Use of a non-ICU specialty ward for immediate post-operative management of head and neck free flaps; a randomized controlled trial.

OBJECTIVES: Compare length of stay, flap failure rate, medical and surgical complications and cost when patients undergoing head and neck free flap reconstruction are monitored in an intensive care unit (ICU) versus a specialty ward unit postoperatively. MATERIALS AND METHODS: A prospective, non-inferiority, randomized controlled trial was conducted from 7/22/2016 to 9/12/2018 at a single institution. Patients were randomized to the ICU or specialty ward unit. Flap check protocols were identical between the groups. Perioperative and postoperative outcome variables were assessed and compared. RESULTS: 131 patients were enrolled in the study and 118 ultimately underwent head and neck free flap reconstruction. 57 were randomized to the ICU and 61 to the specialty ward unit. There were no significant differences between the ICU and specialty ward unit groups with regard to demographic variables including age, gender, co-morbidities, tobacco or alcohol use, prior chemotherapy or radiation therapy treatment. There were no significant differences in perioperative variables including need for transfusion, tracheostomy, ischemia time, blood loss, fluid administration or post-operative antibiotic use. There was no significant difference in the primary outcome variable, length of stay. There were no significant differences in the number of the medical or surgical complications, flap failure rate, or hospital costs. CONCLUSION: In this prospective, randomized controlled trial, head and neck free-flap patients cared for on a specialty ward in the immediate post-operative period had equivalent outcomes to those cared for in the ICU.

Pathological margins and advanced cutaneous squamous cell carcinoma of the head and neck.

OBJECTIVE: The recommended treatment for cutaneous squamous cell cancer (CuSCC) of the head and neck is Mohs surgical excision or wide local excision. Excision is recommended to a gross surgical margin of 4-6 mm however this is based on limited evidence and specify a goal histologic margin. The objective of this study was therefore to examine the reported histological margin distance following WLE of advanced CuSCC and its association with recurrence and survival. STUDY DESIGN: Retrospective database review. SETTING: All patients included received treatment at UC Davis Department of Otolaryngology-Head and Neck Surgery and/or Radiation Oncology in Sacramento, California. SUBJECTS AND METHODS: The patients included were treated for advanced CuSCC with primary surgery with or without adjuvant therapy. Kaplan Meier survival curves with log rank analysis were then performed to compare 5-year recurrence free survival, and disease-specific survival for patients with different margin distances. RESULTS: Total number of subjects was 92. The overall 5-year DSS and RFS was 68.8 and 51.0% respectively. When the pathological margin distance was ≥5 mm, 5-year disease specific survival was improved when compared to margin distance less than 5 mm (94.7 vs 60.7 p = 0.034). CONCLUSION: The findings of this study suggest that a histologic margin of at least 5 mm may increase survival in advanced head and neck CuSCC patients.

Autofluorescence lifetime augmented reality as a means for real-time robotic surgery guidance in human patients.

Due to loss of tactile feedback the assessment of tumor margins during robotic surgery is based only on visual inspection, which is neither significantly sensitive nor specific. Here we demonstrate time-resolved fluorescence spectroscopy (TRFS) as a novel technique to complement the visual inspection of oral cancers during transoral robotic surgery (TORS) in real-time and without the need for exogenous contrast agents. TRFS enables identification of cancerous tissue by its distinct autofluorescence signature that is associated with the alteration of tissue structure and biochemical profile. A prototype TRFS instrument was integrated synergistically with the da Vinci Surgical robot and the combined system was validated in swine and human patients. Label-free and real-time assessment and visualization of tissue biochemical features during robotic surgery procedure, as demonstrated here, not only has the potential to improve the intraoperative decision making during TORS but also other robotic procedures without modification of conventional clinical protocols.

Time-resolved fluorescence spectroscopy for the diagnosis of oral lichen planus.

