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Objectives Signaling between cancer stem cells (CSC) and their extracellular matrix has a crucial role in CSC progression and maintenance. However, mediators of this signaling pathway in head and neck squamous cell carcinoma (HNSCC) are largely unknown. Here, we explored whether integrin β1, which is one of the key regulators of the communication between cells and their microenvironment, affected the stemness of HNSCC cells. Materials and methods We examined self-renewal capacity, chemoresistance, and xenograft tumorigenicity after knockdown of integrin β1 in primary HNSCC cells. In addition, we studied the role of focal adhesion kinase (FAK), an intracellular downstream molecule of integrin signaling, in influencing stemness of HNSCC. The relevance of Notch1 and integrin β1 interactions in HNSCC cells was also examined. Finally, immunohistochemical analysis was carried out to test whether the coexpression of integrin β1 and Notch1 in the samples from HNSCC patients correlated with their survival. Results Targeting integrin β1 in HNSCC cells inhibited self-renewal, chemoresistance, and in vivo tumor-forming capacity. Treatment with an inhibitor of FAK decreased self-renewal capacities and expression of various putative stem cell markers (Oct4, Sox2, and Nanog) in a dose-dependent manner. Moreover, knockdown of integrin β1 decreased the expression of Notch1 and its target genes (Hey1 and Hes1). Notably, HNSCC patients demonstrating simultaneous expression of integrin β1 and Notch1 in their tissue samples had significantly worse survival rate. Conclusion Integrin β1/Notch1 axis has a significant role in the regulation of stemness in HNSCC.

Objective According to American Thyroid Association (ATA) guideline, thyroid lobectomy is recommended for the management of papillary thyroid microcarcinomas (PTMC) with a diameter lesser than 1 cm. However, this procedure is associated with a risk of potential complications such as vocal cord palsy. Thus, we considered the applicability of conservative thyroidectomy, involving partial removal of the thyroid cancer lesion, not the entire ipsilateral thyroid lobe. Methods A retrospective analysis of all PTMC patients who underwent conservative thyroidectomy at Konkuk University Hospital between August 2008 and February 2014 was performed. Oncologic results of these patients along with the incidence of postoperative complications were evaluated. Seventy-nine patients who underwent conservative thyroidectomy for the treatment of PTMC were enrolled in the present study. Results Four of the 79 patients (5.0%) showed recurrence, 2 local (2.5%) and 2 regional (2.5%), respectively. All of these patients consequently underwent surgery alone and were salvaged. Temporary postoperative complications such as vocal cord palsy and hypocalcemia developed in 1 and 1 case, respectively, but completely recovered over time. Conclusions Conservative thyroidectomy is an oncologically and functionally safe procedure for surgical treatment of PTMC and can be considered as an alternative to thyroid lobectomy for the surgical management of PTMC.

The canonical Wnt/β-catenin pathway is involved in diverse cancer development mechanisms, such as proliferation, migration, and invasion. However, its role in head and neck squamous cell carcinoma (HNSCC) remains largely unknown. We investigated whether the canonical Wnt/β-catenin signaling pathway acts as a controller of invasion and lymph node metastasis (LNM) in HNSCC. Loss of function experiments against the canonical Wnt/β-catenin pathway were conducted to evaluate its invasive and metastatic role in HNSCC cells. Slug was evaluated as a downstream protein in canonical Wnt/β-catenin-mediated invasion. In addition, canonical Wnt/β-catenin and Slug expression levels were examined in 119 HNSCC tissue samples to study the relevance of these proteins in LNM and prognosis of patients post-treatment. In vitro suppression of β-catenin expression led to decreased migration and invasion of HNSCC cells. Using an in vivo mouse orthotopic LNM model, a decrease in LNM was observed with mitigated β-catenin expression. Slug expression upregulation mediates invasion and LNM by the canonical Wnt/β-catenin pathway. Simultaneous expression of β-catenin and Slug is the major predictive factor of LNM and survival rate in patients with HNSCC. In conclusion, the canonical Wnt/β-catenin/Slug signaling axis significantly contributes to cancer cell invasion and LNM. Its blockade may be a treatment strategy for LNM and tumor recurrence in HNSCC.

The association between obstructive sleep apnea (OSA) and malignant brain tumors has yet to be fully investigated. Therefore, the purpose of this study was to elucidate the effect of OSA on brain tumor incidence based on the Korea National Health Insurance Service (KNHIS) dataset. The KNHIS data between 2007 and 2014 were analyzed, and the primary endpoint was newly diagnosed malignant brain tumor. A total of 198,574 subjects aged ≥ 20 years with newly diagnosed OSA were enrolled in the study, and 992,870 individuals were selected as a control group based on propensity score matching (PSM) by gender and age. The average follow-up duration was 4.8 ± 2.3 years. The hazard ratios (HRs) for brain tumor for patients with OSA were 1.78 (95% confidence interval [CI]: 1.42–2.21) in Model 1 (not adjusted with any covariate) and 1.67 (95% CI: 1.34–2.09) in Model 2 (adjusted for income level, diabetes, hypertension, dyslipidemia, and COPD). In subgroup analysis by gender, the odds ratios (OR) of OSA were 1.82 (95% CI: 1.41–2.33) in men and 1.26 (95% CI: 0.74–2.03) in women. The ORs were 1.97 (95% CI: 1.15–3.24) in the older (age ≥ 65 years) group, 1.66 (95% CI: 1.25–2.17) in the middle-aged (40 ≤ age < 65 years) group, and 1.41 (0.78–2.44) in the young (20 ≤ age < 40 years) group. In conclusion, OSA may increase the incidence of brain tumors.

Some studies have argued that obstructive sleep apnoea (OSA) increases the risk of breast cancer. However, the results are often conflicting. This study aimed to investigate associations between OSA and breast cancer incidence using the Korea National Health Insurance Service (KNHIS) database. This retrospective cohort study analyzed data from the KNHIS database. A total of 45,699 women (≥20 years of age) newly diagnosed with OSA between 2007 and 2014 were included. The control groups were a 5-fold, age-matched women who had not been diagnosed with OSA. Mean follow-up duration was 3.7 ± 2.3 years. The primary endpoint was newly diagnosed breast cancer. The breast cancer hazard ratio (95% confidence interval) was calculated for patients with OSA and compared with that of the control group. The incidence of breast cancer among patients with OSA was significantly higher than that among the controls (1.20 [1.04–1.39]). In particular, the incidence of breast cancer was higher among patients aged ≥65 years (1.72 [1.10–2.71]). The result suggests that OSA may be a risk factor for breast cancer in women.

Objective Untreated obstructive sleep apnea (OSA) is a risk factor for cardiovascular disease including myocardial infarction (MI), congestive heart failure (CHF), and atrial fibrillation (AF). Continuous positive airway pressure (CPAP) is an effective treatment for OSA; however, compliance with CPAP can be challenging for some patients. The objective of this study was to investigate whether uvulopalatopharyngoplasty (UPPP) reduced the risk of cardiovascular complications for patients with OSA. Methods Data from Korea National Health Insurance Corporation, a national health care database in South Korea, were analyzed. All patients with a new diagnosis of OSA from 2007 to 2014 were identified. Propensity score matching by age and sex was used to identify a control group five times larger than the OSA group for comparison. Patient demographics and comorbidities were collected. The OSA group was further divided into patients who had an UPPP and patients who did not undergo surgery. The primary endpoints were newly diagnosed MI, CHF, and AF. Results Of 192,316 patients with a new diagnosis of OSA, 22,213 had undergone UPPP. For the control group, 961,590 individuals were selected. Patients with OSA had an increased risk of CHF and AF, compared to control patients. UPPP reduced the incidence of CHF and AF significantly. Age, gender, and hypertension were also found to be risk factors for cardiac complications for patients with OSA. Conclusion OSA increases the risk of CHF and AF. UPPP in this population can significantly reduce the risk of cardiac complications in patients with OSA.

