microscope. We reconstructed the 3D images und videos recorded by digital microscope afterwards and classified the endonasal lesions of HHT in two classes: Grade A, presence of only flat telangiectasias in the mucosa level and Grade B, (additional) presence of raised berry or wart-like telangiectasia spots. We investigated also Haemoglobin level by routine laboratory procedures, plasma VEGF level by ELISA, Severity of epistaxis by epistaxis severity score (ESS) and quality of life by a linear visual analogue scale (VAS). RESULTS: We found a higher quality of life and a lower severity of epistaxis in Grade A patients in comparison to Grade B patients. No difference in plasma VEGF level and in Haemoglobin between Grad A patients and Grade B patients could be detected. Plasma VEGF levels showed no gender specific differences. It could also not be correlated to the extranasal manifestation. CONCLUSION: The classification for endonasal manifestation of HHT proposed in this study indicates severity of epistaxis und quality of life. Digital microscopy with the ability of 3D reconstruction of images presents a useful tool for such classifications. The classification of endonasal HHT lesions using digital microscopy allows to evaluate the dynamic of HHT lesions in the course of time independent of examiner. This allows also to evaluate the efficacy of the different treatment modalities by dynamic of HHT lesions. Moreover digital microscopy is very beneficial in academic teaching of rare diseases.

[Hygiene during otorhinolaryngological examinations : Prevention of nosocomial infections]. / Hygiene bei der HNO-Untersuchung : Vermeidung nosokomialer Infektionen.

Awareness of the importance of working as aseptically as possible first emerged in the 19th century. In the meantime, there is an obligation to prevent transmission and further spread of pathogens, including adherence to the Infection Protection Act. Pathogens can also survive for a long time on inanimate surfaces, from where they can be transferred via the hands of personnel and thus lead to infections. Studies have shown that even contamination of untouched instruments after an otorhinolaryngological examination is not a rare occurrence. The Kommission für Krankenhaushygiene und Infektionsprävention (KRINKO) of the Robert Koch Institute gives recommendations for general hygiene measures (basic or standard hygiene). These must be adapted and implemented accordingly for the otorhinolaryngological examination. Due to the increasing development of resistance of nosocomial pathogens and the current pandemic, consistent implementation of these infection-prevention measures is important.

Effect of HBO therapy on adipose-derived stem cells, fibroblasts and co-cultures: In vitro study of oxidative stress, angiogenic potential and production of pro-inflammatory growth factors in co-cultures1.

BACKGROUND: A key moderator of wound healing is oxygen. Wound healing is a dynamic and carefully orchestrated process involving blood cells, cytokines, parenchymal cells (i.e. fibroblasts and mesenchymal stem cells) and extracellular matrix reorganization. Human adipose derived stem cells as well as human fibroblasts produce soluble factors, exhibit diverse effects on inflammation and anti inflammation response and are involved in wound healing processes.Hyperbaric oxygen therapy is an effective adjunct treatment for ischemic disorders such as chronic infection or chronic wounds. In vitro effects of hyperbaric oxygen therapy on human cells were presented in many studies except for those on mono- and co-cultures of human adipose derived stem cells and fibroblasts. OBJECTIVE: The aim of this study was to investigate the effects of hyperbaric oxygen therapy on mono- and co-cultures of human adipose derived stem cells and fibroblasts. METHODS: Mono- and co-cultures from human adipose derived stem cells and fibroblasts were established. These cultures were exposed to hyperbaric oxygen therapy every 24 h for five consecutive days. Measuring experiments were performed on the first, third and fifth day. Therapy effects on the expression of VEGF, IL 6 and reactive oxygen species were investigated. RESULTS: After exposure to hyperbaric oxygen, cell culturess showed a significant increase in the expression of VEGF after 3 and 5 days. All cultures showed significantly reduced formation of reactive oxygen species throughout the experiments. The expression of IL-6 decreased during the experiment in mono-cultures of human adipose derived stem cells and co-cultures. In contrast, mono-cultures of human skin fibroblasts showed an overall significantly increased expression of IL-6. CONCLUSIONS: Hyperbaric oxygen therapy leads to immunmodulatory and proangiogenetic effects in a wound-like enviroment of adipose derived stem cells and fibroblasts.

