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Background: Uterine leiomyomas are the most common benign tumors in women of childbearing age. Although there are several studies reporting the positive association of drinking alcohol with the incidence of uterine leiomyomas, studies targeting Korean women are lacking., Objective: This study aimed to investigate the association between alcohol consumption and the risk of new-onset uterine leiomyomas in Korean women of early reproductive-age., Study Design: This was a retrospective nationwide population-based cohort study using the Korean National Health Insurance Service database. Participants comprised 2,512,384 asymptomatic Korean women aged 20 to 39 years who underwent a national health examination from 2009 to 2012. The follow-up period was from the date of the first national health examination to the date of diagnosis of new-onset uterine leiomyomas or December 2018 if no uterine leiomyomas were detected. The diagnosis of uterine leiomyomas required 2 outpatient records within a year or 1 inpatient record of International Classification of Diseases, Tenth Revision (ICD-10) codes of uterine leiomyomas (D25) in the Korean National Health Insurance Service. Exclusion criteria were previously diagnosed uterine leiomyomas during the screening period (January 2002 to the date of first health examination) or uterine leiomyoma diagnosis within 1 year of baseline examination. The associations of alcohol consumption, amount drunk per drinking session, and sustained drinking over time with the risk of new-onset uterine leiomyomas were investigated., Results: Approximately 6.1% of women aged 20 to 39 years were diagnosed with uterine leiomyomas after an average of 4.3 years. Alcohol consumption was associated with an increased incidence of new-onset uterine leiomyomas of 12% to 16% (hazard ratio, 1.12; 95% confidence interval, 1.11-1.14 for mild-to-moderate drinkers; hazard ratio, 1.16; 95% confidence interval, 1.12-1.20 for heavy drinkers). Drinking ≥1 days per week was associated with increased risk of uterine leiomyomas (hazard ratio, 1.11; 95% confidence interval, 1.10-1.12 for drinking 1 day per week; hazard ratio, 1.15; 95% confidence interval, 1.12-1.17 for drinking ≥3 days per week), and the association increased proportionately to the amount of alcohol consumed per drinking session (hazard ratio, 1.17; 95% confidence interval, 1.15-1.19 for ≥7 glasses per drinking session). Women who also reported alcohol consumption in the questionnaire administered 2 years later (sustained drinkers) exhibited a 20% increased risk of new-onset uterine leiomyomas (hazard ratio, 1.20; 95% confidence interval, 1.17-1.22) compared with women who answered that they did not drink alcohol at both times (sustained nondrinkers). In women who discontinued drinking, the risk was 3% (hazard ratio, 1.03; 95% confidence interval, 1.01-1.06), whereas in women who became drinkers, the risk was 14% (hazard ratio, 1.14; 95% confidence interval, 1.11-1.16)., Conclusion: Having an alcohol drinking habit, the amount of alcohol consumed per drinking session, and sustained drinking over 2 years were significantly associated with the risk of new-onset uterine leiomyomas. Avoiding or discontinuing drinking could lower the risk of new-onset uterine leiomyomas in early reproductive-age women., (Copyright © 2023 Elsevier Inc. All rights reserved.)

