Assessment Of Recurrence Risk Research Articles

A larger detrusor wall thickness increases the risk of non muscle invasive bladder cancer recurrence and progression: result from a multicenter observational study.

Recent experimental study showed a higher incidence of bladder cancer in presence of bladder detrusor muscle thickening. The aim of this study is to assess whether a higher detrusor muscle thickness (DWT) may be a risk factor of recurrence of non-muscle invasive urothelial bladder cancer (NMIBC). Men with histologically-confirmed diagnosis of NMIBC were prospectively enrolled in 4 centers between December 2015 and April 2017. DWT was measured by ultrasound and DWT>2.5 mm was used as threshold for detrusor muscle thickening. Patients underwent to adjuvant local treatment in according to their progression and recurrence risk computed by European Organization Research and Treatment of Cancer (EORTC) Score for NMIBC. Every three months cystoscopy and urinary cytology were used to detect disease recurrence and progression. The main clinic-pathological variables were compared between patients with DWT≤2.5 mm and DWT>2.5 mm. One hundred patients (49.8%) with DWT >2.5 mm were significantly older, had larger and more tumors and experienced more prior NMIBC than 101 (50.2%) patients with a DWT≤2.5 mm. Recurrence and progression disease occurred more often and briefly in patients with a detrusor muscle thickening. At univariate analysis, DWT>2.5 was a predictive risk factors of cancer recurrence and progression, respectively: OR 4.9 (95% CI: 2.5-9.5) P=0.001 and OR 2.21 (95% CI: 1.71-4.73), P=0.001. Enclosing DWT in EORTC risk calculator significantly increased by 3% and 1% recurrence and progression risk assessment, respectively. Detrusor muscle thickening may have a role in NMIBC course with a higher recurrence rate, however further confirmatory and elucidating studies are required.

Leveraging ectopic Hsp90 expression to assay the presence of tumor cells and aggressive tumor phenotypes in breast specimens

Hsp90 has been studied extensively as a therapeutic target in breast cancer in pre-clinical and clinical trials, demonstrating a variety of roles in metastatic progression. The evidence to date suggests a compelling opportunity to leverage attributes of Hsp90 expression beyond therapeutics with potential applications in breast cancer diagnosis, prognosis, and recurrence risk assessment. In this study, we developed a completely non-destructive strategy using HS-27, a fluorescently-tethered Hsp90 inhibitor, to assay Hsp90 expression on intact tissue specimens with comparable contrast to in vivo administration routes, and demonstrate the feasibility of our approach in breast cancer patients. In addition to Hsp90 inhibition being most effective in glycolytic tumors, we found ectopic Hsp90 expression to be highest in glycolytic tumors reinforcing its role as an indicator of aggressive disease. This work sets the stage for immediately using Hsp90 to improve outcomes for breast cancer patients without affecting traditional care pathways.

A Novel Breast Cancer Index for Prediction of Distant Recurrence in HR+ Early-Stage Breast Cancer with One to Three Positive Nodes.

Purpose: The study objective was to characterize the prognostic performance of a novel Breast Cancer Index model (BCIN+), an integration of BCI gene expression, tumor size, and grade, specifically developed for assessment of distant recurrence (DR) risk in HR+ breast cancer patients with one to three positive lymph nodes (pN1).Experimental Design: Analysis was conducted in a well-annotated retrospective series of pN1 patients (N = 402) treated with adjuvant endocrine therapy with or without chemotherapy using a prespecified model. The primary endpoint was time-to-DR. Results were determined blinded to clinical outcome. Kaplan-Meier estimates of overall (0-15 years) and late (≥5 years) DR, HRs, and 95% confidence interval (CIs) were estimated. Likelihood ratio statistics assessed relative contributions of prognostic information.Results: BCIN+ classified 81 patients (20%) as low risk with a 15-year DR rate of 1.3% (95% CI, 0.0%-3.7%) versus 321 patients as high risk with a DR rate of 29.0% (95% CI, 23.2%-34.4%). In patients DR-free for ≥5 years (n = 349), the late DR rate was 1.3% (95% CI, 0.0%-3.7%) and 16.1% (95% CI, 10.6%-21.3%) in low- and high-risk groups, respectively. BCI gene expression alone was significantly prognostic (ΔLR-χ2 = 20.12; P < 0.0001). Addition of tumor size (ΔLR-χ2 = 13.29, P = 0.0003) and grade (ΔLR-χ2 = 12.72; P = 0.0004) significantly improved prognostic performance. BCI added significant prognostic information to tumor size (ΔLR-χ2 = 17.55; P < 0.0001); addition to tumor grade was incremental (ΔLR-χ2 = 2.38; P = 0.1) with considerable overlap between prognostic values (ΔLR-χ2 = 17.74).Conclusions: The integrated BCIN+ identified 20% of pN1 patients with limited risk of recurrence over 15 years, in whom extended endocrine treatment may be spared. Ongoing studies will characterize combined clinical-genomic risk assessment in node-positive patients. Clin Cancer Res; 23(23); 7217-24. ©2017 AACR.