[Diagnosis and treatment of Osler's disease]. / Diagnostik und Therapie des M. Osler.

Osler's disease is an autosomal dominant hereditary syndrome which belongs to the group of orphan diseases. Affected patients suffer primarily from severe epistaxis. Diagnosis is based on the Curaçao criteria and molecular genetic tests. Organ manifestations can be found in the form of arteriovenous shunts in the lung, liver, and gastrointestinal tract; more rarely also in the central nervous system (CNS) and other parts of the body. Many patients with gastrointestinal and other organ manifestations are frequently clinically asymptomatic; therefore, organ screening is essential to avoid later complications and should be performed in centers with particular expertise. No curative therapy currently exists. From the otolaryngologist's perspective, nasal mucosa treatments and endonasal laser applications are important and effective therapeutic approaches to epistaxis. Pharmacological interventions are focused on compensation of haploinsufficiency as well as antiangiogenetic approaches. Severe side effects have to be considered.

[Injection of Lipotransplants for Wound Healing Complications after Radiotherapy]. / Injektion von Bauchfett bei radiogenen Wundheilungsstörungen.

Wound healing complications in irradiated tissues represent a major clinical challenge. Fistula or even major vessel rupture may occur. The injection of adipose tissue derived stem cells seem to be a promising therapeutical strategy. The article describes the clinical case of a patient suffering from a pharyngo-cutaneous fistula after laryngectomy and radiotherapy. The patient was successfully treated by the injection of fat tissue.

Platelet-rich plasma stimulates dermal microvascular endothelial cells and adipose derived stem cells after external radiation.

BACKGROUND: Platelet-rich plasma (PRP) products are currently suggested in the treatment of chronic wounds due to possible pro-angiogenic effects. Microvascular compromise represents the major component in radiogenic wound healing complications. The effects of PRP on irradiated cells of the cutaneous wound healing process are still poorly understood. MATERIAL AND METHODS: Human dermal microvascular endothelial cells (HDMEC) and human adipose derived stem cells (hASC) were cultured and irradiated with doses of 2 to 12 Gy. PRP was activated, characterized and added to the incubation media in different concentrations after external radiation. Cell count was determined 48 h after radiation using a semi-automated cell counting system. Levels of interleukin-6 (IL-6), basic fibroblast growth factor (bFGF) and soluble intercellular adhesion molecule-1 (sICAM-1) in the supernatants of HDMEC and hASC co-cultures were determined by enzyme-linked immunosorbent assay (ELISA). Non-irradiated hASC and HDMEC served as controls. RESULTS: The employed PRP preparations were characterized and contained platelet derived growth factor (PDGF-AB), vascular endothelial growth factor (VEGF), bFGF and high levels of sICAM-1. Addition of PRP to irradiated cultures of HDMEC and hASC prevented profound radiation-induced decline in cell numbers. 10% PRP restored cell numbers to levels of untreated, non-irradiated cultures. Basic FGF expression was decreased significantly in hASC monocultures treated with 10% PRP without external radiation and after irradiation with 6 and 12 Gy. These inhibitory effects of PRP were also observed in HDMEC. In contrast, co-cultures of HDMEC-ASC showed a dose-dependent increase in bFGF expression when treated with 5 or 10% PRP. Doses of 6 and 12 Gy increased IL-6 expression in cultures stimulated with 5% PRP. CONCLUSIONS: Use of PRP in co-cultures of hASC and HDMEC restores proliferative defects caused by external radiation probably by induction of bFGF. Under irradiated conditions, PRP might induce pro-inflammatory stimuli which could be beneficial in treatment of chronic wounds where healing processes are defective. Combined use of hASC and PRP products might be helpful in the treatment of radiogenic wounds.

[Potential of adipose-derived stem cells concerning the treatment of wound healing complications after radiotherapy]. / Potenzial adipogener Stammzellen bei radiogenen Wundheilungsstörungen.

