PIEZO1 activation may serve as an early tissue biomarker for the prediction of irradiation-induced salivary gland dysfunction.

Irradiation (IR)-induced xerostomia is the most common side effect of radiation therapy in patients with head and neck cancer (HNC). Xerostomia diagnosis is mainly based on the patient's medical history and symptoms. Currently, no direct biomarkers are available for the early prediction of IR-induced xerostomia. Here, we identified PIEZO1 as a novel predictive tissue biomarker for xerostomia. Our data demonstrate that PIEZO1 is significantly upregulated at the gene and protein levels during IR-induced salivary gland (SG) hypofunction. Notably, PIEZO1 upregulation coincided with that of inflammatory (F4/80) and fibrotic markers (fibronectin and collagen fibers accumulation). These findings suggest that PIEZO1 upregulation in SG tissue may serve as a novel predictive marker for IR-induced xerostomia.

Establishment and characterization of patient-derived xenografts as paraclinical models for head and neck cancer.

BACKGROUND: We investigated whether head and neck squamous cell carcinoma (HNSCC) patient-derived xenografts (PDXs) reaffirm patient responses to anti-cancer therapeutics. METHODS: Tumors from HNSCC patients were transplanted into immunodeficient mice and propagated via subsequent implantation. We evaluated established PDXs by histology, genomic profiling, and in vivo anti-cancer efficacy testing to confirm them as the authentic in vivo platform. RESULTS: From 62 HNSCCs, 15 (24%) PDXs were established. The primary cancer types were tongue (8), oropharynx (3), hypopharynx (1), ethmoid sinus cancer (1), supraglottic cancer (1), and parotid gland (1); six PDXs (40%) were established from biopsy specimens from advanced HNSCC. PDXs mostly retained donor characteristics and remained stable across passages. PIK3CA (H1047R), HRAS (G12D), and TP53 mutations (H193R, I195T, R248W, R273H, E298X) and EGFR, CCND1, MYC, and PIK3CA amplifications were identified. Using the acquisition method, biopsy showed a significantly higher engraftment rate when compared with that of surgical resection (100% [6/6] vs. 16.1% [9/56], P < 0.001). Specimens obtained from metastatic sites showed a significantly higher engraftment rate than did those from primary sites (100% [9/9] vs. 11.3% [6/53], P < 0.001). Three PDX models from HPV-positive tumors were established, as compared to 12 from HPV-negative (15.8% [3/19] and 27.9% [12/43] respectively, P = 0.311), suggesting that HPV positivity tends to show a low engraftment rate. Drug responses in PDX recapitulated the clinical responses of the matching patients with pan-HER inhibitors and pan-PI3K inhibitor. CONCLUSIONS: Genetically and clinically annotated HNSCC PDXs could be useful preclinical tools for evaluating biomarkers, therapeutic targets, and new drug discovery.

Objective Assessment of Postoperative Swallowing Difficulty Through Ultrasound in Patients Undergoing Thyroidectomy.

Swallowing discomfort is a common postoperative complaint in patients undergoing thyroidectomy. Contraction of the strap muscles might cause resistance to elevation of the laryngotracheal unit, and downward movement of the laryngotracheal unit may lead to swallowing discomfort. However, few studies have evaluated the mechanism related to limited laryngotracheal elevation after thyroidectomy. We aimed to objectively verify the presence of postoperative impaired laryngotracheal elevation through ultrasound evaluation in patients undergoing thyroidectomy and evaluate its relationship with limitation of laryngotracheal elevation. This is a prospective clinical study. Among patients undergoing hemithyroidectomy and total thyroidectomy, the patients who were followed up for ≥ 6 months were selected (N = 40). Ultrasound evaluation was done preoperatively and at 1, 3, and 6 months postoperatively. Laryngotracheal movement was recorded and the length of elevation was measured. Symptom after thyroidectomy was evaluated through swallowing-related items of thyroidectomy-related voice questionnaire. Ultrasound evaluation verified the presence of limited laryngotracheal elevation postoperatively in patients undergoing thyroidectomy. After thyroidectomy, the swallowing-related score was significantly increased, and was recovered time-dependently at 1 month. Laryngotracheal elevation showed significant decrease after thyroidectomy. The symptom score of swallowing was significantly correlated with the length of laryngotracheal elevation. Post-thyroidectomy ultrasound evaluation verified that laryngotracheal elevation was significantly impaired. Presence of adhesion between the laryngotracheal unit and the superficial soft tissue was the probable cause of the limitation at 6 months after thyroidectomy. The length of laryngotracheal elevation was related to the symptom score of swallowing after thyroid surgery.

A Case of Unexpected Clinostomum complanatum Infection Initially Presenting as Foreign Body in Pharynx.