Background: Head and neck squamous cell carcinomas (HNSCCs) are highly lethal epithelial tumours containing self-renewal cancer stem cells (CSCs). CSCs in HNSCCs are strongly associated with tumour initiation, invasion, and chemoradiation resistance. However, the important factors regulating stemness in HNSCCs remain unclear. Here, we investigated the molecular roles and clinical significance of inhibitor of DNA binding 2 (Id2) protein to determine if it constitutes a novel therapeutic target for ablating HNSCC cells with stemness. Methods: We performed in vitro and in vivo studies of Id2 function and its effects on stemness using HNSCC cells. We also examined whether Id2 expression could be used as a prognostic indicator through immunohistochemical staining of 119 human HNSCC tumours. Results: Expression of Id2 was higher in HNSCC cells with stemness compared with differentiated HNSCC cells. Overexpression of Id2 increased proliferation, self-renewal, and expression of the putative stemness marker CD44 in HNSCC cells in vitro and in vivo. In contrast, silencing of Id2 using short hairpin RNA attenuated the stemness phenotype of HNSCC cells by reducing self-renewal, CD44 expression, cisplatin chemoresistance, and xenograft tumourigenicity. Most importantly, increased expression of Id2 was closely associated with poorer post-treatment survival rates in HNSCC patients. Conclusions: Inhibitor of DNA binding2 represents a novel and promising therapeutic target for treating and improving the clinical outcomes for patients with HNSCC.

Objectives To investigate the association between menopausal hormone therapy (MHT) and chronic rhinitis. Methods The data used in this study were derived from the Korea National Health and Nutrition Examination Survey. The analysis included 2967 postmenopausal women under 70 years of age, and there were no missing data. Questionnaire responses regarding MHT, current life habits, reproductive history, and rhinitis were reviewed. The levels of total immunoglobulin E (IgE) and specific IgE for Dermatophagoides farinae , cockroaches, and dogs were measured, using approximately 10% of all samples. We compared women who were users of MHT and non-users of MHT. We also compared women with and without chronic rhinitis. Results Of 2967 women matching the study criteria, 567 were MHT users. The proportion of general rhinitis symptoms was greater among MHT users (24.5%) than among MHT non-users (18.9%, p = 0.003). The proportion of cases of rhinorrhea or posterior nasal drip was also greater among MHT users (6.3% vs. 4.3%, p = 0.042), while there were no differences between the two groups in the proportion of cases of nasal obstruction. There were no differences in total IgE and specific IgE levels between the two groups. MHT was used by 23.4% of women with chronic rhinitis and 18.0% of women without chronic rhinitis. Age, waist circumference, and body mass index were also greater among women without chronic rhinitis than among those with chronic rhinitis. Conclusions MHT may cause non-allergic rhinitis in postmenopausal women. Age and obesity may also affect the occurrence of non-allergic rhinitis in postmenopausal women.

Background This study analyzed the incidence, pattern, and predictive factors for lateral lymph node (LN) recurrence in patients with papillary thyroid cancer (PTC) without clinical evidence of lateral LN metastasis. Methods A retrospective analysis was performed on 246 patients with PTC who underwent total thyroidectomy and central neck dissection from 2004 to 2010. None of the patients had clinical evidence of lateral LN metastasis at the time of diagnosis. Predictive factors for lateral LN recurrence were evaluated using the chi-square test. Binary logistic regression was used for the multivariate analysis. Recurrence-free survival rates were estimated by the Kaplan–Meier and Cox regression methods. Results Of the 246 patients, 11 (4.5%) developed lateral LN recurrence with a median follow-up of 49 months. In the multivariate analysis, tumor size >1 cm (odds ratio [OR], 8.14; 95% confidence interval [CI], 1.01–65.68; p = 0.049) and central LN metastasis (OR, 10.59; 95% CI, 1.32–85.17; p = 0.026) were independent predictive factors of lateral LN recurrence. Especially, extranodal extension of a metastatic central LN (OR, 38.82; 95% CI, 5.71–264.10; p Conclusions Tumor size and central LN metastasis were independent predictors of lateral LN recurrence in patients with PTC without initial clinical lateral neck metastasis who underwent total thyroidectomy and central neck dissection. Close surveillance may be necessary for early detection of lateral LN recurrence in PTC patients with tumor size ⩾1 cm, and central LN metastasis with extranodal extension.

Notch1 is associated with the initiation and progression of various solid tumors. However, the exact role of Notch1 expression in head and neck squamous cell carcinoma (HNSCC) remain unclear. We created cells ectopically expressing notch intracellular domain (NICD) from previously established HNSCC cells and examined self-renewal capacity and stem cell markers' expression compared with control cells. In addition, we knocked Notch1 down in primary spheres obtained from HNSCC tumor tissue and assessed the attenuation of stemness-associated traits in these cells in vitro and in vivo. Furthermore, we examined clinical relevance of Notch1 expression in HNSCC patients. Constitutive activation of NICD promoted the self-renewal capacity of HNSCC cells by activating sphere formation and increased the expression of stem cell markers such as Oct4, Sox2, and CD44. In contrast, Notch1 knockdown in primary HNSCC cancer stem cells (CSCs) attenuated CSC traits and augmented the chemosensitizing effects of cisplatin along with the decreased expression of almost all of ABC transporter genes. In addition, Notch1 knockdown in HNSCC CSCs inhibited tumor formation and increased survival of mice in a xenograft model. Also, Notch1 acted upstream of canonical Wnt signaling in HNSCC cells. Finally, elevated Notch1 expression is associated with poor prognosis in patients with HNSCC. In conclusion, Notch1 may be a critical regulator of stemness in HNSCC cells, and inactivation of this pathway could be a potential targeted approach for the treatment of HNSCC.

Summary Objectives Increasing evidence suggests that epigenetic regulation is responsible for tumor initiation and progression in head and neck squamous cell carcinoma (HNSCC). Although the polycomb group protein enhancer zeste homolog 2 (EZH2) is upregulated and a key epigenetic modifier implicated in various cancers, its molecular mechanism in HNSCC remains unknown. Herein, we investigated the role of EZH2 in HNSCC progression and its clinical implication as an HNSCC risk predictor. Materials and method A retrospective analysis was performed on 90 HNSCC patients who had curative surgery between 1999 and 2011. Patients with high and low EZH2 expression were compared by the various clinicopathological factors. Survival rates were estimated by the Kaplan–Meier method and log-rank test was used to determine significance. For functional in vitro analysis, migration/invasion assay and Western blotting were performed after EZH2 knockdown using siRNA. In addition, cell proliferation was measured to clarify the role of EZH2 on cisplatin chemotherapy. Results In patients with HNSCC, high EZH2 expression was correlated with advanced T stage and poor survival outcome. RNAi analysis revealed that EZH2 silencing increased E-cadherin expression while decreasing that of N-cadherin and Vimentin without altering Snail/Slug signaling, which led to decreased cell migration/invasion. EZH2 is also associated with tumor aggressiveness via regulating the epithelial-to-mesenchymal transition. Furthermore, we show that high EZH2 expression decreases sensitivity to cisplatin-based chemotherapy. Conclusion Our results indicate that EZH2 may not be only a predictive and prognostic biomarker but also a potential personalized therapeutic target for the treatment of HNSCC.

Summary Background We investigated the risk factors of the regional lymph node (LN) recurrence in papillary thyroid cancer (PTC) patients underwent thyroidectomy and neck dissection according to the clinicopathologic features, preoperative clinical nodal status and the recurrence in previously dissected or undissected compartment of the neck. Methods A retrospective analysis was performed on 297 patients who underwent total thyroidectomy and LN dissection between 2004 and 2010. Patients with and without regional recurrence were compared by the various clinicopathological factors. Recurrence-free survival rates were estimated by the Kaplan–Meier and Cox regression method. Results With a median follow-up of 53 months, 22 (7.4%) patients developed regional LN recurrence. Initial LN metastasis and tumor size ⩾1 cm were independent predictive factors for regional recurrence. In patients without preoperative clinical LN, Tumor size ⩾1 cm and extrathyroidal extension were significant risk factors for regional recurrence. In cases with preoperative clinical LN, there was no specific significant factor for recurrence. Tumor size ⩾1 cm, capsular invasion, extrathyroidal extension, and lymphovascular invasion were significant risk factors of regional recurrence in previously dissected compartments. Tumor size ⩾1 cm and extrathyroidal extension were significant predictive factors of regional recurrence in previously undissected compartments. Conclusions Tumor size and LN metastasis were independent predictors of regional LN recurrence in PTC patients after total thyroidectomy and central neck dissection. Patients with tumor size >1 cm or extrathyroidal extension were more likely to have tumor recur both within the previously dissected field as well as the un-dissected compartments.

