The Effect of Proximal Row Carpectomy and Trapeziectomy on First Ray Stability: A Cadaveric Study.

PURPOSE: Wrist and thumb pathology can coexist leading to potential indications for proximal row carpectomy (PRC) and trapeziectomy. In this setting, the axial stability of the first ray is not known. We sought to evaluate axial subsidence of the first metacarpal in cadavers following trapeziectomy and trapeziectomy with PRC to determine the mechanical effects of the procedures performed concurrently. METHODS: Eleven fresh-frozen cadaveric distal forearm specimens were used in this study. The specimens were fixed in cement and mounted to a material test system frame. A predetermined force (20 N) was applied to the thumb metacarpal to simulate forces observed with lateral pinch. Axial displacement of the thumb metacarpal was measured. The application of force was repeated following trapeziectomy on each hand and then again following PRC. Analysis was performed to compare thumb metacarpal subsidence of the 3 groups: native, trapeziectomy, and trapeziectomy with PRC. RESULTS: Before trapeziectomy, native cadaver specimens had an average of 5.1 ± 1.9 mm of thumb metacarpal subsidence under the material test system load (20 N), compared to 16.2 ± 3.4 mm following trapeziectomy, and 25.0 ± 5.5 mm for trapeziectomy with PRC. CONCLUSION: We observed a significant increase in thumb metacarpal subsidence following concurrent trapeziectomy with PRC when compared to trapeziectomy alone. Our results suggest that performing both operations together would lead to a substantial risk of first ray subsidence. CLINICAL RELEVANCE: When treating concurrent basilar thumb and wrist arthritis, it may be more effective to stage the procedures or use a form of thumb metacarpal suspension or arthrodesis.

Preclinical evidence for pioglitazone and bexarotene combination in oral cancer chemoprevention.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) requires new treatments and targeted approaches to improve survival. The peroxisome proliferator-activated receptor γ (PPARγ) and retinoic X receptor alpha (RXRα) nuclear receptor pathways may be targetable with repurposed Food and Drug Administration (FDA)-approved agents for prevention and treatment. METHODS: Oral cancer and leukoplakia cell lines were treated with the PPARγ agonist (pioglitazone) and RXRα activator (bexarotene). PPARγ activation, cellular proliferation, apoptosis activity and phenotype, including the pharmacodynamic marker, involucrin (IVL), were subsequently analyzed using a reporter gene assay, genomic data, MTT assay and western blot. RESULTS: Microarray analysis of HNSCC tumor versus normal tissue shows IVL expression is significantly increased in normal tissue compared to HNSCC tumors (p < 0.0001). In MSK Leuk1 and CA 9-22 cell lines, pioglitazone increases PPARγ DNA binding activity and IVL promoter activity in a dose dependent manner (p < 0.01 and p < 0.0001). Combination treatment with pioglitazone and bexarotene increases PPARγ DNA binding activity and IVL promoter activity (p < 0.01 and p < 0.0001). MTT analysis shows decreases in cell proliferation when cells are treated with pioglitazone and bexarotene. Decreases in cell proliferation are significant to at least p < 0.05 for all combination versus single agent treatments. Western blot on whole-cell lysate from cells treated with pioglitazone and bexarotene alone or in combination for IVL showed increased protein levels with combination treatment. CONCLUSIONS: Targeting the PPARγ/RXRα heterodimer with pioglitazone and bexarotene was effective in this preclinical project. This was functional in both preneoplastic and oral cancer cell lines. A better understanding of the molecular mechanism on downstream effects on cellular proliferation could potentially have implications clinically, both in oral preneoplasia and possibly head and neck cancer; however, more research needs to be done to explore the potential these medications have in chemoprevention.

Survival and Gastrostomy Prevalence in Patients With Oropharyngeal Cancer Treated With Transoral Robotic Surgery vs Chemoradiotherapy.

IMPORTANCE: Treatment of oropharyngeal squamous cell carcinoma (OPSCC) presents unique challenges and can be associated with significant morbidity. Transoral robotic surgery (TORS) has emerged as a treatment modality for OPSCC, but data comparing outcomes between patients treated with TORS-based therapy and nonsurgical therapy are limited. OBJECTIVE: To compare survival and gastrostomy prevalence between patients with OPSCC treated with TORS-based therapy and those treated with nonsurgical therapy. DESIGN, SETTING, AND PARTICIPANTS: This retrospective matched-cohort study identified patients with OPSCC treated at the University of Washington and University of Minnesota tertiary care medical centers from January 1, 2005, to December 31, 2013. Each patient treated with TORS-based therapy was matched by stage with as many as 3 patients treated with nonsurgical therapy. Final follow-up was completed on April 1, 2015. MAIN OUTCOMES AND MEASURES: Disease-free survival, overall survival, and gastrostomy tube prevalence. RESULTS: One hundred twenty-seven patients met the study criteria (113 men [89.0%]; 14 women [11.0%]; median [interquartile range] age, 57 [52-63] years); 39 patients who underwent TORS were matched to 88 patients who underwent nonsurgical therapy. Compared with the nonsurgical group, more patients had p16-positive tumors in the TORS group (30 of 31 [96.8%] vs 30 of 37 [81.1%] among patients with known p16 status). No statistically significant difference in survival between treatment groups was found in multivariable analysis (disease-free survival hazard ratio, 0.22; 95% CI, 0.04-1.36; P = .10). Patients who received TORS-based therapy had lower gastrostomy tube prevalence after treatment (13 of 39 [33.3%] vs 74 of 88 [84.1%]) for a univariable relative risk of 0.43 (95% CI, 0.27-0.67; P < .001) and a multivariable relative risk of 0.43 (95% CI, 0.27-0.68; P < .001). Gastrostomy prevalence decreased by time after treatment for both groups (TORS group: 3 of 34 [9%] at 3 months to 1 of 33 [3%] at 12 months; nonsurgical group: 37 of 82 [45%] at 3 months to 7 of 66 [11%] at 12 months). CONCLUSIONS AND RELEVANCE: Patients undergoing TORS for OPSCC have statistically indistinguishable survival but lower gastrostomy prevalence compared with patients undergoing nonsurgical therapy for stage-matched OPSCC. TORS offers promise for improved swallowing function in patients with OPSCC.