Pretreatment pain predicts perineural invasion in patients with head and neck squamous cell carcinoma.

OBJECTIVES: Perineural invasion (PNI) in head and neck cancer (HNC) is a distinct pathological feature used to indicate aggressive tumor behavior and drive treatment strategies. Our study examined the prevalence and predictors of PNI in HNC patients stratified by tumor site. STUDY DESIGN AND METHODS: A retrospective analysis of head and neck squamous cell carcinoma (HNSCC) patients who underwent surgical resection at the University of Pittsburgh Medical Center between 2015 and 2018 was performed. Pretreatment pain was assessed at least 1 week before surgery using the Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N). Demographics, clinical characteristics, and concomitant medications were obtained from medical records. Patients with cancers at the oropharynx and non-oropharynx (i.e., cancer at oral cavity, mandible, larynx) sites were separately analyzed. Tumor blocks were obtained from 10 patients for histological evaluation of intertumoral nerve presence. RESULTS: A total of 292 patients (202 males, median age = 60.94 ± 11.06) were assessed. Pain and PNI were significantly associated with higher T stage (p < 0.001) and tumor site (p < 0.001); patients with non-oropharynx tumors reported more pain and had a higher incidence of PNI compared to oropharynx tumors. However, multivariable analysis identified pain as a significant variable uniquely associated with PNI for both tumor sites. Evaluation of nerve presence in tumor tissue showed 5-fold higher nerve density in T2 oral cavity tumors compared to oropharyngeal tumors. CONCLUSIONS: Our study finds that PNI is associated with pretreatment pain and tumor stage. These data support the need for additional research into the impact of tumor location when investigating targeted therapies of tumor regression.

The effect of opioids on the efficacy of immunotherapy in recurrent/metastatic squamous cell carcinoma of the head and neck.

OBJECTIVES: Head and neck squamous cell carcinoma (HNSCC) causes severe pain and opioids, the mainstay of pain management, may have immunomodulatory effects. We evaluated the effect of opioids on immunotherapy efficacy in recurrent/metastatic (R/M) HNSCC patients. MATERIALS AND METHODS: In a retrospective study of 66 R/M HNSCC patients from 2015 to 2020, opioid dosage, calculated as mean morphine milligram equivalent per day, was assessed on the day of anti-PD-1 monoclonal antibody (mAb) treatment and most recent prior visit. Intratumoral T cells were evaluated by single cell RNAseq and immunohistochemistry prior to treatment. Univariable and multivariable Cox proportional hazards and logistic regression models were used to estimate the association between opioid usage, progression-free survival (PFS), overall survival (OS), disease control rate. RESULTS: Patients were 79% male, 35% oropharynx, 35% oral cavity, 40% locoregional recurrence, and 56% platinum failure. Higher opioid dosage by continuous variable was significantly associated with lower PFS (p = 0.016) and OS (p < 0.001). In multivariable analysis, including platinum failure status and PD-L1, higher opioids were associated with lower OS. Opioid usage by categorical variable was associated with significantly lower intratumoral CD8+ T cells. Opioid receptor, OPRM1, expression was identified in intratumoral and circulating T cells. CONCLUSIONS: In our study cohort of anti-PD-1 mAb treatment in R/M HNSCC patients, higher opioids were associated with significantly lower PFS and OS and lower CD8+ T cells in the tumor microenvironment. To our knowledge, this is the first analysis in R/M HNSCC patients and further research into the clinical and biologic effect of opioids is warranted.

Functional outcomes of hyoid suspension in anterior oromandibular reconstruction.

BACKGROUND: Hyoid suspension can be considered in major oromandibular reconstruction. The impact of hyoid suspension on flap viability, swallowing outcomes, airway, and long term radiographic hyoid position is unknown. The objective of this study is to describe outcomes after hyoid suspension in anterior mandibular reconstruction with fibular free flaps. We hypothesized hyoid suspension would not affect flap viability and would benefit functional outcomes. METHODS: A retrospective cohort study was conducted in an academic tertiary medical center. The study consisted of 84 adults who underwent anterior mandibular reconstruction from February 2014 to September 2020. The primary outcome studied was the post-suspension flap viability. Secondary outcomes include pre/post-operative hyomental distance on computed-tomography, duration of perioperative tracheostomy, postoperative feeding tube dependence, and post-operative aspiration pneumonia. RESULTS: A total of 84, predominantly male (66.5 %), patients with an average age of 58.9 ± 11.5 were included in the study. Of those that met inclusion criteria, 25 (29.4 %) underwent intraoperative hyoid suspension. Univariable analysis showed no significant association between resuspension and post-operative total flap loss (p = 0.864) or partial flap loss (p = 0.318). There was no association between hyoid suspension and any of the studied postoperative functional outcomes or radiographic measures. CONCLUSIONS: Hyoid suspension is an option during oromandibular reconstruction and does not impact flap viability. The impact on functional outcomes and long-term hyoid position in this patient subset remains unclear.

Effect of Oblique Tendon Laceration on Core Suture Strength: A Biomechanical Evaluation.

BACKGROUND: The effect of obliquity of tendon laceration on repair strength is not well studied. The overwhelming majority of biomechanical studies assess repair strength following a laceration that is perpendicular to the long axis of the tendon. The aim of this study was to investigate whether the angle of tendon laceration affects the core suture strength. METHODS: In all, 110 fresh human cadaveric flexor tendons were cut at varying angles of 15°, 30°, 45°, and 60° and the control group at 90°. All tendons were repaired with 6-strand modified Tang technique. The repair strength was tested using a custom-made tensioning machine, and the initial static gap force and the ultimate breaking force were measured. RESULTS: The mean gap force and 95% confidence interval (CI) for the 15°, 30°, 45°, 60°, and 90° groups were 15.2 N (11.4-19.0 N), 15.8 N (13.6-18.1 N), 15.6 N (13.1-18.4 N), 16.6 N (13.7-19.5 N), and 22.3 N (16.6-27.9 N), respectively. In the same respective order, the break force and 95% CI were 25.9 N (21.9-29.8 N), 26.5 N (23.2-29.7 N), 31.1 N (26.1-36.1 N), 35.6 N (28.2-43.1 N), and 51.8 N (62.5-41.0), respectively. The Fisher least significant difference demonstrated significant differences between the control group and all experimental groups for both gap force and break force. CONCLUSIONS: Obliquity of tendon laceration affects the core suture strength when compared with a transverse cut. Flexor tendons cut at 90° demonstrated a higher overall gap force and breaking strength that were statistically significant when compared with all obliquely cut groups. These findings should be considered when repairing and starting postoperative therapy for obliquely cut tendons.