The role of adjuvant treatment in early-stage oral cavity squamous cell carcinoma: An international collaborative study.

BACKGROUND: Up to half of patients with oral cavity squamous cell carcinoma (OCSCC) have stage I to II disease. When adequate resection is attained, no further treatment is needed; however, re-resection or radiotherapy may be indicated for patients with positive or close margins. This multicenter study evaluated the outcomes and role of adjuvant treatment in patients with stage I to II OCSCC. METHODS: Overall survival (OS), disease-specific survival, local-free survival, and disease-free survival rates were calculated with Kaplan-Meier analysis. RESULTS: Of 1257 patients with T1-2N0M0 disease, 33 (2.6%) had positive margins, and 205 (16.3%) had close margins. The 5-year OS rate was 80% for patients with clear margins, 52% for patients with close margins, and 63% for patients with positive margins (P < .0001). In a multivariate analysis, age, depth of invasion, and margins were independent predictors of outcome. Close margins were associated with a >2-fold increase in the risk of recurrence (P < .0001). The multivariate analysis revealed that adjuvant treatment significantly improved the outcomes of patients with close/positive margins (P = .002 to .03). CONCLUSIONS: Patients with stage I to II OCSCC and positive/close margins have poor long-term outcomes. For this population, adjuvant treatment may be associated with improved survival. Cancer 2018;124:2948-55. © 2018 American Cancer Society.

Detecting influenza epidemics using search engine query data.

Seasonal influenza epidemics are a major public health concern, causing tens of millions of respiratory illnesses and 250,000 to 500,000 deaths worldwide each year. In addition to seasonal influenza, a new strain of influenza virus against which no previous immunity exists and that demonstrates human-to-human transmission could result in a pandemic with millions of fatalities. Early detection of disease activity, when followed by a rapid response, can reduce the impact of both seasonal and pandemic influenza. One way to improve early detection is to monitor health-seeking behaviour in the form of queries to online search engines, which are submitted by millions of users around the world each day. Here we present a method of analysing large numbers of Google search queries to track influenza-like illness in a population. Because the relative frequency of certain queries is highly correlated with the percentage of physician visits in which a patient presents with influenza-like symptoms, we can accurately estimate the current level of weekly influenza activity in each region of the United States, with a reporting lag of about one day. This approach may make it possible to use search queries to detect influenza epidemics in areas with a large population of web search users.

The prognostic impact of extent of bone invasion and extent of bone resection in oral carcinoma.

OBJECTIVE: The prognostic impact of mandibular invasion by oral squamous cell carcinoma (SCC) is controversial. The objective of this study was to assess the effect that extent of bone invasion has on recurrence and survival in patients treated with marginal and segmental mandible resection. STUDY DESIGN: A retrospective cohort study of patients whose clinicopathologic information had been collected prospectively into a dedicated head and neck database. METHODS: Local control and disease-specific survival were retrospectively reviewed in 111 patients (median follow-up, 44 months) with oral SCC undergoing marginal or segmental mandibulectomy. RESULTS: Bone invasion was present in 46% of marginal and 94% of segmental resections. Five-year local control was similar following marginal (83%) and segmental mandibulectomy (86%). There was no correlation with presence or extent of bone invasion. Survival at 5 years was 71% and this correlated with bone invasion and involved margins (P < .05), but not with extent of mandible invasion or resection. CONCLUSIONS: Marginal mandibulectomy does not adversely alter outcome in selected patients with bone invasion provided margins are not compromised.

Clinical outcome after surgery for 75 patients with parotid sialadenitis.

