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BACKGROUND We aimed to identify the optimal indications of neoadjuvant chemotherapy (NACT) and transoral robotic surgery (TORS) in patients with locoregionally advanced (T3-4 or N2-3) head and neck cancer (HNC). METHODS A total of 50 patients were included in the study. RESULTS T1 was identified in seven cases, T2 in 19, T3 in 22, and T4 in 2. N0 was identified in nine cases, N1 in 18, N2 in 22, and N3 in 1. There were 25 patients (50%) with complete remission of the primary lesion and 25 patients (50%) with partial remission. On pathologic examination of surgical specimens after neoadjuvant chemotherapy and TORS, 2 patients (4%) had a positive surgical margin, and 48 patients (96%) had a negative margin. Pathologic metastatic lymph nodes (LNs) were not observed in 39 cases (78%), and one metastatic LN was observed in 11 cases (22%). The 3-year recurrence-free survival (RFS) of all patients was 85.4%. On multivariate analysis, lymphovascular invasion showed a significant correlation with RFS. CONCLUSIONS In patients with locoregionally advanced HNC, NACT and TORS achieved favorable oncologic and functional outcomes.

Objectives/hypothesis In this study, we retrospectively reviewed medical records of patients who underwent surgery for p16+ oropharyngeal cancer and analyzed the prognostic implications of pathologic lymph node (LN) status, including number of metastatic LNs, LN ratio, and location of metastatic LNs. Study design Retrospective case series. Methods We retrospectively reviewed data on patients diagnosed with p16+ oropharyngeal cancer. Results The study population consisted of 159 males and 29 females with a mean age of 57.2 years. The primary tumor sites were tonsils (n = 160), base of the tongue (n = 24), and soft palate (n = 4). Only recurrence-free survival (RFS) showed a significant correlation with contralateral LN metastasis on multivariate analysis. On Kaplan-Meier analysis, 5-year RFS was 92.4% in patients without contralateral LN metastasis and 68.8% in patients with contralateral LN metastasis. Conclusions Among pathologic LN status in p16+ oropharyngeal cancer, only contralateral LN metastasis showed prognostic significance in disease recurrence of p16+ oropharyngeal squamous cell carcinoma patients. Level of evidence 4 Laryngoscope, 130: 1973-1979, 2020.

In this study, we sought to evaluate the clinical feasibility of indocyanine green (ICG)-guided sentinel lymph node (SLN) sampling during robotic retroauricular neck dissection (RAND) in patients with cN0 oral cancer. Nine adult patients diagnosed with T1 to T2 oral squamous cell carcinoma were consecutively recruited. All of them underwent transoral partial glossectomy and robotic RAND (levels I-III) simultaneously. Twelve hours prior to surgery, ICG was injected into the 4 quadrants around primary tongue tumors. During robotic RAND, intraoperative and ex vivo ICG-stained LNs were identified using the Firefly system and examined for the presence of fluorescence. ICG-stained LNs were identified in all patients. Thirty-one ICG-stained LNs were detected in 313 retrieved LNs (9.9%). Occult metastases were detected among the ICG-stained LNs in 2 patients (22.2%). There was no metastasis identified in the ICG-unstained LNs. Upstaging rates, sensitivity, specificity, and negative predictive value of ICG-guided SLN sampling were 22.2%, 100%, 91.5%, and 100%, respectively.

Objective Previously, we have reported the feasibility of retroauricular (RA) robotic thyroidectomy. Despite its promising surgical outcomes, there were certain intrinsic mechanical limitations inherent to the da Vinci Si System (Intuitive Surgical, Sunnyvale, California, U.S.A.). Since the advent of an upgraded model, the Xi System (Intuitive Surgical), we have actively incorporated the new model into performing RA thyroidectomy. Here, we intend to verify the feasibility of RA robotic thyroidectomy using the new da Vinci Xi System (Intuitive Surgical) with comparison of the former Si-applied surgery (Intuitive Surgical). Study Design Comparative analysis. Methods There were total 165 consecutive patients who received RA robotic thyroidectomy from January 2013 to February 2016. The patients were divided into two groups: Si group (n = 125) and Xi group (n = 40). Perioperative and treatment outcomes were compared and analyzed. Results Compared with the previous system, new da Vinci Xi system (Intuitive Surgical) enabled insertion of an extra third robotic instrumental arm. Unlike the previous robotic surgical technique, the robotic dissection could be initiated immediately after the establishment of working space and the resulting total operation time could be significantly decreased. There was no difference in the surgical completeness, as confirmed by postoperative thyroglobulin levels. Additionally, flexed EndoWrist (Intuitive Surgical) instruments equipped with the Erbe (Erbe USA Inc., Marietta, Georgia, U.S.A.) system could be mounted, which further facilitated the operation. There were no significant differences in postoperative complications between the two groups. Conclusion The RA robotic thyroidectomy with the new Xi System (Intuitive Surgical) can greatly facilitate the robotic surgery with comparable or improved surgical outcomes. Its application is expected to open up a new era of robotic neck surgery. Level of Evidence 4. Laryngoscope, 2017

