Association of histologic variants in FSGS clinical trial with presenting features and outcomes.
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ABSTRACT: Background and objectives
FSGS histologic variants have correlated with outcomes in retrospective studies. The FSGS Clinical Trial provided a unique opportunity to study the clinical impact of histologic variants in a well defined prospective cohort with steroid-resistant primary FSGS.Design, setting, participants, & measurements
Renal biopsies of 138 FSGS Clinical Trial participants aged 2-38 years enrolled from 2004 to 2008 were analyzed using the Columbia classification by core pathologists. This study assessed the distribution of histologic variants and examined their clinical and biopsy characteristics and relationships to patient outcomes.Results
The distribution of histologic variants was 68% (n=94) FSGS not otherwise specified, 12% (n=16) collapsing, 10% (n=14) tip, 7% (n=10) perihilar, and 3% (n=4) cellular. Individuals with not otherwise specified FSGS were more likely to have subnephrotic proteinuria (P=0.01); 33% of teenagers and adults had tip or collapsing variants compared with 10% of children, and subjects with these variants had greater proteinuria and hypoalbuminemia than not otherwise specified patients. Tip variant had the strongest association with white race (86%) and the lowest pathologic injury scores, baseline creatinine, and rate of progression. Collapsing variant had the strongest association with black race (63%, P=0.03) and the highest pathologic injury scores (P=0.003), baseline serum creatinine (P=0.003), and rate of progression. At 3 years, 47% of collapsing, 20% of not otherwise specified, and 7% of tip variant patients reached ESRD (P=0.005).Conclusions
This is the first prospective study with protocol-defined immunomodulating therapies confirming poor renal survival in collapsing variant and showing better renal survival in tip variant among steroid-resistant patients.
SUBMITTER: D'Agati VD
PROVIDER: S-EPMC3586971 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ImportanceTens of thousands of unnecessary operations are performed each year for diagnostic purposes among patients with cytologically indeterminate thyroid nodules. Whereas a diagnostic lobectomy is recommended for most patients with solitary indeterminate thyroid nodules, a total thyroidectomy is preferred for nodules larger than 4 cm.ObjectiveTo determine whether histologic or clinical outcomes of indeterminate thyroid nodules 4 cm or larger are worse than those for nodules smaller than 4 cm, thus justifying a more aggressive initial surgical approach.Design, setting, and participantsIn this retrospective cohort study, 652 indeterminate thyroid nodules (546 nodules <4 cm and 106 nodules ≥4 cm) with surgical follow-up were consecutively evaluated at an academic cancer center from October 1, 2008, through April 30, 2016.ExposureTumor size.Main outcomes and measuresDifferences in cancer rates, rates of invasive features, cancer aggressiveness, and response to therapy between indeterminate thyroid nodules smaller than 4 cm and 4 cm or larger.ResultsA total of 652 indeterminate thyroid nodules (546 nodules <4 cm and 106 nodules ≥4 cm) from 589 patients (mean [SD] age, 53.1 [13.8] years; 453 [76.9%] female) were studied. No differences were found in the baseline characteristics of patients or nodules between the 2 size groups. Tumor size was not associated with the cancer rate as a categorical (140 of 546 [25.6%] for nodules <4 cm and 33 of 106 [31.1%] for nodules ≥4 cm; effect size, 0.05; 95% CI, 0.002-0.12) or continuous (odds ratio [OR], 1.03; 95% CI, 0.92-1.15) variable. No association was found between nodule size and prevalence of extrathyroidal extension, positive margins, lymphovascular invasion, lymph node metastasis, or distant metastasis. Most malignant tumors were low risk in both size groups (70% in the nodules <4 cm and 72% in the nodules ≥4 cm), and tumor size was not associated with tumor aggressiveness as a categorical (effect size, 0.10; 95% CI, 0.03-0.31) or continuous variable (OR for intermediate-risk cancer, 0.91; 95% CI, 0.72-1.14; OR for high-risk cancer, 1.43; 95% CI, 0.96-2.15). At the last follow-up visit, 88 of 105 patients (83.8%) with malignant tumors in the smaller than 4 cm group and 21 of 25 (84.0%) in the 4 cm or greater group had no evidence of disease, and tumor size was not associated with response to therapy (effect size, 0.13; 95% CI, 0.07-0.33).Conclusions and relevanceMost indeterminate thyroid nodules are benign or low-risk malignant tumors regardless of tumor size. In the absence of other indications for total thyroidectomy, this study suggests that a thyroid lobectomy is sufficient initial treatment for most solitary cytologically indeterminate thyroid nodules independent of the tumor size.
