The Sestamibi Paradox: Improving Intraoperative Localization of Parathyroid Adenomas.

Accurate localization of parathyroid adenomas allows for minimally invasive parathyroidectomy. This results in a shorter length of stay and increased patient satisfaction. Preoperative Technetium (99mTc) sestamibi scans accurately localize parathyroid adenomas in 70 to 85 per cent of cases. If a patient has a negative scan, it is logical to believe that with a preoperative sestamibi injection, the gamma probe may fail to help find an adenoma. We hypothesized that the gamma probe would not be useful intraoperatively for patients with primary hyperparathyroidism (PHPTH) and a negative sestamibi scan. We retrospectively reviewed the cases of parathyroidectomy at our institution from 2010 to 2016. We selected patients with PHPTH and negative sestamibi scan. In all cases, an attempt was made to find adenomas intraoperatively with the gamma probe. A frozen section was obtained as well as intraoperative parathyroid hormone levels to confirm removal of hyperfunctioning parathyroid tissue. There were 132 parathyroidectomies of which 22 had PHPTH and a negative sestamibi scan. One case was excluded because of insufficient documentation of the intraoperative use of the gamma probe. In 19 of the 21 patients analyzed, the gamma probe successfully identified the adenoma in the operating room (sensitivity, 90.5%). In two patients, the gamma probe did not aid in localization. There were no false positives. In all cases, the parathyroid resected was confirmed by frozen section. The intraoperative parathyroid hormone levels dropped >50 per cent in all but three cases, two of which corresponded to those cases where the gamma probe did not help. Even in patients with negative sestamibi scans, intraoperative use of the gamma probe after preoperative sestamibi injection is effective in localizing parathyroid adenomas.

Below-the-knee arterial injury: the type of vessel may be more important than the number of vessels injured.

BACKGROUND: There are few data regarding limb salvage following below-the-knee (BK) arterial trauma. Based on published data and clinical experience, we hypothesized that any single patent vessel BK would allow for limb viability and salvage. METHODS: The trauma center registry was retrospectively queried, from 2007 through 2012, for patients presenting with BK arterial injuries (BKAIs), defined as injury below the popliteal artery. Logistic regression, Pearson's χ, and Student's t test were used to analyze data. RESULTS: A total of 122 patients were identified. The mean age was 35 years, 84% were male, and 43% were non-white. Of the patients, 83 (68%) sustained blunt and 39 (32%) sustained penetrating injuries. Fifty-one (41%) had an injury to a single BK vessel, and 12 (23.5%) of these underwent attempted repair. All seven patients with two-vessel, and one of two patients with three-vessel BKAIs had attempted repair. No patient had endovascular repair. Amputation was not associated with Injury Severity Score (ISS), sex, or age. Patients with blunt injury had higher amputation rates than those with penetrating injury (26.8% vs. 7.5%, p = 0.01). Of 51 patients, 9 (17.6%) with a single BK vessel injury required amputation; when either two or three vessels were injured, amputation rates were 29% and 50%, respectively (p = 0.09). In patients with a single-vessel injury following blunt trauma, an injured anterior tibia (AT) was associated with a higher amputation rate (6 of 17 patients, 35.3%) when compared with those patients with either posterior tibial (PT) or peroneal (P) injuries (3 of 34 patients, 8.8%, p = 0.045). The adjusted odds ratio of requiring an amputation after blunt injury to the AT alone, compared with a PT or P injury, was 22.4 (p = 0.02). CONCLUSION: BKAIs are uncommon. In contrast to the commonly taught surgical dogma, which suggests that any intact single-vessel BK is associated with limb salvage, blunt AT vessel injuries were associated with much higher rates of amputation when compared with P or PT injuries. Further studies should be undertaken to determine when repair BKAI should be attempted. LEVEL OF EVIDENCE: Epidemiologic study, level III.

Inhibition of Polo-like kinase 1 prevents the growth of metastatic breast cancer cells in the brain.

Few therapeutic strategies exist for the treatment of metastatic tumor cells in the brain because the blood-brain barrier (BBB) limits drug access. Thus the identification of molecular targets and accompanying BBB permeable drugs will significantly benefit brain metastasis patients. Polo-like kinase 1 (Plk1) is an attractive molecular target because it is only expressed in dividing cells and its expression is upregulated in many tumors. Analysis of a publicly available database of human breast cancer metastases revealed Plk1 mRNA expression was significantly increased in brain metastases compared to systemic metastases (P = 0.0018). The selective Plk1 inhibitor, GSK461364A, showed substantial uptake in normal rodent brain. Using a breast cancer brain metastatic xenograft model (231-BR), we tested the efficacy of GSK461364A to prevent brain metastatic colonization. When treatment was started 3 days post-injection, GSK461364A at 50 mg/kg inhibited the development of large brain metastases 62% (P = 0.0001) and prolonged survival by 17%. GSK461364A sensitized tumor cells to radiation induced cell death in vitro. Previously, it was reported that mutations in p53 might render tumor cells more sensitive to Plk1 inhibition; however, p53 mutations are uncommon in breast cancer. In a cohort of 41 primary breast tumors and matched brain metastases, p53 immunostaining was increased in 61% of metastases; 44% of which were associated with primary tumors with low p53. The data suggest that p53 overexpression occurs frequently in brain metastases and may facilitate sensitivity to Plk1 inhibition. These data indicate Plk1 may be a new druggable target for the prevention of breast cancer brain metastases.

Archival fine-needle aspiration cytopathology (FNAC) samples: untapped resource for clinical molecular profiling.

Microarray technologies provide high-resolution maps of chromosome imbalances and epigenomic aberrations in the cancer cell genome. Such assays are often sensitive to sample DNA integrity, voiding the utility of many archival pathology specimens and necessitating the special handling of prospective clinical specimens. We have identified the remarkable preservation of higher-molecular weight DNA in archival fine-needle aspiration cytopathology specimens from patients greater than 10 years of age. We further demonstrate the outstanding technical performance of 57 fine-needle aspiration cytopathology samples for aberration detection on high-resolution comparative genomic hybridization array, DNA methylation, and single nucleotide polymorphism genotyping platforms. Forty-four of 46 malignant aspirates in this study manifested unequivocal genomic aberrations. Importantly, matched Papanicolaou and Diff-Quik fine-needle aspiration cytopathology samples showed critical differences in DNA preservation and DNA integrity. Overall, this study identifies a largely untapped reserve of human pathology specimens for molecular profiling studies, with ramifications for the prospective collection of clinical biospecimens.