A change in the study evaluation paradigm reveals that larynx preservation compromises survival in T4 laryngeal cancer patients

Background: Larynx preservation (LP) is recommended for up to low-volume T4 laryngeal cancer as an evidence-based treatment option that does not compromise survival. However, a reevaluation of the current literature raises questions regarding whether there is indeed reliable evidence to support larynx preservation for T4 tumor patients. Methods: In an observational cohort study of 810 laryngeal cancer patients, we evaluated the outcomes of all T4 tumor patients treated with primary chemo-radiotherapy (CRT) or primary radiotherapy alone (RT) compared with upfront total laryngectomy followed by adjuvant (chemo)radiotherapy (TL + a[C]RT). Additionally, we reevaluated the studies that form the evidence base for the recommendation of LP for patients with up to T4 tumors (Pfister et al., J Clin Oncol 24:3693–704, 2006). Results: The evaluation of all 288 stage III and IV patients together did not show a significant difference in overall survival (OS) between CRT-LP and TL + a(C)RT (hazard ratio (HR) 1.23; 95% confidence interval (CI): 0.82–1.86; p = 0.31) using a multivariate proportional hazard model. However, a subgroup analysis of T4 tumor patients alone (N = 107; 13.9%) revealed significantly worse OS after CRT compared with TL + a(C)RT (HR 2.0; 95% CI: 1.04–3.7; p = 0.0369). A reevaluation of the subgroup of T4 patients in the 5 LP studies that led to the ASCO clinical practice guidelines revealed that only 21–45 T4 patients had differential data on survival outcome. These data, however, showed a markedly worse outcome for T4 patients after LP. Conclusions: T4 laryngeal cancer patients who reject TL as a treatment option should be informed that their chance of organ preservation with primary conservative treatment is likely to result in a significantly worse outcome in terms of OS. Significant loss of survival in T4 patients after LP is also confirmed in recent literature

Rekonstruktion von Oberkieferdefekten mit einem freien Skapula-angle-Lappen

Zusammenfassung: Hintergrund: Neben der prothetischen Versorgung von Maxilladefekten gibt es Möglichkeiten der chirurgischen Rekonstruktion: die Weichgeweberekonstruktion mit einem Radialis- oder Latissimus-dorsi-Lappen und die knöcherne Rekonstruktion mittels Fibula, Beckenkamm oder Skapulalappen. Die Rekonstruktion mit einem Skapulalappen wird unterteilt in den traditionellen Skapulalappen mit der A.scapularis circumflexa und den Skapula-angle-Lappen mit der A.angularis aus der A.thoracodorsalis als versorgendem Gefäß. Material und Methoden: Wir berichten über 4Patienten, die zwischen 2009 und 2011 aufgrund von malignen Tumoren der Maxilla nach erfolgter Resektion eine Rekonstruktion mit einem freien Skapula-angle-Lappen erhalten haben. Ergebnisse: Die Möglichkeit vertikaler Positionierung des Skapula-angle-Lappens erlaubt die Rekonstruktion der fazialen Kontur. Bei horizontaler Ausrichtung des mikrovaskulär anastomosierten Skapula-angle-Lappens ist eine zusätzliche knöcherne Rekonstruktion des Gaumens möglich. Schlussfolgerung: Der Skapula-angle-Lappen eignet sich wegen seiner Variabilität, geringer Donormorbidität und aufgrund seiner Form, die der des Hartgaumens ähnelt, gut zur plastischen Rekonstruktion. Die knöcherne Beschaffenheit für eine dentale Rehabilitation mithilfe von Implantaten wird kontrovers diskutiert. Er stellt eine Alternative zur Versorgung ausgewählter Maxilladefekte ≥ GradI nach Okay mit einer Obturatorprothese da

Impaired aldehyde dehydrogenase 1 subfamily member 2A-dependent retinoic acid signaling is related with a mesenchymal-like phenotype and an unfavorable prognosis of head and neck squamous cell carcinoma

