Addarii Institute of Oncology

Bologna, Italy

Addarii Institute of Oncology

Bologna, Italy

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Giunchi F.,Addarii Institute of Oncology | Panzacchi R.,Addarii Institute of Oncology | Capizzi E.,Addarii Institute of Oncology | Schiavina R.,University of Bologna | And 4 more authors.
Clinical Genitourinary Cancer | Year: 2016

Introduction: Pathological staging of bladder cancer (BC) on trans-urethral bladder resection (TURB) specimens is critical for the indication of radical cystectomy (RC). Materials and Methods: We aimed to assess the inter-observer variability among dedicated and not dedicated genito-urinary pathologists (GUP) and the predictive value of the amount of muscularis propria (MP) in the TURB specimens to predict accurate staging in RC. We selected 101 patients with at least 1 diagnosis of pT1 high grade BC who underwent RC during the history of disease. All the pathological TURB and RC specimens were reviewed by 3 GUPs, and concordance among them and with the original pathology report (OPR) was made. The presence and the extent of MP was measured in all the TURB specimens and correlated to stage at RC. Results: Excellent (0.90 ≥ K ≥ 0.74) diagnostic concordance was reached among GUP while only good (0.77 ≥ K ≥ 0.67) with the OPR on stage and grade in TURBs. We found a general up-stage in the OPR compared with the GUP review. After histological review, 34.4% cases were downstaged to pT1 from pT2 and 10.1% from pT1 to pTa. The presence of MP was associated with a better discrimination of the stage at RC (P = .00065), and a trend towards correlation was found with its extent (area under the curve-receiver operator characteristic = 0.752; best cut-off 3.69 mm). Conclusion: The implementation of dedicated GUP can improve diagnostic sensitivity and specificity in BC diagnosis. The amount of MP and perhaps its extent in pT1 TURB speciments can predict more accurate cancer stage at RC. © 2016 Elsevier Inc.


Diemberger I.,University of Bologna | Massaro G.,University of Bologna | Cubelli M.,Addarii Institute of Oncology | Rubino D.,Addarii Institute of Oncology | And 8 more authors.
European Journal of Clinical Pharmacology | Year: 2015

Purpose: Oncological patients are at increasing risk of QT prolongation, a risk factor for ventricular arrhythmia. We assessed impact and risk factors for corrected QT (QTc) prolongation during multiple-cycle chemotherapy. Methods: We enrolled 100 outpatients initiating chemotherapy in a university center specializing in female cancer. Clinical, drug, laboratory, and 12-lead ECG data collection at baseline and at each chemotherapy cycle was performed. Results: Enrolled patients were followed for 992 chemotherapy cycles (median 7; interquartile range 6-13); 2438 ECGs were recorded (20; 18-31) 36.8 % pre-therapy, 36.8 % following chemotherapy, and 22.5 % 7-10 days after chemotherapy. Maximum QTc (Max-QTc) was recorded after 4 chemotherapy administrations in >50 % of the entire cohort and also within every subset of patients with prolonged QTc (57 % 471-480 ms; 54 % 481-500 ms; 66 % >500 ms). No cumulative effect on QTc was shown. QTc prolongation was comparable among the various protocols. Prophylactic/supportive drugs were not associated with additional QTc prolongation. Variables independently associated with QTc prolongation >470 ms were age (OR 1.056 95 % CI 1.006-1.108, p∈=∈0.028) and the baseline-first chemotherapy averaged QTc (BC-QTc) (OR 1.092 95 % CI 1.051-1.136), a novel parameter devised for this study. Only BC-QTc maintained significance for QTc >480 ms. BC-QTc >435 ms identified 100 % of patients with Max-QTc >500 ms, 96 % with Max-QTc 481-500 ms, and 66 % with Max-QTc 471-480 ms. Only 29 % of patients with Max-QTc 470 ms presented a BC-QTc >435 ms. Conclusions: Our results confirm the high prevalence of QTc prolongation after chemotherapy. Most of the patients reached Max-QTc after several cycles. BC-QTc may help in stratifying arrhythmic risk in real-world clinical practice. © 2015 Springer-Verlag Berlin Heidelberg.


