Neoadjuvant therapy improves long-term survival after oesophagectomy, treating oesophageal cancer, but the evidence to date is insufficient to determine which of the two main neoadjuvant therapy ...types, chemotherapy (nCT) or chemoradiotherapy (nCRT), is more beneficial. We aimed to compare the effects of nCT with those of nCRT.
This multicentre trial, which was conducted in Sweden and Norway, recruited 181 patients with carcinoma of the oesophagus or the gastro-oesophageal junction who were candidates for curative-intended treatment. The primary end point was histological complete response after neoadjuvant treatment, which has been shown to be correlated with increased long-term survival. Study participants were randomized to nCT or nCRT, followed by surgery with two-field lymphadenectomy. Three cycles of platin/5-fluorouracil were administered in both arms, whereas 40 Gy of concomitant radiotherapy was added in the nCRT arm.
The trial met the primary end point, histological complete response being achieved in 28% after nCRT versus 9% after nCT (P = 0.002). Lymph-node metastases were observed in 62% in the nCT group versus 35% in the nCRT group (P = 0.001). The R0 resection rate was 87% after nCRT and 74% after nCT (P = 0.04). There was no difference in overall survival between the treatment arms.
The addition of radiotherapy to neoadjuvant chemotherapy results in higher histological complete response rate, higher R0 resection rate, and a lower frequency of lymph-node metastases, without significantly affecting survival.
NCT01362127 (https://clinicaltrials.gov; The full study protocol was registered in the Clinical Trials Database).
Abstract Objective To compare the incidence and severity of postoperative complications after oesophagectomy for carcinoma of the oesophagus and gastro-oesophageal junction (GOJ) after randomized ...accrual to neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT). Background Neoadjuvant therapy improves long-term survival after oesophagectomy. To date, evidence is insufficient to determine whether combined nCT, or nCRT alone, is the most beneficial. Methods Patients with carcinoma of the oesophagus or GOJ, resectable with a curative intention, were enrolled in this multicenter trial conducted at seven centres in Sweden and Norway. Study participants were randomized to nCT or nCRT followed by surgery with two-field lymphadenectomy. Three cycles of cisplatin/5-fluorouracil was administered in all patients, while 40 Gy of concomitant radiotherapy was administered in the nCRT group. Results Of the randomized 181 patients, 91 were assigned to nCT and 90 to nCRT. One-hundred-and-fifty-five patients, 78 nCT and 77 nCRT, underwent resection. There was no statistically significant difference between the groups in the incidence of surgical or nonsurgical complications (P-value = 0.69 and 0.13, respectively). There was no 30-day mortality, while the 90-day mortality was 3% (2/78) in the nCT group and 6% (5/77) in the nCRT group (P = 0.24). The median Clavien-Dindo complication severity grade was significantly higher in the nCRT group (P = 0.001). Conclusion There was no significant difference in the incidence of complications between patients randomized to nCT and nCRT. However, complications were significantly more severe after nCRT. Registration trial database The trial was registered in the Clinical Trials Database (registration number NCT01362127 ).
Ultralight Metallic Microlattices Schaedler, T. A.; Jacobsen, A. J.; Torrents, A. ...
Science (American Association for the Advancement of Science),
11/2011, Letnik:
334, Številka:
6058
Journal Article
Recenzirano
Ultralight (< 10 milligrams per cubic centimeter) cellular materials are desirable for thermal insulation; battery electrodes; catalyst supports; and acoustic, vibration, or shock energy damping. We ...present ultralight materials based on periodic hollow-tube microlattices. These materials are fabricated by starting with a template formed by self-propagating photopolymer waveguide prototyping, coating the template by electroless nickel plating, and subsequently etching away the template. The resulting metallic microlattices exhibit densities ρ > 0.9 milligram per cubic centimeter, complete recovery after compression exceeding 50% strain, and energy absorption similar to elastomers. Young's modulus Å scales with density as E ~ p², in contrast to the £ ~ p³ scaling observed for ultralight aerogels and carbon nanotube foams with stochastic architecture. We attribute these properties to structural hierarchy at the nanometer, micrometer, and millimeter scales.
Background
There are few data comparing health‐related quality of life (HRQoL) after neoadjuvant chemotherapy alone (nCT) compared with neoadjuvant chemoradiotherapy (nCRT) in patients with ...oesophageal cancer.
Methods
In the NeoRes trial, patients were assigned randomly in a 1 : 1 ratio to receive either cisplatin 100 mg/m2 on day 1 and an infusion of 750 mg per m2 5‐fluorouracil over 24 h on days 1–5 in three 21‐day cycles (nCT) or the same chemotherapy regimen, but with the addition of 40 Gy radiotherapy (nCRT). HRQoL data were collected at baseline, after neoadjuvant therapy and at 1, 3 and 5 years after surgery. The European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire QLQ‐C30 and disease‐specific modules were used.
