142 results on '"FIORENTINO M"'
Search Results
2. Final results of a phase III clinical trial of adjuvant chemotherapy with the modified fluorouracil, doxorubicin, and mitomycin regimen in resectable gastric cancer
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Lise, M, Nitti, Donato, Marchet, A, Sahmoud, T, Buyse, M, Duez, N, Fiorentino, M, GUIMARAES DOS SANTOS, J, Labianca, R, Rougier, P, Gignooux, M, and Pedrazzoli, S.
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Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Mitomycin ,medicine.medical_treatment ,Adenocarcinoma ,Disease-Free Survival ,law.invention ,Randomized controlled trial ,Stomach Neoplasms ,law ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Doxorubicin ,Proportional Hazards Models ,Chemotherapy ,business.industry ,Cancer ,medicine.disease ,Combined Modality Therapy ,Surgery ,Europe ,Survival Rate ,Clinical trial ,Regimen ,Chemotherapy, Adjuvant ,Fluorouracil ,Female ,business ,medicine.drug - Abstract
PURPOSE In a randomized clinical trial (European Organization for the Research and Treatment of Cancer [EORTC] no. 40813) on adjuvant chemotherapy in gastric cancer, results obtained after administration of the FAM2 regimen (fluorouracil [5-FU], doxorubicin, and mitomycin) were compared with results obtained after surgery alone to assess the effect of this regimen on overall survival, time to progression, and disease-free interval. PATIENTS AND METHODS Three hundred fourteen patients who had undergone curative resection for stage II or stage III (International Union Against Cancer [UICC] 1978) gastric adenocarcinoma were randomized to receive chemotherapy (treatment arm) or no further treatment (control arm). The chemotherapy schedule was repeated every 43 days for seven cycles. The log-rank test and the Cox model were used for statistical analysis. RESULTS Of 314 patients, 159 comprised the control group and 155 the FAM2 group. Nineteen FAM2 patients never received chemotherapy. The median number of cycles was five. Of the patients started on adjuvant treatment, severe hematologic and nonhematologic toxicity (grades 3 or 4, World Health Organization [WHO] scale) occurred, respectively, in 6% to 9% and in 1% to 29% of cases. The overall 5-year survival rate was 70% for stage II and 32% for stage III patients. No statistically significant difference was found between overall survival of the two treatment arms (P = .295). However, time to progression was significantly delayed in the FAM2 arm (P = .020) and disease-free survival showed borderline significance (P = .068). CONCLUSION FAM2, in view of its high toxicity, cannot be advocated as standard adjuvant treatment for gastric cancer. Large-scale clinical trials using more active, less toxic regimens are required to demonstrate whether adjuvant chemotherapy provides any real benefit.
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- 1995
3. Phase III randomized study of fluorouracil, epirubicin, and cyclophosphamide v fluorouracil, doxorubicin, and cyclophosphamide in advanced breast cancer: an Italian multicentre trial. Italian Multicentre Breast Study with Epirubicin
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Ambrosini G, Palazzotto G, Becchi G, Fornasiero A, Fiorentino M, Calabresi F, Viaro D, Grignani F, Farris A, Foggi Cm, Pastorino G, Rausa L, Bonciarelli G, Fila G, Cartei G, Jirillo A, Bumma C, Di Costanzo F, Capodicasa E, Giuseppe Altavilla, Secondo, Giusto M, Adamo, Lopez M, Lacroix F, Sartori S, Speranza Gb, Palmeri S, Gallo L, Di Lauro L, Minotti, Sacchetti G, Spinelli I, Demicheli R, Maurizio Tonato, Marsilio P, Vici P, Buzzi F, Brugia M, d'Aquino S, Papaldo P, Fosser, Blasina B, Puccetti C, Gambi A, Camilluzzi E, Ardia A, Falchi Am, De Micheli P, Marenco G, Natali M, Cusimano Mp, Zingali G, Daniele O, Poggio R, Moro G, Saccani F, Garusi G, Balli M, D'Alessandro N, Schieppati G, Ciambellotti E, Gebbia N, De Maria D, Padalino D, Bonanni F, Di Carlo A, Bruscagnin G, Bertoncelli P, Chiesa G, Tagliagambe A, Intini C, and Folco U
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Cancer Research ,medicine.medical_specialty ,Cardiotoxicity ,Leukopenia ,Cyclophosphamide ,Performance status ,business.industry ,Nausea ,Gastroenterology ,Oncology ,Fluorouracil ,Internal medicine ,medicine ,Doxorubicin ,medicine.symptom ,business ,medicine.drug ,Epirubicin - Abstract
From February 1983 to January 1985, 497 patients with advanced breast cancer were randomly allocated to receive either epirubicin or doxorubicin in the following combination chemotherapy regimen: fluorouracil (5-FU) 500 mg/m2 intravenous (IV) on days 1 and 8; epirubicin or doxorubicin 50 mg/m2 IV on day 1; cyclophosphamide 500 mg/m2 IV on day 1 (FEC or FAC). Cycles were repeated every 21 days until progression or to cumulative doses of 700 mg/m2 for epirubicin and 550 mg/m2 for doxorubicin. Dose reductions were applied according to the standard criteria. Activity was evaluated in 443 patients (222 in the FEC arm and 221 in the FAC arm). The two experimental groups were comparable in age, performance status, menopausal status, histology, previous treatments, and site of the disease. The overall response rate (complete response and partial response [CR + PR]) was not significantly different: 53.6% for FEC and 56.5% for FAC. The median time to progression was 273 days for FEC and 314 days for FAC; the median survival time was 591 and 613 days, respectively. Leukopenia, anemia, nausea, and vomiting were significantly lower in patients treated with FEC. As for cardiotoxicity, four cases of congestive heart failure (CHF) were recorded among patients treated with FAC while only one was observed in the FEC group. These results indicate that epirubicin in a combination chemotherapy regimen is as active as doxorubicin and is significantly less toxic.
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- 1988
4. De Novo Malignancies after Organ Transplantation: Focus on Viral Infections
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Piselli, P1, Busnach, G, Fratino, L, Citterio, F, Ettorre, Gm, De Paoli, P, Serraino, D, Dal Maso, L, Di Maso, M, Zucchetto, A, Agresta, A, Cimaglia, C, Puro, V, Ippolito, G, Miglioresi, L, Vennarecci, G, Santoro, R, Famulari, A, Delreno, F, Grandaliano, G, Fiorentino, M, Stefoni, S, Todeschini, P, Panicali, L, Valentini, C, Valerio, F, Bossini, N, Setti, G, Michittu, Mb, Murgia, Mg, Onano, B, Veroux, Pierfrancesco, Giuffrida, G, Giaquinta, A, Zerbo, D, Di Leo, L, Perrino, Ml, Colombo, V, Sghirlanzoni, Mc, Leoni, A, Buscemi, B, Lazzarin, M, Zanini, S, Spagnoletti, G, Salerno, Mp, Favi, E, De Luca, L, Lavacca, A, Cascone, C, Virgilio, B, Dossi, F, Fontanella, A, Ambrosini, A, Di Cicco, M., Piselli P, Busnach G, Fratino L, Citterio F, Ettorre GM, De Paoli P, Serraino D, Todeschini P, and Immunosuppression and Cancer Study Group
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SOLID ORGAN TRANSPLANT ,Herpesvirus 4, Human ,medicine.medical_specialty ,Skin Neoplasms ,Settore MED/18 - CHIRURGIA GENERALE ,medicine.medical_treatment ,Lymphoproliferative disorders ,cancer risk ,medicine.disease_cause ,Biochemistry ,Organ transplantation ,Virus ,medicine ,Humans ,Sarcoma, Kaposi ,Molecular Biology ,solid organ transplantation ,Immunosuppression Therapy ,business.industry ,ORGAN ,Cancer ,Kaposi sarcoma ,Immunosuppression ,KAPOSI'S SARCOMA ,General Medicine ,renal transplantation ,medicine.disease ,iatrogenic immunosuppression ,Kidney Transplantation ,neoplasia ,VIRAL INFECTIONS ,Herpesvirus 8, Human ,Immunology ,Molecular Medicine ,POST-TRANSPLANT MALIGNANCY ,Sarcoma ,viral infection ,Carcinogenesis ,business ,Oncovirus - Abstract
Organ transplantation is an increasingly used medical procedure for treating otherwise fatal end stage organ diseases with 107,000 transplants performed worldwide in 2010. Newly developed anti-rejection drugs greatly helped to prolong long-term survival of both the individual and the transplanted organ, and they facilitate the diffusion of organ transplantation. Presently, 5-year patient survival rates are around 90% after kidney transplant and 70% after liver transplant. However, the prolonged chronic use of immunosuppressive drugs is well known to increase the risks of opportunistic diseases, particularly infections and virus-related malignancies. Although transplant recipients experience a nearly 2-fold elevated risk for all types of de-novo cancers, persistent infections with oncogenic viruses - such as Kaposi sarcoma herpes virus, high-risk human papillomaviruses, and Epstein-Barr virus - are associated with up to 100-fold increased cancer risks. This review, focusing on kidney and liver transplants, highlights updated evidences linking iatrogenic immunosuppression, persistent infections with oncogenic viruses and cancer risk. The implicit capacity of oncogenic viruses to immortalise infected cells by disrupting the cell-cycle control can lead, in a setting of induced lowered immune surveillance, to tumorigenesis and this ability is thought to closely correlate with cumulative exposure to immunosuppressive drugs. Mechanisms underlying the relationship between viral infections, immunosuppressive drugs and the risk of skin cancers, post-transplant lymphoproliferative disorders, Kaposi sarcoma, cervical and other ano-genital cancers are reviewed in details.
5. Randomized study of adjuvant chemotherapy for completely resected stage I, II, or IIIA non-small-cell lung cancer
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Scagliotti, G. V., Fossati, R., Torri, V., Crinò, L., Giuseppe Giaccone, Silvano, G., Martelli, M., Clerici, M., Cognetti, F., Tonato, M., Liguori, G., Nittolo, G., Vasta, M., Curcio, C., Borasio, P., Dogliotti, L., Angeletti, C. A., Conte, P. F., Laddaga, M., Rebecchini, S., Spagnesi, S., Lewinski, T., Salvati, F., Marinis, F., Altieri, A., Giordano, F., Puglisi, G., Cipriani, A., Favaretto, A., Fiorentino, M., Giampaglia, G., Loreggian, L., Zuin, R., Jassem, J., Ukmar, R., Buffoni, A., Puricelli, C., Talmassons, G., Morelli, A., Boidi Trotti, A., Bretti, S., Maggi, G., Mussa, A., Sannazzari, G. L., Baldi, S., Ricardi, U., Ruffini, E., Bruni, G., Gridelli, C., Checcaglini, F., Latini, P., Maranzano, E., Todisco, T., Santo Antonio, A., Terzi, A., Pavia, G., Sartirana, A., Ottoni, D., Fontanili, M., Sturani, C., Aiello, L. M., Barbera, S., Baracco, F., Cinquegrana, A., Felletti, R., Scolaro, T., Serrano, J., Felci, U., Manente, P., Drings, P., Zannini, P., Villa, E., Bordone, N., Tordiglione, M., Bandera, M., Fioretti, M., Roviaro, G., Bianco, A. R., Ferrante, G., Rossi, A., Sodano, A., Boni, C., Covacev, L., Lodini, V., Espana, P., Belloni, P. A., Soresi, E., Borghini, U., Cimino, G., Leoni, M., Ravini, M., Luporini, G., Todeschini, G., Campioni, N., Facciolo, F., and Clini, V.
