The influence of genetic variation on late toxicities in childhood cancer survivors: a review

Publication date: Available online 12 April 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): E. Clemens, A.L.F. van der Kooi, L. Broer, E. van Dulmen-den Broeder, H. Visscher, L. Kremer, W. Tissing, J. Loonen, C.M. Ronckers, S.M.F. Pluijm, S.J.C.M.M. Neggers, O. Zolk, T. Langer, A. am Zehnhoff-Dinnesen, C.L. Wilson, M.M. Hudson, B. Carleton, J.S.E. Laven, A.G. Uitterlinden, M.M. van den Heuvel-Eibrink
IntroductionThe variability in late toxicities among childhood cancer survivors (CCS) is only partially explained by treatment and baseline patient characteristics. Inter-individual variability in the association between treatment exposure and risk of late toxicity suggests that genetic variation possibly modifies this association. We reviewed the available literature on genetic susceptibility of late toxicity after childhood cancer treatment related to components of metabolic syndrome, bone mineral density, gonadal impairment and hearing impairment.MethodsA systematic literature search was performed, using Embase, Cochrane Library, Google Scholar, MEDLINE, and Web of Science databases. Eligible publications included all English language reports of candidate gene studies and genome wide association studies (GWAS) that aimed to identify genetic risk factors associated with the four late toxicities, defined as toxicity present after end of treatment.ResultsTwenty-seven articles were identified, including 26 candidate gene studies: metabolic syndrome (n = 6); BMD (n = 6); gonadal impairment (n = 2); hearing impairment (n = 12) and one GWAS (metabolic syndrome). Eighty percent of the genetic studies on late toxicity after childhood cancer had relatively small sample sizes (n < 200), leading to insufficient power, and lacked adjustment for multiple comparisons. Only four (4/26 = 15%) candidate gene studies had their findings validated in independent replication cohorts as part of their own report.ConclusionGenetic susceptibility associations are not consistent or not replicated and therefore, currently no evidence-based recommendations can be made for hearing impairment, gonadal impairment, bone mineral density impairment and metabolic syndrome in CCS. To advance knowledge related to genetic variation influencing late toxicities among CCS, future studies need adequate power, independent cohorts for replication, harmonization of disease outcomes and sample collections, and (international) collaboration.



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Circulating Vascular Basement Membrane Fragments are Associated with the Diameter of the Abdominal Aorta and Their Expression Pattern is Altered in AAA Tissue

Publication date: Available online 12 April 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Mari Holsti, Anders Wanhainen, Christina Lundin, Martin Björck, Gustaf Tegler, Johan Svensson, Malin Sund
ObjectiveAbdominal aortic aneurysm (AAA) is characterised by enhanced proteolytic activity, and extracellular matrix (ECM) remodelling in the vascular wall. Type IV and XVIII collagen/endostatin are structural proteins in vascular basement membrane (VBM), a specialised ECM structure. Here the association between plasma levels of these collagens with the aortic diameter and expansion rate is studied, and their expression in aortic tissue characterised.MethodsThis was a retrospective population based cohort study. Type IV and XVIII collagen/endostatin were analysed in plasma by ELISA assay in 615 men, divided into three groups based on the aortic diameter: 1) normal aorta ≤ 25 mm, 2) sub-aneurysmal aorta (SAA) 26–29 mm, and 3) AAA ≥ 30 mm. Follow up data were available for 159 men. The association between collagen levels and aortic diameter at baseline, and with the expansion rate at follow up were analysed in ordinal logistic regression and linear regression models, controlling for common confounding factors. Tissue expression of the collagens was analysed in normal aorta (n = 6) and AAA (n = 6) by immunofluorescence.ResultsPlasma levels of type XVIII collagen/endostatin (136 ng/mL [SD 29] in individuals with a normal aorta diameter, 154 ng/ml [SD 45] in SAA, and 162 ng/ml [SD 46] in AAA; p = .001) and type IV collagen (105 ng/mL [SD 42] normal aorta, 124 ng/ml [SD 46] SAA, and 127 ng/ml [SD 47] AAA; p = .037) were associated with a larger aortic diameter. A significant association was found between the baseline levels of type XVIII/endostatin and the aortic expansion rate (p = .035), but in the multivariable model, only the initial aortic diameter remained significantly associated with expansion (p = .005). Altered expression patterns of both collagens were observed in AAA tissue.ConclusionPlasma levels of circulating type IV and XVIII collagen/endostatin increase with AAA diameter. The expression pattern of VBM proteins is altered in the aneurysm wall.



