2-Octyl cyanoacrylate to prevent salivary fistula formation following oral cavity microvascular reconstruction: A prospective trial.

BACKGROUND: Salivary fistulas remain a significant problem in patients undergoing major head and neck reconstructive surgery. Surgical sealants have become increasingly used in cutaneous and non-cutaneous wound closure, providing a barrier to fluids/gases and promoting healing. The purpose of this study was to determine the efficacy of a common surgical sealant, 2-Octyl Cyanoacrylate (2-OCA, Dermabond®), in the prevention of salivary fistulas following free flap reconstruction of the oral cavity. METHODS: In this non-randomized, single arm prospective trial, patients undergoing free flap reconstruction of gravity-dependent oral cavity defects were recruited. Application of 2-OCA was performed along flap inset suture lines at the time of surgery. Prospectively collected trial data were propensity score matched to a control cohort to compare outcomes. Data collected include demographics, medical co-morbidities, previous treatments, primary tumor site, and subsites reconstructed. The primary outcome measure was rate of salivary fistula formation. Secondary outcomes were time to development of leak and percentage of patients tolerating oral feeding at one month post-operatively. RESULTS: In the 46 propensity score matched pairs, eight (17.4%) out of 46 patients in the 2-OCA prospective cohort and seven (15.2%) out of 46 patients in the control cohort developed postoperative salivary fistulas within the one-month study interval (p = 1.00). The average time to postoperative leak in the 2-OCA group was 12.5 days versus 7.1 days in the control cohort (p = 0.10). In the 2-OCA group, 30 (65.2%) patients were tolerating regular diet at one month post-operatively compared to 33 (71.7%) in the control cohort (p = 0.65). CONCLUSION: Salivary fistula rates after application of a 2-OCA surgical sealant were not improved compared to a control cohort in this single institutional trial. There are several surgical sealants available, each with varying elasticity and adhesiveness. Future studies are needed to identify surgical sealants that are able to provide sufficient strength and adhesion to seal closures and combat corrosive saliva, but elastic enough to handle motion related tension during swallowing and post-operative movements in the head and neck.

Early feeding after free flap reconstruction of the oral cavity: A systematic review and meta-analysis.

BACKGROUND: Traditionally, patients undergoing free flap reconstruction for oral cavity defects have been given nothing by mouth for 6-14 days post-operatively due to concern for orocutaneous fistula development. METHODS: Multiple databases were screened for studies assessing the rate of orocutaneous fistula formation in early (≤5 days) versus late (>5 days) feeding groups following oral cavity free flap reconstruction. Fixed- and random-effects meta-analyses were used. RESULTS: One randomized controlled trial, one prospective cohort, and three retrospective cohort studies were included. The early feeding group displayed no significant increase in orocutaneous fistula formation (RD = -0.02, p = 0.06) or free flap failure (RD = -0.01, p = 0.39), with a significantly shorter hospital length of stay (mean difference [days] = -2.43, p < 0.01). CONCLUSIONS: While further prospective trials are necessary, initiation of oral intake before post-operative day 5 may be appropriate in properly selected patients following oral reconstruction.

Primary Management of Operable Locally Advanced Oral Cavity Squamous Cell Carcinoma: Current Concepts and Strategies.

INTRODUCTION: Locally advanced oral cavity carcinoma (LAOCSCC) is primarily treated with surgery followed by radiotherapy with or without chemotherapy. METHODS: A review of literature using PubMED was performed for studies reporting the management of LAOCSCC. Based on the reviewed literature and opinions of experts in the field, recommendations were made. RESULTS: Studies have shown that outcomes following resection of T4a and infranotch (inferior to mandibular notch) T4b are comparable. We discuss the concept of compartmental resection of LAOCSCC and issues concerning the management of the neck. Further, patients who refuse or are unable to undergo surgery can be treated with chemoradiotherapy with uncertain outcomes. The role of neoadjuvant chemotherapy has shown promise for organ (mandibular) preservation in a select subset of patients. CONCLUSION: The management strategy for LAOCSCC should be determined in a multidisciplinary setting with emphasis on tumor control, functional preservation, and quality of life of the patient.

Intraoperative Use of Wide-Field Optical Coherence Tomography to Evaluate Tissue Microstructure in the Oral Cavity and Oropharynx.