Background: An inverse correlation between expression of the aldehyde dehydrogenase 1 subfamily A2 (ALDH1A2) and gene promoter methylation has been identified as a common feature of oropharyngeal squamous cell carcinoma (OPSCC). Moreover, low ALDH1A2 expression was associated with an unfavorable prognosis of OPSCC patients, however the causal link between reduced ALDH1A2 function and treatment failure has not been addressed so far. Methods: Serial sections from tissue microarrays of patients with primary OPSCC (n = 101) were stained by immunohistochemistry for key regulators of retinoic acid (RA) signaling, including ALDH1A2. Survival with respect to these regulators was investigated by univariate Kaplan-Meier analysis and multivariate Cox regression proportional hazard models. The impact of ALDH1A2-RAR signaling on tumor-relevant processes was addressed in established tumor cell lines and in an orthotopic mouse xenograft model. Results: Immunohistochemical analysis showed an improved prognosis of ALDH1A2high OPSCC only in the presence of CRABP2, an intracellular RA transporter. Moreover, an ALDH1A2highCRABP2high staining pattern served as an independent predictor for progression-free (HR: 0.395, p = 0.007) and overall survival (HR: 0.303, p = 0.002), suggesting a critical impact of RA metabolism and signaling on clinical outcome. Functionally, ALDH1A2 expression and activity in tumor cell lines were related to RA levels. While administration of retinoids inhibited clonogenic growth and proliferation, the pharmacological inhibition of ALDH1A2-RAR signaling resulted in loss of cell-cell adhesion and a mesenchymal-like phenotype. Xenograft tumors derived from FaDu cells with stable silencing of ALDH1A2 and primary tumors from OPSCC patients with low ALDH1A2 expression exhibited a mesenchymal-like phenotype characterized by vimentin expression. Conclusions: This study has unraveled a critical role of ALDH1A2-RAR signaling in the pathogenesis of head and neck cancer and our data implicate that patients with ALDH1A2low tumors might benefit from adjuvant treatment with retinoids

Opposing function of MYBBP1A in proliferation and migration of head and neck squamous cell carcinoma cells

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is one of the most prevalent and lethal cancers worldwide and mortality mostly results from loco-regional recurrence and metastasis. Despite its significance, our knowledge on molecular, cellular and environmental mechanisms that drive disease pathogenesis remains largely elusive, and there are limited therapeutic options, with only negligible clinical benefit. METHODS: We applied global gene expression profiling with samples derived from a recently established mouse model for oral cancer recurrence and identified a list of genes with differential expression between primary and recurrent tumors. RESULTS: One differentially expressed gene codes for Myb-binding protein 1a (MYBBP1A), which is known as a transcriptional co-regulator that physically interacts with nuclear transcription factors, such as NFκB and p53. We confirmed significantly reduced MYBBP1A protein levels on tissue sections of recurrent mouse tumors compared to primary tumors by immunohistochemistry, and found aberrant MYBBP1A protein levels also in tumor samples of HNSCC patients. Interestingly, silencing of MYBBP1A expression in murine SCC7 and in human HNSCC cell lines elicited increased migration but decreased cell growth. CONCLUSION: We provide experimental evidence that MYBBP1A is an important molecular switch in the regulation of tumor cell proliferation versus migration in HNSCC and it will be a major challenge for the future to proof the concept whether regulation MYBBP1A expression and/or function could serve as a novel option for anti-cancer therapy

Kraft-basierte lokale Navigation zur robotergestützten Implantatbettanlage im Bereich der lateralen Schädelbasis