MDC1, a mediator of DNA damage response, recruits other repair proteins on double-strand break (DSB) sites. MDC1 is necessary for activating checkpoint kinases Chk1 and Chk2. It is unclear whether Chk1 interacts with MDC1. MDC1 also comprises many discrete domains. The role of the proline-serine-threonine (PST)-repeat domain of MDC1 in the DNA damage response is unclear. Here, we showed that MDC1 directly binds Chk1 through this PST-repeat region. Phosphorylation of Chk1 by ionizing radiation (IR) also required this PST-repeat domain. Degradation of intact MDC1 was accelerated depending on the PST-repeat domain after IR exposure. In the IR damage response, the PST-repeat-deleted MDC1 levels remained elevated with slow degradation. This abnormal regulation of MDC1 was F-box- and WD40 repeat-containing 7 (FBXW7)-dependent. The mutation of lysine 1413 within the PST-repeat of MDC1 deregulated MDC1 with or without damage. K1413R mutant and PST-deleted MDC1 displayed reduced ability to repair the damaged genome post-IR exposure. These results provide that the PST domain of MDC1 is involved in Chk1 and DNA repair activation. The findings suggest new insights into how MDC1 connects the checkpoint and DNA repair in the DNA damage response., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Suppressor of cytokine signaling (SOCS) proteins are primarily feedback inhibitors of cytokine signaling. The two conserved domains of SOCS proteins have distinct functions. Src homology 2 (SH2) domain inhibits cytokine receptor, while SOCS box acts as an E3 ubiquitin ligase. SOCS2, a cytokine signaling suppressor, has been primarily implicated in regulating inflammatory conditions in neuronal diseases. However, SOCS proteins have been suggested to play diverse roles in healthy and diseased nervous system including neurodegenerative disorders. In this study, SOCS2 was found to be upregulated in Huntington's disease and was substantially induced in extended polyglutamine (polyQ)-expressing striatal cells. The induced level was augmented under aging conditions. In extended polyQ-expressing cells, downregulated SOCS2 improved autophagic dysfunction rather than altered inflammatory conditions. Overall, we suggest that SOCS2 involves in regulating autophagy by functioning as an E3 ligase in extended polyQ conditions, and consequently regulates cell damage and cell death type., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Sarcopenia may result in negative outcomes in patients with cancer, but its impact on surgical and oncological outcomes in older adult patients with head and neck squamous cell carcinoma (HNSCC) has not been systematically studied. This study evaluated the clinical impact of sarcopenia on postsurgical and oncological outcomes in older adult patients with HNSCC., Methods: This is a prospective study of 190 consecutive HNSCC patients aged ≥65 years who underwent curative surgery at a tertiary referral hospital. Sarcopenia was determined from measurement of the cross-sectional area of skeletal muscles at the level of the third lumbar vertebra on pretreatment images of whole body 18 F-fluorodeoxyglucose positron emission tomography/computed tomography. Primary outcomes were early complications and overall survival. Factors of early complications and readmission were identified using binary logistic regression analyses, and factors of overall survival and disease-free survival were identified using univariate and multivariate Cox proportional hazards regression analyses., Results: Pretreatment sarcopenia were found in 64 (33.7%) patients. In multivariate analysis, sarcopenia and N classification were significantly associated with early complications, while sarcopenia and T classification were associated with readmission. Independent factors of overall survival outcomes were age, sarcopenia, and extranodal extension (all P < .005). Sarcopenia was also an independent factor predictive of disease-free survival outcome (P < .001). Sarcopenia was associated with a 3.2-fold increase in the early complication rate and 4.5-fold increase in mortality in older adult surgical patients with HNSCC., Conclusion: Sarcopenia may predict early complications and survival after curative surgery in older adult patients with HNSCC., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Huntington's disease (HD) is caused by a mutant huntingtin (mHtt) protein that contains abnormally extended polyglutamine (polyQ) repeats. The process of autophagy has been implicated in clearing mHtt aggregates, and microRNAs (miRNAs) have been reported as new players to regulate autophagy. However, the autophagy-associated target molecule of let7b miRNA remains unclear in HD. The present study showed that extended polyQ in mouse striatal neurons increased lysosomal membrane-associated protein 2A (LAMP2A) levels and influenced the inflammatory conditions, and these augmented levels correlated to the let7b miRNA expression level. The upregulated let7b increased LAMP2A and reduced the extended polyQ in mouse striatal cells. The let7b level was highly expressed in the striatum of pre-onset HD mice, whereas it was significantly reduced in the post-onset HD striatum. Considering the level changing pattern of let7b, LAMP2A protein levels were increased in the striatum of pre-onset HD mice, but decreased in the striatum of post-onset HD mice. These results suggest that LAMP2A related to chaperone-mediated autophagy (CMA) capacity might play an important role in HD symptom onset and progression., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: Pre- and post-treatment 18 F-FDG PET/CT may have a prognostic role in human cancers. 18 F-FDG PET/CT after primary surgery for head and neck cancer might also predict survival. Therefore, we evaluated the prognostic value of post-treatment 18 F-FDG PET/CT in primary surgical patients with advanced-stage head and neck squamous cell carcinoma (HNSCC)., Materials and Methods: This prospective study involved 225 patients with previously untreated advanced-stage HNSCC who underwent primary surgery with or without postoperative radiotherapy or chemoradiotherapy. The patients also had 18 F-FDG PET/CT scanning at a median 6 months after surgery. Post-treatment 18 F-FDG PET/CT was considered positive, based on interpretation by experienced nuclear medicine physicians with integrating clinical information. Positive and negative predictive values (PPV and NPV) for positive 18 F-FDG PET/CT in association with recurrence were calculated. Predictors for positive post-treatment 18 F-FDG PET/CT were evaluated using binary logistic regression. Survival analysis was performed using Cox proportional hazard regression analysis., Results: PPV and NPV for post-treatment PET/CT for overall recurrence were 75.8% and 98.7%, respectively. A positive post-treatment PET/CT was an independent predictive factor for overall and disease-free survival (both P < 0.001). Five-year overall survival rates for patients with positive and negative PET/CT were 48.1% and 92.3%, respectively. Corresponding 5-year disease-free survival rates were 22.5% and 82.4%, respectively. Perineural invasion, positive resection margin, positive pathological node, and extranodal extension were the independent predictors of positive 18 F-FDG PET/CT (all P < 0.05)., Conclusions: Post-treatment 18 F-FDG PET/CT predicts survival and recurrence in patients undergoing curative surgery for advanced-stage HNSCC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: Soft tissue sarcomas of the head and neck (HNSTS) show various histological types and clinical behaviour. Recently, the 8th edition of the American Joint Committee on Cancer (AJCC) proposed a staging system for HNSTS independent of other body soft tissue sarcomas, which requires validation. Therefore, we evaluated the prognostic factors for the survival of HNSTS patients through a comparison between previous and current AJCC staging systems., Materials and Methods: This study involved 135 consecutive HNSTS patients who underwent primary surgery, chemoradiotherapy or chemotherapy. Patients were grouped into staged (S) and not staged (NS) cancer according to the AJCC 8th edition staging. Cox proportional-hazard regression analyses were used to identify factors associated with overall survival (OS), and progression-free survival (PFS) in all, S or NS patients., Results: Median follow-up period was 75 months and the 5-year OS and PFS rates of all patients were 67.8% and 53.4%, respectively, which was similar between S and NS groups. Age, tumour size and grade, overall stage (7th edition) and resection margin were the significant prognostic factors for OS and PFS in all patients and NS group (all P < 0.05), whereas positive resection margin was the only significant factor for OS and PFS in the S group (P < 0.001). While OS was poorly discriminated among different 8th edition T-categories, different 7th edition showed good discrimination among overall stages in all patients and the NS group., Conclusion: The revised staging system may not provide an improved risk stratification for survival of HNSTS patients., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Neutrophil-to-lymphocyte ratio (NLR), may predict treatment response and outcomes in some human malignancies. However, NLR has rarely been examined in older patients with head and neck squamous cell carcinoma (HNSCC). This study evaluated factors, including pre-treatment evaluation tests, predictive of mortality in older patients with HNSCC., Methods: This study prospectively enrolled 233 consecutive HNSCC patients aged 65 years or older. Pre-treatment evaluations included patient demographics, comorbidity, body weight loss, voice handicap index, dysphagia, Beck's depression inventory, comprehensive geriatric assessment, and circulating biomarkers. Cumulative incidence and cause-specific hazard functions were used to analyse the risk factors for overall mortality (OM), cancer mortality (CM), and non-cancer mortality (NCM)., Results: Multivariate analyses showed that age, performance scale, NLR, and nodal stage were independent predictors of OM and CM (all P < .05). Age, body weight loss, frailty, and NLR were independent predictors of NCM (all P < .05). Older age ≥ 75 years and NLR showed strong association with all OM, CM, and NCM (all P < .05). NLR >2.5 was related to a higher risk of OM (hazard ratio [HR] = 1.77, 95% confidence interval [CI]: 1.05-2.97, P = .031), CM (HR = 1.89, 95% CI: 1.09-3.29, P = .023), and NCM (HR = 6.29, 95% CI: 2.16-18.37, P = .001)., Conclusion: Cancer and non-cancer mortalities among older patients with HNSCC may be predicted by several clinical and haematological data. NLR might be used as a circulating prognostic marker for mortality in older patients with HNSCC., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Preoperative body weight and nutritional status are related to prognosis in patients with gastric cancer; however, the prognostic impact of postoperative in these variables is unclear. We aimed to investigate the association of preoperative/postoperative body mass index (BMI) and prognostic nutritional index (PNI) with prognosis in patients with gastric cancer., Materials and Methods: We retrospectively 1868 patients with stage II/III gastric cancer treated with gastrectomy between January 2006 and December 2010. We divided the populations into 3 groups according to BMI; underweight, normal, and overweight. Patients were divided into 3 groups according to BMI (underweight, normal-weight, overweight). PNI was classified into low and high (cutoff value; 49.7). The association of preoperative BMI/PNI and their changes (6 months postoperatively) with clinicopathologic characteristics were evaluated., Results: Preoperative underweight and low PNI were related to poor prognosis (log-rank p < 0.001 for both). There was a positive correlation between preoperative BMI and PNI (mean preoperative PNI: 51.13 [underweight], 53.37 [normal-weight], and 55.16 [overweight]; p < 0.001). Preoperative BMI and PNI were independent prognostic factors for disease-free survival along with age and TNM stage (p < 0.001 for both). BMI changes from normal-weight to underweight and from overweight to normal/underweight were related to poor prognosis (log-rank p = 0.021 and p = 0.013, respectively). PNI changes were related to prognosis in both the preoperative low and high PNI groups (p < 0.001 and p = 0.019, respectively)., Conclusion: Preoperative BMI and PNI and their postoperative changes are related to prognosis in patients with stage II/III gastric cancer. Careful nutritional intervention after gastrectomy can improve prognosis., Competing Interests: Declaration of competing interest None., (Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background/objective: The number of gastric cancer and type II diabetes mellitus is increasing in Korea. Metabolic surgery could be extended to gastric cancer patients with type II diabetes, especially those who are expected to achieve long-term survival. This study aimed to investigate change of diabetic status in patients undergoing long-limb Roux-en-Y bypass reconstruction compared with conventional Billroth II after curative gastrectomy. In total, 130 patients from five university hospital centers underwent long-limb Roux-en Y reconstruction after radical distal gastrectomy., Methods: In the long-limb group, the length of biliopancreatic limbs was more than 80 cm, and the length of the Roux limb was more than 80 cm. The control group comprised 96 patients who underwent conventional Billroth II reconstruction after distal gastrectomy. Follow-up data at three, six, nine, and 12 months were compared between the two groups., Results: Fasting blood sugar (FBS) and hemoglobin (Hb) A1c levels decreased more significantly in the long-limb Roux-en-Y group (FBS: 28.8 mg/dL; HbA1c: 0.72%). However, decreases in body mass index, albumin, and hemoglobin did not differ significantly between the two groups. Diabetes control significantly improved in the long-limb group. In multivariate analysis, long-limb bypass reconstruction was the significant factor for glycemic outcomes., Conclusion: Roux-en-Y bypass with increased length of limbs after gastrectomy shows a favorable glycemic control for gastric cancer patients with type II diabetes without nutritional deficit and anemia. To obtain future perspectives, large-scale prospective studies with long-term outcomes are needed., (Copyright © 2019. Published by Elsevier Taiwan LLC.)

