Clinical characteristics of pediatric cutaneous lupus erythematosus: experience from a tertiary referral center in Korea.

The clinical characteristics of cutaneous lupus erythematosus (CLE) are well delineated in adults, but pediatric data, particularly in Asian populations, are limited. Therefore, we evaluated the characteristics of pediatric cases by retrospectively reviewing the medical records of children with CLE during a 15-year period in a tertiary care dermatology clinic in South Korea. The study included 21 children (8 males and 13 females), 4 of whom had neonatal lupus erythematosus (NLE). Among 17 patients with CLE, discoid lupus erythematosus (DLE) was most common (47.1%), followed by acute CLE (ACLE, 35.3%). All ACLE cases had systemic lupus erythematosus (SLE). Female predominance was conspicuous in ACLE/SLE (6/11 females versus 0/6 males), as was older age, whereas DLE and NLE showed near-equal sex distributions. The median age at the diagnosis of CLE was significantly higher in females than in males (15 years versus 4.5 years, p = 0.02). All patients with ACLE/SLE simultaneously showed skin and systemic symptoms from onset. The kidney was the most commonly involved organ. This study revealed unique characteristics of pediatric CLE, further warranting a comprehensive review among various ethnicities to understand the wide spectrum of CLE in the pediatric population.

Oral tolerance modulates the skin transcriptome in mice with induced atopic dermatitis.

Defective gut immune reactions have been implicated in the development of atopic dermatitis (AD), whereas oral tolerance (OT), that is, the immune unresponsiveness induced by oral antigen administration, protects mice against AD. To investigate this protective role of OT, the transcriptomic profiles of skin were obtained by RNA sequencing from mice that were epicutaneously sensitized, orally tolerized prior to epicutaneous sensitization, or neither (control). Oral tolerance inhibited the upregulation of keratin- and allergic inflammation-associated genes that occurred in the epicutaneously sensitized group. Compared to the controls, mice that were orally tolerized and epicutaneously sensitized showed an upregulation of genes that regulate inflammation or keratinocyte differentiation. Knocking down two of those genes, SCGB1A1 and TSC22D3, upregulated Th2 inflammatory mediators and downregulated a cornified cell envelope-related gene. Based on our findings, OT may protect skin against allergic inflammation by promoting the expression of genes that regulate Th2 inflammatory responses and skin barrier function.

Nodal factors predictive of recurrence and survival in patients with oral cavity squamous cell carcinoma.

OBJECTIVES: Lymph node (LN) metastasis of oral cavity squamous cell carcinoma (OSCC) is associated with survival outcomes. However, the relationship between different metastatic nodal factors and treatment outcomes requires further elucidation. This study examined nodal factors predictive of recurrence and survival in patients with OSCC. METHODS: This prospective observational study included 157 patients with OSCC who underwent surgery between 2010 and 2015. Clinicopathological and follow-up information were recorded. Univariate and multivariate Cox proportional hazard models were performed to identify factors associated with recurrence-free survival, disease-specific survival and overall survival. RESULTS: Sixty-five of 157 patients (41.4%) had neck metastasis. During a median follow-up of 46 months, any recurrences and all deaths occurred in 43 (27.4%) and 43 (27.4%) of cases, respectively. All nodal factors (LN classification, size, number and ratio) and extra-nodal extension were significantly associated with all survival outcomes (P < .001). Multivariate analyses indicated that a tumour size >2 cm and LN ratio were independently associated with all survival (P < .05). Patients with LN ratio >0.05 had sixfold higher recurrence and mortality rates than other patients (P < .001). CONCLUSION: Lymph node ratio is an independent and predictive determinant of post-treatment recurrence and survival.

Oral tolerance inhibits atopic dermatitis-like type 2 inflammation in mice by modulating immune microenvironments.