OBJECTIVE: To analyze the clinical outcome of patients treated surgically for chronic parotid sialadenitis. STUDY DESIGN: A retrospective cohort study of patients whose clinicopathologic information had been collected prospectively onto a dedicated head and neck database. METHODS: Between 1987 and 2006, a total of 75 patients had 78 parotidectomies, 17 superficial and 61 near-total, to treat chronic parotid sialadenitis. The clinicopathologic data including treatment morbidity and outcome were analyzed. RESULTS: Temporary postoperative facial weakness occurred in 26 (33%) patients, and this was permanent, although partial, in one (1%) patient. There was no significant difference (P > .05) in the incidence of temporary facial nerve neuropraxia in the superficial (35%) and near-total parotidectomy (33%) groups. Recurrence of symptoms was noted in two patients who had undergone near-total parotidectomy and none of the patients who had undergone superficial parotidectomy. Chronic parotid sialadenitis was effectively treated in 97% of patients undergoing parotidectomy. CONCLUSION: Near-total parotidectomy is a safe and efficacious surgical treatment in the management of patients with debilitating severe chronic parotid sialadenitis.

Squamous cell carcinoma from an unknown head and neck primary site: a "selective treatment" approach.

OBJECTIVE: To assess the efficacy of limiting treatment to the involved neck by way of neck dissection and adjuvant radiotherapy and reserving other therapies for salvage in the management of metastatic cervical squamous cell carcinoma from an unknown head and neck primary site. DESIGN: Retrospective study of patients whose clinicopathological data had been prospectively collected in a comprehensive head and neck database. SETTING: A tertiary referral university hospital. PATIENTS: The study population comprised 70 patients with metastatic cervical squamous cell carcinoma from an unknown head and neck primary site. INTERVENTIONS: Neck dissection alone in patients with pN1 disease confined to the lymph node. All remaining patients received neck dissection and adjuvant postoperative irradiation of the involved (dissected) neck. MAIN OUTCOME MEASURES: Incidence of primary, regional, and distant recurrence and disease-specific and overall survival. RESULTS: Nodal stage was pN1 in 5 patients (7%); pN2a in 13 (19%); pN2b in 30 (43%); pN2c in 4 (6%); and pN3 in 18 (26%). Neck dissection alone was performed in 10 patients (14%), while 60 patients (86%) underwent neck dissection and adjuvant irradiation. Median follow-up was 45 months. The primary tumor site emerged in 8 patients (11%). The 5-year control rates were 84% in the ipsilateral (dissected) neck and 93% in the contralateral (undissected) neck. The 5-year disease-specific and overall survival rates were 62% and 56%, respectively. Macroscopic extracapsular spread was the only statistically significant adverse prognostic factor (P < .001). CONCLUSIONS: The results of our selective treatment approach compare favorably with the results of other reported protocols using comprehensive irradiation or concurrent chemoradiation. However, patients with extracapsular spread and pN2 or pN3 disease were at high risk of treatment failure and may benefit from adjuvant chemoradiation. Although our protocol spares patients of potentially morbid therapies, salvage is rarely successful.

Predicting lymph node metastases in cutaneous squamous cell carcinoma: use of a morphological scoring system.

BACKGROUND: Predicting which patients will develop nodal metastasis from cutaneous squamous cell carcinoma (cSCC) remains difficult. This study evaluates a recently described histological risk model validated for mucosal head and neck SCC (HNSCC) when applied to cutaneous tumours. In this model, morphologic variables including worst pattern of invasion, lymphocytic host response and perineural invasion were shown to predict disease recurrence, loco regional recurrence and overall survival in mucosal HNSCC. METHODS: Patients with cSCC and known metastatic spread were identified from the author's database over a 5-year period between July 2007 and July 2012. Histology specimens from the original primary tumour were separately analysed by 2 histopathologists. Scores were compared against T-Stage matched control specimens without metastatic spread. RESULTS: 27 patients with metastatic cSCC were identified. Scores for worst pattern of invasion (WPOI) were significantly higher in individuals with lymph node metastases (p=0.02). CONCLUSIONS: Adverse pattern of invasion, defined as presence of small tumour islands or tumour satellites may be an independent risk factor for developing nodal metastases in cSCC. These tumours are difficult to investigate histopathologically as it is difficult to be confident the correct primary is chosen for study.

Morning salivary cortisol versus short Synacthen test as a test of adrenal suppression.

