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Gori S.,S. Maria della Misericordia Hospital | Montemurro F.,Institute for Cancer Research and Treatment | Spazzapan S.,Italian National Cancer Institute | Metro G.,S. Maria della Misericordia Hospital | And 11 more authors.
Annals of Oncology | Year: 2012

Background: Preclinical data suggest that treatment with lapatinib reinduces sensitivity to trastuzumab in human epidermal growth factor receptor 2(HER2)-positive breast cancer cells. Patients and methods: Between January 2007 and November 2010, 179 HER2-positive metastatic breast cancer patients were treated with lapatinib and capecitabine at nine Italian institutions. We evaluated the clinical outcome of 69 patients (38.5%) retreated with trastuzumab after lapatinib progression. Results: Visceral metastases were identified in 51 (74%) and brain metastases in 16 patients (23%). All patients were pretreated with both trastuzumab- and lapatinib-based therapy. We observed with retreatment with trastuzumab-based therapy: 1 complete remission (2%), 18 partial remission (29%) and 10 stable disease ≥6 months (14%) and 47% of clinical benefit (CB). Median duration of response was 8.1 months [95% confidence interval (CI) 5.5-10.7]. No unexpected toxic effects occurred. At a median follow-up of 13 months, median progression-free survival was 4.9 months (95% CI 4.2-5.6) and overall survival (OS) 19.4 months (95% CI 14.0-25.0). Median OS was longer for patients experiencing CB (not reached versus 13.4 months for patients without CB, P = 0.002). Brain involvement was associated with lower median OS (17.3 versus 23.3 months for patients without brain disease; P = 0.021). Conclusion: Retreatment with trastuzumab-based therapy showed CB in 47% of patients progressing during lapatinib-based therapy, leading to a prolonged OS. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. Source


Partelli S.,MD | Partelli S.,Marche Polytechnic University | Tamburrino D.,MD | Crippa S.,PhD | And 5 more authors.
American Journal of Surgery | Year: 2014

Background Amylase value in drains (AVD) is a predictor of pancreatic fistula (PF). We evaluated the accuracy of an AVD-based modelMethods: Two hundred thirty-one patients underwent pancreatoduodenectomy with pancreaticojejunostomy (PDPJ) or pancreatoduodenectomy with duct-to-mucosa (PDDTM) and distal pancreatectomy (DP). Patients with AVD greater than 5,000 U/L on postoperative day (POD) 1 underwent AVD measurement on POD5Results: Sensitivity and specificity of POD1 AVD greater than 5,000 in predicting PF were 71% and 90%, respectively. The sensitivity and specificity of POD5 AVD greater than 200 were 90% and 83%, respectively. AVD greater than 1,000 (for PDPJ) and 2,000 U/L (PDDTM and DP) represented the most accurate cutoffs on POD1. AVD greater than 200 (PDPJ), 300 (PDDTM), and 50 U/L (DP) represented the cutoffs with the highest sensitivity in predicting PF on POD5. Conclusion AVD-based model for predicting PF after pancreatic resection is an accurate tool, although AVD cutoffs should be evaluated for each type of operation. © 2014 Elsevier Inc. Source


Torres A.,Medical University of Lublin | Torres K.,Medical University of Lublin | Pesci A.,Ospedale Sacro Cuore Don Calabria | Paszkowski T.,Medical University of Lublin | And 4 more authors.
International Journal of Cancer | Year: 2013

