Faculty Bibliography

OBJECTIVES/HYPOTHESIS/OBJECTIVE:To determine if a long segment of trachea can be transplanted as a vascularized organ and to determine if a tracheal transplant is a potential surgical option for a long-segment circumferential tracheal defect. STUDY DESIGN/METHODS:Animal model. METHODS:Four (two donors and two recipients) adult domestic Yorkshire swine were used. Two sets of transplants were performed from a donor to recipient pig. The transplant was placed heterotopically (not in continuity with the airway), and the recipient animals were monitored for 14 days to ensure the transplants were well vascularized. Immunosuppressive therapies included methylprednisolone, cyclosporine, and azathioprine. Gross as well as histological examination of multiple tissues types including mucosa, cartilage, muscle, and blood vessels were performed postsacrifice on day 14. RESULTS:Recipient animal weights ranged from 40 to 42 kilograms. Both recipient pigs survived the full 14 days of study and exhibited normal activity and appetite. Ischemia time of transplanted grafts ranged from 63 to 72 minutes. Transplanted tracheas included a minimum of 15 cartilaginous rings and measured greater than 10 cm in length. Both grafts maintained a robust blood supply throughout the duration of study. CONCLUSIONS:The entire visceral compartment can be reliably transplanted, either as a single component (trachea) or as a chimeric flap with multiple components (trachea, esophagus, larynx, and pharynx). Further studies in the swine model should be considered to study the effects of transplanting the trachea orthotopically into the native airway. Further studies are needed into the reliability of this technique of transplantation in humans. LEVEL OF EVIDENCE/METHODS:NA Laryngoscope, 128:S1-S9, 2018.

PURPOSE: Squamous cell carcinoma of unknown primary (SCCHNUP) is commonly treated with comprehensive radiation to the laryngopharynx and bilateral necks. In 1998, we established a departmental policy to treat SCCHNUP with radiation directed to the oropharynx and bilateral neck. METHODS: From 1998-2011, 60 patients were treated - N1: 18%, N2: 75% and N3: 7%. 82% underwent neck dissection. 55% received IMRT and 62% underwent concurrent chemoradiotherapy. RESULTS: At median follow-up of 54months, 5 patients failed regionally and 4 emerged with a primary (tongue base, hypopharynx and thoracic esophagus). Five-year rates of regional control, primary emergence, distant metastasis, disease-free survival and overall survival were 90%, 10%, 20%, 72% and 79%, respectively. The 5year rate of primary emergence in a non-oropharynx site was 3%. CONCLUSION: This is the first demonstration that an oropharynx-directed approach yields low rates of primary emergence in SCCHNUP with excellent oncologic outcomes.

BACKGROUND: Unilateral radiotherapy (RT) of oropharyngeal carcinomas is accepted for patients with lateralized primary and low-volume nodal disease. Utilizing prospectively defined criteria of laterality and staging positron emission tomography (PET)/CT, we studied outcomes in patients with advanced-stage oropharyngeal cancer undergoing unilateral RT. METHODS: Thirty-seven patients with oropharyngeal tumors >1 cm from midline regardless of node status underwent unilateral RT and were followed prospectively. Patient characteristics: T1 = 11; T2 = 22; T3 = 4; N0 = 3; N1 = 9; N2a = 3; N2b = 21; and Nx = 1. Dosimetry were determined and weekly National Comprehensive Cancer Network (NCCN) distress thermometer data were collected. RESULTS: At median follow-up of 32 months, 3-year locoregional control, contralateral regional failure, distant metastasis-free survival, and disease-free survival were 96%, 0%, 7%, and 93%, respectively. CONCLUSION: Low rates of contralateral neck failure are demonstrated utilizing prospectively defined criteria for unilateral RT. The tolerances of contralateral organs are respected and patients report low to moderate levels of distress throughout treatment.

Background - The use of bridge therapy with low-molecular-weight heparin during warfarin interruption for elective surgical and invasive diagnostic procedures leads to excess bleeding compared to interrupting warfarin alone. Other predictors of periprocedural bleeding during warfarin interruption are not well described. Aims - The purpose of this analysis was to identify predictors of major bleeding during and within 37 days after warfarin interruption for invasive procedures. Methods - BRIDGE was a double-blind, placebo controlled trial that randomized patients with atrial fibrillation requiring warfarin interruption to either bridge therapy with dalteparin 100IU/kg every 12 hours or matching placebo injections. Bleeding and thromboembolic outcomes were collected up to 37 days after the procedure. Multiple logistic regression models were used for baseline prediction of major bleeding. Time-dependent hazard models were used to add the effect of concomitant variables such as aspirin use and elevated INR values. Results - Nine hundred and fifty patients were assigned to placebo and 934 to dalteparin. Aspirin use at baseline was identified in 34.7% of the cohort (n=653) of which 60.5% (n=395) continued uninterrupted throughout the study period. The majority of procedures (89.4%) were considered low bleeding risk based on the planned surgical procedure. The median time to major bleeding was 7.0 days after surgery (interquartile range 4.0 to 18.0). Dalteparin administration was a baseline predictor of major bleeding (Odds Ratio (OR) = 2.5; 95% Confidence Interval (CI) 1.2-5.0, p=0.01), as was history of heart failure (OR=1.9; 95% CI 1.0-3.5, p=0.04) and major surgery (versus minor procedure) (OR=2.5; 95% CI 1.2-5.3, p=0.02). The current use of aspirin (OR=4.6; 95% CI 1.6-13.0, p=0.007) was significant as a time-dependent predictor of major bleeding. The presence of an elevated INR value (above 3.0) was not found to be significant when aspirin use was included in the model. Several factors known to contribute to bleeding risk during chronic anticoagulation were not found to predict bleeding around invasive procedures including age, history of hypertension, and history of gastrointestinal bleeding. The effect of history of diabetes, history of vascular disease, and gender were also evaluated but likewise these factors were not found to be significant predictors of bleeding. Conclusions - Major surgery, a history of heart failure and aspirin increase the risk of major bleeding during surgical and invasive diagnostic procedures requiring warfarin interruption. The risk and benefit of aspirin use during invasive procedures should be carefully assessed to minimize bleeding risk in this setting

Hypocalcemia is a well-known complication of total thyroidectomy. Patients who have previously undergone gastric bypass surgery may be at increased risk of hypocalcemia due to gastrointestinal malabsorption, secondary hyperparathyroidism, and an underlying vitamin D deficiency. We present the case of a 58-year-old woman who underwent a total thyroidectomy for the follicular variant of papillary thyroid carcinoma. Her history included Roux-en-Y gastric bypass surgery. Following the thyroid surgery, she developed postoperative hypocalcemia that required large doses of oral calcium carbonate (7.5 g/day), oral calcitriol (up to 4 mug/day), intravenous calcium gluconate (2.0 g/day), calcium citrate (2.0 g/day), and ergocalciferol (50,000 IU/day). Her serum calcium levels remained normal on this regimen after hospital discharge despite persistent hypoparathyroidism. Bariatric surgery patients who undergo thyroid surgery require aggressive supplementation to maintain normal serum calcium levels. Preoperative supplementation with calcium and vitamin D is strongly recommended.