A 46-year old man visited our outpatient clinic with complaint of foreign body sensation in throat after consuming raw freshwater fish 5 days ago. Laryngoscopic examination revealed a motile worm attached on posterior pharyngeal wall. The worm was removed using biopsy forceps under transnasal endoscopy and evidently identified as Clinostomum complanatum after microscopic examination. Patient's subjective foreign body sensation of throat and hyperemia of laryngeal mucosa remained for approximately 2 weeks post-removal, which were eventually resolved after administration of non-steroidal anti-inflammatory drug and anti-refluxant drug for 2 weeks. Treatment was ended at three weeks since the first visit. C. complanatum infections in humans are rare, and only four cases have been reported in Korea. Symptoms resembling pharyngitis or laryngitis occurs by consumption of raw, infected freshwater fish and treatment is done by mechanically removing the parasite.

Fibroblast growth factor receptor 3-mediated reactivation of ERK signaling promotes head and neck squamous cancer cell insensitivity to MEK inhibition.

Recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) has been a longstanding challenge for head and neck oncologists, and current treatments still have limited efficacy. ERK is aberrantly overexpressed and activated in HNSCC. Herein, we aimed to investigate the cause of the limited therapeutic effect of selumetinib, a selective inhibitor of MEK in HNSCC, as MEK/ERK reactivation inevitably occurs. We assessed the effects of combining selumetinib with fibroblast growth factor receptor 3 (FGFR3) inhibitor (PD173074) on tumor growth. Selumetinib transiently inhibited MAPK signaling and reactivated ERK signaling in HNSCC cells. Rebound in the ERK and Akt pathways in HNSCC cells was accompanied by increased FGFR3 signaling after selumetinib treatment. Feedback activation of FGFR3 was a result of autocrine secretion of the FGF2 ligand. The FGFR3 inhibitor PD173074 prevented MAPK rebound and sensitized the response of HNSCC cells to selumetinib. These results provided rational therapeutic strategies for clinical studies of this subtype of patients that show a poor prognosis with selumetinib. Our data provide a rationale for combining a MEK inhibitor with inhibitors of feedback activation of FGFR3 signaling in HNSCC cells. ERK rebound as a result of the upregulation of FGFR3 and the ligand FGF2 diminished the antitumor effects of selumetinib, which was overcome by combination treatment with the FGFR3 inhibitor.

Clinicopathological significance of cancer-associated fibroblasts in papillary thyroid carcinoma: a predictive marker of cervical lymph node metastasis.

PURPOSE: Most tumors have obvious biologically active fibroblasts known variously as myofibroblasts or cancer-associated fibroblasts (CAFs) in the stroma. CAFs have been known as an important factor of cancer invasion and metastasis. This study aimed to investigate the presence of CAFs in patients with papillary thyroid carcinoma (PTC) and evaluate the correlation between CAFs and cervical lymph node (LN) metastasis in PTC through immunohistochemistry. METHODS: The medical records of 128 patients who were diagnosed with PTC from January 1, 2010 to December 31, 2010 were reviewed, and 78 patients who underwent total thyroidectomy with or without neck dissection, were included in this study. A retrospective pathological evaluation was performed to verify the presence of CAFs. CD34 and α-smooth muscle actin (SMA) were used as markers of CAFs. RESULTS: Among 78 patients with PTC, 65 had desmoplastic stromal reaction around the PTC. Through immunohistochemical study of anti-CD34 and α-SMA antibodies, CAFs were found in 42 (64.6%) cases with desmoplastic stroma around the PTC. Univariate analysis showed that tumor size and CAFs were the risk factors of LN metastasis in patients with PTC, while multivariate analysis revealed that CAFs were the only independent risk factor of LN metastasis in patients with PTC. CONCLUSION: This study revealed the presence of CAFs in PTC. Furthermore, CAFs were found to be a risk factor of LN metastasis in PTC. Therefore, CAFs may be used as a predictive marker for LN metastasis in patients with PTC.

Odontoid osteomyelitis with atlantoaxial subluxation in an infant.

PURPOSE: To report a rare case of odontoid osteomyelitis with atlantoaxial subluxation in a 6-month-old infant. BACKGROUND: Odontoid osteomyelitis with atlantoaxial subluxation is extremely rare in children. Although several cases have been reported, there have been no studies concerning proper surgical drainage and immobilization in this disease. METHODS: A 6-month-old infant with odontoid osteomyelitis with atlantoaxial subluxation was surgically treated. The patient underwent a 3-month intravenous and oral antibiotic course and the Minerva body jacket cast was used for 3 months. Follow-up was carried out with computed tomographic scans and a cervical spine dynamogram. RESULTS: At 18 months post-surgery, the patient had completely recovered with no cervical instability. Computed tomographic scans revealed complete fusion of odontoid synchondrosis. The infant remained asymptomatic with a full range of head movement. CONCLUSION: Surgical drainage and proper immobilization appears to be a satisfactory treatment for pyogenic osteomyelitis of odontoid synchondrosis secondary to retropharyngeal abscess and atlantoaxial subluxation. LEVEL OF EVIDENCE: N/A.

c-Met-mediated reactivation of PI3K/AKT signaling contributes to insensitivity of BRAF(V600E) mutant thyroid cancer to BRAF inhibition.