BACKGROUND: Oral tolerance is immune unresponsiveness induced by oral administration of innocuous antigens. Oral administration of allergens has been shown to be effective for suppressing IgE production in allergic responses. However, whether oral tolerance has a role in protection from allergic skin inflammation has not been fully investigated. Here, we evaluated the potential protective role of oral tolerance in a murine model of atopic dermatitis (AD) and investigated the underlying immunologic mechanisms. METHODS: Mice were fed with ovalbumin (OVA) in drinking water then epicutaneously sensitized by repeated application of OVA to tape-stripped skin. Skin biopsies were analyzed for immunohistopathologic features. Levels of antibodies in sera and intestinal washes were measured by ELISA. Flow cytometry and real-time PCR analysis of the skin and mesenteric lymph nodes (MLN) were performed to investigate the immunologic effects of oral tolerance in epicutaneous (EC) sensitization-induced allergic responses. RESULTS: Induction of oral tolerance effectively inhibited inflammatory responses provoked by EC sensitization. Tolerogenic immune mediators were significantly increased in the skin and MLN of EC-sensitized mice following induction of oral tolerance. A marked increase in Il5 and Il13 expression and infiltration of eosinophils and type 2 innate lymphoid cells (ILC2) in the skin of EC-sensitized mice were significantly inhibited by oral tolerance. CONCLUSIONS: Oral tolerance plays a protective role in the development of AD in a murine model by modulating immune microenvironments to be more favorable for immune regulation. This modulation involves inhibition of ILC2 infiltration in skin lesions.

Utility of digital subtraction angiography-based collateral evaluation in medically treated acute symptomatic basilar artery stenosis.

BACKGROUND AND PURPOSE: Although a stroke from atherosclerosis in the basilar artery (BA) often presents with mild initial stroke severity, it has heterogeneous clinical courses. We investigated the efficacy of digital subtraction angiography (DSA)-based collateral perfusion evaluation in association with long-term outcomes of medically treated symptomatic basilar artery stenosis. METHODS: From a registry database of all consecutive patients with stroke, we included 98 medically treated patients (due to mild initial stroke severity) [National Institute of Health Stroke Scale (NIHSS) scores ≤ 4; symptomatic basilar artery stenosis, 70-99%] with available initial diagnostic DSA. Basilar collateral scoring was performed via the DSA, using a modified version of the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology grading system in both the superior cerebellar artery and anterior/posterior-inferior cerebellar artery territories (score 0-8). The outcomes were designated as the 90-day modified Rankin Scale (mRS90) score (poor, 3-6). Student's t-test, chi-square test and logistic regression analyses were used to identify factors associated with a poor outcome. RESULTS: The median initial NIHSS score was 2 [interquartile range (IQR), 0-3], median posterior circulation Alberta Stroke Program Early CT Score was 8 (IQR, 7-10), median collateral score was 7 (IQR, 7-8) and 20 (20.4%) had poor mRS90 scores. In multivariate analysis, poorer collateral scores (P = 0.003), higher NIHSS scores (P = 0.005) and lower posterior circulation Alberta Stroke Program Early CT Score (P = 0.017) were independently associated with a poor mRS90 score. CONCLUSIONS: The DSA-based collateral scoring of the BA large branches might predict long-term outcome in medically treated symptomatic basilar artery stenosis with mild initial severity. Evaluation of BA collateral perfusion status might be useful to determine appropriate treatment strategies.

Risk of malignancy according to sub-classification of the atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) category in the Bethesda system for reporting thyroid cytopathology.

