The Impact of Metastatic Lymph Node Size on Long-term Outcomes for pStage III Colon Cancer

Aim: To clarify the impact of metastatic lymph node size on long-term outcomes in patients undergoing curative colectomy for pathological stage III colon cancer. Patients and Methods: This study enrolled patients who underwent curative colectomy for pStage III colon cancer between January 2013 and December 2015. All patients were divided into four groups based on the short-axis diameter of the largest MLN: Group A, <5 mm; Group B, ≥5 mm and <10 mm; Group C, ≥10 mm and <15 mm; Group D, ≥15 mm. Results: A total of 209 patients were analyzed. The 5-year recurrence-free survival rates of Groups A, B, C, and D were 82.3%, 74.6%, 74.5% and 60.7%, respectively. In multivariate analysis, Group D (hazard ratio=3.95; 95% confidence interval, 1.34-11.65; p=0.01) was independently associated with worse RFS. Conclusion: Bulky MLNs might be a poor prognostic factor in node-positive colon cancer.

A Retrospective Study of Clinical and Histopathological Features of 81 Cases of Canine Apocrine Gland Adenocarcinoma of the Anal Sac: Independent Clinical and Histopathological Risk Factors Associated with Outcome

Canine apocrine gland anal sac adenocarcinoma (AGASAC) is a malignant tumour with variable clinical progression. The objective of this study was to use robust multivariate models, based on models employed in human medical oncology, to establish clinical and histopathological risk factors of poor survival. Clinical data and imaging of 81 cases with AGASAC were reviewed. Tissue was available for histological review and immunohistochemistry in 49 cases. Tumour and lymph node size were determined using the response evaluation criteria in the solid tumours system (RECIST). Modelling revealed tumour size over 2 cm, lymph node size grouped in three tiers by the two thresholds 1.6 cm and 5 cm, surgical management, and radiotherapy were independent clinical variables associated with survival, irrespective of tumour stage. Tumour size over 1.3 cm and presence of distant metastasis were independent clinical variables associated with the first progression-free interval. The presence of the histopathological variables of tumour necrosis, a solid histological pattern, and vascular invasion in the primary tumour were independent risk factors of poor survival. Based upon these independent risk factors, scoring algorithms to predict survival in AGASAC patients are presented.

