Comparison of low-cost phantoms for ultrasound-guided fine-needle aspiration biopsy training.

INTRODUCTION: Phantoms and simulators are widely accepted methods to gain valuable experience and confidence for inexperienced trainees prior to seeing their patient and for refining their skills. A phantom model that is durable, simple, and inexpensive to produce and use would be ideal to train practitioners in ultrasound-guided fine-needle aspiration biopsy (USFNA) technique. MATERIALS AND METHODS: In this study, we systematically compared several low-cost phantom models including gelatin, extra firm tofu, canned cooked pork, ballistics gel, and chicken breast for their haptic properties, echogenicity, teaching utility, and overall performance based on a Likert scale (1-5; 5 = best). Nine cytopathologists and cytopathology fellows who perform FNA regularly evaluated these models and completed the survey. RESULTS: The gelatin phantom, with a gelatin to water ratio of 1:8 by weight, was found to be the best for USFNA practice and overall performance, followed by the 1:10 gelatin phantom. Tofu and chicken breast phantoms were also good low-cost alternatives that needed only a few minutes of total preparation time. CONCLUSIONS: Low-cost, homemade phantoms can serve as excellent alternatives to commercial phantoms for practicing and teaching USFNA.

Optical coherence tomography and Scheimpflug imaging of the iridocorneal angle following intravitreal injection of different medications: A longitudinal analysis.

PURPOSE: Intravitreal injection of medications induces a sudden increase in posterior segment volume and pushes iris plane anteriorly to narrow iridocorneal angle. The aim of this study to follow and define longitudinal course of these changes following intravitreal injection of 3 different anti-vascular endothelial growth factor (VEGF) medications or dexamethasone implant. MATERIALS AND METHODS: This prospective, longitudinal study included 89 eyes of 89 patients that had an intravitreal injection of bevacizumab (n = 20) or ranibizumab (n = 26) or aflibercept (n = 22) or dexamethasone implant (n = 21). All the participants had a detailed ophthalmological examination including anterior segment optical coherence tomography (AS-OCT) and Scheimpflug imaging of the iridocorneal angle, evaluation of anterior chamber depth (ACD), axial length with optical biometry and endothelial cell counts with specular microscopy just before the injection, at post-injection day 1, and post-injection 1st month. RESULTS: Iridocorneal angle became significantly wider following intravitreal injection of dexamethasone implant at nasal and temporal quadrants at the post-injection 1st month both in AS-OCT (p = 0.006, p = 0.002, respectively) and Scheimpflug imaging (p = 0.003, p = 0.004, respectively). Small changes were observed in iridocorneal angle following anti-VEGF injections but these small could not be confirmed in both imaging techniques. There were also no changes in ACD, axial length and endothelial counts in all groups. CONCLUSION: Dexamethasone implants induced widening of iridocorneal angle that persisted at the post-injection 1st month both at nasal and temporal quadrants. However, intravitreal injection of anti-VEGF agents did not have a comparable effect on iridocorneal angle.

Bacterial contamination of multi-use antibiotic steroid eye ointments and drops.

PURPOSE: This comprehensive prospective study aimed to investigate the bacterial contamination of antibiotic steroid eye ointments and drops frequently used by eye patients. METHOD: In this comprehensive prospective study, a total of 410 multi-use topical eye medications containing 15 different ingredients from 22 pharmaceutical companies used by 185 patients were analyzed. Four groups were formed as follows: group 1: antibiotic ointments (n: 109); group 2: antibiotic drops (n: 103); group 3: steroid ointments (n: 67); and group 4: steroid drops (n: 131). Topical multi-use eye drops and ointments used by patients at home for at least 1 week were randomly collected. The caps and contents were separately bacteriologically examined in a chocolate agar medium. RESULTS: Our study detected bacterial contamination in 23 containers (5.6%) of the total 410 topical drugs. According to the groups, bacterial contamination was detected in 10 of 67 (14.9%) steroid ointments, 6 of 109 (5.5%) antibiotic ointments, 4 of 131(3.1%) steroid drops, and 3 of 103 (2.9%) antibiotic drops. While the bacterial contamination rate in ointments was 9.1%, this rate was 3% in drops. The difference between them was statistically significant (p = 0.015). According to the post-hoc pairwise comparisons, the difference between steroid drops and steroid ointment (p = 0.0023) was statistically significant. Among all drugs, contamination was detected in 12 of the 93 (12.9%) containers used after keratitis, conjunctivitis, and inflammatory conditions. It was determined that preservatives statistically reduced bacterial growth on the cap. The preservatives did not have a statistically significant effect on the bacterial contamination of the contents compared to the caps. While all contaminations were detected in illiterate and primary school graduates, no contamination was seen in the drugs used by any secondary school or university graduate. CONCLUSION: Our study detected contamination in all topical ophthalmic drug groups. Contamination rates were found to be higher in ointments and steroids. Bacterial contamination was also seen in drugs containing preservatives. We should be careful in the use of topical medications. We do not recommend the bilateral use of ointments and drops in infected eyes, such as those with keratitis, or after intraocular surgeries, such as those for cataracts.