Background The purpose of this study was to determine whether pretreatment 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) volumetric parameters add more prognostic information to p16-positive oropharyngeal squamous cell carcinoma (SCC). Methods We retrospectively analyzed 86 patients with p16-positive oropharyngeal SCC who underwent surgery and postoperative radiotherapy (RT) or chemoradiotherapy (CRT). Maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured. Results Higher total MTV (tMTV), nodal MTV (nMTV), and tumor TLG (tTLG) were significantly associated with lower disease-free survival (DFS) (all p < .05) and higher distant metastasis rates (all p < .05). Multivariate analysis of DFS revealed that tMTV (p = .032), nMTV (p = .004), and tTLG (p = .018) were independently significant prognosticators. Conclusion Patients with p16-positive disease with high metabolic tumor burden were associated with higher distant metastasis rates, translating into worse survival. These patients may not be optimal candidates for treatment deintensification. © 2016 Wiley Periodicals, Inc. Head Neck, 2016

Background We performed transoral robotic surgery (TORS) or conventional surgery via a transoral or mandibulotomy approach in patients with tonsillar cancer and prospectively analyzed the oncologic outcomes and functional recovery of the 3 groups. Methods Between May 2008 and October 2011, 57 patients were enrolled in this prospective study. Results Although there was no significant difference in the survival rate of the TORS group (100%) and the conventional surgery group (96.7%), a higher rate of margin negativity was observed in the TORS group, especially in cases in which the tumor extends inferiorly. Patients who received TORS or conventional transoral procedures showed more rapid recovery of swallowing, shorter hospitalization, and shorter operation time than the mandibulotomy group. Conclusion Despite the weakness of this nonrandomized trial and the differences in T classification, TORS seemed to have distinct advantages over conventional transoral surgery and other conventional open surgery, but further studies are needed. © 2013 Wiley Periodicals, Inc. Head Neck 36: 1138–1145, 2014

Objectives/Hypothesis: The objective of this prospective study was to confirm the validity of transoral robotic supraglottic partial laryngectomy as a conservation surgery for treating supraglottic cancer. Study design: Prospective case study. Methods: Between December 2009 and November 2011, 16 patients were enrolled in this study. Acoustic waveform analysis was conducted and Voice Handicap Index 10 was measured to assess voice status. Videopharyngogram study and the functional outcome swallowing scale were administered to evaluate swallowing function. Overall survival and disease-free survival were analyzed using the Kaplan-Meier method. Results: A negative margin was reported in 88% patients. During the follow-up period, distant metastasis occurred in one patient at 6 months. The Kaplan-Meier disease-free survival at 1 year was 91%. Patients exhibited complete recovery of swallowing ability after an average of 8.3 days. Videopharyngogram study showed aspiration in one patient. The cannula could be removed at an average 11.2 days. The average hospital stay was 13.5 days. Concerning the results of the functional outcome swallowing scale and Voice Handicap Index 10, most patients (90.9%) subjectively reported favorable swallowing and voice function. Conclusions: Transoral robotic surgery was a safe and feasible modality of treating supraglottic cancer. According to our data, transoral robotic surgery demonstrated oncologically and functionally acceptable results in supraglottic cancer patients. Laryngoscope, 2013

Objectives/Hypothesis: Recently, the Harmonic scalpel (HS) has been used in head and neck surgery as an alternative to conventional hand-tied ligation for hemostasis. Limited data have been published on the evidence of its safety in neck dissection (ND), especially in radical ND. We intended to investigate the safety and efficacy of the HS in ND, while using conventional hand-tied ligation to a minimum. Method: Fifty-nine patients who underwent ND with primary head and neck cancer resection were enrolled in this study. The group using HS consisted of 29 patients, and the conventional hand-tied ligation technique (CT) group comprised of 30 patients. The following variables were examined: operating time, intraoperative bleeding, incidence of perioperative complications, the number of lymph nodes, total amount of drainage, duration of drain placement, and days of hospital stay. Result: The use of the HS reduced the operating time of comprehensive ND by an average of 46.5 minutes (P < 0.001), and blood loss was significantly decreased in the HS group than the CT group (163.8 ± 33.8 cc vs. 203.8 ± 36.5 cc, P = 0.002). The number of lymph nodes was not significantly different between the two groups. No significant difference was observed in the total amount of drainage, duration of drain placement, days of hospital stay, and perioperative complications. Conclusions: The HS is a relatively safe and effective alternative method for hand-tie ligation in ND. Moreover, the HS significantly reduced the operating time and amount of blood loss.

