Is Lymph-node Ratio a Superior Predictor than Lymph Node Status for Recurrence-free and Overall Survival in Patients with Head and Neck Squamous Cell Carcinoma?

Introduction: TNM status is questioned as an exact predictor of survival in different tumour entities. Recently, lymph node ratio (LNR) has been described as a predictor of survival in patients with HNSCC. The purpose of this study was to evaluate to which degree LNR could be used as a more accurate predictor than TNM staging? Methods: A total of 291 patients, with a follow-up of at least 3years, were analyzed using log-rank statistic, univariate and multivariate data analyzes, and p values, for prediction of lymph node ratio on overall and recurrence-free survival. Results: Survival differed significantly if patients were stratified for LNR. Impact of LNR on survival was significantly different even in patients with extracapsular spread. Patients with pN0 had no survival benefit compared with patients with pN1 or higher with a LNR lower than 6%. Conclusions: LNR is a prognostic tool in patients with a lymph node status pN0-pN2b. LNR remained significant even in patients with extracapsular spread, contrary to TNM status. With LNR, stratification for high-risk patients (higher than 6% LNR) can be evaluated easily. We would suggest using LNR in the clinical routine

Is lymph-node ratio a superior predictor than lymph node status for recurrence-free and overall survival in patients with head and neck squamous cell carcinoma?

INTRODUCTION: TNM status is questioned as an exact predictor of survival in different tumour entities. Recently, lymph node ratio (LNR) has been described as a predictor of survival in patients with HNSCC. The purpose of this study was to evaluate to which degree LNR could be used as a more accurate predictor than TNM staging? METHODS: A total of 291 patients, with a follow-up of at least 3 years, were analyzed using log-rank statistic, univariate and multivariate data analyzes, and p values, for prediction of lymph node ratio on overall and recurrence-free survival. RESULTS: Survival differed significantly if patients were stratified for LNR. Impact of LNR on survival was significantly different even in patients with extracapsular spread. Patients with pN0 had no survival benefit compared with patients with pN1 or higher with a LNR lower than 6 %. CONCLUSIONS: LNR is a prognostic tool in patients with a lymph node status pN0-pN2b. LNR remained significant even in patients with extracapsular spread, contrary to TNM status. With LNR, stratification for high-risk patients (higher than 6 % LNR) can be evaluated easily. We would suggest using LNR in the clinical routine

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Influence of histopathologic factors on pattern of metastasis in squamous cell carcinoma of the head and neck

OBJECTIVES/HYPOTHESIS: Knowledge of histopathological factors, such as perineural invasion (PNI), extracapsular spread (ECS), angiolymphatic vessel invasion, and conglomerate lymph nodes, in patients with head and neck squamous cell carcinoma is important for appropriate treatment decisions. Given the availability of aggressive therapeutic options with known side effects and burdens for the patient, choosing the correct treatment option is vital. STUDY DESIGN: Retrospective patient database. METHODS: Using a retrospective database of patients treated over a 10-year period, independent prognostic factors for disease-free survival and overall survival were assessed. Univariate analysis was used to identify significant variables, and multivariate Cox regression analysis was used to determine independent prognostic factors. RESULTS: Between January 1, 1999 and December 31, 2009, 291 patients with head and neck squamous cell carcinoma were analyzed to identify influence of histopathological factors on pattern of metastasis. PNI tends to set metastasis locoregional, both in ipsilateral and contralateral lymph nodes. Lymphangiosis eases the way toward ipsilateral lymph node metastasis. ECS spread and hemangiosis demonstrated a significantly higher risk of distant metastasis. With the occurrence of conglomerate lymph nodes, patient data demonstrated a highly significant accumulation of distant metastasis. CONCLUSIONS: Patients with PNI and lymph vessel invasion tend toward locoregional lymph node metastasis on the ipsilateral side of the neck. In cases of PNI, the patient is at risk for a contralateral neck recurrence of the tumor. In patients with ECS, blood vessel invasion, or conglomerate disease, disseminated spread of the disease to distant locations is more likely and has a high negative impact on survival of the patient. LEVEL OF EVIDENCE: 4 Laryngoscope, 2013

Preservation of ipsilateral submandibular gland is ill advised in cancer of the floor of the mouth or tongue

OBJECTIVES/HYPOTHESIS: Preservation of the submandibular gland (SMG) during a neck dissection is gaining popularity and is showing an increasing tendency. The potential benefit, if the SMG is preserved, can be manifold. The aim of this study was to assess the benefit of the preservation of the SMG and the associated risk of recurrent disease in patients with oropharyngeal or oral cavity squamous cell carcinoma. STUDY DESIGN: Retrospective data analysis of 168 patients, with a follow-up of at least 3 years. METHODS: Log-rank test, univariate, and multivariate data analyses and P values for prediction of the excision of SMG on overall-, recurrence free-, and lymph node recurrence free survival. RESULTS: In patients with cancer of the floor of the mouth or tongue, lymph node recurrence-free survival was highly influenced by excision of the SMG (P < 0.001) and occurred in 28.5% of patients in whom the SMG was preserved. In all other tumor sites of the oral cavity and oropharyngeal region, excision of the SMG did not influence lymph node recurrence-free survival (P = 0.455). CONCLUSIONS: Patients with squamous cell carcinoma (SCC) of the oral cavity or oropharyngeal region will benefit from preservation of the ipsilateral SMG. This is not true for patients with SCC of the surrounding tissue nearest the SMG (i.e., floor of the mouth or the tongue). In such patients, the SMG must be excised

