Nicotinic Acetylcholine Receptors in Head and Neck Cancer and Their Correlation to Tumor Site and Progression

Background: Nicotine contributes to tumorigenesis through stimulation of nicotinic acetylcholine receptors (nAChRs) in head and neck squamous cell carcinoma (SCC). Although many factors have been found to be involved in the pathogenesis of head and neck cancer, the effect of nAChRs is still unclear. The study provides information on different subtypes in SCC and normal mucosa (NM) and their clinicopathological correlation to tumor progression. Methods: SCC (n = 34) of oropharynx, hypopharynx, larynx and corresponding NM (n = 38) were analyzed by quantitative real-time polymerase chain reaction, immunoblotting and immunohistochemistry and correlated to tumor grading and Union for International Cancer Control (UICC) stage. Results: nAChR subtypes α1, α3, α5 and α7 were found in NM and SCC of the upper aerodigestive tract with high rates of α1 and α5 in SCC. An overexpression of α1 was found in laryngeal and hypopharyngeal SCC, while α3 and α7 subunits were downregulated. The expression of α1 and α5 subunits increased with tumor progression. Conclusion: The nAChR subunit pattern shows a difference between NM and SCC and changes in the process of tumor progression. Therefore, it is conceivable that it contributes to tumorigenesis. The findings provide a basis for further studies in prognostic assessment and identifying carcinogenic changes from NM to SCC

Postoperative management of antithrombotic medication in microvascular head and neck reconstruction: a comparative analysis of unfractionated and low-molecular-weight heparin

Purpose!#!Free flap reconstruction is a valuable technique to preserve function in oncological head and neck surgery. Postoperative graft thrombosis is a dreaded risk. This study aims to compare low-dose unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) in perioperative thrombosis prophylaxis.!##!Methods!#!This is a retrospective analysis of 266 free flaps performed at our academic center. A comparison was made between 2 patient groups, based on their respective postoperative prophylaxis protocols either with UFH (n = 87) or LMWH (n = 179). Primary endpoints were the frequency of transplant thrombosis and the number of flap failures. Secondary endpoints were the occurrence of peri- and postoperative complications.!##!Results!#!The flap survival rate was 96.6% and 93.3% for the groups UFH and LMWH, respectively (P = 0.280). The rate of postoperative bleeding requiring revision was 4.6% and 6.7% for each group, respectively (P = 0.498). We found a hematoma formation in 4.6% and 3.9% (P = 0.792).!##!Conclusion!#!The free-flap survival rate using low-dose UFH seems to be equivalent to LMWH regimens without compromising the postoperative outcome. Consequently, for risk-adapted thrombosis prophylaxis, either LMWH or UFH can be administrated

Salivary gland carcinoma (SGC) with perineural spread and/or positive resection margin – high locoregional control rates after photon (chemo) radiotherapy - experience from a monocentric analysis

Abstract Background The aim was to evaluate the outcome, especially locoregional control of patients with locally advanced salivary gland carcinoma (SGC) with perineural spread (Pn1) and/or positive resection margins (R1/2) after postoperative photon (chemo) radiotherapy in a single centre. Methods We retrospectively reviewed data of 65 patients with newly diagnosed locally advanced SGC without distant metastases who underwent radio (chemo) therapy in the department of radiation oncology of the university hospital of Erlangen from January 2000 until April 2017. Kaplan Meier method was used to calculate survival and recurrence rates. In univariate analysis the log-rank test was used to correlate patient−/tumor- and treatment-related parameters to survival and recurrence rates. Results Median follow-up was 45 months (range: 6; 215). After 1, 3, 5 years cumulative incidence of local and locoregional failure was 3.1, 7.0, 7.0% and 3.1, 9.7, 12.9%, whereas cumulative incidence of distant metastases (DM) was 15.6, 36.0, 44.0%. After 1,3, 5 years cumulative Overall (OS) and Disease-free survival (DFS) was 90.5, 74.9, 63.9% and 83.0, 54.8, 49.4%. The only significant predictor for decreased local and locoregional control was a macroscopic resection margin(R2) (p = 0.002 and p = 0.04). High-grade histology (p = 0.006), lymph node metastases with extracapsular spread (p = 0.044) and an advanced T-stage (p = 0.031) were associated with an increased rate of DM. High-grade histology was the only factor predicting for a decreased DFS (p = 0.014). Conclusion Photon radiotherapy leads to high local and locoregional control rates in a high-risk patient population with SGC with microscopically positive resection margins and/or perineural spread. The most common site of disease recurrence was distant metastases. Therefore the real challenge for the future should be to prevent distant metastases

Zeitmanagement im OP – eine Querschnittstudie zur Bewertung der subjektiven und objektiven Dauer chirurgischer Prozeduren im HNO-Bereich