BACKGROUND: The short Synacthen test (SST) is the most commonly used test for the assessment of adrenal suppression. We investigated the potential of a simpler and more cost-effective procedure [morning salivary cortisol (MSC)] as an outpatient screening tool to detect adrenal suppression in patients using topical intranasal corticosteroids for rhinosinusitis. METHOD: Forty-eight patients who were using topical corticosteroids underwent adrenal function assessment by way of SST and MSC measurement. RESULTS: Sixteen of the 48 patients had impaired MSCs. Of these 16 patients, 15 had an impaired SST (sensitivity 100%) and one had a normal SST. All patients with normal MSCs also had normal SSTs (specificity 97%). CONCLUSION: The morning salivary cortisol measurement is a useful screening tool for adrenal suppression in this setting.

Efficacy and systemic tolerability of mometasone furoate and betamethasone sodium phosphate.

This study evaluates the efficacy and systemic tolerability of licensed doses of mometasone furoate (Nasonex) and betamethasone sodium phosphate (Betnesol) in allergic chronic rhinosinusitis patients. It also assesses the diagnostic accuracy of morning salivary cortisol (MSC) concentrations to screen for adrenal suppression in these patients. Forty-eight patients were prospectively randomized to two treatment limbs. Symptom scores and adrenal function assessments were performed immediately prior to commencement and at the end of treatment. One (4 per cent) mometasone furoate and 14 (58 per cent) betamethasone sodium phosphate patients developed biochemical evidence of adrenal suppression. There were statistically significant (p < 0.005) reductions in symptom scores following treatment, but no significant difference (p > 0.05) between the drug groups regarding post-treatment symptom scores. As a screening tool for iatrogenic adrenal suppression, MSC had a sensitivity of 100 per cent and a specificity of 97 per cent. This study demonstrates the high risk of developing adrenal suppression secondary to betamethasone sodium phosphate therapy. The salivary cortisol assay is an accurate tool for monitoring adrenal function and is ideally suited to the out-patient setting.

Parotid metastatic disease from cutaneous squamous cell carcinoma: prognostic role of facial nerve sacrifice, lateral temporal bone resection, immune status and P-stage.

BACKGROUND: Recognized prognostic indicators for metastatic cutaneous squamous cell carcinoma (SCC) of the head and neck include facial nerve involvement, immune status, and "parotid" staging system (P-stage). We sought to examine the impact of lateral temporal bone resection (LTBR) on prognosis. METHODS: We conducted a retrospective analysis of 160 patients with metastatic cutaneous SCC to the parotid. All patients had parotidectomy and neck dissection; 27% had additional LTBR when the tumor was adherent to the temporal bone. RESULTS: Overall 5-year survival was 48%, disease-specific survival 77%, and locoregional control 83%. Corresponding results for immunocompetent versus immunocompromised were 55%, 86%, and 87% versus 12%, 48%, and 64%. On Cox regression analysis, only immunocompromised status (ie, lymphoproliferative disorder, organ-transplant patient) was prognostically significant (p < .001). CONCLUSION: More radical resection that may include LTBR mitigates the poorer prognosis with advanced disease in our series. Treatment must be individualized in immunocompromised patients who have shortened overall survival.

Outcomes of squamous cell cancer of the oral tongue managed at the Princess Margaret Hospital.

BACKGROUND: The purpose of this study was to analyze the outcomes and treatment in patients with squamous cell carcinoma (SCC) of the oral tongue, as well as validate previously reported predictors of survival. METHODS: We retrospectively reviewed 259 patients treated with curative intent between 1994 and 2004. Kaplan-Meier estimates, log-rank test, and Cox regression models were used for statistical analysis. RESULTS: Two hundred fifty-nine patients were managed with surgery; 67 patients (25%) received adjuvant radiotherapy. Mean follow-up was 60 months. The 5-year local and regional control rates were 78% and 69.4%, respectively. The 5-year overall, disease-specific, and recurrence-free survival rates were 69%, 70.9%, and 53%, respectively. The only significant predictor of both overall survival (OS) and disease-free survival (DFS) on multivariable analysis was pathologic N classification. CONCLUSION: Treatment of early tongue SCC effectively achieves local control and DFS. Nodal disease remains to be 1 of the most important prognostic factors in terms of recurrence and survival.