BACKGROUND: Although radiation resistance is a primary issue in radiation therapy, attempts to find predictors of radiation resistance have met with little success. The authors therefore aimed to determine predictors for radiation resistance to improve the prognosis of head and neck squamous cell carcinoma (HNSCC). METHODS: HNSCC cell lines, SCC15, SCC25, and QLL1, irradiated with an acute dose of 4 grays (Gy) (RR-4), a cumulative dose of 60 Gy (RR-60), and a booster dose of 4 Gy over 60 Gy (RR-60 + 4), were used with nonirradiated cell lines. Those were used in cDNA microarray, proteomics, Western blotting, and immunofluorescence, respectively. One hundred five HNSCC tissue samples with radiation resistance were analyzed by immunohistochemistry. RESULTS: Western blot analysis of RR-60 cell lines was identical to the data of Nm23-H1 overexpression by cDNA array and proteomic screening. Immunofluorescence demonstrated significant nuclear translocation of Nm23-H1 in RR-4 and RR-60 cell lines, and less but still intense nuclear shuttling in RR-60 + 4. Similarly, Nm23-H1 nuclear localization was observed in 20% (21 of 105) of tissue samples. Univariate analysis demonstrated that Nm23-H1 nuclear localization was strongly associated with overall and recurrence-free survival. Multivariate stepwise Cox regression analysis showed that Nm23-H1 nuclear localization (odds ratio [OR], 7.48) and N stage (OR, 2.13) were associated with overall survival, and Nm23-H1 nuclear localization (OR, 3.02), T stage (OR, 1.43), and insufficient tumor margin (OR, 3.27) were associated with recurrence-free survival. CONCLUSIONS: Overexpression of Nm23-H1, specifically its nuclear translocation, may be a powerful predictor of radiation resistance in HNSCC. Cancer 2011. © 2010 American Cancer Society.

This work was supported by a grant from the Creative Research Initiative Program of the Ministry of Education, Science and Technology for ‘‘Complementary Hybridization of Optical and Fluidic Devices for Integrated Optofluidic Systems.’’ Supporting Information is available online from Wiley InterScience or from the author.

This work was supported a grant from the Creative Research Initiative Program of the Ministry of Science and Technology for ‘‘Complementary Hybridization of Optical and Fluidic Devices for Integrated Optofluidic Systems.’’ The authors also appreciated partial support from the Brain Korea 21 Program. Supporting Information is available online from Wiley InterScience or from the author.

The prevalence of human papillomavirus (HPV) infection is high in the oropharyngeal mucosal regions, of which the tonsil is the most commonly affected. There may be a link between HPV and the pathogenesis of tonsillar cancer (TC), because of common anatomical characteristics between cervical and tonsillar cancer. We aimed to clarify whether HPV directly affects the oncogenesis and biologic behavior of TC by making a comparison between infection prevalence, physical status and viral loading numbers, and clinicopathologic prognostic factors. To compare HPV-related molecules between TC and tonsillitis (CFT), p16, survivin, HIF-1alpha, skp-1, cyclin A, cyclin B1, c-myc and EGFR were investigated. We observed a significant difference in HPV prevalence between 52 TCs and 69 CFTs (73.1% vs. 11.6%), and most of the HPVs were type 16 (87.2%) and nonepisomal (94.1%). Most TCs associated with HPV arose from the tonsillar crypts, and tended to be inverted and poorly differentiated. Compared with HPV-negative TC, HPV-positive TC showed a strong association with p16 overexpression (p