Results
Of 181 patients randomized, 165 were included in the analysis of HRQoL. In a direct comparison between the allocated treatments, odynophagia after completion of neoadjuvant therapy but before surgery (P = 0·047) and troublesome coughing at 3 years' follow‐up (P = 0·011) were more pronounced in the nCRT arm. In the longitudinal analyses within each treatment arm, a large deterioration in HRQoL was noted at 1 year. Some recovery was seen in both arms over time but, after 3 and 5 years, patients in the nCRT arm reported more symptoms compared with baseline than patients in the nCT arm.
Conclusion
HRQoL after multimodal treatment for cancer of the oesophagus or gastro‐oesophageal junction was impaired and more pronounced in patients who underwent nCRT, with only partial recovery over time.
Antecedentes
Se dispone de poca información sobre la calidad de vida relacionada con la salud (health‐related quality of life, HRQOL) en pacientes con cáncer de esófago después de quimioterapia neoadyuvante sola en comparación con quimiorradioterapia neoadyuvante.
Métodos
En el ensayo NeoRes, los pacientes fueron asignados de forma aleatoria 1:1 a tratamiento con cisplatino 100 mg/m2 en el día uno y 5‐Fluorouracilo 750 mg/m2/infusión de 24 horas en los días 1‐5 en tres ciclos de 21 días (nCT) o al mismo régimen de quimioterapia, pero con la adición de radioterapia 40 Gy (nCRT). Los datos de HRQOL se recogieron al inicio, tras el tratamiento neoadyuvante y al cabo de 1, 3 y 5 años tras la cirugía. Se utilizaron los cuestionarios QLQ‐C30 de la European Organisation for Research and Treatment of Cancer (EORTC) y los módulos específicos para la enfermedad.
Resultados
De 181 pacientes aleatorizados, 165 fueron incluidos en el análisis de la HRQOL. En la comparación directa entre los tratamientos asignados, la odinofagia tras terminar nCRT pero antes de la cirugía (P = 0,047) y la tos molesta a los 3 años de seguimiento (P = 0,011), fueron más acentuadas en el brazo de nCRT. En el análisis longitudinal dentro de cada rama de tratamiento hubo un fuerte deterioro en la HRQOL al año. Se observó cierta recuperación en ambas ramas con el tiempo, pero a los 3 y 5 años de seguimiento, los pacientes de la rama de nCRT describieron más síntomas en comparación con la situación de inicio que los pacientes de la rama de nCT.
Conclusión
La HRQOL después del tratamiento multimodal del cáncer de esófago o de la unión gastroesofágica se ve afectada, siendo dicha afectación más pronunciada en pacientes que recibieron nCRT, recuperándose solo parcialmente con el tiempo.
Analysis of health‐related quality of life in the NeoRes trial found that patients allocated to neoadjuvant chemoradiotherapy (nCRT) reported more symptoms at 3 and 5 years' follow‐up compared with those who had neoadjuvant chemotherapy (nCT) for oespophageal cancer.
More impairment after chemoradiation
NeoRes I is a randomized phase II trial comparing neoadjuvant chemoradiotherapy with neoadjuvant chemotherapy in the treatment of resectable cancer of the esophagus or gastroesophageal junction. ...Patients with biopsy-proven adenocarcinoma or squamous cell carcinoma, T1N1 or T2-3N0-1 and M0-M1a (AJCC 6th ed.), were randomized to receive three 3-weekly cycles of cisplatin 100 mg/m2 day 1 and fluorouracil 750 mg/m2/24 hours, days 1-5 with or without the addition of concurrent radiotherapy 40 Gy, 2 Gy/fraction, 5 days a week, followed by esophageal resection with two-field lymphadenectomy. Primary endpoint was complete histopathological response rate in the primary tumor. Survival and recurrence patterns were evaluated as secondary endpoints. Between 2006 and 2013, 181 patients were enrolled in Sweden and Norway. All three chemotherapy cycles were delivered to 73% of the patients allocated to chemoradiotherapy and to 86% of the patients allocated to chemotherapy. 87% of those allocated to chemoradiotherapy received full dose radiotherapy. 87% in the chemoradiotherapy group and 86% in the chemotherapy group underwent tumor resection. Initial results showed that patients allocated to chemoradiotherapy more often responded with complete histopathological response in the primary tumor (28% vs. 9%). Treatment-related complications were similar between the groups although postoperative complications were more severe in the chemoradiotherapy group. This article reports the long-term results. Five-year progression-free survival was 38.9% (95% CI 28.9%-48.8%) in the chemoradiotherapy group versus 33.0% (95% CI 23.6%-42.7%) in the chemotherapy group, P = 0.82. Five-year overall survival was 42.2% (95% CI 31.9%-52.1%) versus 39.6% (95% CI 29.5%-49.4%), P = 0.60. There were no differences in recurrence patterns between the treatment groups. This is to our knowledge that the largest completed randomized trial comparing neoadjuvant chemotherapy with neoadjuvant chemoradiotherapy followed by esophageal resection in patients with cancer in the esophagus or gastroesophageal junction. Despite a higher tumor tissue response in those who received neoadjuvant chemoradiotherapy, no survival advantages were seen. Consequently, the results do not support unselected addition of radiotherapy to neoadjuvant chemotherapy as a standard of care in patients with resectable esophageal cancer.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
•MUNIX is almost entirely dependent on CMAP amplitude in healthy controls and patients.•MUNIX is particularly misleading for muscles with normal or small MUs, due to superimposition of MUPs.•MUNIX ...should not be used as a measure of the number of functional motor units in a muscle.
