Search

Objectives. Head and neck squamous cell carcinomas (HNSCs) are frequently diagnosed at the locoregional advanced stage (stage IVa), but controversy remains regarding whether stage IVa HSNCs should be treated with upfront surgery or definitive chemoradiation therapy (CRT). The purpose of this study was to compare overall survival (OS) and disease-free survival (DFS) in patients with stage IVa HNSC treated primarily by surgery with curative intent with/without (neo)adjuvant treatment (surgery group) versus those treated primarily with CRT (CRT group).Methods. We reviewed data of 1,033 patients with stage IVa HNSC treated with curative intent at 17 cancer centers between 2010 and 2016.Results. Among 1,033 patients, 765 (74.1%) received upfront surgery and 268 (25.9%) received CRT. The 5-year OS and DFS rates were 64.4% and 62.0% in the surgery group and 49.5% and 45.4% in the CRT group, respectively. In multivariate analyses, OS and DFS were better in the surgery group than in the CRT group (odds ratio [OR] for death, 0.762; 95% confidence interval [CI], 0.592–0.981; OR for recurrence, 0.628; 95% CI, 0.492–0.802). In subgroup analyses, the OS and DFS of patients with oropharyngeal cancer were better in the surgery group (OR for death, 0.548; 95% CI, 0.341–0.879; OR for recurrence, 0.598; 95% CI, 0.377–0.948). In the surgery group, patients with laryngeal cancer showed better OS (OR for death, 0.432; 95% CI, 0.211–0.882), while those with hypopharyngeal cancer DFS was improved (OR for recurrence, 0.506; 95% CI, 0.328–0.780).Conclusion. A survival benefit from surgery may be achieved even in patients with stage IVa HNSC, particularly those with oropharyngeal and laryngeal cancer. Surgery led to a reduction in the recurrence rate in patients with hypopharyngeal cancer.

BACKGROUND This study aimed to evaluate whether computed tomography (CT)-based volumetric body composition analysis has prognostic value in head and neck cancer (HNC) patients. METHODS This single-center retrospective study included 79 patients with HNC treated with definitive radiotherapy from March 2009 to December 2018. The patients were assessed for (a) weight-based variables and (b) pretreatment and posttreatment CT-based body composition variables. Overall survival (OS) and recurrence-free survival (RFS) analyses were conducted using Cox proportional hazards analyses. RESULTS Depletion of cervical skeletal muscle volume on presentation was associated with poor OS (hazard ratio [HR] = 3.1; 95% CI = 1.2-7.8; P = .016). Low fat proportions before and after treatment were associated with poor OS (HR = 2.5-3.5; 95% CI = 1.3-9.3; P = .013-.026). In multivariate Cox analysis, increased posttreatment fat attenuation demonstrated the greatest prognostic value for both OS (HR = 4.7; 95% CI = 2.2-10.3; P

Objective The incidence of SGS has been reported to be less than 8% after endotracheal intubation. Therefore there is an increasing trend in the number of patients with acute acquired SGS due to mechanical ventilation in the intensive care unit. However, there have been no reports describing the treatment of SGS in children in South Korea. The objective of this study was to evaluate the management and outcomes of children with SGS at a pediatric tertiary center in South Korea over an 8-year period. Methods All patients underwent microlaryngobronchoscopy (MLB) with bougination, incision using cold knife or laser and balloon dilatation. Data on age, sex, grade of SGS, number of management interventions, tracheostomy, comorbidities, mean follow-up period, complications, and outcome were reviewed from patient medical charts. Results Twenty patients (13 [65%] males, 7 [35%] females; mean [±SD] age at the diagnostic procedure 15.26 ± 22.54 months) underwent MLB between March 2009 and December 2017. According to the Myer-Cotton scale, twelve of the 20 (60%) patients had grade III SGS, 7 (35%) had grade II and 1 (5%) had grade 1; there were no patients with grade IV SGS. Nine (45%) patients were diagnosed with acute SGS, and 11 (55%) with chronic SGS. Patients with SGS underwent MLB with interventions (mean 2.41 ± 2.23 per patient). Tracheostomy was performed in 13 of 20 (65%) patients, 2 of 9 (22.2%) with acute SGS, and 11 of 11 (100%) with chronic SGS. Two of 13 (15.3%) patients underwent successful decannulation. One of 2 (50%) patients with acute SGS underwent successful decannulation. Seven of 9 (77.7%) patients with acute SGS underwent MLB only without tracheostomy. Conclusions In patients with acute acquired SGS, the outcome was good due to the lower rate of tracheostomy and higher decannulation rate. Therefore, it is recommended that MLB with balloon laryngoplasty be performed at the earliest in patients with acute acquired SGS.

Transoral endoscopic thyroidectomy vestibular approach is expected to be a safe alternative to open surgery for certain patients and has been used increasingly by several surgeons around the world for the past 2 years. The purpose of this paper is to review our 2-year experience and describe in detail our preoperative considerations, patient selection, operating room settings, anesthetic considerations, surgical technique, postoperative management, and outcomes. We reviewed the medical records of 65 consecutive patients who underwent transoral endoscopic thyroidectomy between July 2016 and May 2018 in our hospital. We have performed 65 thyroid surgeries (54 thyroid lobectomies, 1 completion thyroidectomy, and 10 total thyroidectomies) in 64 patients. Postoperative pathology revealed papillary carcinoma in 55 patients (84.6%), follicular carcinoma in two (3.1%), hyalinizing trabecular tumor in one (1.5%), and other benign tumor in seven (10.8%). All surgical margins were negative. Two (3.1%) patients developed transient vocal cord palsy but recovered within 2 months. One (1.5%) patient with vocal cord palsy had not recovered by 3 months after surgery. Five (7.7%) patients who underwent total thyroidectomy developed transient hypocalcemia but recovered within 2 months. Although transoral thyroid surgery is a relatively recent technique requiring further validation, it affords several advantages. Transoral thyroid surgery has not yet been universally accepted, but may be the best choice for thyroid surgery in the future.

Background Positron-emission tomography (PET) is widely used to detect malignancies, but consensus on its prognostic value in oropharyngeal cancer has not been established. The purpose of this study was to analyze the PET parameters associated with tumor extent and survival in resectable oropharyngeal cancer. Methods The PET parameters in oropharyngeal cancer patients with regional node metastasis who underwent surgery and postoperative radiotherapy between January 2005 and January 2019 were analyzed. We calculated the SUVmax, tumor-to-liver ratio (TLR), metabolic tumor volume (MTV, volume over SUV 2.5), and total lesion glycolysis (TLG, MTV x mean SUV) of the primary lesion and metastatic nodes. Histologic findings, patient survival, and recurrence were reviewed in the medical records. Results Fifty patients were included, and the PET parameters were extracted for 50 primary lesions and 104 nodal lesions. In the survival analysis, MTV and TLG of the primary lesions showed significant differences in overall survival (OS) and recurrence-free survival (RFS). In the multiple regression analysis, TLG of the primary lesion was associated with the depth of invasion (DOI). MTV of the nodes was a significant factor affecting extranodal extension (ENE). Conclusions PET parameters could be related with OS, RFS, DOI of the primary tumor, and ENE. PET would be expected to be a useful diagnostic tool as a prognosticator of survival and pathologic findings in oropharyngeal cancer.