OBJECTIVE: According to the Bethesda System for Reporting Thyroid Cytopathology, atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) is a heterogeneous category that includes cases with architectural and/or nuclear atypia insufficient to warrant classification as malignant neoplasms. The ambiguous and descriptive characteristics of the AUS/FLUS category mean that the impact of the present guidelines on repeat fine needle aspiration (FNA) is unclear. The present study reclassified AUS/FLUS cases into four sub-categories and then correlated them with histological or cytological follow-up data to clarify the risk of malignancy. METHODS: Ninety-four cases of AUS/FLUS with available follow-up data were reviewed and assigned to one of four sub-categories: (i) AUS-N (nuclear atypia); (ii) AUS-A (architectural atypia); (iii) AUS-O (predominant oncocytic changes); and (iv) AUS-N/A (both nuclear and architectural atypia). The four sub-categories were correlated with subsequent histological or cytological follow-up data, including core needle biopsy, resection, or repeat FNA. RESULTS: Malignancy was identified in 34 of 94 cases (36.2%). The upper limit estimate for malignancy was 43.6%, and the lower limit estimate was speculated as 9.8%. The malignancy rate was highest in cases within the AUS-N sub-category (65.8%, range 16.6%-78.1%). CONCLUSIONS: The present study suggests that cases in the AUS/FLUS category have a higher risk of malignancy than previously thought. Because of the heterogeneous nature of the AUS/FLUS category, further sub-classification might be more effective in achieving appropriate risk stratification and better clinical management.

Incidence and risk factors of late recurrence in patients with salivary gland cancer.

OBJECTIVES: Recurrence in the late post-treatment period is relatively common in salivary gland cancer (SGC), but risk factors and survival associated with late recurrence have been rarely studied. We investigated the incidence and risk factors of SGC recurrence >5 years after treatment and associated survival. DESIGN: A retrospective cohort study. SETTING: University hospital. PARTICIPANTS: A total of 240 patients with previously untreated SGC who underwent definitive treatment. MAIN OUTCOME MEASURES: Late recurrence was defined as recurrence at a time point >5 years after treatment. Univariate and multivariable analyses were used to identify the association of clinicopathologic factors with recurrence-free survival (RFS), cancer-specific survival (CSS) and late recurrence. RESULTS: Of the 240 patients, 124 (51.7%) patients developed recurrence during a median follow-up of 160.0 months (range 121.5-282.2 months). Sixteen (6.7%) patients developed late recurrence; the median time to late recurrence was 92.5 months (range 60.2-138.3 months) after treatment. Multivariable analysis showed that primary site, histologic grade and N classification were independent variables of both RFS and CSS (P < 0.05 each). Extraparenchymal extension was also an independent variable of CSS (P = 0.022). In addition, a non-parotid tumour location was a significant factor for late recurrence in multivariable analysis (P = 0.017). The median overall survival after the development of late recurrence was 79.7 months (range 0.2-163.4 months), significantly longer than that after early recurrence (19.7 months) (P = 0.043). CONCLUSION: Late recurrence occurs in some SGC patients. Long-term close surveillance may be required for patients with non-parotid SGC.

Oxaliplatin and 5-FU/folinic acid (modified FOLFOX6) with or without aflibercept in first-line treatment of patients with metastatic colorectal cancer: the AFFIRM study.