Background: The challenging issues are to prevent anastomotic leakage and provide sufficient flap monitoring in circumferential hypopharyngeal reconstruction. In this study, a newly designed flag-shaped anterolateral thigh (ALT) free flap was used for circumferential hypopharyngeal reconstruction to address these issues., Methods: Eighteen ALT flaps were harvested for reconstruction of circumferential hypopharyngeal defects from 2013 to 2016. The harvested ALT flap was sutured into a cylinder shape, and a triangular extension of the flap was used for dead space obliteration and flap monitoring. All data regarding outcomes and complications including radiographic investigations were collected retrospectively., Results: The flap had a rectangular shape with dimensions of 29 cm × 8 cm (range, 25-31 cm × 6-10 cm). For each flap, 2-4 perforators were included (average, 2.6 perforators/flap). All flaps survived. One venous thrombosis was diagnosed early through the monitoring portion of the flap, and the flap was salvaged after thrombectomy with a vein graft. The mean follow-up period was 28.9 months (10.3). There was one case of definitive fistula (4%), which never healed because of early tumor recurrence. Three postoperative strictures were noted (21.4%)., Conclusions: For a complete circumferential hypopharyngeal defect, the flag-shaped ALT free flap design offers monitoring flap and dead space obliteration and prevents anastomotic leakage., (Copyright © 2019 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Introduction: Small ground-glass nodules (GGNs) or those with an indeterminate risk on low-dose computed tomography (LDCT) of the chest are recommended at 5-year follow-up, but the rationale for follow-up beyond 5 years is unclear., Methods: An observational study was conducted to investigate the natural course of GGNs that had been stable for 5 years by LDCT over 10 years. All eligible GGNs were detected during regular health checkups. Baseline characteristics were compared between GGNs with and without growth. Risk factors for GGN growth were evaluated., Results: A total of 208 GGNs were detected in 160 participants. GGN growth was identified in 27 (13.0%) GGNs during a follow-up of 136 months on LDCT scans. In approximately 95% of these GGNs, the initial size was less than 6 mm, with 3.2 mm of growth over 8.5 years. Biopsies were performed in 3 of 27 GGNs, revealing adenocarcinoma. In 8 of 27 cases, GGN growth preceded the development of a new solid component. In a multivariate analysis, bubble lucency (p = 0.001), a history of cancer other than lung cancer (p = 0.036), and development of a new solid component (p < 0.001) were significant risk factors for GGN growth., Conclusions: GGNs should not be ignored, even when smaller than 6 mm and stable for 5 years, especially when a new solid component appears during follow-up., (Copyright © 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Objectives: Diminished skeletal muscle mass (SMM) is a reliable marker of poor survival outcomes in patients with cancer. SMM or body composition is generally assessed at the third lumbar vertebra (L3) by abdominal computed tomography (CT) scans, not routinely evaluated in patients with head and neck squamous cell carcinoma (HNSCC). Therefore, we evaluated the effectiveness of head and neck CT images to assess SMM in patients with HNSCC for predicting their overall survival., Materials and Methods: SMM was assessed in 305 consecutive patients with stage III-IV HNSCC by measuring the cross-sectional area (CSA) at the third lumbar and cervical (C3) vertebrae levels. A formula for predicting the L3 SMM was established using linear regression analysis obtained from C3 CSA and other clinical factors. The actual SMM CSAs measured at L3 level and those obtained from the prediction model were compared using correlation analysis. The predictive power of our formula for estimating overall survival was compared using C-index., Results: Median SMM CSAs at the L3 and C3 levels were 174.5 cm 2 and 56.3 cm 2 , respectively, and were not strongly correlated (adjusted R 2  = 0.421). Prediction model 2 included the strongest predictive factors including sex, age, weight, and C3 SMM CSA, and significantly increased the L3 SMM correlation power (adjusted R 2  = 0.721). The C-index of the prediction model was 0.713 (95% confidence interval 0.692-0.747)., Conclusions: Head and neck CT imaging might be useful to estimate L3 SMM and predict overall survival in HNSCC patients., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objectives: Tumor multifocality or bilaterality is associated with increased risk of papillary thyroid carcinoma (PTC) recurrence. However, its prognostic value in clinical outcomes remains controversial. This study aimed to evaluate the association of multifocality or bilaterality with recurrence and survival after total thyroidectomy., Methods: This was a retrospective study of 2390 consecutive patients with pathologically confirmed PTC who underwent total thyroidectomy. Multifocality and bilaterality were decided based on the final pathology results, that is, if there were two or more tumor foci and bilateral location, respectively. Primary outcomes were recurrence-free survival (RFS). Cox proportional hazards regression analyses were used to assess the associations of multifocality, bilaterality, and other clinicopathological factors with RFS., Results: Multifocal and bilateral PTC were found in 892 (37.3%) and 593 (24.8%) patients, respectively. Multivariate analyses showed that multifocality, lymphovascular invasion, N category, and number of positive lymph node (>5) were significant independent variables predictive of RFS (all P < 0.05). Multifocality was associated with adjusted hazard ratios for RFS of 1.93 (95% confidence interval = 1.33-2.80; P = 0.001). In a subset analysis, the prognostic value of multifocality was found to be significant in those patients with PTC > 1 cm, but not in papillary thyroid microcarcinoma., Conclusions: Tumor multifocality is an independent risk factor of PTC recurrence after total thyroidectomy. This indicate a more progressive state of disease, being included in risk stratification., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objectives: Current guidelines recommend chest computed tomography (CT) with locoregional CT/magnetic resonance imaging for patients with head and neck squamous cell carcinoma (HNSCC), and 18 F-fluorodeoxyglucose (FDG) positron-emission tomography (PET)/CT is suggested for stage III-IV patients. However, whole body screening with 18 F-FDG PET/CT may provide better detection of distant metastases and synchronous cancer than conventional imaging. We evaluated the utility of 18 F-FDG PET/CT in detecting distant metastasis and synchronous cancer., Methods: This prospective study enrolled 740 consecutive patients with previously untreated HNSCC diagnosed between September 2010 and December 2015. Synchronous cancer was histologically confirmed and distant metastases were confirmed by biopsy or serial imaging follow-ups. McNemar test was used to compare the true-positive detection rates of chest radiography (CXR) + head and neck CT (hnCT) (A) versus 18 F-FDG PET/CT (C) and chest CT + hnCT (B) versus 18 F-FDG PET/CT., Results: Distant metastases and synchronous cancer were found in 23 (3.1%) and 55 (7.4%) patients, respectively. A, B, and C detected distant metastases in 10 (1.3%), 19 (2.6%), and 21 (2.8%) patients, respectively. The absolute differences were 1.5% (A versus C, P = 0.003) and 0.3% (B versus C, P = 0.687). A, B, and C detected synchronous cancer in 15 (2.0%), 22 (2.9%), and 36 (4.9%) patients, respectively. The absolute differences were 2.8% (A versus C, P < 0.001) and 1.4% (B versus C, P = 0.013)., Conclusions: 18 F-FDG PET/CT detected more distant metastases and synchronous cancer than CXR + hnCT and more synchronous cancer than chest CT + hnCT., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objectives: The recently published 8th edition of the American Joint Committee on Cancer (AJCC) tumour-node-metastasis (TNM) staging system was significantly updated following the thyroid cancer-related guidelines to provide better predictability of survival but not focus on recurrence. Therefore, we compared the predictive values of the 7th and 8th editions of the AJCC staging systems for recurrence-free survival (RFS) and overall survival (OS) after thyroidectomy for papillary thyroid carcinoma (PTC)., Methods: This retrospective study included 2930 patients who underwent thyroidectomy and neck dissection for previously untreated PTC between 2006 and 2014. TNM stage was defined according to 7th and 8th editions. Univariate and multivariate Cox proportional hazard regression analyses were used to identify associations between variables and RFS or OS. Multivariate models for the AJCC TNM stages were adjusted for clinical and pathological variables., Results: A significant number of patients classified as T3 with overall TNM stages II-IV in the AJCC 7th edition were down-staged in the 8th edition. Unadjusted T classification and overall TNM staging in both the 7th and 8th editions were significantly associated with RFS and OS rates (P < 0.001). After adjustment for clinicopathological factors, the overall TNM stage according to the AJCC 8th edition, but not the 7th edition, remained significantly associated with RFS and OS (P < 0.05), with better predictability of recurrence and survival, in patients with PTC., Conclusions: The 8th edition AJCC staging system down-staged a large proportion of PTC patients, resulting in better predictability of recurrence and survival compared to the previous staging system., Condensed Abstract: This study compared the abilities of the 7th and 8th edition AJCC staging systems to predict recurrence and overall survival in 2930 patients with papillary thyroid carcinoma. The updated guidelines down-staged a large proportion of patients, resulting in better prediction of recurrence and survival than the previous staging system., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: A decreased flap volume can be an obstacle to proper phonation and swallowing. In this study we verified the proportion of volume decrease using 3D reconstructed images and identified the contributors to flap volume loss., Methods: We retrospectively analyzed all patients who underwent radical excision of tongue cancer and reconstructive surgery in our institution from January 2003 to October 2016. Segmentation of the DICOM images, 3D rendering of the neotongue flap, and analysis of the reconstructed images were performed using SPlanner V1 ® software., Results: The first postoperative imaging work-up was performed within an average of 22 days (T1). The last follow-up images were taken at an average of 6.25 months (T2). The mean flap volume at T2 was reduced to 82.99 per cent compared with T1, and flap height was reduced to 91.85 per cent, giving mean volume and height decreases of 17.01 per cent and 8.15 per cent, respectively. Neither the volume/height difference between T1 and T2 nor the flap volume/height discrepancy compared with the preoperative tongue affected speech or feeding function. The difference between the flap and preoperative tongue volumes was significantly related to the presence of complications (p = 0.0153). Initial flap volume was significantly related to the flap volume reduction (p = 0.0159)., Conclusions: The mean flap volume reduction is the only factor significantly related to initial flap volume. Our realistic 3D reconstructed image and novel software enables us to more precisely predict the flap volume of the postoperative state and preoperatively evaluate the required flap size for covering defects., (Copyright © 2018 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Objective: The aim of this study was to investigate the prevalence and characteristics of nodular lesions in the anterior mediastinum that had been found incidentally on screening chest computed tomography (CT) in asymptomatic subjects., Methods: We included 56,358 consecutive participants (mean age 52.4 ± 10.5 years; male-female ratio 35,306:21,052) who underwent a baseline low-dose chest CT scan as part of a health checkup from 2006 through 2013. After the presence of anterior mediastinal nodular lesion had been confirmed, their CT findings, confirmatory diagnosis, and interval CT scan were reviewed. The standardized prevalence ratio for thymic epithelial tumor was calculated on the basis of the Republic of Korea cancer statistics for 2014., Results: Of the 56,358 participants, 413 (0.73%) had lesions (95% confidence interval: 0.66-0.80%); the prevalence increased with age (p <0.001) and a history of malignancy (p = 0.005). Of the lesions, 85.2% were smaller than 2 cm, 61.3% were round, and 80.2% had CT attenuation higher than 20 Hounsfield units. Among 51 proven cases, 39 lesions (76.9%) were benign and 12 (23.1%) were malignant. The standardized prevalence ratio for thymic epithelial tumor was 2.04 (95% confidence interval: 1.01-3.42). Of 11 resected thymic epithelial tumors, five were carcinomas, 10 were stage I or II, and all were completely resected without recurrence. Of the 237 unconfirmed cases with a follow-up CT scan, 82.2% were stable, 8.9% had increased, and the other 8.9% had decreased., Conclusions: The prevalence of incidental nodular lesion was 0.73%. Most lesions had CT features that were indistinguishable from thymic epithelial tumors, but a considerable portion of the lesions were suspected to be benign. Incidental thymic epithelial tumors were more prevalent than clinically detected tumors, were early-stage cancer, and showed favorable outcomes., (Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Objectives: Adenoid cystic carcinoma (AdCC) in the salivary gland shows a high rate of distant metastasis, which is related to the resulting poor prognosis. We therefore examined the role of pretreatment 18 F-FDG PET/CT for prediction of distant metastasis, recurrence/progression, and survival in AdCC., Methods: This study included 52 patients who underwent pretreatment 18 F-FDG PET/CT scanning and subsequent treatments for AdCC. Maximum, mean, and peak standardized uptake value (SUV max , SUV mean , and SUV peak ), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured on 18 F-FDG PET/CT. Univariate and multivariate Cox proportional hazards regression analyses were used to identify associations between the quantitative measurements of 18 F-FDG PET, and progression-free survival (PFS), distant metastasis-free survival (DMFS), and disease-specific survival (DSS)., Results: Distant metastases were found in 20 (39%) patients: 6 (12%) at initial diagnosis and 14 (27%) during the median follow-up of 72 months after treatment. Univariate analyses showed that all the 18 F-FDG PET parameters of SUV max , SUV mean , SUV peak , MTV, and TLG were significantly associated with overall PFS, DMFS, and OS (all P < .05). After controlling for clinicopathological variables, SUV max remained an independent factor predictive of PFS (P = .001), while MTV and TLG were independent predictors of DMFS (P = .009) and DSS (P = .017). Patients with MTV > 14.8 mL showed a 5.9-fold higher risk of distant metastasis and a 4.2-fold higher risk of disease-specific death than those with a lower MTV., Conclusions: Quantitative measurements using 18 F-FDG PET/CT are useful for predicting tumor progression, distant metastasis, and survival in patients with AdCC., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