The aim of our study was to define tissue and plasma miRNA signatures, which could potentially serve as diagnostic and prognostic markers in endometrioid endometrial cancer (EEC) and to investigate miRNA profiles in regard to clinicopathological characteristics. Tissue and plasma samples were collected from 122 women (77 EEC and 45 controls). Expression profiling of 866 human miRNAs and 89 human viral miRNAs was performed in 24 samples and was followed by qPCR validation in 104 patients. Expression of 16 miRNAs was analyzed in 48 plasma samples. Microarray study revealed regulation of 21 miRNAs in EEC tissues comparing to normal endometrium. Altered expression of 17 miRNAs was confirmed by qPCR performed in 104 tissue samples. Seven miRNAs were upregulated and two were downregulated in EEC plasma samples. Expression of a number of miRNAs was associated with International Federation of Gynecology and Obstetrics stage, grade, relapse and nodal metastases. Two miRNA signatures: miR-92a/miR-410 and miR-92a/miR-205/miR-410 classified tumor tissues with higher accuracy in comparison to single miRNAs (AUC: 0.977, 95% CI: 0.927-0.996 and 0.984, 95% CI: 0.938-0.999, respectively). miRNA signature composed of miR-205 and miR-200a predicted relapse with AUC of 0.854 (95% CI: 0.691-0.951). Tissue miRNA signatures were independent prognostic markers of overall (miR-1228/miR-200c/miR-429, HR: 2.98) and progression-free survival (miR-1228/miR-429, HR: 2.453). Plasma miRNA signatures: miR-9/miR-1228 and miR-9/miR-92a, classified EEC plasma samples with high accuracy yielding AUCs of 0.909 (95% CI: 0.789-973) and 0.913 (95% CI: 0.794-0.976), respectively. We conclude that miRNA signatures hold a great promise to become noninvasive biomarkers for early EEC detection and prognosis. What's new? Endometrial cancer is the most common cancer of the female reproductive tract. In this study the authors identified microRNA (miRNA) signatures that allow distinguishing between endometrioid endometrial cancer (EEC) and control tissues and plasma samples. The microRNA signatures were also significantly associated with disease relapse as well as overall and progression-free survival. Moreover, the work revealed associations of several miRNAs with clinicopathological characteristics, which contributes to the understanding of miRNAs involvement in EEC pathogenesis. The study suggests that miRNA signatures hold a great promise to become non-invasive biomarkers for early EEC detection and prognosis. Copyright © 2012 UICC. Source


Torres A.,Medical University of Lublin | Torres K.,Medical University of Lublin | Pesci A.,Ospedale Sacro Cuore Don Calabria | Paszkowski T.,Medical University of Lublin | And 4 more authors.
BMC Cancer | Year: 2012

Background: Alterations of mTOR gene expression have been implicated in the pathogenesis of endometrioid endometrial cancer however only few studies explored the cause of increased mTOR activation in this malignancy. miRNAs are small, noncoding RNAs, which were proven to regulated gene expression at the posttranscriptional level. The study aimed to explore deregulation of miRNAs targeting mTOR kinase (miR-99a, miR-100 and miR-199b) as a possible cause of its altered expression in EEC tissues. In addition expression of the three miRNAs was investigated in plasma of EEC patients and was assessed in terms of diagnostic and prognostic utility.Methods: We investigated expression of mTOR kinase transcripts in 46 fresh tissue samples. Expression of miR-99a, miR-100 and miR-199b was investigated in the same group of fresh samples, and in additional 58 FFPE sections as well as in 48 plasma samples using qPCR. Relative quantification was performed using experimentally validated endogenous controls.Results: mTOR kinase expression was increased in EEC tissues and was accompanied by decreased expression of all three miRNAs. Down-regulation of the investigated miRNAs was discovered in plasma of EEC patients and miRNA signatures classified EEC tissues (miR-99a/miR-100/miR-199b) and plasma (miR-99a/miR-199b) samples with higher accuracy in comparison to single miRNAs. We also revealed that miR-100 was an independent prognostic marker of overall survival.Conclusions: We conclude that increased expression of mTOR kinase coexists with down-regulation of its targeting miRNAs, which could suggest a new mechanism of mTOR pathway alterations in EEC. In addition, our findings implicate that miRNA signatures can be considered promising biomarkers for early detection and prognosis of endometrioid endometrial carcinoma. © 2012 Torres et al.; licensee BioMed Central Ltd. Source


Zamboni G.,University of Verona | Hirabayashi K.,Ospedale Sacro Cuore Don Calabria | Hirabayashi K.,Tokai University | Castelli P.,Ospedale Sacro Cuore Don Calabria | Lennon A.M.,Johns Hopkins Hospital
Best Practice and Research: Clinical Gastroenterology | Year: 2013

Pancreatic cancer has a very poor prognosis, with a five year survival of only 5%. New studies have shown that it takes over 11 years for cells to develop invasive capability. This provides an opportunity to intervene if precursor lesions can be detected. This paper reviews the molecular, pathological, clinical findings and management of pancreatic intraepithelial neoplasia (PanIN), intraductal pancreatic mucinous neoplasm (IPMN) and mucinous cystic neoplasm (MCN), three precursor lesions which can give rise to invasive carcinoma of the pancreas. © 2013 Elsevier Ltd. All rights reserved. Source

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