Importance: Involvement of deep margins represents a significant challenge in the treatment of oropharyngeal cancer, and given practical limitations of frozen-section analysis, a need exists for real-time, nondestructive intraoperative margin analysis. Wide-field optical coherence tomography (WF-OCT) has been evaluated as a tool for high-resolution adjunct specimen imaging in breast surgery, but its clinical application in head and neck surgery has not been explored. Objective: To evaluate the utility of WF-OCT for visualizing microstructures at margins of excised oral and oropharyngeal tissue. Design, Setting, and Participants: This nonrandomized, investigator-initiated qualitative study evaluated the feasibility of the Perimeter Medical Imaging AI Otis WF-OCT device at a single academic center. Included participants were adults undergoing primary ablative surgery of the oral cavity or oropharynx for squamous cell carcinoma in 2018 and 2019. Data were analyzed in October 2019. Exposures: Patients were treated according to standard surgical care. Freshly resected specimens were imaged with high-resolution WF-OCT prior to routine pathology. Interdisciplinary interpretation was performed to interpret WF-OCT images and compare them with corresponding digitized pathology slides. No clinical decisions were made based on WF-OCT image data. Main Outcomes and Measures: Visual comparisons were performed between WF-OCT images and hematoxylin and eosin slides. Results: A total of 69 specimens were collected and scanned from 53 patients (mean [SD] age, 59.4 [15.2] years; 35 [72.9%] men among 48 patients with demographic data) undergoing oral cavity or oropharynx surgery for squamous cell carcinoma, including 42 tonsillar tissue, 17 base of the tongue, 4 buccal tissue, 3 mandibular, and 3 other specimens. There were 41 malignant specimens (59.4%) and 28 benign specimens (40.6%). In visual comparisons of WF-OCT images and hematoxylin and eosin slides, visual differentiation among mucosa, submucosa, muscle, dysplastic, and benign tissue was possible in real time using WF-OCT images. Microarchitectural features observed in WF-OCT images could be matched with corresponding features within the permanent histology with fidelity. Conclusions and Relevance: This qualitative study found that WF-OCT imaging was feasible for visualizing tissue microarchitecture at the surface of resected tissues and was not associated with changes in specimen integrity or surgical and pathology workflow. These findings suggest that formal clinical studies investigating use of WF-OCT for intraoperative analysis of deep margins in head and neck surgery may be warranted.

Robotic surgery for oropharynx cancer: promise, challenges, and future directions.

Epidemiologic studies have shown a rise in the incidence of oropharyngeal cancer without a corresponding increase in oral cavity cancers. These diverging trends are explained by human papilloma virus, which preferentially affects the oropharynx. Cancers resulting from this viral infection bear a better prognosis than those that are smoking-related. Treatment of oropharyngeal cancers has typically involved the use of radiation and chemotherapy to avoid the morbidity of mandibular splitting surgery. The use of transoral robotic surgery (TORS) has obviated the need for large-scale open approaches but still provides the pathologic staging data that is unavailable from non-surgical approaches. Although TORS is in its infancy, early functional and oncologic outcome data are promising. The complex management of oropharyngeal cancers should utilize the available treatment modalities to optimize outcomes and stratify patients to different treatment based on risk status.

Reconstruction of transoral robotic surgery defects: principles and techniques.

Early functional and oncological outcome studies suggest that transoral robotic surgery (TORS) may have a role for early stage cancers of the oropharynx. Unlike with traditional mandibular swing or pharyngotomy approaches, access to the oropharynx for reconstruction in TORS cases is limited. Maintaining a good functional result necessitates preserving physiological function where possible. The principles that should guide reconstructive surgeons include maintaining a velopharyngeal sphincter to prevent velopharyngeal insufficiency, maintaining sensate mucosa and restoring bulk in the tongue base to prevent aspiration, maintaining separation between the cervical and pharyngeal components, and covering exposed vessels in the pharynx. We present here principles and surgical techniques of TORS to reconstruct oropharyngeal defects using a subsite-based approach using secondary healing, local musculomucosal flaps, and free tissue transfer guided by the above principles.

Combined VSV oncolytic virus and chemotherapy for squamous cell carcinoma.