BRAF (V600E) mutation is the most commonly detected genetic alteration in thyroid cancer. Unlike its high treatment response to selective BRAF inhibitor (PLX4032) in metastatic melanoma, the treatment response in thyroid cancer is reported to be low. The purpose of this study is to investigate the resistance mechanism responsible for this low treatment response to BRAF inhibitor in order to maximize the effect of targeted therapy. We examined the expression of feedback regulation mechanisms and alterations in the upper signal transduction pathway in thyroid cancer cell lines harboring BRAF mutation. Also, we investigated the effect of dual inhibition from combinatorial therapy. Two thyroid cancer cell lines, 8505C (anaplastic thyroid cancer) and BCPAP (papillary thyroid cancer) were selected and treated with PLX4032 and its drug sensitivity were examined and compared. Further investigation on the changes in signals responsible for the different treatment response to PLX4032 was carried out and the same experiment was performed on orthotopic xenograft mouse models. Unlike BCPAP cells, 8505C cells presented drug resistance to PLX4032 treatment and this was mainly due to increased expression of c-Met. Effective inhibitions of c-Met, p-AKT, and p-ERK were achieved after dual treatment with BRAF inhibitor (PLX4032) and c-Met inhibitor (PHA665752). Similar results were confirmed by in vivo study with orthotopic xenograft mouse model. c-Met-mediated reactivation of the PI3K/AKT pathway and MAPK pathway contributes to the relative insensitivity of BRAF (V600E) mutant anaplastic thyroid cancer cells to PLX4032. Dual inhibition of BRAF and c-Met leads to sustained treatment response. © 2015 Wiley Periodicals, Inc.

Endoscopic retroauricular thyroidectomy: preliminary results.

BACKGROUND: We sought to seek the potential role of endoscopic thyroidectomy with the retroauricular (RA) approach prior to future comparative study with the robotic RA thyroidectomy. Therefore, this study aims to verify the surgical feasibility of endoscopic RA thyroidectomy. METHODS: Eighteen patients who underwent endoscopic RA thyroidectomy for clinically suspicious papillary thyroid carcinoma or benign lesions from January to December 2013 were retrospectively reviewed and analyzed. RESULTS: All endoscopic operations via RA or modified facelift approach were successfully performed, without any significant intraoperative complications or conversion to open surgery. Based on patient-reported outcome questionnaires, all patients were satisfied with their postoperative surgical scars. CONCLUSION: Endoscopic RA thyroidectomy is technically feasible and safe with satisfactory cosmetic results for patients where indicated.

Microcystic Adnexal Carcinoma of the Nasal Tip Treated With Surgical Excision and Rotational Forehead Skin Flap.

Microcystic adnexal carcinoma (MAC) is a rare malignant cutaneous adenocarcinoma that typically occurs in the head and neck, particularly at the central face. There are only slightly more than 300 patients reported worldwide, and most patients occur in Caucasians. A 72-year-old man was referred to our hospital for definitive treatment of known MAC from previous biopsy. Wide excision of nasal tip and reconstruction of nasal defect with paramedian forehead flap and nasolabial flap transposition were performed rather than conventional Mohs surgery, due to grossly evident disease. Pathological examination verified 4.5 × 3 cm sized MAC with free resection margins. The patient is being followed up without any evidence of disease.

A Study Comparing Free-Flap Reconstruction via the Retroauricular Approach and the Traditional Transcervical Approach for Head and Neck Cancer: A Matched Case-Control Study.

BACKGROUND: Free-flap reconstruction via a retroauricular approach (RRA) after robot-assisted neck dissection (RAND) could have cosmetic benefits. This study aimed to compare the surgical outcomes of free-flap reconstruction via a RRA and via a transcervical approach in head and neck cancer. METHODS: For this matched case-control study, 50 patients with head and neck cancer requiring free-flap reconstruction were divided into two groups: those reconstructed via a RRA group and those reconstructed via a transcervical approach (RTA group). The total operation time for free-flap reconstruction, the flap survival rate, the length of the hospital stay, the complications, and the scar satisfaction scores were compared between the two groups. RESULTS: The RRA group comprised 25 patients, and the RTA group had 25 patients. The mean operation time for reconstruction was 288 ± 77 min in the RRA group and 250 ± 98 min in the RTA group (p = 0.132). Flap failure occurred for two patients in the RRA group (8 %) and for one patient in the RTA group (4 %) (p = 1.000). The mean hospital stay was 21 ± 18 days in the RRA group and 23 ± 14 days in the RTA group (p = 0.669). The complications were comparable between the two groups. However, the overall scar satisfaction was significantly higher in the RRA group (p = 0.000). CONCLUSIONS: For patients with head and neck cancer, RRA has better cosmetic outcomes than RTA. The RRA approach could be used for select patients who undergo RAND and prefer to avoid a visible anterior neck scar.