Capturing Circulating Tumor Cells through a Combination of Hierarchical Nanotopography and Surface Chemistry

Circulating tumor cells (CTCs) have become known as minimally invasive multifunctional biomarkers for earlier diagnosis, prognosis, recurrence risk assessment, and therapeutic monitoring in recent years. However, effectively capturing these CTCs is still difficult because of the extremely low abundance of CTCs and the diverse phenotypes of cancer cells. In this study, we present a novel necklace-like polydopamine nanosphere (PDA NS)/alginate composite nanofiber with a hierarchical nanotopographical structure and a surface chemical signal for capturing the CTCs. The height of the nanotopography, which is formed by connecting PDA NSs with nanofibers via electrospinning, can be easily adjusted by changing the size of the PDA NSs. Four types of cancer cells are employed to investigate the capture efficiency of the fiber. More importantly, in a blood environment containing rare cancer cells, the fiber still has a great ability to capture these cells. Therefore, this nanofiber is identified as a potential device for the diagnosis of cancer.

Response to Pre-Operative Radiotherapy in Relation to Gene Expression Patterns in Breast Cancer Patients

Current risk assessment for local recurrence after breast conserving therapy for breast cancer is based on clinicopathological factors. In addition, variability in tumor radiosensitvity is likely to influence local control. Genomic markers may help to predict the response to radiotherapy (RT) and may facilitate individualized treatment by identifying which patients will benefit from RT. The aim of our study is to identify a radiosensitivity signature and changes in gene expression after RT. Fresh frozen tumour material was collected from low-risk breast cancer patients (age ≥ 60 years; cT1-2pN0; unifocal lesion) treated within the multi-institution Pre-operative Accelerated Partial Breast Irradiation (PAPBI) trial (NCT01024582). Patients were treated with pre-operative RT (10x4 Gy in 10 days/5x6 Gy in 5 days) and a lumpectomy 6 weeks thereafter. The tumour response to RT was evaluated by pathological assessment by comparing pre-RT biopsies to surgical resection specimens. RNA-seq using next-generation sequencing was performed on all available samples. Unsupervised and supervised clustering was performed to analyze the gene expression data. Differential mRNA expression in pretreatment biopsies between responders and non-responders and between paired pre-and post RT samples was evaluated (DESEQ2). Genes with a false-discovery rate <0.01 were considered as differentially expressed. 72 samples of 58 patients were analyzed: 48 pre-RT biopsies and 24 post-RT surgery specimens. Based on the biopsies, 14 tumours were grade 1 and 29 grade 2. 41 tumours were luminal A, 4 luminal B and 3 basal type. 6 patients had a (near) complete pathological response; 22 patients any response; 16 patients no or very limited response. 2 of 3 basal types showed a complete pathological response. For 16 patients (7 no response, 9 partial response) both pre-treatment biopsies and surgical resection specimens were available. Unsupervised hierarchical clustering showed co-clustering of pre- and post RT samples of 11 patients and very close clustering of 2 patients. The biopsies of responders and non-responders did not cluster in separate groups.No genes were differentially expressed between responders and non-responders. Comparison of pre-and post RT samples identified significant changes in gene expression of 485 genes of which 146 genes were involved in connected pathways. Most genes were involved in p53 signaling, cell cycle, DNA repair and inflammatory response. To date, this is the largest study of gene expression profiles associated with response to pre-operative RT. Using supervised classification no gene expression profile associated with response to RT could be identified. Larger studies will be required to identify such a predictive gene expression profile, which can be of considerable clinical utility in personalized treatment. RT results in altered gene expression of genes involved in p53 signaling, cell cycle, DNA repair and inflammation.

