Novel double injection technique for sentinel lymph node biopsy in oral cancer.

The development of new lymphatic tracers and the advancement of hybrid tracers, such as indocyanine green (ICG)-Nanocoll (GE Healthcare), represent an exciting step in the future of sentinel lymph node biopsy (SLNB). These tracers aim to improve our ability to detect sentinel lymph nodes by enhancing their localisation. The aim of this study was to assess the performance of a novel dual tracer, double injection technique of ICG-'cold'-Nanocoll and radiolabelled Nanocoll, in SLNB for early-stage oral cancer. A double injection technique was performed first using 99mTc-Nancoll prior to sentinel node imaging followed by ICG-'cold'-Nanocoll injection in theatre. Analysis involved examination of the number, labelling, and location of the nodes harvested, sentinel node status, survival analysis, false negative rate, and complications associated with use of the technique. ICG 'cold' Nanocoll results showed concordance of fluorescence and radioactivity detection in 74 nodes in 24 patients. Most importantly, all nodes found positive for metastasis (6 nodes) were discovered to be both 'hot' and fluorescent; 74 nodes removed were both 'hot' and fluorescent, eight fluorescent only and six 'hot' only. Our results indicate that two sets of tracer injections given at two different time points will flow to the same sentinel nodes. This double labelling increased our confidence that the retrieved node was a sentinel node.

Neck failure following pathologically node-negative neck dissection (pN0) in oral squamous cell carcinoma: a systematic review and meta-analysis.

Due to the risk of occult cervical metastasis, elective neck dissection (END) is recommended in the management of patients with early oral cavity squamous cell carcinoma (OSCC) and a clinically node-negative (cN0) neck. This paper presents a systematic review and meta-analysis of studies that recorded isolated regional recurrence (RR) in the pathologically node-negative neck dissection (pN0) neck following END in order to quantify the failure rate. Pubmed and Ovid databases were systematically searched for relevant articles published between January 2009 and January 2019. Studies reporting RR following END in patients with OSCC who had no pathological evidence of lymph node metastasis were eligible for inclusion in this meta-analysis. In addition, a selection of large head and neck units were invited to submit unpublished data. Search criteria produced a list of 5448 papers, of which 18 studies met the inclusion criteria. Three institutions contributed unpublished data. This included a total of 4824 patients with median follow-up of 34 months (2.8 years). Eight datasets included patients staged T1-T4 with RR 17.3% (469/2711), 13 datasets included patients staged T1-T2 with RR 7.5% (158/2113). Overall across all 21 studies, isolated neck recurrence was identified in 627 cases giving a RR of 13.0% (627/4824) on meta-analysis. Understanding the therapeutic effectiveness of END provides context for evaluation of clinical management of the cN0 in these patients. A pathologically negative neck does not guarantee against future recurrence.

Do we have a robust method for preoperative tumour depth assessment for oral cavity tumours with clinically negative necks?

Tumour depth is an important prognostic factor in head and neck cancer and has recently been included in the eighth edition of the Union for International Cancer Control TNM classification of malignant tumours for oral squamous cell carcinoma (OSCC). It is important to appraise the accuracy of depth assessments; however, there is little current evidence in the literature. Accurate depth assessment is particularly pertinent in cT1-T2N0 OSCC where it may influence neck management. A retrospective study was performed at two tertiary referral centres, in which surgically treated patients with cT1-T4N0 OSCC were audited. Preoperative tumour depth assessments from multimodality radiological staging scans were compared with the final histopathological depth. The predictive accuracy of intraoral ultrasound (IOUS), computed tomography (CT), and magnetic resonance imaging (MRI) for tumour depth was evaluated. Accuracy to within 3mm of the histopathological depth was seen in 56.7% of MRI scans and 57.1% of CT scans. IOUS appeared to have superior prediction, with 78.2% of measurements within 3mm. Over one third of CT and MRI imaging failed to detect a lesion; IOUS scans detected the lesions in all of these case. In conclusion, the reliability of preoperative imaging assessment of tumour depth should be considered when recommending treatment.