BACKGROUND: Lichen planus (LP) is a T-cell mediated autoimmune disorder of unknown aetiology that affects the skin, nails, oral and genital mucous membranes. Conventionally, oral LP (OLP) is diagnosed through clinical assessment and histopathological confirmation by oral biopsy. AIM: To explore the use of time-resolved fluorescence spectroscopy (TRFS) to detect fluorescence lifetime changes between lesional OLP and perilesional normal mucosa. METHODS: In this pilot study, measurements of lesional and perilesional buccal and mouth floor mucosa were conducted in vivo with a TRFS system. Histopathological findings were consistent with OLP in 8 out of 10 patients biopsied. Two patients with histopathological diagnoses of frictional hyperkeratosis and oral candidiasis, respectively, were excluded from the study. RESULTS: Our preliminary data show that lifetime values in the 360-560 nm spectral range indicate a significant differentiation between normal and diseased tissue. In contrast to the standard oral biopsy procedure, this technique is noninvasive, painless, time-efficient and safe. CONCLUSIONS: Future studies are needed to better elucidate the diagnostic capability of TRFS and to further explore the sources of fluorescence contrast. This pilot study suggests that, based on fluorescence lifetime parameters, TRFS is a very promising technology for the development of a novel OLP diagnostic technique.

Efficacy of laryngectomy alone for treatment of locally advanced laryngeal cancer: A stage- and subsite-specific survival analysis.

OBJECTIVE: Total laryngectomy is a well-established treatment for locally advanced laryngeal cancer. Evidence for the benefit of post-operative radiotherapy after laryngectomy in patients with locally advanced primaries and N0 or N1 nodal disease is limited. This study aimed to determine whether total laryngectomy alone is adequate therapy for certain patient subgroups with locally advanced laryngeal cancer. DESIGN: We performed a retrospective survival analysis of patients in the surveillance epidemiology and end results (SEER) database with locally advanced laryngeal cancer between 2004 and 2012. OUTCOME MEASURES: Primary outcome measure was overall survival. RESULTS: For all patients with T3-4aN0-1 tumours, overall survival was worse for those treated with laryngectomy only when compared using the Kaplan-Meier with a log-rank test and when accounting for demographic and tumour data using a Cox multivariate regression. Other independent predictors of poor survival included age >65 years old, Medicaid or uninsured payor status, supraglottic primary and N1 nodal disease. Stage- and subsite-specific analysis revealed that patients with T4a primary tumours, N1 nodal disease and supraglottic subsite had worse overall survival when treated with laryngectomy alone. Alternatively, patients with T3 primary tumours, N0 nodal disease, glottic subsite had equivalent overall survival and disease-specific survival when treated with laryngectomy alone vs laryngectomy with post-operative radiotherapy. CONCLUSION: Locally advanced laryngeal cancer patients with T3 primaries, no nodal disease or primaries of the glottis may not benefit from post-operative radiotherapy when treated with primary total laryngectomy.

Helical tomotherapy with simultaneous integrated boost dose painting for the treatment of synchronous primary cancers involving the head and neck.

OBJECTIVE: To demonstrate the feasibility of helical tomotherapy (HT)-based intensity-modulated radiotherapy (IMRT) for the treatment of synchronous primary cancers arising from the head and neck. METHODS: 14 consecutive patients with histologically proven squamous cell carcinoma of the head and neck were determined to have a second primary cancer in the upper aerodigestive tract on further evaluation and were treated with HT using simultaneous integrated boost IMRT. Megavoltage CT scans were acquired daily as part of an image-guided registration protocol. Concurrent platinum-based systemic therapy was given to nine patients (64%). RESULTS: HT resulted in durable local control in 21 of the 28 primary disease sites irradiated, including a complete clinical and radiographic response initially observed at 17 of the 20 sites with gross tumour. The mean displacements to account for interfraction motion were 2.44 ± 1.25, 2.92 ± 1.09 and 2.31 ± 1.70 mm for the medial-lateral (ML), superior-inferior (SI) and anteroposterior (AP) directions, respectively. Table shifts of >3 mm occurred in 19%, 20% and 22% of the ML, SI and AP directions, respectively. The 2-year estimates of overall survival, local-regional control and progression-free survival were 58%, 73% and 60%, respectively. CONCLUSION: The effectiveness of HT for the treatment of synchronous primary cancers of the head and neck was demonstrated. ADVANCES IN KNOWLEDGE: HT is a feasible option for synchronous primary cancers of the head and neck and can result in long-term disease control with acceptable toxicity in appropriately selected patients.

