Co-expression patterns of cancer associated fibroblast markers reveal distinct subgroups related to patient survival in oropharyngeal squamous cell carcinoma.

Background: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) is rapidly increasing in high income countries due to its association with persistent high-risk human papilloma virus (HPV) infection. Recent scientific advances have highlighted the importance of the tumor microenvironment in OPSCC. In this study, including 216 OPSCC patients, we analyze the composition of four established markers of cancer associated fibroblasts (CAFs) in the context of intratumoral CD8 T-cell infiltration. Methods: Immunohistochemical staining for fibroblast activation protein (FAP), platelet-derived growth factor receptor beta (PDGFRb), periostin, alpha smooth muscle actin (α-SMA) and CD8 were analyzed digitally and their association with survival, tumor- and patient characteristics was assessed. Results: Co-expression of CAF markers was frequent but not associated with HPV status. FAPhigh and PDGFRbhigh expression were associated with increased CD8 T-cell infiltration. Low expression of PDGFRb improved patient survival in female patients but not in male patients. We identified PDGFRblow periostinlow α-SMAlow status as an independent predictor of improved survival (hazard ratio 0.377, p = 0.006). Conclusion: These findings elucidate the co-expression of four established CAF markers in OPSCC and underscore their association with T-cell infiltration and patient survival. Future analyses of CAF subgroups in OPSCC may enable the development of individualized therapies.

Predictors for Survival of Patients with Squamous Cell Carcinoma of Unknown Primary in the Head and Neck Region.

BACKGROUND: Human papillomavirus (HPV) status is the most important predictor of survival in oropharyngeal squamous cell carcinoma (OPSCC). In patients with cervical lymph node metastases of squamous cell carcinoma of unknown origin (CUPHNSCC), much less is known. METHODS: We assessed a consecutive cohort of CUPHNSCC diagnosed from 2000-2018 for HPV DNA, mRNA, p16INK4a (p16) expression, and risk factors to identify prognostic classification markers. RESULTS: In 32/103 (31%) CUPHNSCC, p16 was overexpressed, and high-risk HPV DNA was detected in 18/32 (56.3%). This was mostly consistent with mRNA detection. In recursive partitioning analysis, CUPHNSCC patients were classified into three risk groups according to performance status (ECOG) and p16. Principal component analysis suggests a negative correlation of p16, HPV DNA, and gender in relation to ECOG, as well as a correlation between N stage, extranodal extension, and tobacco/alcohol consumption. CONCLUSIONS: Despite obvious differences, CUPHNSCC shares similarities in risk profile with OPSCC. However, the detection of p16 alone appears to be more suitable for the classification of CUPHNSCC than for OPSCC and, in combination with ECOG, allows stratification into three risk groups. In the future, additional factors besides p16 and ECOG may become important in larger studies or cases with special risk profiles.

Reanimation of the Smile with Neuro-Vascular Anastomosed Gracilis Muscle: A Case Series.

BACKGROUND: The aim of our manuscript was to evaluate the time course of clinical and electromyographical (EMG) reinnervation after the reanimation of the smile using a gracilis muscle transplant which is reinnervated with the masseteric nerve. METHODS: We present a case series of five patients with a longstanding peripheral facial palsy, who underwent a reanimation of the lower face using a gracilis muscle transplant with masseteric nerve reinnervation from June 2019 to October 2020. Trial-specific follow-up examinations were carried out every three months using clinical assessment and EMG, up to 12 months after the surgery. The grading was carried out using the House-Brackmann scale (HB), the Stennert Index, and a self-designed Likert-like scale for graft reinnervation and smile excursion. RESULTS: The surgery was feasible in all of the patients. The reanimation was performed under general anesthesia in an inpatient setting. Postoperative complications which resulted in prolonged hospitalization occurred in two of the five patients. All of the patients showed a preoperative flaccid facial palsy. The first single reinnervation potentials were detected 3.1 ± 0.1 months after surgery. After 5.6 (±1.4) months, in three (3/5) patients, clear reinnervation patterns were present. Clinically, the patients obtained symmetry of the face at rest after 5.6 (±1.4) months, and could spontaneously smile without the co-activation of the jaw after an average time of 10.8 (±1.8) months. All of the patients were able to express a spontaneous emotion-stimulated smile after one year. CONCLUSION: Micro-neurovascular gracilis muscle transfer reinnervated with a masseteric nerve is a sufficient and reliable rehabilitation technique for the lower face, and is performed as a single-stage surgery. The nerve supply via the masseteric nerve allows the very rapid and strong reinnervation of the graft, and results in a spontaneous smile within 10 months.

Initial Load Stability of Different Trachea Suture Techniques: Tests on an Ex Vivo Model.

Objective Tracheal anastomosis can be performed with different suture techniques. In this experimental work, the resilience of anastomotic techniques to pressure and tensile stress was studied. Study Design Ex vivo pig model. Setting Experimental. Subjects and Methods The trachea with the 2 main bronchi in freshly slaughtered pigs was isolated and intubated (CH 8.0). Both main bronchi were closed distally by a stapler. After resection of the trachea, an anastomosis (n = 15 per group) was created: group 1, single interrupted sutures; group 2, continuous running suture; group 3, mixed technique. A continuous tensile stress of 0, 500, 1000, or 1500 g was applied to the preparations. Mechanical ventilation with a maximum pressure of 70 mbar was initiated. The airtightness of the anastomosis was verified by submerging the entire preparation under water. Results At tensile loads of 0.5 and 1.0 kg, all anastomoses created in the single-stitch technique were airtight; at 1.5 kg, 93.3% were without leaks. In the continuous suture technique, the airtightness of anastomoses decreased with increasing tensile load: from 93.3% at 500 g to 73.3% at 1 kg and 66.6% at 1.5 kg ( P = .02 at 1.5 kg). Anastomoses in the mixed technique were airtight in 80% at 500 g, 66.6% at 1 kg, and 46.6% at 1.5 kg ( P = .01 in comparison with single stitches). Conclusion Anastomoses created with single interrupted sutures showed the highest resilience against combined pressure and tensile stress.