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2009-12-22 | GSE14767 | GEO
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Project description:The goal of this study is to define biologically distinct subsets of Very Low Risk Wilms Tumors (VLRWT) using oligonucleotide arrays. Description: 52 tumors from the original case:cohort of 600 tumors from NWTS-5 met the criteria for VLRWT. Thirteen tumors were excluded for quality control reasons, resulting in 39 tumors for analysis. Global gene expression analysis was performed on these 39 tumors. A total of 4,000 probesets representing the greatest variability according to coefficient of variation was utilized for hierarchical clustering, and three clusters were identified. Two subsets within VLRWT are identified that have pathogenetic and molecular differences and apparent differences in risk for relapse. If these predictors can be prospectively validated, this would enable future clinical stratification and broadening the definition of VLRWT. Experiment Overall Design: Global gene expression analysis was performed on 39 tumors that met the criteria of VLRWT and passed quality control parameters in order to define biologically distinct subsets. Experiment Overall Design: Hierarchical clustering identified three tumor clusters (C1, C2 and C3). The top differentially expressed genes were identified by first filtering out probesets with a maximum expression of less than 6.5 in all 39 tumors. Using the remaining 14,452 probesets, the expression of each cluster was compared with the expression in the remaining tumors, and those genes with a p-value <0.00001 and positive or negative fold-change (FC) of greater than 2.5 were identified. This resulted in 161 probesets from the comparison of C1 with C2+C3, 43 probesets from the comparison of C2 with C1+C3, and 71 probesets from the comparison of C3 with C1+C2. The false discovery rates were 0.02%, 0.06% and 0.05% for C1, C2, and C3, respectively. These three lists were combined, resulting in 239 probesets (161 genes) which are provided in Supplemental Table 1, linked below.
2010-01-19 | E-GEOD-14767 | biostudies-arrayexpress
Project description:BackgroundMany studies have shown that clinical characteristics and outcomes differ depending on pathologic variants of focal segmental glomerulosclerosis (FSGS). However, these are not well defined in Asian populations.MethodsThis retrospective study evaluated clinical features and outcomes of pathologic FSGS variants in 111 adult patients between January 2004 and December 2012. Primary outcome was the composite of doubling of baseline serum creatinine concentrations (D-SCr) or onset of end-stage renal disease (ESRD). Secondary outcome included complete (CR) or partial remission (PR).ResultsThere were 70 (63.1%), 20 (18.0%), 17 (15.3%), 3 (2.7%), and 1 (0.9%) patients with not-otherwise specified (NOS), tip, perihilar, cellular, and collapsing variants, respectively. At presentation, nephrotic-range proteinuria occurred more commonly in tip lesion than in other variants. The overall 5-year renal survival rate was 76.8%. During a median follow-up of 34.5 months, only 1 (5.0%) patient with a tip lesion reached the composite end point compared to 2 (11.8%) and 12 (17.1%) patients in perihilar and NOS variants, but this difference was not statistically significant in an adjusted Cox model. However, tip lesion was associated with a significantly increased probability of achieving CR (P?=?0.044).ConclusionSimilar to other populations, Korean adult patients with FSGS have distinct clinical features with the exception of a rare frequency of cellular and collapsing variants. Although pathologic variants were not associated with overall outcome, the tip variant exhibited favorable outcome in terms of achieving remission. Further studies are required to delineate long-term outcome and response to treatment of the pathologic variants.
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