There are many conflicting reports about the clinical implications of BRAFCarcinoma tissues from 60 patients with PTC were genotyped for BRAFThe BRAFA high extent more than 25% of BRAF

c-Met proto-oncogene, which is a receptor of ligand hepatocyte growth factor (HGF), has been associated with cancer cell invasion. There have been no reports on the relationship between the expression of c-Met and tumor invasion and metastasis in small (T(1-2)) squamous cell carcinoma of the oral tongue (SCCOT). We analyzed the relationship between c-Met expression and tumor invasion depth and lymph node metastasis in 71 surgically treated patients with small SCCOT using immunohistochemistry. Furthermore, we investigated the associations between the c-Met expression status and patient survival. In addition, we explored whether overexpression of c-Met enhances tumor growth and invasion of tongue cancer cells in vitro and in vivo. Positive immunohistochemical staining of c-Met was observed in 39 (55%) samples. Presence of neck metastasis, and >4mm depth of tumor invasion, strongly correlated with c-Met expression in small SCCOT both by the univariate and multivariate analysis (p

Differentiation therapy is a novel approach to eradicate cancer stem cells (CSCs), including head and neck squamous carcinoma CSC (HNSC CSC). All-trans-retinoic acid (ATRA) is a potent differentiating agent. We studied the anti-tumour effect of ATRA on HNSC CSC. HNSC CSCs were differentiated by ATRA in a serum-free conditioned medium. The effect of differentiation on tumour growth was assessed in vitro and in vivo, and chemosensitisation was examined using a colorimetric viability assay. In addition, the involvement of Wnt/β-catenin signalling as an underlying mechanism of the anti-tumour effect of retinoic acid (RA) on HNSC CSCs was assessed. ATRA suppressed the expression of the stem cell markers Oct4, Sox2, Nestin and CD44 in HNSC CSCs and inhibited the proliferation of HNSC CSCs in vitro and in vivo. Furthermore, ATRA treatment augmented the chemosensitising effects of cisplatin. The anti-tumour effects of ATRA may be associated with down-regulation of Wnt/β-catenin signalling. In conclusion, ATRA may be potentially valuable in treatment of HNSC CSC, especially in combination with cisplatin.

Although head and neck squamous carcinoma cancer stem cells (HNSC-CSCs) can be enriched in serum-free suspension cultures, it is difficult to stably expand HNSC-CSC lines in suspension due to spontaneous apoptosis and differentiation. Here, we investigated whether HNSC-CSCs can be expanded without loss of stem cell properties by adherent culture methods. Cell culture plates were coated with type IV collagen, laminin, or fibronectin. We examined cancer stem cell traits of adherent HNSC-CSCs grown on these plates using immunocytochemistry for stem cell marker expression and analyses of chemo-resistance and xenograft tumorigenicity. We also assessed the growth rate, apoptosis rate, and gene transduction efficiency of adherent and suspended HNSC-CSCs. HNSC-CSCs grew much faster on type IV collagen-coated plates than in suspension. Adherent HNSC-CSCs expressed putative stem cell markers (OCT4 and CD44) and were chemo-resistant to various cytotoxic drugs (cisplatin, fluorouracil, paclitaxel, and docetaxel). Adherent HNSC-CSCs at the limiting dilution (1000 cells) produced tumors in nude mice. Adherent HNSC-CSCs also showed less spontaneous apoptotic cell death and were more competent to lentiviral transduction than suspended HNSC-CSCs. In conclusion, compared to suspension cultures, adherence on type IV collagen-coated culture plates provides better experimental conditions for HNSC-CSC expansion, which should facilitate various refined cellular studies.

Background The frequencies, pattern, and predictive factors for occult contralateral central lymph node (LN) metastases in papillary thyroid carcinoma (PTC) patients with unilateral lateral neck metastases are still unsettled. Study Design We reviewed the medical records of 70 consecutive PTC patients with unilateral positive lateral neck who have initially received total thyroidectomy and comprehensive neck dissection including bilateral central LN dissection. The relationships between occult LN metastases to the contralateral central neck compartment and preoperative image findings and clinicopathologic factors were analyzed. Results Central neck LN metastases were present in 82.9%, in which 34.3% had bilateral central neck involvement and 48.6% had unilateral ipsilateral central neck involvement. Isolated contralateral central LN metastases without ipsilateral central LN metastases were not found. Multivariate analysis showed that the multifocality of primary thyroid tumor (p = 0.010, odds ratio=5.120) and the presence of metastases in all lateral neck levels (p = 0.017, odds ratio=5.130) were independent risk factors for the presence of contralateral central LN metastases. Conclusions The rate of occult contralateral central LN metastases was relatively high (34.3%) in PTC with ipsilaterally positive lateral neck, and multifocal primary tumor and positive LN involvement in all lateral neck levels are associated with contralateral central LN metastases.

Anaplastic thyroid carcinoma (ATC) is one of the most lethal solid tumors arising thyroid gland with dismal prognosis. One of the constituents of garlic, diallyl sulfide (DAS) was shown to inhibit chemically induced carcinogenesis in many animal models. This study examined whether DAS could induce growth inhibition and apoptosis in ATC cells. In MTT assay, DAS treatment inhibited the proliferation of ARO cells in a dose-dependent manner. Flow cytometric analysis showed that DAS treatment increased the accumulation of sub-G1 DNA and concomitant accumulation of cells in the G2/M phase in a dose-dependent manner. In addition, DAS-induced apoptosis was associated with a decrease in the level of Bcl-2 expression and an increase in the level of Bax expression, and cytochrome c was remarkably released from mitochondrial into the cytosol by DAS. Furthermore, caspase-9 and caspase-3 were activated by DAS, and DAS cleaved PARP. Taken together, DAS decreased cell proliferation and induced apoptosis via mitochondrial signaling pathway in ATC cells.

Background The extent of lateral neck dissection for clinically evident nodal metastases in the lateral neck in a patient with papillary thyroid cancer (PTC) continues to remain controversial. Methods We reviewed retrospectively the medical records between March 2005 and March 2008 of 70 patients with PTC who underwent therapeutic lateral neck dissections (level II–V) to establish indications for omission of a level V lymphadenectomy. No patient in the study had a clinically positive level V lymph node. Neck dissection specimens were obtained for histologic analysis for node metastasis with respect to the individual neck levels. Results Thirty-four (49%), 52 (74%), and 48 (69%) patients had histologically positive lymph nodes in levels II, III, and IV, respectively. Occult metastases in level V were observed in 11 (16%) patients. Isolated positive level V lymph nodes were never found, while all patients with positive level V lymph nodes had simultaneous positive level IV lymph nodes. In addition, there was no instance of a pathologically positive lymph node in level V without a suspicious metastatic lymph node in level IV by preoperative ultrasonography. In multivariate analysis, simultaneous multilevel involvement (level II, III, and IV) of lymphatic metastases was associated with level V metastasis. Conclusion Level V lymphadenectomy may be omitted in the treatment of PTC patients if positive nodes are not found on histologic exam (frozen section analysis) or by ultrasonography in level IV.

The optimal resection extent for papillary thyroid microcarcinoma (PTMC) confined within a unilateral lobe remains controversial.We reviewed the medical records of 132 consecutive patients who underwent total thyroidectomy for the treatment of clinically unilateral PTMC between March 2005 and March 2009. The frequency, pattern, and predictive factors for occult contralateral carcinoma in these patients were analyzed with respect to the following variables: age, gender, tumor size, multifocality of primary tumor, presence of perithyroidal invasion, lymphovascular invasion or capsular invasion, presence of central lymph node metastasis, and the presence of coexistent benign nodules in the contralateral lobe based on preoperative evaluation and final pathology.A total of 22 patients (16.7%) had occult PTMC in the contralateral lobe. In multivariate analysis, multifocality of the primary tumor (P = 0.026, odds ratio = 7.714) and the presence of coexistent benign nodule in the contralateral lobe by preoperative evaluation (P = 0.036, odds ratio = 3.500) were independent predictive factors for occult contralateral PTMC presence. However, there were no significant differences between the presence of occult contralateral carcinomas and age, gender, tumor size, perithyroidal invasion, lymphovascular invasion, capsular invasion, central lymph node metastasis, and coexistent benign nodules by final pathology.Based on our findings, total thyroidectomy, including the contralateral lobe, should be considered for the treatment of unilateral PTMC if it presents as a multifocal tumor in the unilateral lobe and/or if nodules are found in the contralateral lobe during preoperative evaluation.