TopBP1 has been identified as a direct activator of ATR and interacts with the Nbs1 subunit of the Mre11-Rad50-Nbs1 (MRN) complex in egg extracts in a checkpoint-regulated manner. In this study, we show that Mdc1 associates with both TopBP1 and Nbs1 in egg extracts and human cells. We cloned a cDNA encoding the full-length version of Xenopus Mdc1. The association between Mdc1 and TopBP1 involves the first pair of BRCT repeats in TopBP1. The N-terminal region (161-230) of Mdc1 is required for this binding. The interaction between Mdc1 and Nbs1 involves the two tandem BRCT repeats of Nbs1. Functional studies with mutated forms of Mdc1, TopBP1, and Nbs1 indicate that the BRCT-dependent association of these proteins is critical for a normal checkpoint response to DSBs. TopBP1 cannot interact with Nbs1 in Mdc1-depleted egg extracts, suggesting that Mdc1 connects TopBP1 and Nbs1 together. These findings suggest that Mdc1 is a crucial mediator of the DNA damage checkpoint response., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Human papillomavirus (HPV) (+) tonsil squamous cell carcinoma (TSCC) responds well to concurrent chemoradiation therapy (CCRT) and demonstrates a favorable prognosis. However, cases of HPV (+) TSCC-related death remain unresolved. We evaluated the distribution and prognostic value of inflammatory cells in HPV (+) TSCC., Methods: We reviewed the medical records of 53 patients who were diagnosed with TSCC. HPV (+) TSCC was confirmed using HPV DNA PCR and immunohistochemical p16 overexpression. The numbers of CD4 (+), CD8 (+), and CD68 (+) stained cells were used to evaluate peritumoral lymphocyte infiltration. Patients were divided into two groups according to the mean numbers of stained cells and the mean ratios of each cell type., Results: HPV (+) was noted in 39 patients. During the follow-up period, 27 patients had no evidence of disease, 2 patients showed disease, and 10 patients died of disease. In this group, advanced T and N stages were not related to overall or disease-specific survival outcomes. The overall survival rate was affected by a high CD68 (+) (HR=19.8; P=0.040) and low CD8/CD4 ratio (HR=7.7, P=0.025). The disease-specific survival rate was affected by a high number of CD68 (+) cells (HR=15.2; P=0.03) and low CD8 (+)/CD4 (+) ratio (HR=3.3; P=0.04)., Conclusions: The number of CD68 (+) cells and the distribution of cytotoxic or immunosuppressive T lymphocytes could be determining factors for CCRT outcomes in HPV (+) TSCC patients., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: Colorectal adenoma and coronary atherosclerosis have similar risk factors. The aim of this study was to investigate the association between colorectal adenoma and coronary artery calcification (CAC), which is used as a surrogate marker for coronary atherosclerosis., Methods: This is a cross-sectional study of 398 Koreans (290 males, mean age of 56.8 ± 8.1 years) who underwent CAC scoring by multi-slice computed tomography and colonoscopy on the same day as the screening examination. The CAC scores were divided into the following three categories according to severity: absent (CAC score = 0), mild (0 < CAC score ≤ 100), and moderate-to-severe CAC (CAC score > 100)., Results: Colorectal adenoma was detected in 149 (37.4%) subjects and was significantly associated with a CAC score of >0 (OR = 1.66, 95% CI = 1.05-2.64, P = 0.032), including both mild (OR = 1.80, 95% CI = 1.06-3.03, P = 0.029) and moderate-to-severe CAC (OR = 1.95, 95% CI = 1.05-3.63, P = 0.035), in multivariate analysis after adjusting for age, gender and other risk factors. The proportion of subjects with colorectal adenoma and advanced adenoma progressively increased with increasing CAC score (colorectal adenoma 28.9%-54.1%, P for trend < 0.001; advanced adenoma 7.0%-16.4%, P for trend = 0.026)., Conclusion: Colorectal adenoma is related to coronary artery calcification independent of traditional risk factors for asymptomatic Koreans. The prevalence of advanced adenoma is more common in individuals with severe coronary atherosclerosis., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Purpose: We examined the effect of extranodal extension (ENE) and its thickness (ENET) of metastatic lymph node (LN) on the disease course of patients with head and neck squamous cell carcinoma., Methods: Data from 438 patients who were initially treated surgically at our center was retrospectively analyzed. ENE presence and ENET were examined in metastatic LN from each patient. Clinicopathologic characteristics, recurrence, and survival were then compared., Results: Of 438 patients, 219 (50%) showed positive nodal status, and ENE was identified in 84 (19.6%). Forty-five of 219 (20.5%) node-positive patients were classified with ENET ≥ 2 mm, which was associated with an increase in both the size and number of positive LN, bilateral cervical involvement, and a higher LN ratio. ENE-positive patients had a higher risk of recurrence and a lower overall survival rate; however, multivariate analysis failed to identify a significant difference in cancer-specific survival (CSS) between those with and those without ENE. On the contrary, ENET ≥ 2 mm was significantly associated with a poor CSS, even in multivariate analysis., Conclusion: ENET ≥ 2 mm might be a complementary prognostic marker in CSS estimation for ENE positivity., (Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Study Objective: To investigate whether the type of anesthetic agent administered affects the antitussive effect of remifentanil., Design: Prospective randomized study., Setting: Operating room of a university hospital., Patients: 78 ASA physical status 1 and 2 women, aged 20 to 65 years, who were scheduled to undergo a thyroidectomy., Interventions: Patients were randomly assigned to three groups to receive anesthesia with propofol (Group P), sevoflurane (Group S), or desflurane (Group D). The main anesthetics were titrated to maintain a target Bispectral Index for hypnosis of 40 to 60. Remifentanil was administered via effect-site target-controlled infusion (TCI). To determine the effective remifentanil effect-site concentration (Ce) to suppress coughing in each group, the up-and-down sequential allocation design was used., Measurements: The half maximal effective concentration (EC50) values of remifentanil for preventing coughing in the groups were estimated using isotonic regression and compared among the groups., Main Results: The EC50 of remifentanil for cough suppression in Group P [1.60 ng/mL (98.3% CI, 0.92-1.75 ng/mL)] was statistically lower than in Group D [1.96 ng/mL (98.3% CI, 1.81-2.50 ng/mL)]. The EC50 in Group S was 1.75 ng/mL (98.3% CI, 1.39-2.13 ng/mL), which was higher than in Group P and lower than in Group D, but did not differ significantly from either group., Conclusions: Remifentanil administration for cough suppression during emergence should be customized to the anesthetic agent., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: This study examined prognostic factors in patients with head and neck squamous cell carcinoma with advanced neck disease., Study Design: The records of 191 patients with previously untreated head and neck squamous cell carcinoma and metastatic cervical lymph node (LN) >6 cm (cN, n = 70) and 3.01 to 6 cm (control, n = 121) in the greatest dimension were reviewed. Univariate and multivariate analyses were used to identify factors associated with disease-free survival (DFS) and locoregional control (LRC)., Results: In the cN3 group, independent variables for DFS were age, active drinking, LN size, and extranodal extension (P < .05), and that for LRC was age (P = .025). In the control group, independent variables for DFS were tumor location and differentiation and LN bilaterality (P < .05), and that for LRC was LN bilaterality (P = .011)., Conclusions: The survival of cN3 patients is affected by host and nodal characteristics including age, drinking, nodal size, and extranodal extension., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Inverse correlations of high serum bilirubin with metabolic and cardiovascular disease have been suggested. However, anti-atherogenic effects of bilirubin have not been well-established in terms of the presence of plaques and stenosis identified in coronary computed tomography (CT)., Methods: A cross-sectional study was conducted on 2862 men who were free of cardiovascular disease and underwent coronary CT as part of a routine medical screening examination. Coronary stenotic lesions were considered to be incidences of coronary atherosclerosis, and stenosis was classified as stenosis <50% or ≥50%, according to degree of stenosis., Results: The prevalences of coronary atherosclerosis and stenosis ≥50% in subjects with elevated bilirubin levels (>1.2 mg/dL) were lower than those in subjects with normal bilirubin levels (≤1.2 mg/dL) (19.9% vs. 27.9%, p < 0.001, 8.5% vs. 10.3%, p = 0.044). Bilirubin was inversely associated with total plaques (odds ratio [OR] 0.59, 95% confidence interval [CI] 0.48-0.73 in the 4th quartile vs. 1st quartile) and calcified plaques (OR 0.60, 95% CI 0.49-0.75) in univariate analysis. After adjusting for traditional risk factors, it was found that coronary atherosclerosis (OR 0.73, 95% CI 0.56-0.94 in the 4th quartile vs. 1st quartile) and calcified plaque (OR 0.66, 95% CI 0.53-0.84) were inversely associated with the bilirubin grade in a dose-dependent manner., Conclusions: The serum bilirubin level was inversely associated with coronary atherosclerosis and calcified plaques in a dose-dependent manner. These results suggested that serum bilirubin could be used as a protective biomarker of coronary artery disease., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objectives: Central compartment lymph node metastasis (CLNM) in patients with laryngeal, hypopharyngeal, or cervical esophageal squamous cell carcinoma is associated with unfavorable clinical outcomes, but cannot be reliably detected using computed tomography (CT)/magnetic resonance imaging (MRI). Therefore, we assessed the clinical utility of using (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT to identify CLNM in these patients., Patients and Methods: A total of 62 patients were preoperatively evaluated using (18)F-FDG PET/CT and CT/MRI. Histopathologic analysis of the dissected neck tissues was used as the gold standard for assessing these imaging techniques. The diagnostic value of (18)F-FDG PET/CT for detecting CLNM was calculated and compared with CT/MRI. Univariate and multivariate analyses were utilized to determine the factors predictive of CLNM., Results: Of the 62 patients in the study cohort, 12 (19%) had CLNM. Compared with histology, both (18)F-FDG PET/CT and CT/MRI demonstrated low sensitivity for detecting CLNM (58% vs 42%, respectively, P = 0.625). The specificities of (18)F-FDG PET/CT and CT/MRI for the detection of CLNM were 88% and 90%, respectively (P = 1.000). Univariate and multivariate analyses showed that clinical metastasis to any cervical lymph node was significantly associated with CLNM (P = 0.018)., Conclusions: Neither (18)F-FDG PET/CT nor CT/MRI is a sensitive diagnostic imaging modality for detecting CLNM. Routine elective central compartment dissection or radiotherapy should be advocated for the treatment of these patients., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objectives: Human papillomavirus (HPV), a causative agent of oropharyngeal squamous cell carcinoma (SCC), may be detected in metastatic cervical lymph nodes (MCNs). We investigated whether HPV and p16 expression in MCNs can help identify oropharyngeal primaries in patients with cervical lymph node metastases from an unknown primary tumor (CUP) and predict their survival outcomes., Materials and Methods: SCC MCNs of 58 patients with CUP were assayed for HPV by in situ hybridization and for p16 and p53 expression by immunohistochemistry. The presence of HPV and p16 in MCN was correlated with oropharyngeal tumor location and prognosis., Results: Oropharyngeal primaries were found in 20 patients. The sensitivity and negative predictive value (NPV) of HPV for oropharyngeal localization were 90.0% and 92.6%, respectively, and the sensitivity and NPV of p16 were 80.0% and 86.2%, respectively. Multivariate analyses showed that the location of the largest MCN (P=0.035) and HPV (P=0.004) were independent predictors of oropharyngeal tumors. Multivariate analyses showed that p16 expression was an independent predictor of disease-free survival (P=0.030; hazard ratio (HR)=0.286; 95% CI, 0.092-0.887) and that p53 expression (P=0.017; HR=3.154, 95% CI=1.288-8.103) and extracapsular extension of MCN (P=0.010; HR=3.924, 95% CI=1.387-11.097) were independent predictors of overall survival., Conclusion: Detection of HPV and p16 may help identify hidden oropharyngeal primaries in CUP patients and predict their survival outcomes., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objectives: Significant laryngeal edema (SLE) after radiotherapy for squamous cell carcinoma of the larynx and hypopharynx may be associated with upper airway obstruction or tumor recurrence. We assessed the risk factors predictive of SLE and those differentiating tumor recurrence from SLE., Patients and Methods: We evaluated 127 patients with laryngohypopharyngeal squamous cell carcinomas who were primarily treated with radiotherapy with/without chemotherapy, had no previous major head and neck surgery, and underwent laryngoscopic examinations after radiotherapy. SLE was defined as RTOG grades ≥ 2 and patient characteristics and imaging, treatment and survival results were compared in patients with and without SLE., Results: Of the 127 patients, 56 (44%) had SLE. Univariate analyses showed that tumor location, T and N classifications, overall stage, pathologic differentiation, and chemotherapy were significantly predictive of SLE (P<0.05). Multivariate analysis revealed that T classification remained an independent predictor of SLE (T1 vs. T2-4; odds ratio=5.070, 95% confidence interval=1.999-12.857; P=0.001). Twenty-seven (21%) patients had tumor recurrences, diagnosed by PET/CT (sensitivity 88%; specificity 92%) and CT (sensitivity 68%; specificity 88%). Twenty-seven patients with severe SLE were treated but only 9 (33%) had improvement. Tumor recurrence rate was higher (39% vs. 7%, P<0.001) and 3-year overall survival rate lower (54% vs. 87%, P<0.001) in patients with than without SLE., Conclusion: Patients with T2-4 laryngohypopharyngeal cancers are at higher risk of SLE development and tumor recurrence after radiotherapy that can be properly detected by (18)F-FDG PET/CT., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

