Search

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.

BACKGROUND: Information on the treatment of pancreatic endocrine tumours (PETs) comes mostly from small, retrospective, uncontrolled studies. METHODS: Newly diagnosed, histologically proven PETs, observed from June 2004 to March 2007 in 24 Italian centres, were included in a specific dataset. RESULTS: Three-hundred and ten patients (mean age 57.6 years, females 46.6%) were analysed. At the time of recruitment, 262 (84.5%) underwent surgery. The percentage of operated patients was 91.9% and 62.0% in surgical and non-surgical centres, respectively. A curative resection was carried out in 83.6% (n = 219) of cases, a palliative resection (debulking) in 10.7% (n = 28), an exploratory laparotomy in 4.6% (n = 12), and a bypass procedure in 1.1% (n = 3). Laparoscopy was performed in 8.0% (n = 21) of cases. Resection consisted of a pancreatoduodenectomy in 46 cases (21.0%), a distal pancreatectomy in 95 (43.4%), an enucleation in 50 (22.8%), a middle pancreatectomy in 16 (7.3%) and a total pancreatectomy in 12 (5.5%). Liver resection was associated with pancreatic resection in 26 cases (9.9%). Post-operative mortality was 1.5% and morbidity 39.7%, respectively. A curative resection was performed more frequently in asymptomatic, small, non-metastatic, benign and at uncertain behaviour tumours, with low Ki67 values. CONCLUSIONS: This study strongly indicates the fact that surgical resection represents the cornerstone treatment of PETs.

Objectives: Information on pancreatic endocrine tumors (PETs) comes mostly from small, retrospective, uncontrolled studies conducted on highly selected patients. The aim of the study was to describe the clinical and pathological features of PETs in a prospective, multicenter study.Methods: Newly diagnosed, histologically proven, sporadic PETs observed from June 2004 to March 2007 in 24 Italian centers were included in a specific data set.Results: Two hundred ninety-seven patients (mean age 58.614.7 years, females 51.2%, males 48.8%) were analyzed. In 73 cases (24.6%), the tumor was functioning (F) (53 insulinomas, 15 gastrinomas, 5 other syndromes) and in 232 (75.4%) it was non-functioning (NF); in 115 cases (38.7%), the diagnosis was incidental. The median tumor size was 20 mm (range 2-150). NF-PETs were significantly more represented among carcinomas (P0.001). Nodal and liver metastases were detected in 84 (28.3%) and 85 (28.6%) cases, respectively. The presence of liver metastases was significantly higher in the NF-PETs than in the F-PETs (32.1% vs. 17.8%; P0.05), and in the symptomatic than in the asymptomatic patients (34.6% vs. 19.1%; P

Background Complete surgical resection of gastric cancer is potentially curative, but long-term survival is poor. Methods Patients with histologically proven adenocarcinoma of the stomach of stages IB, II, IIIA and B, or IV (T4N2M0) and treated with potentially curative surgery were randomly assigned to follow-up alone or to intravenous treatment with four cycles (repeated every 21 days) of PELF (cisplatin [40 mg/m 2 , on days 1 and 5], epirubicin [30 mg/m 2 , days 1 and 5], L-leucovorin [100 mg/m 2 , days 1-4], and 5-fluorouracil [300 mg/m 2 , days 1-4] in a hospital setting. Frequencies and severity of adverse events were determined. Overall survival (OS) and disease-free survival (DFS) were compared between the treatment arms using Kaplan-Meier analysis and a Cox proportional hazards regression model. All statistical tests were two-sided. Results From January 1995 through September 2000, 258 patients were randomly assigned to chemotherapy (n = 130) or surgery alone (n = 128). Patient characteristics were well balanced between the two arms. Among those who received chemotherapy, grade 3 or 4 toxic effects including vomiting, mucositis, and diarrhea were experienced by 21.1%, 8.4%, and 11.8% of patients, respectively. Leucopenia, anemia, and thrombocytopenia of grade 3 or 4 were experienced by 20.3%, 3.3%, and 4.2% of patients, respectively. After a median follow-up of 72.8 months, 128 patients (49.6%) experienced recurrence and 139 (53.9%) deaths were observed, one toxicity-related. Relative to treatment with surgery alone, adjuvant chemotherapy did not increase disease-free survival (hazard ratio [HR] of recurrence = 0.92; 95% confidence interval [Cl] = 0.66 to 1.27) or overall survival (HR of death = 0.90; 95% Cl = 0.64 to 1.26). Conclusions Our results failed to provide proof of an effect of adjuvant chemotherapy with PELF on overall survival or disease-free survival. The estimated effect of chemotherapy (10% reduction in the hazard of death or relapse) is modest and consistent with the results of meta-analyses of adjuvant chemotherapy without platinum agents.

The synthesis of conformationally constrained amino acids is an important tool for the preparation of oligomers that assume a well defined secondary structure. We have recently described the synthesis of oligomers of L-Oxd and L-pGlu and we have demonstrated that these molecules fold in ordered structures characterized by a semi-extended helical conformation. As a part of this project, we report here a straightforward synthesis of 4(S)-oxazolidineacetic acid, 2-oxo benzyl ester (H-Oxac-OBzl), a beta-amino acid derivative, the preparation of its homo-oligomers up to the tetramer level by solution methods and their conformational analysis in structure supporting solvents.