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Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Vindesine ,Mitomycin ,Gastroenterology ,Disease-Free Survival ,Drug Administration Schedule ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Biomarkers, Tumor ,Odds Ratio ,medicine ,Clinical endpoint ,Humans ,Prospective Studies ,Progression-free survival ,Lung cancer ,Survival analysis ,Aged ,Neoplasm Staging ,Proportional Hazards Models ,business.industry ,Patient Selection ,Hazard ratio ,Middle Aged ,medicine.disease ,Survival Analysis ,Chemotherapy regimen ,Surgery ,Log-rank test ,Treatment Outcome ,Italy ,Oncology ,Chemotherapy, Adjuvant ,Multivariate Analysis ,Disease Progression ,Patient Compliance ,Female ,Cisplatin ,business ,medicine.drug - Abstract
Background: Surgery is the primary treatment for patients with stage I, II, or IIIA non-small-cell lung cancer (NSCLC). However, long-term survival of NSCLC patients after surgery alone is largely unsatisfactory, and the role of adjuvant chemotherapy in patient survival has not yet been established. Methods: Between January 1994 and January 1999, 1209 patients with stage I, II, or IIIA NSCLC were randomly assigned to receive mitomycin C (8 mg/m 2 on day 1), vindesine (3 mg/m 2 on days 1 and 8), and cisplatin (100 mg/m 2 on day 1) every 3 weeks for three cycles (MVP group; n = 606) or no treatment (control group; n = 603) after complete resection. Randomization was stratified by investigational center, tumor size, lymph-node involvement, and the intention to perform radiotherapy. The primary endpoint was overall survival and secondary endpoints were progression-free survival and toxicity associated with adjuvant treatment. Survival curves were analyzed using the log-rank test. All statistical tests were two-sided. Results: After a median follow-up time of 64.5 months, there was no statistically significant difference between the two patient groups in overall survival (hazard ratio = 0.96, 95% confidence interval = 0.81 to 1.13; P = .589) or progression-free survival (hazard ratio = 0.89, 95% confidence interval = 0.76 to 1.03; P = .128). Only 69% of patients received the three planned cycles of MVP. Grades 3 and 4 neutropenia occurred in 16% and 12%, respectively, of patients in the MVP arm. Radiotherapy was completed by 65% of patients in the MVP arm and by 82% of patients in the control group. In the multivariable analysis, only disease stage and sex were associated with survival. Conclusion: This randomized trial failed to prospectively confirm a statistically significant role for adjuvant chemotherapy in completely resected NSCLC. Given the poor compliance with the MVP regimen used in this study, future studies should explore more effective treatments.
6. The Leydig cell tumour Scaled Score (LeSS): a method to distinguish benign from malignant cases, with additional correlation with MDM2 and CDK4 amplification
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Michelangelo Fiorentino, Anna Maria Paganoni, Costantino Ricci, G.P. Dagrada, Francesca Giunchi, Maurizio Colecchia, Alessia Bertolotti, Biagio Paolini, Andrea Necchi, Colecchia M., Bertolotti A., Paolini B., Giunchi F., Necchi A., Paganoni A.M., Ricci C., Fiorentino M., Dagrada G.P., Colecchia, M., Bertolotti, A., Paolini, B., Giunchi, F., Necchi, A., Paganoni, A. M., Ricci, C., Fiorentino, M., and Dagrada, G. P.
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Adult ,Male ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,Histology ,Leydig cell tumour ,Pathology and Forensic Medicine ,Correlation ,03 medical and health sciences ,0302 clinical medicine ,Testicular Neoplasms ,FISH ,Testis ,medicine ,Humans ,Nuclear atypia ,In Situ Hybridization, Fluorescence ,Aged ,Neoplasm Staging ,Leydig cell ,biology ,business.industry ,Cyclin-Dependent Kinase 4 ,High-Throughput Nucleotide Sequencing ,Proto-Oncogene Proteins c-mdm2 ,General Medicine ,Middle Aged ,Leydig cell tumor ,medicine.disease ,030104 developmental biology ,medicine.anatomical_structure ,Coagulative necrosis ,Leydig Cell Tumor ,NGS ,030220 oncology & carcinogenesis ,immunohistochemistry ,biology.protein ,Immunohistochemistry ,Mdm2 ,business - Abstract
Aims: To investigate the morphological and molecular characteristics of Leydig cell tumours (LCTs) of the testis for the identification of cases that may metastasise. Methods and results: Six parameters for a predictive model of the metastatic risk were evaluated in 37 benign and 14 malignant LCTs of the testis [LCT Scaled Score (LeSS)]. The tumour size (benign LCTs, mean 13.3mm; malignant LCTs, mean 44mm) (P 
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- 2020
7. The Role of [18F]Fluciclovine PET/CT in the Characterization of High-Risk Primary Prostate Cancer: Comparison with [11C]Choline PET/CT and Histopathological Analysis
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Lorenzo Maltoni, Irene Bossert, Lucia Zanoni, Cristina Nanni, Antonietta D'Errico, Antonella Matti, Cristina Fonti, Michelangelo Fiorentino, Cristian Vincenzo Pultrone, Francesca Giunchi, Eugenio Brunocilla, Filippo Lodi, Lorenzo Bianchi, Stefano Fanti, Riccardo Schiavina, Riccardo Mei, Zanoni L., Mei R., Bianchi L., Giunchi F., Maltoni L., Pultrone C.V., Nanni C., Bossert I., Matti A., Schiavina R., Fiorentino M., Fonti C., Lodi F., D'errico A., Brunocilla E., Fanti S., and Zanoni L, Mei R, Bianchi L, Giunchi F, Maltoni L, Pultrone CV, Nanni C, Bossert I, Matti A, Schiavina R, Fiorentino M, Fonti C, Lodi F, D'Errico A, Brunocilla E, Fanti S.
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Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,[11C]Choline ,high risk ,Malignancy ,lcsh:RC254-282 ,Article ,030218 nuclear medicine & medical imaging ,Lesion ,03 medical and health sciences ,Prostate cancer ,primary prostate cancer ,0302 clinical medicine ,staging ,Prostate ,medicine.artery ,medicine ,PET-CT ,[18F]Fluciclovine PET/CT ,business.industry ,Prostatectomy ,Abdominal aorta ,C]Choline ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,F]Fluciclovine PET/CT ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Histopathology ,medicine.symptom ,Nuclear medicine ,business ,[ - Abstract
The primary aim of the study was to evaluate the role of [18F]Fluciclovine PET/CT in the characterization of intra-prostatic lesions in high-risk primary PCa patients eligible for radical prostatectomy, in comparison with conventional [11C]Choline PET/CT and validated by prostatectomy pathologic examination. Secondary aims were to determine the performance of PET semi-quantitative parameters (SUVmax, target-to-background ratios [TBRs], using abdominal aorta, bone marrow and liver as backgrounds) for malignant lesion detection (and best cut-off values) and to search predictive factors of malignancy. A six sextants prostate template was created and used by PET readers and pathologists for data comparison and validation. PET visual and semi-quantitative analyses were performed: for instance, patient-based, blinded to histopathology, subsequently lesion-based, un-blinded, according to the pathology reference template. Among 19 patients included (mean age 63 years, 89% high and 11% very-high-risk, mean PSA 9.15 ng/mL), 45 malignant and 31 benign lesions were found and 19 healthy areas were selected (n = 95). For both tracers, the location of the “blinded” prostate SUVmax matched with the lobe of the lesion with the highest pGS in 17/19 cases (89%). There was direct correlation between [18F]Fluciclovine uptake values and pISUP. Overall, lesion-based (n = 95), the performance of PET semiquantitative parameters, with either [18F]Fluciclovine or [11C]Choline, in detecting either malignant/ISUP2-5/ISUP4-5 PCa lesions, was moderate and similar (AUCs ≥ 0.70) but still inadequate (AUCs ≤ 0.81) as a standalone staging procedure. A [18F]Fluciclovine TBR-L3 ≥ 1.5 would depict a clinical significant lesion with a sensitivity and specificity of 85% and 68% respectively, whereas a SUVmax cut-off value of 4 would be able to identify a ISUP 4-5 lesion in all cases (sensitivity 100%), although with low specificity (52%). TBRs (especially with threshold significantly higher than aorta and slightly higher than bone marrow), may be complementary to implement malignancy targeting.
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- 2021
8. Frozen Section Analysis of Unusual Small Testicular Tumor Masses: Report of 3 Cases
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Francesca Giunchi, Maurizio Colecchia, Riccardo Schiavina, Francesco Vasuri, Michelangelo Fiorentino, Marco Garofalo, Giorgio Gentile, Giunchi, F, Vasuri, F, Colecchia, M, Gentile, G, Garofalo, M, Schiavina, R, Fiorentino, M., and Fiorentino, M
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Adult ,Male ,Cancer Research ,medicine.medical_specialty ,030232 urology & nephrology ,Testicular tumor ,Malignancy ,03 medical and health sciences ,0302 clinical medicine ,Testicular Neoplasms ,Testis ,medicine ,Frozen Sections ,Humans ,Orchiectomy ,Frozen section procedure ,business.industry ,Ultrasound ,Testicular mass ,Histology ,General Medicine ,Middle Aged ,medicine.disease ,Immunohistochemistry ,Treatment Outcome ,Oncology ,030220 oncology & carcinogenesis ,Radiology ,business ,Frozen section analysis of unusual small testicular tumor masses: report of 3 cases - Abstract
PURPOSE: Nonpalpable tumors of the testis are generally incidental findings on ultrasound examination. Most of these tumors are benign but some turn out to be germinal tumors at histology. Therefore, intraoperative histopathologic analysis of nonpalpable testicular lesions is pivotal for guiding a testis-sparing surgical approach. METHODS: We report clinical and pathologic characteristics of 3 small nodules of the testis with challenging histologic features at intraoperative frozen section examination and peculiar histology. One was a known testicular mass, undertreated for 5 years, whose enlargement worried the patient, while the other 2 were incidental findings during clinical testicular examination for non-neoplastic diseases. CONCLUSIONS: The 3 cases reported are characterized by small size, which limited the accuracy of preoperative ultrasound diagnosis. Intraoperative frozen section examination was able to rule out a diagnosis of germ cell malignancy in all cases, but diagnosis was conclusive only at histology. Knowledge of unexpected rare testicular lesions is of great relevance at the time of frozen section examination in view of conservative surgical strategy.v Nonpalpable tumors of the testis are generally incidental findings on ultrasound examination. Most of these tumors are benign but some turn out to be germinal tumors at histology. Therefore, intraoperative histopathologic analysis of nonpalpable testicular lesions is pivotal for guiding a testis-sparing surgical approach. METHODS: We report clinical and pathologic characteristics of 3 small nodules of the testis with challenging histologic features at intraoperative frozen section examination and peculiar histology. One was a known testicular mass, undertreated for 5 years, whose enlargement worried the patient, while the other 2 were incidental findings during clinical testicular examination for non-neoplastic diseases. CONCLUSIONS: The 3 cases reported are characterized by small size, which limited the accuracy of preoperative ultrasound diagnosis. Intraoperative frozen section examination was able to rule out a diagnosis of germ cell malignancy in all cases, but diagnosis was conclusive only at histology. Knowledge of unexpected rare testicular lesions is of great relevance at the time of frozen section examination in view of conservative surgical strategy.
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- 2016
9. The Use of Augmented Reality to Guide the Intraoperative Frozen Section During Robot-assisted Radical Prostatectomy
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Carlo Casablanca, Francesco Chessa, Michelangelo Fiorentino, Stefano Diciotti, Daniele Romagnoli, Simone Lodi, Riccardo Schiavina, A. Mottaran, Alexandre Mottrie, Stefano Puliatti, Caterina Gaudiano, Lorenzo Bianchi, Angelo Porreca, Matteo Droghetti, E. Molinaroli, Andrea Angiolini, Pietro Piazza, Emanuela Marcelli, Francesca Giunchi, Rita Golfieri, Laura Cercenelli, Barbara Bortolani, Bianchi L., Chessa F., Angiolini A., Cercenelli L., Lodi S., Bortolani B., Molinaroli E., Casablanca C., Droghetti M., Gaudiano C., Mottaran A., Porreca A., Golfieri R., Romagnoli D., Giunchi F., Fiorentino M., Piazza P., Puliatti S., Diciotti S., Marcelli E., Mottrie A., and Schiavina R.
