Petra Ambrosch

Head and neck cancer surgery has evolved from radical organ-sacrificing procedures to function-preserving approaches integrated within multidisciplinary frameworks. This comprehensive literature review, concentrating on studies from the past five years while incorporating relevant publications from the last three decades and landmark historical papers, examines the evolving role of surgery emphasizing diagnostic methodologies including comprehensive genomic profiling, validated imaging biomarkers, and their clinical integration for treatment selection and response prediction. Modern surgical practice demonstrates a paradigm shift toward precision medicine through validated diagnostic technologies. Comprehensive genomic profiling identifies clinically actionable alterations in over 90% of head and neck squamous cell carcinomas, with tumor mutational burden serving as a validated predictive biomarker for immunotherapy response. Programmed death-ligand 1 (PD-L1) combined positive score functions as a validated diagnostic biomarker for immunotherapy efficacy, demonstrating significant clinical benefit in biomarker-selected populations. Radiomics-based predictive models utilizing machine learning algorithms achieve diagnostic accuracies exceeding 85% for treatment response prediction when validated across independent cohorts. Quantitative ultrasound spectroscopy combined with magnetic resonance imaging radiomics demonstrates high sensitivity and specificity for radiation response prediction. Habitat imaging techniques characterizing tumor microenvironmental heterogeneity predict pathologic complete response to neoadjuvant chemoimmunotherapy with area under the curve values approaching 0.90 in validation studies. Integration of these diagnostic methodologies enables response-adaptive treatment strategies, with neoadjuvant chemotherapy facilitating mandibular preservation and adjuvant therapy omission in over half of human papillomavirus (HPV)-associated cases following surgical downstaging. Clinical validation of these diagnostic platforms enables accurate treatment response prediction and informed surgical decision-making, though standardization across institutions and demonstration of survival benefits through prospective trials remain essential for broader implementation.

Background: A limited number of single institutions have published retrospective cohort studies on transoral laser microsurgery for supraglottic laryngectomy (TLM-SGL). These studies have shown that the oncologic outcomes of TLM-SGL are comparable to those of open SGL. However, there is limited information available regarding swallowing rehabilitation and quality of life (QoL).Patients and methods: SUPRATOL is a prospective, multicenter trial assessing the functional outcomes of TLM-SGL +/− adjuvant radio-(chemo)-therapy. The primary endpoint was aspiration-free swallowing at 12 months, as established using fibreoptic endoscopic evaluation of swallowing (FEES) and defined as a grade < 6 on the penetration–aspiration scale. Secondary endpoints were swallowing- and voice-related QoL, the prevalence of temporary and permanent tracheostomy and percutaneous gastrostomy, local control, laryngectomy-free survival, overall survival, and disease-free survival, as well as the influence of treatment centers on outcomes.Results: From April 2015 to February 2018, 102 patients were recruited from 26 German Otorhinolaryngology (ORL) hospitals. All patients had TLM-SGL and 96.1% underwent uni- or bilateral, mostly selective neck dissection. To 47.0% of patients, adjuvant radio-(chemo)-therapy (R(C)T) was administered. The median follow-up period was 24.1 months. At 12-month follow-up, completed by 84.3% of patients, 98.2%, 95.5%, and 98.8% were free of aspiration when tested with saliva, liquid, or pulp. Adjuvant R(C)T, pT category, and type of resection had no significant influence on swallowing rehabilitation. A total of 40.2% of patients had been tracheotomized, and in 46.1% of patients, a PEG tube was inserted. At the 24-month follow-up, 5.3% of patients still required a tracheostomy, and 8.0% continued to use a percutaneous endoscopic gastrostomy (PEG) tube. Deterioration of swallowing- and voice-related QoL was observed immediately after treatment, but patients recovered, and baseline values were reached again. The Kaplan–Meier 2-year rates for local control, laryngectomy-free survival, overall survival, and disease-free survival were 88%, 92%, 93%, and 82%, respectively.Conclusions: Our prospective multicenter trial shows that, at 12 months post-TLM-SGL +/− R(C)T, 95.5%–98.8% of patients achieved aspiration-free swallowing. Morbidity was higher than previously reported. The rates of permanent tracheostomy and gastrostomy tube placement correspond to previous cohort studies. The 2-year oncologic outcomes are within the reported range.Clinical trial registration: https://drks.de/search/en/trial/DRKS00004641, identifier (DRKS00004641).

