Daniel Clayburgh

Quantitative Multiplex Immunohistochemistry Reveals Myeloid-Inflamed Tumor-Immune Complexity Associated with Poor Prognosis

Here, we describe a multiplexed immunohistochemical platform with computational image processing workflows, including image cytometry, enabling simultaneous evaluation of 12 biomarkers in one formalin-fixed paraffin-embedded tissue section. To validate this platform, we used tissue microarrays containing 38 archival head and neck squamous cell carcinomas and revealed differential immune profiles based on lymphoid and myeloid cell densities, correlating with human papilloma virus status and prognosis. Based on these results, we investigated 24 pancreatic ductal adenocarcinomas from patients who received neoadjuvant GVAX vaccination and revealed that response to therapy correlated with degree of mono-myelocytic cell density and percentages of CD8+ Txa0cells expressing Txa0cell exhaustion markers. These data highlight the utility of inxa0situ immune monitoring for patient stratification and provide digital image processing pipelines to the community for examining immune complexity in precious tissue sections, where phenotype and tissue architecture are preserved to improve biomarker discovery and assessment.

Cancer Stem Cells in Head and Neck Squamous Cell Carcinoma

Accumulating evidence suggests that self-renewal and differentiation capabilities reside only in a subpopulation of tumor cells, termed cancer stem cells (CSCs), whereas the remaining tumor cell population lacks the ability to initiate tumor development or support continued tumor growth. In head and neck squamous cell carcinoma (HNSCC), as with other malignancies, cancer stem cells have been increasingly shown to have an integral role in tumor initiation, disease progression, metastasis and treatment resistance. In this paper we summarize the current knowledge of the role of CSCs in HNSCC and discuss the therapeutic implications and future directions of this field.

Clinical Manifestations and Treatment of Idiopathic and Wegener Granulomatosis-Associated Subglottic Stenosis

OBJECTIVEnTo compare and contrast the manifestations and surgical management of subglottic stenosis in patients with airway obstruction attributed to granulomatosis with polyangiitis (GPA), previously known as Wegener granulomatosis, and those with idiopathic subglottic stenosis (iSGS).nnnDESIGNnRetrospective medical chart review. Review of subglottic stenosis cases seen in the otolaryngology department of an academic medical center from 2005 through 2010. Data were obtained on disease presentation, operative management. and findings.nnnSETTINGnTertiary referral center.nnnPARTICIPANTSnA total of 24 patients with iSGS and 15 patients with GPA-associated subglottic stenosis (GPA-SGS).nnnRESULTSnAll individuals with iSGS were female, and 40% of patients with GPA-SGS were male (P < .01). Patients with iSGS tended to have a higher Myer-Cotton stenosis grade at the time of dilation than those with GPA-SGS (P = .02). Individuals with GPA-SGS were more likely to undergo tracheotomy as a result of disease-related complications than individuals with iSGS (P < .01). No patients with an open airway reconstruction in the iSGS group required follow-up mechanical dilation. In contrast, all patients with open airway reconstructions in the GPA-SGS group underwent more than 1 subsequent airway dilation (P < .01).nnnCONCLUSIONSnWhile surgical utilization is the mainstay of treatment in iSGS and GPA-SGS, iSGS occurs almost exclusively in females and presents with a greater degree of stenosis at the time of endoscopic dilation. In contrast, GPA-SGS is associated with greater rates of tracheotomy. Open airway reconstruction may be used in the treatment of iSGS and GPA-SGS but is much more effective in iSGS.

Prospective Study of Venous Thromboembolism in Patients With Head and Neck Cancer After Surgery

IMPORTANCEnVenous thromboembolism (VTE) is associated with significant morbidity and mortality in surgery patients, but little data exist on the incidence of VTE in head and neck cancer surgical patients.nnnOBJECTIVEnTo determine the incidence of VTE in postoperative patients with head and neck cancer.nnnDESIGN, SETTING, AND PARTICIPANTSnA prospective study of 100 consecutive patients hospitalized at a tertiary care academic surgical center who underwent surgery to treat head and neck cancer. Routine chemoprophylaxis was not used. On postoperative day (POD) 2 or 3, participants received clinical examination and duplex ultrasonographic evaluation (US). Participants with negative findings on clinical examination and US were followed up clinically; participants with evidence of deep venous thrombosis (DVT) or pulmonary embolism (PE) were given therapeutic anticoagulation. Participants with superficial VTE underwent repeated US on POD 4, 5, or 6. Participants were monitored for 30 days after surgery.nnnMAIN OUTCOME AND MEASUREnTotal number of new cases of VTE (superficial and deep) identified within 30 days of surgery and confirmed on diagnostic imaging.nnnRESULTSnOf the 111 participants enrolled, 11 withdrew before completing the study; thus, 100 participants were included. The overall incidence of VTE was 13%. Eight participants were identified with clinically significant VTE: 7 DVT and 1 PE. An additional 5 participants had asymptomatic lower extremity superficial VTE detected on US alone. Fourteen percent of patients received some form of postoperative anticoagulation therapy; the rate of bleeding complications in these patients (30.1%) was higher than that in patients without anticoagulation therapy (5.6%) (P = .01).nnnCONCLUSIONS AND RELEVANCEnHospitalized patients with head and neck cancer not routinely receiving anticoagulation therapy after surgery have an increased risk of VTE. Bleeding complications are elevated in patients receiving postoperative anticoagulation.

Progression and management of Wegener's granulomatosis in the head and neck.

To describe the otolaryngologic presentation and natural history of granulomatosis with polyangiitis (GPA), previously known as Wegeners granulomatosis, and to compare otolaryngologic outcomes of patients with systemic GPA to those with a limited form of GPA confined to the head and neck.