MUNIX (motor unit number index), derived from the compound muscle action potential (CMAP) and surface EMG interference pattern (SIP) has become popular as a substitute for motor unit number estimation (MUNE). This study was undertaken to determine why, in recent recordings from amyotrophic lateral sclerosis (ALS) patients and healthy controls, we found that MUNIX values resembled CMAP amplitudes more closely than MUNE values.
The relationship between MUNIX and CMAP and SIP amplitudes was investigated by a theoretical analysis and by reanalysing the data from the previous study.
Theory indicates that when motor unit potentials overlap extensively, information about motor unit size and number is lost, and MUNIX depends only on CMAP area and power. Accordingly, MUNIX values were found to be sensitive to changes in CMAP amplitude but insensitive to changes in SIP amplitude. The reproducibility of MUNIX measurements in healthy controls was found to depend almost entirely on correlation with CMAP properties.
MUNIX gives misleading information about motor unit numbers in healthy controls, and provides little information about loss of motor units in ALS patients beyond that given by simple CMAP amplitude measurements.
MUNIX should not be interpreted as a MUNE method.
Summary
Discussions of eosinophils are often descriptions of end‐stage effector cells with destructive capabilities mediated predominantly by released cytotoxic cationic granule proteins. Moreover, ...eosinophils in the medical literature are invariably associated with the pathologies linked with helminth infections or allergic diseases such as asthma. This has led to an almost fatalist view of eosinophil effector functions and associated therapeutic strategies targeting these cells that would make even William of Ockham proud – eosinophil effector functions have physiological consequences that increase patient morbidity/mortality and ‘the only good eosinophils are dead eosinophils’. Unfortunately, the strengths of dogmas are also their greatest weaknesses. Namely, while the repetitive proclamation of dogmatic concepts by authoritative sources (i.e. reviews, meeting proceedings, textbooks, etc.) builds consensus within the medical community and lower the entropies surrounding difficult issues, they often ignore not easily explained details and place diminished importance on alternative hypotheses. The goal of this perspective is twofold: (i) we will review recent observations regarding eosinophils and their activities as well as reinterpret earlier data as part of the synthesis of a new paradigm. In this paradigm, we hypothesize that eosinophils accumulate at unique sites in response to cell turnover or in response to local stem cell activity(ies). We further suggest that this accumulation is part of one or more mechanisms regulating tissue homeostasis. Specifically, instead of immune cells exclusively mediating innate host defence, we suggest that accumulating tissue eosinophils are actually regulators of Local Immunity And/or Remodeling/Repair in both health and disease – the LIAR hypothesis; (ii) we want to be inflammatory (pun intended!) and challenge the currently common perspective of eosinophils as destructive end‐stage effector cells. Our hope is to create more questions than we answer and provoke everyone to spend countless hours simply to prove us wrong!
Cite this as: J. J. Lee, E. A. Jacobsen, M. P. McGarry, R. P. Schleimer and N. A. Lee, Clinical & Experimental Allergy, 2010 (40) 563–575
The enigmatic eosinophil has emerged as an exciting component of the immune system, involved in a plethora of homeostatic and inflammatory responses. Substantial progress has been achieved through ...experimental systems manipulating eosinophils in vivo, initially in mice and more recently in humans. Researchers using eosinophil knockout mice have identified a contributory role for eosinophils in basal and inflammatory processes and protective immunity. Primarily fueled by the purported proinflammatory role of eosinophils in eosinophil-associated diseases, a series of anti-eosinophil therapeutics have emerged as a new class of drugs. These agents, which dramatically deplete eosinophils, provide a valuable opportunity to characterize the consequences of eosinophil knockout humans. Herein, we comparatively describe mouse and human eosinophil knockouts. We put forth the view that human eosinophils negatively contribute to a variety of diseases and, unlike mouse eosinophils, do not yet have an identified role in physiological health; thus, clarifying all roles of eosinophils remains an ongoing pursuit.
The cBioPortal for Cancer Genomics (http://cbioportal.org) provides a Web resource for exploring, visualizing, and analyzing multidimensional cancer genomics data. The portal reduces molecular ...profiling data from cancer tissues and cell lines into readily understandable genetic, epigenetic, gene expression, and proteomic events. The query interface combined with customized data storage enables researchers to interactively explore genetic alterations across samples, genes, and pathways and, when available in the underlying data, to link these to clinical outcomes. The portal provides graphical summaries of gene-level data from multiple platforms, network visualization and analysis, survival analysis, patient-centric queries, and software programmatic access. The intuitive Web interface of the portal makes complex cancer genomics profiles accessible to researchers and clinicians without requiring bioinformatics expertise, thus facilitating biological discoveries. Here, we provide a practical guide to the analysis and visualization features of the cBioPortal for Cancer Genomics.
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