Summary To evaluate treatment outcomes and the role of primary definitive surgery for T 1–2 , clinically N 0 oropharyngeal squamous cell carcinoma (OPSCC) patients, we performed a retrospective analysis of 46 consecutive cases treated primarily by surgery and/or postoperative radiotherapy at Yonsei University between May 1992 and December 2006. Twelve patients were T 1 and 34 were T 2 . The most common location was the tonsil (54%), followed by the soft palate (19%), the base of the tongue (BOT) (15%) and the posterior wall (12%). Occult lymph node metastasis was noted in 12 cases (26%). Seventeen patients (37%) received adjuvant radiotherapy. The 5-year disease-specific survival rate (DSSR) was 83%: 100% for clinical stage I (T 1 N 0 ) and 74% for clinical stage II (T 2 N 0 ). The 5-year DSSR of patients with surgery alone was 86%. Thirteen of 14 patients (93%) treated with conservative surgery alone without mandible-splitting or adjuvant radiotherapy attained disease-free status. In addition, 25 of 40 patients (63%) with disease-free status were treated with surgery alone. Almost 30% of all patients may be candidates for adjuvant chemotherapy through histopathologic analysis according to the National Comprehensive Cancer Network (2007) guidelines. The results of the present study demonstrate excellent oncologic outcomes with primary surgery for the treatment of early-stage OPSCC and suggest that surgery offers the best opportunity to identify patients in whom adjuvant radio- or chemotherapy may be most appropriately applied.

The extent of neck dissection (ND) appropriate for necks yielding clinical evidence of metastases of papillary thyroid carcinoma (PTC) is controversial. The need for level IIb lymph node (LN) dissection is particularly uncertain in view of its association with postoperative shoulder dysfunction. In the present study, we examined the frequency, pattern, and predictive factors of level IIb LN metastases in PTC patients with clinically positive lateral neck nodes.We reviewed the medical records of 76 PTC patients who underwent therapeutic lateral ND for the treatment of clinically positive lateral neck nodes between March 2005 and July 2008. ND specimens were separately obtained for analyzing LN involvement with respect to neck level.Metastatic disease at levels II, III, IV, and V, was seen in 40 (52.6%), 55 (72.4%), 52 (68.4%), and 12 (15.8%) of the patients, respectively. The metastasis rate in level IIb was 11.8% (9 of 76). By univariate analysis, the rate of level IIb LN metastasis was significantly higher in patients with positive level IIa LNs and positive LNs in all lateral neck levels (levels IIa + III + IV) (P.05). Multivariate analysis showed that positive LN involvement in all lateral neck levels (IIa + III + IV) was an independent predictive factor of level IIb LN metastasis (P = .044, odds ratio = 9.692).Level IIb LN dissection may be omitted in the treatment of positive neck nodes in PTC patients if multilevel involvement including level IIa involvement is absent.

Our study suggests that routine level I dissection may not be necessary in the surgical management of clinically N + hypopharyngeal squamous cell carcinoma (SCC) in patients who do not have a positive lymph node in neck level I.To determine whether level I lymph node dissection can be saved in patients with clinically N + hypopharyngeal SCC.Retrospective analysis of 64 consecutive clinically N + patients with untreated hypopharyngeal SCC between 1994 and 2006. Forty-seven patients underwent level I lymph node dissection and the remaining 17 did not. Forty-five of the 64 patients were followed for a minimum of 2 years, if alive, or until death. Of these 45 patients, 35 underwent ipsilateral level I dissection of the neck.The incidence of occult metastases to level I was 6% (3 of 47). Six (17%) of 35 patients with level I dissection and 1 (10%) of 10 patients without level I dissection experienced regional recurrence (p0.05). The 2-year disease-specific survival in 47 patients undergoing level I neck dissection was 44% compared with 37% in 17 patients who did not undergo level I neck dissection (p0.05).

Fractures of the clavicle following radical neck dissection (RND) and/or radiation therapy have been previously noted in the literature. Interestingly, we experienced three cases of clavicular fracture, which were considered to have resulted from pectoralis major myocutaneous flap (PMMCF). All of these three cases had received the combined treatment of RND, PMMCF and postoperative radiotherapy on the side of fracture. In all three cases, ipsilateral lower neck received 4,500 cGy and island type of PMMCF was used for reconstruction of surgical defect in head and neck area. All fractures noted between 1 and 3 years postoperatively occurred on the medial portion of the clavicle. Devascularization after stripping of periosteum and altered mechanics of the clavicle following resection of clavicular head of pectoralis major muscle may contribute to develop this rare complication in addition to the effect of radiotherapy and RND. We present three cases of the clavicle fracture following the island type PMMCF with a review of literature.

Post-thyroidectomy hypocalcemia is among the most common complications of total thyroidectomy. The purpose of this study was to evaluate early predictive factors and long-term changes in intact parathyroid hormone (iPTH) levels in patients with transient and permanent hypocalcemia after total thyroidectomy.A total of 349 consecutive patients who underwent total thyroidectomy with or without neck dissection between 2009 and 2011 were reviewed. PTH, total calcium (Ca), and ionized Ca (iCa) levels were evaluated at 1 hour, and 1, 3, 5, and 7 days, and 1, 3, 6, and 12 months postoperatively. Biochemical profiles at 1 hour after total thyroidectomy in patients with transient and permanent hypocalcemia were compared. Patients with postoperative hypocalcemia were followed for 12 months.Lesser preoperative serum levels of Ca and more extensive surgery were significantly associated with postoperative hypocalcemia (P.05). The absolute level and relative decline (%) in iPTH at 1 hour were the most reliable predictors of postoperative hypocalcemia according to the receiver operating characteristics curve, with a threshold of 10.42 pg/mL and 70%. Sensitivity and specificity of the predictors were 83.4% (95% CI, 76.4-89.1), 100% (95% CI, 84.6-100.0), 84.1 (95% CI, 77.2-89.7), and 95.5% (95% CI, 77.2-99.9), respectively. Parathyroid function recovered in the first month after total thyroidectomy in 78 of 99 patients (79%) with transient hypocalcemia. However, 46 of 61 patients (74%) with a subnormal iPTH level at 3 months after surgery had permanent hypocalcemia.Mean postoperative PTH level and the mean relative decline in PTH measured 1 hour postoperatively were the most reliable predictors of postoperative or permanent hypocalcemia.

Objectives: The objectives of this retrospective chart review were to investigate the rate of metastasis to the perifacial lymph node, which was defined as the nodal pads that lie anterior or posterior to the anterior facial vein on top of the facial artery in the submandibular triangle, and to identify its risk factors in patients with oral and oropharyngeal squamous cell carcinoma (OOSCC) with clinically node-positive neck. Methods: Beginning in July 1999, we routinely removed the perifacial lymph node pads of the submandibular triangle (level Ib) from the main therapeutic comprehensive neck dissection (level I–V) specimen for evaluation of metastatic rate to this nodal group in patients with OOSCC with clinically node-positive neck. This study is a retrospective analysis of patients undergoing perifacial node sampling from July 1999 to March 2006. A total of 66 patients (17 patients with oral cavity cancer and 49 with oropharyngeal cancer) underwent perifacial lymph node dissections. Of these, three (two with oral cavity tumors and one with an oropharynx tumor) had clinically positive node in level I. Results: The incidence rate of metastasis to the perifacial lymph node was 35% in oral cavity carcinoma (six of 17) and 8% in oropharynx carcinoma (four of 49). In addition, in patients without clinically positive level I node, the occult metastasis rate of the perifacial node was 27% in oral cavity carcinoma (four of 15) and 6% in oropharynx carcinoma (three of 48). Clinical or pathologic nodal staging above the N2b advanced lesion had a statistically significant association with perifacial lymph node metastasis (P < .05). Conclusion: Our data suggest that these nodal pads should be removed thoroughly for the treatment of node-positive neck in patients with oral cavity carcinoma. In contrast, however, complete removal may be unnecessary in comprehensive neck dissection of patients with oropharyngeal carcinoma with clinically node-positive neck, especially below nodal stage N2a.

The aim of this study was to evaluate the incidence and predictive factors for recurrence of oral squamous cell carcinoma (SCC) and outcome according to salvage treatment modality. A retrospective analysis of 127 oral cavity cancer patients who underwent surgery with or without postoperative radiotherapy as initial treatment was performed. Thirty-six patients (28%) were observed with recurrences and/or metastases mostly at the primary site and neck. Seventy-eight percent of recurrences occurred within one year, and 92% within two years after the initial treatment. The rate of recurrence and/or metastases was significantly higher in patients with an advanced pathologic stage, pathologic lymph node and positive resection margin compared to those with an early pathologic stage, negative lymph node and negative resection margin (p0.05). Especially, regarding the relationship between the rate of locoregional recurrence and local or regional factors, resection margin status was a particularly important, and potentially preventable, independent predictor for locoregional control. Patients who underwent salvage surgery with or without postoperative radiotherapy had significantly improved salvage and total survival times compared with patients who received chemotherapy and/or radiation therapy for their recurrence.