BACKGROUND: The combination of aflibercept with FOLFIRI has been shown to significantly prolong overall survival in patients with metastatic colorectal cancer (mCRC) after progression on oxaliplatin-based therapy. This trial evaluated the addition of aflibercept to oxaliplatin-based first-line treatment of patients with mCRC. PATIENTS AND METHODS: Patients with mCRC were randomized to receive first-line therapy with mFOLFOX6 plus aflibercept (4 mg/kg) or mFOLFOX6 alone. The primary end point of this phase II study was the progression-free survival (PFS) rate at 12 months in each arm. The analysis of efficacy between the arms was a pre-planned secondary analysis. RESULTS: Of 236 randomized patients, 227 and 235 patients were evaluable for the primary efficacy analysis and safety, respectively. The probabilities of being progression-free at 12 months were 25.8% [95% confidence interval (CI) 17.2-34.4] for the aflibercept/mFOLFOX6 arm and 21.2% (95% CI 12.2-30.3) for the mFOLFOX6 arm. The median PFS was 8.48 months (95% CI 7.89-9.92) for the aflibercept/mFOLFOX6 arm and 8.77 months (95% CI 7.62-9.27) for the mFOLFOX6 arm; the hazard ratio of aflibercept/mFOLFOX6 versus mFOLFOX6 was 1.00 (95% CI 0.74-1.36). The response rates were 49.1% (95% CI 39.7-58.6) and 45.9% (95% CI 36.4-55.7) for patients treated with and without aflibercept, respectively. The most frequent treatment-emergent grade 3/4 adverse events (AEs) excluding laboratory abnormalities reported for aflibercept/mFOLFOX6 versus mFOLFOX6 were neuropathy (16.8% versus 17.2%) and diarrhea (13.4% versus 5.2%). Neutropenia grade 3/4 occurred in 36.1% versus 29.3%. The most common vascular endothelial growth factor inhibition class-effect grade 3/4 AEs for aflibercept/mFOLFOX6 versus mFOLFOX6 were hypertension (35.3% versus 1.7%), proteinuria (9.2% versus 0%), deep vein thrombosis (5.9% versus 0.9%) and pulmonary embolism (5.9% versus 5.2%). CONCLUSION: No difference in PFS rate was observed between treatment groups. Adding aflibercept to first-line mFOLFOX6 did not increase efficacy but was associated with higher toxicity. CLINICAL TRIAL NUMBER: NCT00851084, www.clinicaltrials.gov, EudraCT 2008-004178-41.

Interobserver reproducibility of cervical lymph node measurements at CT in patients with head and neck squamous cell carcinoma.

AIM: To determine the interobserver reproducibility of measuring cervical lymph nodes at computed tomography (CT) in patients with head and neck squamous cell carcinoma (HNSCC) and to investigate the influence of finding extracapsular spread (ECS) at CT on measurement reliability. MATERIALS AND METHODS: The institutional review board approved the study protocol, and informed consent was obtained. A total of 146 patients with 224 suspicious lymph nodes underwent CT before treatment. Two observers independently measured the diameters (minimal axial, maximum axial, and maximum longitudinal diameter) and assessed the ECS using CT. The greatest diameter was defined as the largest among the three measured diameters. Interobserver variability was determined by the within-subject coefficient of variation, and interobserver agreement was determined by the intraclass correlation coefficient (ICC). RESULTS: The within-subject coefficients of variation were 7.8%, 7.6%, and 11.4% for the minimal axial, maximum axial, and greatest diameters, respectively. The ICC values for interobserver agreement were excellent for all diameter measurements (i.e., ICC >0.9). Minimum and maximum axial diameter measurements were statistically more reliable than the greatest diameter measurement (p=0.008 and p=0.0001, respectively). The presence of ECS on CT does not significantly affect the reliability of lymph node diameter measurements (p>0.05). CONCLUSION: Lymph node diameter measurement on CT is a highly reproducible and robust method. Additionally, imaging features of ECS do not affect reliability. Therefore, the measurement of lymph node diameter can be confidently performed in daily clinical practice or clinical trials.

Routine endoscopic screening for synchronous esophageal neoplasm in patients with head and neck squamous cell carcinoma: a prospective study.

Early detection of synchronous esophageal squamous cell neoplasm (ESCN) in head and neck squamous cell carcinoma (HNSCC) patients can significantly affect their prognosis. We investigated the prevalence of synchronous ESCN and the risk factors for developing ESCN in patients with HNSCC, and evaluated the effect of routine endoscopic screening in these patients. Subjects who were diagnosed as HNSCC from May 2010 to January 2014 were eligible. All patients underwent conventional white light endoscopic examinations with narrow band imaging and Lugol chromoendoscopy. Among 458 subjects screened, 28 synchronous ESCN were detected in 24 patients (5.2%). The prevalence of ESCN was greatest in patients with hypopharyngeal cancer (20.9%). In multivariate analysis, pyriform sinus involvement was independent risk factor for developing synchronous ESCN (odds ratio 171.2, P < 0.001). During the follow-up period (median, 24 months), the 3-year overall survival rates was significantly lower in patients with ESCN than in patients without ESCN (54.2% vs. 78.3%, P = 0.0013). Routine endoscopic screening for detecting synchronous ESCN should be recommended for patients with HNSCC, especially those with pyriform sinus involvement.

