Joshua D. Waltonen

Nitric oxide: Perspectives and emerging studies of a well known cytotoxin

The free radical nitric oxide (NO•) is known to play a dual role in human physiology and pathophysiology. At low levels, NO• can protect cells; however, at higher levels, NO• is a known cytotoxin, having been implicated in tumor angiogenesis and progression. While the majority of research devoted to understanding the role of NO• in cancer has to date been tissue-specific, we herein review underlying commonalities of NO• which may well exist among tumors arising from a variety of different sites. We also discuss the role of NO• in human physiology and pathophysiology, including the very important relationship between NO• and the glutathione-transferases, a class of protective enzymes involved in cellular protection. The emerging role of NO• in three main areas of epigenetics—DNA methylation, microRNAs, and histone modifications—is then discussed. Finally, we describe the recent development of a model cell line system in which human tumor cell lines were adapted to high NO• (HNO) levels. We anticipate that these HNO cell lines will serve as a useful tool in the ongoing efforts to better understand the role of NO• in cancer.

Parathyroid hormone early percent change: an individualized approach to predict postthyroidectomy hypocalcemia☆

PURPOSE The purpose of this study is to evaluate a percent change model of postoperative parathyroid hormone level in thyroidectomy patients as a predictor of hypocalcemia. MATERIALS AND METHODS Chart review was completed on patients who had undergone total or completion thyroidectomy over a 22-month period in our department. Only those patients with a preoperative ionized calcium and parathyroid hormone (PTH) level and at least 1 postoperative result were included. Ionized calcium levels served as an internal control. The Student t test was used to compare PTH level between the normocalcemic and hypocalcemic groups at each time point. Logistic regression analysis was used to predict hypocalcemia based on the diagnostic criteria. Receiver operator curves were used to maximize sensitivity. RESULTS Fifty-two patients met the inclusion criteria during the study period. A total of 22 patients (42%) experienced hypocalcemia. We were unable to maximize both sensitivity and specificity at the same time point. When comparing preoperative to 6-hour postoperative PTH percent change, patients with a greater than 44% decrease are likely to have hypocalcemia, with a sensitivity of 100%. Likewise, in those patients without a greater than 44% decrease at 6 hours, early discharge can be considered safe, given the negative predictive value of 100%. CONCLUSION In our series, patients with a greater than 44% PTH decrease from preoperative to 6-hour postoperative are very likely to develop hypocalcemia. We would propose that these patients need further inpatient monitoring to progress to safe discharge. Likewise, patients with a less than 44% decrease at the 6-hour time point are unlikely to develop hypocalcemia and may be considered safe for discharge.

Disposition of Elderly Patients After Head and Neck Reconstruction

IMPORTANCE A patients needs at discharge, particularly the need for nursing facility placement, may affect hospital length of stay and health care costs. The association between age and disposition after microvascular reconstruction of the head and neck has yet to be reported in the literature. OBJECTIVE To determine whether elderly patients are more likely to be discharged to a nursing or other care facility as opposed to returning home after microvascular reconstruction of the head and neck. DESIGN, SETTING, AND PARTICIPANTS From January 1, 2001, through December 31, 2010, patients undergoing microvascular reconstruction at an academic medical center were identified and their medical records systematically reviewed. During the study period, 457 patients were identified by Current Procedural Terminology codes for microvascular free tissue transfer for a head and neck defect regardless of cause. Seven patients were excluded for inadequate data on the postoperative disposition or American Society of Anesthesiologists (ASA) score. A total of 450 were included for analysis. MAIN OUTCOMES AND MEASURES Demographic and surgical data were collected, including the patient age, ASA score, and postoperative length of stay. These variables were then compared between groups of patients discharged to different posthospitalization care facilities. RESULTS The mean age of participants was 59.1 years. Most patients (n = 386 [85.8%]) were discharged home with or without home health services. The mean age of those discharged home was 57.5 years; discharge to home was the reference for comparison and odds ratio (OR) calculation. For those discharged to a skilled nursing facility, mean age was 67.1 years (OR, 1.055; P < .001). Mean age of those discharged to a long-term acute care facility was 71.5 years (OR, 1.092; P = .002). Length of stay also affected the disposition to a skilled nursing facility (OR, 1.098), as did the ASA score (OR, 2.988). CONCLUSIONS AND RELEVANCE Elderly patients are less likely to be discharged home after free flap reconstruction. Age, ASA score, and length of stay are independent factors for discharge to a nursing or other care facility.