Objectives: It is well established that tonsillar squamous cell carcinomas have a high probability of disseminating to the neck. An ipsilateral neck treatment is mandatory during initial treatment of stages II to IV tonsillar carcinomas. However, as of yet, no consensus exists whether to perform elective contralateral neck management. Materials and Methods: A retrospective analysis of 43 N0-3 tonsillar cancer patients with contralateral clinically negative necks from 1992 to 2002 was performed. All patients had a contralateral elective neck dissection. Surgical treatment was followed by postoperative radiotherapy in 33 patients. The follow-up period ranged from 2 to 120 (mean 38) months. The Kaplan-Meier method and log-rank test were used to calculate the disease-specific survival rates and prognostic significance of contralateral occult lymph node metastasis. Results: Clinically negative, but pathologically positive, contralateral lymph nodes occurred in 16% (7 of 43). Of the 33 cases with an ipsilateral node positive neck, contralateral occult lymph node metastases developed in 21% (7 of 33), in contrast with 0% in ipsilateral N0 necks. On the basis of the clinical staging of the tumor, 5% (1 of 22) of the cases showed lymph node metastases in T2 tumors, 36% (5 of 14) in T3, and 25% (1 of 4) in T4. None of the T1 tumors (3 cases) had pathologically positive lymph nodes (T1 + T2 vs. T3 + T4, P < .05). Patients with no evidence of contralateral nodal cancer had significantly improved disease-specific survival over patients with any pathologically positive nodes (5 year disease-specific survival rate 92% vs. 28%, P = < .05). Conclusion: The risk of contralateral occult neck involvement in above T3 staged tonsillar squamous cell carcinomas with unilateral metastases was high (approximately 21%), and patients who present with a contralateral metastatic neck have a worse prognosis than those who are staged as N0. Therefore, we advocate an elective contralateral neck treatment in tonsillar squamous cell carcinoma patients with ipsilateral node metastases.

This work was fully supported by the Corporate Research & Development Center of Samsung SDI Co.Ltd.

PURPOSE Cyclin D1 regulates the G1 checkpoint of the cell cycle and is overexpressed in a number of cancers. This study was designed to determine if cyclin D1 overexpression had prognostic value in patients undergoing surgery with curative intent for primary retroperitoneal soft-tissue sarcoma. METHODS Tissue was available for analysis on 79 patients who underwent resection between September 1983 and May 1997. Clinicopathologic data and follow-up was obtained from a prospective sarcoma database and a patient and family interview. Immunohistochemical analysis was used to determine overexpression (≥ 5% of nuclei labeled). Survival was analyzed using the Kaplan–Meier method, and statistical analysis was performed by using log rank testing and the Cox regression model. RESULTS Median follow-up was 3.5 years. On univariate analysis of disease-specific mortality, significant prognostic factors were high grade (n = 42, 53%), positive microscopic margins (n = 36, 46%) or macroscopic margins (n = 15, 19%), and cyclin D1 overexpression (n = 37, 47%). On multivariate analysis, macroscopically positive margins (P = 0.02) and the combination of high grade and cyclin D1 overexpression (P = 0.04) both were associated independently with poor survival. CONCLUSION High grade retroperitoneal sarcomas demonstrating cyclin D1 overexpression have had an extremely poor prognosis. Continued study of multiple biological markers, exemplified by cyclin D1, may aid characterization of tumor behavior and response to treatment in this diverse group of tumors. Cancer 2001;91:428–34. © 2001 American Cancer Society.

Introduction Radiation therapy is an integral part of the treatment of head and neck cancer. Factors predicting radiation response are ill defined. The aim of this study was to identify genetic aberrations associated with radiation response in cell lines derived from head and neck squamous cell carcinomas (HNSCC) using comparative genomic hybridization (CGH) for genome-wide screening. Methods Five cell lines derived from HNSCC were subjected to a single course of radiation (400 cGy) in parallel with a similarly handled, untreated control. Cellular response to radiation was determined on posttreatment days 1, 2, 3, 4, and 5 using a cell viability assay (MTT assay). Radiation response was defined as 35% or greater decrease in cell survival relative to control. Tumor doubling time was determined by cell counts performed at day 0 and 1 for each cell line. All experiments were done in quadruplicate. CGH analysis was performed by differentially labeling DNA from tumor and normal tissue with fluorescent agents. The labeled DNAs were simultaneously hybridized to normal metaphase chromosomes. Image analysis for fluorescence intensity along the entire length of each metaphase chromosome allowed generation of a color ratio, which was used to detect copy number changes. Results Radioresistance was identified in two of five cell lines. The tumor doubling time was not a predictor of radiation response. CGH identified a complex pattern of aberrations, with gain of 3q common to all cell lines. The number of genetic aberration was higher in radiation-sensitive cell lines than in radiation-resistant ones. No recurrent aberrations were unique to the radiation-resistant cell lines. Recurrent gains at 7p and 17q and losses at 5q, 7q, and 18q were unique to the radiation-sensitive cell lines. Conclusions The number of aberrations identified by CGH analysis may be a predictor of radiation response. A large study of primary tumors is warranted to confirm this association and identify specific genetic aberrations associated with radiation response.