OBJECTIVES: Vesicular stomatitis virus (VSV) is a negative-strand ribonucleic acid (RNA) virus that replicates specifically in tumor cells and has oncolytic effects in a variety of malignant tumors. We previously demonstrated recombinant VSV vectors incorporating viral fusion protein (rVSV-F) and interleukin 12 (rVSV-IL12) to have significant antitumor effects against squamous cell carcinoma (SCC) in a murine model. Here we evaluate the potential to combine a potent chemotherapeutic agent for SCC (cisplatin) with rVSV-F and rVSV-IL12 to improve efficacy. STUDY DESIGN: In vitro, three SCC cell lines were tested using rVSV-F and rVSV-IL12 with cisplatin, monitoring viral replication and cell survival. In an orthotopic floor of mouth murine SCC model, intratumoral injections of virus combined with systemic cisplatin were tested for tumor control and animal survival. RESULTS: In vitro, virus and cisplatin combination demonstrated rapid replication and enhanced tumor cell kill. Human keratinocytes were unaffected by virus and cisplatin. In vivo, combined rVSV-F with cisplatin reduced tumor burden and improved survival (P = .2 for both), while rVSV-IL12 monotherapy had better tumor control (P = .06) and survival (P = .024) than combination therapy. CONCLUSIONS: Addition of cisplatin did not affect the ability of either virus to replicate in or kill murine SCC cells in vitro. In vivo, combination therapy enhancedrVSV-F antitumor activity, but diminished rVSV-IL12 antitumor activity. Combination therapy may provide useful treatment for SCC with the development of more efficient viral vectors in combination with different chemotherapy agents or immunostimulatory agents.

The administration of IL-12/GM-CSF and Ig-4-1BB ligand markedly decreases murine floor of mouth squamous cell cancer.

OBJECTIVE: To assess immune-based gene therapy in a murine floor of mouth (FOM) squamous cell carcinoma (SCC) model. STUDY DESIGN: In vitro and in vivo testing of immune therapy for SCC. METHODS: Multiple SCC lines were infected by using advRSV-interleukin-12 (IL-12) and advCMV-interleukin-12/granulocyte macrophage colony-stimulating factor (IL-12/GM-CSF) and monitored for production of IL-12 and GM-CSF. Intratumoral injections of viral vectors were administered with systemic Ig-4-1BB ligand in an orthotopic murine FOM SCC model and followed for tumor size and survival. RESULTS: In vitro, all cell lines produced substantial levels of IL-12 and GM-CSF. In vivo, tumors treated with advCMV-IL-12/GM-CSF and Ig-4-1BBL showed a striking reduction in tumor volume (vs control P<0.0001) and improved median survival (38 days vs 19 days for control, P<0.0001). CONCLUSION: Combination immune-based therapies effectively improve survival in mice bearing FOM SCC over single-modality therapy.

Parameters Associated With Mandibular Osteoradionecrosis.

The objective of this review is to discuss factors related to the risk of osteoradionecrosis (ORN) and how to minimize the likelihood of this complication. A PubMed search for publications pertaining to ORN within the last 3 years was conducted revealing 44 publications. The bibliographies of these publications were reviewed to identify additional references spanning a longer time period. The incidence of ORN is 5% to 10% with a median latency period of 1 to 2 years or less. The likelihood of ORN depends on a number of factors including primary site and extent of disease, dental status, treatment modality, radiotherapy (RT) dose, volume of mandible included in the planning target volume, RT fractionation schedule and technique, and teeth extractions. The risk of ORN may be reduced by limiting the RT dose and volume of mandible irradiated without increasing the risk of a local-regional recurrence due to a marginal miss.

Interleukin-12 expression enhances vesicular stomatitis virus oncolytic therapy in murine squamous cell carcinoma.

