Rates of Malignancy in Cytology Indeterminate Thyroid Nodules: A Single Center Surgical Series.

BACKGROUND: Due to the high variability in malignancy rate among cytologically indeterminate thyroid nodules (Bethesda categories III-V), the American Thyroid Association recommends that each center define its own categorical cancer risk. OBJECTIVES: To assess cancer risk in patients with cytologically indeterminate thyroid nodules who were operated at our center. METHODS: In a retrospective study, we analyzed the pathology results of all the patients whose fine needle aspiration results showed Bethesda III-V cytology and who subsequently underwent total thyroidectomy or lobectomy from December 2013 to September 2017. RESULTS: We analyzed 56 patients with indeterminate cytology on fine needle aspiration. Twenty-nine (52%) were defined as Bethesda III, 19 (34%) Bethesda IV, and 8 (14%) Bethesda V category. Malignancy rates were 38%, 58%, and 100% for Bethesda categories III, IV, and V, respectively. Most malignancies in Bethesda categories III and IV were follicular in origin (follicular thyroid carcinoma and follicular type papillary thyroid carcinoma), while 100% of the patients with Bethesda category V were diagnosed with classical papillary thyroid carcinoma. No correlation was found between sonographic and cytological criteria of nodules with Bethesda categories III and IV and rates of malignancy. CONCLUSIONS: We found higher than expected rates of malignancy in indeterminate cytology. This finding reinforces the guidelines of the American Thyroid Association to establish local malignancy rates for thyroid nodules with indetermined cytology.

Limitations of ultrasound in predicting bilaterality vs unilaterality of well-differentiated carcinoma of the thyroid.

PURPOSE: The purpose of this study is to assess the efficacy of ultrasonography in the differentiation of a bilateral and a unilateral WDTC to help physicians decide on performing a total or a partial thyroidectomy. MATERIALS AND METHODS: Retrospective chart review of all patients diagnosed with papillary thyroid carcinoma following a total thyroidectomy or a complete thyroidectomy between January 2013 and December 2015 at the Department of Otorhinolaryngology and Head and Neck Surgery in Soroka University Medical Center in southern Israel. The preoperative ultrasound images of the thyroid were compared to the final pathology in the contralateral lobe. RESULTS: Seventy seven patients (77) were included in this study, There was no correlation between the sonography in the contralateral lobe and the malignancy on that side (p = 0.479). US had a 39% false negative rate and 69% false positive rate. CONCLUSION: The patients with a well-differentiated carcinoma of the thyroid, a benign nodule detected sonographically in the contralateral lobe should not bear a high weight in decision making regarding the extent of surgery.

Tumor Tissue Explant Culture of Patient-Derived Xenograft as Potential Prioritization Tool for Targeted Therapy.

Despite of remarkable progress made in the head and neck cancer (HNC) therapy, the survival rate of this metastatic disease remain low. Tailoring the appropriate therapy to patients is a major challenge and highlights the unmet need to have a good preclinical model that will predict clinical response. Hence, we developed an accurate and time efficient drug screening method of tumor ex vivo analysis (TEVA) system, which can predict patient-specific drug responses. In this study, we generated six patient derived xenografts (PDXs) which were utilized for TEVA. Briefly, PDXs were cut into 2 × 2 × 2 mm3 explants and treated with clinically relevant drugs for 24 h. Tumor cell proliferation and death were evaluated by immunohistochemistry and TEVA score was calculated. Ex vivo and in vivo drug efficacy studies were performed on four PDXs and three drugs side-by-side to explore correlation between TEVA and PDX treatment in vivo. Efficacy of drug combinations was also ventured. Optimization of the culture timings dictated 24 h to be the time frame to detect drug responses and drug penetrates 2 × 2 × 2 mm3 explants as signaling pathways were significantly altered. Tumor responses to drugs in TEVA, significantly corresponds with the drug efficacy in mice. Overall, this low cost, robust, relatively simple and efficient 3D tissue-based method, employing material from one PDX, can bypass the necessity of drug validation in immune-incompetent PDX-bearing mice. Our data provides a potential rationale for utilizing TEVA to predict tumor response to targeted and chemo therapies when multiple targets are proposed.

Necrotizing Otitis Externa-Analysis of 83 Cases: Clinical Findings and Course of Disease.