Iron Nanoparticles as Magnetic Resonance Imaging Contrast Agents

<p>Magnetic nanoparticles are effective in a range of biomedical applications including magneticresonance imaging (MRI) contrast enhancement. The efficacy of nanoparticles ascontrast agents depends mainly on the surface chemistry and magnetic properties of theparticles, with a large magnetic moment inducing efficient transverse (T₂) relaxation ofprotons. This results in improved negative enhancement of MRI contrast on T₂ weightedsequences. Iron oxide nanoparticles (FeOx NPs) have been used in MRI for 20 years andare the only commercially available T₂ contrast agents. A significantly larger magneticmoment can potentially be achieved with iron nanoparticles (Fe NPs), but developmenthas been hampered by difficulty in preparing stable particles. In this study, stable Fe NPwere prepared by a novel, simple, synthesis and compared with FeOx NP as T₂ contrastagents in a range of MRI-based biomedical applications.The effectiveness of Fe NPs versus FeOx NPs to negatively enhance MRI contrast onT₂ weighted sequences was first examined in vitro. The Fe NPs and FeOx NPs werecharacterised by electron microscopy and found to be of similar size (16nm). The Fe NPspossessed a core of highly magnetic α-Fe inside a 3nm shell of FeOx of the same crystalstructure as the pure FeOx NPs. Both types of NP were coated with the same molecule,DMSA, to produce aqueous dispersions with similar hydrodynamic particle sizes andpharmacokinetics. When dispersed in gels and examined by MRI, the Fe NPs were foundto produce more than twice the amount of T₂ contrast change per unit concentrationrelative to FeOx NPs. When cells were labelled in vitro, Fe NPs produced greater T₂contrast enhancement in all cell types tested, whilst there was no significant difference in the uptake of iron or the cytotoxicity between cells labelled with Fe or FeOx NPs.To assess the clinical applicability of the nanoparticles in vivo, FeOx NPs and Fe NPswere administered to mice and MRI experiments were performed at 1.5 T. Contrast effectsof the NPs were examined in the liver, spleen and lymph nodes, as tissues in theseorgans are rich in phagocytic cells and have a strong tendency to take up circulatingNPs. In all three organs studied, the Fe NPs produced noticeably darker contrast thanthe FeOx NPs, providing twice the contrast improvement.One of the most intensely researched applications of magnetic nanoparticles in MRI is improving detection of cancer in the lymph nodes. To model the size and NP uptake ofsmall lymph node metastases in humans, a mouse model was developed by injecting 4T1breast cancer cells directly into the mouse spleen. Analysis of mice bearing 4T1 tumoursperformed at 1.5 T showed that Fe NPs produced better contrast than FeOx NPs andimproved the detection of small tumours in the spleen as determined by two blindedradiologists. Indeed, the heightened sensitivity and specificity improved the threshold ofcancer detection on previous studies performed at 1.5 T.It was then examined whether the improved T₂ contrast could enable new MRI applicationsin vivo. A novel assay to detect induced immune responses following dendriticcell-based vaccination using MRI was developed. By tracking cells labelled with ironnanoparticles, a difference in contrast could be detected between nave mice and thosethat had developed a strong immune response after vaccination. This assay only reachedstatistical significance with Fe NPs and not with FeOx NPs.As a consequence of these studies, another MRI-based technique for assessing inductionof an immune response was developed, based on the simple observation that lymph nodesdraining the injection site became enlarged. This enlargement was seen as early as 12 hours after vaccination and was caused by a cellular in filtrate dominated by lymphoidcells. In experiments where vaccination was performed multiple times using different tumoursas a source of antigen, incremental increases in lymph node size were detectableby MRI, which was shown to be a highly antigen-specific response. In the vaccine modelstudied, the increase in lymph node size was associated with protection from a tumour challenge. Thus, Fe NPs produce a significant improvement of T₂ contrast over FeOx NPs in a rangeof applications without any differences found in uptake or cytotoxicity. These findingsare substantial enough to justify further investigations into the application of Fe NPs ina variety of clinical settings.</p>

