Postoperative Chyle Leak Rate Following Neck Dissection for Squamous Cell Carcinoma Versus Papillary Thyroid Cancer.

OBJECTIVES: Compare the rates of post-operative chyle leak following therapeutic lateral neck dissection during treatment of papillary thyroid carcinoma (PTC) versus squamous cell carcinoma (SCC) of the head and neck. METHODS: A retrospective analysis of 226 consecutive neck dissections in 201 patients who underwent therapeutic neck dissection involving at least levels II-IV with a final pathologic diagnosis of mucosal SCC of the head and neck or PTC from 2010 to 2020. Specific cases of chyle leak were reviewed. Surgical factors associated with chyle leak were analyzed using logistic regression analysis. Duration of chyle leak was assessed by the Kaplan-Meier curve, and time-to-resolution was analyzed by Cox proportional hazard analysis. RESULTS: Postoperative chyle leak was encountered in 15 (6.6%) neck dissections, eight (12.3%) in PTC, and seven (4.3%) in SCC. High-volume chyle leak and chyle leak requiring operative intervention were only encountered in neck dissections performed for PTC. Chyle leak was significantly associated with PTC on univariable analysis (OR 3.08, p = 0.037), but not on multivariable analysis (OR 1.35, p = 0.711). High-volume chyle leak and the need for operative intervention were associated only with PTC patients (OR 23.6, p = 0.006; OR 18.09, p = 0.023 respectively). Median duration of chyle leak was 12.1 days among patients with SCC, and 20.5 days among patients with PTC (p = 0.089). CONCLUSIONS: Among 201 patients undergoing therapeutic neck dissection, chyle leak was associated with PTC pathology on univariable but not multivariable analysis. However, high-volume leaks and leaks requiring operative intervention only occurred among patients with PTC. LEVEL OF EVIDENCE: level III Laryngoscope, 133:2959-2964, 2023.

Occult Metastases During Salvage Oral Cavity and Oropharyngeal Free Flaps: Oncologic Outcomes.

OBJECTIVES: To define rates of occult metastases in salvage oral cavity and oropharyngeal cancer resection requiring free flap, to examine the location of occult metastases, and to determine associations between occult metastasis and survival. STUDY DESIGN: Retrospective cohort study. SETTING: Two tertiary care referral centers. METHODS: We identified previous cases of irradiation with recurrent or second primary oral cavity or oropharyngeal squamous cell carcinoma that had no evidence of regional metastasis and required free tissue transfer reconstruction of the primary site. Patients who underwent elective neck dissection or exploration were reviewed. The main outcome measures were the presence and location of occult nodal metastasis. Disease-free survival and overall survival were measured. Odds ratios and hazard ratios were used for analysis. RESULTS: A total of 83 patients were included: 52 with oral cavity primary tumors and 31 with oropharynx. An overall 78 (94%) underwent elective salvage neck dissection. Occult metastases were found in 9 (11.5%) patients. The most common nodal station for occult metastasis was level 2. Neither elective neck dissection nor the presence of occult metastasis was significantly associated with regional disease-free or overall survival. Oropharyngeal primary tumors were associated with higher risk of occult metastasis (odds ratio, 1.38; P < .01) and worse overall survival (hazard ratio, 2.09; P = .01). CONCLUSION: There is a low incidence of occult metastasis in postradiated recurrent or second primary oral cavity and oropharyngeal tumors. Elective neck dissection and occult nodal metastases were not associated with regional or overall survival. This series may help surgeons make decisions regarding the extent of neck surgery after prior radiation, especially when free flap reconstruction is required.

Effectiveness of gabapentin in reducing opioid requirements after radiation in head and neck cancer in a single institution.