Objective The aim of this study was to find an effective treatment method for preauricular sinus (PAS) in the pediatric population. We also investigated if the prognosis of treatment differed according to the location of the PAS. Methods From May 2015 to April 2020, a retrospective chart review was conducted on pediatric patients who underwent surgical excision of PAS at a tertiary referral medical center. Patients were divided into classical and variant groups according to the location of the PAS. The recurrence and postoperative complications, along with the preoperative history, were confirmed through medical chart review. Results A total of 88 patients (112 ears) were included in the study (n = 77 in the classical group and n = 11 in the variant group). The mean age of the patient was 6.5 years, and there were 48 males and 40 females. To reduce recurrence after surgical treatment, a temporalis muscle fascia anchoring suture was used in combination with preoperative pit dye staining, probe use, and surgical microscopy. The overall recurrence rate was 2.4% (2 cases), and postoperative minor complications were chronic pain (4.5%, n = 4), minor skin inflammation (10.2%, n = 9), and subcutaneous suture knot discomfort (13.6%, n = 12). Between the classical and variant groups, no clinical differences such as recurrence rate or complication rate were found, except for the long hospitalization period in the variant group (p = 0.043). Conclusions The use of a temporalis muscle fascia anchoring suture in combination with pit dye staining, probe use, and surgical microscopy in pediatric patients with PAS showed relatively low recurrence and complication rates compared to what has been previously reported in the literature. PAS in the variant position did not affect prognosis.

Objectives To find out the role of resection margin involvement in surgically managed HPV-positive tonsil cancer. Materials and methods The study included 94 subjects with HPV-positive tonsil cancer undergoing surgical treatment. We evaluated the relationships between the resection margin status, clinicopathological factors, and oncological outcome. Results The rate of resection margin involvement was 22.3% (21/94) after ablative surgery. Margin involvement, lymphatic invasion, and extracapsular spread were associated with the 5-year disease-free survival (DFS) and disease-specific survival (DSS) rate in univariate analysis. Multivariate Cox regression analysis confirmed a significant association between the margin involvement and 5-year DFS rate (HR = 4.602; 95% CI = 1.202–17.620; p = 0.026) and 5-year DSS rate (HR = 12.826; 95% CI = 1.399–117.593; p = 0.024). The incidence of resection margin involvement was significantly higher in patients with larger tumors (35.19 ± 15.07 mm vs. 25.53 ± 10.32 mm, p = 0.011) and more invasive tumors (17.84 ± 7.90 mm vs. 13.46 ± 6.88 mm, p = 0.037). The cutoff value of tumor size and depth of invasion for resection margin involvement was 29.5 mm (74% sensitivity and 63% specificity) and 14.5 mm (74% sensitivity and 61% specificity), respectively. Conclusion Resection margin involvement was significantly correlated with tumor size and the depth of invasion in HPV-positive tonsil cancer. Furthermore, resection margin involvement was associated with adverse outcomes.

Objectives The aim of this study was to evaluate the impact of CSC on insensitivity to radiotherapy in HNSCC. Methods A radioresistant cell line, FaDu-R, was established using fractionated ionizing radiation. Cells with high and low CD44/ALDH activity were isolated. Results FaDu-R cells demonstrated significantly increased cell viability after radiation exposure compared with parental cells. CD44 high /ALDH high FaDu-R cells demonstrated significantly faster wound closure (p high /ALDH high FaDu cells or the CD44 low /ALDH low FaDu-R cells. There was a significant difference in tumor volume between the CD44 high /ALDH high FaDu-R cells and the CD44 high /ALDH high FaDu cells (p low /ALDH low FaDu-R cells (p Conclusion Cancer stem cells (CSC) were associated with invasion and tumorigenesis in a radioresistant head and neck squamous cell carcinoma (HNSCC) cell line. This concept might help to improve the understanding of these mechanisms and to develop drugs that can overcome radioresistance during radiotherapy.

Highlights • The current study extracted radiomics—a large quantitative data of imaging features—from magnetic resonance images of patients with nasopharyngeal carcinoma. • The survival model fitted with radiomic features showed good prognostic performance in predicting the progression-free survival of patients with nasopharyngeal carcinoma (integrated area under the curve, 0.71; 95% confidence interval, 0.71–0.72). • Addition of radiomics to clinical survival model improved the prognostication of progression-free survival in patients diagnosed with nasopharyngeal carcinoma (integrated area under the curve from 0.76 to 0.81, p, Objectives To assess the additive prognostic value of MR-based radiomics in predicting progression-free survival (PFS) in patients with nasopharyngeal carcinoma (NPC) Methods Patients newly diagnosed with non-metastatic NPC between June 2006 and October 2019 were retrospectively included and randomly grouped into training and test cohorts (7:3 ratio). Radiomic features (n=213) were extracted from T2-weighted and contrast-enhanced T1-weighted MRI. The patients were staged according to the 8th edition of American Joint Committee on Cancer Staging Manual. The least absolute shrinkage and selection operator was used to select the relevant radiomic features. Univariate and multivariate Cox proportional hazards analyses were conducted for PFS, yielding three different survival models (clinical, stage, and radiomic). The integrated time-dependent area under the curve (iAUC) for PFS was calculated and compared among different combinations of survival models, and the analysis of variance was used to compare the survival models. The prognostic performance of all models was validated using a test set with integrated Brier scores. Results This study included 81 patients (training cohort=57; test cohort=24), and the mean PFS was 57.5 ± 43.6 months. In the training cohort, the prognostic performances of survival models improved significantly with the addition of radiomics to the clinical (iAUC, 0.72–0.80; p=0.04), stage (iAUC, 0.70–0.79; p=0.001), and combined models (iAUC, 0.76–0.81; p

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with poor prognosis, and the situation has not improved despite extensive clinical and scientific research. Here, we report proteogenomic analysis of PDAC. Mutation-phosphorylation correlations identified signaling pathways associated with somatic mutations in significantly mutated genes. mRNA-protein abundance correlations revealed oncogene and tumor suppressor candidates correlating with patient survival. Integrated clustering of mRNA, protein, and phosphorylation data identified six PDAC subtypes (Sub1-6), which were indistinguishable using mRNA data alone. mRNA and protein signatures defining Sub1-6 revealed that Sub1, Sub2-4, and Sub5-6 were precursor, invasive, and immunogenic tumors, respectively. In the Sub2-4 group, proliferation was highest for Sub4; Sub6 in the Sub5-6 group had an increased pancreatic secretion capacity. Orthotopic mouse PDAC models revealed higher numbers of pro-tumorigenic immune cells in Sub4 tumors, inhibiting T cell proliferation. Our proteogenomic analysis provides therapeutic targets and improves understanding of cancer biology and patient stratification in PDAC.

Purpose Lung cancer is among the most common cancers. Bronchoalveolar lavage fluid (BALF) can be easily obtained from patients with lung cancers. The aim is to develop a novel proteomic method of the molecule-based sensitive detection of biomarkers from BALF. Experimental design BALF samples are collected from segmental bronchus of 14 patients with lung cancers from Kyung Hee University Hospital. First, BALF proteome is depleted using a depletion column, and then peptides are prepared from the enriched low abundant proteins and fractionated by high pH reverse phase liquid chromatography prior to LC-MS/MS. Data are available via ProteomeXchange with identifier PXD012645. Results A novel method is developed for in-depth proteomic analysis of BALF by combining antibody-based depletion of high abundant proteins from BALF with high pH peptide fractionation. Peptides are analyzed on a high resolution Orbitrap Fusion mass spectrometer. MaxQuant search result in the identification of 4615 protein groups mapped to 4534 genes. Conclusions and clinical relevance It is found that the method outperformed conventional BALF proteomic methods and it is believed that this method will facilitate the biomarker research for lung cancer. In addition, it is shown that BALF will be a great source of biomarkers of lung diseases.