Die Domäne der Operationsroboter liegt heute in Fräsarbeiten an knöchernen Strukturen. Da Roboter über eine extreme Präzision verfügen und nicht ermüden bietet sich ihr Einsatz insbesondere bei langwierigen und zugleich hochpräzisen Fräsvorgängen im Bereich der lateralen Schädelbasis an. In jüngsten Arbeiten wurden Prozessparameter zur Anlage eines Implantatlagers bspw. für ein Cochlea Implantat oder für eine roboterunterstützte Mastoidektomie ermittelt. Gemessen wurden die Parameter Kraft, Moment, Vibration und Temperatur bei unterschiedlichen Vorschüben, Drehzahlen, Bahnkurven und unterschiedlichem Knochenmaterial (Mastoid, Kalotte). Hieraus ergaben sich Optimierungsparameter für solche Fräsvorgänge. Auffallend waren unvermittelt auftretende und extrem weit über dem Grenzwert liegende Spitzenwerte für Kräfte, bei im Normbereich liegenden Mittelwerten. Aus diesem Grunde wurde ein Verfahren entwickelt, welches aus einer geometrischen Beschreibung des Implantates eine geeignete Fräsbahn errechnet und eine Kraft-geregelte Prozesskontrolle des Fräsvorganges implementiert. Mit einem 6-achsigen Knickarmroboter erfolgten die Untersuchungen primär an Tierpräparaten und zur Optimierung an Felsenbeinpräparaten.Durch intraoperative online Rückkopplung der Kraft - Sensorik war eine lokale Navigation möglich. Bei steigenden Kräften über den Grenzwert wurde die Vorschubgeschwindigkeit automatisch reguliert, auch konnte das Errreichen der Dura an Hand der Werte detektiert werden. Das Implantatlager ließ sich durch das entwickelte Computerprogramm exakt ausfräsen. Die Untersuchungen ergaben, dass eine zufriedenstellende Anlage eines Implantatbettes in der Kalotte durch einen Kraft-geregelten Fräsvorgang mit einem Roboter, im Sinne einer lokalen Navigation, gelingt

General and disease-specific quality of life in patients with chronic suppurative otitis media - a prospective study

Background: Chronic suppurative otitis media (CSOM) is frequently associated with symptoms of inflammation like discharge from the ear or pain. In many cases, patients suffer from hearing loss causing communication problems and social withdrawal. The objective of this work was to collect prospective audiological data and data on general and disease-specific quality of life with validated quality of life measurement instruments to assess the impact of the disease on health-related quality of life (HR-QOL). Methods: 121 patients were included in the study. Patients were clinically examined in the hospital before and 6 months after surgery including audiological testing. They filled in the quality of life questionnaires SF-36 and Chronic Otitis Media Outcome Test 15 (COMOT-15) pre-operatively and 6 and 12 months post-operatively, respectively. Results: Complete data records from 90 patients were available for statistical analysis. Disease-specific HR-QOL in patients with CSOM improved after tympanoplasty in all the scales of the COMOT-15. There was no difference in HR-QOL assessment between patients with mesotympanic respectively epitympanic CSOM. However, we did find the outcome to be worse in patients who received revision surgery compared with those receiving primary surgery. Audiometric findings correlated very well with the subscale hearing function from the COMOT-15 questionnaire. General HR-QOL measured with the SF-36 was not significantly changed by tympanoplasty. Conclusions: Tympanoplasty did lead to a significant improvement of disease-specific HR-QOL in patients with CSOM while general HR-QOL did not change. Very well correlations were found between the subscale hearing function from the COMOT-15 questionnaire and audiological findings. Revision surgery seems to be a predictor for a worse outcome