BACKGROUND: Compromised wound healing in irradiated tissues is a common and challenging clinical problem. The pathophysiology and underlying cellular mechanisms including the complex interaction of cytokines and growth factors are still incompletely understood. OBJECTIVES: In this article, the potential of adipose-derived stem cells concerning the treatment of wound healing complications after radiotherapy is discussed. METHODS: Human dermal fibroblasts (NHF), microvascular endothelial cells (HDMEC) and human adipose-derived stem cells (ASC) were cultured in a co-culture setting and irradiated with doses of 2-12Gy. Cell count was determined and levels of cytokines and growth factors relevant for wound healing were measured using enzyme-linked immunosorbent assays (ELISA) and qPCR techniques. Irradiated NHF, HDMEC and ASC as well as non-irradiated mono and co-cultures, NHF, HDMEC or ASC respectively were used as controls. RESULTS: Cell count was significantly reduced in irradiated co-cultures of NHF, HDMEC and ASC compared to non-irradiated controls. Levels of IL-6, bFGF, ICAM-1 and VCAM-1 in the supernatants of the co-cultures were significantly less affected by external radiation in comparison to HDMEC. Levels of IL-6 and VEGF in the supernatants of co-cultures were significantly less affected by external radiation in comparison to NHF. DISCUSSION: The increased expression of cytokines and adhesion molecules by NHF and HDMEC after external radiation is mitigated in the co-culture setting with ASC. These in vitro changes seem to support the clinical observation that ASC may have a stabilizing effect when injected into irradiated wounds.

Effects of radiation on the expression of adhesion molecules and cytokines in a static model of human dermal microvascular endothelial cells.

BACKGROUND: Radiation-induced wound healing complications represent an important clinical problem. Microvascular compromise is an important component of its pathogenesis and the microvascular endothelial cell is the key representative affected at the cellular level. MATERIAL AND METHODS: Human dermal microvascular endothelial cells (HDMEC) were cultured and irradiated with doses of 2 to 12 Gy. Cell density was determined 48 h after radiation using a semi-automated cell counting system. Levels of interleukin-6 (IL-6), basic fibroblast growth factor (FGF), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in the supernatants of HDMEC were determined by polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Non irradiated HDMEC were used as controls. RESULTS: Cell density was significantly impaired in irradiated cells compared to non irradiated controls. Radiation resulted in significant elevation of levels of IL-6, FGF, ICAM-1 and VCAM-1 in the supernatants of HDMEC in a dose dependent manner. CONCLUSION: The inflammatory response observed clinically after radiation seems to correlate with elevated expression of cytokines and adhesion molecules by microvascula endothelial cells. The model of HDMEC documents the impairment of microcirculation. These in vitro changes may enhance our understanding of the pathomechanisms leading to radiation-induced vasculitis and associated wound healing problems.

[Rare malignant tumor of the parotid gland. Myoepithelial carcinoma]. / Seltener maligner Tumor der Gl. parotis. Myoepitheliales Karzinom.

A parotid mass in a 62-year-old woman presented intraoperatively as a highly malignant tumor with facial nerve infiltration. Classification by means of rapid section histology was not possible. Immunohistochemical studies were necessary to diagnose this rare case of myoepithelial carcinoma of the parotid gland. We performed a total parotidectomy including partial nerve resection and neck dissection on the tumor side. The patient was referred to radiotherapy postoperatively.

[Simultaneous injection of lidocaine improves predictability of effect of botulinum toxin]. / Simultane Injektion mit Lidocain verbessert die Vorhersehbarkeit des Effekts von Botulinumtoxin.

Injection of botulinum toxin A is a common procedure in Otorhinolaryngology, Ophtalmology and Neurolgy. Recently botulinum toxin treatment has been described to improve woundhealing after facial injuries. The lack of immediate predictibility of the ensuing paralytic effect is one of the daily challenges of botulinum toxin injections. In the present report we describe the simultaneous injection of botulinum toxin and lidocaine with the purpose to gain immediate feed back of the treatment effect. Furthermore we recommend the addition of adrenalin to reduce possible systemical toxin circulation.