Objectives: Postoperative shoulder dysfunction has been significantly associated with any dissection of level V secondary to traction or with ischemic injury to the spinal accessory nerve. The aim of this study was to determine whether the dissection of level V lymph node pads is absolutely necessary in therapeutic neck dissection as a treatment for oral and oropharyngeal squamous cell carcinoma (OOSCC) patients with clinically N+ neck. Study Design: Retrospective chart review. Methods: We performed a retrospective analysis of 93 OOSCC patients who underwent surgical treatment of the primary lesion along with a simultaneous comprehensive neck dissection from January 1992 to December 2003. Of these, only one patient had a clinically positive neck node at level V. During the neck dissection, the contents of the level V lymph nodes were dissected, labeled, and processed separately from the remainder of the major neck dissection specimen. We studied the incidence of pathologic metastasis to level V lymph nodes. In addition, we also evaluated several potential risk factors for metastatic disease in the level V lymph nodes such as sex, age, T stage, N stage, histologic grade, and presence of other positive lymph nodes. Results: A total of 96 comprehensive neck dissections were performed in this series. The prevalence of metastases in the level V lymph nodes was 5% (5 of 93) in ipsilateral and 0% (0 of 3) in contralateral necks. One case with clinically positive node at level V had a pathologic positive node in level II, III, IV, and V. Occult metastasis rate of ipsilateral level V was 4% (4 of 92). There was a statistically significant association between level V metastases and a positive N stage above N2b (P = .01). The presence of metastasis in other multiple neck levels, particularly the combined neck levels II, III, and IV, also have a statistically significant association with level V metastasis (P = .023). Conclusion: Level V lymph node pads may be preserved in modified neck dissections on OOSCC patients with clinically N+ neck below the nodal stage N2a.

Background. The purpose of this study was to evaluate the incidence and predictive factors of contralateral occult lymph node metastasis in squamous cell carcinomas of the oral cavity to form a rational basis for elective contralateral neck management. Methods. We performed a retrospective analysis of 66 patients with cancer of the N0-2 oral cavity undergoing elective neck dissection for contralateral clinically negative necks from 1991 to 2003. Results. Clinically negative but pathologically positive con- tralateral lymph nodes occurred in 11% (7 of 66). Of the 11 cases with a clinically positive ipsilateral node neck, contralat- eral occult lymph node metastases developed in 36% (4 of 11), in contrast with 5% (3 of 55) in the cases with clinically N0 ipsilat- eral necks (p < .05). Based on the clinical staging of the tumor, 8% (3 of 37) of the cases showed lymph node metastases in T2 tumors, 25% (2 of 8) in T3, and 18% (2 of 11) in T4. None of the T1 tumors (10 cases) had pathologically positive lymph nodes. The rate of contralateral occult neck metastasis was significantly higher in advanced-stage cases and those crossing the midline, compared with early-stage or unilateral lesions (p < .05). Patients with no evidence of contralateral nodal cancer had sig- nificantly improved disease-specific survival over patients with any pathologically positive nodes (5-year disease-specific sur- vival rate was 79% vs. 43%, p < .05). Conclusions. The risk of contralateral occult neck involve- ment in the oral cavity squamous cell carcinomas above the T3 classification or those crossing the midline with unilateral metas- tases was high, and patients who presented with a contralateral metastatic neck had a worse prognosis than those whose dis- ease was staged as N0. Therefore, we advocate an elective con- tralateral neck treatment with surgery or radiotherapy in patients with oral cavity squamous cell carcinoma with ipsilateral node metastases or tumors, or both, whose disease is greater than T3 or crossing the midline. V C 2006 Wiley Periodicals, Inc. Head Neck 28: 896-901, 2006

Summary A prospective study of 73 previous untreated consecutive patients with clinically N0 laryngeal squamous cell carcinoma (SCC) from January 1997 to October 2002 was undertaken to determine whether level IV lymph nodes can be saved in elective lateral neck dissection (LND) performed as a treatment for the N0 neck. The incidence of pathological metastases to level IV lymph nodes was evaluated, as were the incidence of regional recurrence after elective LND, and postoperative complications such as chylous leakage and phrenic nerve paralysis. A total of 142 LNDs were enrolled in this prospective study. The mean number of harvested lymph nodes by level was as follows; 13.1 in level II, 7.1 in level III, and 9.2 in level IV. Pathologic examination revealed nodal involvement in 25 neck specimens (17.6%, 25 of 142). Five necks had lymph nodes which were positive for microscopic metastasis in level IV (3.5%, 5 of 142). These necks were all ipsilateral (6.8%, 5 of 73) and none of the 69 contralateral neck specimens had level IV lymph node metastasis (0%, 0 of 69). With regard to T stage, 3.3% (1 of 30) of ipsilateral necks of T2 tumors exhibited occult metastasis in level IV lymph nodes, 5.9% (2 of 34) for T3 tumors, and 33.3% (2 of 6) for T4 tumors. There were no cases of T1 (n = 3). Separate skip metastasis in level IV lymph nodes was observed in two necks (1.4%, 2 of 142). Four cases of regional recurrence (5.5%, 4 of 73) were observed. Postoperative chylous leakage and phrenic nerve paralysis occurred in four cases (5.5%, 4 of 73) and two cases (2.7%, 2 of 73), respectively. The results of the present study demonstrate the rare incidence of level IV occult lymph node metastasis, as well as infrequent nodal recurrence after elective LND in the treatment of clinically N0 laryngeal SCC. Therefore, dissection of level IV lymph node pads, especially in the ipsilateral neck of early T staged tumors or the contralateral neck, may be unnecessary for the treatment of laryngeal SCC patients with a clinically N0 neck.

A conservative parotidectomy is defined as any procedure that is less than a classic superficial parotidectomy, and where less than a full facial nerve is dissected. The aim of this study was to evaluate the oncologic effects of a conservative parotidectomy in a series of patients with malignant tumors of the parotid gland. The medical records of 43 patients treated at Severance Hospital from 1992 to 2002 who had been diagnosed with parotid cancers confined to the superficial lobe, and had also undergone conservative parotidectomies were reviewed. There were 16 males and 27 females, ranging in age from 8 to 84 years. Sixteen tumors (37%) were high-grade and 27 tumors (63%) were low-grade cancers. Twenty-four patients underwent neck dissection simultaneously with the primary lesion. Surgical treatment was followed by radiotherapy in 10 patients. The follow-up period ranged from 8 to 130 months, with a mean duration of time at 57.7 months. The overall survival rate and the disease-free rate at five years were 88% and 79%, respectively. Univariate analyses showed histologic tumor grade (p = 0.003) and pathologic neck node metastasis (p0.001) to be significant variables. Based on multivariate analysis, only the presence of pathologically positive lymph nodes proved to be significant (p = 0.001). Occult metastases rates was 25% (3 of 12 cases) for high-grade tumors and none of the low-grade tumors had microscopic metastases. Recurrences developed in eight cases (19%). Four cases (9%) had a local or locoregional failure. Of these cases, two cases were high-grade tumors (13%, 2 of 16) and the other two cases were low-grade tumors (7%, 2 of 27). The six cases (14%) of which four cases were high-grade (25%) and two cases were low-grade (7%) had positive surgical margin but showed no evidence of local recurrence after additional postoperative radiotherapy. The incidence of postoperative facial nerve paralysis (HB1) was 12% (5 out of 43) for a temporary deficit, but there was no permanent paralysis. Conservative parotidectomy with appropriate postoperative radiotherapy may be an acceptable procedure without potential morbidity, such as postoperative facial palsy, in the treatment of low-grade parotid cancers confined to the superficial lobe if the facial nerve is sufficiently distant from the tumor.

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.

Identification of a novel biomarker of subclinical lymph node metastasis (SLNM) in papillary thyroid microcarcinoma (PTMC) could provide important clues regarding SLNM in PTMC. We evaluated the significance of HGF and c-Met expression in surgically removed tumor tissue from PTMC patients as a predictive marker of SLNM.We analyzed the immunohistochemical relationship between HGF and c-Met expression and SLNM in 113 surgically treated PTMC patients with clinically negative nodes presurgery. In addition, we explored whether HGF/c-Met pathway activation enhanced the in vitro migration and invasion of PTC cells.Positive immunohistochemical HGF and c-Met staining was found in 107 (95 %) and 103 (91 %) cases, respectively. The HGF staining distribution was as follows: no staining in 6 cases, weak staining in 43, moderate staining in 55, and strong staining in 9. Of the nine cases with strong HGF staining, eight (89 %) had SLNM. The c-Met staining distribution was as follows: no staining in 10 cases, weak staining in 39, moderate staining in 59, and strong staining in 5. Of the five cases with strong c-Met staining, three (60 %) had SLNM. The presence of SLNM was strongly correlated with HGF and c-Met expression in PTMC in a univariate analysis (P0.05). HGF overexpression was also associated with SLNM in a multivariate analysis (P0.05). Stimulation with exogenous HGF and constitutive activation of c-Met enhanced the migration and invasion of PTC cells in vitro by enhancing VEGF-A expression.HGF/c-Met pathway activation is associated with SLNM of the central neck in PTMC.

