Photochemical separation of plutonium from uranium.

Plutonium-based technologies would benefit if chemical hazards for purifying plutonium were reduced. One critical processing step where improvements could be impactful is the adjustment of plutonium oxidation-states during separations. This transformation often requires addition of redox agents. Unfortunately, many of the redox agents used previously cannot be used today because their properties are deemed incompatible with modern day processing facilities and waste stream safety requirements. We demonstrated herein that photochemistry can be used as an alternative to those chemical agents. We observed that (1) Pu4+ → Pu3+ and UO22+ → U4+ photoreduction proceeded in HCl(aq) and HNO3(aq) and (2) photogenerated Pu3+(aq) and U4+(aq) could be separated using anion exchange chromatography (high yield, >90%; good separation factor, 322).

EIF1AX Mutation in a Patient with Hürthle Cell Carcinoma.

The EIF1AX gene is a novel cancer gene that has been reported in the tumorigenesis of papillary thyroid carcinoma, follicular variant papillary thyroid carcinoma, and anaplastic thyroid carcinoma. A 71-year-old woman presented with a right thyroid mass, which was follicular neoplasm on cytology. The fine needle aspirate of the nodule was examined by next-generation sequencing and found to harbor EIF1AX and TP53 mutations. Right thyroid lobectomy was performed with final pathology showing Hürthle cell carcinoma with capsular and vascular invasion. We report an EIF1AX mutation in a patient found to have Hürthle cell carcinoma.

Using ultrasonic preoperative thyroid volume to determine incision length for minimally invasive thyroid surgery.

The determination of the volume of a diseased thyroid lobe or an entire gland by preoperative ultrasonography may enable surgeons to select candidates for a minimally invasive approach to thyroid lobectomy or total thyroidectomy. We retrospectively reviewed the charts of 71 adults who had undergone minimally invasive nonendoscopic thyroid surgery at our hospital from January 2007 through May 2009. We compiled data on ultrasonic preoperative thyroid volumes and operative incision lengths. Of the 71 patients, 40 had undergone lobectomy and 31 had undergone total thyroidectomy. The lobectomy group was evenly subdivided into two groups based on the median volume of the affected lobe; 20 patients had a volume of <28.32 ml and 20 had a volume of >28.32 ml. The incision length ranged from 2.0 to 3.8 cm (mean: 3.1 ± 0.53) in the smaller-volume lobectomy group and from 2.5 to 5.0 cm (mean: 3.7 cm ± 0.71) in the larger-volume lobectomy group; the difference was statistically significant (p < 0.01). The 31 patients in the total thyroidectomy group were subdivided on the basis of the median volume of the entire thyroid gland; 16 patients had a volume of <49.24 ml and 15 had a total volume of >49.24 ml. The incision length in those two groups ranged from 2.5 to 4.0 cm (mean: 3.4 ± 0.53) and 3.6 to 6.0 (mean: 5.1 ± 0.99), respectively; again, the difference was statistically significant (p < 0.001). The findings of our study suggest that preoperative ultrasonographic thyroid lobe volume or total thyroid gland volume can be used to determine the appropriate minimum length for the surgical incision.

Ovarian leydig cell hyperplasia: an unusual case of virilization in a postmenopausal woman.

Objective. To report an unusual case of ovarian Leydig cell hyperplasia resulting in virilization in a postmenopausal woman. Methods. Patient's medical history and pertinent literature were reviewed. Results. A 64-year-old woman presented with virilization with worsening hirsutism, deepening of her voice, male musculature, and male pattern alopecia. Her pertinent past medical history included type 1 diabetes, hyperlipidemia, and hypertension. Her pertinent past surgical history included hysterectomy due to fibroids. On further work-up, her serum total testosterone was 506 ng/dL (nl range: 2-45) and free testosterone was 40 pg/mL (nl range: 0.1-6.4). After ruling out adrenal causes, the patient underwent an empiric bilateral oophorectomy that showed Leydig cell hyperplasia on pathology. Six weeks postoperatively, serum testosterone was undetectable with significant clinical improvement. Conclusion. Postmenopausal hyperandrogenism can be the result of numerous etiologies ranging from normal physiologic changes to ovarian or rarely adrenal tumors. Our patient was found to have Leydig cell hyperplasia of her ovaries, a rarely reported cause of virilization.

False-positive FNA due to highly sensitive BRAF assay.