The new era of robotic neck surgery: The universal application of the retroauricular approach.

Recent advances in technology has triggered the introduction of surgical robotics in the field of head and neck surgery and changed the landscape indefinitely. The advent of transoral robotic surgery and robotic thyroidectomy techniques has urged the extended applications of the robot to other neck surgeries including remote access surgeries. Based on earlier reports and our surgical experiences, this review will discuss in detail various robotic head and neck surgeries via retroauricular approach.

Robotic excision of a huge parathyroid adenoma via a retroauricular approach.

Primary hyperparathyroidism results from the overproduction of parathyroid hormone by 1 or more autonomously hyperfunctioning parathyroid glands and often causes hypercalcemia. Once this condition has been diagnosed, the treatment of choice is surgical removal. There have been many attempts to remove the hyperfunctioning gland with minimally invasive surgical techniques, with cure rates comparable with those of conventional techniques. On the basis of our initial surgical experiences of robotic thyroidectomy and other head and neck surgeries via a retroauricular (RA) approach, we have recently successfully performed robotic excision of a huge parathyroid tumor via an RA approach on a 44-year-old woman who had been diagnosed with a parathyroid adenoma. It is the first to describe in detail the successful completion of a robotic parathyroidectomy via an RA approach.

Robotic total thyroidectomy with modified radical neck dissection via unilateral retroauricular approach.