Normative data for interpreting the SNOT-22

Objectives: The Sino-Nasal Outcome Test 22 (SNOT-22) is a validated patient-reported outcome instrument to evaluate the health-related quality of life (HRQoL) in patients with chronic rhinosinusitis (CRS). There are no published normative SNOT-22 scores, limiting its interpretation. Methods: Symptom scores from 1,000 SNOT-22 questionnaires were analysed by principal component analysis (PCA) and exploratory factor analyses. Data were derived from a survey with 1,000 healthy Europeans (reference cohort) who were recruited using the Respondi panel for market and social science research. This subsample was quoted to the population distribution of the German Microcensus and selected from a non-probability panel. Results: The overall normative SNOT-22 score can be detected to be 20.2 ± 19.44. Male (18.49 ± 19.15) and older (> 50 years old; 18.3 ± 17.49) participants had overall lower SNOT-22 mean results than females (21.8 ± 19.6) and younger (21.4 ± 20.55) participants, indicating higher levels of satisfaction. PCA proposed two SNOT-22 domains ("physiological well-being" and "psychological well-being"), which explained 65% of the variance. Conclusions: These are the first published (German) normative scores for the SNOT-22 and provide a clinical reference point for the interpretation of data

Patient-specific factors to differentiate between branchial cleft cysts and CUP syndrome: a 10 year unicenter study

Objectives: Due to its generally-poor prognosis and varied clinical presentation, cervical cancer of unknown primary (CUP) poses particular challenges for clinical and imaging diagnosis. Differential diagnoses of CUP syndrome may also include lateral cervical cysts. When a benign neck cyst is initially suspected, squamous cell carcinoma is often diagnosed after receiving histopathology. Our study investigates the risk factors to differentiate between CUP syndrome and lateral neck cysts (LNC) to possibly improve the prognosis. Methods: Between 2013 and 2023, 244 patients with an initial diagnosis of LNC (n = 121) or CUP (n = 123) were recruited from the Department of Otorhinolaryngology of Heidelberg University Hospital and underwent panendoscopy with lymph node removal. In general, disease- and progression-free survival, prognostic relevant risk factors, and treatment data were recorded and analyzed. Results: The mean age of patients with CUP was significantly higher at 65 ± 13.2 years than that of patients with LNC (41 ± 15.8 years; P = .000). The calculated cutoff value was 50 to 59 years for a 50% chance of CUP syndrome or other malignant neck mass. Alcohol and tobacco consumption were not found to be risk factors. Previous tumor diseases were diagnosed more frequently in patients with CUP than in patients with LNC (P = .045). The 5 year overall survival for patients with CUP was 77.0% and did not differ significantly between the other various tumor entities (P = .423). Conclusions: The consideration of patient-specific factors such as age or synchronous/asynchronous malignancies is crucial in the diagnostic decision-making process. In the age group of 50 to 59 years, there is ~50% probability of diagnosing CUP syndrome with unilateral painless neck swelling. A thorough clinical examination using panendoscopy with at least 1 unilateral tonsillectomy and biopsies from the base of the tongue is essential to detect a possible primarius early and improve the prognosis

Long-term outcomes and quality of life following parotidectomy for benign disease

Objective: Parotidectomy worsens quality of life (QoL) in the short-term, but the long-term impact is unknown. In this study, we analysed the long-term effects of parotidectomy on QoL. Methods: In this prospective long-term follow-up study, participants were divided into three groups: short-term (ST) follow-up of six weeks, long-term (LT) follow-up of 13 years and short- and long-term (SLT) follow-up. QoL was assessed using the Parotidectomy Outcome Inventory (POI-8). Parotidectomies were classified based on whether the great auricular nerve (GAN) had been preserved or sacrificed. Results: In total, 164 observations were analysed, 74 in the LT group, 57 in the ST group and 33 in the SLT group. Hypoaesthesia was a major problem and facial palsy was a minor problem. Pain (p < 0.01) and hypoaesthesia (p < 0.001) were significantly lower after 13 years compared with after six weeks, and QoL was higher after 13 years compared with after six weeks (p = 0.04). The disease-specific impairment rate decreased from 70% at short-term follow-up to 30% at long-term follow-up. Removal of the GAN was associated with hypoaesthesia in the ST group (p = 0.028). Conclusions: Hypoaesthesia has a long-term impact on the QoL, and this should be emphasised during preoperative discussions