Early neurocognitive improvements following parathyroidectomy for primary hyperparathyroidism.

OBJECTIVES: To establish a time frame for postoperative improvements in neurocognitive function in patients who undergo parathyroidectomy for primary hyperparathyroidism by utilizing repeat neuropsychological assessment at multiple time points before and after surgery. STUDY DESIGN: Prospective cohort study. METHODS: A prospective study was conducted at a tertiary academic medical center between August 2014 and December 2015, including 50 patients with primary hyperparathyroidism who underwent parathyroidectomy. A panel of neurocognitive tests was administered at two separate time points: preoperative and 1-week postoperative. Validated neuropsychological assessment tools were utilized, including Rey Auditory-Verbal Learning Test, Trail Making Test A and B, Benton Controlled Oral Word Association, WAIS-IV Digit Span, Hospital Anxiety and Depression Scale, Positive and Negative Affect Schedule, and Insomnia Severity Index. Barona Information Sheet was used to collect demographic data. Paired t tests were to compare pre- and postoperative scores. RESULTS: Thirty-five patients completed the preoperative and 1-week postoperative testing. In cognitive testing, significant improvement was noted in immediate recall (P < 0.001), working memory (P = 0.011), and attention (P = 0.008) at 1-week postoperative. In mood testing, depression (P < 0.001), anxiety (P < 0.001), and negative affect (P = 0.001) scores were significantly improved at 1-week postoperative. Insomnia scores also were significantly improved at 1 week (P < 0.001). CONCLUSION: Objective improvements in neurocognitive function following parathyroidectomy for primary hyperparathyroidism were noted as early as 1 week after surgery, which is earlier than previously reported. LEVEL OF EVIDENCE: 2b. Laryngoscope, 128:775-780, 2018.

Altered molecular profile in thyroid cancers from patients affected by the Three Mile Island nuclear accident.

OBJECTIVES/HYPOTHESIS: In 1979, Three Mile Island (TMI) nuclear power plant experienced a partial meltdown with release of radioactive material. The effects of the accident on thyroid cancer (TC) in the surrounding population remain unclear. Radiation-induced TCs have a lower incidence of single nucleotide oncogenic driver mutations and higher incidence of gene fusions. We used next generation sequencing (NGS) to identify molecular signatures of radiation-induced TC in a cohort of TC patients residing near TMI during the time of the accident. STUDY DESIGN: Case series. METHODS: We identified 44 patients who developed papillary thyroid carcinoma between 1974 and 2014. Patients who developed TC between 1984 and 1996 were at risk for radiation-induced TC, patients who developed TC before 1984 or after 1996 were the control group. We used targeted NGS of paired tumor and normal tissue from each patient to identify single nucleotide oncogenic driver mutations. Oncogenic gene fusions were identified using quantitative reverse transcription polymerase chain reaction. RESULTS: We identified 15 patients in the at-risk group and 29 patients in the control group. BRAFV600E mutations were identified in 53% patients in the at-risk group and 83% patients in the control group. The proportion of patients with BRAF mutations in the at-risk group was significantly lower than predicted by the The Cancer Genome Atlas cohort. Gene fusion or somatic copy number alteration drivers were identified in 33% tumors in the at-risk group and 14% of tumors in the control group. CONCLUSIONS: Findings were consistent with observations from other radiation-exposed populations. These data raise the possibility that radiation released from TMI may have altered the molecular profile of TC in the population surrounding TMI. LEVEL OF EVIDENCE: 4 Laryngoscope, 127:S1-S9, 2017.

Sorafenib and Quinacrine Target Anti-Apoptotic Protein MCL1: A Poor Prognostic Marker in Anaplastic Thyroid Cancer (ATC).

PURPOSE AND EXPERIMENTAL DESIGN: Anaplastic thyroid cancer (ATC) comprises approximately 2% of all thyroid cancers, and its median survival rate remains poor. It is responsible for more than one third of thyroid cancer-related deaths. ATC is frequently resistant to conventional therapy, and NFκB signaling has been proposed to be a feature of the disease. We aimed to assess the activity of the antimalaria drug quinacrine known to target NFκB signaling in combination with the clinically relevant kinase inhibitor sorafenib in ATC cells. The presence of NFκB-p65/RELA and its target MCL1 was demonstrated in ATC by meta-data gene set enrichment analysis and IHC. We assessed the responses of a panel of human ATC cell lines to quinacrine and sorafenib in vitro and in vivo RESULTS: We detected increased expression of NFκB-p65/RELA and MCL1 in the nucleus of a subset of ATC compared with non-neoplastic thyroid. ATC cells were found to respond with additive/synergistic tumor cell killing to the combination of sorafenib plus quinacrine in vitro, and the drug combination improves survival of immunodeficient mice injected orthotopically with ATC cells as compared with mice administered either compound alone or doxorubicin. We also demonstrate that the combination of sorafenib and quinacrine is well tolerated in mice. At the molecular level, quinacrine and sorafenib inhibited expression of prosurvival MCL1, pSTAT3, and dampened NFκB signaling. CONCLUSIONS: The combination of quinacrine and sorafenib targets emerging molecular hallmarks of ATC and shows promising results in clinically relevant models for the disease. Further testing of sorafenib plus quinacrine can be conducted in ATC patients. Clin Cancer Res; 22(24); 6192-203. ©2016 AACR.

Decisional Conflict and Regret in Parents Whose Children Undergo Tonsillectomy.

OBJECTIVE: To determine if decisional regret (DR) in parents following tonsillectomy/adenotonsillectomy (TA) in their children is related to preoperative decisional conflict, perceived outcome of surgery, complications of surgery, or other factors. STUDY DESIGN: Observational analytic cohort study. SETTING: Tertiary care children's hospital. SUBJECTS AND METHODS: Preoperative decisional conflict (DC) and SURE tests were administered to a parent of a child scheduled for TA between July 2014 and July 2015. The DR tests were given 1 to 3 months postoperatively. Data were collected on patient age, sex, perceived outcome of surgery, complications (including bleeding), emergency room visits, and clinic phone calls. RESULTS: A total of 102 families were studied, including 48 female and 54 male patients with an average age of 6.29 years. Parental respondents included 83 mothers, 14 fathers, and 5 grandmothers. Overall, DC and DR were both low in this group, with a median of 0 for each (means: 7.74 for DC and 8.78 for DR). DC was higher in parents who canceled surgery or failed to keep follow-up appointments (27.19) versus parents who brought their children for surgery (6.78; P < .05). DR was significantly higher in parents with DC (20.00 vs 7.59; P < .05). It was not related to age of the patient, sex, parental perception of resolution of preoperative complaints, complications (including bleeding or dehydration), emergency department visits, or parental phone calls to the otolaryngology clinic. SURE tests indicated that every parent was confident of his or her decision on the day of surgery. CONCLUSION: Preoperative DC is likely the most important factor in determining parental DR after the child undergoes TA.