BACKGROUND: Gabapentin has been shown to reduce opioid use in head and neck cancer patients. Here, we examine the efficacy of prophylactic gabapentin at reducing opioid use in these patients at our institution. METHODS: A retrospective study of patients receiving radiation was performed, using patients from our previous study as controls. Risk factors for opioid use at 3 and 6 months were determined using univariate and multivariate analyses. RESULTS: In total, 53/185 patients were treated with gabapentin, 39.6% of which took opioids at 3 months vs. 58.3% in the non-gabapentin cohort (p = 0.021). Gabapentin was independently associated with less opioid use on multivariate analysis at 3 months (OR 0.47, 95% CI 0.24-0.9). Gastrostomy tube dependence and pretreatment opioid use were associated with chronic opioid use despite gabapentin. CONCLUSIONS: Gabapentin is effective at expediting opioid tapering in head and neck cancer patients who are not gastrostomy tube dependent or taking opioids pretreatment.

Safety of the "incidental" neck dissection or exploration during free tissue transfer after head and neck irradiation.

IMPORTANCE: Patients with either local recurrence of head and neck cancer or osteoradionecrosis after prior radiation treatment often require free tissue transfer for optimal reconstruction. In this setting, neck exploration for vessels is necessary, and an "incidental" neck dissection is often accomplished despite clinically negative cervical lymph nodes. While neck surgery in the post-radiated setting is technically challenging, the safety of post-radiated elective neck dissection or neck exploration for vessels is not well-studied, especially for patients undergoing non-laryngectomy salvage resections. OBJECTIVE: To define intraoperative and postoperative surgical complications for patients undergoing elective neck dissection or exploration with free tissue transfer reconstruction in the post-radiated setting, with attention to complications from neck surgery. DESIGN: Retrospective cohort study. Patient charts from May 2005 to April 2020 were reviewed. SETTING: Tertiary care referral center. PARTICIPANTS: Patients underwent free tissue transfer after prior head and neck irradiation for non-laryngeal local cancer recurrence or second primary, osteoradionecrosis, or for sole reconstructive purposes. Patients with clinically positive neck disease were excluded. MAIN OUTCOMES AND MEASURES: Intraoperative and postoperative complications including unplanned vessel or nerve injury, hematoma, chyle leak, wound dehiscence, wound infection, fistula formation, flap failure, and perioperative medical complications. Neck exploration and neck dissection patient outcomes were compared by Fisher exact test. RESULTS: Seventy-two patients (56 men and 16 women) of average age sixty-one (range 34-89) were identified with average follow-up 25.7 months. Most patients (78%) underwent salvage neck dissection, and the rest underwent neck exploration for vessels only. There were five intraoperative neck complications: three vessel injuries and two nerve injuries. There were twenty-six postoperative surgical complications among eighteen patients. There was no difference in surgical complications whether patients underwent neck dissection or exploration only. Two partial and two complete flap failures occurred. There were nine perioperative medical complications among six patients. CONCLUSIONS AND RELEVANCE: Elective neck dissection or exploration among patients undergoing free tissue transfer in the post-radiated setting carries a risk of both intraoperative and postoperative surgical complications. The present study defines risk of complications and helps to inform patient discussions for risk of complications in the post-radiated setting.

Travel distance is associated with stage at presentation and laryngectomy rates among patients with laryngeal cancer.

BACKGROUND: The impact of travel distance on stage at presentation and management strategies of laryngeal squamous cell carcinoma (SCC) is unknown. We investigated this relationship. METHODS: Retrospective review of patients with laryngeal SCC in the National Cancer Data Base from 2004 to 2016. Multivariate analysis determined relationships between travel distance, sociodemographic, geographic, and hospital factors. Logistic regression determined the influence of travel distance on T-stage and overall stage at presentation, and receipt of total laryngectomy. RESULTS: Sixty thousand four hundred and thirty-nine patients were divided into groups based on distance to treatment: short (<12.5 miles); intermediate (12.5-49.9 miles); and long (>50 miles). Increased travel was associated with T4-stage (intermediate vs. short OR 1.11, CI 1.04-1.18, p = 0.001; long vs. short OR 1.5, CI 1.36-1.65, p < 0.001), and total laryngectomy (intermediate vs. short OR 1.40, CI 1.3-1.5, p ≤ 0.001; long vs. short OR 2.52, CI 2.28-2.79, p ≤ 0.001). In T4 disease, total laryngectomy was associated with improved survival compared to nonsurgical treatment (HR 0.75, CI 0.70-0.80, p < 0.001) regardless of travel distance. CONCLUSION: Longer travel distance to care is associated with increased stage at presentation, rate of laryngectomy, and improved survival in advanced laryngeal SCC. Health policy efforts should be directed towards improving early access to diagnosis and care.