Vertical partial laryngectomy with temporoparietal free flap reconstruction for recurrent laryngeal squamous cell carcinoma: technique and long-term outcomes.

OBJECTIVES: To present a technique for reconstruction of the vertical partial laryngectomy defect using a vascularized carrier consisting of a temporoparietal free flap, cartilage graft, and buccal mucosal graft; to evaluate the oncologic outcomes with respect to locoregional control and overall survival; and to provide an assessment of patient quality of life and functional outcomes. DESIGN: Retrospective medical record review and prospective cross-sectional analysis of functional outcomes. SETTING: Princess Margaret Hospital-University Health Network and the Odette Cancer Centre-Sunnybrook Health Sciences Centre. METHODS: We collected data on patient demographic characteristics, tumor staging, initial treatment, recurrence, management, and follow-up. Prospectively, a cross-sectional study was performed using the European Organization for Research and Treatment of Cancer Quality of Life of Cancer Patients Questionnaire C30 and HN35 module and voice and swallowing results using the Voice Handicap Index and Swallowing Quality of Life index. MAIN OUTCOME MEASURES: Local recurrence-free survival, cause-specific survival, and overall survival. RESULTS: Forty men met inclusion criteria (median age, 65.0 years). Local recurrence-free survival was 84% at 3 years and 75% at 5 years. Cause-specific survival was 88% at 3 years and 78% at 5 years. Thirty-eight patients were successfully decannulated; all patients tolerated oral intake after the surgical procedure. The C30 and HN35 symptomatic results were comparable with patients with standardized stages I and II head and neck tumors. The Voice Handicap Index results were comparable with patients with functional dysphonia. Patients' swallowing was in the normal range. CONCLUSIONS: Patients receiving vertical partial laryngectomy with temporoparietal free flap reconstruction for recurrent glottic carcinoma following radiation treatment failure have high rates of locoregional control. The use of the temporoparietal free flap in this patient population produces high-quality voice results and normal swallowing and has no major effect on quality of life.

Supraclavicular artery island flap for reconstructing defects in the head and neck region.

PURPOSE OF REVIEW: The supraclavicular artery island flap is a rotation flap that offers a versatile reconstructive option for head and neck defects. Recent anatomical studies have improved our understanding of the vascular supply of the supraclavicular artery island flap. Furthermore, several published large series describe the utility and reliability of this flap. In this article, we review the scientific literature describing the vascular anatomy of the supraclavicular artery island flap, its clinical application, and limitations in reconstructing defects in the head and neck region. RECENT FINDINGS: The vascular anatomy and surface markings, optimal flap design, surgical techniques employed to improve reliability, and aesthetic and functional outcomes of the supraclavicular artery island flap in head and neck reconstruction are well documented in the literature. SUMMARY: The supraclavicular artery island flap offers a versatile and well tolerated option in reconstruction of head and neck defects with several advantages over more traditional regional flaps and distant-free flaps.

Clinical utility of colour flow Doppler ultrasonography in planning anterolateral thigh flap harvest.

BACKGROUND: The anatomic variability of cutaneous perforators contributes to the technical challenges of anterolateral thigh (ALT) free flap harvest. The objective of this study was to assess the accuracy and clinical utility of preoperative colour flow Doppler (CFD) ultrasonography in evaluating planned ALT flap donor sites. METHODS: A prospective study of the infrainguinal vasculature (profunda femoris and lateral circumflex femoral arteries) in 16 consecutive patients scheduled for ALT free flap transfer for reconstruction of head and neck surgical defects was undertaken. All patients underwent CFD ultrasonography. The location of perforators and the thigh thickness determined by CFD ultrasonography were correlated with the actual intraoperative findings using a scatter plot and paired t-test. RESULTS: Two patients were diagnosed with bilateral silent infrainguinal claudication, which precluded safe use of the ALT donor site. In two other patients, the planned ALT donor site ipsilateral to the defect was not used because of silent infrainguinal claudication diagnosed by CFD ultrasonography. In the 14 patients who underwent ALT flap harvest, CFD ultrasonography identified 48 perforators, which coincided with 43 actual perforators found intraoperatively. CFD ultrasonography demonstrated a statistically significant correlation with the actual perforator locations (Spearman coefficient .76; p = .55). Although CFD ultrasonography tended to underestimate flap thickness, there was a statistically significant correlation (Spearman coefficient .94; p ≤ .0001) with the actual flap thickness. CONCLUSION: CFD ultrasonography has clinical utility in facilitating decision making and planning ALT flap harvest.