Efficacy of HVT-IBD vector vaccine compared to attenuated live vaccine using in-ovo vaccination against a Korean very virulent IBDV in commercial broiler chickens.

The production performance, efficacy, and safety of two types of vaccines for infectious bursal disease virus (IBDV) were compared with in-ovo vaccination of Cobb 500 broiler chickens for gross and microscopic examination of the bursa of Fabricius, bursa/body weight (b/B) ratio, flow cytometry, and serologic response to Newcastle disease virus (NDV) vaccination. One vaccine was a recombinant HVT-IBD vector vaccine (HVT as for herpesvirus of turkeys) and the other was an intermediate plus live IBDV vaccine. A significant difference was detected at 21 d. Eight of 10 chickens that received the IBDV live vaccine had severe bursal lesions and a relatively low b/B ratio of 0.95, and an inhibited NDV vaccine response. On the other hand, the HVT-IBD vector vaccine resulted in mild bursal lesions and a b/B ratio of 1.89. Therefore, the live vaccine had lower safety than that of the HVT-IBD vector vaccine. To determine the protective efficacy, chickens were intraocularly challenged at 24 d. Eight of 10 chickens in the IBDV live vaccination group showed gross and histological lesions characterized by hemorrhage, cyst formation, lymphocytic depletion, and a decreased b/B ratio. In contrast, the HVT-IBD vector vaccinated chickens showed mild gross and histological lesions in three of 10 chickens with a b/B ratio of 1.36, which was similar to that of the unchallenged controls. Vaccinated chickens showed a significant increase in IBDV antibody titers, regardless of the type of vaccine used. In addition, significantly better broiler flock performance was observed with the HVT-IBD vector vaccine compared to that of the live vaccine. Our results revealed that the HVT-IBD vector vaccine could be used as an alternative vaccine to increase efficacy, and to have an improved safety profile compared with the IBDV live vaccine using in-ovo vaccination against the Korean very virulent IBDV in commercial broiler chickens.

Postoperative hypoalbuminemia as a risk factor for surgical site infection after oral cancer surgery.

OBJECTIVES: Postoperative surgical site infection (SSI) is a frequent postoperative complication in patients with oral cancer and significantly affects patient recovery and medical expenses. The aim of this study was to examine the predictors of SSI in patients undergoing major surgery for oral or oropharyngeal squamous cell carcinoma (OSCC) and to determine the relationship between perioperative albumin and the development of SSI. SUBJECTS AND METHODS: In 337 consecutive patients who underwent clean-contaminated surgery for OSCC, serum albumin, glucose, and hemoglobin levels were perioperatively measured. Differences between the groups were examined using Fisher's exact test, Mann-Whitney U-test, and multiple logistic regression analysis. RESULTS: Surgical site infection was detected in 88 (26.1%) patients with median time to development of 10 (2-25) days. Multiple logistic regression analysis showed that only postoperative serum albumin < 2.5 g dl(-1) was an independent variable predictive of SSI (P = 0.003). The duration of hospital stay was negatively correlated with postoperative albumin (R(2) = -0.302, P < 0.001). CONCLUSION: Early postoperative hypoalbuminemia <2.5 g dl(-1) is an independent risk factor for the development of SSI in patients undergoing oral cancer surgery. Clinicians should be aware of the implications of postoperative hypoalbuminemia and consider more intensive postoperative care in these patients.

Noncancer health events as a leading cause of competing mortality in advanced head and neck cancer.