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Alterations in the microstructure of white matter in children and adolescents with Tourette syndrome measured using tract-based spatial statistics and probabilistic tractography

Publication date: Available online 12 April 2018
Source:Cortex
Author(s): Hilmar P. Sigurdsson, Sophia E. Pépés, Georgina M. Jackson, Amelia Draper, Paul S. Morgan, Stephen R. Jackson
Tourette syndrome (TS) is a neurodevelopmental disorder characterised by repetitive and intermittent motor and vocal tics. TS is thought to reflect fronto-striatal dysfunction and the aetiology of the disorder has been linked to widespread alterations in the functional and structural integrity of the brain. The aim of this study was to assess white matter abnormalities in a large sample of young patients with TS in comparison to a sample of matched typically developing control individuals (CS) using diffusion MRI. The study included 35 patients with TS (3 females; mean age: 14.0 ± 3.3) and 35 CS (3 females; mean age: 13.9 ± 3.3). Diffusion MRI data was analysed using tract-based spatial statistics (TBSS) and probabilistic tractography. Patients with TS demonstrated both marked and widespread decreases in axial diffusivity (AD) together with altered WM connectivity. Moreover, we showed that tic severity and the frequency of premonitory urges were associated with increased connectivity between primary motor cortex (M1) and the caudate nuclei, and increased information transfer between M1 and the insula, respectively. This is to our knowledge the first study to employ both TBSS and probabilistic tractography in a sample of young patients with TS. Our results contribute to the limited existing literature demonstrating altered connectivity in TS and confirm previous results suggesting in particular, that altered insular function contributes to increased frequency in premonitory urges.



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Anosognosia

Publication date: Available online 12 April 2018
Source:Cortex
Author(s): Daniel C. Mograbi, Robin Morris




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Beyond total mesorectal excision in locally advanced rectal cancer with organ or pelvic side-wall involvement

Publication date: Available online 12 April 2018
Source:European Journal of Surgical Oncology
Author(s): A.B. Mariathasan, K. Boye, K.E. Giercksky, B. Brennhovd, H.P. Gullestad, H.L. Emblemsvåg, K.K. Grøholt, S. Dueland, K. Flatmark, S.G. Larsen
BackgroundIn locally advanced rectal cancer (LARC), beyond total mesorectal excision (bTME) is often necessary to obtain complete resection (R0). The aim of this study was to identify prognostic determinants and compare morbidity and survival in LARC cases requiring bTME or TME surgery.MethodSingle centre cohort study of LARC cases where all patients received neoadjuvant radiotherapy (n=332). Data was registered prospectively in an institutional database linked to the National Registry.ResultsbTME surgery was performed in 224 patients, 171 with resections of adjacent organs (bTME-o group) and 53 with pelvic side-wall resections (bTME-pw group). TME surgery was performed in 108 patients. Six deaths occurred within 100 days and severe morbidity was registered in 23.8% of the whole cohort and in 25.4% of the bTME groups. The R0 rates were 93.5%, 84.2%, and 75.5% in the TME, bTME-o, and bTME-pw groups, respectively. Five-year disease free survival (DFS) was 67.3% (TME group), 54.5% (bTME-o group) and 48.7% (bTME-pw group), and five-year overall survival (OS) 78.7%, 69.0% and 60.4% respectively. Patients with involved resection margins (R1), high pT-stage, pN-postivity or poor response to neoadjuvant therapy were associated with inferior DFS and OS.ConclusionIn organ-threatening or infiltrating LARC, bTME surgery can be performed with low mortality and acceptable morbidity to obtain a good long-term outcome. Patients with pelvic side-wall infiltration were identified as a subgroup with increased risk of R1 resection and inferior long-term outcome.