187P - Summary of head-to-head comparisons of patient (pt) risk classifications by the 21-gene recurrence score (RS) assay and other genomic assays for early breast cancer (EBC)

Background: Many genomic assays that assess recurrence risk in EBC are prognostic, but they differ in risk group stratification, which can affect clinical utility. Prospective outcomes of > 50K pts treated based on 21-gene RS results have shown that pts with low RS EBC can safely forgo chemotherapy. Because of its extensive validation and wide clinical use, the RS assay is a common comparator in head-to-head studies with other assays. Methods: Published/presented studies of the RS assay performed on same tumor samples with Breast Cancer Index (BCI), EndoPredict (EP) or EP+clinical features (EPclin), MammaPrint (MMP), and/or Prosigna (ROR) assays were reviewed. Study findings were summarized descriptively. Results: 14 studies were found that compared the RS assay with BCI (1), BCI, EPclin, and ROR (1), EP/EPclin (2), MMP (6), and ROR (4). Overall discordance in risk stratification ranged from 43% to 66% between assays (Table). The RS assay classifies 12% of pts as high risk, compared with EP (63%), EPclin (48%), and MMP (46%), assays with low/high risk groups, and compared with BCI (16%) and ROR (33%), assays that, like the RS assay, use three risk groups.Table187PDiscordancea Between the RS Assay and Other AssaysBCIROREP/EPclinMMPStudyb1-level2-levelOverall1-level2-levelOverall1-level2-levelOverall1-level2-levelOverallSestak 201637%5%42%Bartlett 2016c40%10%50%Alvarado 201537%10%46%Dowsett 201341%3%43%Sinn 201745%20%66%Varga 201329%/29%18%/21%47%/50%Clough 201338%19%57%Denduluri 201134%25%58%Maroun 201531%22%53%Shivers 201326%19%44%a. Overall=any discordance in risk classification between the RS assay and other; 1-level=discordance of one risk category (low ↔ intermediate or intermediate ↔ high); 2-level=discordance of two risk categories (low ↔ high). b. Four studies lacked risk classification information appropriate for inclusion in this table. c. Study used nonstandard RS cutoffs for the RS vs. MMP comparison. Open table in a new tab a. Overall=any discordance in risk classification between the RS assay and other; 1-level=discordance of one risk category (low ↔ intermediate or intermediate ↔ high); 2-level=discordance of two risk categories (low ↔ high). b. Four studies lacked risk classification information appropriate for inclusion in this table. c. Study used nonstandard RS cutoffs for the RS vs. MMP comparison. Conclusions: The five most common genomic assays in clinical use for EBC risk-stratify pts differently and thus are not interchangeable. Of these, the RS assay classifies the smallest proportion of pts as high risk. Legal entity responsible for the study: Zsuzsanna Varga Funding: Genomic Health Disclosure: Z. Varga: Consultant/advisor: Genomic Health, Roche. P. Sinn: Advisor: Genomic Health. D. McCullough, A. Lau, M.C. Stöppler, F.L. Baehner, C. Chao: Employment and stock ownership: Genomic Health. A. Seidman: Consultant/speaker: Genomic Health.

MammaPrint versus EndoPredict: Poor correlation in disease recurrence risk classification of hormone receptor positive breast cancer.

IntroductionCorrect risk assessment of disease recurrence in patients with early breast cancer is critically important to detect patients who may be spared adjuvant chemotherapy. In clinical practice this is increasingly done based on the results of gene expression assays. In the present study we compared the concordance of the 70-gene signature MammaPrint (MP) with the 12 gene assay EndoPredict (EP).MethodsRepresentative tissue of 48 primary tumours was analysed with the MP during routine diagnostic purposes. Corresponding formalin-fixed, paraffin-embedded tissue was thereafter analysed by the EP test. Risk categories of both tests were compared.Results41 of 48 tumours could be directly compared by both tests. Of the 17 MP low risk cases, only 9 were considered low risk by EP (53% agreement) and of the 24 MP high risk cases, 18 were high risk by EP (75% agreement). Discrepancies occurred in 14 of 41 cases (34.1%). There was only a weak and non-significant correlation between the MP and EP test with an overall concordance of only 66%. The original therapeutic recommendation was based on the MP and would have been changed in 38% of the patients following EP test results. 4 patients developed distant metastases. The respective tumours of these patients were all classified as high risk by the EP, but only 3 were classified as high risk by the MP.ConclusionBoth tests resulted in different treatment recommendations for a significant proportion of patients and cannot be used interchangeably. The results underscore the urgent need for further comparative analyses of multi-genomic tests to avoid misclassification of disease recurrence risk in breast cancer patients.