Most solid cancers including head and neck squamous carcinoma (HNSC) are believed to be initiated from and maintained by cancer stem cells (CSCs) that are responsible for treatment resistance, resulting in tumour relapse. Epigallocatechin-3-gallate (EGCG), the most abundant polyphenol in green tea, can potently inhibit cancer growth and induce apoptosis in various cancers, including HNSC. However, its effect on HNSC CSCs is not well elucidated. In this study, we examined the anti-tumour effect of EGCG on HNSC CSCs. We demonstrated that EGCG inhibits the self-renewal capacity of HNSC CSCs by suppressing their sphere forming capacity, and attenuates the expression of stem cell markers, such as Oct4, Sox2, Nanog and CD44. EGCG treatment augmented cisplatin-mediated chemosensitivity by suppressing ABCC2 and ABCG2 transporter genes, which are putative molecules of treatment resistance of CSC. In addition, the combination treatment of EGCG and cisplatin inhibited tumour formation and induced apoptosis in a xenograft model. As one of mechanisms of suppression of HNSC CSC traits, EGCG decreased the transcriptional level of Notch, resulting in the inhibition of Notch signalling. Collectively, our data suggest that EGCG in combination with cisplatin can be used for the management of HNSC CSCs.

The purpose of this study was to examine the frequency, pattern, and predictive factors associated with occult level II lymph node (LN) metastases in papillary thyroid carcinoma (PTC) patients with clinically metastatic lymph nodes in the lateral neck (level III, IV, and/or V) by preoperative ultrasonography.We retrospectively reviewed the medical records of 52 PTC patients with clinically positive neck lymph nodes in level III, IV, and/or V based on preoperative ultrasonography, who underwent therapeutic lateral neck dissection (ND) (level II-V) between March 2004 and October 2009. All patients had no suspicion of clinically positive neck nodes in level II. Histopathological analysis of neck specimens according to each node level of the neck was performed, with special attention given to level II.Forty-two (81%), 41 (79%), and 6 (12%) patients had histologically positive lymph nodes in level III, IV, and V, respectively. Occult metastases in level II were observed in ten (19%) patients. Patients without suspicious positive LNs in both neck level III and IV by preoperative ultrasonography, and patients without pathologic LN metastases in level III, had no occult LN metastases occurrence to level II. Based on multivariate analysis, presence of more than four metastatic LNs was an independent predictive factor for occult level II metastases [P = 0.022, odds ratio (OR) = 7.738].Prophylactic level II LN dissection may be omitted in PTC patients with clinically positive neck nodes if suspicious positive lymph nodes in level III are absent during preoperative ultrasonography.

Summary Incidence of isolated distant metastasis (IDM) was relatively low in patients who achieved locoregional control after primary definitive surgery. However, the prognosis of patients with IDM was dismal. The aim of this study was to evaluate the clinical outcome of patients with IDM and identify independent predictive factors of IDM after primary definitive surgery for head and neck squamous cell carcinoma (HNSCC). A retrospective data review was conducted for 795 patients who underwent primary definitive surgery without any systemic treatment for squamous cell carcinoma (SCC) of the oral cavity, oropharynx, larynx, and hypopharynx. Distant metastasis-free survival was calculated and independent predictive factors for IDM were determined by Cox proportional-hazards model. For the entire study cohort, IDM developed in 75 patients (9.4%). Among 631 patients who achieved locoregional control, IDM occurred in 44 patients (7%). The median time to IDM after primary surgery was 13 months, ranging from 2 to 70 months. The overall salvage rate was 9% (4 of 44) after salvage treatment for IDM. In the Cox proportional-hazards model, clinical N status, and histological grade were independent predictive factors of IDM. Patients who had clinically palpable neck disease and a histologically poor grade were more likely to develop IDM after primary definitive surgery. Patients with these factors should be considered candidates for proper adjuvant systemic treatment and evaluated more thoroughly for early detection of IDM during follow-up.

The aim of this study was to evaluate the outcome and predictive factors for salvage treatment of isolated neck recurrence after primary curative surgery for head and neck squamous cell carcinoma (HNSCC).Case series with chart review.Head and neck cancer clinic in a tertiary care university hospital.A retrospective study was conducted with 236 patients who developed a recurrence after primary curative surgery with or without radiotherapy for HNSCC.Isolated neck recurrence developed in 61 (26%) patients. Salvage treatment was offered to 49 patients, and the overall salvage rate was 33 percent (20 of 61). The salvage rate for the surgical salvage group was 46 percent (16 of 35) and 28 percent (4 of 14) for the nonsurgical salvage group (chemoradiation) (P = 0.14). The three-year overall survival rate was 36 percent for patients with surgical salvage and 12 percent for patients with nonsurgical salvage (P = 0.101). There were no survivors of the supportive care group (0 of 12). Univariate analysis of individuals with isolated neck recurrence showed that patients who had previous treatment with surgery alone, a disease-free time longer than one year, previous pathologic N- status, recurrence in the undissected neck, or recurrent N1 had significantly improved salvage time (P0.05). However, in multivariate analysis, the factors previous treatment with surgery alone and recurrent N1 submitted to the salvage treatment were independent predictors of a successful salvage of isolated neck recurrence.Our results suggest that the ideal candidates for salvage neck treatment include those patients with recurrent N1 disease and those whose previous treatment was surgery only.

To investigate the incidence and the risk factors for occult ipsilateral or contralateral central neck lymph node (LN)metastasis in patients with unilateral papillary thyroid carcinoma (PTC) and a clinically negative neck.Elective central lymph node dissection (CLND) in patients with PTC remains controversial. There have been few prospective studies assessing accurate histopathologic information and predictive factors for the presence of metastasis to the ipsilateral or contralateral central compartment of the neck in patients with PTC and clinically negative neck nodes.We reviewed a prospective protocol of 111 unilateral PTC patients with clinically node-negative necks who have received total thyroidectomy and elective bilateral CLND from 2005 to 2007. The relationships between LN metastasis to the ipsilateral or contralateral central neck compartment and clinico-pathologic factors such as age, sex, size of primary tumor, perithyroidal invasion, lymphovascular invasion, and capsular invasion were analyzed.Occult central neck LN metastasis was present in 54.1% (60/111). Of these patients, bilateral central LN metastases were present in 50% (30/60), unilateral ipsilateral central LN metastasis in 43.3% (26/60), and unilateral contralateral central LN metastasis in 6.7% (4/60). In the univariate analysis, the rate of ipsilateral central LN metastasis was significantly higher in male patients, high risk MACIS score, carcinoma with a maximal diameter of greater than 1 cm, and carcinoma with lymphovascular invasion (P0.05). The rate of contralateral central LN metastasis was significantly higher in cases of carcinoma with a maximal diameter of greater than 1 cm, lymphovascular invasion or histologically proven metastasis to the ipsilateral central LN (P0.05). Multivariate analysis showed that the tumor size was an independent risk factor for the presence of ipsilateral central LN metastasis, and the presence of ipsilateral central LN metastasis was the only independent predictor for the presence of contralateral central LN metastasis.Unilateral PTC with a maximal diameter of greater than 1 cm is associated with a high rate of ipsilateral central neck LN metastasis. Moreover, ipsilateral central LN metastasis is a potential independent predictor of synchronous contralateral central LN metastasis. These findings suggest that contralateral as well as ipsilateral elective CLND, performed during the initial thyroid operation, may be effective in the management of patients with unilateral PTC having a maximal diameter of greater than 1 cm and ipsilateral central LN metastasis.

Surgery alone may be a reliable and feasible treatment of choice in selected patients with squamous cell carcinoma (SCC) of the oral cavity, given the proper indications.To evaluate the results of treatment of oral cavity SCC patients with surgery alone in a single institution.Between 1992 and 2004, 76 patients with previously untreated SCC of the oral cavity who had surgery alone without any other adjuvant treatment modalities were included in our study.The 5-year overall rate, disease-specific survival rates, and locoregional control rate of all 76 patients were 69%, 83%, and 73%, respectively. A total of 16 patients (21%) presented with recurrences (8 with regional recurrences, 5 with local, 2 with locoregional, and 1 with distant metastasis). Four (6%) of the patients with primary T1 or T2 stage and one (50%) of those with T4 stage had recurrence at the primary site. The regional recurrence rate of patients withor = N1 andor = N2b was 10% (6 of 59) and 67% (2 of 3), respectively. Three of four patients who had recurrence at the primary site and attempted salvage treatment have been cured. However, only one of five patients with nodal recurrence and salvage treatment has recovered.