Prognostic impact of intraoperative microscopic cut-through on frozen section in oral cavity squamous cell carcinoma.

OBJECTIVE: Although the literature suggests that a positive tumour margin on permanent section portends a poor oncologic outcome, the prognostic implication of microscopic tumour cut-through (ie, positive tumour margin on intraoperative frozen section) that is surgically revised to a negative final margin on permanent section is currently unclear. Therefore, this study aimed to analyze the influence of microscopic tumour cut-through on disease recurrence and survival and to establish clinicopathologic variables associated with tumour cut-through. DESIGN: A retrospective chart review. SETTING: The Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto. METHODS: Comprehensive clinicopathologic data were collected, including demography, clinical tumour staging (TNM), treatment, histopathologic details, recurrence, management, and follow-up. MAIN OUTCOME MEASURES: Local cancer control and disease-specific survival were the main outcome measures of interest. The Kaplan-Meier method was used to assess outcome measures by patient group, and the log-rank test was used to compare survival curves. Univariate and multivariate Cox proportional hazard regression analyses were used to test the association of various clinical factors and to identify independent prognostic factors of local control and disease-specific survival. RESULTS: Sixty-five patients met inclusion criteria for our study (37 males; median age 64.4 years). Both local control and disease-specific survival were statistically significantly reduced in patients with positive intraoperative frozen section despite revision to obtain negative margins (p < .05). Multivariate analysis showed that microscopic tumour cut-through independently predicted poorer local control and disease-specific survival (p < .05). CONCLUSIONS: This study in patients receiving primary surgery for oral squamous cell carcinoma shows that microscopic tumour cut-through on intraoperative frozen section independently portends a poorer oncologic prognosis, regardless of ultimate tumour margin pathology.

Circumferential pharyngeal reconstruction: history, critical analysis of techniques, and current therapeutic recommendations.

Reconstruction of circumferential pharyngeal defects following total pharyngolaryngectomy presents major challenges with respect to surgical morbidity and restoration of functional deficits, which are often made more demanding by the increasing trend to utilize primary chemoradiation protocols with surgery reserved for salvage cases. The present review evaluates the reconstructive techniques described in the literature, including historical techniques as well as more recent innovative methods. Each technique is critically appraised with particular reference to postoperative morbidity and functional rehabilitation. Treatment recommendations are made based on the available evidence.

Clinicopathologic and therapeutic risk factors for perioperative complications and prolonged hospital stay in free flap reconstruction of the head and neck.

BACKGROUND: We aimed to determine predictors of morbidity in patients undergoing microvascular free flap reconstruction of the head and neck. METHODS: We prospectively evaluated 796 cases between 1999 and 2007 using univariate and multivariate analysis to determine predictors of morbidity and prolonged hospital stay. RESULTS: Two hundred thirty-nine patients (30%) developed major complications. Age, body mass index (BMI), American Society of Anesthesiology (ASA) score, Kaplan Feinstein comorbidity index (KFI) score, preoperative hemoglobin, and tracheostomy were independent predictors of major complication. Predictors of prolonged hospital stay included age, recent weight loss, alcohol excess, ASA, KFI, preoperative hemoglobin, mucosal surgery, anesthesia duration, and crystalloid replacement volume. CONCLUSION: Several variables are associated with an increased risk of development of major complications following free flap reconstruction of the head and neck. Although many of these variables are irreversible, they aid risk stratification of patients undergoing free flap reconstruction, and assist clinicians in making treatment decisions, consenting, and providing patients with realistic expectations regarding their perioperative course.