Influence of Irradiation Temperature on Oxidative and Network Properties of X-Ray Cross-Linked Vitamin E Stabilized UHMWPE for Hip Arthroplasty.

Previous studies have shown that increased cross-link density, reduced free radicals, and increased antioxidant grafting resulting from electron-beam irradiation at elevated temperatures improved the wear performance and the oxidative stability of vitamin E blended UHMWPE. The current study explores the impact of elevated irradiation temperature on vitamin E blended UHMWPE using X-ray. We hypothesize that the effects of temperature would be similar to those observed after electron-beam irradiation due to the relatively high dose rate of X-rays. Two X-ray doses of 80 and 100 kGy and two irradiation temperatures, that is, room temperature and 100°C were considered. The reference was Vitelene®, a vitamin E stabilized polyethylene cross-linked with 80 kGy by e-beam at 100°C. Oxidation index and oxidation induction time, as well as cross-link density, gel fraction, and trans-vinylene index, were determined, as the oxidative and network properties are decisive for the long-term implant performance. Gel fraction and oxidation induction time were significantly improved subsequently to warm irradiation in comparison with the material irradiated at room temperature. In conclusion, X-ray irradiation at elevated temperatures resulted in an increase of cross-linking and oxidative resistance of vitamin E stabilized polyethylene comparable to those of e-beam irradiated UHMWPE.

CeO2-x nanorods with intrinsic urease-like activity.

The large-scale production and ecotoxicity of urea make its removal from wastewater a health and environmental challenge. Whereas the industrial removal of urea relies on hydrolysis at elevated temperatures and high pressure, nature solves the urea disposal problem with the enzyme urease under ambient conditions. We show that CeO2-x nanorods (NRs) act as the first and efficient green urease mimic that catalyzes the hydrolysis of urea under ambient conditions with an activity (kcat = 9.58 × 101 s-1) about one order of magnitude lower than that of the native jack bean urease. The surface properties of CeO2-x NRs were probed by varying the Ce4+/Ce3+ ratio through La doping. Although La substitution increased the number of surface defects, the reduced number of Ce4+ sites with higher Lewis acidity led to a slight decrease of their catalytic activity. CeO2-x NRs are stable against pH changes and even to the presence of transition metal ions like Cu2+, one of the strongest urease inhibitors. The low costs and environmental compatibility make CeO2-x NRs a green urease substitute that may be applied in polymer membranes for water processing or filters for the waste water reclamation. The biomimicry approach allows the application of CeO2-x NRs as functional enzyme mimics where the use of native or recombinant enzyme is hampered because of its costs or operational stability.

Biopsy of the sentinel lymph node in oral squamous cell carcinoma: analysis of error in 100 consecutive cases.

UK national guidelines in 2016 recommended that sentinel lymph node biopsy should be offered to patients with early oral cancer (T1-T2 N0) in which the primary site can be reconstructed directly. This study describes the pitfalls that can be avoided in the technique of biopsy to improve outcomes. We retrospectively analysed the data from 100 consecutive patients and recorded any adverse events. Lymphatic drainage of tracer failed in two patients as a result of procedural errors. Two patients with invaded nodes developed recurrence after total neck dissection, one after micrometastases had been diagnosed, and the other as a result of extranodal spread that had led to understaging and therefore undertreatment. Two results would not have been mistakenly classified as clear if all the harvested nodes had been analysed histologically according to the protocol. The disease-specific (96%) and disease-free (92%) survival were better than expected for a group of whom a third had stage 3 disease. If all harvested nodes had been analysed by the correct protocol then two of the three nodes wrongly designated clear would have been detected, two deaths potentially avoided, and the false-negative rate would have fallen from 8.3% to 2.7%. We conclude that minor deviations from protocol can result in a detrimental outcome for the patient.

