Larissa Sweeny

Impact of Pharyngeal Closure Technique on Fistula After Salvage Laryngectomy

IMPORTANCE No consensus exists as to the best technique, or techniques, to optimize wound healing, decrease pharyngocutaneous fistula formation, and shorten both hospital length of stay and time to initiation of oral intake after salvage laryngectomy. We sought to combine the recent experience of multiple high-volume institutions, with different reconstructive preferences, in the management of pharyngeal closure technique for post-radiation therapy salvage total laryngectomy in an effort to bring clarity to this clinical challenge. OBJECTIVE To determine if the use of vascularized flaps in either an onlay or interposed fashion reduces the incidence or duration of pharyngocutaneous fistula after salvage laryngectomy compared with simple primary closure of the pharynx. DESIGN Multi-institutional retrospective review of all patients undergoing total laryngectomy after having received definitive radiation therapy with or without chemotherapy between January 2005 and January 2012, conducted at 7 academic medical centers. SETTING Academic, tertiary referral centers. PATIENTS The study population comprised 359 patients from 8 institutions. All patients had a history of laryngeal irradiation and underwent laryngectomy between 2005 and 2012. They were grouped as primary closure, pectoralis myofascial onlay flap, or interposed free tissue. All patients had a minimum of 4 months follow-up. MAIN OUTCOMES AND MEASURES Fistula incidence, severity, and predictors of fistula. RESULTS Of the 359 patients, fistula occurred in 94 (27%). For patients with fistula, hospital stay increased from 8.9 to 12.1 days (P < .001) and oral diet initiation was delayed from 10.5 days to 29.9 days (P < .001). Patients were grouped according to closure technique: primary closure (n = 99), pectoralis onlay flap (n = 40), and interposed free tissue (n = 220). Incidence of fistula with primary closure was 34%. For the interposed free flap group, the fistula rate was lower at 25% (P = .07). Incidence of fistula was the lowest for the pectoralis onlay group at 15% (P = .02). Multivariate analysis confirmed a significantly lower fistula rate with either flap technique. For patients who developed fistula, mean duration of fistula was significantly prolonged with primary closure (14.0 weeks) compared with pectoralis flap (9.0 weeks) and free flap (6.5 weeks). CONCLUSIONS AND RELEVANCE Pharyngocutaneous fistula remains a significant problem following salvage laryngectomy. Use of nonirradiated, vascularized flaps reduced the incidence and duration of fistula and should be considered during salvage laryngectomy.

Outcomes in head and neck reconstruction by surgical site and donor site

Define surgical outcomes of specific donor sites for free tissue transfer in head and neck reconstruction.

Assessment and incidence of salivary leak following laryngectomy.

To determine the incidence and risk factors of pharyngocutaneous fistula formation in patients undergoing either primary or salvage laryngectomies and evaluate the role of barium esophagram in these patients.

Mammary analog secretory carcinoma, low-grade salivary duct carcinoma, and mimickers: a comparative study.

Mammary analog secretory carcinoma (MASC) is a recently recognized low-grade salivary carcinoma characterized by a specific ETV6 rearrangement. We describe 14 new MASCs and examine their immunophenotypic and genetic profiles in the context of look-alikes, namely, low-and high-grade salivary duct carcinoma and acinic cell carcinoma. ETV6 rearrangement, and robust expression of mammaglobin and S100, were demonstrated in 11/11, 14/14, and 12/14 MASCs, respectively. All low-grade salivary duct carcinomas coexpressed S100/mammaglobin (6/6); none harbored ETV6 rearrangements (0/5). Given that S100/mammaglobin coexpression and absence of zymogen granules are features of both MASC and low-grade salivary duct carcinoma, these two are best distinguished histologically. The former is predominantly an extraductal neoplasm with bubbly pink cytoplasm, whereas the latter is a distinct intraductal micropapillary and cribriform process. Querying ETV6 gene status may be necessary for difficult cases. No acinic cell carcinoma expressed mammaglobin (0/13) or harbored an ETV6 rearrangement (0/7); only 1/13 acinic cell carcinomas weakly expressed S100. DOG1 expression was limited or absent among all tumor types, except acinic cell carcinoma which expressed DOG1 diffusely in a canalicular pattern. Therefore, histology and immunohistochemistry (mammaglobin, S100, DOG1) suffices in distinguishing acinic cell carcinoma from both MASC and low-grade salivary duct carcinoma. HER2 (ERBB2) amplification was detected in only 1/10 acinic cell carcinomas, but none of the MASCs or low-grade salivary duct carcinomas tested. High-grade salivary duct carcinomas frequently expressed mammaglobin (11/18) and harbored HER2 amplifications (13/15); none harbored ETV6 rearrangements (0/12). High-grade salivary duct carcinomas can easily be distinguished from these other entities by histology and HER2 amplification.