Detecting interictal discharges in first seizure patients: ambulatory EEG or EEG after sleep deprivation?

PurposeUncertainty about recurrence after a first unprovoked seizure is a significant psychological burden for patients, and motivates the need for diagnostic tools with high sensitivity and specificity to assess recurrence risk. As the sensitivity of a routine EEG after a first unprovoked seizure is limited, patients often require further diagnostics. Here, we study if ambulatory EEG (aEEG) has similar diagnostic accuracy as sleep deprived EEG (sdEEG). MethodsIn this retrospective cohort, we included patients with an unprovoked first seizure and a normal routine EEG who subsequently underwent an sdEEG or aEEG. All EEGs were reviewed for the presence of interictal epileptiform discharges (IEDs). We calculated specificity and sensitivity of sdEEG and aEEG, using the clinical diagnosis of epilepsy as golden standard. All patients had a follow-up of one year. ResultsWe included 104 patients. Sensitivities for sdEEG and aEEG were 45% (specificity 91%) and 63% (specificity 95%), respectively. Independent risk factor for recurrent seizure were IEDs on the additional EEG, with a relative risk of 1.5 of having a recurrent seizure within a year. ConclusionDiagnostic accuracies of sdEEG and aEEG are similar and depending on patients’ and clinicians’ preference both can be considered in patients with a first seizure and a normal routine EEG to determine recurrence risk.

Clinical utilization of Breast Cancer Index (BCI) for late recurrence risk assessment and prediction of extended endocrine therapy (EET) benefit in early stage HR+ breast cancer.

551 Background: Randomized trials demonstrated a modest (3-5%) absolute benefit from EET in patients (pts) with early stage HR+ breast cancer (BC), but also a risk of toxicities. BCI is a validated gene expression-based assay that provides 2 results: BCI Prognostic, based on the algorithmic combination of HoxB13/IL17BR (H/I ratio) and a set of proliferation-based genes, reports individualized risk of late distant recurrence (DR); BCI Predictive, based on H/I alone, reports a prediction of high vs low likelihood of benefit from EET. The objective of this study was to assess clinical and pathologic patient characteristics, prognostic and predictive assay results, and physician testing patterns in &gt;14,000 clinical cases. Methods: The BCI Clinical Database for Correlative Studies is a de-identified database developed under an IRB approved protocol that contains &gt;50 clinicopathologic and molecular variables from cases submitted for BCI in clinical practice. Clinicopathologic variables were abstracted from pathology reports, and were available for a subset of cases. Results: Across all pts (N=14,463), median age was 58.2y (range: 23-92y; 73.9% ≥50y). The majority were Stage I (47.3% IA, 3.5% IB, 29.1% IIA, 14.1% IIB, 6% III). Cases were 29%, 51%, and 20% Grade 1, 2, and 3, respectively. Most pts were ER+/PR+ (87.7%) or ER+/PR- (11.3%); 11.3% were HER2+. The majority of cases (55.7%) were ordered 4-6y postdiagnosis, with 23.1% &gt;6y, 14.4% between 1-4y, and 6.8% &lt;1y postdiagnosis. In LN- pts (n=3395), BCI Prognostic identified 50.6% as low risk for late DR vs 49.4% as high risk, while BCI Predictive (H/I) classified 41.0% as high vs 59.0% as low likelihood of benefit. In LN+ pts tested with the BCIN+ Prognostic algorithm (BCI + size/grade, n=818), 77.3% were classified as high risk vs 22.7% as low risk, while BCI Predictive (H/I) classified 44.6% and 55.4% as high vs low likelihood of benefit. Conclusions: Findings from this large cohort characterize utilization of BCI in clinical practice for pts with early-stage, HR+ BC. BCI stratification of pts with high risk and high likelihood of benefit from EET may facilitate selection of pts for prolonged regimens.