OBJECTIVES: Replication-competent, vesicular stomatitis virus (VSV) has been demonstrated to be an effective oncolytic agent in a variety of malignant tumors. Cytokine gene transfer has also been used as immunomodulatory therapy for cancer. To test the use of combining these two approaches, an oncolytic VSV vector (rVSV-IL12) was designed to express the murine interleukin 12 (IL12) gene. This cytokine-carrying oncolytic virus was compared with an analogous noncytokine-carrying fusogenic virus (rVSV-F) in the treatment of murine SCC VII squamous cell carcinoma (SCC). STUDY DESIGN AND SETTING: The authors performed in vitro testing of recombinant VSV-F and recombinant VSV-IL12 in SCC cell lines. In vivo testing of multiple direct intratumoral injections of rVSV-F or rVSV-IL12 in an orthotopic floor of mouth murine model was performed. Each cell line was tested using rVSV-F or rVSV-IL12 at multiplicity of infection of 0.01. The ability of each virus to replicate was tested by real-time reverse transcriptase-polymerase chain reaction over 48 hours to determine viral copies of RNA. Cell survival was determined by MTT assay over 72 hours. IL12 expression by rVSV-IL12-treated cells was determined by enzyme-linked immunosorbent assay. RESULTS: Both viruses demonstrated similar infection efficiency, viral replication, and cytotoxicity in vitro. In an SCC VII orthotopic floor of mouth model in immunocompetent C3H/HeJ mice, multiple intratumoral injections with each virus caused a significant reduction in tumor volume when compared with saline injections alone. The rVSV-IL12-treated tumors showed a striking reduction in tumor volume when compared with rVSV-F and saline-treated tumors (P < .005). This striking reduction in tumor volume translated into a substantial survival benefit in rVSV-IL12-treated animals. No treatment-related toxicity was observed in either group. CONCLUSION/SIGNIFICANCE: rVSV-IL12 is a novel oncolytic vesicular stomatitis virus that effectively expresses IL12 and significantly enhances the treatment of head and neck murine carcinoma. Such combined oncolytic and immunomodulatory strategies hold promise in the treatment of head and neck cancers.

Fusogenic vesicular stomatitis virus for the treatment of head and neck squamous carcinomas.

OBJECTIVES: This study investigates the efficacy of recombinant fusogenic VSV [rVSV-NDV/F(L289A) or rVSV-F] in the treatment of head and neck squamous cell carcinoma (HNSCC). STUDY DESIGN AND SETTING: The in vitro replication and cytotoxicity of rVSV-F were studied in two human SCC cell lines, in one murine SCC cell line, and in human keratinocytes. The effects on tumor size and animal survival were investigated following in vivo rVSV-F treatment of floor-of-mouth tumor model C3H/HeJ mice. RESULTS: Recombinant VSV-F preferentially induced rapid syncytia formation, and replicated in (P < 0.04) and killed (P < 1 x 10(-13)) all three SCC lines tested. The virus had no observable effect on human keratinocytes. Tumor size was smaller (P < 0.03) and overall survival was better (P < 0.001) for treated animals than for control animals. CONCLUSION/SIGNIFICANCE: Recombinant VSV-F confers a modest survival benefit for HNSCC in this orthotopic murine model. This oncolytic virus holds promise as a novel cancer treatment for recurrent HNSCC.

The price of free tissue transfer after tongue reconstruction: quantifying the risks.

OBJECTIVES/HYPOTHESIS: To evaluate the preoperative variables, mean operative time, morbidity, and mortality associated with reconstruction of partial glossectomy defects. STUDY DESIGN: Retrospective data analysis. METHODS: The National Surgical Quality Improvement Program database was queried for patients having undergone glossectomy procedures. The study sample was split into two groups based on the lack or presence of a flap reconstruction. A total of 1,012 glossectomy patients were identified, with 805 undergoing nonflap reconstruction and 207 undergoing free flap reconstruction. Variables evaluated included wound complications, major and minor morbidity, return to the operating room, mortality, and mean operative time. RESULTS: Patients undergoing free flap reconstruction experienced significantly longer mean operative times (482.1 vs. 183.0 minutes, P < .001), were more likely to return to the operating room (odds ratio [OR] = 2.39, 95% confidence interval [CI] = 1.33-4.29, P = .003), and had higher likelihood of wound complications (OR = 5.78, 95% CI = 2.72-12.26, P < .001), major morbidity (OR = 12.39, 95% CI = 7.02-21.85, P < .001), and minor morbidity (OR = 4.20, 95% CI = 2.12-8.33, P < .001). There was no difference in mortality between groups (OR = 8.62, 95% CI = 0.53-141.7, P = .131). CONCLUSIONS: Free flap reconstruction of glossectomy defects involving up to half of the tongue is associated with increased morbidity and operative time when compared with nonflap reconstruction. Currently available functional outcomes data for tongue reconstruction are poor. Possible functional impairment must be weighed against the associated morbidity when deciding which defects require reconstruction, and the decision to reconstruct should not be taken lightly. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:1551-1557, 2017.