BACKGROUND: Traditionally, total thyroidectomy was performed through an open transcervical incision; in cases where there was evident nodal metastasis, the conventional surgical approach was to extend the incision into a large single transverse incision to complete the required neck dissection. However, recent innovation in the surgical technique of thyroidectomy has offered the opportunity to reduce the patient's burden from these prominent surgical scars in the neck. Minimally invasive surgical techniques have been developed and applied by many institutions worldwide, and more recently, various techniques of remote access surgery have been suggested and actively applied.1-6 Since the advent of robotic surgical systems, some have adopted the concept of remote access surgery into developing various robotic thyroidectomy techniques. The more former and widely acknowledged robotic thyroidectomy technique uses a transaxillary (TA) approach, which has been developed by Chung et al. in Korea.7,8 This particular technique has some limitations in the sense that accessing the lymph nodes of the central compartment is troublesome. Terris et al. realized some shortcomings of robotic TA thyroidectomy, especially in their patients in the United States, and developed and reported the feasibility of robotic facelift thyroidectomy.9-13 In cases of thyroid carcinomas with lateral neck node metastases, most abandoned the concept of minimally invasive or remote access surgery and safely adopted conventional open surgical methods to remove the tumor burden. However, Chung et al. have attempted to perform concomitant modified radical neck dissection (MRND) after robotic thyroidectomy through the same TA port.14 This type of robot-assisted neck dissection (RAND) had some inherent limitations, due to fact that lymph nodes of the upper neck were difficult to remove. Over the past few years, we have developed a RAND via modified facelift (MFL) or retroauricular (RA) approach and reported the feasibility and safety of this technique.15, 16 Since then, we have actively applied such RAND techniques in various head and neck cancers. In our country, almost all cases of robotic total thyroidectomy utilize the TA approach. According to the reports made by Terris et al., robotic facelift thyroidectomy technique has been solely applied for ipsilateral hemithyroidectomy. For total thyroidectomy, Terris et al. performed the robotic surgery with bilateral RA incisions. Here, we intend to introduce our novel surgical method after successfully attempting simultaneous robotic total thyroidectomy and RAND via a single RA approach without an axillary incision. To our knowledge, this is the first to report in the medical literature. METHODS: We present four cases of our surgical experience since the beginning of 2013. All patients received robotic total thyroidectomy with MRND via single RA port without axillary incision after approval from the institutional review board at Severance Hospital, Yonsei University College of Medicine. The inclusion criteria for this operation were as follows: (1) patients with malignant carcinomas of the thyroid gland with evident cervical lymph node metastasis on preoperative imaging studies which are indicated for surgery; (2) patients with no previous history of treatment for thyroid carcinoma. The exclusion criteria were as follows: (1) patients with recurred thyroid tumors; (2) patients with thyroid carcinomas that showed gross invasion to local structures or extensive extrathyroidal capsular spread; (3) patients with clinically evident neck nodal metastasis with extracapsular spread; (4) patients with past history of neck surgery of any kind. In order to assess the extent of disease, neck ultrasonography with fine needle aspiration, neck CT or MRI and PET-CT were performed as preoperative evaluation. All patients were given full information of the possible treatment options for their thyroid cancer comprising of open transcervical approach and robotic surgery via RA approach, including the advantages and disadvantages of each treatment choice and provided written, informed consents before the surgery. General clinical information of the patients is outlined in Table 1. The skin incision for the operation was designed just like the approach for robotic facelift thyroidectomy by Terris et al. and RAND, which has been first reported by our institution.11 (,) 16 The operation was performed by the following sequence. Initially, the skin-subplatysmal flap was elevated after making the skin incision to create sufficient working space. During this process, the elevated skin flap was retracted and maintained by retractors held by the assistant. After application of the self-retaining retractor (Sangdosa Inc., Seoul), neck dissection of the upper neck levels was performed under gross vision. Next, RAND through the RA incision was conducted followed by ipsilateral thyroidectomy with central compartment neck dissection (CCND) via the same approach. Finally, contralateral thyroidectomy with CCND was performed via the single RA port. During these steps, the operator is aided by the bedside assistant with long-suction tips to manipulate and direct the dissected specimen to maintain optimal surgical view or to suck out the fume created by the thermocoagulation from the Harmonic shears. The da Vinci robotic surgical system (Intuitive Surgical, Sunnyvale, CA) was introduced via the RA port with a facedown 30° dual-channel endoscopic arm placed in the center, and two instrument arms equipped at either side with 5-mm Maryland forceps and Harmonic curved shears. During the step of robotic contralateral thyroidectomy, a ProGrasp forceps was utilized at times, instead of 5-mm Maryland forceps. The rest of the surgery was completed with the robotic system (see Video for demonstration of operation for patient 2). Table 1 Clinical characteristics of the patients Patient Sex/age (yr) BMI Side(a) Approach Pathology(b) Tumor size(c) (cm) CCND(d) MRND(d) Drain removal day Drainage amount (ml) Hospital stay (days) 1 F/38 23.8 L RA PC 0.7 2/5 8/23 8 788 11 2 F/18 18.3 L RA PC 0.8 2/8 7/35 6 398 9 3 F/44 23.1 L RA PC 0.9 5/12 5/27 6 607 9 4 F/26 32.9 L RA PC 1.4 3/14 9/48 7 476 15 BMI body mass index, RA retroauricular approach, PC papillary carcinoma, CCND central compartment neck dissection, MRND modified radical neck dissection (a)Side refers to the site of main lesion (b)Pathology refers to the primary tumor within the thyroid gland (c)Tumor size refers to the diameter of the largest tumor in the thyroid gland (d)For each type of lymph node dissection, the number of positive nodes/total number of retrieved nodes is stated RESULTS: For all of the patients, robotic total thyroidectomy with MRND (levels II, III, IV, V) via unilateral RA approach was successfully completed without any significant intraoperative complications or conversion to open or other approach methods. The total operation time was defined as the time from initial skin incision to removal of the final specimen, which was an average 306.1 ± 11.1 min (Table 2). This included the time for skin flap elevation and neck dissection under gross vision (87 ± 2.8 min), setting up the robotic system for RAND (6.8 ± 2.4 min), console time using the robotic system for RAND (59.3 ± 2.2 min), flap elevation for thyroidectomy (11.3 ± 2.5 min), robotic arms docking for ipsilateral thyroidectomy (6.3 ± 2.5 min), console time for ipsilateral thyroidectomy (61.3 ± 2.1 min), robotic arms docking for contralateral thyroidectomy (6.3 ± 2.5 min), and console time for contralateral thyroidectomy (61.8 ± 2.1 min). The working space created from RA incision was sufficient, and manipulations of the robotic instruments through this approach were technically feasible and safe without any mutual collisions throughout the entire operation. It also allowed for an excellent magnified surgical view enabling visualization of important local anatomical structures. There was no postoperative vocal cord palsy due to recurrent laryngeal nerve injury. However, two patients developed transient hypoparathyroidism, which resolved in the end without the need for calcium or vitamin D supplementation after certain period of medical management (Table 3). Also, there was no incidence of postoperative hemorrhage or hematoma formation, although a single patient developed a postoperative seroma on postoperative day 9, which was managed conservatively without the need for further surgical intervention. On average, the wound catheter was removed 6.8 ± 1 days after surgery and the patient was discharged from the hospital at an average 11 ± 2.8 days from admission (Table 1). Final surgical pathology confirmed the diagnosis of papillary carcinoma for every patient. The total number of cervical nodes retrieved from CCND and MRND was 9.8 ± 4 and 33.1 ± 11 respectively, and the number of positive metastatic nodes was 3 ± 1.4 and 7.3 ± 1.7 respectively (Table 1). In three patients (patients 2, 3, and 4), the presence of one parathyroid gland was each verified in the pathology specimen. All four patients have received high-dose (150 mCi) radioiodine ablation (RAI) therapy after the operation and are being followed up (average 11.3 months, range 9-13 months) on a regular basis with no evidence of recurrence (post-RAI, most recent, nonsuppressed thyroglobulin range 0.1-0.4 ng/ml, antithyroglobulin antibody range 13.7-147.5 IU/ml). (ABSTRACT TRUNCATED)

Clinical outcomes of transoral robotic surgery for head and neck tumors.