Incidence and Outcomes of Stricture Formation Postlaryngectomy

Objective. Postlaryngectomy stricture formation and dysphagia negatively affect quality of life and result in nutritional compromise. Understanding risk factors and successful treatment strategies may improve treatment outcomes. Study Design. Historical cohort study. Setting. Tertiary care medical center. Subjects and Methods. Patients at a tertiary care center who underwent a total laryngectomy between 2003 and 2009 (N = 263) were evaluated in a retrospective manner. Patient demographics, comorbidities, tobacco and alcohol usage, dietary outcomes, feeding tube dependence, and treatment modalities were assessed. Management strategies and outcomes were evaluated. Results. Strictures developed in 19% (n = 49) of patients, and the majority (82%) occurred in the first year. Incidences of stricture formation were similar for primary (19%) and salvage laryngectomy (19%) patients. Patients undergoing salvage laryngectomy were 2 times more likely to be reconstructed with a free flap, whereas those undergoing a primary laryngectomy were 3 times more likely to be closed primarily. Tubed flap reconstruction significantly increased the incidence of stricture formation compared to primary closure (P = .02) in salvage laryngectomy cases. In primary laryngectomy patients, stricture formation did not correlate with flap reconstruction (P = .34) or adjuvant radiation therapy (P = .79). Patients who required a single dilation had better dietary outcomes compared to patients who required serial dilations (P = .14). There was no difference in overall disease-free survival in primary vs salvage laryngectomy patients (P = .95). Conclusion. Rates of stricture formation were the same in patients undergoing salvage compared to primary total laryngectomy.

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.

CD147 and AGR2 expression promote cellular proliferation and metastasis of head and neck squamous cell carcinoma

The signaling pathways facilitating metastasis of head and neck squamous cell carcinoma (HNSCC) cells are not fully understood. CD147 is a transmembrane glycoprotein known to induce cell migration and invasion. AGR2 is a secreted peptide also known to promote cell metastasis. Here we describe their importance in the migration and invasion of HNSCC cells (FADU and OSC-19) in vitro and in vivo. In vitro, knockdown of CD147 or AGR2 decreased cellular proliferation, migration and invasion. In vivo, knockdown of CD147 or AGR2 expression decreased primary tumor growth as well as regional and distant metastasis.

Assessment of tissue autofluorescence and reflectance for oral cavity cancer screening.

Objective. Although approved by the US Food and Drug Administration for clinical use, the utility of handheld tissue reflectance and autofluorescence devices for screening head and neck cancer patients is poorly defined. There is limited published evidence regarding the efficacy of these devices. The authors investigated the sensitivity and specificity of these modalities compared with standard examination. Study Design. Prospective, cross-sectional analysis. Setting. Tertiary care medical center. Subjects and Methods. Patients who were treated previously for head and neck cancer (n = 88) between 2009 and 2010 were included. Patients were screened using white light visualization (standard of care) and compared with tissue reflectance and autofluorescence visualization. Screening results were compared with biopsy or long-term follow-up. Results. Autofluorescence visualization had a specificity of 81% and a sensitivity of 50% for detecting oral cavity cancer, whereas white light visualization had a specificity of 98% and a sensitivity of 50%. Tissue reflectance visualization had low sensitivity (0%) and good specificity (86%). The power of this study was insufficient to compare the positive and negative predictive values of standard white light examination (50% and 98%, respectively) to tissue autofluorescence (11% and 97%) or reflectance (0% and 95%). In addition, stratification by previous radiation therapy found no statistically significant difference in screening results. Conclusion. Standard clinical lighting has a higher specificity than tissue reflectance and autofluorescence visualization for detection of disease in patients with a history of head and neck cancer. This study does not support the added costs associated with these devices.

EGFR expression in advanced head and neck cutaneous squamous cell carcinoma

The significance of epidermal growth factor receptor (EGFR) expression in advanced cutaneous squamous cell carcinoma (SCC) of the head and neck remains poorly understood.

Microvascular Anastomotic Coupler Assessment in Head and Neck Reconstruction

Objective To assess the advantages of using mechanical anastomotic systems in head and neck free tissue transfer. Study design Case series with chart review. Setting A university-based tertiary care center. Subjects and Methods A retrospective review of mechanical venous coupler devices in head and neck reconstruction performed between October 2004 and December 2006. A total of 261 venous anastomoses were performed in 234 consecutive patients. Five types of flaps were performed: radial forearm (66%), anterior lateral thigh (12%), fibula (9%), rectus abdominis (8%), and latissimus dorsi (2%). Demographic data were collected, and the outcomes measured were flap survival and microvascular complications. Results The size of the venous anastomosis ranged from 1.5 to 4.0 mm, with most being 3.0 mm (56%) followed by 3.5 mm (23%). The most common recipient vein used was a stump off the internal jugular vein (76%) followed by the external jugular vein (17%). Microvascular complications occurred in <5% (n = 11) of patients, with >50% of those being arterial insufficiency (n = 7). Total failures occurred in 3% (n = 7) of patients: 1.5% (n = 4) acute failures (<5 days) and 1.5% (n = 3) late failures. Of the acute failures, causes included venous congestion (n = 1) and arterial insufficiencies (n = 3). The venous coupler used in the failures was 3.0 mm in diameter. Free flap failures resulting from arterial insufficiency involved coupling to the external jugular vein, while the remaining free flap failures (n = 4) used the internal jugular vein. Conclusion With an early venous failure rate of 0.38%, mechanical anastomosis is an adequate alternative to hand-sewn techniques.