PubMed | Fondazione IRCCS Instituto Nazionale dei Tumori, University of Bologna, Candiolo Cancer Institute FPO, Biomedical University of Rome and Addarii Institute of Oncology
Type: | Journal: Molecular cancer research : MCR | Year: 2017

Quadruple wild-type (WT) gastrointestinal stromal tumors (GIST) is a genomic subgroup lacking KIT/PDGFRA/RAS pathways mutations, with an intact succinate dehydrogenase (SDH) complex. The aim of this work is to perform a wide comprehensive genomic study on quadruple WT GIST to improve the characterization of these patients. We selected 14 clinical cases of quadruple WT GIST, of which nine cases showed sufficient DNA quality for Whole Exome Sequencing (WES). NF1 alterations were identified directly by WES. Gene expression from Whole Transcriptome Sequencing (WTS) and miRNA profiling were performed using fresh-frozen, quadruple WT GIST tissue specimens and compared to SDH and KIT/PDGFRAmutant GIST. WES identified an average of 18 somatic mutations per sample. The most relevant somatic oncogenic mutations identified were in TP53, MEN1, MAX, FGF1R, CHD4 and CTDNN2. No somatic alterations in NF1 were identified in the analyzed cohort. A total of 247 mRNA transcripts and 66 miRs were differentially expressed specifically in quadruple WT GIST. Overexpression of specific molecular markers (COL22A1, CALCRL) and genes involved in neural and neuroendocrine lineage (ASCL1, Family B GPCRs) were detected and further supported by predicted miRNA target analysis. Quadruple WT GIST show a specific genetic signature that deviates significantly from that of KIT/PDGFRA-mutant and SDH-mutant GIST. Mutations in MEN1 and MAX genes, a neural-committed phenotype and up-regulation of the master neuroendocrine regulator ASCL1, support a genetic similarity with neuroendocrine tumors, with whom they share also the great variability in oncogenic driver genes.This study provides novel insights into the biology of quadruple WT GIST that potentially resembles neuroendocrine tumors than to GIST and should promote the development of specific therapeutic approaches.


PubMed | Addarii Institute of Oncology and University of Bologna
Type: Journal Article | Journal: Clinical genitourinary cancer | Year: 2016

Pathological staging of bladder cancer (BC) on trans-urethral bladder resection (TURB) specimens is critical for the indication of radical cystectomy (RC).We aimed to assess the inter-observer variability among dedicated and not dedicated genito-urinary pathologists (GUP) and the predictive value of the amount of muscularis propria (MP) in the TURB specimens to predict accurate staging in RC. We selected 101 patients with at least 1 diagnosis of pT1 high grade BC who underwent RC during the history of disease. All the pathological TURB and RC specimens were reviewed by 3 GUPs, and concordance among them and with the original pathology report (OPR) was made. The presence and the extent of MP was measured in all the TURB specimens and correlated to stage at RC.Excellent (0.90 K 0.74) diagnostic concordance was reached among GUP while only good (0.77 K 0.67) with the OPR on stage and grade in TURBs. We found a general up-stage in the OPR compared with the GUP review. After histological review, 34.4% cases were downstaged to pT1 from pT2 and 10.1% from pT1 to pTa. The presence of MP was associated with a better discrimination of the stage at RC (P= .00065), and a trend towards correlation was found with its extent (area under the curve-receiver operator characteristic= 0.752; best cut-off 3.69mm).The implementation of dedicated GUP can improve diagnostic sensitivity and specificity in BC diagnosis. The amount of MP and perhaps its extent in pT1 TURB speciments can predict more accurate cancer stage at RC.

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