Iron Nanoparticles as Magnetic Resonance Imaging Contrast Agents

<p>Magnetic nanoparticles are effective in a range of biomedical applications including magneticresonance imaging (MRI) contrast enhancement. The efficacy of nanoparticles ascontrast agents depends mainly on the surface chemistry and magnetic properties of theparticles, with a large magnetic moment inducing efficient transverse (T₂) relaxation ofprotons. This results in improved negative enhancement of MRI contrast on T₂ weightedsequences. Iron oxide nanoparticles (FeOx NPs) have been used in MRI for 20 years andare the only commercially available T₂ contrast agents. A significantly larger magneticmoment can potentially be achieved with iron nanoparticles (Fe NPs), but developmenthas been hampered by difficulty in preparing stable particles. In this study, stable Fe NPwere prepared by a novel, simple, synthesis and compared with FeOx NP as T₂ contrastagents in a range of MRI-based biomedical applications.The effectiveness of Fe NPs versus FeOx NPs to negatively enhance MRI contrast onT₂ weighted sequences was first examined in vitro. The Fe NPs and FeOx NPs werecharacterised by electron microscopy and found to be of similar size (16nm). The Fe NPspossessed a core of highly magnetic α-Fe inside a 3nm shell of FeOx of the same crystalstructure as the pure FeOx NPs. Both types of NP were coated with the same molecule,DMSA, to produce aqueous dispersions with similar hydrodynamic particle sizes andpharmacokinetics. When dispersed in gels and examined by MRI, the Fe NPs were foundto produce more than twice the amount of T₂ contrast change per unit concentrationrelative to FeOx NPs. When cells were labelled in vitro, Fe NPs produced greater T₂contrast enhancement in all cell types tested, whilst there was no significant difference in the uptake of iron or the cytotoxicity between cells labelled with Fe or FeOx NPs.To assess the clinical applicability of the nanoparticles in vivo, FeOx NPs and Fe NPswere administered to mice and MRI experiments were performed at 1.5 T. Contrast effectsof the NPs were examined in the liver, spleen and lymph nodes, as tissues in theseorgans are rich in phagocytic cells and have a strong tendency to take up circulatingNPs. In all three organs studied, the Fe NPs produced noticeably darker contrast thanthe FeOx NPs, providing twice the contrast improvement.One of the most intensely researched applications of magnetic nanoparticles in MRI is improving detection of cancer in the lymph nodes. To model the size and NP uptake ofsmall lymph node metastases in humans, a mouse model was developed by injecting 4T1breast cancer cells directly into the mouse spleen. Analysis of mice bearing 4T1 tumoursperformed at 1.5 T showed that Fe NPs produced better contrast than FeOx NPs andimproved the detection of small tumours in the spleen as determined by two blindedradiologists. Indeed, the heightened sensitivity and specificity improved the threshold ofcancer detection on previous studies performed at 1.5 T.It was then examined whether the improved T₂ contrast could enable new MRI applicationsin vivo. A novel assay to detect induced immune responses following dendriticcell-based vaccination using MRI was developed. By tracking cells labelled with ironnanoparticles, a difference in contrast could be detected between nave mice and thosethat had developed a strong immune response after vaccination. This assay only reachedstatistical significance with Fe NPs and not with FeOx NPs.As a consequence of these studies, another MRI-based technique for assessing inductionof an immune response was developed, based on the simple observation that lymph nodesdraining the injection site became enlarged. This enlargement was seen as early as 12 hours after vaccination and was caused by a cellular in filtrate dominated by lymphoidcells. In experiments where vaccination was performed multiple times using different tumoursas a source of antigen, incremental increases in lymph node size were detectableby MRI, which was shown to be a highly antigen-specific response. In the vaccine modelstudied, the increase in lymph node size was associated with protection from a tumour challenge. Thus, Fe NPs produce a significant improvement of T₂ contrast over FeOx NPs in a rangeof applications without any differences found in uptake or cytotoxicity. These findingsare substantial enough to justify further investigations into the application of Fe NPs ina variety of clinical settings.</p>

External-memory Dictionaries in the Affine and PDAM Models

Storage devices have complex performance profiles, including costs to initiate IOs (e.g., seek times in hard drives), parallelism and bank conflicts (in SSDs), costs to transfer data, and firmware-internal operations. The Disk-access Machine (DAM) model simplifies reality by assuming that storage devices transfer data in blocks of size B and that all transfers have unit cost. Despite its simplifications, the DAM model is reasonably accurate. In fact, if B is set to the half-bandwidth point, where the latency and bandwidth of the hardware are equal, then the DAM approximates the IO cost on any hardware to within a factor of 2. Furthermore, the DAM model explains the popularity of B-trees in the 1970s and the current popularity of B ɛ -trees and log-structured merge trees. But it fails to explain why some B-trees use small nodes, whereas all B ɛ -trees use large nodes. In a DAM, all IOs, and hence all nodes, are the same size. In this article, we show that the affine and PDAM models, which are small refinements of the DAM model, yield a surprisingly large improvement in predictability without sacrificing ease of use. We present benchmarks on a large collection of storage devices showing that the affine and PDAM models give good approximations of the performance characteristics of hard drives and SSDs, respectively. We show that the affine model explains node-size choices in B-trees and B ɛ -trees. Furthermore, the models predict that B-trees are highly sensitive to variations in the node size, whereas B ɛ -trees are much less sensitive. These predictions are born out empirically. Finally, we show that in both the affine and PDAM models, it pays to organize data structures to exploit varying IO size. In the affine model, B ɛ -trees can be optimized so that all operations are simultaneously optimal, even up to lower-order terms. In the PDAM model, B ɛ -trees (or B-trees) can be organized so that both sequential and concurrent workloads are handled efficiently. We conclude that the DAM model is useful as a first cut when designing or analyzing an algorithm or data structure but the affine and PDAM models enable the algorithm designer to optimize parameter choices and fill in design details.