Intraoperative Lymph Node Assessment (Touch Preparation Only) for Metastatic Breast Carcinoma in Neoadjuvant and Non-neoadjuvant Settings.

CONTEXT.­: Touch preparation (TP) alone is discouraged for intraoperative lymph node (LN) assessment in the neoadjuvant setting (NAS) owing to overall low sensitivity in detecting metastatic breast cancer. OBJECTIVE.­: To compare the sensitivity, specificity, and negative predictive value of intraoperative LN assessment via TP and examine potential causes of discrepancies along with the clinical, radiologic, and pathologic parameters in the NAS and non-neoadjuvant setting (NNAS). DESIGN.­: A total of 99 LNs from 47 neoadjuvant patients and 108 LNs from 56 non-neoadjuvant patients were identified. Discordant cases were reviewed retrospectively to reveal the discrepancy reasons. Clinical, radiologic, and pathologic data were obtained from chart review and the pathology CoPath database. RESULTS.­: The sensitivity, specificity, and negative predictive value of TP in NAS and NNAS were 34.2% versus 37.5%, 100% versus 100%, and 70.9% versus 90.2%, respectively. In NAS, discrepancy reasons were interpretation challenge due to lobular histotype, poor TP quality secondary to therapy-induced histomorphologic changes, and undersampling due to small tumor deposits (≤2 mm); the latter was the major reason in NNAS. More cases with macrometastasis were missed in NAS compared to NNAS (14 of 25 versus 1 of 10). The parameters associated with discrepancy were lobular histotype, histologic grade 2, estrogen receptor positivity, HER2 human epidermal growth factor receptor 2 negativity, multifocality, and pathologic tumor size greater than 10 mm in NAS; and lymphovascular space involvement and pathologic tumor size greater than 20 mm in NNAS. CONCLUSIONS.­: In NAS, intraoperative TP alone should be used very cautiously owing to a high false-negative rate of macrometastasis, especially for patients with invasive lobular carcinoma and known axillary LN metastasis before neoadjuvant therapy.

HER2 Protein Overexpression and Gene Amplification in Tubo-Ovarian High-grade Serous Carcinomas.

Most tubo-ovarian high-grade serous carcinomas (TO-HGSC) are diagnosed in advanced stages. Although the majority of patients achieve initial remission with cytoreductive surgery and chemotherapy, mortality rate remains high due to recurrent/progressive disease. The addition of trastuzumab to carboplatin-paclitaxel improved progression-free survival of patients with human epidermal growth factor receptor 2 (HER2)-positive uterine serous carcinoma. After this encouraging result of transtuzumab in HER2-positive uterine serous carcinoma, we aimed to determine the frequency of HER2 overexpression/amplification in TO-HGSC and reveal the utility of 2018 ASCO/CAP HER2 testing guideline in breast cancer for TO-HGSC. For 100 cases, HER2 protein expression was assessed by immunohistochemistry and scored from 0 to 3+ according to 2018 ASCO/CAP HER2 testing guideline. HER2 gene amplification was assessed by florescence in situ hybridization for all the 2+ and 3+ cases as well as 5 of the 0/1+ cases. Among 100 cases, immunohistochemistry scores were 0/1+ in 81 cases, 2+ in 18 cases and 3+ in 1 case. By florescence in situ hybridization, the only 3+ case and 1 of the 2+ cases were HER2-amplified and all 5 of the 0/1+ cases were HER2 nonamplified. Subclonal HER2 overexpression/amplification was identified in 1 of the neoadjuvant cases comprising <10% of the entire tumor. In summary, HER2 overexpression/amplification was found in 2% of TO-HGSC. The 2018 ASCO/CAP HER2 testing guideline in breast cancer can be utilized for TO-HGSC. Future studies are needed to explore HER2-targeted therapies in TO-HGSC and expand the patient population who may benefit from HER2-targeted therapies such as patients with activating mutations in HER2 gene without overexpression/amplification.