Retrospective analysis of the impact of HPV status and smoking on mucositis in patients with oropharyngeal squamous cell carcinoma treated with concurrent chemotherapy and radiotherapy

OBJECTIVES The standard concurrent radiotherapy and chemotherapy regimens for patients with oropharyngeal cancer are highly toxic. Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) has recently emerged as a distinct biological and clinical entity with improved response to treatment and prognosis. A tailored therapeutic approach is needed to optimize patient care. The aim of our study was to investigate the impact of HPV and smoking status on early toxicities (primarily mucositis) associated with concurrent chemotherapy and radiotherapy in patients with OPSCC. MATERIALS AND METHODS We retrospectively evaluated 72 consecutive patients with OPSCC and known HPV status treated with concurrent radiotherapy and chemotherapy at our institution. Treatment-related toxicities were stratified by smoking and HPV status and compared using univariate and multivariate logistic regression. RESULTS HPV-positive patients had a 6.86-fold increase in the risk of having severe, grade 3-4 mucositis. This effect was preserved after adjusting for patient smoking status, nodal stage, radiotherapy technique and radiotherapy maximum dose. Additionally, HPV status had significant effect on the objective weight loss during treatment and at three months after treatment. Consistently, non-smokers had a significant 2.70-fold increase in the risk of developing severe mucositis. CONCLUSION Risk factors for OPSCC modify the incidence of treatment-related early toxicities, with HPV-positive and non-smoking status correlating with increased risk of high grade mucositis and associated outcomes. Retrospective single-institution studies need to be interpreted cautiously. However, this finding is important to consider when designing therapeutic strategies for HPV-positive patients and merits further investigation in prospective clinical trials.

Insurance status as a predictor of mortality in patients undergoing head and neck cancer surgery

Explore relationship between insurance status and survival, determine outcomes that vary based on insurance status, and identify potential areas of intervention.

The association between gastrostomy tube placement, poor post-operative outcomes, and hospital re-admissions in head and neck cancer patients *

OBJECTIVES Investigate the relationship of G-tube placement timing on post-operative outcomes. PARTICIPANTS 908 patients underwent resection of head and neck upper aerodigestive tract tumors between 2007 and 2013. Patient charts were retrospectively screened for patient demographics, pre-operative nutrition variables, co-morbid conditions, Tumor-Node-Metastasis staging, surgical treatment type, and timing of G-tube placement. Exclusionary criteria included death within the first three months of the resection and resections performed solely for nodal disease. MAIN OUTCOMES Post-surgical outcomes, including wound and medical complications, hospital re-admissions, length of inpatient hospital stay (LOS), intensive care unit (ICU) time. RESULTS 793 surgeries were included: 8% of patients had G-tubes pre-operatively and 25% had G-tubes placed post-operatively. Patients with G-tubes (pre-operative or post-operative) were more likely to have complications and prolonged hospital care as compared to those without G-tubes (p < 0.001). Patients with pre-operative G-tubes had shortened length of stay (p = 0.007), less weight loss (p = 0.03), and fewer wound care needs (p < 0.0001), when compared to those that received G-tubes post-operatively. Those with G-tubes placed post-operatively had worse outcomes in all categories, except pre-operative BMI. CONCLUSIONS Though having enteral access in the form of a G-tube at any point suggests a more high risk patient, having a G-tube placed in the pre-operative period may protect against poor post-operative outcomes. Post-operative outcomes can be predicted based on patient characteristics available to the physician in the pre-operative period.

A Model for Predicting Gastrostomy Tube Placement in Patients Undergoing Surgery for Upper Aerodigestive Tract Lesions