[Prevalence of sleep-related breathing disorders of inpatients with psychiatric disorders]. / Prävalenz schlafbezogener Atmungsstörungen bei stationären Patienten mit psychischen Erkrankungen.

BACKGROUND: Sleep-related breathing disorders seriously impair well-being and increase the risk for relevant somatic and psychiatric disorders. Moreover, risk factors for sleep-related breathing disorders are highly prevalent in psychiatric patients. The aim of this study was for the first time in Germany to study the prevalence of obstructive sleep apnea syndrome (OSAS) as the most common form of sleep-related breathing disorder in patients with psychiatric disorders. METHODS: In 10 psychiatric hospitals in Germany and 1 hospital in Switzerland, a total of 249 inpatients underwent an 8­channel sleep polygraphy to investigate the prevalence of sleep apnea in this group of patients. RESULTS: With a conspicuous screening result of 23.7% of the subjects, a high prevalence of sleep-related breathing disorders was found to occur among this group of patients. Male gender, higher age and high body mass index (BMI) were identified as positive risk factors for the detection of OSAS. DISCUSSION: The high prevalence indicates that sleep apnea is a common sleep disorder among psychiatric patients. Although OSAS can lead to substantial disorders of the mental state and when untreated is accompanied by serious somatic health problems, screening procedures are not part of the routine work-up in psychiatric hospitals; therefore, sleep apnea is presumably underdiagnosed in psychiatric patients. In view of the results of this and previous studies, this topic complex should be the subject of further research studies.

Micro-CT and micro-FE analysis of pedicle screw fixation under different loading conditions.

Anchorage of pedicle screw instrumentation in the elderly spine with poor bone quality remains challenging. In this study, micro finite element (µFE) models were used to assess the specific influence of screw design and the relative contribution of local bone density to fixation mechanics. These were created from micro computer tomography (µCT) scans of vertebras implanted with two types of pedicle screws, including a full region-or-interest of 10 mm radius around each screw, as well as submodels for the pedicle and inner trabecular bone of the vertebral body. The local bone volume fraction (BV/TV) calculated from the µCT scans around different regions of the screw (pedicle, inner trabecular region of the vertebral body) were then related to the predicted stiffness in simulated pull-out tests as well as to the experimental pull-out and torsional fixation properties mechanically measured on the corresponding specimens. Results show that predicted stiffness correlated excellently with experimental pull-out strength (R2 > 0.92, p < .043), better than regional BV/TV alone (R2 = 0.79, p = .003). They also show that correlations between fixation properties and BV/TV were increased when accounting only for the pedicle zone (R2 = 0.66-0.94, p ≤  .032), but with weaker correlations for torsional loads (R2 < 0.10). Our analyses highlight the role of local density in the pedicle zone on the fixation stiffness and strength of pedicle screws when pull-out loads are involved, but that local apparent bone density alone may not be sufficient to explain resistance in torsion.

Sentinel lymph node biopsy for oral squamous cell carcinoma. Where are we now?

Recent data have confirmed that elective surgical management of the cN0 neck improves survival in patients with early (T1-T2) oral squamous cell carcinoma (SCC), and is better than watchful waiting. However, elective neck dissection (END) may not always be necessary. Sentinel node biopsy (SNB), which is a reliable staging test for patients with early disease and a radiologically N0 neck, can detect occult metastases with a sensitivity of 86%-94%. Patients with no sign of metastases on SNB could avoid neck dissection, and individual treatment should reduce both morbidity and cost. Currently, SNB for oral SCC is available at a limited number of centres in the UK, but this is likely to change as national guidelines have recommended that it is incorporated into the standard treatment pathway. It is therefore important to understand the current evidence that supports its use, its limitations and related controversies, and to plan for a validated training programme.