Risk of recurrence after a first unprovoked seizure in children

ObjectivesThis study aimed to evaluate the first episode of unprovoked epileptic seizure in children and assess recurrence risk factors. MethodsThis was a retrospective observational study, based on the analysis of medical records of patients admitted between 2003 and 2014, with first epileptic seizure, at the pediatric service of a secondary hospital. The data were analyzed using the SPSS 20.0 program. ResultsOf the 103 patients, 52.4% were boys. The median age at the first seizure was 59 (1‐211) months. About 93% of children were submitted to an electroencephalogram (EEG) at the first episode and 47% underwent neuroimaging assessment. Treatment with an antiepileptic drug was started in 46% of patients. The recurrence rate was 38% and of these, 80% had the second seizure within six months after the first event. Of the assessed risk factors, there was a statistically significant association between seizure during sleep and recurrence (p=0.004), and between remote symptomatic etiology seizure and occurrence of new seizure (p=0.02). The presence of EEG abnormalities was also associated with the occurrence of new seizures (p=0.021). No association was found between age, duration of the seizure, and family history of epilepsy with increased risk of recurrence. ConclusionsMost children with a first unprovoked epileptic seizure had no recurrences. The risk of recurrence was higher in patients with seizure occurring during sleep or remote symptomatic ones and those with abnormal EEG results.

Early onset preeclampsia: using population data to assess recurrence risk and adverse pregnancy outcomes

ABSTRACTObjectiveUse linked perinatal data to determine the subsequent pregnancy rate after a pregnancy with early onset preeclampsia and, among those who have a subsequent pregnancy, the risk of recurrence and adverse pregnancy outcomes.&#x0D; ApproachPreeclampsia is a hypertensive disorder of pregnancy associated with adverse outcomes for the mother and baby. Although rare, when preeclampsia occurs before 34 weeks of gestation, the risk of adverse outcomes is markedly increased primarily due to prematurity. Despite the desire for another child, many women are anxious about becoming pregnant again because of concerns of recurrent complications in a next pregnancy but information for counselling is sparse. We undertook a population-based record linkage cohort study using longitudinally-linked birth and hospital records from New South Wales (Australia) to create medical and obstetric histories. The study population included nulliparous women with a singleton pregnancy and early onset preeclampsia who gave birth between 2001 and 2010 (the index pregnancy), with follow-up for a subsequent birth through 2012. Early onset preeclampsia was defined as a hospital record (antenatal and/or delivery hospitalisations) with a diagnosis of preeclampsia and delivery before 34 weeks gestation. Outcomes included subsequent pregnancy, and among women with a consecutive subsequent birth, the preeclampsia recurrence rate and adverse pregnancy outcome rates.&#x0D; ResultsOf 1473 (4.0/1000) nulliparous women who had early onset preeclampsia in the index pregnancy, 60% had evidence of any subsequent pregnancy compared to 66% for women without preeclampsia (P&lt;0.001). Of 758 women with early onset preeclampsia and a subsequent singleton birth ≥20 weeks gestation, 256 (33.8%) had preeclampsia in the subsequent pregnancy but only 57 (7.5%) had recurrent early onset preeclampsia. Most women (717, 94.6%) progressed to a later gestational age in their subsequent pregnancy. The median overall increase in gestational age at delivery was 6 weeks (interquartile range [IQR] 4 to 8) and among the women with recurrent preeclampsia the median increase in gestation in the subsequent pregnancy was 5 weeks (IQR 2 to 7). Outcomes in the subsequent pregnancy included 4.2% postpartum haemorrhage, 3.4% severe maternal morbidity, 2.6% Apgar &lt;7 at 5 minutes, 16.2% small-for gestational-age and 1.7% perinatal deaths.&#x0D; ConclusionsMost women with early onset preeclampsia had good outcomes in their subsequent pregnancy. For rare conditions, linked population data with accurately recorded information can provide robust estimates of outcomes that can inform clinical counselling.

