Risk factors for total laryngectomy associated proximal esophageal stricture formation in head and neck cancer patients.

BACKGROUND: Development of esophageal strictures is common after the total laryngectomy of head and neck cancer patients. While endoscopic techniques like dilatation by balloon or Salvary bougies are well established, risk factors and pathophysiology for development of refractory strictures are less well understood. OBJECTIVE: To evaluate risk factors associated with occurrence and recurrence of total-laryngectomy-associated esophageal strictures in head and neck cancer patients. METHODS: We analyzed retrospectively a cohort of 170 head and neck squamous cell carcinoma patients, who underwent total laryngectomy between 2007 and 2017. The outcome measure was laryngectomy-associated proximal esophageal stricture needing an endoscopic dilatation by using a balloon or Savary dilators. RESULTS: Of the 170 patients in the cohort, 32 (18.8%) developed strictures. Mean time between surgery and first endoscopic intervention was 24.4 months. Significant predictive factors were age ≥ 65 (p=0.017), nodal status N> 1 (p=0.003), continued alcohol abuse after surgery (p=0.005) and diabetes mellitus (p=0.005). In a subgroup, 17 of 32 patients developed refractory strictures and needed more than three dilatations to relieve dysphagia. Postoperative mean (p=0.016) and maximum (p=0.015) C-reactive protein (CRP) were predictive for refractory strictures. CONCLUSION: Symptomatic strictures occurred in 18.8% of the cases. Age, nodal status N>1, continued alcohol abuse and diabetes mellitus were predictive factors. For refractory stenosis (>3 dilatations needed) mean and maximum postoperative CRP were predictive. This may indicate that systemic inflammatory response post-surgery is involved in the stricture formation process.

Bradykinin Receptor B1 and C-Reactive Protein as Prognostic Factors for Pharyngocutaneous Fistula Development After Laryngectomy.

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.

Tumor Budding and Cell Nest Size Are Highly Prognostic in Laryngeal and Hypopharyngeal Squamous Cell Carcinoma: Further Evidence for a Unified Histopathologic Grading System for Squamous Cell Carcinomas of the Upper Aerodigestive Tract.

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.