Suggestions to the article: Overview of Graves Ophthalmopathy Literature From 1999 to 2019: Bibliometric Analysis (Preprint)

UNSTRUCTURED The article published on 28 September 2018 is well-written and of interest, but remains several questions that are required for clarifications, such as (1) the number of publications for each year should be noted at the bottom of Figure 1 so that any reader who is interested in reproducing the exponential growth curve(EGC) can compare them each other; (2) the node size in Figure 2 representing the number of author outputs, with larger size indicating more outputs, should be further clarified about the meaning in social network analysis(SNA); and (3) the burst strength and the corresponding temporal bar graphs(TBG) for keywords and citation references in Figures 7 and 9 requires further interpretations. We listed suggestions and references to the article for improvement made in the future relevant studies, including (1)the inflection point(IP) on the EGC; (2) the node size in Figure 2 should equal the weighted publication in comparison to other nodes in the network; and (3) the improved TBG combined with IP and burst strength using the bar size to represent is demonstrated. The three improved visualization of EGC, SNA, and TBG were suggested to the article and the future studies with deeper insights into the bibliometric analysis and make the data easier and clearer to understand.

Pediatric lymphadenopathy: Which patients need evaluation by an oncologist?

e13605 Background: While lymphadenopathy may be the first sign of cancer in children, it can also be a manifestation of non-malignant illness. Lymphadenopathy is a common reason for referral to a pediatric oncologist, which can result in significant anxiety for parents. Understanding which patients require an oncology referral for lymphadenopathy is key in order to streamline healthcare utilization for this common clinical entity. Methods: In this single institution study, we retrospectively reviewed the medical records of patients referred to pediatric oncology for lymphadenopathy between 2012 and 2020. A logistic regression model was fitted to examine the association between the maximum size of the lymph nodes and cancer diagnosis. We also obtained estimates of odds ratio and area under the ROC curve. Sensitivity and specificity were estimated using exact Clopper-Pearson method for proportion. SAS v9.4 was used to perform statistical analyses. Institutional IRB approved the study. Results: A total of 91 patients aged 1 to 19 years (median 14 years) were included. There was a statistically significant association between lymph node size and a diagnosis of malignancy. For every centimeter increase in maximal dimension of lymph node(s), there was an estimated 2.2-times increase in the odds of cancer (CI 95% 1.5-3.3; p = 0.0002). The estimated area under the curve for this model was 0.8 (95% CI 0.7-0.9) indicating that lymph node size correlated very well with cancer risk. We evaluated the model to find a threshold for lymph node size that provided a high sensitivity for screening purposes. A cut-off of 2 centimeters resulted in an estimated sensitivity of 0.95 (95%CI 0.7-0.99) and specificity of 0.6 (95%CI 0.5-0.7). Conclusions: This study provides preliminary evidence that the estimated odds of a cancer diagnosis doubles for each centimeter increase in lymph node size. This single institution retrospective study suggests that in patients with lymphadenopathy, the maximum lymph node size may be a predictor of malignancy. Our results demonstrate that the sensitivity for cancer increases at a lymph node size of two centimeters or larger. Navigating when to monitor a patient with lymphadenopathy in the primary care setting versus referring to the oncologist can be a challenge for primary care physicians. Our results are consistent with the practice that using a two centimeter cutoff is a good starting point for referrals; however, these results will need to be verified with a larger sample size before they are adopted into clinical guidelines. Further study is underway to evaluate lymphadenopathy referrals to both surgery and oncology in order to reduce potential bias that may be associated with oncology referrals, which may have a predilection for malignancy. This study underlines the importance of a physical examination by the primary care physician as the crucial step in determining if a patient requires an oncology referral.