Airway reconstruction in Wegener's granulomatosis-associated laryngotracheal stenosis†‡§

Open airway reconstruction is considered definitive treatment of laryngotracheal stenosis (LTS). Although most cases of LTS are not autoimmune, there are few data reported in patients with Wegeners granulomatosis. In this study, we aimed to assess outcomes of airway reconstruction in LTS patients with Wegeners compared to nonautoimmune patients.

Effects of epidermal growth factor receptor and insulin-like growth factor 1 receptor inhibition on proliferation and intracellular signaling in cutaneous SCCHN: potential for dual inhibition as a therapeutic modality.

Combined inhibition of epidermal growth factor receptor (EGFR) and insulin‐like growth factor‐1 receptor (IGF‐1R) has been proposed as a therapy for cutaneous squamous cell carcinoma of the head and neck (SCCHN).

Efficacy of Tonsillectomy for Pediatric Patients With Dysphagia and Tonsillar Hypertrophy

OBJECTIVEnTo determine the effectiveness of tonsillectomy for the treatment of dysphagia related to tonsillar hypertrophy.nnnDESIGNnProspective cohort study.nnnSETTINGnTertiary care pediatric otolaryngology practice.nnnPARTICIPANTSnEighty-five children aged 2 to 14 years referred for tonsillectomy owing to dysphagia related to tonsillar hypertrophy (dysphagia cohort) or for other indications (control cohort).nnnINTERVENTIONSnSwallowing Quality of Life (SWAL-QOL) dysphagia questionnaires were administered at the initial clinic visit, on the day of surgery, and at 1 month and 6 months after surgery. Patients were weighed on the day of surgery and at 1 month after surgery.nnnMAIN OUTCOME MEASURESnThe primary outcome measure was the SWAL-QOL score. Secondary outcome measures were the type of diet consistency patients tolerated at home and the weight percentile for age.nnnRESULTSnOf 85 patients enrolled, 57 went on to have surgery, completed at least 1 postoperative questionnaire, and were included in the data analysis. At 1 month after tonsillectomy, the dysphagia cohort (nxa0=xa018) demonstrated improved SWAL-QOL scores (mean [SD], 58.4 [4.8] before surgery vs 82.4 [5.3] after surgery; Pxa0<xa0.001), more patients tolerating a regular diet (12 of 37 patients [33.3%] before surgery vs 22 of 36 [60.0%] after surgery, Pxa0=xa0.01), and increased weight percentile for age (mean [SD], 36.5 [10.7] before surgery vs 50.0 [10.6] after surgery; Pxa0=xa0.01). Similarly, at 1 month after tonsillectomy, the control cohort (nxa0=xa039) demonstrated improved SWAL-QOL scores (mean [SD], 80.8 [2.6] before surgery vs 91.7 [1.8] after surgery; Pxa0<xa0.001), more patients tolerating a regular diet (30 of 37 patients [81.1%] before surgery vs 34 of 36 patients [94.4%] after surgery, Pxa0=xa0.04), and increased weight percentile for age (mean [SD], 62.8 [5.4] before surgery vs 70.4 [5.1] after surgery; Pxa0=xa0.003).nnnCONCLUSIONSnDysphagia related to tonsillar hypertrophy is a significant problem not only among children with dysphagia with a primary complaint but also among a large subset of patients referred for tonsillectomy for other indications. Following tonsillectomy, both groups experience significant improvement in swallowing-related quality of life, ability to tolerate a regular diet, and weight percentile for age. Tonsillectomy is an effective treatment for the management of dysphagia related to tonsillar hypertrophy in children.

Human papillomavirus (HPV) 16 antibodies at diagnosis of HPV-related oropharyngeal cancer and antibody trajectories after treatment

OBJECTIVESnDespite the fact that HPV-driven oropharyngeal cancer (HPV-OPC) has relatively low recurrence rates, intensive post-therapy monitoring remains the standard of care. Post-treatment biomarkers are needed to risk stratify HPV-OPC patients for more individualized surveillance intensity and which remain at higher recurrence risk.nnnMATERIALS AND METHODSn115 HPV-OPC patients (ascertained by p16 immunohistochemistry and/or in-situ hybridization) from a multicenter prospective case study (HOTSPOT) had blood collected at diagnosis, and 64 of these also had blood collected at post-treatment follow-up visits for up to two years. Samples were centrally tested for antibodies to the L1, E1, E2, E4, E6, and E7 proteins of HPV16.nnnRESULTSnAt diagnosis, most HPV-OPC cases were seropositive to HPV16 E6 (85%). In post therapeutic samples, HPV16 antibody level decreased slowly over time, but only 3 (of 51 cases seropositive at enrollment) dropped low enough to be classified as seronegative. At 3years after diagnosis, cumulative risk of recurrence was 10.2% and 0% in HPV16 E6 seropositive and E6 seronegative HPV-OPC cases, respectively (p=0.18). Risk of recurrence was increased, although not statistically significant, in those with higher HPV16 E6 antibody levels at diagnosis (per log antibody level, hazard ratio [HR]=1.81, 95%CI=0.47-6.92).nnnCONCLUSIONnThis study confirms the high seroprevalence of HPV oncogenic antibodies at diagnosis of HPV-OPC. HPV16 E6 antibody levels decrease after treatment, but most cases remain seropositive for up to two years. HPV16 E6 antibody levels at diagnosis did not appear to be a strong predictor of recurrence.

Factors associated with supracricoid laryngectomy functional outcomes

Supracricoid partial laryngectomy (SCPL) is an option for laryngeal cancer resection that preserves laryngeal function; however, little information exists regarding factors that are associated with functional outcomes.