Predictors of gastrostomy tube dependence in surgically managed oropharyngeal squamous cell carcinoma.

OBJECTIVES: To elucidate predictive factors in the perioperative period resulting in gastrostomy tube (G-tube) dependence for patients undergoing primary surgical treatment of oropharyngeal squamous cell carcinoma (OPSCC) in the modern era. METHODS: Two hundred and thirty patients with known OPSCC treated with primary surgery were screened and selected from a retrospective database spanning from 2002 to 2012 at The Ohio State University Wexner Medical Center (Columbus, Ohio), with univariable and multivariable logistic regression modeling used to determine independent predictive factors resulting in G-tube dependence (defined as tube persistence/presence 1 year after surgery). RESULTS: Surgical approach, baseline characteristics, tumor (T)-nodal-metastasis stage, human papillomavirus status, extent of tissue resected, surgical complications, reconstructive technique, preoperative G-tube presence, and adjuvant treatment were recorded. Patients undergoing open surgery for OPSCC without adjuvant treatment had 42.9% G-tube dependence (44.6% with adjuvant chemoradiation [CRT]) compared to 0% for those undergoing transoral nonrobotic surgery (8.1% with adjuvant CRT) and 0% for those undergoing transoral robotic surgery (10.3% with adjuvant CRT). In multivariable analysis, greater than 25% of the oral tongue resected (odds ratio [OR] 12.29; P = 0.03), an open surgical approach (OR 5.72; P < 0.01) and T3/T4 tumor stage (OR 2.84; P = 0.02) were independent and significant predictors of G-tube dependence. CONCLUSION: Surgical approach, advanced tumor stage, and oral tongue resection may influence the development of nutritional dependence for surgically treated patients with OPSCC. LEVEL OF EVIDENCE: 4 Laryngoscope, 129:415-421, 2019.

Nuclear PRMT5, cyclin D1 and IL-6 are associated with poor outcome in oropharyngeal squamous cell carcinoma patients and is inversely associated with p16-status.

Protein arginine methyltransferase-5 (PRMT5) plays an important role in cancer progression by repressing the expression of key tumor suppressor genes via the methylation of transcriptional factors and chromatin-associated proteins. However, very little is known about the expression and biological role of PRMT5 in head and neck cancer. In this study, we examined expression profile of PRMT5 at subcellular levels in oropharyngeal squamous cell carcinoma (OPSCC) and assessed its correlation with disease progression and patient outcome. Our results show that nuclear PRMT5 was associated with poor overall survival (p < 0.012) and these patients had 1.732 times higher hazard of death (95% CI: 1.127-2.661) as compared to patients in whom PRMT5 was not present in the nucleus of the tumors. Nuclear PRMT5 expression was inversely correlated with p16-status (p < 0.001) and was significantly higher in tumor samples from patients who smoked > 10 pack-years (p = 0.013). In addition, nuclear PRMT5 was directly correlated with cyclin D1 (p = 0.0101) and IL-6 expression (p < 0.001). In a subgroup survival analysis, nuclear PRMT5-positive/IL-6-positive group had worst survival, whereas nuclear PRMT5-negative/IL-6-negative group had the best survival. Similarly, patients with p16-negative/nuclear PRMT5-positive tumors had worse survival compared to patients with p16-positive/nuclear PRMT5-negative tumors. Our mechanistic results suggest that IL-6 promotes nuclear translocation of PRMT5. Taken together, our results demonstrate for the first time that nuclear PRMT5 expression is associated with poor clinical outcome in OPSCC patients and IL-6 plays a role in the nuclear translocation of PRMT5.

Surgical management of oropharyngeal squamous cell carcinoma: Survival and functional outcomes.

