To update the Memorial Sloan-Kettering Cancer Center's experience with intensity-modulated radiotherapy (IMRT) in the treatment of oropharyngeal cancer (OPC).
Between September 1998 and April 2009, ...442 patients with histologically confirmed OPC underwent IMRT at our center. There were 379 men and 63 women with a median age of 57 years (range, 27-91). The disease was Stage I in 2%, Stage II in 4%, Stage III in 21%, and Stage IV in 73% of patients. The primary tumor subsite was tonsil in 50%, base of tongue in 46%, pharyngeal wall in 3%, and soft palate in 2%. The median prescription dose to the planning target volume of the gross tumor was 70 Gy for definitive (n = 412) cases and 66 Gy for postoperative cases (n = 30). A total 404 patients (91%) received chemotherapy, including 389 (88%) who received concurrent chemotherapy, the majority of which was platinum-based.
Median follow-up among surviving patients was 36.8 months (range, 3-135). The 3-year cumulative incidence of local failure, regional failure, and distant metastasis was 5.4%, 5.6%, and 12.5%, respectively. The 3-year OS rate was 84.9%. The incidence of late dysphagia and late xerostomia ≥Grade 2 was 11% and 29%, respectively.
Our results confirm the feasibility of IMRT in achieving excellent locoregional control and low rates of xerostomia. According to our knowledge, this study is the largest report of patients treated with IMRT for OPC.
(1) To determine baseline demographic, geographic, clinical, and pathologic characteristics of patients who had transoral robotic surgery (TORS) for oropharyngeal cancer. (2) To analyze margin status ...and unplanned readmission after TORS versus nonrobotic surgery.
Retrospective database review.
National Cancer Database (2010-2011).
Searching the National Cancer Database for adults with oropharyngeal cancer, we identified 877 patients who had TORS and 4269 patients who had nonrobotic surgery. Outcomes of interest included likelihood of adjuvant therapy, margin status, and unplanned readmission. Statistical analysis included chi-square, t tests, and multivariate regression.
From 2010 to 2011, there was a 67% increase in the use of TORS for oropharyngeal cancer. Compared with patients who had nonrobotic surgery, TORS patients were more likely to be at academic centers (80.8% vs 49.1%, P < .001), to have private insurance (62.2% vs 57.4%, P < .001), and to have human papilloma virus (HPV)-positive tumors (48.3% vs 27.1%, P < .001). TORS (odds ratio, 0.50; 95% CI, 0.39-0.63) and HPV positivity (odds ratio, 0.73; 95% CI, 0.53-0.99) were independently associated with decreased likelihood of adjuvant chemoradiation versus radiation therapy. TORS patients were less likely to have positive margins than were patients who had nonrobotic surgery (20.2% vs 31.0%, P < .001). High-volume TORS centers had lower rates of positive margins (15.8% vs 26.1%, P < .001) and unplanned readmissions (3.1% vs 6.1%, P < .03) than did low-volume centers.
TORS is being rapidly adopted by academic and community cancer centers. TORS is associated with a lower rate of positive margins than nonrobotic surgery, and high-volume centers have the lowest rates of positive margins and unplanned readmissions.
Disruption of naturally evolved spatial patterns of genetic variation and local adaptations is a growing concern in wildlife management and conservation. During the last decade, releases of native ...taxa with potentially non-native genotypes have received increased attention. This has mostly concerned conservation programs, but releases are also widely carried out to boost harvest opportunities. The mallard,
Anas platyrhynchos
, is one of few terrestrial migratory vertebrates subjected to large-scale releases for hunting purposes. It is the most numerous and widespread duck in the world, yet each year more than three million farmed mallard ducklings are released into the wild in the European Union alone to increase the harvestable population. This study aimed to determine the genetic effects of such large-scale releases of a native species, specifically if wild and released farmed mallards differ genetically among subpopulations in Europe, if there are signs of admixture between the two groups, if the genetic structure of the wild mallard population has changed since large-scale releases began in the 1970s, and if the current data matches global patterns across the Northern hemisphere. We used Bayesian clustering (S
tructure
software) and Discriminant Analysis of Principal Components (DAPC) to analyze the genetic structure of historical and present-day wild (
n
= 171 and
n
= 209, respectively) as well as farmed (
n
= 211) mallards from six European countries as inferred by 360 single-nucleotide polymorphisms (SNPs). Both methods showed a clear genetic differentiation between wild and farmed mallards. Admixed individuals were found in the present-day wild population, implicating introgression of farmed genotypes into wild mallards despite low survival among released farmed mallards. Such cryptic introgression would alter the genetic composition of wild populations and may have unknown long-term consequences for conservation.