We assessed the risk factors associated with surgical site infection (SSI) in 697 patients who underwent major oncological surgery for head-and-neck cancer (HNC). SSIs within 30days were classified as incision, space, or leakage/fistula. Preoperative and operative risk factors for SSIs were assessed by univariate and multivariate analyses. Of these 697 patients, 128 (18.4%) had SSIs. Univariate analysis showed that SSIs were associated with tumor location, advanced tumor stage, smoking and alcohol habits, diabetes, history of prior radiotherapy or chemotherapy, anemia, hypoalbuminemia, mandible cutting, flap reconstruction, tracheotomy, clean-contaminated wounds, blood transfusion, and operation times. Multivariate analysis showed that independent risk factors for developing SSIs were oral cavity cancer (odds ratio [OR]: 6.06, 95% confidence interval [CI]: 1.209-30.378), history of prior radiotherapy (OR: 2.85, 95% CI: 1.172-6.931), tracheotomy (OR: 9.757, 95% CI: 2.609-36.491), and clean-contaminated wounds (OR: 13.953, 95% CI: 2.231-87.275). In contrast, thyroid malignancy was an independent predictor of not developing SSI (OR: 0.152, 95% CI: 0.035-0.658). High-risk patients of SSIs after major HNC surgery are predicted. Preventive measures or close monitoring in these patients may be required to reduce the likelihood of postoperative SSIs. Our data may help identify and properly manage high-risk patients., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