Objective: Recently, various robotic surgical procedures have been performed, and most reports have proved that the application of robotic technology for surgery is technically feasible and safe. The feasibility and safety of robotic thyroid surgery was examined via transaxillary single port approach without gas insufflation.Method: The study included 109 consecutive patients with papillary thyroid cancer who underwent robot-assisted endoscopic thyroid surgery using a gasless transaxillary single port approach by a single surgeon (Y.W.K.) between May 2010 and August 2011 at the department of otorhinolaryngology, Yonsei University College of Medicine.Results: The console time for 50 hemithyroidectomy (HT) with ipsilateral central compartment neck dissection (CCND) was 45.67 min, and that of 59 total thyroidectomy (TT) with ipsilateral or bilateral CCND was 93.77 min. The amount of drainage was 194.07 mL, and the duration of drainage was 3.5 days. The hospital stay was 6.09 days. Mean primary tumor size was...

Objective: Compare the efficacy and feasibility of alternative approaches: endoscopic resection via retro-auricular (RA) approach and transoral (TO) approach for submandibular gland (SMG) resection.Method: Retrospective analysis of surgical outcomes. We performed 21 endoscopic resections of benign lesions of SMG via RA approach and 11 resections via TO approach since 2010. The following variables were assessed: age, gender, tumor size, histopathologic type, operation time, length of hospital stay, scar satisfaction, and complications.Results: There were no statistically significant differences in patient profiles, tumor size, and histopathologic type between 2 groups. The cosmetic result was generally excellent and all patients were satisfied with the outcomes. However, in the first endoscopic surgery which was done for a large tumor in SMG, temporary weakness in the marginal branch of facial nerve was observed. There was no permanent palsy. Five patients in TO approach group had complaints of limitations...

Objective: The aim of the study was to investigate the treatment outcomes of malignant parotid tumors. This investigation is to report our experience with the management of patients with malignant parotid tumors that were treated with combinations of surgery, radiation, and chemotherapy.Method: From January 1999 to December 2008, 126 patients with primary parotid cancer were treated. Data including age, sex, histologic findings, tumor stage, surgery type, complications, and prognosis were collected retrospectively from medical charts.Results: Their mean age was 55.4 years (range, 15-96 years). Mean follow-up was 29.7 months. Thirty three patients were stage I, 40 stage II, 30 stage III, 23 stage IVA. Fifteen patients had recurrences: 6 patients had local, 2 had locoregional, and 1 had regional failure, 6 had distant metastasis. The most common malignant tumor was mucoepidermoid carcinoma (38, 29.5%). Sixty-one patients underwent superficial, 43 had total, and 22 had radical parotidecomy. Postoperative rad...

Objective: Quality of life could be deteriorated by surgical treatment of tongue cancer. Adjuvant therapy may also affect the functional outcome. Therefore, we intend to evaluate the influence of radiotherapy on the postoperative functional outcome after partial glossectomy with free flap reconstruction in early tongue cancer patients.Method: We measured the functional outcome and reviewed the charts of 31 oral tongue cancer patients. We evaluated speech integrity with Diadochokinetic test (DDK). Mobility of tongue was checked with measurement of upward, protrusion, and lateral deviation distance. We also evaluated swallowing capacity with the M.D. Anderson Dysphagia Inventory.Results: DDK rates of the surgery-only group and the postoperative radiotherapy group were 27.8 and 23.9, respectively, which was statistically different. Swallowing capacity was significantly superior in the surgery only group. Tongue mobility was not statistically different between the groups.Conclusion: The functional outcome reg...

Objective: Conventional surgical approaches for hypopharyngeal carcinomas have a great risk for developing treatment-related morbidity. To minimize this morbidity, hypopharyngectomy by transoral robotic surgery (TORS) was performed, and the efficacy and feasibility of this procedure were evaluated.Method: TORS was performed using Surgical Robot in 18 patients with T1 or T2 pyriform sinus cancer. Pyriform sinus was totally resected. Laterally, the inner perichondrium of the thyroid cartilage was peeled off to make sure of the safe margin. We evaluated the surgical margins, swallowing, decannulation, and surgery related complications.Results: Transoral robotic hypopharyngectomy was performed successfully in all eighteen patients. The mean robotic operation time was 62.4 minutes, and an average of 17.5 minutes was required for the setting of the robotic system. There was no significant perioperative complication in the cases. Swallowing function returned to all patients within 8.3 days average. Decannulation...