Kristine E. Day

Use of Panitumumab-IRDye800 to Image Cutaneous Head and Neck Cancer in Mice

Objective To assess the feasibility of panitumumab in real-time fluorescent imaging and histologic processing of cutaneous squamous cell carcinoma (cSCC) in mice. Design A near-infrared (NIR) fluorescent probe (IRDye800CW) was covalently linked to a monoclonal antibody–targeting epidermal growth factor receptor (panitumumab) or nonspecific IgG and injected into mice bearing flank xenografts from a cSCC cell line (SCC-13 or SRB-12; n = 7), human split-thickness skin grafts (STSGs; n = 3), or a human tumor explant (n = 1). The tumor and lymph nodes were imaged and dissected using fluorescence guidance with the SPY imaging system and verified with a charge-coupled NIR system. An NIR scanning device (Odyssey) was used to measure fluorescence intensity in histological sections. Subjects Immunodeficient mice. Setting In vivo and in vitro imaging lab. Results Tumor tissue could be delineated from the human STSG with tumor-to-background ratios of 4.5 (Pearl) and 3.4 (SPY). Tumor detection was substantially improved with panitumumab-IRDye800 compared with IgG-IRDye800. Biopsies positive for fluorescence were assessed by histology and immunohistochemistry (n = 18/18) to confirm the presence of tumor, yielding a 100% sensitivity. Biopsies of nonfluorescent tissue negative for malignancy (n = 18/18) yielded a specificity of 100%. Furthermore, the SPY system was able to detect residual disease as small as 200 µm in diameter. In addition, the Odyssey confirmed fluorescence of microscopic disease (in tumor samples of frozen and paraffin-embedded histologic specimens) but not in adjacent noncancerous tissue. Conclusions These data suggest panitumumab-IRDye800 may have clinical utility in detection and removal of subclinical cSCC using Food and Drug Administration–approved imaging hardware.

Fluorescently labeled therapeutic antibodies for detection of microscopic melanoma

Detection of microscopic disease during surgical resection of melanoma remains a significant challenge. To assess real‐time optical imaging for visualization of microscopic cancer, we evaluated three US Food and Drug Administration (FDA)‐approved therapeutic monoclonal antibodies.

Risk Factors for Supraglottoplasty Failure

Objective. To review outcomes after supraglottoplasty for laryngomalacia and identify risk factors for supraglottoplasty failure. Study Design. Case series with chart review. Setting. Tertiary care children’s hospital. Subjects and Methods. Retrospective case series evaluating patient outcomes after supraglottoplasty at an academic medical center between 2004 and 2010. Surgical failure was defined as need for revision surgery, tracheostomy tube placement, or gastrostomy tube insertion. Multivariable logistic regression was performed to identify risk factors for failure. Results. The authors identified 95 children who underwent supraglottoplasty. After excluding patients with inadequate follow-up data, 74 patients were included. On the basis of chart review, 12 (16%) of those patients were defined as failures according to the criteria above. Age, history of prematurity (<34 weeks’ gestational age), weight, growth curve percentile, neurologic/developmental problems, genetic syndrome, cardiac abnormality, synchronous airway lesions, and surgical technique were considered in risk factor analysis. Multivariable logistic regression was performed, revealing history of prematurity to be the only independent risk factor for failure (odds ratio = 4.85; 95% confidence interval, 1.07-22.1; P = .041). Conclusions. Outcomes after supraglottoplasty were comparable to previous reports in the literature. History of prematurity should be considered a risk factor for surgical failure.

Identification of the optimal therapeutic antibody for fluorescent imaging of cutaneous squamous cell carcinoma.

Intraoperative, real-time fluorescence imaging may significantly improve tumor visualization and resection and postoperatively, in pathological assessment. To this end, we sought to determine the optimal FDA approved therapeutic monoclonal antibody for optical imaging of human cutaneous squamous cell carcinoma (cSCC). A near-infrared (NIR) fluorescent probe (IRDye800) was covalently linked to bevacizumab, panitumumab or tocilizumab and injected systemically into immunodeficient mice bearing either cutaneous tumor cell lines (SCC13) or cutaneous human tumor explants. Tumors were then imaged and resected under fluorescent guidance with the SPY, an FDA-approved intraoperative imaging system, and the Pearl Impulse small animal imaging system. All fluorescently labeled antibodies delineated normal tissue from tumor in SCC13 xenografts based on tumor-to-background (TBR) ratios. The conjugated antibodies produced TBRs of 1.2–2 using SPY and 1.6–3.6 using Pearl; in comparison, isotype control antibody IgG-IRDye produced TBRs of 1.0 (SPY) and 0.98 (Pearl). Comparison between antibodies revealed them to be roughly equivalent for imaging purposes with both the SPY and Pearl (p = 0.89 SPY, p = 0.99 Pearl; one way ANOVA). Human tumor explants were also imaged and tumor detection was highest with panitumumab-IRDye800 when using the SPY (TBR 3.0) and Pearl (TBR 4.0). These data suggest that FDA approved antibodies may be clinically used for intraoperative detection of cSCC.