BACKGROUND: The survival of patients with head and neck squamous cell carcinoma (HNSCC) can be affected by noncancer health events (NCHE) as well as by index cancer progression and second primary cancer (SPC). This study aimed to investigate the risk factors for NCHE and noncancer mortality (NCM) in patients with advanced-stage HNSCC. PATIENTS AND METHODS: This cohort study involved 600 consecutive patients with overall stage III to IV HNSCC who were treated between 2001 and 2010 at our tertiary referral hospital. NCHE was defined as re-admission (i.e. after the primary treatments for the index tumors) due to noncancer-related causes. The incidences of NCHE and NCM and their risk factors were analyzed by using cumulative incidence and cause-specific hazard functions. RESULTS: During a median follow-up period of 54 months, 224 (37.3%) and 55 (9.2%) of the 600 patients had NCHE and NCM, respectively. The 5-year index cancer mortality, SPC mortality, and NCM rates were 23.8%, 4.2%, and 8.9%, respectively. Multivariate analyses revealed that body mass index <20 kg/m(2) (P = 0.018), Charlson comorbidity index (CCI) ≥1 (P < 0.001), tumor recurrence (P < 0.001), SPC occurrence (P < 0.001), and initial chemotherapy (P = 0.049) were independent NCHE predictors. Older age (P < 0.001), CCI ≥1 (P = 0.008), tumor recurrence (P < 0.001), and SPC occurrence (P = 0.047) were independent NCM predictors. Patients with respiratory NCHE were at a higher risk of NCM than patients with other NCHE types (P < 0.001). CONCLUSIONS: One or more comorbidities, tumor recurrence, and SPC occurrence were independent predictors of both NCHE and NCM. Patients with respiratory NCHE had a particularly high risk of NCM.

Prognostic value of metastatic nodal volume and lymph node ratio in patients with cervical lymph node metastases from an unknown primary tumor.

OBJECTIVE: The presence of metastatic cervical lymph nodes (MCNs) is an unfavorable prognostic factor in head and neck cancer. The total volume of MCNs (MNV) and the lymph node ratio (LNR) may be superior to conventional nodal staging in cervical metastasis from an unknown primary tumor (CUP). We evaluated the prognostic value of MNV and LNR in CUP patients. METHODS: Thirty-nine patients with CUP who underwent surgery plus postoperative radiotherapy were reviewed. MNV was measured by preoperative computed tomography and LNR was determined using neck dissection samples. The association of clinicopathologic factors, MNV, and LNR with disease-free survival (DFS) and overall survival (OS) was analyzed. RESULTS: Five-year DFS and OS were 68.4 and 70.8%, respectively, for a median follow-up of 49 months. In multivariate analysis, MNV (>30 ml) was an independent prognostic factor for both DFS and OS (p = 0.004 and p < 0.001, respectively). LNR (>0.14) was identified as an independent predictive factor for DFS (p = 0.041). CONCLUSION: MNV and LNR are independent prognostic factors in patients with CUP and could facilitate the identification of high-risk patients requiring intensive treatment and surveillance.

(18)F-FDG PET/CT surveillance at 3-6 and 12 months for detection of recurrence and second primary cancer in patients with head and neck squamous cell carcinoma.

BACKGROUND: Early detection of recurrence of head and neck squamous cell carcinoma (HNSCC), which is often obscured by surgical or radiotherapy-induced tissue distortion, is essential for proper patient management. METHODS: A total of 143 consecutive patients with previously untreated HNSCC were evaluated by whole-body fluorine 18-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) and regular clinical follow-up after curative treatment. The (18)F-FDG PET/CT was performed ∼3-6 and 12 months after treatment and findings suspicious for recurrence or SPC were confirmed using histopathology. RESULTS: The sensitivities of 3-6- and 12-month PET/CT scans at patient level were 96% and 93%, respectively, and those of regular clinical follow-up were 11% and 19%, respectively (McNemar test, P<0.001). In patients with no clinical suspicion, PET/CT detected 95% and 91% of recurrent patients at 3-6 and 12 months, respectively. The sensitivity of PET/CT for the identification of SPC was 29% and 80% at 3-6 and 12 months, respectively. A positive interpretation of PET/CT was significantly associated with poor overall survival (log-rank test, P<0.001). CONCLUSION: The (18)F-FDG PET/CT surveillance is beneficial for the detection of recurrence that may be missed by regular follow-up physical and endoscopic examinations of the head and neck area after curative treatment for HNSCC.