Treatment of Cutaneous Melanoma of the Head and Neck With Wide Local Excision Versus Mohs.

OBJECTIVES: Determine if Mohs micrographic surgery (MMS) is associated with improved overall survival compared to wide local excision (WLE) when treating cutaneous melanoma of the head and neck (CMHN) and to report the proportion of patients treated with MMS versus WLE who also underwent sentinel lymph node biopsy (SLNB). METHODS: Retrospective cohort study of the National Cancer Database (NCDB) analyzing the overall survival of patients diagnosed with T1 to T4 CMHN between 2004 and 2016 who were treated with either WLE or MMS. RESULTS: On multivariable analysis, treatment with WLE versus MMS was not significantly associated with overall survival (HR, 1.094; 95% CI, 0.997-1.201). On multivariable analysis, lower Charlson-Deyo score (HR, 0.489; 95% CI, 0.427-0.560), negative margins (HR, 0.754; 95% CI, 0.705-0.807), and N0 classification (HR 0.698; 95% CI, 0.668-0.730) were associated with improved overall survival. Seventy-seven percent of patients treated with MMS did not undergo SLNB, while 45% of patients treated with WLE did not undergo SLNB (P < .001). CONCLUSIONS: No difference in overall survival between MMS and WLE when treating CMHN. Patients treated with MMS were significantly less likely to undergo SLNB, suggesting an opportunity for enhancement of multidisciplinary care. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2490-2496, 2021.

Positive Margins in Cutaneous Melanoma of the Head and Neck: Implications for Timing of Reconstruction.

OBJECTIVE: The aim of this study is to identify clinicopathologic features associated with positive margins after surgical treatment of cutaneous melanoma of the head and neck (CMHN). STUDY DESIGN: Retrospective cohort study. SETTING: National Cancer Database. METHODS: A retrospective analysis of the National Cancer Database was performed of patients diagnosed with CMHN between 2004 and 2016. Univariate and multivariate analyses examining the association of clinicopathologic features with positive margins were performed via logistic regression analysis. RESULTS: A total of 101,560 patients met inclusion criteria. The incidence of positive margins was 5.0% (5128/101,560). Patients were significantly more likely to have positive margins with the following: increasing age (P < .001; odds ratio [OR], 1.028; 95% CI, 1.026-1.031), the lip subsite (P < .001; OR, 1.664; 95% CI, 1.286-2.154), the eyelid subsite (P < .001; OR, 2.380; 95% CI, 1.996-2.838), the face subsite (P < .001; OR, 1.215; 95% CI, 1.133-1.302), the lentigo maligna/lentigo maligna melanoma subtype (P = .019; OR, 1.099; 95% CI, 1.016-1.188), the desmoplastic subtype (P < .001; OR, 1.455; 95% CI, 1.261-1.680), the spindle cell subtype (P = .006; OR, 1.276; 95% CI, 1.073-1.516), and advanced pT classification. Patients with male sex (P < .001; OR, 0.733; 95% CI, 0.687-0.782) and without ulceration (P < .001; OR, 0.803; 95% CI, 0.736-0.876) were significantly less likely to have positive margins. CONCLUSION: The following have been identified as clinicopathologic features associated with positive margins after surgical treatment of CMHN: increasing age, female sex, the lip subsite, the eyelid subsite, the face subsite, ulceration, the lentigo maligna/lentigo maligna melanoma subtype, the desmoplastic subtype, the spindle cell subtype, and increasing pT classification.

Implications of Tumor Size, Subsite, and Adjuvant Therapy on Outcomes in pT4aN0 Oral Cavity Carcinoma.