Impact of positive frozen section microscopic tumor cut-through revised to negative on oral carcinoma control and survival rates.

BACKGROUND: The objective of the study was to evaluate the prognostic and therapeutic implications of an initial positive frozen section margin that was revised until negative (microscopic tumor cut-through), and to analyze the influence of microscopic margin status on oral carcinoma control. METHODS: The approach in our investigation was through a retrospective review of patients treated with primary surgery, with frozen section margin control in oral carcinoma. Inclusion criteria included availability of frozen and permanent section histology reports of resection margins and negative final resection margins. RESULTS: Of 547 patients studied, 175 received adjuvant radiation. Local and regional control and disease-specific survival rates were 81.6%, 78.4%, and 76.3%, respectively. Tumor cut-through and pathologic nodal (pN) stage had an independently adverse effect on local control. Tumor cut-through adversely affected cancer control and survival, but this effect diminished significantly in the absence of regional disease. CONCLUSIONS: Microscopic tumor cut-through revised to negative margins is a powerful prognosticator that is observed only when regional disease is also present. The value of adjuvant therapeutic regimens is questionable in patients with microscopic tumor cut-through, revised to negative margins, and with no regional disease.

Utility of the gastro-omental free flap in head and neck reconstruction.

PURPOSE OF REVIEW: In the current era of organ-preservation therapies, surgical salvage and reconstruction of defects following ablation of mucosa and soft tissue in the head and neck is extremely challenging because of the toxic effects of chemoradiation and intensive radiotherapy on wounds. The anatomical, physiological and immunological properties of the gastro-omental flap make it an ideal reconstructive technique in head and neck surgery. RECENT FINDINGS: Several case series published in the past 12 months highlight the utility of this flap in inhospitable wounds and particularly in restoration of circumferential pharyngeal defects. The gastro-omental flap produces satisfactory functional results and morbidity in this group of high-risk patients. SUMMARY: The gastro-omental free flap provides an alternative to traditional reconstructive techniques that is ideally suited to high-risk complex wounds in the head and neck.

Salvage of failed free flaps used in head and neck reconstruction.

Free flap success rates are in excess of 95%. Vascular occlusion (thrombosis) remains the primary reason for flap loss, with venous thrombosis being more common than arterial occlusion. The majority of flap failures occur within the first 48 hours. With early recognition and intervention of flap compromise salvage is possible. Successful salvage rates range from 28% to over 90%. Rapid re-exploration in this clinical setting is crucial to maximise the chances of flap salvage. If salvage is not feasible or unsuccessful then non-surgical methods of salvage may be employed with some possibility of success. The purpose of this article is to review the causes of free flap failure and to highlight the available options for salvage.

Morbidity and functional outcomes following gastro-omental free flap reconstruction of circumferential pharyngeal defects.

BACKGROUND: In patients with extensive soft tissue fibrosis requiring circumferential pharyngeal reconstruction following definitive radiotherapy and/or chemotherapy, we take advantage of abundant omental progenitor factors in the tubed gastro-omental free flap. This study reviews our experience with this flap. METHODS: Review of 11 patients (median follow-up, 2.8 years) undergoing total pharyngolaryngectomy following organ preservation protocols for recurrent squamous cell carcinoma (n = 9) and stricture (n = 2). RESULTS: Operative morbidity and mortality rates were 54% and 9%, respectively. One patient died following carotid rupture. Complications included: chyle leak (18%), pharyngocutaneous fistula (9%), and late stricture (27%). Ten patients (91%) achieved oral diet, and all 7 patients (100%) considered suitable for tracheoesophageal speech rehabilitation achieved functional speech. Seven patients remain alive without disease at a median of 41 months following surgery. CONCLUSIONS: The gastro-omental flap provides a viable option in high-risk patients undergoing circumferential pharyngeal reconstruction.