Pancreatic ductal adenocarcinoma is a recalcitrant tumor with minimal response to conventional chemotherapeutic approaches. Oncogenic signaling by activated tyrosine kinases has been implicated in cancers resulting in activation of diverse effector signaling pathways. Thus, the discovery of aberrantly activated tyrosine kinases is of great interest in developing novel therapeutic strategies in the treatment and management of pancreatic cancer. Patient-derived tumor xenografts (PDXs) in mice serve as potentially valuable preclinical models as they maintain the histological and molecular heterogeneity of the original human tumor. Here, we employed high-resolution mass spectrometry combined with immunoaffinity purification using anti-phosphotyrosine antibodies to profile tyrosine phosphoproteome across 13 pancreatic ductal adenocarcinoma PDX models. This analysis resulted in the identification of 1199 tyrosine-phosphorylated sites mapping to 704 proteins. The mass spectrometric analysis revealed widespread and heterogeneous activation of both receptor and non-receptor tyrosine kinases. Preclinical studies confirmed ephrin type-B receptor 4 (EphB4) as a potential therapeutic target based on the efficacy of human serum albumin-conjugated soluble EphB4 in mice bearing orthotopic xenografts. Immunohistochemistry-based validation using tissue microarrays from 346 patients with PDAC showed significant expression of EphB4 in &gt, 70% of patients. In summary, we present a comprehensive landscape of tyrosine phosphoproteome with EphB4 as a promising therapeutic target in pancreatic ductal adenocarcinoma.

To date, three main gasotransmitters, that is, hydrogen sulfide (H2S), carbon monoxide (CO), and nitric oxide (NO), have been discovered to play major bodily physiological roles. These gasotransmitters have multiple functional roles in the body including physiologic and pathologic functions with respect to the cellular or tissue quantities of these gases. Gasotransmitters were originally known to have only detrimental and noxious effects in the body but that notion has much changed with years; vast studies demonstrated that these gasotransmitters are precisely involved in the normal physiological functioning of the body. From neuromodulation, oxidative stress subjugation, and cardiovascular tone regulation to immunomodulation, these gases perform critical roles, which, should they deviate from the norm, can trigger the genesis of a number of neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). The purpose of this review is to discuss at great length physical and chemical properties and physiological actions of H2S, NO, and CO as well as shedding light on recently researched molecular targets. We particularly put emphasis on the roles in neuronal inflammation and neurodegeneration and neuronal repair.

Introduction: Subsequent epidemiologic studies have demonstrated a growing predominance of HPV infection in oropharyngeal squamous cell carcinomas (OSCC), particularly involving the tonsils. Detection of p16 overexpression is the most widely used test because it is the least expensive and the easiest to perform. However, this test has a sensitivity of 94% but an insufficient specificity of 82%. OSCC have been examined for other molecular markers including p53. Here, we investigated the prevalence of HPV and its relationship (especially for the inconcordance) with p16 and p53 in patients with OSCC. Materials and Methods: The clinical and pathologic data of total 89 patients who underwent surgical management for squamous cell carcinoma (SCC) of tonsil from 2000 to 2016 with thirty-month minimum follow-up periods were reviewed. We evaluated for demographic, clinical history, survival rate, p16, p53, and HPV association. Results: Among the 89 patients, 20 patients were excluded from p16 and HPV study, because they were incomplete test for study. So, we divided 69 patients into four groups: group 1, p16 positive and HPV positive (n=41, 59.4%); group 2, p16 negative and HPV negative (n=11, 15.9%); group 3, p16 positive and HPV negative (n=13, 18.8%); and group 4, p16 negative and HPV positive (n=4, 5.8%). There was significant difference in early T stage (T1 and 2) rate between group 1 and group 2 (90.2% vs. 36.3%, p=0.001), but not in 5-year overall survival (OS) rate (81.8% vs. 63.6%, p=0.127). Also, there was significant difference N positive rate between group 1 and group 3 (p=0.033), but not in 5-year overall survival (OS) rate (81.8% vs. 75%, p=0.479). Group 3 was also showed significant difference in early T stage rate from group 2 (90.2% vs. 76.9%, p=0.045). Group 4 showed no significant results with any group. For p53 and HPV study, we divided 89 patients into four groups: group 1, p53 negative and HPV positive (n=28, 31.4%); group 2, p53 negative and HPV negative (n=19, 21.3%); group 3, p53 positive and HPV positive (n=23, 25.8%); and group 4, p53 positive and HPV negative (n=19, 21.3%). There was significant difference in early T stage (T1 and 2) rate between group 1 and group 2 (p=0.029), but not in N positivity and 5-year overall survival (OS) rate. Also, there was no significant results with any group. Discussion: We can analyze the influence of p16 according to HPV status through group 2 and group 3. The p16 positive groups showed high early T stage rate regardless of HPV status, but there no statistical difference in N stage and 5-year overall survival. We also estimated that the N positivity was determined by HPV status rather than p16 by comparing group 1 and group 3. In HPV and p53 results, high T 1/2 stage rate is thought to be the result of HPV status, and p53 status showed no significant effect on stage, survival, and recurrence. Conclusion: The p16 test is insufficient when used alone to reliably confirm the viral origin of an OSCC. The combined use of these p16 and HPV tests would be more reliable but cannot eliminate all ambiguity. Citation Format: Geun-Jeon Kim, Inn-Chul Nam, Chung-Soo Kim, Min-Sik Kim. Analysis of inconcordance between p16, p53 immunohistochemistry, and HPV-PCR genotyping in tonsil cancer [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr A37.

Introduction: Supracricoid laryngectomy (SCL) is a conservative surgical technique for the treatment of selected laryngeal carcinomas, currently adopted also in old patients. But in the aging era, elderly patients represent the fastest-growing section of the population. The aim of this study is to compare the oncologic and functional results in elderly and younger patients following SCL. Materials and Methods: We retrospectively reviewed the medical records of 114 patients who underwent SCL between 1994 and 2013. All of the patients underwent surgery at least 5 years before the study was undertaken. We took the cut-off age of elderly patients as 70 years old, and there were 15 elderly patients. We chose another 15 patients with age younger than 60 years who are matched in stage, primary site, and reconstruction methods. Patients older than 70 years were classified to group I, and patients younger than 60 years were classified to group II. In group 1, the mean age was 53.2 years of age (range 46-60), and in group 2 it was 73.3 years of age (range 71-77). Functional evaluation was performed by evaluating the time of decannulation and nasogastric tube removal, final diet, and duration of hospital stay. Patients’ voice quality was assessed perceptually using GRABS scale. Postoperative complications, especially pulmonary complication such as aspiration pneumonia, were also evaluated. Oncologic results were also evaluated in both groups. Results: The total GRABS score of group I was 8.7 and that of group II was 7.3, and there was no significant statistical difference in these two values. The average time of decannulation was slightly longer in group I; however, these values were not significantly different. The average time of nasogastric tube removal and hospitalization time was significantly longer in group I patients. This was due to the longer duration of swallowing exercise. However, all patients could finally intake orally without gastrostomy. The rate of aspiration pneumonia was slightly higher in group I but failed to show statistical difference. All patients underwent surgery as a primary treatment mordality. In group I, one patient underwent adjuvant radiation, and two patients in group II underwent adjuvant radiation. The 5-year overall survival was 66.6%, 5-year disease-specific survival was 72.1%, and the survival rates of the two groups were not significantly different. Conclusion: Age by itself does not have a significant impact on functional and oncologic results following SCPL. Though elderly patients need more time to take oral diet, that is, need longer time of swallowing exercise, they can finally intake oral diet after swallowing training. Meticulous selection of the candidate to SCPL allows the application of this surgical technique with adequate oncologic and functional results. Citation Format: Inn-chul Nam, Choung-soo Kim, Keun-jeon Kim, MIn-sik Kim. Role of supracricoid partial laryngectomy in the aging era [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr B39.