Utilidad del coeficiente de difusión aparente en resonancia magnética como método auxiliar para la diferenciación entre meduloblastomas y ependimomas de la fosa craneal posterior en niños y adultos tratados en el Hospital Carlos Van Buren de Valparaíso: Una experiencia preliminar / Usefulness of apparent diffusion coefficient in magnetic resonance as an auxiliary method for the differentiation between medulloblastomas and ependymomas of the posterior cranial fossa in children and adults treated at the Carlos Van Buren Hospital in Valparaíso: A preliminary experience

The use of the apparent diffusion coefficient (ADC) in magnetic resonance imaging (MRI) has been shown to be useful in the task of differentiating primary brain tumors. Our objective is to evaluate its use to differentiate between medulloblastomas and ependymomas. We analyzed 37 cases: 21 medulloblastomas (average age 12 years) and 16 ependymomas (average age 5 years) of the posterior fossa treated at the Carlos Van Buren Hospital in Valparaíso between december 2005 and June 2015. There were 15 and 5 males in each group respectively. In addition to age and gender, ADC values of tumors (ADCt) and healthy tissue were collected. The ADCt values for medulloblastoma and ependymoma averaged 0.64 and 0.92 [x10-3 mm²/s] respectively (p< 0.001). The multivariate model included gender and ADCt, with a sensitivity of 0.95 and a specificity of 0.87 to predict medulloblastoma. We can conclude that ADC measurement helps differentiate tumors of different cellularity such as medulloblastoma and ependymoma.

El uso del coeficiente de difusión aparente (ADC) en resonancia magnética (RM) ha demostrado ser útil en la tarea de diferenciar tumores cerebrales primarios. Nuestro objetivo es evaluar su uso para diferenciar entre meduloblastomas y ependimomas. Se analizaron 37 casos: 21 meduloblastomas (edad promedio 12 años) y 16 ependimomas (edad promedio 5 años) de fosa posterior tratados en el hospital Carlos Van Buren de Valparaíso, entre diciembre de 2005 y junio de 2015. Hubo 15 y 5 hombres en cada grupo respectivamente. Además de edad y sexo se recolectaron valores ADC tumorales (ADCt) y de tejido sano. Los valores ADCt para meduloblastoma y ependimoma promediaron 0,64 y 0,92 [x 10-3 mm²/s] respectivamente (p<0,001). El modelo multivariado incluyó sexo y ADCt, con sensibilidad de 0,95 y especificidad 0,87 para predecir meduloblastoma. Podemos concluir que la medición de ADC ayuda a diferenciar tumores de distinta celularidad como el meduloblastoma y el ependimoma.

Unilateral laminoplasty with lateral mass screw fixation for less invasive decompression of the cervical spine: a biomechanical investigation.

PURPOSE: To compare the stabilization behavior of additional unilateral mass screw fixation with current standard procedures in patients with cervical spondylotic myelopathy (CSM) in a biomechanical study. METHODS: Ten human C2-C7 cervical specimens were tested under various segment conditions: native (NAT), laminoplasty (LP), laminoplasty with unilateral (LPU) or bilateral (LPB) stabilization, laminectomy with bilateral stabilization (LCB), and laminectomy. The instrumented level was from C3 to C6. For each segment condition, in vitro flexibility tests were performed using a spinal simulator and an applied load of ±2.5 Nm. The three-dimensional kinematics of the entire cervical segment in three main loading directions [flexion-extension (FE), lateral bending (LB), and axial rotation (AR)] was measured with an ultrasonic motion analysis system. Analysis of variance followed by a post hoc test was used to determine differences under the specific segment conditions to assess the parameters range of motion (ROM) and neutral zone (NZ). RESULTS: For FE, the total ROM of laminoplasty (-6.3% difference to NAT) and laminectomy (+6.4%) remained at the level of native (p > 0.56), whereas the instrumentations LPU (-37.1%), LPB (-44%), and LCB (-43.2%) lead to significant reductions (p < 0.01) without significant differences in LPU to LPB and LCB (p > 0.38). The same results were found with LB. For AR, the stabilization of all instrumentations was less pronounced, but had the same tendency seen for FE and AR. The results for the NZ showed equivalent values as that for ROM. CONCLUSION: The degree of stabilization was as expected for LC and LCB; namely, no stabilization for LC and maximal stabilization for LCB. LPU exhibited almost the same degree of stabilization as LCB. LPU could be a new treatment option for less invasive decompression for multilevel CSM.