We evaluated the clinical utility of combined [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET) and computed tomography (CT), as well as CT and magnetic resonance imaging (MRI) in identifying nodal metastases in the contralateral neck in patients with head and neck squamous cell carcinoma (HNSCC). A total of 114 patients were preoperatively evaluated with PET/CT and CT/MRI. Histopathologic analysis from bilateral neck dissection tissues was used as the gold standard in assessing these imaging techniques. Of the 114 patients, 63 (55%) had neck metastases and 26 (23%) had contralateral neck metastases. On a per-level basis, FDG PET/CT was significantly more sensitive and accurate than CT/MRI in the ipsilateral (88% vs. 70%, P<0.01 and 93% vs. 89%, P<0.01, respectively) and contralateral (52% vs. 36%, P<0.01 and 91% vs. 90%, P=0.039, respectively) neck. PET/CT and CT/MRI were less sensitive in detecting contralateral than ipsilateral neck metastases due to the lower incidence of metastases and smaller nodes on the contralateral side. Combined PET/CT is superior to CT/MRI in detecting metastatic neck nodes in HNSCC patients. However, PET/CT may not abrogate the need for contralateral neck surgery or radiotherapy in these patients., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Study Objective: To compare the effects of volume-controlled ventilation (VCV) and pressure-controlled ventilation (PCV) on respiratory mechanics and hemodynamics in steep Trendelenburg position., Design: Prospective, randomized clinical trial., Setting: University hospital., Patients: 34 ASA physical status 1 and 2 patients undergoing RLRP., Interventions: Patients were randomly allocated to either the VCV (n = 17) or the PCV group (n = 17). After induction of anesthesia, each patient's lungs were ventilated in constant-flow VCV mode with 50% O(2) and tidal volume of 8 mL/kg; a pulmonary artery catheter was then inserted. After establishment of 30° Trendelenburg position and pneumoperitoneum, VCV mode was switched to PCV mode in the PCV group., Measurements: Respiratory and hemodynamic variables were measured at baseline supine position (T1), post-Trendelenburg and pneumoperitoneum 60 minutes (T2) and 120 minutes (T3), and return to baseline after skin closure (T4)., Main Results: The PCV group had lower peak airway pressure (AP(peak)) and greater dynamic compliance (C(dyn)) than the VCV group at T2 and T3 (P < 0.05). However, no other variables differed between the groups. Pulmonary arterial pressure and central venous pressure increased at T2 and T3 (P < 0.05). Cardiac output and right ventricular ejection fraction were unchanged in both groups., Conclusions: PCV offered greater C(dyn) and lower AP(peak) than VCV, but no advantages over VCV in respiratory mechanics or hemodynamics., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: Cerebral white matter lesions (WMLs) are radiologic markers of small vessel disease in brain, and inflammatory processes were related to WMLs. We propose to determine if elevated leukocyte count was associated with a higher risk of WMLs., Methods: 1586 asymptomatic subjects who visited our hospital for a routine health check-up were enrolled. Leukocyte counts were measured and the presence of moderate to severe WMLs was determined by brain MRI., Results: Thirty (1.9%) had moderate to severe WMLs, and a significant greater proportion (4.1%) of subjects in the highest leukocyte count quartile had moderate to severe WMLs. After adjusting by C-reactive protein, aspirin use and cardiovascular risk factors, the highest quartile of leukocyte count (≥6.7×10⁹/L) was significantly associated with moderate to severe WMLs compared with the lowest quartile [adjusted odds ratio, 4.03; 95% confidence interval, 1.05-15.5]., Conclusion: The authors report for the first time that an elevated leukocyte count is independently associated with moderate to severe WMLs., (Copyright © 2010. Published by Elsevier B.V.)

The most important therapeutic tool in brain metastasis is radiation therapy. However, resistance to radiation is a possible cause of recurrence or treatment failure. Recently, signal pathways about DNA damage checkpoints after irradiation have been noticed. We investigated the radiosensitivity can be enhanced with treatment of Chk1 inhibitor, AZD7762 in lung cancer cell lines and xenograft models of lung cancer brain metastasis. Clonogenic survival assays showed enhancement of radiosensitivity with AZD7762 after irradiation of various doses. AZD7762 increased ATR/ATM-mediated Chk1 phosphorylation and stabilized Cdc25A, suppressed cyclin A expression in lung cancer cell lines. In xenograft models of lung cancer (PC14PE6) brain metastasis, AZD7762 significantly prolonged the median survival time in response to radiation. Depletion of Chk1 using shRNA also showed an enhancement of sensitivity to radiation in PC14PE6 cells. The results of this study support that Chk1 can be a good target for enhancement of radiosensitivity., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Targeting hypoxia-inducible factor-1 (HIF-1) active cells in tumors may be an excellent strategy to improve the outcome of radiation therapy. On the basis of the reported role of YC-1 as a HIF-1 inhibitor with anti-cancer activity, we tested the therapeutic efficacy of YC-1 against radioresistance in vitro. The AMC-HN3 cancer cell line, developed from squamous cell carcinoma of the larynx, was cultured under hypoxic conditions or in the presence of cobalt chloride. Both treatments induced nuclear accumulation of HIF-1alpha protein. Cells cultured under normoxic or hypoxic conditions with and without YC-1 treatment were irradiated and analyzed using flow cytometry and clonogenic assays. In the absence of YC-1 treatment, irradiation induced a greater cytotoxic effect in normoxic cells than in cobalt-treated cells. Treatment of cobalt-treated cells with YC-1 effectively inhibited HIF-1alpha expression, and enhanced the sensitivity of cells to radiation, decreasing the surviving fraction to that of normoxic cells. Flow cytometry confirmed these results, showing that the sub-G1 fraction was increased in YC-1-treated hypoxic cells after irradiation. Our results suggest that YC-1 treatment may be an effective therapeutic strategy for overcoming the radioresistance of HIF-1alpha-expressing, hypoxic cancer cells.