OBJECTIVE: To determine if tumor size, subsite, and adjuvant radiation therapy (AXRT) are associated with overall survival (OS) in patients with pT4aN0 oral cavity squamous cell carcinoma (OSCC) who underwent mandibulectomy with negative surgical margins (NSMs). STUDY DESIGN: Retrospective cohort study. SETTING: National Cancer Database (NCDB). SUBJECTS AND METHODS: Retrospective analysis of the NCDB that included patients diagnosed with pT4aN0 OSCC who underwent mandibulectomy with NSMs between 2004 and 2015. The association of age, Charlson-Deyo score (CDS), tumor size, subsite, and AXRT with OS was analyzed. The cases were divided into 3 subgroups based on maximal tumor dimension for subgroup analysis; tumors ≤2.0 cm, tumors 2.1 to 4.0 cm, and tumors >4.0 cm. RESULTS: For the entire cohort; age (P < .001; hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.02-1.03), CDS (P = .013; HR, 0.57; 95% CI, 0.37-0.89), tongue subsite (P = .003; HR, 2.01; 95% CI, 1.27-3.40), floor of mouth subsite (P = .001; HR, 1.76; 95% CI, 1.28-2.42), tumor size (P < .001; HR, 0.57; 95% CI, 0.45-0.72), and AXRT (P < .001; HR, 1.46; 95% CI, 1.24-1.72) were associated with OS on multivariate analysis. On subgroup analysis, AXRT not significantly associated with OS in patients with gingival, hard palate, retromolar trigone, and not specified tumors ≤2.0 cm (P = .323; HR, 1.29; 95% CI, 0.78-2.15). CONCLUSIONS: In patients with pT4aN0 OSCC who underwent mandibulectomy with NSMs, age, CDS, tongue subsite, floor of mouth subsite, tumor size, and AXRT are associated with OS. AXRT was not significantly associated with overall survival in patients with gingival, hard palate, retromolar trigone, and not specified tumors ≤2.0 cm.

Impact of PET/CT on Staging and Treatment of Advanced Head and Neck Squamous Cell Carcinoma.

OBJECTIVE: To understand the effects of positron emission tomography/computed tomography (PET/CT) evaluation on patients with previously untreated head and neck squamous cell carcinoma (HNSCC) with clinical evidence of regional lymph node involvement. STUDY DESIGN: Prospective blinded study. SETTING: Tertiary care cancer center. SUBJECTS AND METHODS: Informed consent was obtained and data collected from 52 consecutive previously untreated patients with HNSCC and clinical evidence of cervical metastasis. All patients underwent conventional evaluation for HNSCC and whole body PET/CT. Data were evaluated by 5 independent reviewers, who performed TNM staging per the American Joint Committee on Cancer (seventh edition) manual and proposed a treatment plan prior to viewing, and after reviewing, PET/CT. Cases where at least 3 of 5 reviewers agreed were considered significant. RESULTS: There were 0 patients for whom review of the PET/CT altered the T-class assessment (95% CI, 0-6.8), 12 (23.1%) for whom PET/CT altered N classification (95% CI, 12.5-34.5), and 2 (3.8%) for whom PET/CT altered the M classification (95% CI, 0.5-13.2). For 5 patients (9.6%), overall stage was altered per PET/CT review (95% CI, 3.2-21). For 3 patients (5.8%), PET/CT findings prompted reviewers to alter treatment recommendations (95% CI, 1.2-15.9). CONCLUSION: When added to more conventional patient evaluation, PET/CT results in changes to the TNM categories, but overall staging and treatment were less frequently affected. Whether PET/CT should be used routinely for patients with stage III and IV HNSCC is still subjective and merits further study.

Utility of Intraoperative Frozen Section in Large Thyroid Nodules.