Prognostic significance of neuroepithelial transforming gene 1 in adenocarcinoma of the oesophagogastric junction.

BACKGROUND: Neuroepithelial transforming gene 1 (NET1) mediates tumour invasion and metastasis in a number of cancers, including gastric adenocarcinoma. It is an indicator of poor prognosis in breast cancer and glioma. This study examined NET1 expression and its prognostic significance in patients with adenocarcinoma of the oesophagogastric junction (AOG). METHODS: NET1 expression was measured by immunohistochemistry in a tissue microarray, constructed from biobanked tissue collected over a 10-year interval, and linked to a prospectively maintained clinical database. RESULTS: Using the Siewert classification for AOG, type I tumours expressed significantly higher levels of NET1, with lowest expression in type III and intermediate levels in type II (P = 0.001). In patients with AOG type III, NET1-positive patients were more likely to be female (P = 0.043), have advanced stage cancer (P = 0.035), had a higher number of transmural cancers (P = 0.006) and had a significantly higher median number of positive lymph nodes (P = 0.029). In this subgroup, NET1-positive patients had worse median overall (15 versus 23 months; P = 0·025) and disease-free (11 versus 36 per cent; P = 0.025) survival compared with NET1-negative patients. CONCLUSION: Although existing data show differences in clinical and prognostic indices across AOG subtypes, there are no studies showing differences in tumour biology. These data suggest NET1, a known mediator of an aggressive tumour phenotype in a number of gastrointestinal cancers, is expressed differentially across AOG subtypes and may be of prognostic significance in the clinical management of this condition.

Biotribology of a new bearing material combination in a rotating hinge knee articulation.

The objective of the present study was to evaluate the biotribological behaviour, in terms of wear and particle release, of bushings and flanges made of carbon fibre reinforced poly-ether-ether-ketone (CFR-PEEK) in articulation with a zirconium nitride (ZrN) multilayer surface coating in a rotating hinge knee system. For the bushings of the rotational and flexion axles and the medial and lateral flanges, a CFR-PEEK with 30% polyacrylonitrile fibre content was used in a new bearing combination with ZrN. In vitro wear simulation was performed for patients with metal ion hypersensitivity, using a new rotating hinge knee design with a ZrN surface articulation in comparison with the clinically established cobalt-chromium version. For the bushings and flanges made of CFR-PEEK subjected to wear simulation, the volumetric wear rates were 2.3±0.48mm(3)million(-1) cycles in articulation to cobalt-chromium as reference and 0.21±0.02mm(3)million(-1) cycles in the coupling with ZrN, a 10.9-fold decrease. The released CFR-PEEK particles were comparable in size and shape for the coupling to cobalt-chromium and ZrN with most of the particles in a size range between 0.1 and 2µm. The study reveals comparable low wear and no macroscopic surface fatigue in a new rotating hinge knee design with highly congruent flanges and axles bushings made of CFR-PEEK articulating to a ZrN multilayer surface coating. Favourable wear behaviour of the newly introduced CFR-PEEK/ZrN coupling in comparison with the clinically established CFR-PEEK/cobalt-chromium articulation was found.

The impact of chemotherapy-induced side effects on medical care usage and cost in German hospital care--an observational analysis on non-small-cell lung cancer patients.