The purpose of this study was to evaluate the effect of neuromuscular electrical stimulation (NMES) in patients suffering from dysphagia following treatment for head and neck cancer. In a prospective, double blinded, randomized case control study between January 2006 and December 2007, 14 patients were randomized to 30min of NMES and 30min of traditional swallowing training for 5 days per week for 2 weeks (experimental group), and 12 patients were randomized to sham stimulation plus traditional swallowing training (control group). Effects were assessed using the clinical dysphagia scale (CDS), the functional dysphagia scale (FDS), the American speech-language-hearing association national outcome measurement system (ASHA NOMS) and the M.D. Anderson dysphagia inventory (MADI). Pretreatment evaluation showed no significant differences between the two groups for all parameters. Average changes of FDS score were 11.4+/-8.1 for the experimental group and 3.3+/-14.0 for the control group (P=0.039). CDS, ASHA NOMS and MADI showed some difference with treatment, but the changes were not significant (P>0.05). NMES combined with traditional swallowing training is superior to traditional swallowing training alone in patients suffering from dysphagia following treatment for head and neck cancer.

(18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) has been reported to identify primary tumors in patients with cervical metastases from cancer of unknown primary (CUP). However, few reports have assessed the use of combined FDG-PET/computed tomography (CT) in this setting. We therefore examined the utility of combined FDG-PET/CT in the detection of primary tumors and unrecognized metastases in these patients. Patients with previously untreated CUPs underwent head and neck CT and whole-body FDG-PET/CT before panendoscopy and guided biopsy. The diagnostic accuracy of CT and FDG-PET/CT in detecting primary tumors and cervical metastases was compared with that of histopathology. The ability of FDG-PET/CT to detect distant metastases was also tested. Of the 44 eligible patients, 16 had occult primary tumors in the head and neck. FDG-PET/CT was significantly more sensitive than CT for detecting primary tumors (87.5% vs. 43.7%, P=.016), but their specificity did not differ (82.1% vs. 89.3%, P=.500). Thirty-four of 44 patients underwent neck dissection; 67 of 182 dissected cervical levels had metastatic nodal diseases. On a level-by-level basis, FDG-PET/CT was significantly more sensitive than CT (94.0% vs. 71.6%, P<.001), but the two methods were equally specific (94.8% vs. 96.5%). FDG-PET/CT correctly detected distant metastases in 6 of 6 patients. Combined FDG-PET/CT is a useful screening method for primary tumor detection, accurate nodal staging, and distant metastases in patients with CUPs.

Tumor hypoxia is associated with poorer outcome in patients with head and neck carcinomas, but little is known about hypoxia biomarkers in oral tongue cancer. We evaluated whether hypoxia biomarkers and clinicopathologic variables were prognostic predictors in patients with T2-staged squamous cell carcinoma (SCC) of the oral tongue. Tissue microarrays were constructed from formalin-fixed tumor blocks of 43 patients with T2-staged tongue SCCs treated by surgical resection and neck dissection. Tissue samples were stained with monoclonal antibodies to hypoxia-inducible factor (HIF)-1alpha, HIF-2alpha, carbonic anhydrase (CA)-9, glucose transporter (GLUT)-1, and erythropoietin receptor (EPOR). Locoregional control and survival rates were calculated by the Kaplan-Meier method, and prognostic factors were calculated from uni- and multivariate analyses. Tumor thickness was correlated with expression of CA-9 and GLUT-1 and nodal classification was correlated with GLUT-1 expression. The nodal metastasis rate was 51%, and the 5-year locoregional control and disease-specific survival (DSS) rates were 59% and 69%, respectively. Univariate analysis showed that HIF-1alpha and EPOR expression were significantly related to DSS. Multivariate analysis showed that EPOR expression was an independent predictor of DSS (P=0.030). EPOR expression may be an independent predictor for DSS in patients with T2-staged SCC of the oral tongue.

Endovascular treatments for carotid blowout syndrome (CBS) have been advocated by interventional neuroradiologists. We therefore retrospectively evaluated the efficacy of endovascular treatments of CBS in 16 patients with head and neck cancers (HNC). The clinical, treatment and outcome data were evaluated in 16 HNC patients with CBS, all of whom underwent permanent embolization or covered stent graft of the affected carotid artery. All patients received multimodal treatments, including radiotherapy (mean total dose, 78.5 Gy). CBS was caused by tumor carotid invasion in 8 patients, pharyngocutaneous fistula in 7, and laryngeal chondroradionecrosis in 1, with the external and common carotid arteries being the most common rupture sites. CBS was occluded by embolization or revascularized by covered stent placement. Immediate hemostasis was achieved in all patients; however, 7 patients had recurrent CBS, all of whom were retreated effectively by endovascular management. Three patients had strokes and four had extrusion of intervention materials from the infected wounds. Most patients died of tumor progression, with a mean survival time of five months from initial CBS; only two patients survived. Endovascular therapy, by both permanent occlusion and stent grafts, is effective in hemostasis of CBS but its long-term efficacy may not be high in these HNC patients.

The role of 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) in identifying bone metastases in patients with head and neck cancer is not clear. We compared the ability of FDG-PET and bone scintigraphy (BS) to detect bone metastases in patients with upper aerodigestive tract (UADT) malignancies. Patients with histologically confirmed malignancies in the UADT underwent both FDG-PET and BS at initial staging or follow-up. The two methods were compared in patients and in seven skeletal regions. Maximum standard uptake value (SUVmax) on PET was calculated in each lesion and compared between true- and false-positive lesions. This study included 564 eligible patients, of whom 17 had bone metastases. The spine was the most frequently involved site, followed by the lungs and liver. Both FDG-PET and BS had high specificity, accuracy, and negative predictive values for detecting bone metastases (>95% each), and the two methods did not differ in sensitivity, specificity, and predictive values (P>0.05). Both FDG-PET (n=15) and BS (n=14) yielded a significant number of false-positive results, which could be corrected by further work-ups and follow-up imaging. Compared with true-positive lesions, the false-positive lesions on FDG-PET were usually single (86.7% vs. 12.5%, P<0.001) and had lower mean SUVmax (2.4 vs. 5.6, P<0.001). FDG-PET is not more accurate than BS for detecting bone metastasis in patients with UADT cancer. Positive findings on FDG-PET or BS require further confirmation.

The combination of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and computed tomography (CT) has been reported to be more accurate than CT or PET alone in a preoperative setting. We compared the diagnostic utility of preoperative PET/CT, PET and CT/MRI in 167 patients with newly diagnosed head and neck squamous cell carcinoma (HNSCC), of whom 104 underwent FDG PET and 63 underwent combined PET/CT with all receiving CT/MRI. These preoperative PET, PET/CT, and CT/MRI results were reviewed and their accuracies were compared in patients in whom diagnosis was confirmed histopathologically. Age, sex, primary sites and stage, and nodal involvement were comparable between two groups. The accuracy of PET and PET/CT for detecting primary tumors and cervical metastases was comparable, but significantly higher than that of CT/MRI (98%-97% vs. 86-88% for primary; 92%-93% vs. 85%-86% for neck on a level-by-level basis; P<.05). PET and PET/CT gave false negative results: in 2 (2%) and 2 (3%) patients for primary tumors; in 6 (6%) and 3 (5%) patients for neck metastases, respectively. PET and PET/CT also gave false-positive results for cervical metastases in 5 (5%) and 4 (6%) patients, respectively. Compared with PET alone, preoperative FDG PET/CT may not yield significantly improved diagnostic accuracy in patients with HNSCC. Moreover, despite their high accuracy, PET and PET/CT may not abrogate the need for conventional imaging and pathologic staging based on primary resection and neck dissection.