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medicine.medical_specialty ,Surgical margin ,Intraoperative frozen section ,Prostate cancer ,Index Lesion ,Prostatectomy ,business.industry ,Urology ,medicine.medical_treatment ,Augmented reality ,Three-dimensional reconstruction ,medicine.disease ,Dissection ,Propensity score matching ,Robot-assisted radical prostatectomy ,medicine ,Radiology ,Positive Surgical Margin ,Stage (cooking) ,business - Abstract
Background Multiparametric magnetic resonance imaging (mpMRI) can guide the surgical plan during robot-assisted radical prostatectomy (RARP), and intraoperative frozen section (IFS) can facilitate real-time surgical margin assessment. Objective To assess a novel technique of IFS targeted to the index lesion by using augmented reality three-dimensional (AR-3D) models in patients scheduled for nerve-sparing RARP (NS-RARP). Design, setting, and participants Between March 2019 and July 2019, 20 consecutive prostate cancer patients underwent NS-RARP with IFS directed to the index lesion with the help of AR-3D models (study group). Control group consists of 20 patients matched with 1:1 propensity score for age, clinical stage, Prostate Imaging Reporting and Data System score v2, International Society of Urological Pathology grade, prostate volume, NS approach, and prostate-specific antigen in which RARP was performed by cognitive assessment of mpMRI. Surgical procedure In the study group, an AR-3D model was superimposed to the surgical field to guide the surgical dissection. Tissue sampling for IFS was taken in the area in which the index lesion was projected by AR-3D guidance. Measurements Chi-square test, Student t test, and Mann-Whitney U test were used to compare, respectively, proportions, means, and medians between the two groups. Results and limitations Patients in the AR-3D group had comparable preoperative characteristics and those undergoing the NS approach were referred to as the control group (all p ≥ 0.06). Overall, positive surgical margin (PSM) rates were comparable between the two groups; PSMs at the level of the index lesion were significantly lower in patients referred to AR-3D guided IFS to the index lesion (5%) than those in the control group (20%; p = 0.01). Conclusions The novel technique of AR-3D guidance for IFS analysis may allow for reducing PSMs at the level of the index lesion. Patient summary Augmented reality three-dimensional guidance for intraoperative frozen section analysis during robot-assisted radical prostatectomy facilitates the real-time assessment of surgical margins and may reduce positive surgical margins at the index lesion.
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- 2021
10. PD-L1 Expression in Circulating Tumor Cells as a Promising Prognostic Biomarker in Advanced Non–small-cell Lung Cancer Treated with Immune Checkpoint Inhibitors
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Michelangelo Fiorentino, Filippo Gustavo Dall'Olio, Rita Golfieri, Laura Marcolin, Benedetta Fragomeno, Giada Grilli, Giulia Manferrari, Andrea Ardizzoni, Francesca Sperandi, Mario Terracciano, Nastassja Tober, Francesco Gelsomino, Nicole Conci, Francesca Fontana, Andrea De Giglio, Stefano Brocchi, Dall'Olio F.G., Gelsomino F., Conci N., Marcolin L., De Giglio A., Grilli G., Sperandi F., Fontana F., Terracciano M., Fragomeno B., Tober N., Manferrari G., Brocchi S., Golfieri R., Fiorentino M., and Ardizzoni A.
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Male ,0301 basic medicine ,Pulmonary and Respiratory Medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Immune Checkpoint ,NSCLC ,Predictive ,B7-H1 Antigen ,03 medical and health sciences ,0302 clinical medicine ,Circulating tumor cell ,Advanced cancer ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,PD-1 ,Biomarkers, Tumor ,Clinical endpoint ,medicine ,Humans ,Prospective Studies ,Lung cancer ,Immune Checkpoint Inhibitors ,Aged ,Aged, 80 and over ,biology ,business.industry ,Hazard ratio ,Cancer ,Middle Aged ,medicine.disease ,CTC ,Immune checkpoint ,030104 developmental biology ,030220 oncology & carcinogenesis ,biology.protein ,Biomarker (medicine) ,Female ,Antibody ,business - Abstract
Background: Circulating tumor cells (CTCs) are a promising source of biological information in cancer. Data correlating PD-L1 expression in CTCs with patients’ response to immune checkpoint inhibitors (ICIs) in non–small-cell lung cancer (NSCLC) are still lacking. Methods: This is a prospective single-center cohort study enrolling patients with advanced NSCLC. CTCs were identified and counted with the CellSearch system. PD-L1 expression on CTCs was assessed with phycoerythrin-conjugated anti-human PD-L1 antibody, clone MIH3 (BioLegend, USA). Primary endpoint was the correlation between the CTCs PD-L1 expression and overall survival (OS). Among secondary objectives, we evaluated the correlation between PD-L1 expression on CTCs and matched tumor tissue and the correlation of CTC number and baseline tumor size (BTS). Results: Thirty-nine patients treated with anti-PD-1/PD-L1 agents as second- or third-line therapy were enrolled. Patients were divided into 3 groups: no CTC detectable (CTCnull, n = 15), PD-L1 positive CTC (CTCpos, n = 13), and PD-L1 negative CTC (CTCneg, n = 11). Median OS in patients with CTCneg was 2.2 months, 95% confidence interval (CI), 0.8-3.6 (reference) versus 3.7 months, 95% CI, 0.1-7.5 (hazard ratio [HR] 0.33; 95% CI, 0.13-0.83; P = .019) in patients with CTCpos versus 16.0 months, 95% CI, 2.2-29.8 (HR 0.17; 95% CI, 0.06-0.45; P< .001) in patients with CTCnull. No correlation was found between PD-L1 expression on CTCs and on tumor tissue. CTC number was correlated with BTS. Conclusion: PD-L1 expression on CTCs is a promising biomarker in patients with NSCLC treated with ICIs. Further validation as predictive biomarker is needed.
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- 2021
11. Platinum-based adjuvant chemotherapy for upper tract urothelial carcinoma: a change of paradigm? A meta-analysis of aggregate data
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Michelangelo Fiorentino, Angela Dalia Ricci, Riccardo Schiavina, Francesco Massari, Alessandro Rizzo, Veronica Mollica, Andrea Ardizzoni, Eugenio Brunocilla, Ricci A.D., Rizzo A., Mollica V., Schiavina R., Fiorentino M., Brunocilla E., Ardizzoni A., and Massari F.
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Oncology ,Urologic Neoplasms ,Cancer Research ,medicine.medical_specialty ,urothelial ,Adjuvant chemotherapy ,Locally advanced ,MEDLINE ,Platinum Compounds ,Kaplan-Meier Estimate ,Cochrane Library ,chemotherapy ,adjuvant ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Neoplasm Invasiveness ,Pharmacology (medical) ,Distributed File System ,Urothelial carcinoma ,Pharmacology ,Carcinoma, Transitional Cell ,business.industry ,Survival Analysis ,upper tract ,Upper tract ,Chemotherapy, Adjuvant ,Meta-analysis ,Neoplasm Recurrence, Local ,business ,platinum-based - Abstract
Aim We performed a systematic review and meta-analysis to evaluate the role of platinum-based adjuvant chemotherapy (AC) in upper tract urothelial carcinoma. Materials methods Eligible studies were identified using Pubmed/Medline, Cochrane library, Embase and meeting abstracts. Outcomes of interest included: overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS). Results Platinum-based AC was associated with improved DFS, while the benefit in OS and CSS was not statistically significant compared to observation. Conversely, platinum-based AC showed a modest OS benefit in an analysis combing multivariable HRs with estimated HRs from Kaplan-Meier curves. Conclusion Our results suggest that platinum-based AC is associated with improved DFS and a modest OS benefit in patients with locally advanced urothelial carcinomas.
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- 2021
12. Combination therapy in advanced urothelial cancer: the role of PARP, HER-2 and mTOR inhibitors
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Veronica Mollica, Antonio Lopez-Beltran, Francesco Massari, Alessia Cimadamore, Ilaria Maggio, Michelangelo Fiorentino, Eugenio Brunocilla, Liang Cheng, Francesca Giunchi, Riccardo Schiavina, Alessandro Rizzo, Rodolfo Montironi, Mollica V., Maggio I., Lopez-Beltran A., Montironi R., Cimadamore A., Cheng L., Rizzo A., Giunchi F., Schiavina R., Fiorentino M., Brunocilla E., and Massari F.
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0301 basic medicine ,Metastatic Urothelial Carcinoma ,Combination therapy ,Receptor, ErbB-2 ,Immune checkpoint inhibitors ,Poly ADP ribose polymerase ,Disease ,Poly(ADP-ribose) Polymerase Inhibitors ,DDR ,PI3K ,03 medical and health sciences ,0302 clinical medicine ,Drug Development ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,DNA damage repair ,Urothelial cancer ,Medicine ,Pharmacology (medical) ,PARP inhibitors ,Immune Checkpoint Inhibitors ,urothelial carcinoma ,PI3K/AKT/mTOR pathway ,Neoplasm Staging ,Carcinoma, Transitional Cell ,business.industry ,TOR Serine-Threonine Kinases ,HER-2 ,mTOR ,Discovery and development of mTOR inhibitors ,PARP inhibitor ,030104 developmental biology ,Urinary Bladder Neoplasms ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,business - Abstract
Introduction: Despite significant advances in the treatment of metastatic urothelial carcinoma, including the advent of immune checkpoint inhibitors, this disease is still challenging to treat and associated poor outcomes remain. Genomic characterization of advanced-stage urothelial carcinoma is widening the field of potential treatments due to the identification of novel biologic drivers. Areas covered: In this review, we explore the role of PARP, HER-2, and mTOR inhibitors in the therapeutic scenario of advanced urothelial carcinoma, as these pathways are frequently altered in urothelial carcinoma. We report ongoing clinical trials involving these agents, either in monotherapy or in combination with other compounds, highlighting the dynamic scenario of metastatic urothelial carcinoma treatment. Expert opinion: Several challenges need to be faced in the development of new potential therapeutic strategies, such as inter/intratumoral heterogeneity and the lack of validated biomarkers.
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- 2020
13. Percutaneous Pulmonary Artery Venting via Jugular Vein While on Peripheral Extracorporeal Life Support
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Antonio Loforte, Cinzia Marrozzini, Erika Dal Checco, Davide Pacini, Giuseppe Marinelli, Sofia Martin Suarez, Gregorio Gliozzi, Valeria Lo Coco, Massimo Baiocchi, Mariafrancesca Fiorentino, Mauro Biffi, and Loforte A, Baiocchi M, Dal Checco E, Gliozzi G, Fiorentino M, Lo Coco V, Martin Suarez S, Marrozzini C, Biffi M, Marinelli G, Pacini D.
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Adult ,Male ,medicine.medical_specialty ,Percutaneous ,medicine.medical_treatment ,Shock, Cardiogenic ,Biomedical Engineering ,Biophysics ,Heart failure ,Bioengineering ,Pulmonary Artery ,030204 cardiovascular system & hematology ,Extracorporeal ,Biomaterials ,03 medical and health sciences ,Extracorporeal Membrane Oxygenation ,0302 clinical medicine ,Mechanical circulatory support ,Internal medicine ,medicine.artery ,medicine ,Extracorporeal membrane oxygenation ,Humans ,Myocardial infarction ,Aged ,Heart transplantation ,business.industry ,Cardiogenic shock ,General Medicine ,Middle Aged ,medicine.disease ,surgical procedures, operative ,030228 respiratory system ,Pulmonary artery ,Cardiology ,Female ,Jugular Veins ,Left ventricular venting ,business - Abstract
Peripheral extracorporeal membrane oxygenation (ECMO) setting remains a valid option to treat cardiogenic shock (CS). We investigated a percutaneous approach to unload the left ventricle (LV) while on veno-arterial (v-a) peripheral ECMO support. Between 2017 and 2018, eight patients (three females, mean age: 49.6 years old, and five males, mean age: 58 years old, respectively) suffered refractory CS due to acute myocardial infarction (n = 4), acute myocarditis (n = 2), acute decompensation on chronic heart failure (n = 1), and primary graft failure after heart transplantation (Htx) (n = 1), respectively. After a multidisciplinary CS team discussion, it was decided to proceed with peripheral v-a ECMO placement and percutaneous LV venting via right internal jugular vein access to drain the pulmonary artery (PA), in the hybrid operating room. In a single postcardiotomy case, the PA trunk was vented centrally. Mean ECMO support time was 8.5 days. Seven (87.5%) patients were successfully weaned from ECMO and one (12.5%) successfully bridged to Htx. All patients were successfully discharged after treatment except for a single case who died due to sepsis. In case of not recommended usage of LV apical venting, the adoption of v-a peripheral ECMO support associated with percutaneous PA drainage enables the rapid onset of extracorporeal life support with an effective biventricular unloading.