Prognostic value of metabolic tumor volume measured by 18F-FDG PET/CT in advanced-stage squamous cell carcinoma of the larynx and hypopharynx.

BACKGROUND: Metabolic tumor volume (MTV) of (18)F-FDG PET/CT is a volumetric measurement of tumor cells with increased 18F-FDG uptake. We evaluated the prognostic value of MTV in patients with locoregionally advanced laryngeal and hypopharyngeal cancer. PATIENTS AND METHODS: We evaluated 81 patients with advanced-stage squamous cell carcinoma of the laryngohypopharynx who underwent 18F-FDG PET/CT between January 2004 and September 2009. Clinicopathologic factors and MTV were analyzed for their association with locoregional control (LRC) and overall survival (OS). RESULTS: The 3-year LRC and OS for all patients were 70.9 and 78.7%, respectively, with a median follow-up of 40.4 months (range 24.5-90.1). In univariate analyses, MTV, primary site, and primary treatment strategy were associated with both LRC and OS (P<0.05). On multivariate analysis, MTV was an independent prognostic factor for both LRC [P=0.018; HR=3.141, 95% confidence interval (CI)=1.175-8.399] and OS (P=0.008; HR=3.758, 95% CI=1.415-9.982). Primary site was also a significant prognostic factor for LRC (P=0.047). CONCLUSION: Pretreatment MTV is an independent prognostic factor in patients with locoregionally advanced squamous cell carcinoma of the larynx and hypopharynx.

Risk factors for non-cancer health events in patients with head and neck squamous cell carcinoma.

BACKGROUND: Cancer progression and non-cancer-related morbidities can affect the quality of life and survival of patients with head and neck squamous cell carcinomas (HNSCC). The aim of this study was to investigate the risk factors for the development of non-cancer health events (NCHEs) in HNSCC. PATIENTS AND METHODS: The study involved 465 previously-untreated patients with HNSCC diagnosed between 2005 and 2009 at the Asan Medical Center. Non-cancer-associated morbidity was defined as readmission after treatment of HNSCC due to non-cancer-related causes. NCHEs were defined as the occurrence of non-cancer-associated morbidity or mortality. The incidence and risk factors for NCHEs were analyzed. RESULTS: During the median follow-up of 47.6 months, non-cancer morbidity and mortality occurred in 83 (17.8%) and 25 patients (5.4%), respectively. Thirteen patients (52%) died from non-cancer-related causes with no previous admission for non-cancer causes. Multivariate analysis showed that the incidence of NCHEs was significantly associated with a Charlson comorbidity index ≥1 and stage III/IV disease (P < 0.001). CONCLUSIONS: Patients with comorbidities and advanced diseases may be at higher risk of NCHEs. Because NCHEs are sometimes life-threatening, every effort should be made to avoid unexpected non-cancer-associated mortality in the HNSCC patients.

Preoperative detection and predictors of level V lymph node metastasis in patients with papillary thyroid carcinoma.

BACKGROUND: Papillary thyroid carcinoma (PTC) frequently metastasizes to regional lymph nodes. Metastasis to the posterior neck, level V, is uncommon, and level V lymphadenectomy may lead to spinal accessory nerve injury and associated postoperative morbidities. The aim of this study was to assess the diagnostic efficiency of preoperative ultrasonography and to identify predictors of level V metastasis in patients with PTC. METHODS: This study involved patients with previously untreated PTC that had metastasized to the lateral neck, and who underwent total thyroidectomy with central and lateral neck dissection. Histopathological findings were compared with ultrasound results for various neck levels. Clinical and histopathological factors that predicted level V metastasis were identified. RESULTS: Of 143 patients, 26 (18·2 per cent) had lymph node metastasis at level V. The sensitivity and positive predictive value of ultrasonography for level V metastasis were 46·2 and 30·0 per cent respectively. Univariable analysis showed that male sex, extranodal disease extension, a metastatic lymph node ratio in the ipsilateral lateral neck of more than 0·2, and simultaneous involvement of ipsilateral levels II-IV or level III were associated with ipsilateral level V metastasis. Multivariable analysis revealed an independent association between macroscopic extranodal disease extension and level V metastasis (odds ratio 26·05, 95 per cent confidence interval 5·63 to 120·56; P < 0·001). CONCLUSION: Preoperative ultrasonography frequently failed to detect level V metastasis in patients with metastatic PTC. Level V lymphadenectomy may be considered in patients with lymph node metastasis in the ipsilateral lateral neck with macroscopic extranodal extension.

