Squamous cell carcinoma (SCC) is the most common cancer of the head and neck region including—among others—laryngeal (LSCC) and hypopharyngeal (HSCC) subsites. LSCC/HSCC are heterogenous diseases with respect to patient outcome. Currently, tumor stage–based patient stratification is essential to predict prognosis and thus selection of the appropriate treatment modalities. In contrast, the prognostic impact of the current HSCC/LSCC grading system according to the WHO classification is limited. Recently, a novel grading system based on tumor budding activity (BA) and cell nest size (CNS) has been introduced for SCC in different anatomic regions of the upper aerodigestive tract. To test and transvalidate this grading scheme in LSCC and HSCC, we retrospectively correlated BA, CNS, and additional histomorphologic parameters with clinicopathologic data of 157 treatment-naive patients. In doing so, we demonstrate that a 3-tiered novel grading system (well-differentiated [nG1], intermediately [nG2], and poorly differentiated [nG3]) based on a sum score for BA and CNS is highly and independently prognostic for patient survival in LSCC/HSCC, strongly outperforming the current WHO grading scheme with a hazard ratio for disease-specific survival of 6.6 for nG2 and 13.4 for nG3 cases (P<0.001). This finding contributes to a growing body of evidence that a CNS and BA-based pan-entity grading system in SCC might be useful and seems to capture differences in underlying SCC biology crucial for survival.

Pharyngocutaneous fistulae (PCF) are one of the most common complications after laryngectomy. Predisposing risk factors have been studied, yet knowledge to determine which patients are prone to developing a fistula remains scarce. This study aims to establish prognostic parameters to identify individual patients at risk for PCF development. As PCF and inflammation seem to be interwoven, this work focuses on markers able to detect an inflammatory response. We retrospectively analyzed all patients who had undergone a laryngectomy at our clinic in the years 2007 to 2017 (n = 182). Immunohistochemical expression of bradykinin type 1 and 2 receptor and vascular endothelial growth factor receptor 2 was studied in all available tumor samples. Additionally, the clinical inflammation parameters 'body temperature', 'pain', 'c-reactive protein (CRP)', and 'leucocytes' were postoperatively tracked in all patients. The times between fistula diagnosis, therapeutic approach, and hospital discharge were recorded. We found a strong correlation between inflammation and the formation of a fistula. High bradykinin 1 receptor expression in the tumor samples correlated with postoperative PCF development. Persistently elevated CRP and leukocyte levels beyond the 6th postoperative day were also risk factors. A decreased time lapse between PCF diagnosis and surgical revision clearly correlated with a shorter hospital stay. In this study, we identified a bradykinin 1 receptor positive patient group at high risk for development of PCF. We recommend close monitoring for fistula formation in these patients to ensure timely intervention.

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Material und Methoden Es erfolgte eine retrospektive Analyse aller Patienten unserer Klinik, bei denen im Zeitraum von 2007 bis 2017 eine Laryngektomie durchgeführt worden war (n=182). In allen verfügbaren histologischen Präparaten wurde die immunhistochemische Expression des Bradykinin-1-und-2-Rezeptors (B1/2-R), sowie des Vascular Endothelial Growth Factor Receptors 2 (VEGF-R2) untersucht. Die membranöse /zytoplasmatische Färbung wurden mittels des immunreaktiven Scores (IRS; s. Abb.1) semiquantitativ bestimmt, bei der endothelialen Färbung wurde lediglich zwischen nicht vorhandener, schwacher und starker Färbung unterschieden. Weiter wurde der postoperative Verlauf der klinischen Entzündungsmarker Körpertemperatur, Schmerz, C-reaktives Protein und Leukozyten verfolgt.