Psammoma bodies in Papanicolaou tests and associated factors to predict an underlying malignancy: a clinicopathological analysis of 10 cases.

INTRODUCTION: Psammoma bodies (PBs) are rarely encountered in Papanicolaou tests. They have been described in benign and malignant conditions of the gynecologic tract and peritoneum. The aim of our study was to reveal the associated factors with PBs in Papanicolaou tests to predict an underlying malignancy, particularly in the absence of atypical glandular cells (AGCs). MATERIALS AND METHODS: From 1987 to 2018, all gynecologic cytology reports with PBs were identified from the computerized pathology database of Baystate Medical Center, Springfield, Massachusetts. Patients with previous history of gynecologic and/or peritoneal malignancy were excluded. Clinical information and follow-up data were obtained from chart review. RESULTS: PBs were found in 10 of the 1,497,540 Papanicolaou tests (0.0006%). Six patients with age ranging from 19 to 58 years (mean age, 37.6 years) had benign outcome (eg, endometritis, ovarian serous cystadenofibroma). Four patients with age ranging from 31 to 54 years (mean age, 41.7 years) had borderline/malignant outcome (eg, ovarian borderline serous tumor, peritoneal serous psammocarcinoma). All patients with borderline/malignant outcome had family history of cancer and/or gene mutation (eg, sister with breast cancer, father with BRCA-1 mutation). PBs were accompanied by AGCs in 2 of 4 borderline/malignant cases. CONCLUSIONS: PBs should not be ignored in Papanicolaou tests because of their possible association with an underlying malignancy. To our knowledge, this is the first study demonstrating that relevant family history of cancer and/or gene mutation may be a helpful clue regarding an underlying malignancy, especially in the absence of accompanied AGCs with PBs.

TMIGD1 acts as a tumor suppressor through regulation of p21Cip1/p27Kip1 in renal cancer.

Renal cell carcinoma (RCC) is a high-risk metastasizing tumor with a poor prognosis and poorly understood mechanism. In this study, we demonstrate that transmembrane and immunoglobulin domain-containing 1 (TMIGD1) is a novel tumor suppressor that is highly expressed in normal renal tubular epithelial cells, but it is downregulated in human renal cancer. We have identified CCAAT/enhancer-binding proteinß (C/EBPß, also called LAP) as a key transcriptional regulator of TMIGD1, whose loss of expression is responsible for downregulation of TMIGD1 in RCC. Transcriptionally active C/EBPß/LAP physically interacted with and increased TMIGD1 promoter activity and expression of TMIGD1. Re-introduction of TMIGD1 into renal tumor cells significantly inhibited tumor growth and metastatic behaviors such as morphogenic branching and cell migration. Restoring TMIGD1 expression in renal tumor cells stimulated phosphorylation of p38MAK, induced expression of p21CIP1 (cyclin-dependent kinase inhibitor 1), and p27KIP1 (cyclin-dependent kinase inhibitor 1B) expression, key cell cycle inhibitor proteins involved in regulation of the cell cycle. The present study identifies TMIGD1 as a novel candidate tumor suppressor gene and provides important insight into pathobiology of RCC that could lead to a better diagnosis and possible novel therapy for RCC.

MINAR1 is a Notch2-binding protein that inhibits angiogenesis and breast cancer growth.

Intrinsically disordered proteins (IDPs)/intrinsically unstructured proteins are characterized by the lack of fixed or stable tertiary structure, and are increasingly recognized as an important class of proteins with major roles in signal transduction and transcriptional regulation. In this study, we report the identification and functional characterization of a previously uncharacterized protein (UPF0258/KIAA1024), major intrinsically disordered Notch2-associated receptor 1 (MINAR1). While MINAR1 carries a single transmembrane domain and a short cytoplasmic domain, it has a large extracellular domain that shares no similarity with known protein sequences. Uncharacteristically, MINAR1 is a highly IDP with nearly 70% of its amino acids sequences unstructured. We demonstrate that MINAR1 physically interacts with Notch2 and its binding to Notch2 increases its stability and function. MINAR1 is widely expressed in various tissues including the epithelial cells of the breast and endothelial cells of blood vessels. MINAR1 plays a negative role in angiogenesis as it inhibits angiogenesis in cell culture and in mouse matrigel plug and zebrafish angiogenesis models. Furthermore, while MINAR1 is highly expressed in the normal human breast, its expression is significantly downregulated in advanced human breast cancer and its re-expression in breast cancer cells inhibited tumor growth. Our study demonstrates that MINAR1 is an IDP that negatively regulates angiogenesis and growth of breast cancer cells.