Synaptic plasticity is important for maintaining normal neuronal activity and proper neuronal functioning in the nervous system. It is crucial for regulating synaptic transmission or electrical signal transduction to neuronal networks, for sharing essential information among neurons, and for maintaining homeostasis in the body. Moreover, changes in synaptic or neural plasticity are associated with many neuropsychiatric conditions, such as schizophrenia (SCZ), bipolar disorder (BP), major depressive disorder (MDD), and Alzheimer’s disease (AD). The improper maintenance of neural plasticity causes incorrect neurotransmitter transmission, which can also cause neuropsychiatric conditions. Gas neurotransmitters (gasotransmitters), such as hydrogen sulfide (H2S), nitric oxide (NO), and carbon monoxide (CO), play roles in maintaining synaptic plasticity and in helping to restore such plasticity in the neuronal architecture in the central nervous system (CNS). Indeed, the upregulation or downregulation of these gasotransmitters may cause neuropsychiatric conditions, and their amelioration may restore synaptic plasticity and proper neuronal functioning and thereby improve such conditions. Understanding the specific molecular mechanisms underpinning these effects can help identify ways to treat these neuropsychiatric conditions.

Esophagogastroduodenoscopy (EGD) is considered a relatively safe procedure. However, the procedure and the materials used in EGD with conscious sedation can cause stress to the patient. Adverse events during EGD have been reported, represented by cardiopulmonary complications. To date, five cases have reported worldwide to be associated with gastrointestinal endoscopy. Stress cardiomyopathy (SCMP) is a reversible cardiomyopathy that typically occurs in postmenopausal women due to stress and may resolve within a few weeks. SCMP resembles acute myocardial infarction but differs in terms of treatment and prognosis. Here, we describe two cases of SCMP with shock during EGD with conscious sedation.

Although concomitant chemoradiotherapy (CCRT) has recently become a mainstay of a primary treatment modality in advanced head and neck squamous cell carcinoma (HNSCC), some of the patients experience CCRT failure. If we can predict the CCRT outcomes, we can reduce unnecessary CCRT avoiding risk of CCRT‑related complication. We aimed to identify genetic alteration markers related to treatment failure in HNSCC patients who underwent radical surgery and CCRT. Genome‑wide copy number alterations (CNAs) were analyzed in 18 HNSCC patients with (n=9) or without (n=9) recurrence using oligoarray‑comparative genomic hybridization and candidate CNAs were validated by quantitative RT‑PCR. A total of 15 recurrently altered regions (RARs) were identified in the 18 HNSCC cases. Among them, two RARs were significantly associated with CCRT‑failure: copy number gained RARs of 7p11.2 harboring EGFR (P=0.029) and 18p11.32 harboring TYMS gene (P=0.029). Three RARs (7p11.2, 9p21.3 and 18p11.32) were significantly associated with poor disease‑specific survival in univariate analysis, and 7p11.2 was consistently significant in the multivariate analysis (HR 40.68, P=0.003). In conclusion, we defined novel genomic alterations associated with CCRT‑failure: 7p11.2 (EGFR) and 18p11.32 (TYMS). Our results provide useful clues for the elucidation of the molecular pathogenesis of HNSCC and to predict CCRT‑failure.

Tamoxifen, an estrogen receptor-α (ER) antagonist, is an important agent for the treatment of breast cancer. However, this therapy is complicated by the fact that a substantial number of patients exhibit either de novo or acquired resistance. To characterize the signaling mechanisms underlying this resistance, we treated the MCF7 breast cancer cell line with tamoxifen for over six months and showed that this cell line acquired resistance to tamoxifen in vitro and in vivo. We performed SILAC-based quantitative phosphoproteomic profiling on the tamoxifen resistant and vehicle-treated sensitive cell lines to quantify the phosphorylation alterations associated with tamoxifen resistance. From >5600 unique phosphopeptides identified, 1529 peptides exhibited hyperphosphorylation and 409 peptides showed hypophosphorylation in the tamoxifen resistant cells. Gene set enrichment analysis revealed that focal adhesion pathway was one of the most enriched signaling pathways activated in tamoxifen resistant cells. Significantly, we showed that the focal adhesion kinase FAK2 was not only hyperphosphorylated but also transcriptionally up-regulated in tamoxifen resistant cells. FAK2 suppression by specific siRNA knockdown or a small molecule inhibitor repressed cellular proliferation in vitro and tumor formation in vivo. More importantly, our survival analysis revealed that high expression of FAK2 is significantly associated with shorter metastasis-free survival in estrogen receptor-positive breast cancer patients treated with tamoxifen. Our studies suggest that FAK2 is a potential therapeutic target for the management of hormone-refractory breast cancers.

Background The purpose of this study was to evaluate the long-term swallowing function in patients with vertical hemipharyngolaryngectomy (VHPL) for hypopharyngeal cancer. Methods A retrospective review of 30 patients followed for more than 2 years with VHPL between 1998 and 2011 was performed. Results Five patients (16.7%) experienced gastrostomy tube placement, 4 patients (13%) had pharyngoesophageal stricture, and 13 patients (45%) had aspiration pneumonia. There was a significant difference in the fraction of gastrostomy tube placement among type II VHPL (35.7%), type I VHPL (0%), and type III VHPL (0%; p = .014). Gastrostomy tube dependence was significantly associated with flap size (larger than 70 cm2; p = .043) and aspiration pneumonia (p = .009). A significant positive correlation was found between current smokers and aspiration pneumonia (p = .030). Conclusion Type II VHPL, large flap reconstruction, and aspiration pneumonia had predictable values for gastrostomy tube dependence. Smoking status correlated with aspiration pneumonia. Better counseling and vigilance concerning swallowing difficulties may be possible. © 2015 Wiley Periodicals, Inc. Head Neck, 2015

Background We evaluated the use of fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT for the identification of extracapsular spread (ECS) with supporting histologic correlations in laryngeal cancer. Methods We reviewed the medical records of 89 patients with laryngeal cancer who underwent FDG PET/CT before surgery. Results ECS was present in 38.2% (18 of 47) of dissected necks and in 32.2% (20 of 62) of dissected cervical levels. There was a significant difference in the standardized uptake value maximum (SUVmax) between cervical lymph nodes with and without ECS (6.39 ± 4.53 vs 1.21 ± 1.70; p < .001); the cutoff value for differentiating nodes with ECS from those without ECS was 2.8, with a sensitivity of 85.7% and specificity of 85.6%. Conclusion A median SUVmax cutoff value >2.8 was associated with an increased risk of cervical lymph node metastasis and ECS in patients with laryngeal cancer. © 2014 Wiley Periodicals, Inc. Head Neck, 2015