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- 2020
14. New Hormonal Agents in Patients With Nonmetastatic Castration-Resistant Prostate Cancer: Meta-Analysis of Efficacy and Safety Outcomes
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Eugenio Brunocilla, Riccardo Schiavina, Michelangelo Fiorentino, Andrea Ardizzoni, Lidia Gatto, Vincenzo Di Nunno, Matteo Santoni, Francesco Massari, Veronica Mollica, and Di Nunno V, Mollica V, Santoni M, Gatto L, Schiavina R, Fiorentino M, Brunocilla E, Ardizzoni A, Massari F
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Male ,Oncology ,medicine.medical_specialty ,Antineoplastic Agents, Hormonal ,Urology ,Population ,030232 urology & nephrology ,Darolutamide ,Metastases-free survival ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Internal medicine ,Apalutamide ,Enzalutamide ,Odds Ratio ,medicine ,Humans ,Adverse effect ,education ,Proportional Hazards Models ,Randomized Controlled Trials as Topic ,education.field_of_study ,business.industry ,Hazard ratio ,Absolute risk reduction ,medicine.disease ,Survival Analysis ,Clinical trial ,Prostatic Neoplasms, Castration-Resistant ,Treatment Outcome ,030220 oncology & carcinogenesis ,Meta-analysis ,Relative risk ,business - Abstract
In the past few years several hormonal agents have been tested in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) leading to an impressive improvement in terms of metastases-free survival (MFS). We performed a meta-analysis aimed to: (1) estimate the pooled effect of new hormonal compounds in terms of MFS, overall survival (OS) in overall and specific subpopulations; and (2) estimate the effect of high-grade toxicities of these drugs. We identified 881 studies published between January 1, 2010 and February 16, 2018 on PubMed/Medline, Cochrane Library, and Scopus. Three randomized placebo controlled clinical trials were selected (PROSPER, SPARTAN, and ARAMIS). Because of the absence of individual data, all of the analyses performed were made on aggregated data provided in selected studies. We used the inverse variance technique for the meta-analysis of the hazard ratios collected for MFS and OS analysis. Fixed and randomized models were used. Relative risk and 95% confidence intervals and risk difference were estimated considering the number of Grade 3 adverse events in treatment and control arms. Administration of new hormonal compounds in nmCRPC patients led to a significant benefit in MFS in the overall population and in all subgroups analyzed. These agents might also improve OS but longer follow-up is needed to confirm this hypothesis. Indeed results of OS analysis should be carefully evaluated because none of the studies selected provided mature OS data. Administration of these agents resulted in a significant increased risk of treatment-related death, high cardiovascular toxicity, hypertension, fractures, and falls. Administration of new hormonal compounds prolongs the time of metastases occurrence and might prolong also survival in patients with nmCRPC. Treatment-related toxicity is an important issue because these agents increase the risk of death, cardiovascular toxicity, hypertension, fractures, and risk of falls.
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- 2019
15. Giant (pseudo) vascular spiradenoma: a case report of an extremely rare entity with the immuno-histological demonstration of the coexistence of vascular and pseudo-vascular components
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Francesca Ambrosi, Michelangelo Fiorentino, Costantino Ricci, Emi Dika, Barbara Corti, Martina Lambertini, Stefano Chillotti, Ricci C., Ambrosi F., Dika E., Lambertini M., Chillotti S., Fiorentino M., and Corti B.
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Pathology ,medicine.medical_specialty ,Adenoma, Sweat Gland ,business.industry ,Hematopoietic System ,Acrospiroma ,Rare entity ,Dermatology ,medicine.disease ,Sweat Gland Neoplasms ,Infectious Diseases ,medicine ,Humans ,Spiradenoma ,business ,Human - Published
- 2021
16. The impact of cancer on the risk of death with a functioning graft of Italian kidney transplant recipients
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Franco Citterio, Pierluca Piselli, Ghil Busnach, Claudia Cimaglia, Andrea Ambrosini, Luigi Biancone, Martina Taborelli, Diego Serraino, Maria Rosaria Campise, Giuseppe Tisone, Lucrezia Furian, Paola Todeschini, Nicola Bossini, Francesco Pisani, Maurizio Iaria, Massimiliano Veroux, Margherita Mangino, Flavia Caputo, Vincenzo Cantaluppi, Davide Argiolas, Marco Fiorentino, Taborelli M., Serraino D., Cimaglia C., Furian L., Biancone L., Busnach G., Todeschini P., Bossini N., Iaria M., Campise M.R., Veroux M., Citterio F., Ambrosini A., Cantaluppi V., Mangino M., Pisani F., Tisone G., Fiorentino M., Argiolas D., Caputo F., and Piselli P.
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Nephrology ,Graft Rejection ,medicine.medical_specialty ,nephrology ,Malignancy ,Cohort Studies ,Risk Factors ,Internal medicine ,Neoplasms ,Epidemiology ,medicine ,Immunology and Allergy ,cancer ,Humans ,Pharmacology (medical) ,Index case ,Kidney transplantation ,science ,Transplantation ,business.industry ,Hazard ratio ,Graft Survival ,Cancer ,medicine.disease ,Kidney Transplantation ,Transplant Recipients ,Settore MED/18 ,neoplasia ,translational research ,Cohort ,Kidney Failure, Chronic ,epidemiology ,business ,kidney transplantation ,malignancy - Abstract
This study assessed the impact of cancer on the risk of death with a functioning graft of kidney transplant (KT) recipients, as compared to corresponding recipients without cancer. A matched cohort study was conducted using data from a cohort of 13245 individuals who had undergone KT in 17 Italian centers (1997–2017). Cases were defined as subjects diagnosed with any cancer after KT. For each case, two controls matched by gender, age, and year at KT were randomly selected from cohort members who were cancer-free at the time of diagnosis of the index case. Overall, 292 (20.5%) deaths with a functioning graft were recorded among 1425 cases and 238 (8.4%) among 2850 controls. KT recipients with cancer had a greater risk of death with a functioning graft (hazard ratio, HR=3.31) than their respective controls. This pattern was consistent over a broad range of cancer types, including non-Hodgkin lymphoma (HR=33.09), lung (HR=20.51), breast (HR=8.80), colon-rectum (HR=3.51), and kidney (HR=2.38). The survival gap was observed throughout the entire follow-up period, though the effect was more marked within 1year from cancer diagnosis. These results call for close posttransplant surveillance to detect cancers at earlier stages when treatments are more effective in improving survival.
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- 2021
17. Inferior Cancer Survival for Men with Localized High-grade Prostate Cancer but Low Prostate-specific Antigen
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Michelangelo Fiorentino, Thomas Hermanns, Amparo G. Gonzalez-Feliciano, Mark A. Preston, Travis Gerke, Brandon A. Mahal, Konrad H. Stopsack, Kathryn L. Penney, Christian D. Fankhauser, Massimo Loda, Noel W. Clarke, Lorelei A. Mucci, Fankhauser C.D., Penney K.L., Gonzalez-Feliciano A.G., Clarke N.W., Hermanns T., Stopsack K.H., Fiorentino M., Loda M., Mahal B., Gerke T.A., Preston M.A., Mucci L.A., and University of Zurich
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Oncology ,medicine.medical_specialty ,business.industry ,Urology ,MEDLINE ,610 Medicine & health ,Cancer survival ,medicine.disease ,Article ,10062 Urological Clinic ,Prostate-specific antigen ,Prostate cancer ,Text mining ,Internal medicine ,Medicine ,business ,Not available, Research letter - Abstract
Not available, Research letter
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- 2020
18. A Meta-Analysis Evaluating Clinical Outcomes of Patients with Renal Cell Carcinoma Harboring Chromosome 9P Loss
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Matteo Brunelli, Michelangelo Fiorentino, Matteo Santoni, Riccardo Schiavina, Francesco Massari, Albino Eccher, Veronica Mollica, Anna Caliò, Guido Martignoni, Lidia Gatto, Michele Milella, Vincenzo Di Nunno, Rodolfo Montironi, Eugenio Brunocilla, and Di Nunno V, Mollica V, Brunelli M, Gatto L, Schiavina R, Fiorentino M, Santoni M, Montironi R, Caliò A, Eccher A, Milella M, Martignoni G, Brunocilla E, Massari F
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Renal oncocytoma ,Population ,03 medical and health sciences ,0302 clinical medicine ,Renal cell carcinoma ,Neoplasms ,Internal medicine ,Genetics ,medicine ,Carcinoma ,Humans ,Genetic Predisposition to Disease ,Renal Cell Carcinoma, Chromosome 9P Loss, Clinical Outcomes ,education ,Carcinoma, Renal Cell ,Genetic Association Studies ,Survival analysis ,Pharmacology ,education.field_of_study ,business.industry ,Hazard ratio ,Renal Cell ,General Medicine ,Prognosis ,medicine.disease ,Survival Analysis ,Kidney Neoplasms ,Confidence interval ,Patient Outcome Assessment ,030104 developmental biology ,Carcinoma, Renal Cell, Neoplasms, Renal oncocytoma ,030220 oncology & carcinogenesis ,Relative risk ,Meta-analysis ,Molecular Medicine ,Chromosome Deletion ,Chromosomes, Human, Pair 9 ,business - Abstract
CONTEXT: 9p loss appears a reliable and promising marker able to differentiate specific categories of patients with renal cell carcinoma associated with a worse prognosis. OBJECTIVE: The aim was to systematically evaluate relative risk of death, cancer-specific survival (CSS) and disease-free survival (DFS) among patients harboring 9p loss. EVIDENCE SYNTHESIS: We found a total of 92 potentially relevant articles focused on the detection of 9p loss in patients with renal cell carcinoma and clinical outcomes of this population. Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines were employed to carry out this work. Fourteen studies resulted to be eligible for this analysis; 11 of these reported data on 5-year overall survival, six on CSS and four on DFS. An increased risk of death has been observed in patients harboring 9p loss (pooled relative risk of 3.965; 95% confidence interval [CI] 2.647-5.940, p
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- 2019
19. BAP1 in solid tumors
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Giovanni Brandi, Giorgio Frega, Lidia Gatto, Nicola Battelli, Francesco Massari, Vincenzo Di Nunno, Rodolfo Montironi, Matteo Santoni, Michelangelo Fiorentino, Di Nunno V., Frega G., Santoni M., Gatto L., Fiorentino M., Montironi R., Battelli N., Brandi G., and Massari F.
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0301 basic medicine ,renal cell carcinoma ,Cancer Research ,DNA damage ,Cell ,Environment ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Neoplasms ,melanoma ,Biomarkers, Tumor ,Animals ,Humans ,Medicine ,BAP1 ,Molecular Targeted Therapy ,Gene ,Thymic carcinoma ,business.industry ,Tumor Suppressor Proteins ,Melanoma ,General Medicine ,Prognosis ,medicine.disease ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,mesothelioma ,030220 oncology & carcinogenesis ,Mutation ,Cancer cell ,Cancer research ,Gene-Environment Interaction ,Disease Susceptibility ,cholangiocarcinoma ,thymic carcinoma ,business ,Ubiquitin Thiolesterase - Abstract
One of the most attractive cancer-related genes under investigation is BAP1. Reasons of this growing interest are related to the wide spectrum of pathways directly or indirectly modulated by this gene and shared by several solid tumors. Programmed cell-death, cell metabolisms, immune cells development, ferroptosis and defects in DNA damage response are only some of the multitude of processes depending on BAP1. Loss of this gene seems to occur in different times of tumor history. Moreover, times of BAP1 loss strongly diverge among primary tumors suggesting the presence of several and different triggering factors. Regardless of when it happens, BAP1 loss usually results in prognosis worsening and in the acquisition of more aggressive clinical features by cancer cells.
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- 2019
20. The Decision-Making Process in Acute Type A Aortic Dissection: When to Replace the Aortic Arch
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Roberto Di Bartolomeo, Giuditta Coppola, Alessandro Leone, Maria francesca Fiorentino, Giacomo Murana, Ciro Amodio, Luca Di Marco, Davide Pacini, Leone A., Di Marco L., Murana G., Coppola G., Fiorentino M., Amodio C., Di Bartolomeo R., and Pacini D.