Background Transoral laser microsurgery (TLM) is an accepted and effective treatment strategy for supraglottic carcinomas. Data on oncologic and to a lesser extent functional outcomes have been published by mainly European specialized single institutions. TLM for supraglottic carcinomas has never been tested in a multicenter trial on its applicability as surgical standard at every hospital. Objectives To test the efficacy of TLM supraglottic laryngectomy (TLM-SGL) in terms of swallowing function, oncologic outcome parameters, morbidity, complications of treatment, and quality of life in a multicenter setting. Methods The study is designed as a multicenter (approximately 25 centers), non-randomized, single-arm study with a targeted number of 200 previously untreated patients with squamous cell carcinomas (SCC) of the supraglottic larynx T2/T3 N0–3 M0; UICC stage II–IVa. The surgical treatment consists of TLM-SGL and elective or therapeutic uni- or bilateral selective neck dissection (SND). After pathologic risk stratification adjuvant radio- (RT) or radiochemotherapy (RCT) is indicated. Patients are followed-up for 2 years post surgically. Swallowing function is assessed by fibreoptic endoscopic evaluation of swallowing (FEES). The primary endpoint is aspiration-free swallowing at 12 months as established using FEES and defined as grade < 6 of penetration-aspiration scale (PAS). Secondary endpoints include local control, larynx preservation, overall and disease-free survival, complications and side effects of treatment, prevalence of tracheostomy and percutaneous endoscopic gastrostomy (PEG)-tube-feeding, and dysphagia-specific quality of life (QoL) assessed by the MD Anderson Dysphagia Inventory (MDADI) as well as voice-related QoL assessed by the Voice Handicap Index (VHI).

Palytoxin (PTX), a marine toxin isolated from the Cnidaria (zooanthid) Palythoa caribaeorum is one of the most potent non-protein substances known. It is a very complex molecule that presents both lipophilic and hydrophilic areas. The effect of PTX was investigated in a series of experiments conducted in head and neck squamous cell carcinoma (HNSCC) cell lines and xenografts. Cell viability, and gene expression of the sodium/potassium-transporting ATPase subumit alpha1 (ATP1AL1) and GAPDH were analyzed in HNSCC cells and normal epithelial cells after treatment with PTX using cytotoxicity-, clonogenic-, and enzyme inhibitor assays as well as RT-PCR and Northern Blotting. For xenograft experiments severe combined immunodeficient (SCID) mice were used to analyze tumor regression. The data were statistically analyzed using One-Way Annova (SPSS vs20). Significant toxic effects were observed in tumor cells treated with PTX (LD50 of 1.5 to 3.5 ng/ml) in contrast to normal cells. In tumor cells PTX affected both the release of LDH and the expression of the sodium/potassium-transporting ATPase subunit alpha1 gene suggesting loss of cellular integrity, primarily of the plasma membrane. Furthermore, strong repression of the c-Jun N-terminal kinase 3 (JNK3) mRNA expression was found in carcinoma cells which correlated with enhanced toxicity of PTX suggesting an essential role of the mitogen activated protein kinase (MAPK)/JNK signalling cascades pathway in the mechanisms of HNSCC cell resistance to PTX. In mice inoculated with carcinoma cells, injections of PTX into the xenografted tumors resulted within 24 days in extensive tumor destruction in 75% of the treated animals (LD50 of 68 ng/kg to 83 ng/kg) while no tumor regression occurred in control animals. These results clearly provide evidence that PTX possesses preferential toxicity for head and neck carcinoma cells and therefore it is worth further studying its impact which may extend our knowledge of the biology of head and neck cancer.

Introduction: In granulomatosis with polyangiitis (GPA), a complex autoimmune small-vessel vasculitis frequently associated with chronic necrotizing inflammation of the nasal mucosa, elevated nasal Staphylococcus (S.) aureus carrier rates are a risk factor for relapse. As cytokines are primarily involved in the regulation of defense against potentially pathogenic microorganisms, the aim of this study was to compare healthy individuals and GPA patients with respect to their baseline cytokine expression of nasal epithelial cells (NEC), which form the first barrier against such triggers. The ability of S. aureus to influence the nasal microenvironment's cytokine secretion was assessed by exemplary stimulation experiments. Methods: Baseline expression of 19 cytokines of primary NEC of GPA patients and normal controls (NC) was quantified by a multiplex cytokine assay. Stimulation experiments were performed with supernatants of S. aureus and expression of interleukin-8 was determined by ELISA. Results: In GPA, an altered pattern of baseline cytokine expression with significantly up-regulated G-CSF and reduced interleukin (IL)-8 concentrations was observed. Both NEC of GPA patients and NC responded to stimulation with S. aureus, but GPA patients displayed a significantly lower IL-8 secretion and a diminished dynamic range of response towards the stimulus. Conclusions: The data presented underline the hypothesis of a disturbed epithelial nasal barrier function in GPA. The dysregulated baseline expression of G-CSF and IL-8 and the reduced response to microbial stimulation may facilitate changes in the composition of the nasal flora and favour an imbalanced inflammatory response, which might be relevant for the disease course.