Background The purpose of this study was to determine prognostic factors influencing outcomes of surgical treatment in patients with T4a hypopharyngeal cancer. Methods The present study enrolled 93 patients diagnosed with T4a hypopharyngeal cancer who underwent primary surgery between January 2005 and December 2015 at six medical centers in Korea. Primary tumor sites included pyriform sinus in 71 patients, posterior pharyngeal wall in 14 patients, and postcricoid region in 8 patients. Seventy-two patients received postoperative radio(chemo)therapy. Results Five-year disease-free survival (DFS) and disease-specific survival (DSS) rates were 38% and 45%, respectively. In univariate analysis, 5-year DFS was found to have significant and positive correlations with margin involvement (p

Colchicine is an alkaloid widely used for the treatment of inflammatory diseases, such as gout. It suppresses cell division by inhibiting mitosis. We investigated the anticancer effects of colchicine on human hypopharyngeal cancer cells and the mechanisms underlying its anticancer effects. XTT cell proliferation assay showed that colchicine inhibited the growth and proliferation of human hypopharyngeal cancer cells (FaDu and SNU1041) in a dose- and time-dependent manner. Colchicine also inhibited the migration, invasion, and adhesion of hypopharyngeal cancer cells in a dose-dependent manner. The levels of mRNA expression and activity of matrix metalloproteinase-9 (MMP9) and urokinase-type plasminogen activator (uPA) decreased after treatment with colchicine. Further investigation revealed that colchicine inhibited the phosphorylation of the FAK/SRC complex and paxillin. Tumor volume ratios in colchicine-treated mice (0.1 mg/kg, every 2 days for 14 days) increased less than in control mice. To our knowledge, this is the first report showing that colchicine can suppress cell invasion, migration, and adhesion through reduced expression of MMP9, the uPA system, and the FAK/SRC complex. Colchicine has the potential to prevent disease progression in hypopharyngeal cancer and may have application as an adjunctive treatment.

Many patients with pancreatic cancer have metastases to distant organs at the time of initial presentation. Recent studies examining the evolution of pancreatic cancer at the genetic level have shown that clonal complexity of metastatic pancreatic cancer is already initiated within primary tumors, and organ-specific metastases are derived from different subclones. However, we do not yet understand to what extent the evolution of pancreatic cancer contributes to proteomic and signaling alterations. We hypothesized that genetic heterogeneity of metastatic pancreatic cancer results in heterogeneity at the proteome level. To address this, we employed a model system in which cells isolated from three sites of metastasis (liver, lung, and peritoneum) from a single patient were compared. We used a SILAC-based accurate quantitative proteomic strategy combined with high-resolution mass spectrometry to analyze the total proteome and tyrosine phosphoproteome of each of the distal metastases. Our data revealed distinct patterns of both overall proteome expression and tyrosine kinase activities across the three different metastatic lesions. This heterogeneity was significant because it led to differential sensitivity of the neoplastic cells to small molecule inhibitors targeting various kinases and other pathways. For example, R428, a tyrosine kinase inhibitor that targets Axl receptor tyrosine kinase, was able to inhibit cells derived from lung and liver metastases much more effectively than cells from the peritoneal metastasis. Finally, we confirmed that administration of R428 in mice bearing xenografts of cells derived from the three different metastatic sites significantly diminished tumors formed from liver- and lung-metastasis-derived cell lines as compared with tumors derived from the peritoneal metastasis cell line. Overall, our data provide proof-of-principle support that personalized therapy of multiple organ metastases in a single patient should involve the administration of a combination of agents, with each agent targeted to the features of different subclones.

Human papillomavirus (HPV) infection plays a significant role in the development and progression of head and neck squamous cell carcinoma (HNSCC). Expression of miR-21 has a prognostic role in a wide variety of cancers. The upregulation of miR-21 suppresses a number of target genes, including phosphatase tensin homologue (PTEN) and programmed cell death 4 (PDCD4). We investigated the association between the expression of miR-21 and the clinical features of HNSCC using stratified analysis based on HPV infection status. HPV status and miR-21 expression in HNSCC tissues from 167 patients were evaluated using in situ hybridization. The expression of PDCD4 and PTEN was examined by immunohistochemistry. The up-regulation of stromal miR-21 expression occurred in 40.6% of HPV-negative samples and 28.3% of the HPV-positive group. In HPV-stratified multivariate analysis, high miR-21 expression was associated with poor cancer-specific survival in HPV-negative tumors, but not in HPV-positive tumors. There was a significant association between miR-21 and cytoplasmic PDCD4 overexpression in HPV-negative HNSCCs. We suggest that stromal miR-21 expression is an independent prognostic factor in HPV-negative tumors and miR-21 may play different roles depending on HPV infection status.

Pancreatic cancer is the fourth leading cause of cancer-related death in the world. The etiology of pancreatic cancer is heterogeneous with a wide range of alterations that have already been reported at the level of the genome, transcriptome, and proteome. The past decade has witnessed a large number of experimental studies using high-throughput technology platforms to identify genes whose expression at the transcript or protein levels is altered in pancreatic cancer. Based on expression studies, a number of molecules have also been proposed as potential biomarkers for diagnosis and prognosis of this deadly cancer. Currently, there are no repositories which provide an integrative view of multiple Omics data sets from published research on pancreatic cancer. Here, we describe the development of a web-based resource, Pancreatic Cancer Database (http://www.pancreaticcancerdatabase.org), as a unified platform for pancreatic cancer research. PCD contains manually curated information pertaining to quantitative alterations in miRNA, mRNA, and proteins obtained from small-scale as well as high-throughput studies of pancreatic cancer tissues and cell lines. We believe that PCD will serve as an integrative platform for scientific community involved in pancreatic cancer research.

Background The purpose of this study was to investigate expression differences of p53, PTEN, PI3K, Akt and mTOR according to the human papillomavirus (HPV) infection and to evaluate clinical significance as prognostic markers in patients with locally advanced tonsillar cancer. Methods Sixty-five patients were reviewed. Tissue microarrays were prepared from surgical specimens and stained with antibodies against p53, PTEN, PIK3CA, Akt and mTOR. Results Twenty-six patients were HPV-positive. Expression of P53 as well as PIK3CA, Akt and mTOR were not significantly different between the 2 groups. However, total PTEN (nuclear and cytoplasmic PTEN) expression was significantly frequent in HPV-positive group. Both overall survival (OS) and disease-free survival (DFS) were significantly different between the 2 groups. Nuclear PTEN expression in the cancer area and pathological nodal stage were significantly correlated with DFS. Conclusion Our study suggests that the presence of PTEN expression with predisposition to nucleus more frequently observed in HPV-positive tonsillar cancers are significantly associated with favorable survival outcome, independent of activated PI3K/Akt/mTOR cell survival pathway. © 2014 Wiley Periodicals, Inc. Head Neck 37: 636–643, 2015

SummaryMutations in leucine-rich repeat kinase 2 (LRRK2) are a common cause of familial and sporadic Parkinson’s disease (PD). Elevated LRRK2 kinase activity and neurodegeneration are linked, but the phosphosubstrate that connects LRRK2 kinase activity to neurodegeneration is not known. Here, we show that ribosomal protein s15 is a key pathogenic LRRK2 substrate in Drosophila and human neuron PD models. Phosphodeficient s15 carrying a threonine 136 to alanine substitution rescues dopamine neuron degeneration and age-related locomotor deficits in G2019S LRRK2 transgenic Drosophila and substantially reduces G2019S LRRK2-mediated neurite loss and cell death in human dopamine and cortical neurons. Remarkably, pathogenic LRRK2 stimulates both cap-dependent and cap-independent mRNA translation and induces a bulk increase in protein synthesis in Drosophila, which can be prevented by phosphodeficient T136A s15. These results reveal a novel mechanism of PD pathogenesis linked to elevated LRRK2 kinase activity and aberrant protein synthesis in vivo.

