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Ewing’s Sarcoma Family Tumors (ESFT) include classic Ewing’s sarcoma of bone, extra-skeletal Ewing’s sarcoma (EES), malignant small cell tumor of the chest wall (Askin tumor), and soft tissue-based Peripheral Primitive Neuroectodermal tumors (pPNET). The t(11;22)(q24;q12) translocation is associated with 85% of tumors and leads to EWS-FLI-1 (Ewing’s Sarcoma–Friend Leukemia Integration-1) formation. This is a potent transforming gene that encodes a chimeric protein that plays a role in the genesis of Ewing’s Sarcoma and Primitive Neuroectodermal Tumors. The breast location of ESFT remains exceptional. The prognosis is among the poorest of all subtypes of breast cancer and even poorer than other extraosseous Ewing’s sarcomas. We describe the case report of a 23-year-old patient with a growing breast lump, who required an accurate and challenging diagnostic estimation and who ultimately resulted in a peripheral primary neuroectodermal tumor (pPNET). Through this case description and a brief narrative review of the literature, we aim to highlight the rarity of ESFT located in the breast. Histopathological confirmation is mandatory for all growing masses of the breast to reach a conclusive diagnosis and plan the correct treatment. Patients with rare diagnoses should always be centralized in breast units, conducting multidisciplinary meetings and, when necessary, the diagnosis should be shared through wider national or international registries.

The management of tandem extracranial internal carotid artery and intracranial large vessel occlusion during endovascular thrombectomy (EVT) for acute ischemic stroke (AIS) has been under-investigated. We sought to investigate outcomes of AIS patients with tandem occlusion (TO) treated with carotid artery stenting (CAS) compared to those not treated with CAS (no-CAS) during EVT.We performed a cohort study using data from AIS patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke. Outcomes were 3 months' mortality, functional outcome, complete and successful recanalization, any intracranial hemorrhage, parenchymal hematoma and symptomatic intracerebral hemorrhage.Among 466 AIS patients with TO, CAS patients were 122 and no-CAS patients were 226 (118 excluded). After adjustment for unbalanced variables, CAS was associated with a lower rate of 3 months' mortality (OR 0.407, 95% CI 0.171-0.969, p = 0.042). After adjustment for pre-defined variables, CAS was associated with a lower rate of 3 months' mortality (aOR 0.430, 95% CI 0.187-0.989, p = 0.047) and a higher rate of complete recanalization (aOR 1.986, 95% CI 1.121-3.518, p = 0.019), successful recanalization (aOR 2.433, 95% CI 1.263-4.686, p = 0.008) and parenchymal hematoma (aOR 2.876, 95% CI 1.173-7.050, p = 0.021). CAS was associated with lower 3 months mortality (OR 0.373, 95% CI 0.141-0.982, p = 0.046) and higher rates of successful recanalization (OR 2.082, 95% CI 1.099-3.942, p = 0.024) after adjustment for variables associated with 3 months' mortality and successful recanalization, respectively.Among AIS patients with TO, CAS during EVT was associated with a higher rate of successful reperfusion and a lower rate of 3 months' mortality.

Background. Everolimus (Eve), which is a mammalian target of Rapamicin (mTOR) inhibitor, is part of the therapeutic armamentarium of neuroendocrine tumors (NETs). Currently, there are no validated biomarkers predicting Eve efficacy in NETs. In this study, we explore whether the expression of phosphorilated (p)-mTOR and p70S6-kinase (S6K), a downstream effector of mTOR, correlates with the outcome of patients with NET that were treated with Eve. Methods. Tissue specimens that were derived from NETs treated with Eve at our Institution were examined for the expression levels of p-mTOR and p-S6K by immunohistochemistry. Response rate (RR), progression-free survival (PFS), and overall survival (OS) were analyzed in two groups: p-mTOR/p-S6K positive (group 1) and p-mTOR/p-S6K negative (group 2). Univariate and multivariate Cox regression analysis were performed. Results. Twenty-four patients with advanced NETs that were treated with Eve were included in the analysis. Eight out 24 (33.3%) patients were both p-mTOR and p-S6K positive. A better median PFS and OS in group 1 (18.2 and 39.9 months) as compared to group 2 (13 and 32.4 months) was depicted, with a toxicity profile that was comparable with data literature. Conclusions. Our study suggests that the activation of mTOR pathway can predict better outcomes in patients with NET treated with Eve. However, these results warrant further confirmation in a prospective setting.