OBJECTIVE: False-positive BRAF analysis on fine-needle aspiration (FNA) has rarely been reported in the literature but may become more common with the advent of assays that can detect the BRAF V600E mutation in only 2% of otherwise wild-type thyroid cells. We present the case of an indeterminate BRAF-positive FNA that showed no evidence of cancer on final surgical pathology. METHODS: Case report and literature review. RESULTS: An 87-year-old female with an indeterminate 1.7-cm nodule but BRAF-positive cytology underwent thyroid lobectomy. Final pathology revealed a benign adenomatoid nodule. An area rich in tumor cells from the nodule was identified, labeled, and microdissected for molecular testing, which demonstrated only wild-type BRAF, at the analytical limit of the assay. CONCLUSION: Increasingly sensitive BRAF assays using dual-priming oligonucleotide-based multiplex polymerase chain reaction analysis can detect the BRAF V600E mutation when present in only 2% of a population of wild-type cells. This increases the risk of false-positive results, particularly in cases of indeterminate FNA. Clinicians must caution patients in these circumstances that BRAF molecular testing may not have a 100% positive predictive value.

Is above age 45 appropriate for upstaging well-differentiated papillary thyroid cancer?

OBJECTIVE: Age greater than 45 years old is a prognostic marker in well-differentiated papillary thyroid cancer (PTC) using the American Joint Cancer Committee/Union Internationale Contre le Cancer Tumor Nodes Metastasis (AJCC/UICC TNM) staging system. Our clinical observation has been that patients aged 45 to 64 years have similar outcomes when compared to patients younger than 45 years, and we questioned the origin and accuracy of this prognostic variable. METHODS: Using SEERstat software, we analyzed the Surveillance, Epidemiology, and End Result (SEER) database for PTC using the following International Classification of Diseases for Oncology (ICD-O) codes: 8050, 8260, 8340, 8341, 8342, 8243, and 8344. Data were stratified in 5-year categories by age at diagnosis from 20 to 84 years old, with patients 85 years old and above categorized together. Survival is reported as cause specific. RESULTS: A total of 53,581 patients were identified. The 5-year survival rate decreased with each increasing age category with no inflection point at age 45 in the survival curve. While the prognosis was less favorable in each advancing age group, survival remained above 90% for all age groups under 65 years. CONCLUSION: A review of the literature reveals a lack of data supporting the use of age 45 as a prognostic variable. Our SEER database review revealed a continuum of disease-specific mortality for each incremental 5-year time period above age 45. We conclude that the current use of age 45 as a single prognostic age marker does not accurately reflect the progressive mortality risk that is apparent with each 5-year increment in age.

Calpastatin controls polymicrobial sepsis by limiting procoagulant microparticle release.

RATIONALE: Sepsis, a leading cause of death worldwide, involves widespread activation of inflammation, massive activation of coagulation, and lymphocyte apoptosis. Calpains, calcium-activated cysteine proteases, have been shown to increase inflammatory reactions and lymphocyte apoptosis. Moreover, calpain plays an essential role in microparticle release. OBJECTIVES: We investigated the contribution of calpain in eliciting tissue damage during sepsis. METHODS: To test our hypothesis, we induced polymicrobial sepsis by cecal ligation and puncture in wild-type (WT) mice and transgenic mice expressing high levels of calpastatin, a calpain-specific inhibitor. MEASUREMENTS AND MAIN RESULTS: In WT mice, calpain activity increased transiently peaking at 6 hours after cecal ligation and puncture surgery. Calpastatin overexpression improved survival, organ dysfunction (including lung, kidney, and liver damage), and lymphocyte apoptosis. It decreased the sepsis-induced systemic proinflammatory response and disseminated intravascular coagulation, by reducing the number of procoagulant circulating microparticles and therefore delaying thrombin generation. The deleterious effect of microparticles in this model was confirmed by transferring microparticles from septic WT to septic transgenic mice, worsening their survival and coagulopathy. CONCLUSIONS: These results demonstrate an important role of the calpain/calpastatin system in coagulation/inflammation pathways during sepsis, because calpain inhibition is associated with less severe disseminated intravascular coagulation and better overall outcomes in sepsis.

Distinct Ldb1/NLI complexes orchestrate γ-globin repression and reactivation through ETO2 in human adult erythroid cells.