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Pulmonary and Respiratory Medicine ,Aortic arch ,medicine.medical_specialty ,Elephant trunks ,Clinical Decision-Making ,030204 cardiovascular system & hematology ,Prosthesis Design ,Resection ,Blood Vessel Prosthesis Implantation ,03 medical and health sciences ,Postoperative Complications ,0302 clinical medicine ,Risk Factors ,Aneurysm, Dissecting ,medicine.artery ,medicine ,Humans ,Cerebral perfusion pressure ,Elephant trunk ,Aortic dissection ,Endovascular Procedure ,Aorta ,Aortic Aneurysm, Thoracic ,business.industry ,Risk Factor ,Endovascular Procedures ,Acute dissection ,General Medicine ,Aortic surgery ,medicine.disease ,Blood Vessel Prosthesis ,Surgery ,Aortic Dissection ,Blood Vessel Prosthesi ,Treatment Outcome ,030228 respiratory system ,Acute type ,Acute Disease ,Stents ,Postoperative Complication ,Cardiology and Cardiovascular Medicine ,business ,Human - Abstract
The decision-making process is crucial for the surgery of acute type A aortic dissection (AAAD). Often surgeons have to face different challenges, taking prompt decisions in emergency setting, during the pre- and intraoperative phase. Choosing if operate or not a patients with AAAD as well as the management of the dissected aortic arch can be challenging. Different factors need to be evaluated as: the patients age, the presence of organ malperfusion, the intimal tear location, and last but not least the surgeon personal experience in aortic surgery. During the last decade, different milestone steps have been achieved in aortic surgery as the antegrade perfusion of the aorta through different cannulation sites, open distal repair, antegrade selective cerebral perfusion, and systematic resection of the proximal intimal tear, allowing complex repair for dedicated team as well as simpler repair for not dedicated surgeons. We reviewed different scenarios and techniques used for the aortic arch replacement in patients with AAAD, taking into consideration that the aim of surgery is to save patients life.
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- 2019
21. Case Report: The Complete Remission of a Mixed Germ Cell Tumor With Somatic Type Malignancy of Sarcoma Type With a GCT-Oriented Therapy: Clinical Findings and Genomic Profiling
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Maria A. Pantaleo, Marcella Mandruzzato, Valentina Indio, Milena Urbini, Margherita Nannini, Lidia Gatto, Angela Schipani, Michelangelo Fiorentino, Tania Franceschini, Valentina Ambrosini, Valerio Di Scioscio, Maristella Saponara, Manuela Ianni, Sergio Concetti, Annalisa Altimari, Andrea Ardizzoni, Annalisa Astolfi, Pantaleo M.A., Mandruzzato M., Indio V., Urbini M., Nannini M., Gatto L., Schipani A., Fiorentino M., Franceschini T., Ambrosini V., Di Scioscio V., Saponara M., Ianni M., Concetti S., Altimari A., Ardizzoni A., and Astolfi A.
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Oncology ,Cancer Research ,medicine.medical_specialty ,sarcoma ,Carcinoid tumors ,RNA-sequencing ,030232 urology & nephrology ,Salvage therapy ,Case Report ,Malignancy ,lcsh:RC254-282 ,NO ,Hemangioendothelioma ,03 medical and health sciences ,0302 clinical medicine ,exome sequencing ,germ cell tumor ,PEB ,teratoma with malignant transformation ,Internal medicine ,Medicine ,Teratoma with Malignant Transformation ,business.industry ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Primary tumor ,030220 oncology & carcinogenesis ,Adenocarcinoma ,Sarcoma ,business - Abstract
Somatic malignant transformation in a germ cell tumor (GCT) is the development of non-germ malignancies; much of available literature refers to teratoma with malignant transformation (TMT). There are various transformation histologies such as sarcoma, adenocarcinoma, primitive neuroectodermal tumors, and more rarely carcinoid tumors, hemangioendothelioma, lymphoma, or nephroblastoma. The treatments of these entities include surgery and/or chemotherapy. A standard approach in choosing chemotherapy in TMT cases has not yet been established. Many authors suggest using chemotherapeutic agents based on the transformed histology, while others recommend GCT-oriented therapy combined with surgery as the primary treatment, reserving histology-driven chemotherapies for metastatic relapse. We report the clinical findings and the genomic profile of a mixed GCT case with somatic-type malignancy of sarcoma type. We achieved a complete radiological response with GCT-oriented chemotherapy performed as salvage therapy after sarcoma-histology therapy. In addition, molecular profiles with RNA-sequencing and exome sequencing analyses of the primary tumor and the tumor with somatic-type malignancy of sarcoma type were explored.
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- 2021
22. Antitissue transglutaminase antibodies' normalization after starting a gluten-free diet in a large population of celiac children-a real-life experience
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Francesca Sbravati, Paola Sogno Valin, Sara Pagano, P. Alvisi, A.G. Grondona, Annarita Di Biase, Beatrice Righi, Angela Salerno, Anita Cosentino, Michelangelo Fiorentino, Francesca Ambrosi, Laura Bruni, Jacopo Lenzi, Flavio Labriola, Barbara Battistini, S. Brusa, Sbravati F., Cosentino A., Lenzi J., Fiorentino M., Ambrosi F., Salerno A., Di Biase A., Righi B., Brusa S., Valin P.S., Bruni L., Battistini B., Pagano S., Grondona A.G., Labriola F., and Alvisi P.
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Male ,Pediatrics ,medicine.medical_specialty ,Trend of serology normalization ,Tissue transglutaminase ,Population ,Disease ,Thyroiditis ,Serology ,Diet, Gluten-Free ,Diabetes mellitus ,medicine ,Humans ,Stage (cooking) ,education ,Child ,Autoantibodies ,Retrospective Studies ,education.field_of_study ,Independent predictor ,Transglutaminases ,Hepatology ,biology ,business.industry ,Gastroenterology ,medicine.disease ,Immunoglobulin A ,Celiac Disease ,Treatment Outcome ,biology.protein ,Patient Compliance ,Gluten free ,Female ,business - Abstract
Introduction Few data are available regarding the trend of IgA anti-transglutaminase antibodies (TGA-IgA) in children with celiac disease (CD) on a gluten-free diet (GFD). Our aim is to examine the normalization time of CD serology in a large pediatric population, and its predictors. Material and methods We retrospectively evaluated the normalization time of TGA-IgA and its predictive factors (age, sex, ethnicity, symptoms, associated diabetes/thyroiditis, Marsh stage, TGA-IgA and endomysial antibody levels at diagnosis, diet adherence), in 1024 children diagnosed from 2000 to 2019 in three pediatric Italian centers, on a GFD. Results TGA-IgA remission was reached in 67,3%, 80,7%, 89,8% and 94,9% after 12, 18, 24 and 36 months from starting a GFD, respectively (median time = 9 months). TGA-IgA >10´upper limit of normal at diagnosis (HR = 0.56), age 7–12 years old (HR = 0.83), poor compliance to diet (HR = 0.69), female sex (HR = 0.82), non-Caucasian ethnicity (HR = 0.75), and comorbidities (HR = 0.72) were independent factors significantly associated with longer time to normalization. Conclusions Our population is the largest in the literature, with the majority of patients normalizing CD serology within 24 months from starting a GFD. We suggest a special attention to patients with comorbidities, language barriers or age 7–12 years for a proper management and follow-up.
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- 2021
23. Impact of HER2 assessment by CISH in urothelial carcinoma: A retrospective single-center experience
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Matteo Rosellini, Filippo Gustavo Dall'Olio, Veronica Mollica, Francesco Massari, Tania Franceschini, Eugenio Brunocilla, Francesca Giunchi, Andrea Marchetti, Andrea Ardizzoni, Riccardo Schiavina, Michelangelo Fiorentino, Alessandro Rizzo, Rizzo A., Mollica V., Giunchi F., Dall'Olio F.G., Rosellini M., Marchetti A., Franceschini T., Schiavina R., Brunocilla E., Fiorentino M., Ardizzoni A., and Massari F.
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0301 basic medicine ,Oncology ,Male ,medicine.medical_specialty ,Urologic Neoplasms ,Receptor, ErbB-2 ,Population ,Chromogenic in situ hybridization ,Single Center ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,Predictive Value of Tests ,HER2 ,Statistical significance ,Internal medicine ,Biomarkers, Tumor ,Medicine ,Humans ,ERBB2 ,skin and connective tissue diseases ,education ,CISH ,In Situ Hybridization ,Aged ,Retrospective Studies ,Aged, 80 and over ,education.field_of_study ,Bladder cancer ,business.industry ,Carcinoma ,Gene Amplification ,Retrospective cohort study ,Cell Biology ,Middle Aged ,medicine.disease ,Prognosis ,HER family ,Confidence interval ,030104 developmental biology ,Italy ,030220 oncology & carcinogenesis ,Urothelial carcinoma ,Female ,Urothelium ,business - Abstract
Background In recent years, HER2 amplification has been evaluated as a potential prognostic biomarker and therapeutic target in urothelial carcinoma (UC). In this retrospective study, we aimed at exploring the prognostic role of HER2 amplification in UC, measured by chromogenic in situ hybridization (CISH). Methods We retrospectively evaluated the presence of HER2 amplification by using CISH in 31 UC patients followed at a single institution between 2018 and 2020. The primary objective was to assess the frequency of HER2 amplification and to compare clinical outcomes of HER2-amplified patients with non-amplified UCs. Results HER2 amplification was identified in 4 out of 31 patients (12.9 %). After a median follow-up of 28.1 months (95 % Confidence Intervals [CI] 11.2–45.1), median overall survival (OS) in the whole population was 10.9 months (95 % CI 3.5–22.1). Despite not reaching statistical significance, median OS was shorter in HER2-amplified patients (6.8 months, 95 % CI 3.9–9.7) compared to HER2-negative UCs (15.4 months, 95 % CI 7.5–23.3) (p = 0.45). Conclusions Although limited by the small sample size, the results of our study suggest that HER2 amplifications by CISH could represent a prognostic factor for shorter survival in UC patients.
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- 2021
24. The molecular characteristics of non‐clear cell renal cell carcinoma: What’s the story morning glory?
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Elisa Tassinari, Alessandro Rizzo, Matteo Santoni, Michelangelo Fiorentino, Veronica Mollica, Francesco Massari, Matteo Rosellini, Alessia Cimadamore, Andrea Marchetti, Giacomo Nuvola, Rodolfo Montironi, Marchetti A., Rosellini M., Mollica V., Rizzo A., Tassinari E., Nuvola G., Cimadamore A., Santoni M., Fiorentino M., Montironi R., and Massari F.
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0301 basic medicine ,Oncology ,medicine.medical_treatment ,Cell ,Review ,Papillary RCC ,0302 clinical medicine ,Renal cell carcinoma ,Medicine ,Biology (General) ,Spectroscopy ,Kidney ,Molecular target ,MTOR ,TOR Serine-Threonine Kinases ,Kidney Neoplasm ,General Medicine ,Proto-Oncogene Proteins c-met ,TKI ,Kidney Neoplasms ,Computer Science Applications ,Chemistry ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,MET ,Molecular targets ,Immunotherapy ,Human ,medicine.medical_specialty ,QH301-705.5 ,Protein Kinase Inhibitor ,Catalysis ,Inorganic Chemistry ,03 medical and health sciences ,VEGFR ,Internal medicine ,Chromophobe RCC ,Non‐clear cell renal cell carcinoma ,Pathways ,Biomarkers, Tumor ,Humans ,Physical and Theoretical Chemistry ,Molecular Biology ,QD1-999 ,Protein Kinase Inhibitors ,Carcinoma, Renal Cell ,PI3K/AKT/mTOR pathway ,Chemotherapy ,business.industry ,Organic Chemistry ,medicine.disease ,non-clear cell renal cell carcinoma ,Clinical trial ,Clear cell renal cell carcinoma ,030104 developmental biology ,business ,Pathway - Abstract
Non-clear cell renal cell carcinomas are a miscellaneous group of tumors that include different histological subtypes, each one characterized by peculiarity in terms of genetic alteration, clinical behavior, prognosis, and treatment response. Because of their low incidence and poor enrollment in clinical trials, alongside their heterogeneity, additional efforts are required to better unveil the pathogenetic mechanisms and, consequently, to improve the treatment algorithm. Nowadays, tyrosine kinase inhibitors, mTOR and MET inhibitors, and even cisplatin-based chemotherapy and immunotherapy are potential weapons that are still under evaluation in this setting. Various biomarkers have been evaluated for detecting progression and monitoring renal cell carcinoma, but more studies are necessary to improve this field. In this review, we provide an overview on the molecular characteristics of this group of tumors and the recently published trials, giving an insight into what might become the future therapeutic standard in this complex world of non-clear cell kidney cancers.
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- 2021
25. Donor risk analysis and validation in heart transplants: A single-centre experience
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Gregorio Gliozzi, Antonio Loforte, Sofia Martin Suarez, Mariafrancesca Fiorentino, Davide Pacini, Luca Di Marco, Giacomo Murana, Luciano Potena, Murana G., Fiorentino M., Gliozzi G., Di Marco L., Potena L., Martin Suarez S., Pacini D., and Loforte A.