Overstaging of cartilage invasion by multidetector CT scan for laryngeal cancer and its potential effect on the use of organ preservation with chemoradiation.

OBJECTIVE: The two currently acceptable treatment options for locally advanced laryngeal cancer are total laryngectomy and organ preservation using chemoradiation. To facilitate therapeutic decision making, the accurate pre-treatment evaluation of cartilage invasion is of paramount importance. The purpose of this study was to evaluate the positive predictive value (PPV) and negative predictive value (NPV) of detecting neoplastic cartilage invasion in laryngeal cancer patients using fast-speed multidetector CT (MDCT). METHODS: 61 consecutive patients with clinically staged T3 or T4 squamous cell carcinoma of the larynx or hypopharynx who underwent total laryngectomy were analysed. All patients had MDCT of the neck within 2 weeks prior to surgery. Central radiographic and pathological review was performed in an attempt to correlate findings. MDCT invasion of cartilage was graded based on objective criteria. RESULTS: MDCT scan was found to have a PPV of 78% and an NPV of 100% for detection of invasion through cartilage, with sensitivity being 100% and specificity 96%. For detection of any cartilage invasion (minor, major or through cartilage invasion), PPV and NPV were 63% and 92%, respectively. The sensitivity was 85% and specificity was 75%. For the detection of tumour invasion through cartilage or major cartilage invasion, MDCT scan had a PPV of 53% and an NPV of 95%. 47% (9/19) patients were down-staged from T4 to T3 after central pathology review. CONCLUSION: The low PPV for cartilage destruction using MDCT suggests that a significant proportion of patients who were treated by total laryngectomy could have been appropriately offered organ preservation if more accurately staged at initial diagnosis.

An endoscopic grading system for vocal process granuloma.

BACKGROUND: A reliable grading system allows the clinician to classify disease severity, monitor progress and evaluate treatment efficacy. There is no currently accepted grading system for vocal process granuloma of the larynx. AIM: To evaluate the reliability of a new grading system for vocal process granuloma. METHODS: All vocal process granuloma images from a digital laryngeal image library were abstracted. Granulomas were graded on a one to four system, as follows: grade one, sessile, non-ulcerative granuloma limited to vocal process; grade two, pedunculated or ulcerated granuloma limited to vocal process; grade three, granuloma extending past vocal process but not crossing midline of airway in fully abducted position; and grade four, granuloma extending past vocal process and past the midline of the airway in the fully abducted position. The granulomas were additionally graded A if unilateral and B if bilateral. Two laryngologists and two otolaryngology residents rated the granulomas on two separate occasions. Intra- and inter-observer reliability was evaluated with the kappa (kappa) test statistic. RESULTS: Thirty-five vocal process granulomas were identified. The percentage intra-observer agreement for the two laryngologists was 97 and 100 per cent (kappa = 0.94 and 1.00, respectively). The percentage inter-observer agreement between the two laryngologists was 91 per cent (kappa = 0.83). The percentage intra-observer agreement for the two residents was 89 and 91 per cent (kappa = 0.83 and 0.77, respectively). The percentage inter-observer agreement between the two residents was 83 per cent (kappa = 0.67). CONCLUSIONS: The proposed grading system for vocal process granuloma displayed excellent intra- and inter-observer reliability among residents and experienced laryngologists.

Hybrid Optical-Ultrasonic Technique for Biomedical Diagnostics.

We report the development of a diagnostic system combining time-resolved fluorescence spectroscopy and ultrasound backscatter microscopy and its application in diagnosis of tumors and atherosclerotic disease. This system allows for concurrent evaluation of distinct compositional, functional, and micro-anatomical features of normal and diseased tissues.

Transnasal oesophagoscopy-guided in-office secondary tracheoesophageal puncture.