Transoral laser microsurgery has developed in recent years into a surgical method that combines a minimally invasive approach with the surgical precision of laser and microscope. The outcomes of laser microsurgical treatment of laryngeal carcinomas are reviewed and compared with the results of competitive standard procedures. Laser microsurgery is widely acknowledged to have advantages in the treatment of early glottic carcinoma. In the treatment of glottic carcinoma causing impaired mobility or fixation of the vocal cord the role of laser surgery has not yet been definitively assessed. Based on published results, primary laser therapy can achieve local tumor control with a functional residual larynx in approximately 70–80% of cases. In patients with early or moderately advanced supraglottic carcinoma, laser microsurgery is comparable to open supraglottic laryngectomy in terms of local control and survival. With regard to organ preservation, laser microsurgery is comparable to open supraglottic laryngectomy but superior to radiotherapy. Microsurgery can preserve functionally important structures, allowing for early swallowing rehabilitation while avoiding tracheotomy. This review elucidates the role of laser microsurgical partial resections of the larynx in comparison with other treatment modalities.

The effectiveness of screening for metachronous second primary tumours by routine follow-up after curative treatment of carcinoma of the upper aerodigestive tract (UADT) was investigated. Data relating to epidemiology, treatment, follow-up (8,014 consultations), and survival from 819 previously untreated patients were analysed to identify risk factors for second primary tumours and to evaluate their impact on survival. During the follow-up period (median 45.2 months), 10.7% of the patients developed a second carcinoma. The annual incidence, which depended on the localisation of the index tumour, was 1.6% for glottic, 3.0% for oropharyngeal, 3.4% for oral cavity, 3.6% for supraglottic, and 4.6% for hypopharyngeal carcinoma. Male sex and the site of the index tumour were identified as relevant prognostic factors for the time to occurrence of a second carcinoma. Radiotherapy as part of initial treatment was associated with a decreased risk for second tumour. Second primary tumour-specific survival was influenced by age, treatment of the index carcinoma, site and stage of the second carcinoma. Patients with curatively treated UADT cancer should have a long-term follow-up with an annual otolaryngologic examination to screen for second primary tumours. More intensive follow-up strategies do not appear to be beneficial.

Die transorale Lasermikrochirurgie entwickelte sich in den letzten Jahren zu einer Operationsmethode, die den minimal-invasiven Zugangsweg mit den besonderen Vorzügen des Lasers - der chirurgischen Präzision, der leichten Steuerbarkeit, der optimierten Gewebewirkung und der berührungslosen Vorgehensweise - in sich vereinigt. Die Prinzipien der lasermikrochirurgischen Resektion von Mundhöhlen-, Oro-, Hypopharynx- und Larynxkarzinomen werden beschrieben und die onkologischen und funktionellen Ergebnisse der Lasermikrochirurgie den Ergebnissen der konkurrierenden Standardtherapieverfahren gegenübergestellt. Die Vorteile der Lasermikrochirurgie in der Behandlung früher Stimmlippenkarzinome sind weithin anerkannt. Der Stellenwert der Laserchirurgie in der Behandlung von Stimmlippenkarzinomen mit Bewegungseinschränkung oder Fixation der Stimmlippe ist noch nicht abschließend zu beurteilen. Nach den bisher vorliegenden Ergebnissen kann in etwa 70 % der Fälle mit der primären Therapie lokale Tumorfreiheit mit funktionsfähigem Restkehlkopf erzielt werden. Beim Larynxkarzinomrezidiv nach primärer Strahlentherapie ist die Lasermikrochirurgie den klassischen Larynxteilresektionen in onkologischer Hinsicht vergleichbar, sie hat jedoch weniger Komplikationen. Beim frühen und beim mäßig weit fortgeschrittenen supraglottischen Karzinom ist die Lasermikrochirurgie der klassischen Kehlkopfteilresektion im Hinblick auf die lokale Kontrolle und das Überleben vergleichbar. Gemessen am Organerhalt ist sie den klassischen Teilresektionen vergleichbar, der primären Strahlentherapie jedoch überlegen. Durch die Mikrochirurgie können funktionell wichtige Strukturen geschont werden, so dass eine frühe Schluckrehabilitation unter Vermeidung der Tracheotomie möglich ist. Auch Karzinome des Hypopharynx können unter Organ- und Funktionserhalt mit guten onkologischen Ergebnissen mit dem Laser operiert werden. Verglichen mit der Standardtherapie und neueren Protokollen mit dem Ziel des Organerhalts (neoadjuvante Chemotherapie und Radiotherapie, simultane Chemo-Radiotherapie) stellt die Lasermikrochirurgie eine therapeutische Alternative dar. Bei Mundhöhlen- und Oropharynxkarzinomen bedeutet der en- oder transorale Zugangsweg durch den Verzicht auf Pharyngotomie, Unterkieferspaltung bzw. Unterkieferteilresektion und Tracheotomie weit weniger Morbidität für den Patienten. Auch große Defekte in Mundhöhle und Oropharynx müssen nicht plastisch verschlossen werden. Der Verzicht auf eine plastische Deckung muss für die postoperative Schluck- und Sprechfunktion nicht nachteilig sein.