Objectives/Hypothesis: The presence of distant metastasis after the initial treatment of oral and oropharyngeal squamous cell carcinoma (OOSCC) is often associated with a poor prognosis. The purpose of our study was to evaluate the frequency of isolated distant metastasis (IDM) that occurred without any local or regional failure, and to identify its predictive factors in patients who were surgically treated. Study Design: Retrospective chart review. Methods: We performed a retrospective analysis of 230 OOSCC patients who underwent surgical treatment of the primary lesion along with a simultaneous neck dissection between May 1992 and August 2004. We evaluated the frequency of IDMs without local or regional recurrences and the influence of different variables in their appearance. Results: The frequency of IDMs was 6%. Patients with oropharyngeal carcinoma had higher isolated distant failure compared with patients with oral cavity carcinoma (P < .05). In univariate analysis, the following conditions were significant predictors of IDM in patients with OOSCC: advanced local stage; clinical or pathologic positive neck node; the presence of more than two pathologic neck nodes; more than two bilateral pathologic nodal metastases; use of adjuvant radiotherapy; and advanced American Joint Committee on Cancer (AJCC) stage. However, in multivariate analysis, only the presence of pathologic positive lymph node, especially bilateral neck metastases, was an independent risk factor for the appearance of IDMs. Conclusions: The incidence of IDMs in patients with OOSCC is relatively low. These events were significantly associated with bilateral neck node metastases.

We conclude that increased expression level of the high mobility group I (HMGI(Y)) is closely associated with malignant transformation in head and neck squamous cell carcinomas (HNSCCs), and the measurement of HMGI(Y) levels in HNSCCs may be useful as a prognostic marker.To investigate whether HMGI overexpression is observed in HNSCCs, and its value as a prognostic marker in HNSCCs.HMGI(Y) expression was determined at the protein level by immunohistochemisty using a HMGI(Y)-specific antibody and RT-PCR in 10 surgically resected specimens of non-neoplastic tissue (normal palatal tissue) and 40 HNSCCs. We also evaluated the association of HMGI(Y) overexpression within clinicopathologic parameters, i.e. clinical stage, pathologic grade, status of cervical lymph node metastasis, recurrence rate.Expression of HMGI(Y) by immunohistochemical staining was observed in 35 of 40 (87.5%) HNSCC samples, whereas normal mucosa and/or the mucosa adjacent to the tumor tissue showed negative or weakly positive staining (p0.05). Semi-quantification of HMGI(Y) by RT-PCR was 2.98+/-2.24 in cancer and 0.47+/-0.25 in normal tissue (p0.001). High expression of HMGI(Y) was observed in recurrent cases, compared with non-recurrent cases (p0.05). However, no significant correlation was observed between the levels of HMGI(Y) expression and other clinical factors such as clinical stage, pathologic grade, and status of cervical lymph node metastasis.

Objectives: This study sought to investigate the patterns and distributions of lymph node metastases in oropharyngeal squamous cell carcinoma (SCC) and improve the rationale for elective treatment of N0 neck. Materials and Methods: One hundred four patients with oropharyngeal SCC who underwent neck dissection between 1992 and 2003 were analyzed retrospectively. All patients had curative surgery as their initial treatment for the primary tumor and neck. A total of 161 neck dissections on both sides of the neck were performed. Therapeutic dissections were done in 71 and 5 necks and elective neck dissection was done on 33 and 52 necks on the ipsilateral and contralateral sides, respectively. Surgical treatment was followed by postoperative radiotherapy for 78 patients. The follow-up period ranged from 1 to 96 months (mean, 30 months). Results: Of the 161 neck dissection specimens evaluated, 90 (56%) necks were found to have lymph node metastases found by pathologic examination. These consisted of 76 (73% of 104 necks) of the ipsilateral side and 14 (25% of 57 necks) of the contralateral side dissections. The occult metastatic rate was 24% (8 of 33) of ipsilateral neck samples and 21% (11 of 52) of contralateral neck samples. Of the 68 patients who had a therapeutic dissection on the ipsilateral side and had lymphatic metastasis, the incidence rate of level IV and level I metastasis was 37% (25 of 68) and 10% (7 of 68), respectively. Isolated metastasis to level IV occurred on the ipsilateral side in three patients. There were no cases of isolated ipsilateral level I pathologic involvement in an N-positive neck or occult metastasis to this group. The incidence rate of level IV metastasis in patients with ipsilateral nodal metastasis was significantly higher in base of tongue cancer (86% [6 of 7]) compared with tonsillar cancer (34% [20 of 59]) (P = .013). Patients with level IV metastasis had significantly worse 5-year disease-free survival rates than patients with metastasis to other neck levels (54% versus 71%; P = .04). Conclusion: These results suggest that elective N0 neck treatment in patients with oropharyngeal SCC, especially base of tongue cancer, should include neck levels II, III, and IV instead of levels I, II, and III.

Objective: The hypopharynx has a rich lymphatic network that places patients with tumors of the hypopharynx at high risk for early dissemination of the disease into the cervical lymphatics. Therefore, ipsilateral elective neck dissection of clinically N0 neck in lateralized lesions of hypopharyngeal squamous cell carcinomas (SCCs) is widely accepted as a standard treatment. However, the management of the contralateral N0 neck is still controversial. The aim of this study was to evaluate the incidence and predictive factors of contralateral occult lymph node metastasis in pyriform sinus SCC. Materials and Methods: We performed a retrospective analysis of 43 patients with N0 to 3 pyriform sinus SCC with contralateral clinically node-negative necks who had also received contralateral elective neck dissections from 1994 to 2003. Surgical treatment was followed by postoperative radiotherapy in 41 patients. The follow-up period ranged from 4 to 135 months (mean, 40 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: Contralateral occult lymph node metastases occurred in 16% (seven of 43) of the subjects. Twenty-six percent of the 27 subjects with clinically node-positive ipsilateral neck developed contralateral occult lymph node metastases, whereas 0% of the 16 subjects with N0 ipsilateral necks (P = .035) developed the disease. Moreover, in cases with primary site extension across the midline, the rate of contralateral occult neck metastasis was significantly higher (P = .010). However, there were no statistically significant differences in age, sex, early versus advanced T stage, number of ipsilateral positive nodes, lymph nodes with extracapsular spread, primary subsite of medial versus lateral pyriform sinus, pyriform sinus apex involvement, and growth type. 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, 66% vs. 33%, P < .05). Conclusion: The patients with pyriform sinus SCC with clinically ipsilateral N+ neck and/or extension across the midline are at greater risk for contralateral occult neck metastases. Furthermore, patients who present with a contralateral metastatic neck have a worse prognosis than those staged as N0. Therefore, we advocate bilateral neck treatment in patients with pyriform sinus SCC with clinically ipsilateral node metastases and/or extension across the midline.

Objectives/Hypothesis: Prophylactic treatment of contralateral N0 neck in early squamous cell carcinoma (SCC) of the oral tongue is a controversial issue. The aim of this study was to analyze the rates of occult metastases and their prognostic effects in stage I and stage II SCC of the oral tongue, and to compare the results of elective neck dissection to observation of the contralateral N0 neck in the treatment of these patients. Study Design: Retrospective review. Methods: We reviewed the medical records of 54 patients who were treated at Severance Hospital from 1992 to 2003 and had been diagnosed with stage I or stage II SCC of the oral tongue and had not received prior treatment. All patients underwent an ipsilateral elective neck dissection simultaneously with the primary lesion. The management of the contralateral N0 necks involved “watchful waiting” in 29 patients and elective neck dissection in 25 patients. Surgical treatment was followed by radiotherapy in 20 patients. Of these, seven patients belonged to the “observation” group who did not receive contralateral elective neck dissection. The follow-up period ranged from 3 to 110 months, with a mean of 56.3 months. Data were analyzed using the Kaplan-Meier method, the log-rank test, and the ξ2 test. Results: Fifteen patients (28%, 15 of 54) had occult metastases. Of these, 14 patients (26%, 14 of 54) had ipsilateral pathologic metastases. The remaining case (4%, 1 of 25) had the only contralateral level II occult neck metastasis without ipsilateral metastasis. Disease recurred in 17 of 54 patients (31%). Of these, eight cases (47%, 8 of 17) had regional recurrences. All regional recurrences developed in the ipsilateral neck; there were no cases of contralateral neck recurrence. The 5-year actuarial disease-free survival rates were 82% for the “observation” group and 68% for the elective neck dissection group. This difference was not statistically significant (P = .182). The 5-year actuarial disease-free survival rates were 83% for the “observation” group when those patients who underwent radiotherapy were excluded (n = 22) and 68% for the elective supraomohyoid neck dissection group (n = 25), which showed no statistically significant difference (P = .127). Conclusions: This study showed that ipsilateral elective neck management is indicated for stage I and II SCC of the oral tongue. On the other hand, our series suggests that contralateral occult lymph node metastasis was unlikely in early-stage oral tongue SCC, and that there was no survival benefit for patients who underwent elective neck dissection in place of observation. Thus, it may not harmful to observe the contralateral N0 neck in the treatment of early oral tongue cancer.

