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Silva invasion pattern can help predict lymph node metastasis risk in endocervical adenocarcinoma. We analysed Silva pattern of invasion and lymphovascular invasion to determine associations with clinical outcomes in stage IA and IB1 endocervical adenocarcinomas. International Federation of Gynecology and Obstetrics (FIGO; 2019 classification) stage IA-IB1 endocervical adenocarcinomas from 15 international institutions were examined for Silva pattern, presence of lymphovascular invasion, and other prognostic parameters. Lymph node metastasis status, local/distant recurrences, and survival data were compared using appropriate statistical tests. Of 399 tumours, 152 (38.1%) were stage IA [IA1, 77 (19.3%); IA2, 75 (18.8%)] and 247 (61.9%) were stage IB1. On multivariate analysis, lymphovascular invasion (p=0.008) and Silva pattern (p0.001) were significant factors when comparing stage IA versus IB1 endocervical adenocarcinomas. Overall survival was significantly associated with lymph node metastasis (p=0.028); recurrence-free survival was significantly associated with lymphovascular invasion (p=0.002) and stage (1B1 versus 1A) (p=0.002). Five and 10 year overall survival and recurrence-free survival rates were similar among Silva pattern A cases and Silva pattern B cases without lymphovascular invasion (p=0.165 and p=0.171, respectively). Silva pattern and lymphovascular invasion are important prognostic factors in stage IA1-IB1 endocervical adenocarcinomas and can supplement 2019 International Federation of Gynecology and Obstetrics staging. Our binary Silva classification system groups patients into low risk (patterns A and B without lymphovascular invasion) and high risk (pattern B with lymphovascular invasion and pattern C) categories.

Granular cell tumor (GCT) is a rare neurogenic neoplasm originating from Schwann cells that predominantly affects women and can involve skin and mucousae. In the respiratory system it most frequently involves bronchi and larynx, while it is rare in the trachea.A 26-year old female smoker was hospitalized for a suspected hypoechoic nodule in the right thyroid lobe closely adherent to the trachea. At preoperative computed tomography tracheal lumen was totally clear. The patient underwent a total thyroidectomy with lymph node dissection and tracheal shaving. The postoperative course was complicated by an extensive subcutaneous bilatreral emphysema associated with respiratory distress appeared on the fifth day. Bronchoscopy revealed a right anterolateral subcentimeter lesion near the second tracheal ring. Histologically, the diagnosis was consistent with a tracheal GCT developing into the thyroid parenchyma. The patient was discharged on the twentieth postoperative day. At the follow-up bronchoscopy the lesion was completely healed and at the last 12 month follow-up the patient is doing well.Tracheal tumors are uncommon neoplasms accounting for about 2% of the total respiratory tree tumors. In literature we found50 papers concerning tracheal GCT and in almost all of the cases patients complained about respiratory symptoms.We report here a rare case of benign GCT of the trachea with extraluminal development, in a young patient who did not complain about preoperative respiratory symptoms, presented on ultrasound as a thyroid nodule with suspected cytology.

Background: Inflammation is a key hallmark of psoriasis and pro-inflammatory cytokines are produced by the transcription factor Nuclear factor-κB (NF-κB). Canonical Wnt/β-catenin pathway blunts the immune-mediated inflammatory cascade in psoriasis. Adenosine A2A receptor activation either blocks NF-κB and boosts the Wnt/β-catenin signalling. PDRN (Polydeoxyribonucleotide) is a biologic agonist of the A2A receptor and its effects were studied in an experimental model of psoriasis. Methods: Psoriasis-like lesions were induced by a topical daily application of imiquimod cream (IMQ; 62.5 mg/day for 7 days) on the shaved back skin of mice. Animals were randomly assigned to the following groups: Sham psoriasis challenged with vaseline cream; IMQ animals challenged with imiquimod and IMQ animals challenged with IMQ and treated with PDRN (8 mg/kg/ip). In histological experiments an additional arm of IMQ animals was treated with PDRN plus istradefylline (KW6002; 25 mg/kg/ip) as an A2A antagonist. Findings: PDRN administration reduced squamous lesions, erythema, epidermal thickness and acanthosis, trying to restore a normal skin architecture. Istradefylline administration abrogated PDRN positive effects, thus pointing out the mechanistic role of the A2A receptor. PDRN decreased pNF-κB and TNF-α IL-6 and IL-12 expression compared to untreated psoriatic animals. Furthermore, A2Areceptor activation prompted Wnt signalling, reduced IL-2 expression and increased IL-10 mRNA expression in psoriatic skin. Finally, PDRN reduced CD3+ cells in superficial psoriatic dermis. Interpretations: PDRN anti-psoriasis potential may be linked to a "dual mode" of action: NF-κB pathway inhibition and Wnt/β-catenin signalling stimulation. Funding: The work has been performed with Departmental funding assigned to FS. Competing Interest Declaration: The authors declare that the research was conducted in the absence of any commercial or financial conflict of interest. Ethics: The procedures were evaluated and approved by the Ethics Committee of the University of Messina (OPBA, #820/2016).

Uveal melanoma is the most frequent primary intraocular neoplasm in adults. Although malignant melanoma may be located at any point in the uveal tract, the choroid and ciliary body are more frequent locations than the iris. In the present study, we examined ADAM10 expression levels in primary uveal melanoma both with and without metastasis, and we evaluated their association with other high risk characteristics for metastasis in order to assess if ADAM10 can be used to predict metastasis. This study included a total of 52 patients, 23 men and 29 women, with uveal melanoma. A significantly high expression of ADAM-10 was seen in patients with metastasis (11/13, 84.6%), but not in patients without metastasis (15/39, 38.5%). In conclusion we found that ADAM10 expression was associated with a more rapid metastatic progression confirming its role in uveal melanoma metastasis.

