Cytopathological characteristics of solitary fibrous tumour involving the pancreas by fine needle aspiration: Making an accurate preoperative diagnosis in an uncommon location.

BACKGROUND: Solitary fibrous tumour (SFT) is a unique mesenchymal neoplasm with classic features on histology and is characterised by the NAB2-STAT6 gene fusion. There are rare reports of SFTs with pancreatic involvement and only two cases in the literature reporting its features by preoperative fine needle aspiration (FNA). Herein, we characterise the cytomorphological features of four SFTs involving the pancreas by FNA to establish a preoperative diagnostic approach. METHODS: The anatomic pathology archives of two academic medical centres were searched to identify patients with a pancreatic FNA cytology specimen and a confirmed diagnosis of SFT by surgical resection. The clinical history, pathological diagnosis, cytomorphological findings, and results of immunohistochemistry (IHC) were reviewed. RESULTS: Four SFTs were identified from four patients with a median age of 59 years. The morphological features were variable but most frequently showed a bland spindled-to-epithelioid proliferation in fragments and single cells with small, oval, elongated, and hypochromatic nuclei in a haphazard arrangement with or without dense collagen. One tumour presented with a concurrent metastasis and showed a pure epithelioid component with necrosis and enlarged, hyperchromatic nuclei with conspicuous nucleoli and scattered mitoses. IHC was necessary for all diagnoses which were confirmed by surgical resection. CONCLUSIONS: SFTs with pancreatic involvement are rare, and non-specific features and tumour heterogeneity can pose a diagnostic challenge on FNA; however, IHC can be used to make a definitive diagnosis. As a result, FNA is a simple, safe, cost-effective, and accurate approach that can be used to diagnose SFT in the pancreas.

Acute Ethanol Inhibition of Adult Hippocampal Neurogenesis Involves CB1 Cannabinoid Receptor Signaling.

BACKGROUND: Chronic ethanol (EtOH) exposure has been found to inhibit adult hippocampal neurogenesis in multiple models of alcohol addiction. However, acute EtOH inhibition of adult neurogenesis is not well studied. Although many abused drugs have been found to inhibit adult neurogenesis, few have studied cannabinoids or cannabinoids with EtOH, although human use of both together is becoming more common. We used an acute binge alcohol drinking model in combination with select cannabinoid receptor agonists and antagonists to investigate the actions of each alone and together on hippocampal neurogenesis. METHODS: Adult male Wistar rats were treated with an acute binge dose of EtOH (5 g/kg, i.g.), cannabinoid 1 receptor (CB1R) or cannabinoid 2 receptor (CB2R) agonists, as well as selective cannabinoid (CB) antagonists, alone or combined. Hippocampal doublecortin (DCX), Ki67, and activated cleaved caspase-3 (CC3) immunohistochemistry were used to assess neurogenesis, neuroprogenitor proliferation, and cell death, respectively. RESULTS: We found that treatment with EtOH or the CB1R agonist, arachidonoyl-2'-chloroethylamide (ACEA), and the combination significantly reduced DCX-positive neurons (DCX + IR) in dentate gyrus (DG) and increased CC3. Further, using an inhibitor of endocannabinoid metabolism, for example, JZL195, we also found reduced DCX + IR neurogenesis. Treatment with 2 different CB1R antagonists (AM251 or SR141716) reversed both CB1R agonist and EtOH inhibition of adult neurogenesis. CB2R agonist HU-308 treatment did not produce any significant change in DCX + IR. Interestingly, neither EtOH nor CB1R agonist produced any alteration in cell proliferation in DG as measured by Ki67 + cell population, but CC3-positive cell numbers increased following EtOH or ACEA treatment suggesting an increase in cell death. CONCLUSIONS: Together, these findings suggest that acute CB1R cannabinoid receptor activation and binge EtOH treatment reduce neurogenesis through mechanisms involving CB1R.

The perceptual responses to high-velocity, low-load and low-velocity, high-load resistance exercise in older adults.

The present study examined exercise affect during volume-load matched, high-velocity, low-load and low-velocity, high-load resistance exercise conditions in older adults. Ten older adults completed three sets of eight exercises on six separate occasions (three high-velocity, low-load and three low-velocity, high-load sessions) in a crossover study design. High-velocity, low-load was performed at 40% of predicted one repetition maximum, and low-velocity, high-load at 80%. The Physical Activity Affect Scale, Felt Arousal Scale, Feeling Scale, Rating of Perceived Exertion, Visual Analogue Scales, and the Physical Activity Enjoyment Scale examined exercise intensity and affect. There were moderate effects of exercise condition on positive exercise affect (P = 0.067; [Formula: see text] = 0.33), and trivial effects on negative exercise affect (P = 0.904; [Formula: see text] = 0.002). Rating of perceived exertion (P < 0.001; [Formula: see text] = 0.41) and fatigue (P = 0.012; [Formula: see text] = 0.52) were greater during low-velocity, high-load. Furthermore, high-velocity, low-load facilitated statistically insignificant, favourable changes (less exertion, more enjoyment etc.) for all other measures. These findings combined with emerging evidence that high-velocity, low-load is superior for improving muscle power and/or functional performance, indicates that high-velocity, low-load should be prescribed preferentially. However, both exercise conditions were enjoyed similarly, demonstrating that individual preference is an important consideration.