OBJECTIVES: In order to reduce treatment-related morbidity rates and increase patients' quality of life, robot-assisted surgery using the da Vinci surgical system (Intuitive Surgical Inc, Sunnyvale, California) has been studied actively in the field of head and neck surgery. This study analyzes our experiences therewith in order to evaluate the feasibility and efficacy of robot-assisted surgery via a transoral approach in the head and neck area. METHODS: Between April 2008 and December 2011, 141 patients were treated with robot-assisted surgery via a transoral approach. RESULTS: Robot-assisted surgeries were successfully completed via a transoral approach in all patients. The mean robotic operative time was 69.3 minutes, and the mean time for setup of the robotic system was 10.4 minutes. The average blood loss during the operation was 29.6 mL (range, 0 to 300 mL). Patients who underwent robot-assisted surgery were satisfied with their cosmetic results and treatment outcomes. CONCLUSIONS: Robot-assisted surgery via a transoral approach was confirmed to be feasible and efficient in the field of head and neck surgery. Further research is needed to investigate the long-term functional and oncological results of robot-assisted surgery.

Transoral robotic retropharyngeal lymph node dissection with or without lateral oropharyngectomy.

Retropharyngeal lymph node (RPLN) metastases can occur from advanced head and neck malignancies. Surgical access to RPLNs can be challenging. Considering the more aggressive conventional approach methods, there is an increasing need for minimally invasive techniques. Applying transoral robotic surgery (TORS) to access the RPLN has never been reported in the literature. The purpose of this study was to describe our experience with transoral robotic RPLN dissection for oropharyngeal and hypopharyngeal squamous cell carcinomas. We conducted a retrospective review of TORS cases performed at Severance Hospital, a tertiary care medical center from December 2011 to July 2012. Demographic, clinicopathologic, and treatment characteristics were abstracted from the medical record as well as complications and were analyzed descriptively. A total of 5 TORS procedures with transoral robotic RPLN dissection have been performed at Severance Hospital. Of these, 4 patients were treated for oropharyngeal squamous cell carcinoma and 1 for hypopharyngeal squamous cell carcinoma. The mean operation time for TORS including the robotic RPLN dissection was 84 ± 18.5 minutes. The operation time included time for docking of the robotic arms (4.8 ± 1.3 minutes), console working time for primary tumor removal (50 ± 8.9 minutes), and console working time for RPLN dissection (29.2 ± 9.4 minutes). No patients experienced complications related to the transoral robotic RPLN dissection. Transoral robotic RPLN dissection is a feasible approach for accessing retropharyngeal lymph nodes. This particular operative technique can serve as a minimal invasive surgery in removing pathologic RPLNs.

Carcinoma ex pleomorphic adenoma in the oral cavity: a huge oral cavity mass with neck metastasis.

Carcinoma ex pleomorphic adenoma (CEPA) is a rare, aggressive, poorly understood malignancy. In CEPA, an epithelial malignancy develops in association with a primary or recurrent benign pleomorphic adenoma. Carcinoma ex pleomorphic adenoma is very difficult to identify before surgery because the clinical presentation of many cases is similar to that of pleomorphic adenomas. The risk for malignancy increases with the duration of a mixed tumor. Treatment of CEPA must be individualized on the basis of the tumor location, involvement of adjacent structures, histologic subtype, and grade. The authors recently experienced a case of CEPA arising in the oral cavity with neck metastasis. The patient was a 70-year-old man presenting a huge mass that was present for 20 years and that slowly grew on the left side of the neck. We treated it with a total excision with wide margins and neck dissection. There was no recurrence during the follow-up period of 5 years up until now. We present a case of an unusually huge CEPA in the oral cavity.

Guidelines for the Use of Botulinum Toxin in Otolaryngology From the Korean Society of Laryngology, Phoniatrics and Logopedics Guideline Task Force.