OBJECTIVE: To determine if the routine use of intraoperative frozen section (iFS) results in cost savings among patients with nodules >4 cm with nonmalignant cytology undergoing a thyroid lobectomy. STUDY DESIGN: Case series with chart review; cost minimization analysis. SETTING: Single academic center. SUBJECTS AND METHODS: Records were reviewed on a consecutive sample of 48 patients with thyroid nodules >4 cm and nonmalignant cytology who were undergoing thyroid lobectomy in which iFS was performed between 2010 and 2015. A decision tree model of thyroid lobectomy with iFS was created. Comparative parameters were obtained from the literature. A cost minimization analysis was performed comparing lobectomy with and without iFS and the need for completion thyroidectomy with costs estimated according to 2014 data from Medicare, the Bureau of Labor Statistics, and the Nationwide Inpatient Sample. RESULTS: The overall malignancy rate was 25%, and 33% of these malignancies were identified intraoperatively. When the malignancy rates obtained from our cohort were applied, performing routine iFS was the less costly scenario, resulting in a savings of $486 per case. When the rate of malignancy identified on iFS was adjusted, obtaining iFS remained the less costly scenario as long as the rate of malignancies identified on iFS exceeded 12%. If patients with follicular lesions on cytology were excluded, 50% of malignancies were identified intraoperatively, resulting in a savings of $768 per case. CONCLUSIONS: For patients with nodules >4 cm who are undergoing a diagnostic lobectomy, the routine use of iFS may result in decreased health care utilization. Additional cost savings could be obtained if iFS is avoided among patients with follicular lesions.

Impact of perioperative hyperglycemia in patients undergoing microvascular reconstruction.

BACKGROUND: The effects of perioperative hyperglycemia on complications and outcomes in microvascular reconstruction have not been reported in the literature. METHODS: A retrospective cohort of 203 patients undergoing microvascular reconstruction was generated. Perioperative glucose levels and clinical factors were tested for associations with complications using simple and multivariate analyses. RESULTS: Hyperglycemia (blood glucose ≥ 180 mg/dL) occurred in 91 patients (44.8%) perioperatively, and was associated with increased rates of surgical complications, medical complications, surgical site infections, fistulas, and wound dehiscence. On univariate analysis, a more strict definition of hyperglycemia (blood glucose ≥ 165 mg/dL) was significantly associated with greater rates of venous thrombosis, although this lost statistical significance on multivariate analysis. CONCLUSION: Perioperative hyperglycemia occurs commonly in patients undergoing microvascular reconstruction and is associated with higher rates of complications, independent of a preexisting diagnosis of diabetes mellitus. Further research is needed to define the ideal glycemic target in this population.

Economic Impact of Frozen Section for Thyroid Nodules with "Suspicious for Malignancy" Cytology.

Objective To perform a cost analysis of the routine use of intraoperative frozen section (iFS) among patients undergoing a thyroid lobectomy with "suspicious for malignancy" (SUSP) cytology in the context of the 2015 American Thyroid Association guidelines. Study Design Case series with chart review; cost minimization analysis. Setting Academic. Subjects and Methods Records were reviewed for patients with SUSP cytology who underwent thyroid surgery between 2010 and 2015 in which iFS was utilized. The diagnostic test performance of iFS and the frequency of indicated completion/total thyroidectomies based on the 2015 guidelines were calculated. A cost minimization analysis was performed comparing lobectomy, with and without iFS, and the need for completion thyroidectomy according to costs estimated from 2014 data from Medicare, the Bureau of Labor Statistics, and the Nationwide Inpatient Sample. Results Sixty-five patients met inclusion criteria. The malignancy rate was 61.5%, 45% of which was identified intraoperatively. The specificity and positive predictive value were 100%. The negative predictive value and sensitivity were 83% and 95%, respectively. Completion/total thyroidectomy was indicated for 9% of patients; 83% of these individuals had findings on iFS that would have changed management intraoperatively. Application of the new guidelines would have resulted in a significant reduction in the frequency of conversion to a total thyroidectomy when compared with the actual management (26.1% vs 7.7%, P = .005). Performing routine iFS was the less costly scenario, resulting in a savings of $474 per case. Conclusion For patients with SUSP cytology undergoing lobectomy, routine use of iFS would result in decreased health care utilization.

The futility of intraoperative frozen section in the evaluation of follicular thyroid lesions.