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Can low grade PMP be divided into prognostically distinct subgroups based on histological features? A retrospective study and the importance of using the appropriate classification

Publication date: Available online 12 April 2018
Source:European Journal of Surgical Oncology
Author(s): Aditi Bhatt, Suniti Mishra, Robin Prabhu, Veena Ramaswamy, Antony George, Sonal Bhandare, Mita Shah, Sanket Mehta
IntroductionThe pathological classification of PMP of appendiceal origin has prognostic and treatment implications. Our goals were to •Classify low grade mucinous carcinoma peritonei (LGMCP) into prognostically distinct subgroups based on histological features •Compare the reproducibility of the WHO and the PSOGI classifications for both PMP and the appendiceal primary tumor.Patients and MethodsA retrospective analysis of patients undergoing CRS and HIPEC or debulking surgery was done. All the tumors were re-classified according to the PSOGI classification. LGMCP was further classified into three histological subgroups and the impact on survival was evaluated.ResultsFrom Jun 2011 to June 2016, 101 patients underwent CRS with HIPEC (n=89) or debulking surgery (n=12). The median PCI was 28 (3-39) and 74.1% patients had CC-0/1 resections. Of the 76.2 % patients who had LGMCP, 4 patients (5.1%) were classified as group 1, 54 (70.1%) as group 2 and 19 patients (24.6%) as group 3. At a median follow up of 21 months, the disease free survival was not reached, 30 and 14 months for groups 1, 2 and 3 respectively (p=0.09). There was no difference in overall survival. Using the WHO classification, there was a discordance in the grade of the primary tumor and the peritoneal lesions in 19.8% and conflicting terminology was used in 62 % of patients.ConclusionsThe subgroups of LGMCP described here are prognostically different though this needs further prospective evaluation in larger series. The PSOGI classification is more uniformly reproducible and should be preferred to the WHO classification.



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Erratum to the abstract: 1383: Breast cancer and HIV in the era of highly active antiretroviral therapy-a prospective, multi-centre study.EJSO 44S1 (2018)

Publication date: Available online 12 April 2018
Source:European Journal of Surgical Oncology
Author(s): Boitumelo Phakathi, Raquel Duarte, Caroline Dickens, Maureen Joffe, Sarah Nietz, Herbert Cubasch, Ines Buccimazza, Chas Cacala, Judith Jacobson, Alfred Neugat, Paul Ruff




https://ift.tt/2JC2tg1

The Hepatic Bridge

Publication date: Available online 11 April 2018
Source:European Journal of Surgical Oncology
Author(s): Paul H. Sugarbaker
BackgroundThe hepatic bridge forms a tunnel of liver parenchyma that may obscure peritoneal metastases associated with the round ligament. Visualization and then resection of nodules associated with this structure is necessary.Materials and methodsThe incidence of a hepatic bridge and the extent that it covered the round ligament was determined in consecutive patients. Extent of coverage of the round ligament by the hepatic bridge was determined: Class 1 indicates up to one-third of the round ligament obscured, Class 2 up to two-thirds and Class 3 more than two-thirds.ResultsIn 102 patients in whom the round ligament of the liver could be completely visualized, 50 had a hepatic bridge. Class 1 was 22 (44%) of the bridges, Class 2 was 16 (32%) and Class 3 was 12 (24%). A hepatic bridge was more frequently present in 28 of 45 male patients (62%) vs. 22 of 57 female patients (38%).ConclusionsApproximately one-half of our patients having cytoreductive surgery for peritoneal metastases were observed to have a hepatic bridge. Up to 56% of these patients have Class 2 or 3 hepatic bridge and may require division of the hepatic bridge to completely visualize the contents of the tunnel created by this structure.



https://ift.tt/2v8emao

Networking in rare cancers: what was done, what’s next

Publication date: Available online 12 April 2018
Source:European Journal of Surgical Oncology
Author(s): Anna Maria Frezza, Annalisa Trama, Jean-Yves Blay, Paolo G. Casali
Rare cancers represent approximately one fourth of all cancers. Despite being a heterogeneous group of diseases, they share similar problems including lack of expertise, issues in quality of care, discrepancies in outcome and limitations in research. Traditionally, centralization of rare cancer patients to dedicated reference centres has been recommended to ensure expertise, multidisciplinarity and access to innovation. However, centralization entails health migration, rationing of resources and a potential failure in routine care. By ensuring appropriate care to all patients regardless the point of access, networking seems the most appropriate answer to the problem of rare cancers. The launch of the Joint Action on Rare Cancers as well as the recent establishment of the European Reference Networks represent for the first time a concrete opportunity to make networking a reality and ultimately reduce disparities and improve outcome in these diseases.