Unknown primary of the head and neck: A long-term follow-up

BACKGROUND: A diagnosis of squamous cell carcinoma of an unknown primary (CUP) is a major burden for patients. Because the location of the primary tumor is unclear, patients remain fearful of recurrence, which aggravates the uncertain prognosis of the disease. This study evaluates factors associated with long-term recurrence-free and overall survival of patients with CUP of the head and neck. Additionally, patient survival rates are compared with those of patients with head and neck squamous cell carcinoma (HNSCC). METHODS: A total of 293 consecutive patients operated on between January 1999 and December 2009 with at least a 5-year follow-up (survival permitting), were evaluated retrospectively. RESULTS: Twenty-six patients with a CUP of the head and neck were identified. Patients with CUP had a low overall survival rate, comparable with that of patients with pN + HNSCC, and recurrent disease occurred with a similar likelihood as in patients with pN + HNSCC. The median recurrence-free survival in the CUP group was 28.5 months compared with 48 months in the whole of the HNSCC group. The median overall survival of the CUP group was 56 months versus 65 months for the HNSCC group. Extracapsular spread was the only independent prognostic factor for overall survival for CUP patients. CONCLUSION: Patients diagnosed with CUP syndrome have a poorer prognosis for overall survival compared with other HNSCC patients. Postoperative radiotherapy diminished disease recurrence and improved overall survival. Omission of postoperative radiotherapy resulted in a very high recurrence rate (75%) for CUP patients. Based on these results we suggest postoperative radiotherapy including the oral mucosa for all patients, regardless of histopathological results, possible favorable nodal disease, or favorable lymph node ratios

The AST/ALT (De Ritis) Ratio Predicts Survival in Patients with Oral and Oropharyngeal Cancer

Aminotransaminases, including aspartate aminotransaminase (AST) and alanine aminotransaminase (ALT), are strongly involved in cancer cell metabolism and have been associated with prognosis in different types of cancer. The purpose of the present study was to evaluate the prognostic significance of the pre-treatment AST/ALT ratio in a large European cohort of patients with oral and oropharyngeal squamous cell cancer (OOSCC). Data from 515 patients treated for OOSCC at a tertiary academic center from 2000&ndash;2017 were retrospectively analyzed. Levels of AST and ALT were measured prior to the start of treatment. Uni- and multivariate Cox regression analyses were applied to evaluate the prognostic value of the AST/ALT ratio for cancer-specific survival (CSS) and overall survival (OS), survival rates were calculated. Univariate analyses showed a significant association of the AST/ALT ratio with CSS (hazard ratio (HR) 1.71, 95% confidence interval (CI) 1.38&ndash;2.12; p &lt; 0.001) and OS (HR 1.69, 95% CI 1.41&ndash;2.02; p &lt; 0.001). In multivariate analysis, the AST/ALT ratio remained an independent prognostic factor for CSS and OS (HR 1.45, 95% CI 1.12&ndash;1.88, p = 0.005 and HR 1.42, 95% CI 1.14&ndash;1.77, p = 0.002). Applying receiver operating characteristics (ROC) curve analysis, the optimal cut-off level for the AST/ALT ratio was 1.44, respectively. In multivariate analysis, an AST/ALT ratio &gt; 1.44 was an independent prognostic factor for poor CSS and OS (HR 1.64, 95% CI 1.10&ndash;2.43, p = 0.014 and HR 1.55, 95% CI 1.12&ndash;2.15; p = 0.008). We conclude that the AST/ALT ratio is a prognostic marker for survival in OOSCC patients and could contribute to a better risk stratification and improved oncological therapy decisions

The nerve hemoglobin of the bivalve mollusc Spisula solidissima: molecular cloning, ligand binding studies, and phylogenetic analysis

Members of the hemoglobin (Hb) superfamily are present in nerve tissue of several vertebrate and invertebrate species. In vertebrates they display hexacoordinate heme iron atoms and are typically expressed at low levels (mu M). Their function is still a matter of debate. In invertebrates they have a hexa- or pentacoordinate heme iron, are mostly expressed at high levels ( mM), and have been suggested to have a myoglobin-like function. The native Hb of the surf clam, Spisula solidissima, composed of 162 amino acids, does not show specific deviations from the globin templates. UV-visible and resonance Raman spectroscopy demonstrate a hexacoordinate heme iron. Based on the sequence analogy, the histidine E7 is proposed as a sixth ligand. Kinetic and equilibrium measurements show amoderate oxygen affinity (P-50 similar to 0.6 torr) and no cooperativity. The histidine binding affinity is 100-fold lower than in neuroglobin. Phylogenetic analysis demonstrates a clustering of the S. solidissima nerve Hb with mollusc Hbs and myoglobins, but not with the vertebrate neuroglobins. We conclude that invertebrate nerve Hbs expressed at high levels are, despite the hexacoordinate nature of their heme iron, not essentially different from other intracellular Hbs. They most likely fulfill a myoglobin-like function and enhance oxygen supply to the neurons