Objectives: Selective neck dissection, despite preservation of the spinal accessory nerve, can lead to some degree of postoperative shoulder dysfunction as a result of removal of level IIb lymph nodes. The aim of this study was to determine whether level IIb lymph nodes can be preserved in elective or therapeutic neck dissection as a treatment for patients with laryngeal squamous cell carcinoma (SCC). Study Design: This was a prospective analysis of a case series. Methods: A prospective analysis of 65 patients with laryngeal SCC who underwent surgical treatment of the primary lesion with simultaneous neck dissection from January 1999 to December 2002 was performed. During the neck dissection, the contents of the level IIb lymph nodes were dissected, labeled, and processed separately from the remainder of level II nodes and the main neck dissection specimen. The incidence of pathologic metastasis to level IIb lymph nodes and the regional recurrence within this area were evaluated. In addition, several potential risk factors for metastatic disease in the level IIb lymph nodes such as sex, age, cT stage, cN stage, and the presence of other positive lymph nodes were also evaluated. Results: A total of 125 neck dissections were performed in this series. Of these dissections, 102 (82%) were elective and 23 (18%) were therapeutic. The prevalence of metastases in the level IIb lymph nodes was 1% (one of 46) and 0% (zero of 56) in clinically node-negative (N0) ipsilateral and contralateral necks, respectively, and 37% (seven of 19) and 0% (zero of four) in clinically node-positive ipsilateral and contralateral necks, respectively. There was a statistically significant association between level IIb metastases and clinically positive N stage (P < .001). The presence of other positive lymph nodes was also shown to have a statistically significant association with metastasis in the level IIb lymph nodes (P = .001). Only two of 46 patients (4%) with clinically N0 necks developed a regional recurrence. However, three of eight cases (38%) with positive pathologic level IIb lymph nodes developed regional recurrence. Conclusion: Level IIb lymph node pads may be preserved in elective neck dissection in patients with laryngeal SCC. However, this area should be removed thoroughly during therapeutic neck dissection in the treatment of clinically node-positive necks.

Hereditary angioneurotic edema (HAE) is an autosomal dominant disease resulting from a deficiency of functional C1-esterase inhibitor. If not recognized promptly and treated properly the disease can result in a fatal outcome as it causes laryngeal edema, which can lead to a life-threatening acute upper airway obstruction. We present the case of a 37-year-old female with HAE of the larynx, who was diagnosed early and treated properly, together with a review of the literature.

This study investigated the oncologic safety of preserving level IIb lymph nodes in ipsilateral and/or contralateral elective neck dissection (END) in patients with oropharyngeal squamous cell carcinoma (SCC). Fifty-one oropharyngeal SCC patients who underwent surgery as an initial treatment were reviewed. Twenty-one patients had clinically node negative necks (cN0) while 30 patients had ipsilateral clinically node positive necks (cN+). Of the cN0 patients, bilateral or ipsilateral END was performed in 15 and six patients, respectively. For the cN+ cases, ipsilateral therapeutic neck dissection with contralateral END was performed in 24 of 30 patients. In the cN0 patients, nodal metastasis to level IIb lymph nodes was not observed in any ipsilateral (21) or contralateral necks (15). Of the 24 cN+ patients who underwent contralateral END, two cases (8.3%) showed contralateral occult level IIb lymph node metastasis. Our data suggest that in cN0 oropharyngeal cancer patients, level IIb lymph nodes may be preserved in ipsilateral and contralateral neck dissection. However, caution is advised when preserving contralateral level IIb nodes in ipsilateral cN+ cases.

We have shown previously that hypoxia activates the cyclin D1 promoter via the Jak2/STAT5b pathway in breast cancer cells. Most solid tumors contain hypoxic components and overexpression of cyclin D1. The purpose of the present study was to investigate the molecular mechanism by which momilactone B exerts its inhibitory effects on breast cancer cells. Momilactone B, extracted from Korean rice hulls, suppressed hypoxia-induced increases in phospho-STAT5, STAT5b, cyclin D1, and cdk4 protein levels in human breast cancer cells. STAT5b expression was inhibited by siRNA experiments leading to decreased cyclin D1. The effects of momilactone B on cell growth and apoptosis-related gene expression were investigated in breast cancer cells under hypoxic conditions (2% O2). Bax and p21 expression was found to be up-regulated, whereas ppRb and bcl-2 were down-regulated in momilactone B-treated cells under hypoxic conditions. However, the p53 protein level did not change. Flow cytometry with Annexin-FITC staining showed that the number of apoptotic cells increased in hypoxic cells treated with momilactone B compared with untreated hypoxic cells. Furthermore, caspase activity increased upon treatment with momilactone B under hypoxic conditions. These results indicate that momilactone B inhibits the growth of breast cancer cells, regulates the expression of apoptosis-related genes, and induces apoptosis through STAT5b and a caspase-3 dependent pathway. We suggest that momilactone B accelerates hypoxia-induced apoptosis of human breast cancer cells through STAT5b, and may represent an effective chemopreventive or therapeutic agent against breast cancer.

Objectives To evaluate the prevalence of level IIb lymph node (LN) metastasis and to identify potential clinical risk factors when level IIb metastatic diseases are present in patients with clinically node-negative (N0) and node-positive (N+) necks with hypopharyngeal squamous cell carcinoma (HPSCC). This will provide a basis for determining whether this region can be excluded in elective or therapeutic neck dissection in patients with HPSCC. Design Prospective analysis of a case series. Setting University hospital. Patients Fifty patients with HPSCC who underwent surgical treatment for a primary lesion and simultaneous neck dissection from January 1998 to February 2004. Main Outcome Measures The incidences and clinical risk factors for level IIb LN metastasis and regional recurrence according to the presence or absence of pathologic LN involvement in level IIb. Results A total of 93 neck dissections were analyzed in this study. Of these dissections, 59 (63%) were elective and 34 (37%) were therapeutic. Three percent (2 of 59) of all N0 necks and 32% (11 of 34) of all N+ necks had level IIb LN metastases. Level IIb nodal metastases were significantly more prevalent in N+ necks ( P = .007) than in N0 necks and in the presence of other positive LNs ( P = .01) than in the absence of other positive LNs. Of the 35 patients with pathologic LNs, the regional recurrence rate was significantly higher in cases with positive level IIb LNs (33% [4 of 12]) than without (4% [1 of 23]; P = .04). Conclusions Level IIb LN pads may be preserved during elective neck dissection in the treatment of patients with clinically N0 necks with HPSCC. This area should be removed during therapeutic neck dissection in the treatment of clinically N+ necks.

Chondrosarcoma of the head and neck region is a rare disease, representing approximately 0.1% of all head and neck neoplasms. The 5-year survival rate of chondrosarcoma is 70-80%, showing relatively good prognosis; however, it is known to progress slowly and eventually cause multiple metastases. In this study, we reviewed chondrosarcoma cases experienced at Yonsei University Medical College during the last 15 years to investigate its clinical characteristics and treatment outcome. The medical records of 8 patients who were diagnosed with chondrosarcoma of the head and neck region and underwent surgical treatment between December 1990 and December 2002 were retrospectively reviewed. The primary sites were sinus, mastoid, jugular foramen and thyroid cartilage. In all patients, the initial treatment modality was surgery, and postoperative radiation therapy was performed in 4 cases. The pathological findings showed chondrosarcoma in 7 cases and mesenchymal chondrosarcoma in 1 case. The treatment outcome resulted in 3 cases of recurrence, of which 2 cases were treated successfully and the other case expired of disease, indicating a survival rate of 87.5%. In the case that resulted in death, complete excision could not be achieved. Therefore, we concluded that wide excision is a beneficial initial treatment of this rare disease.