Angiomyolipomatous Lesions of the Nasal Cavity (Sinonasal Angioleiomyoma with Adipocytic Differentiation): A Multi-Institutional Immunohistochemical and Molecular Study.

Purpose: Mesenchymal neoplasms composed of vascular, smooth muscle, and adipocytic components are uncommon in the nasal cavity. While angioleiomyoma (AL) is a smooth muscle tumor in the Head & Neck WHO classification, it is considered of pericytic origin in the Skin as well as Soft Tissue and Bone classifications. For nasal AL with an adipocytic component, the terms AL with adipocytic differentiation and angiomyolipoma (AML) have been applied, among others. AML is a type of perivascular epithelioid cell tumor (PEComa), most often arising in the kidney, sometimes associated with the tuberous sclerosis complex (TSC). It is uncertain whether nasal cavity AML and AL are best considered hamartomas or neoplasms, as their genetics are largely unexplored. Methods: We performed a multi-institutional retrospective study of nasal cavity mesenchymal lesions. Patient demographics, clinical histories, and histologic and immunohistochemical findings were collected. DNA and RNA were extracted from formalin-fixed, paraffin-embedded tissue and analyzed by SNP-based chromosomal microarray, targeted RNA fusion sequencing, and whole-exome sequencing. Results: Fifteen lesions (3 to 42 mm) were identified predominantly in male (87%) patients with a median age of 60. Patients typically presented with obstructive symptoms, and none had a history of TSC. One AL was a recurrence from six years prior; 11 cases showed no recurrence (median 4.7 years, range: 0.88-12.4). Morphologically, 11 AMLs contained 30-80% smooth muscle, 10-25% vasculature, and 2-60% adipose tissue, while four ALs contained 70-80% smooth muscle and 20-30% vasculature. Other histologic observations included surface ulceration, vascular thrombosis, chronic inflammation, and myxoid change; no well-developed epithelioid cell morphology was identified. Immunohistochemically, all cases were positive for smooth muscle markers (actin and/or desmin) and negative for melanocytic markers. Molecular analysis revealed loss of 3p and 11q in a single AML. No other known pathogenic copy number or molecular alterations were seen, including in TSC1/2, TFE3, or NOTCH2. Conclusion: Nasal cavity AML lacks morphologic, immunophenotypic, and genetic features of PEComa family AMLs. The significant histologic overlap between nasal AML and AL without distinguishing molecular features in either entity suggests "sinonasal angioleiomyoma with adipocytic differentiation" may be the most appropriate terminology for hybrid vascular and smooth muscle lesions containing adipocytic components.

A Pineal Parenchymal Tumor of Intermediate Differentiation in an Octogenarian Contains a Rare KBTBD4 Insertion.

Pineal parenchymal tumors are rare central nervous system tumors that pose diagnostic challenges for surgical pathologists. Due to their paucity, their clinicopathologic features are still being defined. We report an 86-year-old woman with a remote history of breast lobular carcinoma who presented with a 2-month neurologic history that included gait instability, blurry vision, and headaches. Magnetic resonance imaging revealed a lobular, heterogeneously enhancing pineal region mass compressing the aqueduct of Sylvius. A biopsy performed concomitant with endoscopic third ventriculostomy consisted of small sheets of cells with eosinophilic to clear cytoplasm, multipolar processes, and ovoid nuclei with stippled chromatin. Whole exome sequencing revealed a small in-frame insertion (duplication) in exon 4 of KBTBD4 (c.931_939dup, p.P311_R313dup/ p.R313_M314insPRR), which has very recently been reported in 2 pineal parenchymal tumors of intermediate differentiation (PPTID). Additionally, variants of uncertain significance in CEBPA (c.863G > C, p.R288P) and MYC (c.655T > C, p.S219P) were identified. Although PPTID is considered a disease of young adulthood, review of 2 institutional cohorts of patients with pineal region tumors revealed that 25% of individuals with PPTID were over 65 years of age. In conclusion, PPTID should be considered in the differential diagnosis of pineal region tumors in older adults.

Context-dependent activation of SIRT3 is necessary for anchorage-independent survival and metastasis of ovarian cancer cells.