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Histopathologic Patterns as markers of Prognosis in Patients undergoing Hepatectomy for Colorectal Cancer Liver Metastases - Pushing growth as an independent risk factor for decreased survival

Publication date: Available online 11 April 2018
Source:European Journal of Surgical Oncology
Author(s): Daniela Falcão, Henrique Alexandrino, Rui Caetano Oliveira, João Martins, Luís Ferreira, Ricardo Martins, Marco Serôdio, Mónica Martins, José Guilherme Tralhão, Maria Augusta Cipriano, Francisco Castro e Sousa
IntroductionLiver resection combined with neoadjuvant chemotherapy (NAC) has reported notable results in patients with colorectal liver metastasis (CRLM). Tumoral response to NAC is associated with specific histopathologic patterns with prognostic implications. The main objective of this study was to evaluate the influence of pathological findings on overall survival (OS), disease-free survival (DFS) and liver recurrence-free survival (LRFS).Patients and MethodsAnalysis of clinical and outcome data from 110 patients who underwent first CRLM resection between January 2010 and July 2013. Blinded pathological review of histological material of several parameters: resection margin, tumor regression grade (TRG), tumor thickness at the tumor-normal interface (TTNI) and the growth pattern (GP).ResultsThe median survival following hepatic resection was 52 months and 3- and 5- year Kaplan-Meier estimates were 69 and 48%, respectively. Seventy-four patients developed recurrent disease. Oxaliplatin-based chemotherapy was significantly associated with a pushing GP. A positive resection margin was an independent predictor of decreased DFS (p=0.018) but not of decreased OS. LRFS was strongly reduced by the absence of histologic tumor response (p=0.018). The pushing pattern had an adverse impact on both OS (p=0.007) and DFS (p=0.004) on multivariate analysis.ConclusionThe prognostic value of histopathological features in patients who underwent CRLM's resection is undeniable. The pushing GP was related with worse prognosis. Further studies are required to clarify the biological mechanisms underlying these findings in order to enhance a more personalized and efficient treatment of these patients.



https://ift.tt/2vdIHVg

Biological control of Meloidogyne javanica on tomato with Dazitol® and soil solarization

Abstract

Pot and greenhouse trials were conducted for the management of root-knot nematode, Meloidogyne javanica, infestation in tomato. Growth parameters, gall index, soil, and root nematode populations were measured to assess the effect of a novel bio-pesticide (Dazitol®), made from mustard oil and oleoresin of Capsicum, on plant growth and nematode reproduction. Data generated within the pot experiment showed that the tested bio-pesticide did not improve plant growth, but it reduced significantly root-knot nematode damage resulting in a decrease in gall index and root (91%) and soil (62%) population of M. javanica compared with untreated plants. The greenhouse experiment showed that Mocap® and Dazitol® decreased nematode incidence significantly (P < 0.05) on tomato. The result of this study suggested that the best nematode control was obtained by combining soil solarization with chemical or botanical nematicides as an integrated pest management approach.

https://ift.tt/2EGTBC3

Biosorption of strontium ions from simulated high-level liquid waste by living Saccharomyces cerevisiae

Abstract

In this study, the Saccharomyces cerevisiae (S. cerevisiae) was modified by γ-ray. The RNA-seq results reflect that the high γ-ray energies could change some gene fragments, such as deletion, recombination, and mutation. The biosorption of strontium ions (Sr²⁺) to different types of S. cerevisiae (S. cerevisiae (K-0), modified S. cerevisiae (Y-7), and non-living S. cerevisiae (H-K)) from the simulated high-level liquid waste (S-HLLW) was assessed at different experimental conditions. The sorption experimental results show that, under an appropriate condition, γ-ray radiation can enhance its biosorption capacity slightly of Sr²⁺ to S. cerevisiae. The maximum metal uptake and efficiency of Y-7 under S-HLLW were 11.656 mg g⁻¹ and 37.91% at 32 h (wet weight), respectively. They decreased to 9.46 mg g⁻¹ and 30.76% under radiation conditions. SEM-EDX and TEM analysis indicates that Sr²⁺ was adsorbed both on the cellular surface and the inner parts of the cells. Our experimental results fit well to the Langmuir and Freundlich model isotherms (r² > 0.94), and the maximum biosorption capacity values reached q_max > 24.74 mg g⁻¹ at 32 °C. Negative values of ΔG⁰ and positive values of ΔH⁰ were observed, indicating the spontaneous and endothermic nature of Sr²⁺ biosorption on modified S. cerevisiae. The biosorption kinetics follow a pseudo-second-order equation at 32 °C (r² > 0.94). The desorption efficiency of Sr²⁺ adsorbed onto Y-7 was 7.65 ± 0.52%, 76.51 ± 2.13%, and 65.62 ± 2.42% by deionized water, 1 M HCl, and 0.1 M EDTA-Na, respectively. However, they were lower than H-K (18.82, 83.32, and 73.32%). Our findings demonstrate that living S. cerevisiae (Y-7) is a promising sorbent material for the treatment of radioactive process streams.

