Re-visiting the ATA 2015 sonographic guidelines - who are we missing?: A retrospective review.

BACKGROUND: The American Thyroid Association published revised guidelines in 2015 on the management of differentiated thyroid cancer in adults. One of the key changes introduced in the revision proposes that diagnostic biopsy be based on ultrasound findings (i.e. size and nodule characteristics). The overall effect of these changes results in fewer nodules requiring biopsy. This study was conducted to determine if the changes to the guidelines will result in overlooked thyroid cancers, specifically malignancies with aggressive characteristics measuring between 1 and 1.49 cm. METHODS: Patients (n = 2083) with thyroid nodules who underwent total or subtotal/hemi thyroidectomy with or without neck dissection by a single surgeon between 2006 and 2016 were retrospectively enrolled. Demographic information and nodule characteristics were collected for all patients. Ultrasonography and final pathology reports were reviewed for patients with thyroid nodules between the sizes of 1-1.49 cm (n = 155). RESULTS: 45% (n = 70) of patients with nodules between 1 and 1.49 cm were "low suspicion" nodules according to ultrasound. 47 of these nodules contained malignancies on final histopathological examination, 100% of which were of the papillary subtype. 21% (n = 10) of these malignant nodules demonstrated extrathyroidal extension and 34% (n = 16) were associated with regional metastases. CONCLUSIONS: Reliance on sonographic patterns alone could result in missed cancer diagnoses in patients with thyroid nodules measuring between 1 and 1.49 cm. Moreover, a portion of these malignancies may be associated with aggressive features. The effect of this finding on long-term outcomes is unclear.

Can preoperative thyroglobulin antibody levels be used as a marker for well differentiated thyroid cancer?

BACKGROUND: It has been reported that thyroglobulin antibody are more frequently elevated in patients with thyroid cancercompared to general population. This study aims at evaluating whether preoperative thyroglobulin antibody (TgAb) levels increase the likelihood that a thyroid nodule is malignant. METHODS: A retrospective review of 586 patients who underwent thyroidectomy was conducted. Demographic data, TgAb levels, and final histopathology were recorded. Patients were divided into two groups: TgAb positive (defined as TgAb ≥ 30 IU/ml) and TgAb low/negative (defined as TgAb < 30). RESULTS: Preoperative TgAb levels were available in 405 patients. There were 353 (87 %) patients in the TgAblow/negative group (malignancy rate: 50.42 %) and 52 (13 %) patients in the TgAb positive group (malignancy rate: 65.38 %). The sensitivity, specificity, positive predictive value and negative predictive value of TgAb ≥ 30 IU/ml for thyroid malignancy were 16.04 %, 90.67 %, 65.38 % and 49.58 %, respectively. The relative risk of having a malignant thyroid nodule when the TgAb titers were≥30 IU/ml was 1.30 (CI1.04-1.62) and the odds ratio was 1.86 (CI 1.01-3.41). Both the Pearson chi-square test (p = 0.024) and Fisher's exact test (p = 0.017) yielded statistical significance between the two groups. CONCLUSIONS: In this study, patients with preoperative TgAb ≥ 30 IU/ml had a higher rate of malignancy when compared topatients with TgAb < 30 IU/ml. This suggests that an elevated TgAb level may indicate that a thyroid nodule is at an increased risk for malignancy.

Short polyglutamine tracts in the androgen receptor are protective against breast cancer in the general population.

We studied the association of breast cancer with the polymorphic polyglutamine repeat of the androgen receptor (AR) in 255 incident cases of breast cancer and 461 matched controls from the Quebec City metropolitan area. Women for whom the sum of both of the AR (CAG)n-repeats alleles is 39 or less (short-allele AR genotypes) have one-half the risk of breast cancer compared with women for whom the sum of AR (CAG)n-repeats is 40 or more [odds ratio (OR), 0.5; 95% confidence interval (CI), 0.3-0.83; P = 0.007]. This association is stronger in postmenopausal women (180 cases, 297 controls; OR, 0.36; 95% CI, 0.19-0.7; P = 0.003). We also observed an interaction between the type of menopause (natural versus surgical) and the AR genotype on breast cancer risk. Alternately, when subjects were grouped according to their (CAG)n-repeat genotype [homozygous for short alleles (CAG)n < or = 20; other genotypes ("long allele")], results were similar (OR. 0.5; 95% CI, 0.27-0.82; P = 0.007). Thus, women with short-alleles AR genotypes appear to be protected against breast cancer. Short-alleles AR genotypes were observed in 16% of the general population as represented by the control group. Short polyglutamine repeats in the AR protein have been reported to be associated with an increase in the capacity of the receptor to activate transcription of reporter genes in vitro. Furthermore, androgens have been previously shown to inhibit in vitro the growth of breast cancer cell lines. This suggests that differences in the number of polyglutamines in the AR protein may influence individual risk of breast cancer, especially in postmenopausal women, and that this apparent protection could be the consequence of an increased response/sensitivity to androgens.

A prospective longitudinal study of platelet angiotensin II receptors for the prediction of preeclampsia.

OBJECTIVES: We developed a simplified method using a relatively small volume of blood for the determination of platelet angiotensin II receptors by saturation analysis and we evaluated its performance for the prediction of preeclampsia. DESIGN AND METHODS: A platelet suspension with minimal contamination by leukocytes and erythrocytes is obtained by centrifugation and washing. The platelet concentrate is incubated in a multi-well plate with increasing concentration of radiolabelled angiotensin II in the presence or absence of an excess of unlabelled angiotensin II. Bound and free fractions are separated using an oil mixture. Maximum binding is determined by Scatchard plot. This method was compared with a previously reported method. Our method was prospectively evaluated in 801 women attending our institution for routine prenatal care. A specimen was obtained at each trimester of pregnancy whenever possible. Diagnosis of preeclampsia was done postnatally by an experienced obstetrician. RESULTS: The method showed acceptable correlation with a previously published method although a proportional bias of 2.1 was observed between the two methods. No differences in mean maximum binding were observed between normal and affected pregnancies at either trimester. Even when the results were analyzed longitudinally, using the change in maximum binding between two trimesters for each patient, no significant increase could be documented in preeclamptic pregnancies. CONCLUSIONS: Platelet angiotensin II receptor measurement is not a clinically useful marker for the prediction of preeclampsia.