Thyroid nodule molecular profiling: The clinical utility of Afirma Xpression Atlas for nodules with Afirma Genomic Sequencing Classifier-suspicious results.

BACKGROUND: The Afirma Genomic Sequencing Classifier uses whole transcriptome RNA sequencing to identify thyroid nodules as benign or suspicious. The Afirma Xpression Atlas became available in 2018 and reports findings across 593 genes, including 905 variants and 235 fusions. When an alteration is identified, its risk of malignancy and associated neoplasm type is listed. We report the results of Afirma Xpression Atlas testing at our institution during its first 2 years of clinical use. METHODS: All patient charts with indeterminate thyroid nodules and Afirma Xpression Atlas results at our institution were reviewed. Thyroid nodule characteristics, cytology, Afirma Genomic Sequencing Classifier results, Afirma Xpression Atlas results, and final histopathology were reported. RESULTS: Afirma Xpression Atlas was performed on 136 indeterminate nodules since May 2018, and 103 met inclusion criteria. Forty-three nodules had positive Afirma Xpression Atlas results, and of these, 83.7% were follicular cell-derived thyroid cancer on surgical histopathology. This is similar to the overall 82.5% positive predictive value among Afirma Genomic Sequencing Classifier-suspicious indeterminate nodules during the same time period. Of the 60 nodules with negative Afirma Xpression Atlas, 73.3% were follicular cell-derived thyroid cancer on surgical histopathology. CONCLUSION: Afirma Xpression Atlas positivity is predictive of follicular cell-derived thyroid cancer, but its positive predictive value is similar to that of Genomic Sequencing Classifier-suspicious results alone at our institution, which is higher than previously published. Specific mutations likely predict follicular cell-derived thyroid cancer with higher accuracy, but our current sample size of any given mutation is too small to evaluate this further. Larger studies are needed to determine whether Afirma Xpression Atlas results predictably inform the risk of malignancy and tumor characteristics in thyroid nodules.

Risk factors associated with positive resection margins in patients with adrenocortical carcinoma.

BACKGROUND: Positive resection margins are associated with worse survival after surgery for adrenocortical carcinoma (ACC). We aimed to identify risk factors for positive margins post-resection. METHODS: The NCDB was queried for ACC patients from 2006 to 2015. Patients with positive versus negative resection margins post-surgery were compared using Chi-square tests. Survival based on adjuvant treatment was assessed using Kaplan-Meier curves. RESULTS: 1,973 patients with ACC were identified, 217 (11.0%) with positive margins. Multivariable analysis identified extra-adrenal extension (HR 4.92, p < 0.001), lymph node metastases (HR 2.64, p = 0.001), and distant metastases (HR 1.53, p = 0.03) as risk factors for positive margins. No significant difference in margin status existed between patients who had an open versus minimally invasive procedure (p = 0.6). Positive margin patients receiving adjuvant radiation (p = 0.007) or combined chemo-radiation (p = 0.001) had the longest survival. CONCLUSION: No modifiable risk factors were identified, but patients with positive margins receiving adjuvant radiation or chemo-radiation had the longest survival.

Should 68Ga-DOTATATE PET/CT be Performed Routinely in Patients with Neuroendocrine Tumors Before Surgical Resection?

BACKGROUND: The only potential cure for neuroendocrine tumors (NETs) is operative resection, which may also offer a survival benefit for advanced disease. We aimed to assess the role of 68Ga-DOTATATE PET/CT in preoperative planning and compared its performance to CT with IV contrast and MRI with Eovist®, for abdominal NETs. METHODS: Records of patients who underwent 68Ga-DOTATATE PET/CT in addition to MRI with Eovist® and/or CT with IV contrast were retrospectively evaluated. The effect of imaging findings on surgical management and characteristics of detected lesions were analyzed. Descriptive statistics were used. RESULTS: Of 21 patients who underwent 68Ga-DOTATATE PET/CT prior to surgical resection, five (24%) had a change in surgical management due to findings. In three patients, 68Ga-DOTATATE PET/CT identified the primary tumor. In two patients, 68Ga-DOTATATE PET/CT helped clarify equivocal hepatic lesions seen on MRI with Eovist®. MRI with Eovist® had the highest number of lesions found (median 13, versus 9 on CT and 9.5 on 68Ga-DOTATATE PET/CT). DOTATATE-avid lesions were on average larger than lesions seen only on MRI with Eovist® (1.6 cm versus 0.6 cm, p = 0.0002). The optimal cutoff point for detection by 68Ga-DOTATATE PET/CT was a size of 0.95 cm, with a sensitivity of 56% and specificity of 98%. CONCLUSIONS: Preoperative 68Ga-DOTATATE PET/CT is useful only in a subset of patients undergoing surgical resection for NETs. MRI with Eovist® is superior at identifying liver metastases when compared to 68Ga-DOTATATE PET/CT and should therefore be used routinely before hepatic cytoreduction of NETs.

Microwave assisted synthesis of polyacrylamide grafted dextrin (Dxt-g-PAM): Development and application of a novel polymeric flocculant.

An efficient polymeric flocculant was synthesized by microwave assisted grafting of polyacrylamide to dextrin. By varying the reaction conditions, various grades of graft copolymers were synthesized to obtain the optimized one. Viscometry, elemental analysis, FTIR spectroscopy, (13)C NMR spectroscopy, determination of molecular weight and radius of gyration using SLS analysis, thermal analysis and SEM analysis were employed to confirm that polyacrylamide has been grafted onto the dextrin backbone. The flocculation efficiency of the grafted products in kaolin suspension was dependent on the molecular weight, radius of gyration and length of the grafted polyacrylamide chains. The flocculant obtained by microwave assisted grafting method was superior to dextrin and polyacrylamide-based commercial flocculant (Rishfloc 226 LV) in flocculation tests.

Rhizobium sp. strain NGR234 NodZ protein is a fucosyltransferase.

Rhizobium sp. strain NGR234 produces a large family of lipochitooligosaccharide Nod factors carrying specific substituents. Among them are 3-O- (or 4-O-) and 6-O-carbamoyl groups, an N-methyl group, and a 2-O-methylfucose residue which may bear either 3-O-sulfate or 4-O-acetyl substitutions. Investigations on the genetic control of host specificity revealed a number of loci which directly affect Nod factor structure. Here we show that insertion and frameshift mutations in the nodZ gene abolish fucosylation of Nod factors. In vitro assays using GDP-L-fucose as the fucose donor show that fucosyltransferase activity is associated with the nodZ gene product (NodZ). NodZ is located in the soluble protein fraction of NGR234 cells. Together with extra copies of the nodD1 gene, the nodZ gene and its associated nod box were introduced into ANU265, which is NGR234 cured of the symbiotic plasmid. Crude extracts of this transconjugant possess fucosyltransferase activity. Fusion of a His6 tag to the NodZ protein expressed in Escherichia coli yielded a protein able to fucosylate both nonfucosylated NodNGR factors and oligomers of chitin. NodZ is inactive on monomeric N-acetyl-D-glucosamine and on desulfated Rhizobium meliloti Nod factors. Kinetic analyses showed that the NodZ protein is more active on oligomers of chitin than on nonfucosylated NodNGR factors. Pentameric chitin is the preferred substrate. These data suggest that fucosylation occurs before acylation of the Nod factors.