Oncologic outcomes of surgically treated early-stage oropharyngeal squamous cell carcinoma.

BACKGROUND: The purpose of this study was to characterize oncologic outcomes in early (T1-T2, N0) and intermediate (T1-T2, N1) oropharyngeal squamous cell carcinoma (SCC) after surgery. METHODS: Patients with oropharyngeal SCC treated with surgery were identified from 2 academic institutions. RESULTS: Of 188 patients, 143 met the inclusion criteria. Eighty-six (60%) had T1 to T2 N0 and 57 (40%) had T1 to T2 N1 disease. Sixty-five patients (45%) underwent a robotic-assisted resection, whereas the remaining had transoral (n = 60; 42%), mandible-splitting (n = 11; 8%), or transhyoid approaches (n = 7; 5%). Human papillomavirus (HPV) status was known for 97 patients (68%), and 54 (55%) were HPV positive. Three-year recurrence-free survival (RFS) was 82% (95% confidence interval [CI] = 0.75-0.89). Since 2008, HPV infection was protective of recurrence (log-rank p = .0334). A single node did not increase the risk of recurrence (p = .467) or chance of a second primary (p = .175). CONCLUSION: Complete surgical resection is effective therapy for early and intermediate oropharyngeal SCC. HPV-negative patients were at increased risk for locoregional recurrence or second primary disease. © 2016 Wiley Periodicals, Inc. Head Neck 38: First-1471, 2016.

Management of mandibular invasion: when is a marginal mandibulectomy appropriate?

There has been a great deal of controversy regarding the appropriate method of management of oral cavity and oropharyngeal tumors that invade the mandible. The inability to acquire intraoperative bone margins can make the decision process complex. Preoperative imaging offers several advantages, however, there is no single modality that has proven accurate. Intraoperative assessment has been suggested as a method of evaluation, however, this approach does not allow for preoperative planning. The following is a review of the current literature regarding mandibular invasion and the indications for a marginal mandibulectomy.

Prosthodontic Considerations in Post-cancer Reconstructions.

The restoration of function after oncologic surgery of the oral cavity constitutes one of the major challenges facing head and neck oncology. Within the general objective of securing esthetic as well as functional reconstructions, dental rehabilitation is crucial for achieving a good outcome. Adequate dental rehabilitation allows the patient to chew food and considerably improves speech and swallowing. These reconstructions will be driven biologically or prosthetically following surgical design and outcome.

Management of cancer of the retromolar trigone.

Treatment of cancer of the retromolar trigone (RMT) is controversial. While early lesions may be managed with single-modality, more advanced lesions may invade the mandible, pterygoid musculature, and the adjacent mucosa of the tonsillar pillar and soft palate, therefore making therapeutic decisions more complicated. Treatment options traditionally include surgical resection, external beam irradiation, and combined modality therapy. The choice of therapy is dependent on the extent of the tumor, nodal metastasis, and the medical status of the patient and comorbid conditions. The following review outlines the current issues relevant to the diagnosis and therapy of patients with RMT malignancy.

Subcutaneous mandibulotomy: a new surgical access for large tumors of the parapharyngeal space.

OBJECTIVES: Surgery for tumors of the parapharyngeal space (PPS) requires adequate exposure to identify and protect vital structures. Transcervical and transcervical-transparotid approaches to the PPS may be enhanced by mandibulotomy. However, midline mandibulotomy traditionally requires lip-splitting and extensive intraoral incisions, often necessitating tracheostomy and nasogastric feeding. We describe a new technique to gain exposure to the PPS while avoiding these consequences. STUDY DESIGN: Case series. METHODS: Five patients with PPS tumors underwent surgery using a new technique, the subcutaneous mandibulotomy approach (SMA). Each case was retrospectively assessed for tumor size, intraoperative access to the PPS, perioperative complications, and length of hospitalization. RESULTS: In this series, the additional exposure achieved by SMA was adequate to safely remove large PPS tumors that could not be delivered through the transcervical-transparotid approach. All patients started oral diets on postoperative day 1 and were discharged within 3 days. There were no intraoperative complications, and postoperative complications were self-limited. The pathologic entities were a venous malformation, a paraganglioma, and three large, deep-lobe pleomorphic adenomas of the parotid. CONCLUSIONS: We introduce a new technique, the SMA, which affords excellent access to the PPS without the lip-split, chin-split, and floor of mouth incisions. The SMA avoids both nasogastric feeding and a tracheostomy and offers improved cosmesis compared with a traditional midline mandibulotomy. Our current stepwise approach to achieve exposure to the PPS includes use of the SMA as an intermediate step for extensive PPS lesions, which are inaccessible through the transcervical approach yet do not require full labiomandibulotomy for safe and complete removal.