Background!#!Accurate planning of operating times in surgical clinics is essential. Moreover, high-capacity utilization of operating rooms (ORs) is necessary for economic efficiency.!##!Objective!#!Most planning of operating times is performed by surgeons. Herein, surgeons' estimated times and the objective times for performing surgical procedures were compared to detect sources of error.!##!Materials and methods!#!In a retrospective analysis, the durations of 1809 operations using general anesthesia (22 types of surgery) by 31 surgeons (12 specialists and 19 residents) were compared. Comparisons were analyzed by Mann-Whitney U‑tests.!##!Results!#!The comparison of objective times of surgical action showed significant differences between specialists and residents in 6 of 15 types of surgeries. The post-processing times estimated by specialists deviated from the objective times in 2 out of 22 surgery types, while the post-processing times estimated by residents deviated in 7 of 15 types. Specialists misjudged the incision-to-suture times in 7 of 22 surgery types, and residents misjudged these times in 3 of 15 types. The preparation times estimated by specialists deviated from the objective times in 16 of 22 types of surgeries and in 7 of 15 types estimated by residents.!##!Conclusion!#!A surgeon's routine must be carefully considered in order to estimate operating times. Specialists generally underestimated preparation and post-processing times and overestimated incision-to-suture times, whereas residents underestimated all three. Preparation and post-processing times must be considered in planning and, ideally, determined together with anesthesiologists and surgical assistants

Dose Reduction to the Swallowing Apparatus and the Salivary Glands by De-Intensification of Postoperative Radiotherapy in Patients with Head and Neck Cancer: First (Treatment Planning) Results of the Prospective Multicenter DIREKHT Trial

Aim: Evaluating radiotherapy treatment plans of the prospective DIREKHT trial (ClinicalTrials.gov, NCT02528955) investigating de-intensification of radiotherapy in patients with head and neck cancer. Patients and Methods: The first 30 patients from the DIREKHT trial of the leading study centre were included in this analysis. Standard treatment plans and study treatment plans derived from the protocol were calculated for each patient. Sizes of planning target volumes (PTVs) and mean doses to organs at risk were compared using the Student’s t-test with paired samples. Results: Mean PTV3 including primary tumor region and ipsilateral elective neck up to a dose of 50 Gy in the study treatment plans was 662 mL (+/− 165 mL standard deviation (SD)) and therefore significantly smaller than those of the standard treatment plans (1166 mL (+/− 266 mL SD). In the medial and inferior constrictor muscles, cricopharyngeal muscle, glottic and supraglottic laryngeal areas, arytenoid cartilages, contralateral major salivary glands highly significant dose reductions (p < 0.0001) of more than 10 Gy were achieved in study treatment plan compared to standard treatment plan. Conclusion: De-intensification of radiotherapy led to smaller planning target volumes and clinical relevant dose reductions in the swallowing apparatus and in the contralateral salivary glands

Secondary Tracheoesophageal Puncture After Laryngectomy Increases Complications With Shunt and Voice Prosthesis

Objectives/Hypothesis To evaluate the demographics, clinical features, management, and prognostic indicators of tracheoesophageal puncture complications in patients undergoing placement of voice prosthesis following cancer treatment. Study Design Retrospective analysis. Methods A retrospective analysis was conducted of cases from a tertiary referral center diagnosed between 1996 and 2015. Multivariate logistic regression was used to determine factors associated with tracheoesophageal puncture (TEP) and voice prostheses–complication‐free survival (TEP/VP‐CFS). Results One hundred fourteen cases were identified. Most patients were males (92.9%) with pT3 (26.8%) or pT4 (58.1%) N+ (53.6%) tumors. All patients received laryngectomy as the primary treatment, with 75% of patients receiving adjuvant radiation therapy or chemoradiotherapy. Complications with TEP were common (65.2%). The most frequent problem was salivary leakage (50.0%), which at the same time was the most common reason for changing the prosthesis. On univariate regression analysis, prosthesis placement time after adjuvant radiotherapy (hazard ratio [HR]: 4.17, 95% confidence interval [CI]: 2‐8.69), secondary prosthesis placement after primary surgery (HR: 3.97, 95% CI: 1.99‐7.9), and laryngectomy with flap reconstruction (HR: 1.96, 95% CI: 0.99‐3.89) were significant prognosticators for complications. Multivariate regression analysis revealed secondary prosthesis placement after adjuvant radiotherapy (HR: 3.66, 95% CI: 1.39‐9.68) or after primary surgery (HR: 2.57, 95% CI: 0.92‐7.2) to be the strongest predictors of reduced TEP/VP‐CFS. Conclusions Secondary prosthesis placement after primary surgery, placement after previous irradiation, and laryngectomy with flap reconstruction are predictors of poor TEP/VP‐CFS. Planned adjuvant radiotherapy is not a contraindication for TEP with prosthetic placement, but it is very important to place the prosthesis during the primary surgery or at least before scheduled radiotherapy. Level of Evidence 4 Laryngoscope, 202