Corrigendum: Study Protocol of Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro)

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Study Protocol of Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro)

BACKGROUND: The ongoing Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) aims to observe the natural course of papillary thyroid microcarcinoma (PTMC), develop a protocol for active surveillance (AS), and compare the long-term prognosis, quality of life, and medical costs between the AS and immediate surgery groups. METHODS: This multicenter prospective cohort study of PTMC started in June 2016. The inclusion criteria were suspicious of malignancy or malignancy based on fine needle aspiration or core needle biopsy, age of ≥18 years, and a maximum diameter of ≤1 cm. If there was no major organ involvement, no lymph node/distant metastasis, and no variants with poor prognosis, the patients were explained of the pros and cons of immediate surgery and AS before selecting AS or immediate surgery. Follow-up visits (physical examination, ultrasonography, thyroid function, and questionnaires) are scheduled every 6 months during the first 2 years, and then every 1 year thereafter. Progression was defined as a maximum diameter increase of ≥3, ≥2 mm in two dimensions, suspected organ involvement, or lymph node/distant metastasis. RESULTS: Among 439 enrolled patients, 290 patients (66.1%) chose AS and 149 patients (33.9%) chose immediate surgery. The median follow-up was 6.7 months (range, 0.2 to 11.9). The immediate surgery group had a larger maximum tumor diameter, compared to the AS group (7.1±1.9 mm vs. 6.6±2.0 mm, respectively; P=0.014). CONCLUSION: The results will be useful for developing an appropriate PTMC treatment policy based on its natural course and risk factors for progression.

Clinical Features and Outcomes of Patients in Neonatal Intensive Care Requiring Laryngologic Consultation for Airway Disorders / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Airway problems frequently occur in neonatal patients requiring intensive care due to high prevalence of intubation history and congenital conditions that are linked to craniofacial or upper aerodigestive tract anomalies. However, many investigations on airway disorders have examined large populations of hospitalized children without focusing on those treated in the intensive care unit (ICU). Here we present the clinical features and outcomes in infants hospitalized with airway-related problems at the neonatal ICU. SUBJECTS AND METHOD: A total 69 patients were studied from May 2005 to December 2012, with each examined by an otolaryngologist while in neonatal ICU (NICU) for possible airway problems. Descriptive analysis was used in evaluating illnesses suffered and subsequent upper airway treatments. Factors associated with tracheostomy were identified by multivariate analysis. RESULTS: The median age of infants was 30 days (range, 1-237 days), with a male-to-female ratio of 1.38. The median gestational age was 35⁺³ weeks, and the mean birth weight was 2.35±0.89 kg. Overall, 40 patients had histories of intubation (median duration, 36 days; range, 1-204 days). The most common diagnosis in the upper airway exam was laryngomalacia (n=12), followed by subglottic stenosis (n=10) and micrognathia (n=8). Tracheostomy was performed in 38 patients (55.1%). In multivariate analysis, intubation history was identified as the only variable demonstrating a significant independent association with tracheostomy (p=0.006). CONCLUSION: Upper airway problems in NICU patients are due to a variety of disorders. Precise diagnosis and treatment is achievable through bedside and intraoperative assessments. Patients with a history of intubation are at increased risk of tracheostomy.

Guidelines for the Surgical Management of Laryngeal Cancer: Korean Society of Thyroid-Head and Neck Surgery

Korean Society of Thyroid-Head and Neck Surgery appointed a Task Force to develop clinical practice guidelines for the surgical treatment of laryngeal cancer. This Task Force conducted a systematic search of the EMBASE, MEDLINE, Cochrane Library, and KoreaMed databases to identify relevant articles, using search terms selected according to the key questions. Evidence-based recommendations were then created on the basis of these articles. An external expert review and Delphi questionnaire were applied to reach consensus regarding the recommendations. The resulting guidelines focus on the surgical treatment of laryngeal cancer with the assumption that surgery is the selected treatment modality after a multidisciplinary discussion in any context. These guidelines do not, therefore, address non-surgical treatment such as radiation therapy or chemotherapy. The committee developed 62 evidence-based recommendations in 32 categories intended to assist clinicians during management of patients with laryngeal cancer and patients with laryngeal cancer, and counselors and health policy-makers.