Comparison of functional and quality-of-life outcomes in patients with and without palatomaxillary reconstruction: a preliminary report.

BACKGROUND: Orodental rehabilitation of hemipalatomaxillectomy defects can be accomplished by using a prosthetic obturator or a vascularized bone-containing free flap. Whereas prosthetic obturation offers several advantages, including the opportunity for immediate dental restoration without the need for further surgery, vascularized bone grafts provide permanent closure of the oronasal communication and bone sufficient for the placement of osseointegrated implants. OBJECTIVE: To compare the functional and quality-of-life (QOL) outcomes in patients rehabilitated with a prosthetic obturator with defect-matched patients who underwent reconstruction with a vascularized bone-containing free flap. METHODS: Four hemipalatomaxillectomy patients rehabilitated with a tissue-borne prosthetic obturator were compared with 4 defect-matched hemipalatomaxillectomy patients who underwent reconstruction with a vascularized bone-containing free flap. All of the patients were objectively assessed for speech, mastication, and QOL. Functional status was assessed by mastication testing, voice analysis, and nasorhinometry. Swallowing-related QOL was assessed using a patient-reported, validated swallowing QOL questionnaire, and donor site morbidity was assessed using upper extremity and lower extremity questionnaires. RESULTS: Patients who underwent reconstruction with a vascularized bone-containing free flap achieved higher mastication and speech assessment scores with less oronasal reflux than defect-matched patients rehabilitated with a prosthetic obturator. Swallowing QOL and donor site assessments demonstrated that compared with their prosthetic counterparts, reconstruction patients enjoyed a better QOL without incurring significant donor site morbidity. CONCLUSIONS: Although palatomaxillary reconstruction with vascularized bone-containing free flaps requires a second operative site, this method of orodental rehabilitation of the hemipalatomaxillectomy defect can achieve superior functional and QOL outcomes relative to defect-matched patients rehabilitated with a prosthetic obturator.

Robotic assisted reconstruction of the oropharynx.

PURPOSE OF REVIEW: Oropharyngeal reconstruction has undergone significant advances over the last several decades. Transoral robotic surgery (TORS) is a new approach to managing tumors of this location and requires unique reconstructive principles. RECENT FINDINGS: The advent of TORS has popularized transoral approaches and has presented new challenges related to reconstruction. Although TORS provides a minimally invasive approach to the oropharynx, there is a paucity of data related to reconstruction of extensive defects following TORS. Our institutional practice is to reconstruct defects based on the Classification for Oropharyngeal Robotic Defects (CORD) classification system. The CORD system considers size, location, number of involved oropharyngeal subsites, pharyngocervical communication, and exposure of carotid artery to guide reconstruction. This system uses more advanced reconstructions to manage increasingly complex defects. SUMMARY: Herein, we present principles of robotic assisted oropharyngeal reconstruction and the method for applying the CORD system.

Transoral resection of pharyngeal cancer: summary of a National Cancer Institute Head and Neck Cancer Steering Committee Clinical Trials Planning Meeting, November 6-7, 2011, Arlington, Virginia.

Recent advances now permit resection of many pharyngeal tumors through the open mouth, an approach that can greatly reduce the morbidity of surgical exposure. These transoral techniques are being rapidly adopted by the surgical community and hold considerable promise. On November 6-7, 2011, the National Cancer Institute sponsored a Clinical Trials Planning Meeting to address how to further investigate the use of transoral surgery, both in the good prognosis human papillomavirus (HPV)-initiated oropharyngeal cancers, and in those with HPV-unrelated disease. The proceedings of this meeting are summarized.