A 32-year-old, pluriparous, oriental horse breed mare was presented to the Veterinary Teaching Hospital of the Veterinary Medical School of Messina, with clinical symptoms characterized by vulvar blood drainage for suspicious abortion. Ultrasonographic examination showed the presence of blood in uterine body and a complex-mass structure, echo dense with cystic areas with anechoic content at the basis of the right horn. Uterine leiomyoma was suspected, a partial ovary hysterectomy was proposed to the owner; despite this, the owner refused to submit the mare to surgery. The mare spontaneously died after 18 months, and necropsy was performed. At macroscopic postmortem examination, the right uterine horn showed a well-demarcated pedunculated nodular bulge, variegated in color with large hemorrhages (22 × 18 × 15 cm), and a capsulated sessile nodule (7 × 4 × 3 cm) involving the smooth uterine musculature. Histologic analysis suggested a diagnosis of subserosal leiomyoma (large mass) and submucosal intramural leiomyoma (small nodule).

Microcystic urothelial carcinoma is a rare variant of transitional cell carcinoma with an indefinite prognostic significance. Herein, we report for the first time the acquisition of microcystic histology in the penile metastasis of a high-grade urothelial carcinoma of the urinary bladder. The patient died of disseminated disease six months later. The immunohistochemical evaluation of mucin expression in the primitive and metastatic tumor suggests that the microcystic histotype may descend from the primitive urothelial carcinoma through a process of dedifferentiation and subsequent redifferentiation. In conclusion, the acquisition of microcystic histology seems to be associated with an aggressive clinical course of the urothelial carcinoma, as already suggested by other authors. Future studies investigating mucin expression in microcystic urothelial carcinoma may help to define the histogenesis of this tumor.

OBJECTIVE The authors evaluated the effects of donepezil (10 mg/day) versus placebo on brain glucose metabolism. METHODS This was a randomized, double-blind, parallel-group, 24-week pilot study in 28 patients with mild-to-moderate Alzheimer disease (AD). Functional brain activity was quantified by measuring average glucose metabolism in an axial brain slice and regional brain glucose metabolism using positron emission tomography. RESULTS At Week 24, relative to the pons metabolic rate, mean brain glucose metabolism in an axial slice at the level of the striatum was maintained within 0.5% of mean baseline levels for donepezil-treated patients, whereas it declined by an average of 10.4% in placebo-treated patients. This observation was confirmed by an analysis of differences in the mean slopes of glucose metabolism in the striatal slice in donepezil- and placebo-treated patients during the 24-week period. Significant treatment differences at Week 24 favoring donepezil for the mean percentage change from baseline in regional brain glucose metabolism were observed in four predefined regions of interest: the right parietal lobe 1, left temporal lobe 2, right frontal lobe 2, and left frontal lobe 2. CONCLUSION Placebo-treated patients with AD show a decline in functional brain activity, relative to the pons, in several regions, and treatment with donepezil may slow this decline.

Recent findings suggest that intraperitoneal injections of L-tyrosine at high doses (100 mg/kg) alters amphetamine-induced changes in behavior by restoring amphetamine-induced decreases in whole brain norepinephrine (NE). The present study examined the motor effects of L-dihydroxyphenylalanine (L-dopa) and d-amphetamine sulfate in mice after treatment with a basal casein diet supplemented with L-tyrosine. The basal diet supplemented with 1-4% L-tyrosine, or 1-4% L-phenylalanine, produced no changes in motor activity in otherwise untreated mice. Whereas L-dopa (25-100 mg/kg) following inhibition of extracerebral decarboxylase by Ro 4-4602 (25 mg/kg) slightly decreased activity in diet control (casein) animals, this drug treatment enhanced motor activity in a dose-related fashion when L-tyrosine was added to the diet. Increases in motor activity following low doses of amphetamine (0.75-1.5 mg/kg) in casein control mice were antagonized by dietary L-tyrosine, but a higher dose of d-amphetamine (3 mg/kg) interacted with the addition of L-tyrosine producing an increase in motor activity. Neurochemical changes observed in brain concentrations of tyrosine, dopamine (DA), norepinephrine (NE), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), tryptophan, serotonin (5-HT) and 5-hydroxy-indoleacetic acid (5-HIAA) following drug and diet treatments suggest that 5-HT systems, in addition to catecholamine systems, may be involved in mediating these effects.

OBJECTIVES: Donepezil, an anti-dementia drug, has been associated with delays in nursing home placement (NHP) for patients with Alzheimer's disease (AD). This analysis explores the health care cost-saving implications of such treatment. METHODS: Information on the dates and reasons for NHP was obtained through follow-up interviews with caregivers and chart reviews of 763 AD patients who participated in three randomized, double-blind, placebo-controlled clinical trials and two subsequent open-label studies of donepezil. Patients were categorized according to their experiences in utilizing donepezil during the clinical trials and extension studies. Cox proportional hazards models (adjusted for age, gender, baseline Mini-Mental Status Examination scores, caregiver status and post clinical study use of cholinesterase inhibitors) were used to estimate adjusted survival functions from which median times to NHP were estimated for each donepezil use category. Analyses of the relationship between donepezil use and time to NHP were completed for both first dementia-related placement (data reported here) and for permanent placement (data similar). Standard nursing home cost data were applied to these results. RESULTS: For the least exposure group (dose