Background Gastro Intestinal Stromal Tumors (GISTs) are defined as mesenchymal tumours that develop within the wall of the gastrointestinal tract from the interstitial cells of Cajal. The oncogenic event that leads to GIST development is a gain of function gene mutation in one of the receptor protein tyrosine kinases KIT or PDGFRA. Clinical presentation depends on the location, size and growth rate of the tumor. In most cases, symptoms are absent or vague and the lesion is found incidentally during procedures or surgery executed for other reasons. Methods This study reviews clinical presentation, histo-pathological features and surgical treatment of 9 cases of GISTs treated at Emergency Surgery Department of Bologna between 2011 and 2016. Results Between June 2011 and March 2016, 9 patients were admitted at our institution and received surgical treatment for GISTs. All 9 were male. The mean age at diagnosis was 57 (range 37–75 years). In our study 4 patients were asymptomatic and diagnosis was an incidental finding during radiological workup for other diseases. Five patients were admitted for the onset of complications: 3 GI bleeding, 1 acute abdominal pain and 1 duodenal occlusion. Tumor site was stomach in 7 patients and duodenum in 2. Tumor size was > 2 and ≤ 5 cm in 3 cases, > 5 and ≤ 10 cm in 4 cases. Two patients presented with a giant GIST > 20 cm. Histopathological examination was carried out in all patients. GIST cell morphology was spindle in 6 and mixed (epithelioid and spindle cells) in 3 cases. CD117 and DOG1 were positive in all lesions. CD34 positivity occurred in 3. S-100, SMA, PDGFR and desmin were tested only in a few patients. According to Mienninen criteria, patients were stratified as high (3 patients), intermediate (1), low (2) and very low risk (3). One patient was treated with neoadiuvant Imatinib achieving a partial response and subsequently was able to underwent surgical resection. Laparoscopic wedge resection was performed in 1 patients and conventional open surgery in 8 patients (gastric wedge resection in 3 cases, partial gastrectomy in 2, total gastrectomy in 1. In the two patients with duodenal GIST duodenal resection was preferred to Whipple procedure. All patients in our study were enrolled in a oncological follow-up program and no recurrences were recorded. Conclusions Biopsy is mandatory for the preoperative diagnosis of GIST and useful to decide the therapeutical approach. Surgery is the treatment of choice for patients with localized and potentially resectable lesions and may be indicated for locally advanced or previously non resectable disease after a favorable response to preoperative therapy with tyrosine kinase inhibitors.

Effective systemic therapies for patients with advanced, progressive neuroendocrine tumours of the lung or gastrointestinal tract are scarce. We aimed to assess the efficacy and safety of everolimus compared with placebo in this patient population.In the randomised, double-blind, placebo-controlled, phase 3 RADIANT-4 trial, adult patients (aged ≥18 years) with advanced, progressive, well-differentiated, non-functional neuroendocrine tumours of lung or gastrointestinal origin were enrolled from 97 centres in 25 countries worldwide. Eligible patients were randomly assigned in a 2:1 ratio by an interactive voice response system to receive everolimus 10 mg per day orally or identical placebo, both with supportive care. Patients were stratified by tumour origin, performance status, and previous somatostatin analogue treatment. Patients, investigators, and the study sponsor were masked to treatment assignment. The primary endpoint was progression-free survival assessed by central radiology review, analysed by intention to treat. Overall survival was a key secondary endpoint. This trial is registered with ClinicalTrials.gov, number NCT01524783.Between April 3, 2012, and Aug 23, 2013, a total of 302 patients were enrolled, of whom 205 were allocated to everolimus 10 mg per day and 97 to placebo. Median progression-free survival was 11·0 months (95% CI 9·2-13·3) in the everolimus group and 3·9 months (3·6-7·4) in the placebo group. Everolimus was associated with a 52% reduction in the estimated risk of progression or death (hazard ratio [HR] 0·48 [95% CI 0·35-0·67], p0·00001). Although not statistically significant, the results of the first pre-planned interim overall survival analysis indicated that everolimus might be associated with a reduction in the risk of death (HR 0·64 [95% CI 0·40-1·05], one-sided p=0·037, whereas the boundary for statistical significance was 0·0002). Grade 3 or 4 drug-related adverse events were infrequent and included stomatitis (in 18 [9%] of 202 patients in the everolimus group vs 0 of 98 in the placebo group), diarrhoea (15 [7%] vs 2 [2%]), infections (14 [7%] vs 0), anaemia (8 [4%] vs 1 [1%]), fatigue (7 [3%] vs 1 [1%]), and hyperglycaemia (7 [3%] vs 0).Treatment with everolimus was associated with significant improvement in progression-free survival in patients with progressive lung or gastrointestinal neuroendocrine tumours. The safety findings were consistent with the known side-effect profile of everolimus. Everolimus is the first targeted agent to show robust anti-tumour activity with acceptable tolerability across a broad range of neuroendocrine tumours, including those arising from the pancreas, lung, and gastrointestinal tract.Novartis Pharmaceuticals Corporation.