Analysis of genome-wide copy number variations among fetuses with abnormalities detected by prenatal ultrasouography

To explore the genetic etiology of fetal abnormalities detected by prenatal ultrasound through single nucleotide polymorphism (SNP array) analysis. Two hundred and eight fetuses were tested with SNP array and conventional karyotyping. Complex copy number variations (CNVs) were verified with fluorescence in situ hybridization (FISH), multiplex ligation-dependent probe amplification (MLPA) and quantitative fluorescence polymerase chain reaction (QF-PCR). For the 208 cases, the diagnostic yields of conventional karyotping and SNP assay were 8.2%(17/208) and 13.9%(29/208), respectively. For fetuses with malformations of the cardiovascular system, central nervous system or multiple systems, pathogenic CNVs was detected in 4.6% (8/174), 2.3%(4/174), and 1.1% (2/174) of all fetuses, respectively. No pathogenic CNVs was detected among those with abnormalities of the renal system, digestive system, skeletal system, facial dysmorphism or respiratory system. CNVs are significantly related with birth defects. Compared with conventional karyotyping, SNP array is a better platform for CNVs detection and can provide more clues for genetic counseling, recurrence risk assessment and prenatal diagnosis.

Association between TLR9 rs5743836 polymorphism and risk of recurrent venous thromboembolism

Recent gene knockout studies on mice have shown the role of toll-like receptor 9 (TLR9) in resolution of venous thromboembolism (VTE) through sterile inflammation. However, the role of a putative functional TLR9 polymorphism (rs5743836) in risk assessment of VTE recurrence remains unknown. The aim of our study was to investigate the TLR9 rs5743836 polymorphism in VTE patients and its association with the risk of VTE recurrence. We analyzed TLR9 rs5743836 polymorphism in Malmö thrombophilia study patients; a prospective follow-up study of 1465 VTE patients by Taqman PCR. From a total of 1465 VTE patients, those who had VTE before inclusion and those who died or had VTE recurrence during anticoagulant treatment were excluded (n = 415). Cox regression analyses were performed on the remaining 1050 VTE patients, including 126 (12.5%) patients that had recurrent VTE during follow-up period. TLR9 polymorphism was significantly associated with higher risk of VTE recurrence in female patients (HR 3.46, 95% CI 1.06–11.33) independent of acquired risk factors for VTE, family history, risk of thrombophilia and deep vein thrombosis (DVT) location. Similarly, in unprovoked VTE patients, TLR9 polymorphism was significantly associated with higher risk of VTE recurrence in female patients (HR 5.94, 95% CI 1.25–28.13) after adjusting for family history, risk of thrombophilia and DVT location. No association between TLR9 polymorphism and risk of VTE recurrence was found in male patients. Our results suggest that TLR9 rs5743836 polymorphism is an independent risk factor for VTE recurrence in female patients but not in males.

Hypophosphatasia: An overview For 2017

Hypophosphatasia (HPP) is the inborn-error-of-metabolism that features low serum alkaline phosphatase (ALP) activity (hypophosphatasemia) caused by loss-of-function mutation(s) of the gene that encodes the tissue-nonspecific isoenzyme of ALP (TNSALP). Autosomal recessive or autosomal dominant inheritance from among >300 TNSALP (ALPL) mutations largely explains HPP's remarkably broad-ranging severity. TNSALP is a cell-surface homodimeric phosphohydrolase richly expressed in the skeleton, liver, kidney, and developing teeth. In HPP, TNSALP substrates accumulate extracellularly. Among them is inorganic pyrophosphate (PPi), a potent inhibitor of mineralization. Superabundance of extracellular PPi explains the hard tissue complications of HPP that feature premature loss of deciduous teeth and often rickets or osteomalacia as well as calcific arthropathies in some affected adults. In infants with severe HPP, blocked entry of minerals into the skeleton can cause hypercalcemia, and insufficient hydrolysis of pyridoxal 5′-phosphate (PLP), the major circulating form of vitamin B6, can cause pyridoxine-dependent seizures. Elevated circulating PLP is a sensitive and specific biochemical marker for HPP. Also, the TNSALP substrate phosphoethanolamine (PEA) is usually elevated in serum and urine in HPP, though less reliably for diagnosis. Pathognomonic radiographic changes occur in pediatric HPP when the skeletal disease is severe. TNSALP mutation analysis is essential for recurrence risk assessment for HPP in future pregnancies and for prenatal diagnosis. HPP was the final rickets/osteomalacia to have a medical treatment. Now, significant successes using asfotase alfa, a mineral-targeted recombinant TNSALP, are published concerning severely affected newborns, infants, and children. Asfotase alfa was approved by regulatory agencies multinationally in 2015 typically for pediatric-onset HPP.