Head and Neck Cutaneous Squamous Cell Carcinoma Requiring Parotidectomy Prognostic Indicators and Treatment Selection

Objective Evaluate characteristics and risk factors for patients with advanced cutaneous squamous cell carcinoma (cSCC). Study Design Retrospective case series. Setting Tertiary care center. Patients and Methods Chart review of patients with cSCC undergoing a parotidectomy (2003-2012). Results Of 218 patients identified, 49% presented with a new primary lesion (n = 107) and 51% with a recurrence (n = 111). Parotid lymph nodes were positive in 52% of patients; 81% had a concurrent neck dissection, and 28% had cervical lymph node metastases. In 18% of patients, both parotid and cervical nodes were positive, while 44% were both parotid and cervical node negative; 33% had positive parotid and negative cervical nodes, and only 5% had negative parotid and positive cervical nodes. The overall 2- and 5-year survival rates were 0.71 and 0.58. Overall 5-year survival was lower for patients presenting with recurrent (0.49) versus new primary disease (0.69; P = .04). In addition, decreased overall 5-year survival rates were associated with cervical lymph node involvement (0.47 vs. 0.62; P = .01). There was no difference in overall survival when stratified by parotid lymph node involvement (P = .85), margin status (P = .67), perineural invasion (P = .42), facial nerve sacrifice (P = .92), or type of parotid operation performed (P = .51). Conclusions In this study, cervical, but not parotid, lymph node involvement was associated with poor outcomes in patients with advanced cSCC requiring a parotidectomy. In patients without evidence of cervical or parotid lymph node involvement, a neck dissection may be spared, given there is a 5% chance of occult disease.

Time-dependent pretreatment with bevacuzimab increases tumor specific uptake of cetuximab in preclinical oral cavity cancer studies

Inadequate delivery of therapeutics into tumors has been suggested as a reason for poor response. We hypothesize that bevacizumab, an antibody to vascular endothelial growth factor (VEGF), can improve cetuximab uptake in squamous cell carcinoma tumors. Athymic nude mice were implanted with OSC19 and SCC1 human cancer lines in a subcutaneous flank model. Mice were imaged daily for 14 days after intravenous tail vein injections of the following groups: IgG-IRDye800 (Control), cetuximab-IRDye800 (CTX800 Only), bevacizumab-IRDye800 (BVZ800 Only), cetuximab-IRDye800 + bevacuzimuab-IRDye800 (Simultaneous), and unlabeled bevacizumab followed by cetuximab-IRDye800 3 days later (Neoadjuvant). Within single-agent groups, the CTX800 Only tumor-specific uptake (TSU) was significantly higher than BVZ800 Only at Day 13 (TSU 8.6 vs 2.8, P < 0.001). The Simultaneous treatment with BVZ800 and CTX800 demonstrated no increase in antibody delivery. However, administration of unlabeled bevacizumab 3 days prior to CTX800 (Neoadjuvant group) resulted in significantly higher tumor specific delivery than administration of both antibodies at the same time (11.8 vs Simultaneous 5.0, P < 0.001). This difference can be attributed to a slower decline in tumor fluorescence intensity (−6.8% vs. Simultaneous −11.5% per day, respectively). Structural changes in pericyte coverage and functional vessel changes demonstrating decreased proliferation and tumor growth corroborate these fluorescence results. Although simultaneous administration of bevacizumab with cetuximab failed to increase antibody delivery to the tumor, pretreatment with bevacizumab improved TSU reflecting an increase in tumor-specific uptake of cetuximab as a result of vessel normalization.

Predictors of clinical outcome after tracheotomy in critically ill obese patients

To identify patient factors associated with outcomes in critically ill obese patients requiring tracheotomy.

