A clinical scoring system for selection of patients for PTEN mutation testing is proposed on the basis of a prospective study of 3042 probands.

Cowden syndrome (CS) and Bannayan-Riley-Ruvalcaba syndrome are allelic, defined by germline PTEN mutations, and collectively referred to as PTEN hamartoma tumor syndrome. To date, there are no existing criteria based on large prospective patient cohorts to select patients for PTEN mutation testing. To address these issues, we conducted a multicenter prospective study in which 3042 probands satisfying relaxed CS clinical criteria were accrued. PTEN mutation scanning, including promoter and large deletion analysis, was performed for all subjects. Pathogenic mutations were identified in 290 individuals (9.5%). To evaluate clinical phenotype and PTEN genotype against protein expression, we performed immunoblotting (PTEN, P-AKT1, P-MAPK1/2) for a patient subset (n = 423). In order to obtain an individualized estimation of pretest probability of germline PTEN mutation, we developed an optimized clinical practice model to identify adult and pediatric patients. For adults, a semiquantitative score-the Cleveland Clinic (CC) score-resulted in a well-calibrated estimation of pretest probability of PTEN status. Overall, decreased PTEN protein expression correlated with PTEN mutation status; decreasing PTEN protein expression correlated with increasing CC score (p < 0.001), but not with the National Comprehensive Cancer Network (NCCN) criteria (p = 0.11). For pediatric patients, we identified highly sensitive criteria to guide PTEN mutation testing, with phenotypic features distinct from the adult setting. Our model improved sensitivity and positive predictive value for germline PTEN mutation relative to the NCCN 2010 criteria in both cohorts. We present the first evidence-based clinical practice model to select patients for genetics referral and PTEN mutation testing, further supported biologically by protein correlation.

The Use of 99mTc-Methoxy-isobutyl-isonitrile (sestaMIBI) Uptake on Scintigraphy (99m-STS) in Amiodarone-Induced Thyrotoxicosis: Case Series and Review of the Literature.

Amiodarone is a class III antiarrhythmic drug, used by cardiologists to treat arrhythmia including atrial fibrillation (A fib) and ventricular fibrillation. However, amiodarone is associated with endocrine dysfunction including both hypo- and hyperthyroidism. In the literature, two types of amiodarone-induced thyrotoxicosis (AIT) were described: AIT-1 and AIT-2. Mixed AIT also called AIT type 3 (AIT-3) has been described in the literature when the cases do not have a typical presentation. In order to differentiate different types of AIT, various clinical, biochemical, and radiological tools have been proposed. The use of 99mTc-methoxy-isobutyl-isonitrile (sestaMIBI) uptake on scintigraphy (99m-STS) has been suggested in the literature in only few studies (no large retrospective or prospective studies have been established in the United States). We present a case series describing 5 patients presenting to the University of Arizona with AIT where we used 99m-STS to assess in diagnosis and treatment of different types of AIT followed by a review of the literature.

Radiographic response to neoadjuvant chemotherapy is a predictor of local control and survival in soft tissue sarcomas.

BACKGROUND: Downstaging of large soft tissue sarcomas can be accomplished by the use of neoadjuvant chemotherapy (NeoCT). The authors tested the hypothesis that radiographic response to NeoCT predicts improved local control and survival. METHODS: The authors reviewed the medical records of 65 patients with Stage II or III soft tissue sarcoma (42 extremity, 23 retroperitoneal) who were treated with doxorubicin or ifosfamide-based NeoCT from January 1991 to December 1996. Radiographic response and impact on surgical therapy were determined retrospectively by comparing imaging studies obtained before and after chemotherapy. RESULTS: The radiographic responses observed were partial response (PR; 22 patients [34%]); minor response (MR; 6 patients [9%]); stable disease (20 patients [31%]); and progressive disease (17 patients [26%]). Downstaging sufficient to decrease the scope of the operation occurred in 13% of the patients, 78% had no change, and 9% had disease progression sufficient to increase the scope of the operation. Patients having any radiographic response (PR or MR) had a higher margin-negative resection rate, a better local recurrence-free survival rate, and a better overall survival rate than did nonresponders. CONCLUSIONS: The NeoCT regimens used in this study resulted in tumor shrinkage sufficient to impact surgical therapy in a few patients. However, radiographic response predicted improved local control and overall survival rate.