IMPORTANCE Identifying high-risk patients in the preoperative period can allow physicians to optimize nutritional status early for better outcomes after head and neck cancer resections. OBJECTIVE To develop a model to predict preoperatively the need for gastrostomy tube (G-tube) placement in patients undergoing surgery of the upper aerodigestive tract. DESIGN, SETTING, AND PARTICIPANTS This retrospective medical record review included all adult patients diagnosed with head and neck cancers who underwent tumor resection from 2007 through 2012 at Wake Forest Baptist Health, a level 1 tertiary care center. Records were screened for patient demographics, tumor characteristics, surgical treatment type, and postoperative placement of G-tube. A total of 743 patients underwent resection of head and neck tumors. Of these, 203 were excluded for prior G-tube placement, prior head and neck resection, G-tube placement for chemoradiotherapy, and resection for solely nodal disease, leaving 540 patients for analysis. MAIN OUTCOMES AND MEASURES Placement of postoperative G-tube. RESULTS Of the 540 included patients, 23% required G-tube placement. The following variables were significant and independent predictors of G-tube placement: preoperative irradiation (odds ratio [OR], 4.1; 95% CI, 2.4-6.9; P < .001), supracricoid laryngectomy (OR, 26.0; 95% CI, 4.9-142.9; P < .001), tracheostomy tube placement (OR, 2.6; 95% CI, 1.5-4.4; P < .001), clinical node stage N0 vs N2 (OR, 2.4; 95% CI, 1.4-4.2; P = .01), clinical node stage N1 vs N2 (OR, 1.6; 95% CI, 0.8-3.3; P = .01), preoperative weight loss (OR, 2.0; 95% CI, 1.2-3.2; P = .004), dysphagia (OR, 2.0; 95% CI, 1.2-3.2; P = .005), reconstruction type (OR, 1.9; 95% CI, 1.1-2.9; P = .02), and tumor stage (OR, 1.8; 95% CI, 1.1-2.9; P = .03). A predictive model was developed based on these variables. In the validation analysis, we found that the average predicted score for patients who received G-tubes was statistically different than the score for the patients who did not receive G-tubes (P = .01). CONCLUSIONS AND RELEVANCE We present a validated and comprehensive model for preoperatively predicting the need for G-tube placement in patients undergoing surgery of the upper aerodigestive tract. Early enteral access in high-risk patients may prevent complications in postoperative healing and improve overall outcomes, including quality of life.

Polymorphous low-grade adenocarcinoma: A 17 patient case series

Polymorphous low-grade adenocarcinoma (PLGA) is a rare malignancy most commonly seen in the minor salivary glands. First described in 1983, this entity has been recognized to have an indolent course with rare metastases or deaths. We describe our experience with 17 patients treated at our institution for PLGA from 1984 to 2012. All tumors were located in the oral cavity or soft palate. All patients were treated surgically, with the exception of one patient who declined therapy. No deaths or metastases have been identified in subsequent follow-up. Three patients in this series had undergone prior surgery up to 20 years previously and were treated for recurrences at our institution; no other recurrences have been noted. In summary, PLGA is best treated with wide excision to negative margins with excellent prognosis, but long-term follow-up is recommended given the propensity for late recurrences.

Donor-Site Outcomes for the Osteocutaneous Radial Forearm Free Flap

Background This study sought to characterize the donor‐site complications associated with the osteocutaneous radial forearm free flap (ORFFF) used for mandibular reconstruction, as well as to compare donor‐site complications between the ORFFF and fasciocutaneous radial forearm free flap (FRFFF). Methods An Institution Review Board approved, retrospective review identified all ORFFF and FRFFF performed for head and neck reconstruction with a single otolaryngology surgeon at an academic medical center over a 3‐year period. Patients requiring an ORFFF underwent harvest of half of the diaphyseal diameter of the radius with prophylactic plating performed by hand surgeons. Donor‐site outcomes including infection, skin graft loss, tendon exposure, neuropathy, radius fracture, hardware complications, and need for additional donor‐site surgery were compared. Results In this study, 25 patients underwent ORFFF harvest, and 52 underwent FRFFF harvest. There was one radius fracture occurring in association with a hardware infection requiring reoperation. No fractures or other major donor‐site complications were seen in the FRFFF group. Similar rates of minor complications were noted with skin graft take less than 50% in 4% (n = 1) and 8% (n = 4) with ORFFF and FRFFF, respectively, and tendon exposure in 8% (n = 2) and 15% (n = 8) with ORFFF and FRFFF, respectively. No soft tissue infections or sensory neuropathies were seen. Mean follow‐up was 14.2 months for the ORFFF group and 11.7 months for the FRFFF group. Conclusion The risk of fracture following ORFFF harvest with prophylactic plating is small. Other donor‐site complication rates were similar with both flap techniques.

Potential for health care cost savings with preoperative gastrostomy tube placement in the head and neck cancer population

The purpose of this study was to examine the cost differences between preoperative and postoperative placement of gastrostomy tubes (G‐tubes) in patients with head and neck cancer.