OBJECTIVE: Investigate the utility of intraoperative frozen section (iFS) in patients with follicular thyroid lesions following publication of the 2015 American Thyroid Association (ATA) guidelines. STUDY DESIGN: Retrospective chart review. METHODS: Patient demographics, preoperative cytology, frozen pathology, and final pathology were reviewed on patients undergoing thyroid surgery at a tertiary care hospital in which iFS was utilized over a 5-year period. The test performance of iFS and the frequency of indicated completion/total thyroidectomies pre- and postpublication of the 2015 ATA guidelines were calculated. RESULTS: One hundred and one patients met inclusion criteria: 54 patients with follicular lesions of undetermined significance (FLUS) and 47 patients with a cytologic diagnosis of suspicious for follicular neoplasm/follicular neoplasm. The malignancy rate was 36%, but only 14% of malignancies were identified on iFS. A definitive benign or malignant diagnosis was given on iFS in only 21% of cases, and operative management was altered in two cases as a result of iFS. There was a statistically significant reduction in the frequency of indicated total/completion thyroidectomies based on high-risk features as a result of the 2015 ATA guidelines compared to prior recommendations (20.8% vs. 5.0%, P = < 0.001). None of these patients had findings on iFS that would have altered management intraoperatively. CONCLUSION: Intraoperative frozen section offers minimal diagnostic utility in the evaluation of follicular thyroid lesions. Updates in the 2015 ATA guidelines further diminish its potential to impact management intraoperatively. Significant improvements in its ability to identify malignancies would be needed to justify its use. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:1501-1505, 2018.

Immunoselected STRO-3+ mesenchymal precursor cells reduce inflammation and improve clinical outcomes in a large animal model of monoarthritis.

BACKGROUND: The purpose of this study was to investigate the therapeutic efficacy of intravenously administered immunoselected STRO-3 + mesenchymal precursor cells (MPCs) on clinical scores, joint pathology and cytokine production in an ovine model of monoarthritis. METHODS: Monoarthritis was established in 16 adult merino sheep by administration of bovine type II collagen into the left hock joint following initial sensitization to this antigen. After 24 h, sheep were administered either 150 million allogeneic ovine MPCs (n = 8) or saline (n = 8) intravenously (IV). Lameness, joint swelling and pain were monitored and blood samples for leukocytes and cytokine levels were collected at intervals following arthritis induction. Animals were necropsied 14 days after arthritis induction and gross and histopathological evaluations were undertaken on tissues from the arthritic (left) and contralateral (right) joints. RESULTS: MPC-treated sheep demonstrated significantly reduced clinical signs of lameness, joint pain and swelling compared with saline controls. They also showed decreased cartilage erosions, synovial stromal cell activation and angiogenesis. This was accompanied by decreased infiltration of the synovial tissues by CD4+ lymphocytes and CD14+ monocytes/macrophages. Over the 3 days following joint arthropathy induction, the numbers of neutrophils circulating in the blood and plasma concentrations of activin A were significantly reduced in animals administered MPCs. CONCLUSIONS: The results of this study have demonstrated the capacity of IV-administered MPCs to mitigate the clinical signs and some of the inflammatory mediators responsible for joint tissue destruction in a large animal model of monoarthritis.

Effect of mesenchymal precursor cells on the systemic inflammatory response and endothelial dysfunction in an ovine model of collagen-induced arthritis.

BACKGROUND AND AIM: Mesenchymal precursor cells (MPC) are reported to possess immunomodulatory properties that may prove beneficial in autoimmune and other inflammatory conditions. However, their mechanism of action is poorly understood. A collagen-induced arthritis model has been previously developed which demonstrates local joint inflammation and systemic inflammatory changes. These include not only increased levels of inflammatory markers, but also vascular endothelial cell dysfunction, characterised by reduced endothelium-dependent vasodilation. This study aimed to characterise the changes in systemic inflammatory markers and endothelial function following the intravenous administration of MPC, in the ovine model. METHODS: Arthritis was induced in sixteen adult sheep by administration of bovine type II collagen into the hock joint following initial sensitisation. After 24h, sheep were administered either 150 million allogeneic ovine MPCs intravenously, or saline only. Fibrinogen and serum amyloid-A were measured in plasma to assess systemic inflammation, along with pro-inflammatory and anti-inflammatory cytokines. Animals were necropsied two weeks following arthritis induction. Coronary and digital arterial segments were mounted in a Mulvaney-Halpern wire myograph. The relaxant response to endothelium-dependent and endothelium-independent vasodilators was used to assess endothelial dysfunction. RESULTS AND CONCLUSION: Arthritic sheep treated with MPC demonstrated a marked spike in plasma IL-10, 24h following MPC administration. They also showed significantly reduced plasma levels of the inflammatory markers, fibrinogen and serum amyloid A, and increased HDL. Coronary arteries from RA sheep treated with MPCs demonstrated a significantly greater maximal relaxation to bradykinin when compared to untreated RA sheep (253.6 ± 17.1% of pre-contracted tone vs. 182.3 ± 27.3% in controls), and digital arteries also demonstrated greater endothelium-dependent vasodilation. This study demonstrated that MPCs given intravenously are able to attenuate systemic inflammatory changes associated with a monoarthritis, including the development of endothelial dysfunction.