Effects of celecoxib on hematoma and edema volumes in primary intracerebral hemorrhage: a multicenter randomized controlled trial.

BACKGROUND AND PURPOSE: We investigated the effect of celecoxib, a selective inhibitor of cyclo-oxygenase 2, in patients with intracerebral hemorrhage (ICH). METHODS: We conducted a multicenter, randomized, controlled, and open with blinded end-point trial of 44 Korean patients 18 years or older with ICH within 24 h of onset. The intervention group (n = 20) received celecoxib (400 mg twice a day) for 14 days. The control group (n = 24) received the standard medical treatment for ICH. The primary end-point was the number of patients with a change in the volume of perihematomal edema (PHE) from the 1st to the 7th ± 1 day (cut-off value, 20%). RESULTS: The time from onset to computed tomography scan slightly differed between groups (177 ± 160 min for control vs. 297 ± 305 min for the celecoxib group; P = 0.10). In the primary end-point analysis using cut-off values, there was a significant shift to reduced expansion of PHE in the celecoxib group (P = 0.005). With respect to the secondary end-points, there was also a significant shift to reduced expansion of ICH in the celecoxib group (P = 0.046). In addition, the expansion rate of PHE at follow-up tended to be higher in the control group than in the celecoxib group (90.6 ± 91.7% vs. 44.4 ± 64.9%; P = 0.058). CONCLUSIONS: In our small, pilot trial, administration of celecoxib in the acute stage of ICH was associated with a smaller expansion of PHE than that observed in controls.

Adverse myocardial effects of B-vitamin therapy in subjects with chronic kidney disease and hyperhomocysteinaemia.

BACKGROUND & AIMS: Hyperhomocysteinaemia (HHCY), a common finding in patients with chronic kidney disease (CKD), has been shown to contribute to adverse cardiac remodelling and failure. We hypothesised that in human subjects with CKD, HHCY would be associated with myocardial dysfunction, and that homocysteine (HCY)-lowering therapy would improve myocardial remodelling and heart-failure (HF) outcomes. METHODS AND RESULTS: Post hoc analysis of the Homocysteinemia in Kidney and End Stage Renal Disease (HOST) trial (n=2056) was performed to determine if HCY-lowering therapy with high dose B vitamins affects HF outcomes in patients with CKD. In addition, effects on myocardial remodelling were assessed in a subgroup of 220 trial subjects who had transthoracic echocardiograms done before study randomisation and during the course of the study as part of their routine clinical care. HF outcomes were not significantly affected by treatment compared to the placebo. HCY levels were inversely correlated with diastolic function (R=-0.21; p=0.038). Vitamin therapy resulted in a significant increase in left atrial size (+0.15±0.8 cm vs. -0.13±0.07 cm; p=0.0095). No other echocardiographic parameters were significantly associated with baseline HCY levels or changes with vitamin therapy. CONCLUSION: HHCY is associated with diastolic dysfunction in patients with CKD. However, B-vitamin therapy did not improve HF outcomes despite lowering of plasma HCY levels, and was associated with an increase in left atrial size, which is a surrogate for worsening left ventricular diastolic dysfunction. These findings suggest that high-dose B vitamin therapy may be harmful in patients with CKD.