- Subjects
Adult ,Male ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,medicine.medical_treatment ,Population ,Heart failure ,030204 cardiovascular system & hematology ,030230 surgery ,Transplant ,Risk Assessment ,Cohort Studies ,Donor ,Risk score ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Odds Ratio ,medicine ,Extracorporeal membrane oxygenation ,Humans ,education ,Heart transplantation ,education.field_of_study ,Framingham Risk Score ,business.industry ,Odds ratio ,Middle Aged ,medicine.disease ,Tissue Donors ,Transplantation ,Treatment Outcome ,Italy ,Cohort ,Heart Transplantation ,Female ,Surgery ,Cardiology and Cardiovascular Medicine ,business - Abstract
OBJECTIVES A heart transplant (Htx) remains the gold standard treatment for patients with advanced heart failure. Considering the limited availability of organs, donor risk scores might improve organ selection and allocation. The objective of the study was to compare United Network for Organ Sharing, RADIAL and Eurotransplant scoring models in calculating post-Htx outcomes in an Italian Htx population. METHODS Between January 2000 and December 2017, a total of 461 adult patients underwent Htxs. United Network for Organ Sharing, RADIAL and Eurotransplant scores were calculated. Clinical features and donor risk scores were tested to identify preoperative, intraoperative and postoperative risk variables and eventually validate the scores on our population. RESULTS Early graft failure was detected in 16.1% (74/461). Post-Htx extracorporeal life support was used in 11.1% (51/461). Of the donor-related factors, the use of noradrenaline (P = 0.015) negatively influenced early outcomes, whereas an ischaemic time >240 min (P = 0.037) influenced early graft failure occurrence. The Eurotransplant donor score did not impact outcomes; the RADIAL score significantly influenced both early and late mortality; and the United Network for Organ Sharing score influenced only late mortality. On the multivariable analysis, after adjustment of scores per cohort, noradrenaline infusion was the main independent predictor of in-hospital mortality for the donors, whereas age of the recipient [odds ratio (OR) 1.003, 1.003–1.081; P = 0.032] and use of preoperative extracorporeal membrane oxygenation (OR 3.320, 1.124–9.805; P = 0.030) were the main independent predictors for the recipients. CONCLUSIONS None of the validated donor scoring systems fully behave as reliable predictors of transplant outcomes. According to our ‘local only’ graft selection, specific donor and recipient risk variables should be monitored in order to predict early and late outcomes satisfactorily.
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- 2021
26. Diagnostic performance of MRI/TRUS fusion-guided biopsies vs. systematic prostate biopsies in biopsy-naïve, previous negative biopsy patients and men undergoing active surveillance
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Michelangelo Fiorentino, Marco Borghesi, Marco Garofalo, Stefano Angelini, U. Barbaresi, Riccardo Schiavina, Beniamino Corcioni, Caterina Gaudiano, Carlo Casablanca, Francesco Chessa, Rita Golfieri, A. Ercolino, Valerio Vagnoni, Lorenzo Bianchi, Francesca Giunchi, Alessandro Bertaccini, Matteo Droghetti, Borghesi M., Bianchi L., Barbaresi U., Vagnoni V., Corcioni B., Gaudiano C., Fiorentino M., Giunchi F., Chessa F., Garofalo M., Bertaccini A., Angelini S., Ercolino A., Casablanca C., Droghetti M., Golfieri R., and Schiavina R.
- Subjects
Adult ,Image-Guided Biopsy ,Male ,medicine.medical_specialty ,Urology ,Biopsy ,Population ,Targeted biopsy ,Therapy naive ,Magnetic resonance imaging ,Prostate ,medicine ,80 and over ,Humans ,Prospective Studies ,Multiparametric Magnetic Resonance Imaging ,education ,Watchful Waiting ,Systematic biopsy ,Aged ,Aged, 80 and over ,education.field_of_study ,Index Lesion ,medicine.diagnostic_test ,business.industry ,Reproducibility of Results ,Middle Aged ,Prostate-Specific Antigen ,medicine.anatomical_structure ,Nephrology ,Radiology ,Prostatic neoplasms ,business ,Magnetic Resonance Imaging ,Prostatic Neoplasms - Abstract
BACKGROUND: We aimed to assess the detection rate of overall PCa and csPCa, and the clinical impact of MRI/TRUS fusion targeted biopsy (FUSION-TB) compared to TRUS guided systematic biopsy (SB) in patients with different biopsy settings. METHODS: Three hundred and five patients were submitted to FUSION-TB, divided into three groups: biopsy naïve patients, previous negative biopsies and patients under active surveillance (AS). All patients had a single suspicious index lesion at mpMRI. Within these groups, we enrolled men underwent both to FUSION-TB and SB in the same session. Overall detection rate of PCa and csPCa for the two biopsy methods were compared separately between the three groups of patients. RESULTS: No differences were observed between the three groups concerning clinical and radiological characteristics. We found no differences in terms of overall PCa detection (66% vs. 63.8%, P=0.617) and csPCa detection (56.4% vs. 51.1%; P=0.225) concerning biopsy naïve patients. In patients previously submitted to a negative biopsy, FUSION-TB showed higher detection rate of csPCa compared to SB alone (41,3% vs. 27% respectively, P=0.038). In patients under AS, no differences were observed between FUSION-TB and SB in terms of overall PCa (50% vs. 73.1%) and csPCa (30.8% vs. 26.9%, respectively; P=0.705) detection. CONCLUSIONS: Our results suggest that in men with previously negative biopsy, FUSION-TB showed significantly higher diagnostic performance for clinically significant PCa as compared to SB. Combination of FUSION-TB and SB should be recommended in AS population to offer higher chance of csPCa diagnosis.
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- 2021
27. A narrative review of individualized treatments of genitourinary tumors: Is the future brighter with molecular evaluations?
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Tania Franceschini, Michelangelo Fiorentino, Francesca Giunchi, Giunchi F., Franceschini T., and Fiorentino M.
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Urology ,medicine.medical_treatment ,Targeted therapy ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Internal medicine ,medicine ,Penile cancer ,Testicular cancer ,Molecular pathology ,business.industry ,Genitourinary system ,Precision medicine ,medicine.disease ,030104 developmental biology ,Reproductive Medicine ,Genitourinary tumor ,030220 oncology & carcinogenesis ,Review Article on Update on Molecular Classification and Individualized Treatments of Genitourinary Tumors ,business ,Kidney cancer - Abstract
Few molecular prognostic and predictive biomarkers have been identified so far in genitourinary tumors. We started from a literature search to explore the status of the art of molecular pathology tests as diagnostic, prognostic, predictive biomarkers in genitourinary cancers. Next generation sequencing approaches now provide mind-changing information in the fields of kidney cancer diagnosis, predictive oncology of urothelial cancer, understanding the causes of testicular and penile cancer, and the comprehension of the drivers of prostate cancer progression beyond androgen regulation. The classification of kidney cancer will be based soon on molecular changes. The causes of non-HPV related penile cancer are largely unknown. The emerging high incidence of testicular cancer could be explained only on the basis of molecular changes. The response to novel therapeutic agents in prostatic and urothelial cancer will require thorough molecular tumor characterization. The hereditary risk of patients with early onset prostate cancer and their potential treatment with targeted therapy requires germline and somatic genetic assays. The implementation of effective biomarkers for the response to immune check-point inhibitors in genitourinary cancer is based on the assessment of inflammatory expression profiles and the tumor mutational burden. This review deals with the current tests and provides a tentative foresee of the future molecular biomarkers of genitourinary cancer.
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- 2021
28. The impact of multiparametric MRI features to identify the presence of prevalent cribriform pattern in the peripheral zone tumors
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Michelangelo Fiorentino, Caterina Gaudiano, Rita Golfieri, Eugenio Brunocilla, Riccardo Schiavina, Antonio De Cinque, Francesca Giunchi, Beniamino Corcioni, Lorenzo Bianchi, Gaudiano C., Bianchi L., De Cinque A., Corcioni B., Giunchi F., Schiavina R., Fiorentino M., Brunocilla E., and Golfieri R.
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Male ,Multivariate analysis ,medicine.medical_treatment ,Lesion ,Prostate cancer ,Prostate ,Multiparametric magnetic resonance imaging ,medicine ,Effective diffusion coefficient ,Humans ,Radiology, Nuclear Medicine and imaging ,Aged ,Retrospective Studies ,Prostatectomy ,PI-RADS version 2.1 ,Receiver operating characteristic ,business.industry ,Area under the curve ,Prostatic Neoplasms ,Gleason Pattern ,General Medicine ,Middle Aged ,medicine.disease ,body regions ,medicine.anatomical_structure ,Cribriform pattern ,medicine.symptom ,business ,Nuclear medicine - Abstract
Purpose: To assess the role of the multiparametric Magnetic Resonance Imaging (mpMRI) in predicting the cribriform pattern in both the peripheral and transition zones (PZ and TZ) clinically significant prostate cancers (csPCas). Material and methods: We retrospectively evaluated 150 patients who underwent radical prostatectomy for csPCa and preoperative mpMRI. Patients with negative (n = 25) and positive (n = 125) mpMRI, stratified according to the presence of prevalent cribriform pattern (PCP, ≥ 50%) and non-PCP (< 50%) at specimen, were included. Difference between the two groups were evaluated. Multivariate logistic regression was used to identify predictors of PCP among mpMRI parameters. The receiver operating characteristic (ROC) analysis was performed to evaluate the area under the curve (AUC) of apparent diffusion coefficient (ADC) and ADC ratio in detecting lesions harboring PCP. Results: Considering 135 positive lesions at the mpMRI, 30 (22.2%) and 105 (77.8%) harbored PCP and non-PCP PCa. The PCP lesions had more frequently nodular morphology (83.3% vs 62.9%; p = 0.04) and significantly lower mean ADC value (0.87 ± 0.16 vs 0.95 ± 0.18; p = 0.03) and ADC ratio (0.52 ± 0.09 vs 0.60 ± 0.14; p = 0.003) when compared with non-PCP lesions. At univariate and multivariate analyses, mean ADC and ADC ratio resulted as independent predictors of the presence of the PCP of the PZ tumors(OR: 0.025; p = 0.03 and OR: 0.001; p = 0.004, respectively). At the ROC analysis, the AUC of mean ADC and ADC ratio to predict the presence of PCP in patients with PZ suspicious lesion at the mpMRI were 0.69 (95% CI 0.56–0.81P, p = 0.003) and 0.72 (95% CI 0.62–0.82P, p = 0.001), respectively. Conclusions: The mpMRI may correctly identify PCP tumors of the PZ and the mean ADC value and ADC ratio can predict the presence of the cribriform pattern in the PCa.
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- 2021
29. The role of multiparametric MRI in active surveillance for low-risk prostate cancer: The ROMAS randomized controlled trial
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Michelangelo Fiorentino, Riccardo Schiavina, Marco Borghesi, Pietro Piazza, Eugenio Brunocilla, Rita Golfieri, Francesca Giunchi, Valeria Panebianco, Angelo Porreca, Paolo Verze, Cristian Vincenzo Pultrone, Beniamino Corcioni, M. Guerra, Lorenzo Bianchi, Matteo Droghetti, Federico Mineo Bianchi, Vincenzo Mirone, Caterina Gaudiano, Giacomo Novara, Schiavina, Riccardo, Droghetti, Matteo, Novara, Giacomo, Bianchi, Lorenzo, Gaudiano, Caterina, Panebianco, Valeria, Borghesi, Marco, Piazza, Pietro, Mineo Bianchi, Federico, Guerra, Marco, Corcioni, Beniamino, Fiorentino, Michelangelo, Giunchi, Francesca, Verze, Paolo, Pultrone, Cristian, Golfieri, Rita, Porreca, Angelo, Mirone, Vincenzo, Brunocilla, Eugenio, Schiavina, R., Droghetti, M., Novara, G., Bianchi, L., Gaudiano, C., Panebianco, V., Borghesi, M., Piazza, P., Mineo Bianchi, F., Guerra, M., Corcioni, B., Fiorentino, M., Giunchi, F., Verze, P., Pultrone, C., Golfieri, R., Porreca, A., Mirone, V., and Brunocilla, E.
