Kiran Kakarala

Transoral robotic surgery for oropharyngeal cancer: long-term quality of life and functional outcomes.

IMPORTANCE Because treatment for oropharyngeal squamous cell carcinoma (OPSCC), especially in patients of older age, is associated with decreased patient quality of life (QOL) after surgery, demonstration of a less QOL-impairing treatment technique would improve patient satisfaction substantially. OBJECTIVE To determine swallowing, speech, and QOL outcomes following transoral robotic surgery (TORS) for OPSCC. DESIGN, PARTICIPANTS, AND SETTING This prospective cohort study of 81 patients with previously untreated OPSCC was conducted at a tertiary care academic comprehensive cancer center. INTERVENTIONS Primary surgical resection via TORS and neck dissection as indicated. MAIN OUTCOMES AND MEASURES Patients were asked to complete the Head and Neck Cancer Inventory (HNCI) preoperatively and at 3 weeks as well as 3, 6, and 12 months postoperatively. Swallowing ability was assessed by independence from a gastrostomy tube (G-tube). Clinicopathologic and follow-up data were also collected. RESULTS Mean follow-up time was 22.7 months. The HNCI response rates at 3 weeks and 3, 6, and 12 months were 79%, 60%, 63%, and 67% respectively. There were overall declines in speech, eating, aesthetic, social, and overall QOL domains in the early postoperative periods. However, at 1 year post TORS, scores for aesthetic, social, and overall QOL remained high. Radiation therapy was negatively correlated with multiple QOL domains (P < .05 for all comparisons), while age older than 55 years correlated with lower speech and aesthetic scores (P < .05 for both). Human papillomavirus status did not correlate with any QOL domain. G-tube rates at 6 and 12 months were 24% and 9%, respectively. Greater extent of TORS (>1 oropharyngeal site resected) and age older than 55 years predicted the need for a G-tube at any point after TORS (P < .05 for both). CONCLUSIONS AND RELEVANCE Patients with OPSCC treated with TORS maintain a high QOL at 1 year after surgery. Adjuvant treatment and older age tend to decrease QOL. Patients meeting these criteria should be counseled appropriately.

Clinical outcomes of transoral robotic supraglottic laryngectomy

Transoral, minimally invasive organ preservation surgeries are being increasingly used for laryngopharyngeal carcinomas to avoid the toxicities of combined chemotherapy and radiation therapy regimens. This study investigates the efficiency, safety, and functional outcomes of transoral robotic surgery (TORS) supraglottic laryngectomy.

Survival in oral cavity minor salivary gland carcinoma

Objective: To describe the epidemiology and comparative survival for minor salivary gland cancer of the oral cavity. Study Design: Historical cohort study. Setting: Academic medical center. Subjects and Methods: Cases of minor salivary gland cancer of the oral cavity were extracted from the Surveillance, Epidemiology, and End Results database (1988-2005) and staged. Kaplan-Meier survivals were compared according to histology as well as T stage and N stage. A Cox proportional hazards model incorporating histology, T stage, N stage, age, and sex was analyzed. Results: A total of 639 salivary gland cancers of the oral cavity (55% female; mean age, 56 years) were identified with complete staging information, consisting of 318 mucoepidermoid, 169 adenoid cystic, 139 adenocarcinoma, and 14 acinic cell cancers. The hard palate and gums were the most common subsites involved (87.6%), followed by lip (7.2%) and tongue (5.2%). At presentation, T1 and T4 tumors predominated (42.6% and 35.2%, respectively); 93.4 percent were N0. Overall mean survival (months) was 157.9 and was similar across histologic subtypes: mucoepidermoid (172.4), adenoid cystic (141.4), acinic cell (138.7), and adenocarcinoma (147.2). Survival for low- and intermediate-grade mucoepidermoid carcinoma (171.0 and 182.3, respectively) was better than survival for high-grade mucoepidermoid carcinoma (50.3, P < 0.001). On multivariate analysis, N stage (P < 0.001) was the most powerful predictor of survival, along with T stage (P = 0.013), age (P < 0.001), and sex (P < 0.001). Conclusion: T stage and N stage are the most powerful predictors of survival in minor salivary gland carcinoma of the oral cavity. With the exception of high-grade mucoepidermoid carcinoma, survival for these lesions is generally favorable.

Free flap reconstruction in 1999 and 2009: Changing case characteristics and outcomes

To compare free flap reconstructive cases from 1999 and 2009 with respect to patient characteristics, surgical characteristics, outcomes, and complications; and to discuss the evolution in free flap reconstruction at a single institution during this time period.

Mitigation of Tumor-Associated Fibroblast-Facilitated Head and Neck Cancer Progression With Anti-Hepatocyte Growth Factor Antibody Ficlatuzumab.

