Vitamin D favorably alters the cancer promoting prostaglandin cascade.

BACKGROUND: Preclinical studies suggest that 1,25-dihydroxyvitamin D [1,25(OH)2D] and celecoxib inhibit prostaglandins (PGs) associated with cancer through different mechanisms. We determined if there was synergy in their use. PATIENTS AND METHODS: A total of 36 healthy women received daily for one month/menstrual cycle: placebo, 400 international units (IU) vitamin D-3, 2,000 IU vitamin D-3, or 2,000 IU vitamin D-3 plus 400 mg celecoxib. Serum and nipple aspirate fluid (NAF) were analyzed for PGE2 and transforming growth factor (TGF)ß1 and -2; serum for 25(OH)D (total, -D-2, -D-3), plasma for celecoxib; and mammary duct RNA for cyclooxygenase (COX)2. RESULTS: 25(OH)D-3 increased (p<0.01) only in the groups receiving 2,000 IU vitamin D-3. PGE2 decreased in the breast (p=0.01) only after receiving 2,000 IU vitamin D-3; 2,000 IU vitamin D-3 alone was more effective in decreasing PGE2 than 2,000 IU vitamin D-3 plus celecoxib (p=0.018). COX2 expression decreased only in the breasts of women taking 2,000 IU vitamin D-3. Change in circulating 25(OH)D-3 correlated with change in TGFß2 in the breast. CONCLUSION: Vitamin D-3 reduces the PG cascade and increases TGFß2 in a dose-dependent fashion. Adding celecoxib did not provide synergy.

Transoral robotic resection and reconstruction for head and neck cancer.

OBJECTIVES/HYPOTHESIS: To evaluate the patterns of failure, survival, and functional outcomes for patients treated with transoral robotic surgery (TORS) and compare these results with those from a cohort of patients treated with concurrent chemoradiation (CRT). STUDY DESIGN: Prospective non-randomized case control study. METHODS: Between April 2007 and April 2009, 30 patients with head and neck squamous cell carcinoma were treated with primary TORS and adjuvant therapy as indicated on an institutional review board-approved protocol. Patients were evaluated before treatment, after treatment, and at subsequent 3-month intervals after completing treatment to determine their disease and head and neck-specific functional status using the Performance Status Scale for Head and Neck Cancer and the Functional Oral Intake Score (FOIS). Functional scores were compared to a matched group of head and neck patients treated with primary CRT. RESULTS: The TORS patient population included 73% stage III-IV and 23% nonsmokers. The median follow-up was 20.4 months (range, 12.8-39.6 months). The 18-month locoregional control, distant control, disease-free survival, and overall survival were 91%, 93%, 78%, and 90%, respectively. Compared to the primary CRT group, TORS was associated with better short-term eating ability (72 vs. 43, P = .008), diet (43 vs. 25, P = .01), and FOIS (5.5 vs. 3.3, P < .001) at 2 weeks after completion of treatment. In contrast to TORS patients who returned to baseline, the CRT group continued to have decreased diet (P = .03) and FOIS (P = .02) at 12 months. CONCLUSIONS: Our early experience in treating selected head and neck cancers with TORS is associated with excellent oncologic and functional outcomes that compare favorably to primary CRT.

The role of reconstruction for transoral robotic pharyngectomy and concomitant neck dissection.

OBJECTIVE: To evaluate the impact of primary reconstruction of postablative defects following transoral robotic surgery on function and the risk of orocutaneous fistula. DESIGN: Prospective nonrandomized clinical trial. SETTING: Tertiary academic medical center. PATIENTS: Thirty-one patients treated with transoral robotic pharyngectomy for malignant disease. Each case was analyzed for patient age, sex, primary site of the tumor, pathologic characteristics, stage of disease, complications, fistula rate, and functional outcomes. Functional outcomes were assessed using the Performance Status Scale for Head and Neck Cancer Patients and the Functional Oral Intake Scale. INTERVENTIONS: In 25 patients, the primary treatment was with transoral robotic pharyngectomy, and 6 cases were salvage procedures performed for recurrent disease following radiation (3 patients) or chemoradiation (3 patients). Twenty-six patients underwent a concomitant unilateral selective neck dissection, and 3 patients underwent concomitant bilateral selective neck dissections; 2 patients did not require a neck dissection for treatment of the primary malignant tumor. MAIN OUTCOME MEASURES: Complication rate, fistula rate, and oral function. RESULTS: Primary intraoral reconstruction was performed in all 31 patients. Musculomucosal advancement flap pharyngoplasty was performed in 25 patients with a concomitant velopharyngopasty (6 patients), and radial forearm free flap reconstruction was performed in 6 patients. There were no intraoperative complications; however, postoperatively, 1 patient developed a neck hematoma that was treated with bedside drainage and 4 patients sustained minor musculomucosal flap necrosis of the superior aspect of the flap. None of the patients developed a neck infection of salivary fistula. Endoscopic evaluation of swallowing demonstrated that none of the patients experienced aspiration or velopharyngeal reflux, and the performance Status Scale for Head and Neck Cancer Patients and the Functional Oral Intake Scale at 2 weeks, 2 months, 6 months, 9 months, and 1 year demonstrated a progressive improvement in diet, swallowing, and oral function. CONCLUSIONS: Primary transoral robotic reconstruction may provide a benefit by decreasing the fistula rate in patients undergoing concomitant neck dissection. Patients regain excellent function following surgery and adjuvant therapy.