OBJECTIVES: Although T stage is an important prognostic tool for oral tongue cancer, it fails to define the depth of invasion and true three-dimensional volume of primary tumors. The purpose of this paper is to determine the relations between tumor volume and lymph node metastasis and survival in early oral tongue cancer. METHODS: Forty-seven patients with T1-2 tongue cancer were included. Tumor volumes were measured by the computerized segmentation of T2-weighted magnetic resonance imaging. RESULTS: The overall average tumor volume was 27.7 cm(3) (range, 1.4 to 60.1 cm(3)). A significant positive correlation was found between tumor volume and pathological T stage, depth of invasion, and cervical lymph node metastasis (P

Factors that affected prognosis were T stage and extracapsular spread in patients that underwent primary surgery with postoperative radiotherapy for pN2 head and neck carcinoma.The purpose of this study was to examine treatment outcomes and define prognostic factors for pN2 head and neck carcinoma.A total of 209 patients underwent surgery with postoperative radiotherapy between 1994 and 2011. Primary tumor sites were the oropharynx (n = 70), hypopharynx (n = 48), larynx (n = 47), and oral cavity (n = 44). There were 21, 83, 60, and 45 patients with stage T1 to T4 cancers, respectively. The N stages were 20 N2a, 129 N2b, and 60 N2c.The recurrence rate was 40% (83/209) over a mean observation period of 39 months. The 5-year disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS) rates in our cohort were 44%, 60%, and 56%, respectively. The presence of advanced T stage or extracapsular spread had a significant adverse effect on 5-year DFS, DSS, and OS rates according to Kaplan-Meier survival curves. Multivariate Cox regression analysis confirmed the significant association between 5-year DSS rate and advanced T stage (hazard ratio (HR), 2.20; 95% confidence interval (CI), 1.26-3.82; p = 0.005) and extracapsular spread (HR, 2.29; 95% CI, 1.24-4.21; p = 0.008).

18F-FDG PET/CT is clinically useful in the initial staging and follow-up of patients with head and neck squamous cell carcinoma (HNSCC). We studied the potential prognostic significance of preoperative 18F-FDG PET/CT in HNSCC. The medical records of 294 patients who underwent preoperative 18F-FDG PET/CT for HNSCC were retrospectively reviewed. The median SUVmax of the primary lesions (SUVmax-p) and cervical lymph nodes (SUVmax-n) was 7.98 ± 5.04 (range 1.2–28.7) and 3.34 ± 3.70 (range 1.0–20.4), respectively. There was a significant difference between with and without recurrence in SUVmax-p (11.14 ± 5.36 vs. 6.78 ± 4.35, p

The aim of this study was to evaluate the prognostic factors of patients with pathologically negative lymph node (pN0) head and neck cancer. Study Design Case series with chart review.College medical center.The medical records of 120 patients were reviewed. Primary tumor sites included 46 larynx, 45 oral cavity, 17 oropharynx, and 12 hypopharynx.The recurrence rate was 14% (17/120) over a mean observation period of 33 months. Median (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) maximal standardized uptake value (SUVmax; using 8.5 as a cutoff; P = .001), positive surgical margins (P = .005), and pathologic T stage (P = .012) were found to be associated with recurrence. The 5-year disease-specific survival rate (DSSR) in our cohort was 86%. Patients with an SUVmax value higher than 8.5 and positive surgical margins had significantly decreased 5-year DSSR based on Kaplan-Meier survival curves. Multivariate Cox regression analysis confirmed the significant association between median SUVmax (using 8.5 as a cutoff; hazard ratio [HR], 6.13; 95% confidence interval [CI], 1.79-20.93; P = .004) and margin involvement (HR, 4.98; 95% CI, 1.42-17.47; P = .012).A median (18)F-FDG PET/CT SUVmax cutoff values of 8.5 or greater and positive surgical margins were associated with adverse outcomes in patients with pN0 head and neck cancer.

Background To evaluate the association of 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG PET/CT) and high-risk human papillomavirus (HPV) status and to establish the histologic correlates in oropharyngeal cancer (OPSCC). Method The medical records of 78 patients who underwent 18F-FDG PET/CT for OPSCC before surgery were reviewed. Results The positive rate of high-risk HPV in situ hybridization was 36% (28 of 78). The maximum standardized uptake values (SUVmax) of negativity for the high-risk HPV subtypes (10.29 ± 4.30) and positivity (6.69 ± 4.17) were found to be significantly different (p = .001). The SUVmax cutoff value for differentiating negativity for the high-risk HPV subtypes from positivity was 7.10, with the sensitivity of 78% and the specificity of 68%. A median SUVmax (using 7.10 as a cutoff) (p = .041) and high-risk HPV status (p = .040) were found to be associated with 5-year disease-specific survival (DSS). Conclusions Median 18F-FDG PET/CT SUVmax cutoff values 7.10 or greater are associated with a high-risk HPV negativity in OPSCC patients. © 2013 Wiley Periodicals, Inc. Head Neck 36: 323–327, 2014

Purpose We wanted to evaluate the role of postoperative chemoradiotherapy (CRT) for patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). Materials and methods From March 1993 to July 2008, 101 patients with advanced SCCHN and who had undergone macroscopically complete resection were enrolled. Survival and the cumulative incidence of local or regional relapse, metastasis, and acute toxicity were analyzed. Results There was a marginally significant difference of disease-free survival at five years in favor of the CRT arm (51.3% vs. 41.8%, respectively; p=0.10). However, there was no significant difference in overall survival between the two treatment arms (p=0.20). The rate of locoregional failure only for the radiotherapy arm was significantly higher than that for the CRT arm (23.2% vs. 4.4%, respectively; p=0.01). The incidence of grade 3 or 4 hematologic toxicity was significantly higher in the CRT arm than that in the radiotherapy arm (37.7% vs. 1.7%, respectively; p=0.01). In CRT arm, early mortality group within 1 year had low performance status and old age over sixty compared with those of the others. Conclusion After curative-intent surgery, adjuvant CRT is more effective in locoregional tumor control than radiotherapy alone for patients with advanced SCCHN. However, compared with radiotherapy alone, this combined modality treatment had no survival benefit, and was significantly associated with increased toxicity. Thus, patients with low performance status and old age must be cautious in selection of toxic trimodality treatment.