The Korean Society of Laryngology, Phoniatrics and Logopedics created a task force to establish clinical practice guidelines for the use of botulinum toxin (BT) in otolaryngology. We selected 10 disease categories: spasmodic dysphonia, essential vocal tremor, vocal fold granuloma, bilateral vocal fold paralysis, Frey's syndrome, sialocele, sialorrhea, cricopharyngeal dysfunction, chronic sialadenitis, and first bite syndrome. To retrieve all relevant papers, we searched the CORE databases with predefined search strategies, including Medline (PubMed), Embase, the Cochrane Library, and KoreaMed. The committee reported 13 final recommendations with detailed evidence profiles. The guidelines are primarily aimed at all clinicians applying BT to the head and neck area. In addition, the guidelines aim to promote an improved understanding of the safe and effective use of BT by policymakers and counselors, as well as in patients scheduled to receive BT injections.

Robot-assisted Sistrunk's operation, total thyroidectomy, and neck dissection via a transaxillary and retroauricular (TARA) approach in papillary carcinoma arising in thyroglossal duct cyst and thyroid gland.

BACKGROUND: Carcinomas arising in the thyroglossal duct cysts are rare, accounting only for about 0.7-1.5 % of all thyroglossal duct cysts. Synchronous occurrence of thyroglossal duct carcinoma and thyroid carcinoma is reported to be even rarer. Traditionally, surgical treatments of such coexisting thyroglossal duct cyst carcinoma (TGDCa) and papillary thyroid carcinoma (PTC) were typically performed through a single transverse or double incisions on the overlying skin. A longer, extended cervical incision might be required if neck dissection is necessary. Though this method provides the operator with the optimal surgical view, the detrimental cosmetic effect on the patient of possessing a scar cannot be avoided, despite the effort of the surgeon to camouflage the scar by placing the incision in natural skin creases. Recently, the authors have previously reported the feasibility of robot-assisted neck dissections via a transaxillary and retroauricular ("TARA") approach or modified face-lift approach in early head and neck cancers. On the basis of the forementioned surgical technique, we demonstrate our novel technique for robot-assisted Sistrunk's operation via retroauricular approach as well as robot-assisted neck dissection with total thyroidectomy via transaxillary approach. METHODS: This is a case presentation of a 22-year-old woman with synchronous TGDCa and PTC with minimal lymph node metastasis who underwent resection of TGDCa and total thyroidectomy with left neck level III and IV lymph node dissection as well as central compartment lymph node dissection (CCND) via TARA approach with a robotic surgery system after approval from the institutional review board at Severance Hospital, Yonsei University College of Medicine. The incision was just like the TARA approach in head and neck cancer, which has been reported by our institute. The operation was proceeded as follows. First, excision of the TGDCa through the retroauricular incision was done followed by total thyroidectomy with CCND via transaxillary approach. Finally, neck dissection of left level III, IV was conducted via transaxillary approach. The da Vinci surgical system (Intuitive Surgical, Sunnyvale, CA) was introduced via retroauricular or transaxillary port. A 30° dual-channel endoscope was used, and the two instrument arms were equipped with 5 mm Maryland forceps and a 5 mm spatula monopolar cautery for TGDCa excision via retroauricular approach. When conducting total thyroidectomy and neck dissection via transaxillary approach, three instrument arms were utilized, each equipped with 5 mm Maryland forceps, ProGrasp forceps and a 5 mm spatula monopolar cautery or Harmonic curved shears. The rest of the surgery was completed with the robotic system (see Video). RESULTS: The operative procedure was successfully completed utilizing the robotic surgical system with no conversion to open surgery. The operation time for TGDCa excision was 97 min, including the time for skin flap elevation (15 min), setting up the robotic system (5 min), and console time using the robotic system (77 min). Also, the total operation time for the consecutive total thyroidectomy with CCND and level III, IV dissection was 142 min including the time for skin flap elevation (27 min), setting up the robotic system (3 min), and console time using the robotic system (112 min). There were no intraoperative complications. The retroauricular approach for the removal of the TGDCa allowed for an excellent magnified surgical view revealing important structures of the local anatomy. It also created sufficient space for the cutting of the relevant portion of the hyoid bone. Handling of the robotic instruments through the incision was technically feasible and safe without any mutual collisions throughout the operation. The patient's postoperative parathyroid hormone (PTH) level was within normal range and functions of her both vocal cords were intact. The histopathologic results of the specimens revealed thyroglossal duct cyst with internal papillary carcinoma measuring 1.1 cm with infiltrative tumor margins and papillary microcarcinoma measuring 0.9 cm within the left thyroid lobe with extrathyroidal soft tissue extension. There was no evidence of tumor in the right lobe and the pyramidal lobe of the thyroid gland. As for the lymph nodes resected, 7 out of 9 paratracheal nodes and 2 out of 7 left level III, IV nodes revealed metastatic carcinomas. The patient was discharged on the 8th day after the operation with no complications. The patient was extremely satisfied with the cosmetic results. The patient has received high-dose radioiodine ablation (RAI) therapy and is currently doing well with no evidence of recurrence. DISCUSSION: Although there is still a great deal of controversy regarding the treatment of TGDCa, there is little debate that for the cases of synchronous TGDCa and PTC, total thyroidectomy in addition to the Sistrunk procedure must be performed. As for the patient in our case where left level IV lymph node metastasis was detected under preoperative ultrasonography (USG), if the usual method of surgical procedure was to be selected, double incisions or a single extended transverse incision must be adopted for the Sistrunk's operation and total thyroidectomy with lateral neck dissection. The conventional method to remove neck masses was to do so by placing an incision on the overlying skin. This 'open' approach to viewing the lesion has an advantage of providing the operator with the best surgical view, but the recognizable surgical scar that results from the surgery can be displeasing for patients. Therefore the surgeon can try to make a small incision and camouflage the scar by placing the incision in natural skin creases, yet the cosmetic results can still be displeasing for the patient due to its visibility and permanence. This can be an even greater problem if the patient is young and an active member of his/her society and if the lesion is benign or low-grade malignancy which can be simply dissected and excised. Therefore it is the surgeon's best interest to perform an operation successfully with a 'least obvious' or 'hidden' scar whenever possible. Accordingly, we have adopted a novel approach, the transaxillary and retroauricular approach, in view of our increasing surgical experience with various indications such as submandibular gland (SMG) resections and neck dissections in head and neck cancer or thyroid papillary carcinoma. Some investigators have demonstrated that robot-assisted neck dissections performed on patients with thyroid cancer and lateral neck node metastasis are feasible and safe. We conducted total thyroidectomy with bilateral CCND and level III and IV dissection using the same approach. Although the technical feasibility and safety of neck dissection or SMG resection via retroauricular approach has already been reported previously at our institute, Sistrunk's operation via retroauricular approach will be challenging. In spite of that, we were able to demonstrate successfully Sistrunk's operation including the hyoid bone resection through the retroauricular approach. There are however, certain areas of potential difficulties which must be considered with caution during the operation procedure. First, when removing the TGDCa through the retroauricular port, identification of the ipsilateral hyoid bone is primarily important and it is also crucial that dissection along the capsule must be done carefully so as not to rupture the tumor. It is essential that sufficient working space must be created for the comfortable movement of the robotic arms through the retroauricular port and in order to do so, sufficient skin flap elevation in both superior and inferior directions must be performed. It is necessary to elevate the superior skin flap up to the level of the inferior border of the mandible but during this process, the platysma muscle must be identified and meticulous dissection along the subplatysmal plane must be carried out so as not to damage the marginal mandibular branch of the facial nerve. Another area of potential pitfalls concerns the total thyroidectomy with neck dissection through the transaxillary port. Sufficient amount of working space must be secured in order to perform comfortably the contralateral thyroidectomy and neck dissection and in order to do so, skin flap elevation must be done at least 2 cm further based on the ipsilateral omohyoid muscle and the contralateral thyroid gland must be adequately exposed. Using the robotic surgical system in removing the thyroglossal duct cyst, the free movement of wristed instrumentation through the retroauricular incision allowed for efficient dissection and easy handling of the tissue. In this particular case we could not identify the tract beyond the hyoid and up to the foramen cecum, but we anticipate that there would be no technical problems of dissection and excision had it been so. To our knowledge, Sistrunk's operation and total thyroidectomy with lateral neck dissection via TARA approach utilizing the robotic surgical system has never been attempted before. It has some advantages over the conventional surgery in terms of cosmesis. However, careful consideration in selecting appropriate cases is required and prospective trials should be conducted to recognize long-term outcomes and to overcome potential limitations.