The Role of Neoadjuvant Chemotherapy in the Treatment of Nasopharyngeal Carcinoma: A Multi-institutional Retrospective Study (KROG 11-06) Using Propensity Score Matching Analysis / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We compared the treatment results and toxicity in nasopharyngeal carcinoma (NPC) patients treated with concurrent chemotherapy (CCRT) alone (the CRT arm) or neoadjuvant chemotherapy followed by CCRT (the NCT arm). MATERIALS AND METHODS: A multi-institutional retrospective study was conducted to review NPC patterns of care and treatment outcome. Data of 568 NPC patients treated by CCRT alone or by neoadjuvant chemotherapy followed by CCRT were collected from 15 institutions. Patients in both treatment arms were matched using the propensity score matching method, and the clinical outcomes were analyzed. RESULTS: After matching, 300 patients (150 patients in each group) were selected for analysis. Higher 5-year locoregional failure-free survival was observed in the CRT arm (85% vs. 72%, p=0.014). No significant differences in distant failure-free survival (DFFS), disease-free survival (DFS), and overall survival were observed between groups. In subgroup analysis, the NCT arm showed superior DFFS and DFS in stage IV patients younger than 60 years. No significant difference in compliance and toxicity was observed between groups, except the radiation therapy duration was slightly shorter in the CRT arm (50.0 days vs. 53.9 days, p=0.018). CONCLUSION: This study did not show the superiority of NCT followed by CCRT over CCRT alone. Because NCT could increase the risk of locoregional recurrences, it can only be considered in selected young patients with advanced stage IV disease. The role of NCT remains to be defined and should not be viewed as the standard of care.

Human salivary gland stem cells ameliorate hyposalivation of radiation-damaged rat salivary glands

Salivary function in mammals may be defective for various reasons, such as aging, Sjogren's syndrome or radiation therapy in head and neck cancer patients. Recently, tissue-specific stem cell therapy has attracted public attention as a next-generation therapeutic reagent. In the present study, we isolated tissue-specific stem cells from the human submandibular salivary gland (hSGSCs). To efficiently isolate and amplify hSGSCs in large amounts, we developed a culture system (lasting 4-5 weeks) without any selection. After five passages, we obtained adherent cells that expressed mesenchymal stem cell surface antigen markers, such as CD44, CD49f, CD90 and CD105, but not the hematopoietic stem cell markers, CD34 and CD45, and that were able to undergo adipogenic, osteogenic and chondrogenic differentiation. In addition, hSGSCs were differentiated into amylase-expressing cells by using a two-step differentiation method. Transplantation of hSGSCs to radiation-damaged rat salivary glands rescued hyposalivation and body weight loss, restored acinar and duct cell structure, and decreased the amount of apoptotic cells. These data suggest that the isolated hSGSCs, which may have characteristics of mesenchymal-like stem cells, could be used as a cell therapy agent for the damaged salivary gland.

Outcomes and Affecting Factors in the Management of Regional Recurrence in Head & Neck Squamous Cell Carcinoma / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Regional recurrence of head and neck squamous cell carcinoma (HNSCC) is the most common single type of treatment failure, and thus a challenging problem for the clinician. When planning management of regional recurrence, the grave outcome of the recurrence itself, and benefits and morbidity owing to the intervention must be taken into account. We analyzed the factors affecting salvage treatment outcomes of regional recurrence in head & neck squamous cell carcinoma. SUBJECTS AND METHOD: A retrospective analysis of medical records over a 10 year period (1994-2003) was conducted. Sixty-two patients with regional and locoregional recurrence were identified. Patients with local recurrence or distant metastasis were excluded. RESULTS: The median age of the population was 62 years. Sixty percent of the cases were regional, and the remainders were locoregional recurrences. The median time of recurrence was 16 months with an overall survival rate of 46.1%. Recurrence in a surgically virginal neck was associated with a favorable outcome. Factors associated with poor outcomes were node positive at initial presentation, neck dissection at initial treatment, recurrence at contralateral neck, incorporation of chemotherapy for salvage treatment, and subsequent recurrence after salvage treatment. CONCLUSION: In the management of patients with regional recurrence of HNSCC, the factors mentioned above should be taken into consideration regarding patient selection, salvage management plan, and patient counseling.

Efficacy of Fine Needle Aspiration Biopsy and Frozen Section Biopsy in Salivary Gland Malignancies / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: The aim of this study was to investigate the efficacy of fine needle aspiration biopsy (FNAB) and frozen section biopsy in salivary gland malignancies. SUBJECTS AND METHOD: From January 1995 through December 2004, 462 patients underwent operation for salivary gland mass. Of these patients, FNABs and frozen section biopsies were performed in 262 and 241 patients, respectively. The medical and pathologic reports were reviewed retrospectively. Malignancies were found in 57 patients. RESULTS: The sensitivity and the specificity of FNAB to detect salivary gland malignancies were 50.9% and 94.1%, respectively. For the frozen section biopsy, the sensitivity and specificity rose to 90.7% and 99.0%, respectively. When the examination period was divided into period 1 (Jan, 1995-Dec, 1999) and period 2 (Jan, 2000-Dec, 2004), sensitivity showed a significant increase from 33.3% to 57.1%. With respect to pathologic types of the tumors, the sensitivity of FNAB was high in adenocarcinoma (88.9%, 8/9) but low in mucoepidermoid carcinoma (30%, 3/10) and carcinoma ex pleomorphic adenoma (33.3%, 3/9). CONCLUSION: FNAB alone cannot guarantee accurate diagnosis of salivary gland malignancies. Therefore, intraoperative frozen section biopsy is recommended to make an adequate decision for surgical extent. The clinical experience of pathologists is also an important factor in improving the accuracy of fine needle aspiration biopsy.