Background The purpose of this study was to evaluate the use of fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT for the identification of extracapsular spread (ECS) with supporting histologic correlation in hypopharyngeal cancer. Method We retrospectively reviewed the medical records of 57 patients who underwent FDG PET/CT for hypopharyngeal cancer. Results ECS was present in 79% dissected necks (45 of 57 patients) and in 64% dissected cervical levels (55 of 86). A significant difference in standardized uptake value maximum (SUVmax) values was found between cervical lymph nodes with and without ECS (6.10 ± 3.51 vs 1.75 ± 1.46, respectively; p < .001). The cutoff value of SUVmax for differentiating with and without ECS was 2.65 with a sensitivity of 80% and a specificity of 74%. The presence of ECS and median SUVmax were found to have a significant adverse effect on 5-year disease-specific survival. Conclusion Median FDG PET/CT SUVmax cutoff values of 2.65 or greater are associated with a greater risk of ECS in cervical lymph node metastasis from hypopharyngeal squamous cell carcinoma (SCC). © 2013 Wiley Periodicals, Inc. Head Neck 35: 1771–1776, 2013

Excision repair cross complement group 1 (ERCC1) expression is a predictive biomarker for platinum-containing treatment in squamous cell carcinoma of head and neck (SCCHN). However, the prognostic significance after surgical resection is not well understood.Oropharynx (n=143) or oral cavity (n=61) SCCHN patients undergoing surgery were included. ERCC1 protein expression and HPV status were assessed by ERCC1 and p16 immunohistochemistry.The ERCC1, over-expressed in 66.7% of patients, was associated with oral cavity cancer (P0.001), well differentiation (P=0.036), and HPV negativity (P0.001). In TCGA database, ERCC1 mRNA upregulation was enriched in HPV-negative and oral cavity cancers, and associated with HRAS mutation (P0.001). The prognostic role of ERCC1 was not different according to HPV status. High ERCC1 expression showed a trend toward poor prognosis in patients with an advanced stage (P=0.079) with marginal significance.The ERCC1 expression was not prognostic in surgically resected oropharynx/oral cavity SCCHN, irrespective of HPV status. However, it could provide additional prognostic information for advanced stage patients.

Neuronal inflammation is a systematically organized physiological step often triggered to counteract an invading pathogen or to rid the body of damaged and/or dead cellular debris. At the crux of this inflammatory response is the deployment of nonneuronal cells: microglia, astrocytes, and blood-derived macrophages. Glial cells secrete a host of bioactive molecules, which include proinflammatory factors and nitric oxide (NO). From immunomodulation to neuromodulation, NO is a renowned modulator of vast physiological systems. It essentially mediates these physiological effects by interacting with cyclic GMP (cGMP) leading to the regulation of intracellular calcium ions. NO regulates the release of proinflammatory molecules, interacts with ROS leading to the formation of reactive nitrogen species (RNS), and targets vital organelles such as mitochondria, ultimately causing cellular death, a hallmark of many neurodegenerative diseases. AD is an enervating neurodegenerative disorder with an obscure etiology. Because of accumulating experimental data continually highlighting the role of NO in neuroinflammation and AD progression, we explore the most recent data to highlight in detail newly investigated molecular mechanisms in which NO becomes relevant in neuronal inflammation and oxidative stress-associated neurodegeneration in the CNS as well as lay down up-to-date knowledge regarding therapeutic approaches targeting NO.

Risk factors were evaluated for surgical bed soft tissue necrosis (STN) in head and neck cancer patients treated with postoperative radiation therapy (PORT) after transoral robotic surgery (TORS) or wide excision with primary closure. Sixty-seven patients were evaluated. STN was defined as ulceration and necrosis of the surgical bed or persistently unhealed high-grade acute mucositis with pain after PORT. The median RT dose of primary site was 63.6 Gy (range, 45–67.15 Gy) with 2 Gy/fx (range 1.8–2.2 Gy/fx). Total 41 patients (61.2%) were treated with concurrent chemoradiotherapy. The median follow-up period was 26 months. STN was diagnosed in 13 patients (19.4%). Most of the patients were treated with oral steroids, antibiotics, and analgesics and the lesions were eventually improved (median of 6 months after PORT). STN did not influence local control. A depth of invasion (DOI > 1.4 cm, odds ratio [OR] 14.04, p = 0.004) and maximum dose/fraction (CTVpmax/fx > 2.3 Gy, OR 6.344, p = 0.043) and grade 3 acute mucositis (OR 6.090, p = 0.054) were related to STN. The 12 (23.5%) of 51 oropharyngeal cancer patients presented STN, and the risk factors were DOI > 1.2 cm (OR 21.499, P = 0.005), CTVpmax/fx > 2.3 Gy (OR 12.972, P = 0.021) and grade 3 acute mucositis (OR 10.537, P = 0.052). Patients treated with TORS or WE with primary closure followed by PORT had a high risk of surgical bed STN. STN risk factors included DOI (>1.2–1.4 cm) and CTVpmax/fx (>2.3 Gy). Radiation therapy after TORS must be carefully designed to prevent STN.

Tissue microarrays have become a valuable tool for high-throughput analysis using immunohistochemical labeling. However, the large majority of biochemical studies are carried out in cell lines to further characterize candidate biomarkers or therapeutic targets with subsequent studies in animals or using primary tissues. Thus, cell line-based microarrays could be a useful screening tool in some situations. Here, we constructed a cell microarray (CMA) containing a panel of 40 pancreatic cancer cell lines available from American Type Culture Collection in addition to those locally available at Johns Hopkins. As proof of principle, we performed immunocytochemical labeling of an epithelial cell adhesion molecule (Ep-CAM), a molecule generally expressed in the epithelium, on this pancreatic cancer CMA. In addition, selected molecules that have been previously shown to be differentially expressed in pancreatic cancer in the literature were validated. For example, we observed strong labeling of CA19-9 antigen, a prognostic and predictive marker for pancreatic cancer. We also carried out a bioinformatics analysis of a literature curated catalog of pancreatic cancer biomarkers developed previously by our group and identified two candidate biomarkers, HLA class I and transmembrane protease, serine 4 (TMPRSS4), and examined their expression in the cell lines represented on the pancreatic cancer CMAs. Our results demonstrate the utility of CMAs as a useful resource for rapid screening of molecules of interest and suggest that CMAs can become a universal standard platform in cancer research.

Summary Objectives The aims of this study were to evaluate the expression of EGFR, PI3K, Akt, mTOR, and PTEN in the oral cavity and oropharyngeal cancers, and to investigate their clinical significance as prognostic markers. Materials and methods One hundred twenty-one patients who underwent curative surgery for oral cavity or oropharyngeal squamous cell carcinoma in Seoul St. Mary’s Hospital between January 1995 and September 2009 were evaluated. The level of protein expression of EGFR, PIK3CA, pAkt, mTOR, and PTEN was assessed by immunohistochemistry. In situ hybridization was used to detect the existence of human papillomavirus (HPV). Results Nineteen of 61 patients with oropharyngeal cancer showed HPV-positive tumors, and two of 60 patients with oral cavity cancer showed HPV-positive tumors. EGFR and pAkt expression was significantly higher in oral cavity cancers than in oropharyngeal cancers. Loss of PTEN occurred significantly more frequently in oral cavity cancers than in oropharyngeal cancers. The expression levels of PIK3CA, mTOR, and p53 did not differ significantly between the two cancers. Overexpression of EGFR and pAkt and loss of PTEN were observed more frequently in HPV-negative tumors. Multivariate Cox regression analysis showed that pAkt expression had a significantly unfavorable impact on relapse-free survival in oropharyngeal cancer. Conclusion We conclude that the expression levels of EGFR, pAkt, and PTEN differ between oropharyngeal and oral cavity cancer and it may be attributed to HPV-related molecular pathogenesis. The expression of pAkt might be an unfavorable prognostic marker for relapse-free survival in oropharyngeal cancer.