Hardware Removal after Osseous Free Flap Reconstruction

Objective Identifying risk factors for hardware removal in patients undergoing mandibular reconstruction with vascularized osseous free flaps remains a challenge. The purpose of this study is to identify potential risk factors, including osteocutaneous radial forearm versus fibular flap, for need for removal and to describe the fate of implanted hardware. Study Design Case series with chart review Setting Academic tertiary care medical center. Subjects and Methods Two hundred thirteen patients undergoing 227 vascularized osseous mandibular reconstructions between the years 2004 and 2012. Data were compiled through a manual chart review, and patients incurring hardware removals were identified. Results Thirty-four of 213 evaluable vascularized osseous free flaps (16%) underwent surgical removal of hardware. The average length of time to removal was 16.2 months (median 10 months), with the majority of removals occurring within the first year. Osteocutaneous radial forearm free flaps (OCRFFF) incurred a slightly higher percentage of hardware removals (9.9%) compared to fibula flaps (6.1%). Partial removal was performed in 8 of 34 cases, and approximately 38% of these required additional surgery for removal. Conclusion Hardware removal was associated with continued tobacco use after mandibular reconstruction (P = .03). Removal of the supporting hardware most commonly occurs from infection or exposure in the first year. In the majority of cases the bone is well healed and the problem resolves with removal.

Utility of the Surgical Apgar Score in Head and Neck Squamous Cell Carcinoma.

Objectives To recognize the utility of the surgical Apgar score (SAS) in a noncutaneous head and neck squamous cell carcinoma (HNSCC) population. Study Design Retrospective case series with chart review. Setting Academic tertiary medical center. Subjects and Methods Patients (n = 563) undergoing noncutaneous HNSCC resection between April 2012 and March 2015 were included. Demographics, medical history, intraoperative data, and postoperative hospital summaries were collected. SASs were calculated following the published schema. The primary outcome was 30-day postoperative morbidity. A 2-sample t test, analysis of variance, and χ2 (or Fisher exact) test were used for statistical comparisons. A multivariable logistic regression analysis was conducted to identify independent predictors of 30-day morbidity. Results Mean SAS was 6.2 ± 1.5. SAS groups did not differ in age, sex, or race. Sixty-five patients (11.6%) had a SAS between 0 and 4, with 40 incidences of morbidity (61.5%), while 31 (5.5%) patients with SAS from 9 to 10 had 3 morbidity occurrences (9.7%). Results show that 30-day postoperative morbidity is inversely related to increasing SAS (P < .0001). Furthermore, lower SAS was associated with significantly increased operative time (SAS 0-4: 9.3 ± 2.6 hours vs SAS 9-10: 3.0 ± 1.1 hours) and lengths of stay (SAS 0-4: 10.0 ± 7.3 days vs SAS 9-10: 1.6 ± 1.0 days), P < .0001. SAS remained highly significant after adjusting for potential confounding variables in the multivariable analysis (P < .0001). Conclusions An increasing SAS is associated with significantly lower rates of 30-day postoperative morbidities in a noncutaneous HNSCC patient population.

Utility of the Modified Surgical Apgar Score in a Head and Neck Cancer Population

Objective The Surgical Apgar Score (SAS) is a validated postoperative complication prediction model. The purpose of this study was to investigate the utility of the SAS in a diverse head and neck cancer population and to compare it with a recently developed modified SAS (mSAS) that accounts for intraoperative transfusion. Study Design Case series with chart review. Setting Academic tertiary care medical center. Subjects and Methods This study comprised 713 patients undergoing surgery for head and neck cancer from April 2012 to March 2015. SAS values were calculated according to intraoperative data obtained from anesthesia records. The mSAS was computed by assigning an estimated blood loss score of zero for patients receiving intraoperative transfusions. Primary outcome was 30-day postoperative morbidity. Results Mean SAS and mSAS were 6.3 ± 1.5 and 6.2 ± 1.7, respectively. SAS and mSAS were significantly associated with 30-day postoperative morbidity, length of stay, operative time, American Society of Anesthesiologists status, race, and body mass index (P < .05); however, no significant association was detected for age, sex, and smoking status. Multivariable analysis identified SAS and mSAS as independent predictors of postoperative morbidity, with the mSAS (P = .03) being a more robust predictor than the SAS (P = .15). Strong inverse relationships were demonstrated for the SAS and mSAS with length of stay and operative time (P < .0001). Conclusion The SAS serves as a useful metric for risk stratification of patients with head and neck cancer. With the inclusion of intraoperative transfusion, the mSAS demonstrates superior utility in predicting those at risk for postoperative complications.