Clinical Utility of Quantitative Parameters of Salivary Gland Scintigraphy for Diagnosing Burning Mouth Syndrome.

Burning mouth syndrome (BMS) is a chronic disorder characterized by a burning sensation in the oral cavity, often accompanied by xerostomia, with no relevant clinical or laboratory findings. This study aimed to investigate diagnostic values of quantitative parameters of salivary gland scintigraphy for BMS in patients with xerostomia. A total of 164 patients who underwent salivary gland scintigraphy for the workup of xerostomia were retrospectively reviewed. All patients were classified into patient groups with primary BMS, secondary BMS, and non-specific xerostomia. From salivary gland scintigraphy, 22 quantitative parameters were calculated and their diagnostic values were assessed based on the area under the receiver operating characteristic curve (AUC) values. Among salivary gland scintigraphy parameters, uptake speed in the left submandibular gland showed the highest AUC value (0.647) for detecting BMS and pre-stimulatory oral activity showed the highest AUC value (0.710) for detecting primary BMS. A salivary gland scintigraphy scoring system based on these two parameters further enhanced the diagnostic ability, demonstrating AUC values of 0.731 for BMS and 0.782 for primary BMS. These results suggest a potential diagnostic value of the quantitative parameters of salivary gland scintigraphy for detecting BMS in patients with xerostomia.