We aimed to determine the outcome of small (<10 mm) solid noncalcified pulmonary nodules detected by chest computed tomography (CT) scans. Reports of low-dose chest CT scans performed from October 2003 to April 2005 at the Seoul National University Hospital Healthcare System Gangnam Center were reviewed to identify patients with solid noncalcified pulmonary nodules smaller than 10 mm. Partly solid and nonsolid nodules or nodules without follow-up imaging within 1 year were excluded. Records were studied to determine if the initial nodules had changed in size. A total of 3478 chest CT examinations were performed, with 232 patients having small noncalcified nodules (6.7%). One hundred and thirty-eight patients met the criteria (104 men and 34 women) and 213 nodules were identified. The median age was 54 years (range 32-80) and at least 86 patients (62%) were at low to intermediate risk for developing lung cancer. The largest nodule was less than 5 mm in diameter in 87 patients (63%) and 5 mm or more in 51 patients (37%). None of the nodules grew and 29 (14%) decreased in size at follow-up CT scans performed within 12 months. When those individuals at low to intermediate risk for lung cancer were included, solid noncalcified subcentimeter nodules were less frequently found in low-dose CT screening and were nearly unchanged in size when a follow-up CT scan was done within 12 months.

Study Objective: To determine (1) the amount of 8.4% sodium bicarbonate (NaHCO(3)) to adjust the pH of rocuronium to 7.4 (neutralization), (2) to show whether neutralizing the pH of rocuronium can prevent pain, and (3) to confirm that rocuronium mixed with NaHCO(3) does not change the physical property and efficacy of rocuronium., Design: Prospective studies., Setting: University medical center., Patients: 180 ASA physical status I and II women patients undergoing elective gynecologic surgery., Interventions and Measurements: 60 patients were randomly allocated to group 1 (rocuronium only), group 2 (rocuronium 50 mg mixed with 0.9% NaCl 3 mL), and group 3 (rocuronium 50 mg mixed with 8.4% NaHCO(3) 3 mL). All patients received mixtures equal to 0.04 mg/kg of rocuronium and were asked to evaluate their pain with visual analog scale (VAS) and pain scores. In other settings, the onset time and duration of action of each group of rocuronium were measured. The dose of rocuronium required to produce a 50% twitch depression (ED(50)) was calculated., Main Results: The amount of 8.4% NaHCO(3) needed to neutralize 50 mg of rocuronium was 3.1 +/- 0.3 mL. VAS scores were lower in group 3 than in groups 1 or 2 (P < 0.05). There were no differences in onset time, duration of action, or ED(50) values among the groups., Conclusions: Rocuronium neutralized with NaHCO(3) prevents intravenous injection pain. The physical and pharmacologic properties of rocuronium mixed with NaHCO(3) immediately before administration are not altered.

Few studies have used positron emission tomography (PET) to identify metastases or simultaneous thoracic malignancies in patients with head and neck cancer (HNC). We retrospectively investigated the role of (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in detecting thoracic malignancies in patients with previously untreated HNC. Patients (n=86) with HNC and intrathoracic lesions on PET were divided into those who had abnormal FDG uptake in the mediastinum (n=29), lungs (n=34), or both (n=23). Whole body PET and chest computed tomography (CT) results were blindly reviewed and scored by two observers. The accuracy of FDG PET and CT were drawn from patients in whom diagnosis was confirmed, by histopathology or follow-up imaging, and risk factors for thoracic malignancy were analyzed. Malignancy was suspected in 23 of 86 patients (27%) with FDG uptake. Most of the lesions (83%) with abnormal FDG uptake were benign, with thoracic malignancy confirmed in 15 patients (17%). The overall sensitivity, specificity, and accuracy of FDG PET for intrathoracic malignancy in these patients were 80%, 85%, and 84%, respectively. The likelihood of thoracic malignancy in the HNC patients was associated with high FDG uptake of thoracic lesions. FDG PET may reveal lung and mediastinal malignancies with high accuracy in patients with HNC. The thoracic staging by FDG PET may be helpful in therapeutic planning for these patients.

In order to determine the efficacy and proper timing of routine PET scans for surveillance of recurrent head and neck squamous cell carcinoma (HNSCC), we evaluated the diagnostic performance of routine PET scans in relation to time interval from completion of treatment. Amongst 206 retrospectively evaluated post-treatment PET scans of 159 patients with HNSCC, 156 were performed for routine surveillance in subclinical cases. Diagnostic performance of PET scan and follow-up outcome were evaluated in relation to the time interval (2-6months, 6-12months, 12-24months, and >24months) of PET scan from the completion of treatment. Overall sensitivity and NPV of these PET scans for recurrence were 92.5% and 94.8%, compared with 55.0% and 76.9% for conventional evaluation methods. In the 156 routine scans, the diagnostic sensitivity, specificity, and NPV for locoregional recurrence were 90%, 91% and 97%, respectively, and the values for distant metastases and second primary cancers were 100%, 97% and 100%, respectively. The diagnostic accuracy of routine PET scans was not significantly altered by the time interval. Most (97%) of true negative cases on routine PET scans had no recurrence during a median 14months follow-up. PET scan may be a useful tool in routine surveillance for detection of recurrence in subclinical patients. For routine surveillance, the initial PET scan should be performed within 6months after completion of treatment and the proper timing of next routine PET scan for subclinical patient with initial negative PET result might be 1year after initial PET scan.

The aim was to evaluate the efficacy of positron emission tomography (PET) with 2-[F-18]fluoro-2-deoxy-d-glucose (FDG) in early discrimination of response to definitive radiotherapy (RT) in patients with squamous cell carcinoma of the head and neck (SCCHN). Twenty-four patients who underwent FDG-PET scans before and after radiotherapy for nondisseminated SCCHN at the Asan Medical Center between August 2001 and September 2002 were prospectively evaluated. Initial FDG-PET scans were performed within 1 month before RT, and follow-up FDG-PET scans were performed 1 month after completion of RT. FDG-PET images were analyzed by standard uptake value (SUV). All patients were followed for more than 6 months. Pretreatment SUV ranged from 3.4 to 14.0 (median, 6.0), while posttreatment SUV ranged from ground level to 7.7 (median, 2.0). In evaluating residual tumors in these SCCHN patients, the overall sensitivity of FDG-PET was 100%, while its overall specificity was 87%. FDG-PET is effective in evaluating the response to radiation in patients with SCCHN. Timing the follow-up FDG-PET scan 1 month after completion of RT was not too rapid for evaluating the response to radiation.

In this study, we attempted to improve the oral absorption of ceftriaxone (CTX) by using an absorption carrier and the CTX complex together. After the CTX-Ca-carrageenan gel complex was prepared, several kinds of compounds (Capmul MCM C10, Gelucire 44/14, glycyrrhizin) were screened as potential oral enhancers for our experiment and the intestinal morphologies in rats were examined. Of these compounds, the mono- and diglyceride mixtures, Capmul MCM C10 greatly enhanced the gastrointestinal absorption of CTX when this carrier was coadministered with the complex in rats. Percent bioavailability was attained in rats by the enteral route ranging from 55 to 79% when this complex was administered with various doses of Capmul MCM C10. Furthermore, the surface morphology of the complex has a highly smooth appearance as seen under scanning electron microscopy after preparation. No treatment-related signs of any damage were observed on the administrations intestinal membrane when morphologies were examined in rats after the complex and the absorption carrier were coadministered. The results of the observation suggest that Capmul MCM C10 is a promising carrier, having a good balance between bioavailability enhancing activity and safety, for the oral delivery of CTX when it is coadministered with complex., (Copyright 2004 Wiley-Liss, Inc. and the American Pharmacists Association)