The purpose of this study was to examine the treatment outcomes of larynx-preserving partial hypopharyngectomies for hypopharyngeal carcinoma. Forty-three patients underwent partial hypopharyngectomy and reconstruction using faciocutaneous free flaps with and without postoperative radiotherapy between 1998 and 2009. Primary tumor sites were pyriform sinus in 35 and posterior pharyngeal wall in 8 patients. Thirty patients received postoperative radiotherapy. The 5-year overall and disease-specific survival rates were 63% and 67%, respectively. A significant positive correlation was found between pathologic N stage and primary site and disease-specific survival rates (N0/N1 stage; 93% vs. N2/N3 stage; 43%, p

Background Most of the reports about lymph node (LN) metastasis in papillary thyroid carcinoma (PTC) are retrospective studies. Methods We prospectively evaluated the pattern and predictive factors of LN metastasis of 176 patients with PTC who underwent total thyroidectomy and bilateral central LN dissection with or without therapeutic lateral LN dissection. Results Ipsilateral central LNs were involved even in early T classification, and contralateral central LNs were infrequently involved even in late T classification. Most of the lateral LN metastases were in levels II, III, and IV. Male sex was predictive of LN metastasis. Ipsilateral central LN metastasis and central LN metastasis were associated with contralateral central LN metastasis and lateral LN metastasis, respectively. Conclusions Ipsilateral central neck dissection is recommended for all PTC patients. Careful inspection for LN metastasis should be performed when evaluating male patients with PTC, and if central LNs are involved, carefully inspect lateral LNs. © 2012 Wiley Periodicals, Inc. Head Neck, 2013

Summary The purpose of this study was to examine treatment outcomes and define factors that influence survival in patients with pN2 oropharyngeal carcinoma. Fifty-five patients underwent primary surgery with postoperative radiotherapy between 1994 and 2009. Primary tumor sites were 36 tonsil, 13 base of tongue, 3 soft palate, and three posterior pharyngeal wall. There were 15, 26, 5, and 9 patients with stage T1 to T4 cancers, respectively. The N stage were 5 N2a, 37 N2b, and 13 N2c. The 5-year disease-specific survival rates were 66%. A significant positive correlation was found between high risk HPV status and extracapsular spread and disease-specific survival rates (HPV (+); 93% vs. HPV (−); 56%, p = 0.031 and extracapsular spread (−); 93% vs. extracapsular spread (+); 50%, p = 0.008, respectively). Primary surgery with postoperative radiotherapy can be achieved with favorable oncologic outcomes for pN2 oropharyngeal carcinoma. Factors that affected prognosis were HPV status and extracapsular spread.

Background The purpose of this study was to determine the role of high-risk human papillomavirus (HPV) in lymph node metastasis and the depth of invasion in oropharyngeal cancer. Methods The study included patients with 90 oral carcinomas and 66 oropharyngeal carcinomas. High-risk HPV in situ hybridization was performed to detect HPV infection. Results The positive rate of high-risk HPV in situ hybridization was 15.4% (24 of 156). There was a significant difference in the fraction of positive high-risk HPV between oral (6.7%) and oropharyngeal (27.3%) cancers (p < .000). Significant correlations were found between positive high-risk HPV and cervical lymph node metastasis, tumor depth of invasion in patients with oropharyngeal cancer (p = .002, p = .016, respectively). There was a statistically significant association between high-risk HPV positivity and the disease-specific survival in patients with oropharyngeal cancer (p = .035). Conclusion High-risk HPV infection was significantly related to cervical lymph node metastasis and depth of invasion in patients with oropharyngeal cancer. © 2011 Wiley Periodicals, Inc. Head Neck, 2012

Postoperative volume changes in reconstructed flaps are known to influence the functional restoration of resected areas of the upper aerodigestive tract. The purposes of this study were to estimate the volume decreases in flaps and investigate clinical factors affecting the volume decrease. The medical records of 19 patients who underwent ablation and flap reconstruction surgeries for head and neck cancers were reviewed. The volume of the reconstructed flap was measured at 3, 12, and 24 months postoperatively using CT or MR imaging and the 3D-DOCTOR software. The relationships between volume changes and perioperative clinical parameters were examined. The primary tumor locations were the nasal cavity and paranasal sinus, oropharynx, oral cavity, and hypopharynx in 8, 6, 4, and 1 case, respectively. Twelve patients underwent anterolateral thigh flap (ALTF) reconstruction, and seven patients underwent pectoralis major myocutaneous flap (PMMCF) reconstruction. Twelve (63.2%) patients received postoperative radiation. The estimated volume decreases at 12 and 24 months postoperatively for ALTF were 20.9 and 24.8%, respectively, while those for PMMCF were 7.3 and 10.8%, respectively. Among clinical factors, only the type of flap affected the volume change. When determining the volume of reconstructed flaps, the type of flap must be considered. It was recommended to make free and regional flaps at least 20 and 10% larger, respectively than the actual defect.

We assessed the prognostic value of metabolic tumor volume (MTV) measured using(18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) inpatients with locally advanced head and neck squamous cell carcinoma (HNSCC).We retrospectively reviewed 56 patients (51 men, five women; mean age 56.0 ± 8.8years) who had locally advanced HNSCC and underwent FDG PET/CT for initial evaluation. All patients had surgical resection and radiotherapy with or without concurrent chemotherapy. The peak standardized uptake value (SUVpeak) and MTV of the target lesion, including primary HNSCC andmetastatic cervical lymph nodes, were measured from FDG PET/CT images. We compared SUVpeak, MTV, and clinicopathologic variables such as age, Eastern Cooperative Oncology Group (ECOG) performance status, pN stage, pT stage, TNM stage, histologic grade and treatment modality to disease-free survival (DFS) and overall survival (OS).On the initial FDG PET/CT scans, the median SUVpeak was 7.8 (range, 1.8-19.0) and MTV was17.0 cm(3) (range, 0.1-131.0 cm(3)). The estimated 2-year DFS and OS rates were 67.2% and 81.8%. The cutoff points of SUVpeak 6.2 and MTV 20.7 cm(3) were the best discriminative values for predicting clinical outcome. MTV and ECOG performance status were significantly related to DFS and OS on univariate and multivariate analyses (p 0.05).The MTV obtained from initial FDG PET/CT scan is a significant prognostic factor for disease recurrence and mortality in locally advanced HNSCC treated with surgery and radiotherapy with or without chemotherapy.

Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare malignancy derived from antigen-presenting cells, with 55 cases reported thus far. A standard treatment modality is still being debated. This report describes a 56-year-old female who presented with right tonsillar enlargement and right submandibular swelling for 6 months. Treatment with empiric antibiotics did not result in improvement of her symptoms. Fine needle aspiration of the tonsil revealed no malignant cells. Tonsillectomy was eventually performed due to persistent symptoms. Based on microscopic findings, immunohistochemical stains, and review of the literature, the present case was finally diagnosed as IDCS of the tonsil with cervical lymph node involvement. The patient received four cycles of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy, and a clinically complete response was achieved followed by adjuvant radiation.