OBJECTIVES: Evaluate the relationship between clinical findings and course of disease among patients with necrotizing otitis externa (NOE). STUDY DESIGN: Retrospective case series review. SETTING: Tertiary referral center. PATIENTS: Adult patients with no previous history of chronic ear disease, hospitalized due to NOE between the years 1990 to 2015. MAIN OUTCOME MEASURES: 1) Duration of hospitalization and 2) necessity for surgery. RESULTS: Eighty-one patients were included in the study, corresponding to 83 effected ears. Thirty-two patients (38.5%) were hospitalized longer than 20 days and 20 patients (24.0%) underwent surgery. Otalgia was the most common complaint (n = 71, 85.5%). Pseudomonas Aeruginosa (PA) was the most common isolated bacteria (n = 40, 48.1%). Shifting incidence of culture results was noted, as rates of PA NOE decreased and rates of sterile culture and fungal NOE increased. Duration of complaints and presence of aural discharge at admission were associated with prolonged hospitalization (p = 0.010, p = 0.011, respectively). Advanced age, duration of hospitalization, and rates of readmission were associated with surgery (p = 0.037, p < 0.001, p < 0.001 respectively). CONCLUSIONS: Duration of complaints and presence of aural discharge may indicate advanced NOE and require longer in-hospital treatment. Elderly patients are at increased risk for conservative treatment failure and are more likely to require surgery. With shifting incidence of pathogens, a wider empirical treatment covering nontraditional pathogens should be considered.

Seasonal changes in serum calcium, PTH and vitamin D levels in patients with primary hyperparathyroidism.

BACKGROUND: Seasonal variations of 25-hydroxyvitamin D, PTH and calcium levels are not well characterized in primary hyperparathyroidism (PHPT). Our objectives were to characterize seasonal changes in these parameters in PHPT patients, and to assess whether these seasonal changes affect clinical decision making. METHODS: This is a retrospective study based on the electronic medical records of Clalit Health service in the south of Israel between 2000 and 2012. Patients 18years and older with PHPT (PTH>upper limit of norm (ULN) and serum calcium>10.5mg%) were included. Patients with renal failure or on Thiazide diuretics were excluded. All serum levels of calcium, PTH and 25-hydroxyvitamin D were collected and then stratified according to season. RESULTS: 792 patients were classified as PHPT (72.2% female) and had a total of 2659 PTH tests, 1395 25-hydroxyvitamin D tests and 7426 calcium test. Fifty six percent of 25-hydroxyvitamin D levels were <50nmol/L. Seasonality was demonstrated in all three parameters: mean 25-hydroxyvitamin D was 13% higher in the summer compared to the winter (P<0.001), median PTH values showed opposite trend with a fall of about 8.4% in summer compared to winter (P<0.001). Calcium levels were higher during the autumn with a rise of about 0.2mg/dL in the mean calcium levels compared to spring and summer (P<0.001). The odds ratio of calcium level above 11.5mg/dL is highest in the autumn (OR=1.275, P=0.018). CONCLUSION: We show seasonal variation in serum 25-hydroxyvitamin D, PTH, and calcium levels in patients with PHPT. These seasonal variations cause transition to pathological values that may influence diagnosis and treatment of PHPT patients.

Fetal safety of macrolides.

Macrolide antibiotics are largely used in pregnancy for different bacterial infections. Their fetal safety has been studied by several groups, yielding opposing results. In particular, there have been studies claiming an association between macrolides and cardiovascular malformations. Exposure in early infancy has been associated with pyloric stenosis and intussusception. This has led to an avoidance in prescribing macrolides to pregnant women in several Scandinavian countries. The Objectives of the present study was to investigate the fetal safety of this class of drug by linking a large administrative database of drug dispensing and pregnancy outcome in Southern Israel. A computerized database of medications dispensed from 1999 to 2009 to all women registered in the Clalit health maintenance organization in southern Israel was linked with two computerized databases containing maternal and infant hospitalization records. Also, medical pregnancy termination data were analyzed. The following confounders were controlled for: maternal age, ethnicity, maternal pregestational diabetes, parity, and the year the mother gave birth or went through medical pregnancy termination. First- and third-trimester exposures to macrolide antibiotics as a group and to individual drugs were analyzed. During the study period there were 105,492 pregnancies among Clalit women that met the inclusion criteria. Of these, 104,380 ended in live births or dead fetuses and 1,112 in abortion due to medical reasons. In the first trimester of pregnancy, 1,033 women were exposed to macrolides. There was no association between macrolides and either major malformations [odds ratio (OR), 1.08; 95% confidence interval (CI), 0.84 to 1.38)] or specific malformations, after accounting for maternal age, parity, ethnicity, prepregnancy diabetes, and year of exposure. During the third trimester of pregnancy, 959 women were exposed to macrolides. There was no association between such exposure and perinatal mortality, low birth weight, low Apgar score, or preterm delivery. Similarly, no associations were demonstrated with pyloric stenosis or intussusception. Use of macrolides in the first trimester of pregnancy is not associated with an increased risk of major malformations. Exposure in the third trimester is not likely to increase neonatal risks for pyloric stenosis or intussusception in a clinically meaningful manner.