The Ldb1/GATA-1/TAL1/LMO2 complex mediates long-range interaction between the ß-globin locus control region (LCR) and gene in adult mouse erythroid cells, but whether this complex mediates chromatin interactions at other developmental stages or in human cells is unknown. We investigated NLI (Ldb1 homolog) complex occupancy and chromatin conformation of the ß-globin locus in human erythroid cells. In addition to the LCR, we found robust NLI complex occupancy at a site downstream of the (A)γ-globin gene within sequences of BGL3, an intergenic RNA transcript. In cells primarily transcribing ß-globin, BGL3 is not transcribed and BGL3 sequences are occupied by NLI core complex members, together with corepressor ETO2 and by γ-globin repressor BCL11A. The LCR and ß-globin gene establish proximity in these cells. In contrast, when γ-globin transcription is reactivated in these cells, ETO2 participation in the NLI complex at BGL3 is diminished, as is BCL11A occupancy, and both BGL3 and γ-globin are transcribed. In these cells, proximity between the BGL3/γ-globin region and the LCR is established. We conclude that alternative NLI complexes mediate γ-globin transcription or silencing through long-range LCR interactions involving an intergenic site of noncoding RNA transcription and that ETO2 is critical to this process.

Incidental radiologic finding of an anterior superior mediastinal mass masquerading as metastatic thyroid cancer in patients with treated thyroid cancer.

OBJECTIVE: To demonstrate that an anterior superior mediastinal mass on radiologic imaging may represent an incidental finding and not metastases in patients with a history of treated well-differentiated thyroid cancer. METHODS: We report the clinical presentation and outcomes of 4 patients with a history of thyroid cancer who were incidentally found to have anterior superior mediastinal masses on imaging. We also review the relevant literature. RESULTS: Four young adults with a history of stage I papillary thyroid cancer treated with total thyroidectomy and radioiodine were incidentally found to have thymic enlargement on imaging studies within a 3-year posttreatment window. In each case, this enlargement was believed to be secondary to thymic hyperplasia and not metastatic disease, and each patient has exhibited a benign clinical course. Review of the literature revealed few reports of an association between thymic hyperplasia and thyroid cancer. CONCLUSIONS: Thymic hyperplasia may be discovered on posttreatment imaging studies in patients with a history of well-differentiated thyroid cancer, particularly in young adults who have received radioiodine therapy. Recognition of the possible coexistence of this incidental finding in patients with thyroid cancer may help to avoid unnecessary invasive procedures and treatments.

Scintigraphic imaging of body neuroendocrine tumors.

Radionuclide imaging is often used in the diagnosis and work-up of a wide range of neoplasms, on the basis of the biologic behavior of the tumor. Neuroendocrine tumors are a subgroup of neoplasms that are generally small and slow growing, and consequently their identification with conventional anatomic imaging can be difficult. Depending on the physiologic properties of the tumor, functional images obtained with radionuclides are often complementary to anatomic images, not only in the localization of the tumor and its metastases, but also in the assessment of prognosis and response to therapy. Familiarity with the choice of the appropriate radiopharmaceutical, proper imaging protocols, and the wide range of imaging patterns will enable the radiologist to guide the clinician in case management.

Intraoperative pathologic examination: cost effectiveness and clinical value in patients with cytologic diagnosis of cellular follicular thyroid lesion.

OBJECTIVE: Routine use of intraoperative pathologic examination (IOPE), including frozen section (FS) and scrape preparation cytology (SPC), during diagnostic thyroid lobectomy continues to be a source of controversy. We sought to better delineate the usefulness and cost-benefit ratio of IOPE in the context of cytologically diagnosed cellular follicular lesion (CFL) or follicular neoplasm (FN). DESIGN: Records of 205 patients who underwent thyroidectomy for cytologically diagnosed FN or CFL between 1997 and 2005 were retrospectively reviewed. IOPE results, patient demographics, and tumor characteristics were correlated to final histopathologic diagnoses. Sensitivity, specificity, predictive values, accuracy, and costs of IOPE were calculated. MAIN OUTCOME: IOPE correctly identified 3 of 16 follicular carcinomas and 9 of 36 papillary carcinomas. Sensitivity, specificity, and accuracy were 23%, 99%, and 78%, respectively. On univariate analysis, malignancy risk among follicular nodules did not correlate with age, gender, or nodule size. On multivariate analysis, nodule size was predictive of malignancy (p < 0.05). Over the entire patient series, routine IOPE resulted in a net cost savings of $74,304.33. CONCLUSIONS: IOPE reduced costs and limited the number of completion thyroidectomies necessary. IOPE is specific, cost effective, and of minimal additional risk when performed routinely for patients with CFL or FN.