Individualised risk assessment for local recurrence and distant metastases in a retrospective transatlantic cohort of 687 patients with high-grade soft tissue sarcomas of the extremities: a multistate model

ObjectivesThis study investigates the effect of surgical margins and radiotherapy, in the presence of individual baseline characteristics, on survival in a large population of high-grade soft tissue sarcoma of the...

Sidedness matters: Surrogate biomarkers prognosticate colorectal cancer upon anatomic location.

523 Background: Recent evidence indicate that the anatomic location of primary tumors across the colon correlate with survival in the metastatic setting, whereas left-sided tumors may exhibit superior survival compared with right-sided. The Oncotype DX, a 12-gene colon cancer assay, is a clinically validated predictor of recurrence risk in stage II colorectal cancer (CRC) patients. Previous studies had indicated that CDX2-negative colorectal tumors are often associated with several adverse prognostic variables. Recently, it has been shown that without adjuvant chemotherapy, CDX2-negative stage II CRC tumors were associated with a lower rate of disease-free survival than CDX2-positive stage II CRC tumors. We aimed to evaluate whether these validated two prognostic biomarkers may correlate with primary tumor location, and whether tumor location may reflect differential prognosis in stage II CRC. Methods: We retrospectively analyzed a cohort of patients with T3 mismatch repair proficient (MMR-P) stage II CRC for whom 12-gene assay was performed (between 1/2011-2/2016). Pathological report was reviewed for exact primary tumor location and CDX2 immunostaining. Recurrence score (RS) and CDX2 expression were correlated with primary tumor location. Results: The analysis included 1087 patients with MMR-P stage II CRC (median age 69 years (range 29-93)). Tumor distribution across the colon was as follows: 46% (n = 500) were right-sided (cecum, ascending colon, transverse colon) and 54% (n = 587) were left-sided (splenic flexure, descending colon, sigmoid colon and rectum). Recurrence score was higher in right-sided tumors compared with left-sided tumors (p = 0.01). The RS gradually decreased across the colon (cecum - highest score, sigmoid-lowest score, p = 0.04). Right-sided tumors exhibited more CDX2-negative tumors compared with left-sided tumors (p = 0.07). Conclusions: Our study indicate that right-sided colorectal tumors may display worse prognosis compared with left-sided tumors in MMR-P stage II CRC. Primary tumor location may serve as a prognostic factor that should be accounted for recurrence risk assessment and consideration of adjuvant treatment.

En Bloc Resections in the Spine: The Experience of 220 Patients During 25 Years

En bloc resections aim at surgically removing a tumor in a single, intact piece. Approach must be planned for the complete removal of the tumor without violation of its margins. The shared knowledge of the morbidity, mortality, risk assessment for local disease recurrence, complications, and death, related to spine tumors excised en bloc could improve the treating physician's apprehension of the diseases and decision making process before, during, and after surgical treatment. The purpose of this study was to review and report the experience gained during 25 years in one of the world's biggest spine oncologic centers. A retrospective study of prospective collected data of 1681 patients affected by spine tumors, of whom 220 had en bloc resections performed. Most tumors were primary-165 cases (43benign and 122 malignant); metastases occurred in 55patients. A total of 60 patients died from the disease and 33 local recurrences were recorded. A total of 153 complications were observed in 100 of 216 patients (46.2%); 64 of these patients (30%) suffered 1 complication, whereas the rest had 2 or more. All complications were categorized according to temporal distribution and severity. These were further divided into 7 groups according to the type of complication. There were 105 major and 48 minor complications. Seven patients (4.6%) died as a result of complications. There were 33 local recurrences (15.28%) recorded. Contaminated cases, surgical margins of the resected tumor-intralesional, marginal, and malignant tumors-were statistically significant independent risk factors for local recurrence of the tumor. Contamination, local recurrence, neoadjuvant radiotherapy, number of levels resected, and metastatic tumors compared with primary malignant tumor were shown to be independent risk factors for a patient's death. Treatment of spinal aggressive benign and malignant bone tumors with en bloc resection is beneficial in terms of better local control and prognosis, although it is a highly demanding and risky procedure. Margins are the key point of this procedure, thus a careful preoperative oncologic and surgical staging is necessary to define the optimal surgical approach. The adverse event profile of these surgeries is high. Therefore, it should be performed by experienced and multidisciplinary teams in specialized high volume centers.