Management of Pediatric Airway Stenosis using Cold Instruments and Mitomycin-C / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Mitomycin-C is becoming one of the most important agents in the treatment of glottic and subglottic stenosis. This study was conducted to investigate the clinical outcome of endoscopic management in glottic and subglottic stenosis patients using cold instruments and Mitomycin-C. SUBJECTS AND METHODS: A total of 47 patients with glottic and subglottic stenosis who were diagnosed and surgically treated in Seoul National University Children's Hospital from Jan. 2000 through Aug. 2003 were included. All were treated for endoscopic laryngomicrosurgery using cold instruments and bougienage. Thereafter, 0.4 mg/ml Mitomycin-C was directly applied for 5minutes on the surgical site. The surgical treatment outcome was retrospectively analyzed by reviewing medical records. RESULTS: All the studied patients showed improved airway stenosis and subjective symptoms, and twenty-one out of 47 patients have been decannulated successfully without any special complications. Mean number of operation for decannulation was 5.1, and the mean duration from the initial operation to decannulation was 17.3 months. CONCLUSION: Our data suggest that the use of cold instrumentation and topical mitomycin-C application might be a promising, initial choice of management in patients with airway stenosis.

Treatment of Well-differentiated Thyroid Carcinoma with Aerodigestive Tract Invasion / 대한내분비외과학회지

PURPOSE: Well differentiated thyroid carcinomas are mostly curable diseases. Invasion of aerodigestive tract by thyroid carcinoma is rare. However, it is considered as a poor prognostic indicator of survival. Some studies showed that local invasion of thyroid carcinoma was the cause of death in many patients. Therefore, adequate local control of the tumor is critical to avoid the mortality as well as the morbidity of the disease. To find proper and adequate treatment modality of locally invasive thyroid carcinoma, we evaluated treatment modalities and outcomes in the patients with thyroid carcinoma with invasion of aerodigestive tract. METHODS: Forty patients with thyroid carcinoma invading aerodigestive tract who were treated from July 1989 through July 2002 were reviewed retrospectively. RESULTS: Direct intraluminal invasion of the thyroid carcinoma requires definitive resection of the aerodigestive tract. In case that the extent of tumor was thought to be limited to perichondrium or extraluminal invasion, tracheal shaving procedure was performed. Five-year and 10-year local control rates were 81.6% and 57.4%, respectively. Disease-specific survival rates of 5-year and 10-year were 90.1% and 81.1%, respectively. CONCLUSION: For the successful treatment of invasive thyroid carcinoma, the resection of the functional structures or the aerodigestive tract should be determined prudently according to the presence of the intraluminal invasion.

Celecoxib and Indomethacin Inhibit the Growth of Cancer and Oral Keratinocyte Cell Lines via Cyclooxygenase-2 Independent Mechanism / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Overexpression of cyclooxygenase-2 (COX-2), a rate-limiting enzyme in the generation of prostanoids from arachidonic acid, has known to be closely related to tumorigenesis, tumor growth, angiogenesis, and metastasis. Selective or non-selective COX-2 inhibitors have been used for the growth inhibition of cancers with preventative intents ; however, it has been suggested recently that cancer cells have COX-2-independent mechanisms. MATERIALS AND METHOD: Using MTT assat and cell counts, we observed the growth inhibition of SCC VII, CT-26 and B16F10 murine cancer cell lines when treated by celecoxib and indomethacin. SNU-1041 and HOK 16B were used as controls for comparing with the murine cell lines. The COX-2 expression of these cell lines was analyzed by western blotting and compared with the degree of inhibition by the drugs. RESULTS: The growth inhibition of the cell lines by the drugs was clearly demonstrated in a concentration-dependent manner and depended on the type of cell lines and test drug. The in vitro viability assay revealed that CT-26 expressing COX-2 protein was slightly inhibited but SCC VII and B16F10 without COX-2 expression were moderate-to-highly inhibited by the drug treatment. Celecoxib and indomethacin appeared to have no close relation with the COX-2 expression of cell lines in their growth inhibition. HOK 16B showed a resistance by concentrations less than 25 microM of celecoxib, which implies that celecoxib has a more selective effect on tumor cells and is safer than indomethacin. CONCLUSION: The growth of cancer cells was inhibited by celecoxib and indomethacin treatment, which depends on the type of cancer, treated drug, and its concentration. Their suppressive effect is not closely related to the COX-2 expression of cancer cells.