OBJECTIVE: Tracheoesophageal puncture is recognised as an effective and reliable method for voice restoration following total laryngectomy. Several techniques have been described, ranging from rigid oesophagoscopy under general anaesthesia to more recent endoscopic techniques utilising intravenous sedation or local anaesthetic. We describe our technique for secondary tracheoesophageal puncture utilising unsedated transnasal oesophagoscopy in an office setting. METHOD: Retrospective review of all total laryngectomy patients undergoing in-office transnasal oesophagoscopy-assisted tracheoesophageal puncture between October 1 2004 and December 31 2006. RESULTS: Eleven patients undergoing transnasal oesophagoscopy-guided tracheoesophageal puncture were identified. Successful tracheoesophageal puncture placement was achieved in 10 of 11 patients (91 per cent). In one patient tracheoesophageal puncture could not be performed due to anatomic constraints. One patient had bleeding from the puncture site requiring silver nitrate cautery. All patients tolerated the procedure well. Voice results were satisfactory in all cases. CONCLUSIONS: Transnasal oesophagoscopy-guided tracheoesophageal puncture provides a simple, safe option for secondary voice rehabilitation in laryngectomy patients.

Transcriptional activity of multiple copies of a subtelomerically located olfactory receptor gene that is polymorphic in number and location.

We report here on the transcriptional activity of multiple copies of a subtelomerically located olfactory receptor (OR) gene, OR-A. Due to recent duplication events, both the copy number and chromosomal location of OR-A vary among humans. Sequence analyses of 180 copies of this gene, derived from 12 chromosome ends in 22 individuals, show that the main coding exon of all but one copy is an intact open reading frame with 0-5 predicted amino acid differences. We detected transcription of OR-A in both olfactory epithelium and testis tissue using RT-PCR amplification with primers designed on the basis of a computationally predicted gene structure. Two alternatively spliced forms of transcripts, one encoding an isoform with an extended N-terminus, were found in both tissues. A third transcript, derived from a second promoter, was also observed in testes. The start methionine is predicted in all transcripts to lie in an upstream exon rather than the main coding exon, as is typical for most other OR genes. By examining sequence variants among transcripts, we show that transcription of this gene occurs at multiple chromosomal locations. Our results lend credence to the idea that OR diversity could be generated in rearrangement-prone subtelomeric regions and show that polymorphism in subtelomeric regions could lead to individual-to-individual variation in the expressed repertoire of OR genes.

Genetic and epigenetic changes in human epithelial cells immortalized by telomerase.

Exogenous expression of hTERT, the catalytic component of telomerase, is sufficient for the immortalization of human fibroblasts but insufficient for the immortalization of human foreskin keratinocytes (HFKs) and human mammary epithelial cells (HMECs). These latter cell types can overcome senescence by coexpression of hTERT and human papillomavirus (HPV) E7 or by expression of hTERT and loss of p16(INK4a) expression, indicating that the retinoblastoma (Rb) pathway, along with a telomere maintenance pathway, plays a role in determining the life span of epithelial cells. In this study, we further characterize hTERT-immortalized HFKs and human adenoid epithelial cells (HAKs) for genotypic and phenotypic alterations that are associated with immortalization. Of five hTERT-immortalized HFK and HAK cell lines examined, four exhibited repression of p16(INK4a) expression by promoter methylation or specific large-scale deletion of chromosome 9p, the location of p16(INK4a). Interestingly, one cell line exhibited complete down-regulation of expression of p14(ARF), with only slight down-regulation of expression of p16(INK4a). Yet, all of the immortal cells lines exhibited hyperphosphorylated Rb. Cytogenetic analysis revealed clonal chromosome aberrations in three of the five cell lines. All of the cell lines retained a growth block response with the expression of mutant ras. When grown on organotypic raft cultures, however, the hTERT-immortalized cells exhibited a maturation delay on terminal differentiation. Our results indicate that immortalization of epithelial cells may require both activation of telomerase and other genetic and/or epigenetic alterations that abrogate normal differentiation.

Oromandibular reconstruction.