PURPOSE: To evaluate frequency and severity of adverse drug reactions (ADRs) and its economic consequences after standard dose (immuno-)chemotherapy (CT) of non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Subanalysis of a prospective, multicentre, longitudinal, observational cohort study; data were collected from patient interviews and pre-planned chart reviews. Costs were aggregated per CT line and presented from provider perspective. RESULTS: A total of 120 consecutive NSCLC patients (mean age, 63.0 ± 8.4 (SD) years; men, 64.2%; ECOG (Eastern Cooperative Oncology Group) performance status <2, 84.3%; tumour stage III/IV, 85%; history of comorbidity, 93.3%) receiving 130 CT lines were evaluated. 80% of CT lines were associated with grade 3 or 4 ADRs, 22.3% developed potential life-threatening complications, 77.7% were associated with at least one hospital stay (inpatient, 63.9%; outpatient/day clinic 39.2%, ICU 6.9%), with a mean cumulative number of 12.8 (±14.0 SD) hospital days. Mean (median) toxicity management costs per CT line (TMC-TL) amounted to €3,366 (€1,406) and were found to be higher for first-line compared to second-line treatment: €3,677 (€1,599) vs. €2,475 (€518). TMC-TL were particularly high in CT lines with ICU care €12,207 (€9,960). Eight out of 11 ICU stays were associated with grade 3 or 4 infections. Nine CT lines with ICU care accounted for 25% of total expenses (€109,861 out of €437,580). CONCLUSIONS: In first-line NSCLC treatment, in particular, CT toxicity management is expensive. Asymmetric cost distribution seems to be triggered by infection associated ICU care. Its avoidance should reduce patients' clinical burden and have considerable economic implications. Nevertheless, comparative observational studies have to confirm estimated savings.

The influence of contact conditions and micromotions on the fretting behavior of modular titanium alloy taper connections.

Modularity of femoral stems and neck components has become a more frequently used tool for an optimized restoration of the hip joint center and improvement of patient biomechanics. The additional taper interface increases the risk of mechanical failure due to fretting and crevice corrosion. Several failures of titanium alloy neck adapters have been documented in case-reports. An experimental fretting device was developed in this study to systematically investigate the effect of micromotion and contact pressure on fretting damage in contact situations similar to taper interfaces of modular hip prostheses under cyclic loading representative of in vivo load conditions. As a first application, the fretting behavior of Ti-6Al-4V titanium alloy components was investigated. Micromotions were varied between 10µm and 50µm, maximum contact pressures between 400 and 860N/mm(2). All modes of fretting damage were observed: Fretting wear was found for high micromotions in combination with low contact pressures. Fretting fatigue occurred with reduced movement or increased contact pressures. With small micromotions or high normal pressures, low fretting damage was observed. The developed device can be used to evaluate taper design (and especially contact geometry) as well as different materials prior to clinical use.

Cortical thickness of superior frontal cortex predicts impulsiveness and perceptual reasoning in adolescence.

Impulsiveness is a pivotal personality trait representing a core domain in all major personality inventories. Recently, impulsiveness has been identified as an important modulator of cognitive processing, particularly in tasks that require the processing of large amounts of information. Although brain imaging studies have implicated the prefrontal cortex to be a common underlying representation of impulsiveness and related cognitive functioning, to date a fine-grain and detailed morphometric analysis has not been carried out. On the basis of ahigh-resolution magnetic resonance scans acquired in 1620 healthy adolescents (IMAGEN), the individual cortical thickness (CT) was estimated. Correlations between Cloninger's impulsiveness and CT were studied in an entire cortex analysis. The cluster identified was tested for associations with performance in perceptual reasoning tasks of the Wechsler Intelligence Scale for Children (WISC IV). We observed a significant inverse correlation between trait impulsiveness and CT of the left superior frontal cortex (SFC; Monte Carlo Simulation P<0.01). CT within this cluster correlated with perceptual reasoning scores (Bonferroni corrected) of the WISC IV. On the basis of a large sample of adolescents, we identified an extended area in the SFC as a correlate of impulsiveness, which appears to be in line with the trait character of this prominent personality facet. The association of SFC thickness with perceptual reasoning argues for a common neurobiological basis of personality and specific cognitive domains comprising attention, spatial reasoning and response selection. The results may facilitate the understanding of the role of impulsiveness in several psychiatric disorders associated with prefrontal dysfunctions and cognitive deficits.