Risk of recurrence after a first unprovoked seizure in children

ObjectivesThis study aimed to evaluate the first episode of unprovoked epileptic seizure in children and assess recurrence risk factors. MethodsThis was a retrospective observational study, based on the analysis of medical records of patients admitted between 2003 and 2014, with first epileptic seizure, at the pediatric service of a secondary hospital. The data were analyzed using the SPSS 20.0 program. ResultsOf the 103 patients, 52.4% were boys. The median age at the first seizure was 59 (1–211) months. About 93% of children were submitted to an electroencephalogram at the first episode and 47% underwent neuroimaging assessment. Treatment with an antiepileptic drug was started in 46% of patients. The recurrence rate was 38% and of these, 80% had the second seizure within six months after the first event. Of the assessed risk factors, there was a statistically significant association between seizure during sleep and recurrence (p=0.004), and between remote symptomatic etiology seizure and occurrence of new seizure (p=0.02). The presence of electroencephalogram abnormalities was also associated with the occurrence of new seizures (p=0.021). No association was found between age, duration of the seizure, and family history of epilepsy with increased risk of recurrence. ConclusionsMost children with a first unprovoked epileptic seizure had no recurrences. The risk of recurrence was higher in patients with seizure occurring during sleep or remote symptomatic ones and those with abnormal electroencephalogram results.

Drug allergy passport and other documentation for patients with drug hypersensitivity - An ENDA/EAACI Drug Allergy Interest Group Position Paper.

The strongest and best-documented risk factor for drug hypersensitivity (DH) is the history of a previous reaction. Accidental exposures to drugs may lead to severe or even fatal reactions in sensitized patients. Preventable prescription errors are common. They are often due to inadequate medical history or poor risk assessment of recurrence of drug reaction. Proper documentation is essential information for the doctor to make sound therapeutic decision. The European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology have formed a task force and developed a drug allergy passport as well as general guidelines of drug allergy documentation. A drug allergy passport, a drug allergy alert card, a certificate, and a discharge letter after medical evaluation are adequate means to document DH in a patient. They are to be handed to the patient who is advised to carry the documentation at all times especially when away from home. A drug allergy passport should at least contain information on the culprit drug(s) including international nonproprietary name, clinical manifestations including severity, diagnostic measures, potential cross-reactivity, alternative drugs to prescribe, and where more detailed information can be obtained from the issuer. It should be given to patients only after full allergy workup. In the future, electronic prescription systems with alert functions will become more common and should include the same information as in paper-based documentation.

Analysis of risk factors and risk assessment for ischemic stroke recurrence

Objective To screen the risk factors for recurrence of ischemic stroke and to assess the risk of recurrence. Methods Essen Stroke Risk Score (ESRS) was used to evaluate the risk of recurrence in 176 patients with ischemic stroke (96 cases of first onset and 80 cases of recurrence). Univariate and multivariate stepwise Logistic regression analysis was used to screen risk factors for recurrence of ischemic stroke. Results There were significant differences between first onset group and recurrence group on age, the proportion of > 75 years old, hypertension, diabetes, coronary heart disease, peripheral angiopathy, transient ischemic attack (TIA) or ischemic stroke, drinking and ESRS score ( P 3 score was independent risk factor for recurrence of ischemic stroke ( OR = 31.324, 95%CI: 3.934-249.430; P = 0.001). Conclusions ESRS > 3 score is the independent risk factor for recurrence of ischemic stroke. It is important to strengthen risk assessment of recurrence of ischemic stroke. To screen and control risk factors is the key to secondary prevention of ischemic stroke. DOI: 10.3969/j.issn.1672-6731.2016.07.011