https://ift.tt/2JGBXC7

The heterogeneous effects of urbanization and income inequality on CO 2 emissions in BRICS economies: evidence from panel quantile regression

Abstract

This paper empirically examines the effects of urbanization and income inequality on CO₂ emissions in the BRICS economies (i.e., Brazil, Russia, India, China, and South Africa) during the periods 1994–2013. The method we used is the panel quantile regression, which takes into account the unobserved individual heterogeneity and distributional heterogeneity. Our empirical results indicate that urbanization has a significant and negative impact on carbon emissions, except in the 80^th, 90^th, and 95^th quantiles. We also quantitatively investigate the direct and indirect effect of urbanization on carbon emissions, and the results show that we may underestimate urbanization's effect on carbon emissions if we ignore its indirect effect. In addition, in middle- and high-emission countries, income inequality has a significant and positive impact on carbon emissions. The results of our study indicate that in the BRICS economies, there is an inverted U-shaped environmental Kuznets curve (EKC) between the GDP per capita and carbon emissions. The conclusions of this study have important policy implications for policymakers. Policymakers should try to narrow the income gap between the rich and the poor to improve environmental quality; the BRICS economies can speed up urbanization to reduce carbon emissions, but they must improve energy efficiency and use clean energy to the greatest extent in the process.

https://ift.tt/2EDiXRv

Association of Colon Cancer Survival With ACS Guideline Adherence

This cohort study of patients with stage III colon cancer enrolled in the CALGB 89803/Alliance trial evaluated the association of survival rates with adherence to the American Cancer Society Nutrition and Physical Activity Guidelines for Cancer Survivors.

https://ift.tt/2JGTvhR

Study Limitations in HLA-Mismatched Microtransplant in Older Patients With Acute Myeloid Leukemia

To the Editor In the recent article by Guo et al, the authors report outcomes of 4 age-defined cohorts receiving antileukemia drugs and a microtransplant. There are no controls not receiving a microtransplant, so it is impossible to know what impact the microtransplant, if any, had on the reported outcomes. Moreover, there is no attempt to account for obvious selection biases operating in the older subject cohorts. An explanation seems warranted.

https://ift.tt/2EGHtRJ

Hypopigmented Skin Lesions After Immunotherapy

A woman in her 30s with metastatic soft tissue sarcoma being treated with nivolumab presented with diffuse macular cutaneous eruption and pruritus. What is your diagnosis?

https://ift.tt/2JEXxHj

Malignant Abnormalities in Male BRCA Mutation Carriers

This study evaluates the use of a comprehensive screening protocol for prostate, breast, colorectal, and pancreatic cancer and skin malignant abnormalities in male BRCA carriers.

https://ift.tt/2EFcVjp

Helping Colorectal Cancer Survivors Benefit From Changing Lifestyle Behaviors

About 20 years ago, investigators working in the National Cancer Institute (NCI) cooperative group system sought to prove that a novel adjuvant therapy regimen would extend the overall survival of patients with stage III colorectal cancer. The CALGB 89803 study compared weekly administration of irinotecan plus fluorouracil and leucovorin vs the standard care at the time, fluorouracil plus leucovorin. Unfortunately, this trial had negative results, and the investigational arm was far more toxic than the standard care. The report by Van Blarigan et al represents a cancer control gem that came out of the ashes of this trial.

https://ift.tt/2GSrGVS

Study Limitations in HLA-Mismatched Microtransplant in Older Patients With Acute Myeloid Leukemia—Reply

In Reply We appreciate Dr Gale's interest in our recent article in JAMA Oncology. He raised 2 important questions: (1) There were no controls. (2) There was concern about patient selection in the older subject cohorts. We agree.

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Delays in Publication of Important Clinical Trial Findings in Oncology

This review of pharmaceutical company press releases assesses how long it takes for complete data from potentially practice-changing industry-sponsored clinical trials in oncology to be published following the availability of important results.

https://ift.tt/2GRCy6d