There is an urgent need to increase the global data storage capacity, as current approaches lag behind the exponential growth of data generation driven by the Internet, social media, and cloud ...technologies. In addition to increasing storage density, new solutions should provide long‐term data archiving that goes far beyond traditional magnetic memory, optical disks, and solid‐state drives. Here, a concept of energy‐efficient, ultralong, high‐density data archiving is proposed, based on optically active atomic‐size defects in a radiation resistance material, silicon carbide (SiC). The information is written in these defects by focused ion beams and read using photoluminescence or cathodoluminescence. The temperature‐dependent deactivation of these defects suggests a retention time minimum over a few generations under ambient conditions. With near‐infrared laser excitation, grayscale encoding and multi‐layer data storage, the areal density corresponds to that of Blu‐ray discs. Furthermore, it is demonstrated that the areal density limitation of conventional optical data storage media due to the light diffraction can be overcome by focused electron‐beam excitation.
A concept of ultralong, high‐density data archiving based on optically active atomic‐size defects in silicon carbide (SiC) is proposed. The information is written in these defects by focused ion beams and read using photoluminescence or cathodoluminescence. The temperature‐dependent deactivation of these defects suggests a retention time minimum over a few generations under ambient conditions.
The translocation of individuals around the world is leading to rising incidences of anthropogenic hybridization, particularly between domestic and wild congeners. We apply a landscape genomics ...approach for thousands of mallard (Anas platyrhynchos) samples across continental and island populations to determine the result of over a century of supplementation practices. We establish that a single domestic game-farm mallard breed is the source for contemporary release programs in Eurasia and North America, as well as for established feral populations in New Zealand and Hawaii. In particular, we identify central Europe and eastern North America as epicenters of ongoing anthropogenic hybridization, and conclude that the release of game-farm mallards continues to affect the genetic integrity of wild mallards. Conversely, self-sustaining feral populations in New Zealand and Hawaii not only show strong differentiation from their original stock, but also signatures of local adaptation occurring in less than a half-century since game-farm mallard releases have ceased. We conclude that 'wild' is not singular, and that even feral populations are capable of responding to natural processes. Although considered paradoxical to biological conservation, understanding the capacity for wildness among feral and feral admixed populations in human landscapes is critical as such interactions increase in the Anthropocene.
The impacts of hybridization on the process of speciation are manifold, leading to distinct patterns across the genome. Genetic differentiation accumulates in certain genomic regions, while ...divergence is hampered in other regions by homogenizing gene flow, resulting in a heterogeneous genomic landscape. A consequence of this heterogeneity is that genomes are mosaics of different gene histories that can be compared to unravel complex speciation and hybridization events. However, incomplete lineage sorting (often the outcome of rapid speciation) can result in similar patterns. New statistical techniques, such as the D-statistic and hybridization networks, can be applied to disentangle the contributions of hybridization and incomplete lineage sorting. We unravel patterns of hybridization and incomplete lineage sorting during and after the diversification of the True Geese (family Anatidae, tribe Anserini, genera Anser and Branta) using an exon-based hybridization network approach and taking advantage of discordant gene tree histories by re-sequencing all taxa of this clade. In addition, we determine the timing of introgression and reconstruct historical effective population sizes for all goose species to infer which demographic or biogeographic factors might explain the observed patterns of introgression.
We find indications for ancient interspecific gene flow during the diversification of the True Geese and were able to pinpoint several putative hybridization events. Specifically, in the genus Branta, both the ancestor of the White-cheeked Geese (Hawaiian Goose, Canada Goose, Cackling Goose and Barnacle Goose) and the ancestor of the Brent Goose hybridized with Red-breasted Goose. One hybridization network suggests a hybrid origin for the Red-breasted Goose, but this scenario seems unlikely and it not supported by the D-statistic analysis. The complex, highly reticulated evolutionary history of the genus Anser hampered the estimation of ancient hybridization events by means of hybridization networks. The reconstruction of historical effective population sizes shows that most species showed a steady increase during the Pliocene and Pleistocene. These large effective population sizes might have facilitated contact between diverging goose species, resulting in the establishment of hybrid zones and consequent gene flow.
Our analyses suggest that the evolutionary history of the True Geese is influenced by introgressive hybridization. The approach that we have used, based on genome-wide phylogenetic incongruence and network analyses, will be a useful procedure to reconstruct the complex evolutionary histories of many naturally hybridizing species groups.