Oromandibular reconstruction is one of the greatest challenges of the head and neck surgeon. The ideal rehabilitation of the mandible and associated soft tissues requires maintaining premorbid occlusion, providing the opportunity for dental restoration, and preventing salivary incontinence. The approach to each patient must be individualized to maximize speech, swallowing, and mastication. Additionally, the surgeon must strive to fulfill these goals while achieving the most pleasing cosmetic result possible. Although some patients may be treated without reconstruction or with a metal plate and soft tissue flap, the majority of patients benefit from bony reconstruction utilizing a free flap. Reconstruction with free flaps results in more primary healing and fewer wound complications. Challenges specific to reconstructing the temporomandibular joint are discussed. We also review the indications for the different rehabilitative options and the merits of the individual flaps.

Expression of Epstein-Barr virus latent membrane proteins leads to changes in keratinocyte cell adhesion.

Epstein-Barr virus (EBV) has 3 latent membrane proteins (LMPs)--LMP1, LMP2a, and LMP2b--which are expressed in nasopharyngeal carcinoma. Using keratinocyte cell lines expressing LMP2a and LMP2b and coexpressing LMP1/LMP2a, we grew organotypic raft cultures to analyze changes in morphology and expression of the cell adhesion molecule ICAM-1; alpha2, alpha3, alpha5, beta1, and alpha6beta4 integrins; laminin 5; E-cadherin; and desmoplakin. Cells expressing LMP2a or LMP2b were defective in their ability to mature and progress through normal squamous stratification when compared to the parental cell lines. Cells coexpressing LMP1/LMP2a additionally demonstrated "pseudoinvasion" into the raft dermal equivalent. There was a consistent and dramatic up-regulation in the suprabasal expression of laminin 5 and alpha6beta4 and beta1 integrins in the LMP-expressing cell lines. ICAM-1, not expressed in the control cell lines, was up-regulated in the LMP-expressing cell lines. Expression of alpha3 and alpha5 integrins was also up-regulated in the LMP-expressing cell lines, while alpha2 demonstrated a loss of the normal basal layer expression. E-cadherin and desmoplakin expression patterns were essentially unchanged. We conclude that LMP2a and LMP2b singly, and LMP1/LMP2a coexpressed, are capable of altering keratinocyte cell adhesion molecule expression consistent with nasopharyngeal carcinoma.

High-resolution computed tomography of the temporal bone of the Macaca mulatta monkey.

High-resolution computed tomography (CT) slices of the temporal bone of the Macaca mulatta monkey were performed and key anatomical landmarks were identified and labelled. The scans provided detailed anatomical definition of the monkey temporal bone and were considered a useful basis for studying the anatomy of a primate model.

Specificity of pseudorabies virus as a retrograde marker of sympathetic preganglionic neurons: implications for transneuronal labeling studies.

The purpose of the present study was to examine the specificity of the Bartha strain of pseudorabies virus (PRV) as a CNS retrograde marker. This information is critical in assessing whether this virus has potential value as a specific transneuronal marker. The model system chosen for analysis was the intermediolateral cell column (IML)--the principal site of origin of sympathetic preganglionic neurons (SPNs). Two experiments were performed. The first experiment established the usefulness of this model system and the second examined the properties of PRV as a retrograde cell body marker. In the first experiment, injections of two different conventional retrograde cell body markers (cholera toxin-beta subunit (CTb) and Fluoro-Gold) were made in two ipsilateral sympathetic structures (viz., stellate ganglion and adrenal gland) in the same rat. This experiment established that (1) heterogenous SPNs originate in the same cell clusters that form the IML at the T4-T8 levels and 2) SPNs innervate specific sympathetic targets with almost none providing a dual innervation of the stellate ganglion and adrenal gland. This mosaic arrangement of target-specific SPNs makes the IML an excellent CNS site for this type of study. The second experiment followed the same paradigm: PRV was injected into the stellate ganglion and CTb into the adrenal gland (and vice versa). These experiments established that PRV infections of one functional class of SPNs did not produce infections in nearby, functionally unrelated SPNs and did not cause a reduction in the SPN cell population, except under conditions of severe gliosis. These two properties increase the probability that Bartha PRV may be used as a specific retrograde transneuronal marker of central autonomic pathways.