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Male ,medicine.medical_specialty ,Urology ,Population ,030232 urology & nephrology ,Random biopsy ,Active surveillance ,Risk Assessment ,law.invention ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Randomized controlled trial ,law ,Multiparametric magnetic resonance imaging ,Biopsy ,medicine ,Clinical endpoint ,Humans ,Prospective Studies ,education ,Watchful Waiting ,Multiparametric Magnetic Resonance Imaging ,Fusion biopsy ,Indolent prostate cancer ,Reclassification ,Aged ,education.field_of_study ,medicine.diagnostic_test ,business.industry ,Multiparametric MRI ,Prostatic Neoplasms ,Middle Aged ,medicine.disease ,Oncology ,030220 oncology & carcinogenesis ,Radiology ,business - Abstract
Background: We aim to evaluate the impact of multiparametric magnetic resonance imaging and fusion-target biopsy for early reclassification of patients with low-risk Prostate Cancer in a randomized trial. Materials and methods: Between 2015 and 2018, patients diagnosed with Prostate Cancer after random biopsy fulfilling PRIAS criteria were enrolled and centrally randomized (1:1 ratio) to study group or control group. Patients randomized to study group underwent multiparametric magnetic resonance imaging at 3 months from enrollment: patients with positive findings (PIRADS-v2>2) underwent fusion-target biopsy; patients with negative multiparametric magnetic resonance imaging or confirmed ISUP - Grade Group 1 at fusion-target biopsy were managed according to PRIAS schedule and 12-core random biopsy was performed at 12 months. Patients in control group underwent PRIAS protocol, including a confirmatory 12-core random biopsy at 12 months. Primary endpoint was a reduction of reclassification rate at 12-month random biopsy in study group at least 20% less than controls. Reclassification was defined as biopsy ISUP Grade Group 1 in >2 biopsy cores or disease upgrading. Results: A total of 124 patients were randomized to study group (n = 62) or control group (n = 62). Around 21 of 62 patients (34%) in study group had a positive multiparametric magnetic resonance imaging, and underwent fusion-target biopsy, with 11 (17.7%) reclassifications. Considering the intention-to-treat population, reclassification rate at 12-month random biopsy was 6.5% for study group and 29% for control group, respectively (P < 0.001). Conclusions: The early employment of multiparametric magnetic resonance imaging for active surveillance patients enrolled after random biopsy consents to significantly reduce reclassifications at 12-month random biopsy.
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- 2021
30. Exploring the association between metastatic sites and androgen receptor splice variant 7 (AR-V7) in castration-resistant prostate cancer patients: A meta-analysis of prospective clinical trials
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Matteo Santoni, Nicola Battelli, Alessandro Rizzo, Michelangelo Fiorentino, Matteo Rosellini, Angela Dalia Ricci, Francesco Massari, Andrea Marchetti, Veronica Mollica, Rizzo A., Mollica V., Rosellini M., Marchetti A., Ricci A.D., Fiorentino M., Battelli N., Santoni M., and Massari F.
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0301 basic medicine ,Oncology ,Male ,medicine.medical_specialty ,Cochrane Library ,Disease-Free Survival ,Pathology and Forensic Medicine ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Internal medicine ,Cell Line, Tumor ,medicine ,Humans ,Protein Isoforms ,Prospective Studies ,Neoplasm Metastasis ,Prospective cohort study ,Lymph node ,Androgen receptor splice variant 7 ,business.industry ,Metastatic site ,Protein Isoform ,Cell Biology ,Odds ratio ,medicine.disease ,Confidence interval ,Metastatic castration-resistant prostate cancer ,Clinical trial ,Gene Expression Regulation, Neoplastic ,Neoplasm Metastasi ,Prospective Studie ,Prostatic Neoplasms, Castration-Resistant ,030104 developmental biology ,medicine.anatomical_structure ,Receptors, Androgen ,030220 oncology & carcinogenesis ,Meta-analysis ,business ,AR-V7 ,Human - Abstract
Background The Androgen Receptor Splice Variant 7 (AR-V7) has been associated with poor clinical outcomes in patients with castration-resistant prostate cancer (CRPC). Herein, we performed a meta-analysis aimed at systematically exploring the association between metastatic sites and AR-V7 expression in CRPC patients across prospective clinical trials. Methods We retrieved all the relevant prospective clinical trials through PubMed/Medline, Cochrane library, and EMBASE; additionally, proceedings of the main international oncological meetings were also searched for relevant abstracts. Outcomes of interest included metastatic sites (lymph node metastases, any site metastases, visceral metastases, and bone metastases) in AR-V7 positive and AR-V7 negative CRPC patients. Odds Ratios (ORs) and 95 % confidence intervals (CI) were calculated. Results Overall, 14 eligible prospective studies involving a total of 1944 CRPC patients (AR-V7 positive: 467; AR-V7 negative: 1477) were included in the analysis. According to our results, no differences between AR-V7 positive and AR-V7 negative CRPC patients were observed in terms of lymph node (OR 1.01; 95 % CI 0.49–2.09) and visceral metastases (OR 1.23; 95 % CI 0.89–1.71). Conversely, AR-V7 positive CRPC patients presented higher rate of any site metastases (OR 2.22; 95 % CI 1.58–3.12) and bone metastases (OR 2.03; 95 % CI 1.42–2.9) compared to AR-V7 negative subjects. Conclusions The results of this meta-analysis, the first in literature to be specifically focused on this topic so far, suggest that AR-V7 positivity may be associated with any site metastases and bone metastases; conversely, no association has been highlighted between AR-V7 expression and lymph node or visceral metastases. Although this meta-analysis should be interpreted with caution due to some limitations, our findings confirm that AR-V7 status could designate a unique and peculiar subtype of PC. Further studies aimed at improving and standardizing AR-V7 detection in clinical trials on CRPC patients are warranted.
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- 2021
31. Evaluating the performance of clinical and radiological data in predicting prostate cancer in prostate imaging reporting and data system version 2.1 category 3 lesions of the peripheral and the transition zones
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Lorenzo Bianchi, Arianna Rustici, Beniamino Corcioni, Michelangelo Fiorentino, Francesca Giunchi, Lorenzo Braccischi, Federica Ciccarese, Eugenio Brunocilla, Caterina Gaudiano, Rita Golfieri, Riccardo Schiavina, Gaudiano C., Bianchi L., Corcioni B., Giunchi F., Schiavina R., Ciccarese F., Braccischi L., Rustici A., Fiorentino M., Brunocilla E., and Golfieri R.
- Subjects
Male ,medicine.medical_specialty ,Multivariate analysis ,Urology ,PIRADS version 2.1 ,Logistic regression ,Lesion ,Prostate cancer ,Prostate ,Predictive Value of Tests ,Multiparametric magnetic resonance imaging ,medicine ,Effective diffusion coefficient ,Data Systems ,Humans ,Aged ,Retrospective Studies ,Univariate analysis ,business.industry ,Prostatic Neoplasms ,Odds ratio ,Middle Aged ,medicine.disease ,Data Accuracy ,medicine.anatomical_structure ,Nephrology ,PIRADS 3 lesion ,Radiology ,medicine.symptom ,Neoplasm Grading ,business - Abstract
Purpose: To define the value of clinical and radiological data, using multiparametric magnetic resonance imaging (mpMRI), to predict prostate cancer (PCa) in prostate imaging reporting and data system version 2.1 (PIRADSv2.1) 3 lesions of the peripheral and the transition zones (PZ and TZ). Methods: The mpMRI of patients with PIRADSv2.1 3 lesions who had undergone fusion targeted biopsy was reviewed. Morphological pattern, diffusion parameters and vascularisation were evaluated. The radiological/histopathological data of benign and malignant lesions, between the PZ and TZ were compared. Univariate and multivariate analyses were carried out to identify the clinical and radiological data capable of predicting PCa. Results: One hundred and twenty-three lesions were assessed, 93 (76%) in the PZ and 30 (24%) in the TZ. Of these, 56 (46%) were PCa and 67 (54%) were benign. The majority of the PCas were Grade Group System (GGS) 1 (38%) and GGS 2 (39%); tumours having a GGS ≥ 3 were more frequently in the TZ (p = 0.02). Univariate analysis showed a significant correlation between PCa and prostate volume, prostate-specific antigen (PSA) density, lesion zone and the apparent diffusion coefficient. At multivariate logistic regression PSA density > 0.15ng/ml/ml {Odds ratio [OR] 2.38; p = 0.001} and lesion zone (i.e. TZ OR 7.55) were independent predictors of PCa (all p ≤ 0.04). Conclusion: In solitary PIRADSv2.1 3 lesions, the most important predictive factor was the location zone, with a much greater risk for TZ lesions.
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- 2021
32. New disappearance of complicated atheromatous plaques on rechallenge with PD-1/PD-L1 axis blockade in non-small cell lung cancer patient: follow up of an unexpected event
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Michelangelo Fiorentino, Antonio Poerio, Francesca Sperandi, Barbara Melotti, Mauro Gargiulo, Stefano Brocchi, Claudio Borghi, Francesco Gelsomino, Giuseppe Lamberti, Andrea Ardizzoni, Lamberti G., Gelsomino F., Brocchi S., Poerio A., Melotti B., Sperandi F., Gargiulo M., Borghi C., Fiorentino M., and Ardizzoni A.
- Subjects
0301 basic medicine ,PD-L1 ,Pathology ,medicine.medical_specialty ,Disease Response ,medicine.medical_treatment ,Inflammation ,Case Report ,NSCLC ,lcsh:RC254-282 ,03 medical and health sciences ,0302 clinical medicine ,atherosclerosi ,Atezolizumab ,PD-1 ,medicine ,Lung cancer ,Chemotherapy ,biology ,business.industry ,Immunotherapy ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,immunotherapy ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,biology.protein ,Nivolumab ,medicine.symptom ,atherosclerosis ,business - Abstract
Atherosclerosis is considered an irreversible process, with crucial contribution of inflammation and immune cells. Impact of cancer immunotherapy on a partly immune-driven disease, such as atherosclerosis, is poorly understood, but preclinical models suggest its worsening on programmed death/ligand-1 (PD-1/PD-L1) inhibitors. In a previously reported cohort of 11 patients with non-small cell lung cancer (NSCLC) treated with nivolumab and pre-existing complicated atheromatous plaques, 3 patients had a dramatic radiologic reduction of aortic plaques while on nivolumab; of these 3, 2 died receiving no further treatment. The remaining patient was an 83-year-old woman with history of arterial hypertension and hypothyroidism who was diagnosed with locally advanced squamous NSCLC. At relapse, complicated aortic atheromatous plaques were demonstrated on scans. The patient was then treated with nivolumab obtaining stable disease at radiological assessment, which also demonstrated almost complete vanishing of aortic plaques. After relapse and interval treatment with chemotherapy, she experienced new development of aortic atheromatous plaques. At further relapse she received atezolizumab, which yielded disease response and new reduction in aortic plaques, until nearly complete resolution. The observation of a repeated improvement of atheromatous plaques on treatment with PD-1/PD-L1 inhibitors favors the protective role of T cells on atheromatous plaques that is impaired by PD-L1 expression by plaque-associated macrophages. Validation by independent and prospective observation is needed.
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- 2020
33. Tumor protein expression of the DNA repair gene BRCA1 and lethal prostate cancer
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Lorelei A. Mucci, Andreas Pettersson, Travis Gerke, Stephen P. Finn, Konrad H. Stopsack, Meir J. Stampfer, Massimo Loda, Michelangelo Fiorentino, Ericka M. Ebot, Dipanjan Chowdhury, Philip W. Kantoff, Piotr Zareba, Richard Flavin, Stopsack K.H., Gerke T., Zareba P., Pettersson A., Chowdhury D., Ebot E.M., Flavin R., Finn S., Kantoff P.W., Stampfer M.J., Loda M., Fiorentino M., and Mucci L.A.