BACKGROUND: The purpose of this study was to further define the impact of primary surgery in the management of oropharyngeal squamous cell carcinoma (SCC). METHODS: Two hundred ninety-six patients with oropharyngeal SCC treated with primary surgery were included. Multivariable analysis and recursive partitioning analysis (RPA) identified predictors of survival and gastrostomy tube presence. RESULTS: Multivariable analysis identified that HPV negativity (p = .0002), presence of extranodal extension (p = .0025), and advanced T classification (p = .0081) were independent predictors of survival. For HPV-positive patients, surgical approach (p = .0111) and margin status (p = .0287) were significant predictors of survival. For HPV-negative patients, extranodal extension (p = .0021) and advanced T classification (p = .0342) were significant predictors of survival. Smoking status and advanced neck disease did not impact survival, and the addition of adjuvant chemotherapy did not confer survival benefit in HPV-positive or HPV-negative subgroups. CONCLUSION: Independent predictors of survival are unique in patients with oropharyngeal SCC treated with primary surgery. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1794-E1802, 2016.

YM155 reverses cisplatin resistance in head and neck cancer by decreasing cytoplasmic survivin levels.

Cisplatin is one of the commonly used chemotherapeutic drugs for the treatment of head and neck squamous cell carcinoma (HNSCC). However, acquisition of cisplatin resistance is common in patients with HNSCC, and it often leads to local and distant failure. In this study, we showed that survivin expression is significantly upregulated in HNSCC primary tumors and cell lines. In addition, survivin levels were significantly higher in human papilloma virus-negative patients that normally respond poorly to cisplatin treatment. Survivin expression was further increased in cisplatin-resistant cells (CAL27-CisR) as compared with its parent cells (CAL27). Therefore, we hypothesized that targeting of survivin in HNSCC could reverse the resistant phenotype in tumor cells, thereby enhancing the therapeutic efficacy of cisplatin. We used both in vitro and in vivo models to test the efficacy of YM155, a small molecule survivin inhibitor, either as a single agent or in combination with cisplatin. YM155 significantly decreased survivin levels and cell proliferation in a dose-dependent manner. In addition, YM155 pretreatment significantly reversed cisplatin resistance in cancer cells. Interestingly, YM155 treatment altered the dynamic localization of survivin in cells by inducing a rapid reduction in cytoplasmic survivin, which plays a critical role in its antiapoptotic function. In a severe combined immunodeficient mouse xenograft model, YM155 significantly enhanced the antitumor and antiangiogenic effects of cisplatin, with no added systemic toxicity. Taken together, our results suggest a potentially novel strategy to use YM155 to overcome the resistance in tumor cells, thereby enhancing the effectiveness of the chemotherapy in HNSCC.

Modification and comparison of minimally invasive cochleostomy techniques: A pilot study.

OBJECTIVES/HYPOTHESIS: Bimodal stimulation may offer improved auditory function following cochlear implantation. Modification of technique during cochleostomy may minimize trauma and maximize residual hearing. We hypothesize that CO(2) laser use during cochleostomy is useful and may decrease intracochlear trauma. This study examines the utility of CO(2) laser to perform cochleostomy and compares intracochlear sound and temperature levels during laser and drill usage. STUDY DESIGN: Experimental (30 cadaveric temporal bones). METHODS: A CO(2) laser at 3 W (four bones) and 6 W (four bones) and otologic drill (six bones) were utilized to perform a cochleostomy while recording operative time. Subsequently, 16 bones were used to simultaneously record intracochlear sound (in decibels) and temperature (in degrees Fahrenheit) during CO(2) laser (eight bones) and drill cochleostomies (eight bones). RESULTS: Average cochleostomy time for CO(2) laser was 15.5 minutes (3 W) and 7.75 minutes (6 W); it was 8 minutes for the drill. Average intracochlear sound level was 54.9 dB during laser use and 89.9 dB during drill use (P < .001), whereas maximal levels were 75 to 118 dB during laser use and 95 to 136 dB during drill use (P = .018). Average temperature was 63.4°F during laser use and 61.5°F during drill use (P = .151), whereas maximum temperatures ranged from 66 to 120°F during laser use and 62 to 70°F during drill use (P = .045). CONCLUSIONS: CO(2) laser can create cochleostomies comparable in operative time and intracochlear temperature to drilling while decreasing intracochlear sound levels. Further investigation is warranted to minimize trauma and maximize auditory function during cochleostomy.