Objectives/Hypothesis
To define the incidence and risk factors of metastatic disease and the effectiveness of salvage therapy in esthesioneuroblastoma (ENB).
Study Design
Retrospective analysis of 57 ...patients presenting from 1979 through 2009.
Methods
Cumulative incidence of neck failure, distant failure, and survival were assessed using the Kaplan‐Meier method.
Results
Overall survival for all patients was 85% at 5 years and 75% at 10 years. Overall survival was negatively impacted by intracranial tumor extension (P < 0.001), positive resection margins (P = 0.05), and neck metastases (P = 0.017). Neck lymph nodes were not routinely electively irradiated during this time period. Nodal metastases developed in 17% of patients at a median time of 60 months. Kadish stage was not associated with a risk of nodal metastasis (P = 0.78). After treatment for nodal recurrence, locoregional control was achieved in 78% of patients. Of patients developing nodal recurrence, more than half developed distant metastases. The cumulative incidence of distant metastasis was 39% at a median time of 40 months. Patients who presented with Kadish stage C or D had a significantly increased risk of distant failure (P < 0.001). In patients developing nodal (P = 0.017) or distant metastasis (P = 0.001), the probability of survival was significantly decreased.
Conclusion
Regional and distant metastases in patients with esthesioneuroblastoma occur in a delayed fashion and negatively impact survival. Neck nodal recurrence may be a harbinger of distant metastases. At the Memorial Sloan Kettering Cancer Center, New York, New York, we now treat the majority of ENB patients with elective nodal irradiation. However, the chief obstacle to long‐term cure is distant metastases.
Level of Evidence
4. Laryngoscope, 126:1556–1561, 2016
Biodiversity has suffered a dramatic global decline during the past decades, and monitoring tools are urgently needed providing data for the development and evaluation of conservation efforts both on ...a species and on a genetic level. However, in wild species, the assessment of genetic diversity is often hampered by the lack of suitable genetic markers. In this article, we present Random Amplicon Sequencing (RAMseq), a novel approach for fast and cost‐effective detection of single nucleotide polymorphisms (SNPs) in nonmodel species by semideep sequencing of random amplicons. By applying RAMseq to the Eurasian otter (Lutra lutra), we identified 238 putative SNPs after quality filtering of all candidate loci and were able to validate 32 of 77 loci tested. In a second step, we evaluated the genotyping performance of these SNP loci in noninvasive samples, one of the most challenging genotyping applications, by comparing it with genotyping results of the same faecal samples at microsatellite markers. We compared (i) polymerase chain reaction (PCR) success rate, (ii) genotyping errors and (iii) Mendelian inheritance (population parameters). SNPs produced a significantly higher PCR success rate (75.5% vs. 65.1%) and lower mean allelic error rate (8.8% vs. 13.3%) than microsatellites, but showed a higher allelic dropout rate (29.7% vs. 19.8%). Genotyping results showed no deviations from Mendelian inheritance in any of the SNP loci. Hence, RAMseq appears to be a valuable tool for the detection of genetic markers in nonmodel species, which is a common challenge in conservation genetic studies.
To review the role of mesenchymal stem cells (MSC) in bone formation and regeneration, and outline the development of strategies that use MSC in bone healing and regeneration. Literature review. ...Medline review, synopses of authors' published research. The MSC is the basic cellular unit of embryologic bone formation. Secondary bone healing mimics bone formation with proliferation of MSC then their differentiation into components of fracture callus. Bone regeneration, where large amounts of bone must form, mimics bone healing and can be achieved with MSC combined with strategies of osteogenesis, osteoinduction, osteoconduction, and osteopromotion. MSC based strategies first employed isolated and culture expanded stem cells in an osteoconductive carrier to successfully regenerate a critical segmental defect in the femur of dogs, which was as effective as autogenous cancellous bone. Because MSC appeared to be immunologically privileged, a study using mismatched allogeneic stem cells demonstrated that these cells would regenerate bone without inciting an immunologic response, documenting the possibility of banked allogeneic MSC for bone regeneration. A technique was developed for selectively retaining MSC from large bone marrow aspirates at surgery for bone regeneration. These techniques utilized osteoconductive and osteoinductive carriers and resulted in bone regeneration that was similar to autogenous cancellous bone. MSC can be manipulated and combined with carriers that will result in bone regeneration of critically sized bone defects. These techniques can be employed clinically to regenerate bone and serve as an alternative to autogenous cancellous bone.
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