Endothelial dysfunction in an ovine model of collagen-induced arthritis.

BACKGROUND: Rheumatoid arthritis (RA) induces systemic inflammation, producing a range of co-morbidities including cardiovascular disease. An early vascular change is endothelial dysfunction, characterized by reduced endothelium-dependent vasodilation. The aim of this study was to assess endothelial function in isolated coronary and digital arteries using an ovine model of collagen-induced RA. METHODS: Sheep were culled following induction of arthritis, and their endothelial function was compared to that of normal sheep. Paired arterial segments were mounted in a wire myograph and dilated with endothelium-dependent vasodilators [bradykinin, serotonin, carbachol and adenosine diphosphate (ADP); linked to either Gi or Gq signalling pathways] and endothelium-independent dilators (adenosine and sodium nitroprusside) to construct cumulative concentration-response curves. RESULTS: Coronary arteries from arthritic sheep exhibited a significantly greater EC50 value for bradykinin-induced relaxation compared to non-arthritic controls (2.9 × 10(-8) M for arthritic sheep vs. 8.6 × 10(-9) M for controls). Digital arteries from arthritic sheep also exhibited a significantly greater EC50 for relaxation to ADP and a significant decrease in the carbachol maximal response. Responses to sodium nitroprusside were unchanged in both coronary and digital arteries. CONCLUSION: Sheep with RA demonstrated attenuated arterial relaxation to endothelium-dependent vasodilators. This may provide a useful model of endothelial dysfunction in chronic inflammatory conditions. The dysfunction did not appear to be associated with one specific G-protein signalling pathway.

Treatment outcome in the residually positive neck after definitive chemotherapy and irradiation.

OBJECTIVE: Determine prevalence of viable malignancy in patients undergoing neck dissection (ND) for residual neck disease following concomitant chemotherapy and irradiation (chemo/xrt) for upper aerodigestive squamous carcinoma. To determine survival in groups with a neck complete response to those who had residual disease requiring neck dissection. STUDY DESIGN: Retrospective chart review. METHODS: Retrospective chart review of 230 patients who underwent definitive chemo/xrt for primary squamous cell carcinoma cancer (SCCa) of the head and neck from 2005 to 2009 in one institution. RESULTS: Thirty-nine (17%) patients underwent ND for residual neck mass within 4 months posttreatment. Forty-nine percent (19/39) were pathologically positive for malignancy and 51% (20/39) were negative. The probability of a +ND based on original N-stage was not statistically significant (P = .368). Primary site did not yield significant probability of having +ND, except in the oral cavity (P = .02). Patients had similar overall 5-year survival, among those with a delayed complete response in the neck (66%), ND for residual disease (71%), or those with initial complete response (71%). Lower initial N-stage demonstrated improved survival in all outcome groups. Tonsil SCCa patients who underwent ND had improved survival compared to those with delayed complete response (87.5 vs. 75.8%), both of which had increased survival compared to initial complete responders (65%). CONCLUSIONS: This study supports the use of ND in the postchemo/xrt positive neck regardless of primary site or initial N-stage. ND in this setting conveys survival equal to patients with complete response in the neck after chemo/xrt. These survivorship implications of postchemo/xrt neck dissection extend to all sites, including tonsils.