Tumor cells must alter their antioxidant capacity for maximal metastatic potential. Yet the antioxidant adaptations required for ovarian cancer transcoelomic metastasis, which is the passive dissemination of cells in the peritoneal cavity, remain largely unexplored. Somewhat contradicting the need for oxidant scavenging are previous observations that expression of SIRT3, a nutrient stress sensor and regulator of mitochondrial antioxidant defenses, is often suppressed in many primary tumors. We have discovered that this mitochondrial deacetylase is specifically upregulated in a context-dependent manner in cancer cells. SIRT3 activity and expression transiently increased following ovarian cancer cell detachment and in tumor cells derived from malignant ascites of high-grade serous adenocarcinoma patients. Mechanistically, SIRT3 prevents mitochondrial superoxide surges in detached cells by regulating the manganese superoxide dismutase (SOD2). This mitochondrial stress response is under dual regulation by SIRT3. SIRT3 rapidly increases SOD2 activity as an early adaptation to cellular detachment, which is followed by SIRT3-dependent increases in SOD2 mRNA during sustained anchorage-independence. In addition, SIRT3 inhibits glycolytic capacity in anchorage-independent cells thereby contributing to metabolic changes in response to detachment. While manipulation of SIRT3 expression has few deleterious effects on cancer cells in attached conditions, SIRT3 upregulation and SIRT3-mediated oxidant scavenging are required for anoikis resistance in vitro following matrix detachment, and both SIRT3 and SOD2 are necessary for colonization of the peritoneal cavity in vivo. Our results highlight the novel context-specific, pro-metastatic role of SIRT3 in ovarian cancer.

Utilizing Surgical Bootcamps to Teach Core Entrustable Professional Activities to Senior Medical Students.

To promote residency preparedness, the Association of American Medical Colleges defined 13 core entrustable professional activities for entering residency (CEPAERs), which represent tasks that students should be able to perform on day one of residency. At the authors' institution, a four-week surgery boot camp course is offered to senior medical students, which may provide an effective mechanism for teaching the CEPAERs. Nine senior students participating in a surgery boot camp course were subjected to pre- and post-course surveys. Student expectations were closely aligned with the CEPAERs. Competence was demonstrated in all CEPAERs; however, four students did require remediation with Advanced Cardiovascular Life Support before achieving competence. In the "death on the wards module," we found a significant increase in student confidence (19.78, SD 1.47, P > 0.05 vs 31.56, SD 1.49, P < 0.01) and knowledge (16.11, SD 1.32, P > 0.05 vs 31.33, SD 2.04, P < 0.01). In a one-year follow-up survey, all participants agreed that the boot camp course was useful and positively impacted their intern year. Surgical boot camp courses provide an effective and reproducible means for teaching the CEPAERs and was found useful in preparing medical students for residency.

The acute physiological effects of high- and low-velocity resistance exercise in older adults.

The aim of the present study was to determine if workload matched, high-velocity (HVE) and low-velocity (LVE) resistance exercise protocols, elicit differing acute physiological responses in older adults. Ten older adults completed three sets of eight exercises on six separate occasions (three HVE and three LVE sessions). Systolic blood pressure, diastolic blood pressure and blood lactate were measured pre- and post-exercise, heart rate was measured before exercise and following each set of each exercise. Finally, a rating of perceived exertion was measured following each set of each exercise. There were no significant differences in blood lactate (F(1,9) = 0.028; P = 0.872; η P 2  = 0.003), heart rate (F(1,9) = 0.045; P = 0.837; η P 2  = 0.005), systolic blood pressure (F(1,9) = 0.023; P = 0.884; η P 2  = 0.003) or diastolic blood pressure (F(1,9) = 1.516; P = 0.249; η P 2  = 0.144) between HVE and LVE. However, LVE elicited significantly greater ratings of perceived exertion compared to HVE (F(1,9) = 13.059; P = 0.006; η P 2  = 0.592). The present workload matched HVE and LVE protocols produced comparable physiological responses, although greater exertion was perceived during LVE.

Movement velocity during high- and low-velocity resistance exercise protocols in older adults.

The primary aim of the present study was to determine the actual movement velocity of high-velocity, low-load (HVLL) and low-velocity, high-load (LVHL) resistance exercise in a group of older adults. The secondary aim was to examine the differences in velocities produced between male and females. In a crossover study design, four males (age: 67±3years) and five females (age: 68±2years) completed three sets of leg press, calf raise, leg curl, leg extension, chest press, seated row, bicep curl and tricep extension on six separate occasions (three HVLL and three LVHL sessions). The command "as fast as possible" was given for the concentric phase of HVLL, and 2s using a 60-bpm metronome controlled the concentric phase during LVHL. Participants had three days of recovery between each session, and a 7-day period before crossing over to the other protocol. Movement velocity was measured during the concentric and eccentric phases of resistance exercise using two-dimensional video analysis. The concentric phases for all exercises were significantly faster (P<0.001) during HVLL compared to LVHL. Furthermore, males produced significantly greater velocities than females during the concentric phase of the chest press, seated row, bicep curl, and tricep extension for both HVLL and LVHL (P<0.05). These protocols provide a simple solution for exercise professionals to ensure that older adults are training at desired velocities when carrying out resistance exercise, without the need for equipment that measures velocity.