Treatment Results of Pediatric Nonorbital Head and Neck Rhabdomyosarcoma and Related Prognostic Factors / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: The survival rate for rhabdomyosarcoma has been improved much after introduction of multimodality treatment. We reviewed the treatment results and investigated the related prognostic factors of pediatric nonorbital head and neck rhabdomyosarcoma. MATERIALS AND METHOD: Medical records of 27 children treated for nonorbital head and neck rhabdomyosarcoma from January 1986 to December 2000 were analyzed. Patients' ages at diagnosis ranged from 1 to 169 months (mean: 75 months). The pathologic subtypes were predominantly embryonal with 23 patients (85%), followed by alveolar subtype with 1 (4%), and uncertain one with 3 (11%). RESULTS: The overall 5-year survival rate was 69%. Of 27 patients, 20 had parameningeal and 7 had nonparameningeal tumors. Eleven (41%) had cranial nerve involvement with frequent abducens nerve and facial nerve involvement. Ten (37%) had skull base or brain invasion. The 5-year survival of patients with skull base or brain invasion was 40% and without skull base or brain invasion was 88%. Parameningeal site (68% vs 71%) and cranial nerve involvement (64% vs 73%) were not significant prognostic factors. CONCLUSION: Skull base or brain invasion was an important prognostic factor. There is no indication of initial aggressive surgical resection for the tumors located in the parameningeal site, which is difficult to access.

Transseptal-Transsphenoidal Approach: Objective Assessment of Postoperative Nasal Functions

THE AIM OF STUDY: The transseptal-transsphenoidal approach (TSA) for pituitary tumors may alter nasal functions, including nasal respiration and olfaction. The aim of this study was to investigate the efficacy of TSA in terms of nasal functions. MATERIALS AND METHODS: Twenty two cases of pituitary tumors, managed at Seoul National University Hospital from May 1997 through March 1998, were included in this prospective study. Nasal functions were evaluated preoperatively and 2 months after the operation through symptom questionnaires, rhinomanometry, acoustic rhinometry and the butanol thres-hold test. RESULTS: The subjective nasal symptoms, including nasal obstruction and olfaction, were not changed following the operation in 72% and 86% of the cases, respectively. In the objective findings, total nasal resistance was not grossly changed after the operation, however, cross-sectional areas at C-notch and 3.3 cm from the anterior nasal spine increased significantly after the operation. Mucosal response to a topical vasoconstrictor after the operation was less effective than before the preoperation. CONCLUSION: TSA for pituitary tumors may be a safe and effective technique in preserving nasal functions subjectively and objectively.

Anterior and Middle Skull Base Surgery: The SNUH Experience / 대한이비인후과학회지

OBJECTIVES: The purpose of this study is to evaluate the effectiveness of skull base surgery on local control and survival of skull base lesions. In addition, the complications and their impact on the tumor control status as well as postoperative morbidity are considered. MATERIALS AND METHODS: We report our experience on 35 patients with skull base lesions. The patients were divided into two subgroups: (1) anterior skull base group (n=27) and (2) middle skull base group (n=8). RESULTS: For the anterior skull base group, the overall survival rate for malignant tumor (n=15) at 16 months was 53% without regard to histologic types. The overall operative mortality rate was 0% and the complication rate was 25% with craniofacial resection for control of neoplasm (n=20) and all of these complications were managed successfully without any sequelae. The technique of craniofacial resection was applied to the management of skull base trauma (n=4) and encephaloceles (n=3) successfully. The middle skull base group consisted of 5 patients with juvenile nasopharyngeal angiofibroma, and one patient each with malignant meningioma, meningioma, fibrous dysplasia, respectively. All JNA patients were managed with a combined intracranial and transmaxillary/transpalatal approach. Among them, 4 patients were cured and one patient developed a recurrence near the cavernous sinus. Surgical morbidity was minimal and there was no mortality. Facial translocation approach to the skull base was utilized in 2 patients. CONCLUSION: Craniofacial resection is a valid surgical technique for surgical management of tumors involving the anterior skull base and also can be applied to the treatment of selected trauma and malformations. The combined intracranial and transmaxillary/transpalatal approach is a safe and reliable method to remove nasopharyngeal angiofibroma with intracranial invasion.