IMPORTANCE Ficlatuzumab can be used to treat head and neck squamous cell carcinoma (HNSCC) by inhibiting c-Met receptor-mediated cell proliferation, migration, and invasion. OBJECTIVE To understand the effect of ficlatuzumab on HNSCC proliferation, migration, and invasion. DESIGN, SETTING, AND PARTICIPANTS The effects of ficlatuzumab on HNSCC proliferation, invasion, and migration were tested. Mitigation of c-Met and downstream signaling was assessed by immunoblotting. The tumor microenvironment has emerged as an important factor in HNSCC tumor progression. The most abundant stromal cells in HNSCC tumor microenvironment are tumor-associated fibroblasts (TAFs). We previously reported that TAFs facilitate HNSCC growth and metastasis. Furthermore, activation of the c-Met tyrosine kinase receptor by TAF-secreted hepatocyte growth factor (HGF) facilitates tumor invasion. Ficlatuzumab is a humanized monoclonal antibody that sequesters HGF, preventing it from binding to and activating c-Met. We hypothesized that targeting the c-Met pathway with ficlatuzumab will mitigate TAF-mediated HNSCC proliferation, migration, and invasion. Representative HNSCC cell lines HN5, UM-SCC-1, and OSC-19 were used in these studies. EXPOSURES FOR OBSERVATIONAL STUDIES The HNSCC cell lines were treated with ficlatuzumab, 0 to 100 µg/mL, for 24 to 72 hours. MAIN OUTCOMES AND MEASURES Ficlatuzumab inhibited HNSCC progression through c-Met and mitogen-activated protein kinase (MAPK) signaling pathway. RESULTS Ficlatuzumab significantly reduced TAF-facilitated HNSCC cell proliferation (HN5, P < .001; UM-SCC-1, P < .001), migration (HN5, P = .002; UM-SCC-1, P = .01; and OSC-19, P = .04), and invasion (HN5, P = .047; UM-SCC-1, P = .03; and OSC-19, P = .04) through a 3-dimensional peptide-based hydrogel (PGmatrix). In addition, ficlatuzumab also inhibited the phosphorylation of c-Met at Tyr1234/1235 and p44/42 MAPK in HNSCC cells exposed to recombinant HGF. CONCLUSIONS AND RELEVANCE We demonstrate that neutralizing TAF-derived HGF with ficlatuzumab effectively mitigates c-Met signaling and decreases HNSCC proliferation, migration, and invasion. Thus, ficlatuzumab effectively mitigates stromal influences on HNSCC progression.

Bolsterless management for recurrent auricular hematomata.

The objectives were to describe our experience with a bolsterless technique for the management of auricular hematomata and discuss the management options for auricular hematomata and the comparative benefits of the bolsterless technique.

A Comparison of Histopathologic Margin Assessment after Steel Scalpel, Monopolar Electrosurgery, and Ultrasonic Scalpel Glossectomy in a Rat Model

EDUCATIONAL OBJECTIVE At the conclusion of this presentation, the participants should be able to describe the tissue effects of steel scalpel, monopolar electrosurgery, and ultrasonic scalpel glossectomy with respect to histopathologic margin assessment in a rat model. OBJECTIVES Histopathologic margin assessment is important in guiding treatment and determining prognosis for squamous cell cancer of the oral tongue. Energy based devices for glossectomy produce varying degrees of tissue distortion and artifact that can influence margin assessment. The purpose of this study is to compare the tissue effects of three surgical methods of glossectomy with respect to margin assessment by a pathologist. STUDY DESIGN Blinded histopathologic study of three surgical techniques for glossectomy using a rat model. METHODS The anterior tongue of thirty Sprague-Dawley rats was excised using either steel scalpel, monopolar electrosurgery, or ultrasonic scalpel (three groups of ten). Specimens were fixed in formalin and serially sectioned, and hematoxylin and eosin stains were examined by a pathologist blinded to the surgical procedure. Comparison between surgical techniques with respect to effect on the tissue margin was carried out using a previously described grading system for margin assessment. RESULTS Minimal tissue disruption at the surgical margin was produced by the steel scalpel, in contrast to monopolar electrosurgery and harmonic scalpel, which both produced varying levels of tissue distortion. Margin fragmentation, cautery artifact, and artifact depth was greater with monopolar electrosurgery when compared to harmonic scalpel. CONCLUSIONS Energy based devices cause tissue distortion which may in theory effect the ability to accurately assess surgical margins for tumor involvement on histopathology. In our rat model of glossectomy, the harmonic scalpel created less tissue distortion at the surgical margin than monopolar electrosurgery. Further study is required to determine the clinical relevance of these findings.

Secretory Autophagy in Cancer-Associated Fibroblasts Promotes Head and Neck Cancer Progression and Offers a Novel Therapeutic Target

Despite therapeutic advancements, there has been little change in the survival of patients with head and neck squamous cell carcinoma (HNSCC). Recent results suggest that cancer-associated fibroblasts (CAF) drive progression of this disease. Here, we report that autophagy is upregulated in HNSCC-associated CAFs, where it is responsible for key pathogenic contributions in this disease. Autophagy is fundamentally involved in cell degradation, but there is emerging evidence that suggests it is also important for cellular secretion. Thus, we hypothesized that autophagy-dependent secretion of tumor-promoting factors by HNSCC-associated CAFs may explain their role in malignant development. In support of this hypothesis, we observed a reduction in CAF-facilitated HNSCC progression after blocking CAF autophagy. Studies of cell growth media conditioned after autophagy blockade revealed levels of secreted IL6, IL8, and other cytokines were modulated by autophagy. Notably, when HNSCC cells were cocultured with normal fibroblasts, they upregulated autophagy through IL6, IL8, and basic fibroblast growth factor. In a mouse xenograft model of HNSCC, pharmacologic inhibition of Vps34, a key mediator of autophagy, enhanced the antitumor efficacy of cisplatin. Our results establish an oncogenic function for secretory autophagy in HNSCC stromal cells that promotes malignant progression. Cancer Res; 77(23); 6679-91. ©2017 AACR.

Revisiting the argument for 1- versus 2-vein outflow in head and neck free tissue transfers: A review of 317 microvascular reconstructions.

The purpose of this study was to determine the benefit of 1‐vein versus 2‐vein outflow in microvascular free tissue transfers.

Radiofrequency volumetric tissue reduction of the inferior turbinate in a sheep model.

To validate the sheep model for endoscopic nasal surgery, and to utilize this model to compare the immediate and early postoperative histopathologic effects of four electrosurgical turbinate reduction techniques.