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0301 basic medicine ,Oncology ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,DNA Repair ,Aneuploidy ,Neoplasms, Bone Tissue ,Disease ,Metastasis ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Internal medicine ,Biomarkers, Tumor ,Medicine ,Humans ,Neoplasm Metastasis ,Prospective cohort study ,Cancer Biomarkers and Molecular Epidemiology ,Aged ,Tissue microarray ,business.industry ,BRCA1 Protein ,Hazard ratio ,Prostatic Neoplasms ,General Medicine ,Middle Aged ,medicine.disease ,Neoplasm Proteins ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,immunohistochemistry aneuploidy brca1 protein brca1 gene ki-67 antigen neoplasm metastasis diagnosis neoplasms metastatic prostate cancer prostate cancer gleason grading system for prostatic cancer dna repair gene ,030220 oncology & carcinogenesis ,Mutation ,Disease Progression ,Immunohistochemistry ,Neoplasm Grading ,business ,Follow-Up Studies - Abstract
DNA repair genes are commonly altered in metastatic prostate cancer, but BRCA1 mutations are rare. Preliminary studies suggest that higher tumor expression of the BRCA1 protein may be associated with worse prognosis. We undertook a prospective study among men with prostate cancer in the Health Professionals Follow-up Study and evaluated BRCA1 via immunohistochemical staining on tissue microarrays. BRCA1 was expressed in 60 of 589 tumors. Prevalence of BRCA1 positivity was 43% in the 14 men with metastases at diagnosis compared with 9% in non-metastatic tumors [difference, 33 percentage points; 95% confidence interval (CI), 7–59]. BRCA1-positive tumors had 2.16-fold higher Ki-67 proliferative indices (95% CI, 1.18–3.95), higher tumor aneuploidy as predicted from whole-transcriptome profiling, and higher Gleason scores. Among the 575 patients with non-metastatic disease at diagnosis, we evaluated the association between BRCA1 expression and development of lethal disease (metastasis or cancer-specific death, 69 events) during long-term follow-up (median, 18.3 years). A potential weak association of BRCA1 positivity with lethal disease (hazard ratio, 1.61; 95% CI, 0.82–3.15) was attenuated when adjusting for age, Gleason score and clinical stage (hazard ratio, 1.11; 95% CI, 0.54–2.29). In summary, BRCA1 protein expression is a feature of more proliferative and more aneuploid prostate tumors and is more common in metastatic disease. While not well suited as a prognostic biomarker in primary prostate cancer, BRCA1 protein expression may be most relevant in advanced disease.
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- 2020
34. Real-time Augmented Reality Three-dimensional Guided Robotic Radical Prostatectomy: Preliminary Experience and Evaluation of the Impact on Surgical Planning
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Carlo Casablanca, Eugenio Brunocilla, Daniele Romagnoli, Simone Lodi, Caterina Gaudiano, Emanuela Marcelli, Riccardo Schiavina, Lorenzo Bianchi, Matteo Droghetti, Rita Golfieri, Laura Cercenelli, Stefano Diciotti, Francesca Giunchi, Michelangelo Fiorentino, Barbara Bortolani, Angelo Porreca, Francesco Chessa, Schiavina R., Bianchi L., Lodi S., Cercenelli L., Chessa F., Bortolani B., Gaudiano C., Casablanca C., Droghetti M., Porreca A., Romagnoli D., Golfieri R., Giunchi F., Fiorentino M., Marcelli E., Diciotti S., and Brunocilla E.
- Subjects
Male ,medicine.medical_specialty ,Urology ,medicine.medical_treatment ,030232 urology & nephrology ,Three-dimensional reconstruction ,Surgical planning ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Robotic Surgical Procedures ,medicine ,Humans ,Prostatectomy ,Real-time guided surgery ,Augmented Reality ,Index Lesion ,business.industry ,Prostate ,Prostatic Neoplasms ,Robotics ,medicine.disease ,Dissection ,Index lesion ,030220 oncology & carcinogenesis ,Personal computer ,Robot assisted radical prostatectomy ,Augmented reality ,Radiology ,Positive Surgical Margin ,business - Abstract
Background: Augmented reality (AR) is a novel technology adopted in prostatic surgery. Objective: To evaluate the impact of a 3D model with AR (AR-3D model), to guide nerve sparing (NS) during robot-assisted radical prostatectomy (RARP), on surgical planning. Design, Setting, and Participants: Twenty-six consecutive patients with diagnosis of prostate cancer (PCa) and multiparametric magnetic resonance imaging (mpMRI) results available were scheduled for AR-3D NS RARP. Intervention: Segmentation of mpMRI and creation of 3D virtual models were achieved. To develop AR guidance, the surgical DaVinci video stream was sent to an AR-dedicated personal computer, and the 3D virtual model was superimposed and manipulated in real time on the robotic console. Outcome measurements and statistical analysis: The concordance of localisation of the index lesion between the 3D model and the pathological specimen was evaluated using a prostate map of 32 specific areas. A preliminary surgical plan to determinate the extent of the NS approach was recorded based on mpMRI. The final surgical plan was reassessed during surgery by implementation of the AR-3D model guidance. Results and limitations: The positive surgical margin (PSM) rate was 15.4% in the overall patient population; three patients (11.5%) had PSMs at the level of the index lesion. AR-3D technology changed the NS surgical plan in 38.5% of men on patient-based and in 34.6% of sides on side-based analysis, resulting in overall appropriateness of 94.4%. The 3D model revealed 70%, 100%, and 92% of sensitivity, specificity, and accuracy, respectively, at the 32-area map analysis. Conclusions: AR-3D guided surgery is useful for improving the real-time identification of the index lesion and allows changing of the NS approach in approximately one out of three cases, with overall appropriateness of 94.4%. Patient summary: Augmented reality three-dimensional guided robot-assisted radical prostatectomy allows identification of the index prostate cancer during surgery, to tailor the surgical dissection to the index lesion and to change the extent of nerve-sparing dissection. Augmented reality three-dimensional (3D) guided robotic prostatectomy is feasible to improve the real-time identification of index prostate cancer and to modulate the nerve-sparing approach targeted to the index lesion. Augmented reality 3D models revealed good concordance with the whole-mount pathology.
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- 2020
35. Which patients with clinical localized renal mass would achieve the trifecta after partial nephrectomy? The impact of surgical technique
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Cristian Vincenzo Pultrone, Alessandro Bertaccini, Fabio Manferrari, Riccardo Schiavina, Emanuela Marcelli, Carlo Casablanca, Angelo Porreca, Lorenzo Bianchi, Andrea Angiolini, Marco Borghesi, Pietro Piazza, U. Barbaresi, Matteo Ferro, Michelangelo Fiorentino, Federico Mineo Bianchi, A. Ercolino, Francesco Chessa, Eugenio Brunocilla, and Bianchi L, Schiavina R, Borghesi M, Chessa F, Casablanca C, Angiolini A, Ercolino A, Pultrone CV, Mineo Bianchi F, Barbaresi U, Piazza P, Manferrari F, Bertaccini A, Fiorentino M, Ferro M, Porreca A, Marcelli E, Brunocilla E
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Male ,medicine.medical_specialty ,Kidney neoplasms ,Nephrectomy ,Nomograms ,partial nephrectomy ,Urology ,medicine.medical_treatment ,030232 urology & nephrology ,Logistic regression ,surgical technique ,Cohort Studies ,03 medical and health sciences ,Postoperative Complications ,0302 clinical medicine ,Robotic Surgical Procedures ,Predictive Value of Tests ,trifecta ,medicine ,Humans ,Laparoscopy ,Aged ,medicine.diagnostic_test ,business.industry ,Margins of Excision ,Perioperative ,Middle Aged ,Nomogram ,Surgery ,Treatment Outcome ,Nephrology ,clinical localized renal ma ,030220 oncology & carcinogenesis ,Predictive value of tests ,Female ,Positive Surgical Margin ,business - Abstract
BACKGROUND: To develop a clinical nomogram aimed to predict the achievement of trifecta in patients treated with open, laparoscopic and robotic partial nephrectomy (PN) for localized renal masses ( < cT2). METHODS: We retrospectively evaluated 482 consecutive patients who underwent PN with open (OPN: 243), laparoscopic (LPN: 156) and robotic (RAPN: 83) approach for T1 renal mass at single tertiary center. Trifecta was defined as follows: warm ischemia time (WIT)
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- 2020
36. Mechanically Supported Early Graft Failure After Heart Transplantation
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Gregorio Gliozzi, Antonio Loforte, Giulio Giovanni Cavalli, Mariafrancesca Fiorentino, Davide Pacini, Sofia Martin Suarez, Carlo Mariani, Giacomo Murana, Loforte A., Fiorentino M., Murana G., Gliozzi G., Cavalli G.G., Mariani C., Martin Suarez S., and Pacini D.
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Inotrope ,Adult ,Male ,medicine.medical_specialty ,Graft failure ,medicine.medical_treatment ,Population ,Early Graft Failure ,Heart Transplantation ,Extracorporeal ,Extracorporeal Membrane Oxygenation ,Postoperative Complications ,Risk Factors ,medicine ,Odds Ratio ,Humans ,education ,Retrospective Studies ,Heart transplantation ,Transplantation ,education.field_of_study ,business.industry ,Early Graft Failure, Heart Transplantation ,Odds ratio ,Middle Aged ,Surgery ,Survival Rate ,Life support ,Circulatory system ,Female ,Primary Graft Dysfunction ,business - Abstract
Background: The occurrence of early graft failure (EGF) after heart transplantation (Htx) often requires a mechanical circulatory support (MCS) therapy. The aims of our study were to identify risk factors of mechanically supported severe EGF and evaluate their impact on both early and late outcomes. Methods: Between January 2000 and December 2019, 499 consecutive adult patients underwent Htx at our institution. Severe EGF was defined as the need for extracorporeal life support (ECLS) within 24 hours after surgery. All available recipient and donor variables were retrospectively analyzed. Results: Overall, EGF occurred in 58 (11.6%) patients. Post-Htx peripheral or central ECLS was necessary in 32 (6.4%) cases. Independent predictors of severe EGF were, in the recipient group, preoperative transpulmonary gradient (TPG) >12 mm Hg (odds ratio [OR] 4.1, P =. 013), preoperative inotropic score >10 (OR 7.3, P =. 0001), and pre-Htx ECLS support (OR 5.2, P =. 015), while in the donors, a Eurotransplant donor score ≥17 (OR 8.5, P =. 005). The absence of EGF was related with a better survival at 1 year and 5 years (94% and 85%, respectively) compared with EGF requiring ECLS population (36% and 28% at 1 year and 5 years, respectively; P
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- 2020
37. Pemetrexed Enhances Membrane PD-L1 Expression and Potentiates T Cell-Mediated Cytotoxicity by Anti-PD-L1 Antibody Therapy in Non-Small-Cell Lung Cancer
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Mara Bonelli, Maricla Galetti, Andrea Ardizzoni, Pier Giorgio Petronini, Silvia La Monica, Valeria Barili, Michelangelo Fiorentino, Elisa Giovannetti, Graziana Digiacomo, Alessandra Zecca, Marcello Tiseo, Andrea Cavazzoni, Roberta Alfieri, Daniele Cretella, Claudia Fumarola, Medical oncology laboratory, CCA - Cancer biology and immunology, Amsterdam Gastroenterology Endocrinology Metabolism, Cavazzoni A., Digiacomo G., Alfieri R., La Monica S., Fumarola C., Galetti M., Bonelli M., Cretella D., Barili V., Zecca A., Giovannetti E., Fiorentino M., Tiseo M., Petronini P.G., and Ardizzoni A.
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0301 basic medicine ,PD-L1 ,Cancer Research ,medicine.medical_treatment ,Pembrolizumab ,NSCLC ,chemotherapy ,lcsh:RC254-282 ,Article ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Lung cancer ,Cytotoxicity ,pemetrexed ,IFN-γ ,Chemotherapy ,biology ,business.industry ,Immunotherapy ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,030104 developmental biology ,Pemetrexed ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,T cell mediated cytotoxicity ,business ,medicine.drug - Abstract
Immunotherapy has significantly changed the treatment landscape for advanced non-small-cell lung cancer (NSCLC) with the introduction of drugs targeting programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1). In particular, the addition of the anti-PD-1 antibody pembrolizumab to platinum-pemetrexed chemotherapy resulted in a significantly improved overall survival in patients with non-squamous NSCLC, regardless of PD-L1 expression. In this preclinical study, we investigated whether chemotherapy can modulate PD-L1 expression in non-squamous NSCLC cell lines, thus potentially affecting immunotherapy efficacy. Among different chemotherapeutic agents tested, only pemetrexed increased PD-L1 levels by activating both mTOR/P70S6K and STAT3 pathways. Moreover, it also induced the secretion of cytokines, such as IFN-&gamma, and IL-2, by activated peripheral blood mononuclear cells PBMCs that further stimulated the expression of PD-L1 on tumor cells, as demonstrated in a co-culture system. The anti-PD-1/PD-L1 therapy enhanced T cell-mediated cytotoxicity of NSCLC cells treated with pemetrexed and expressing high levels of PD-L1 in comparison with untreated cells. These data may explain the positive results obtained with pemetrexed-based chemotherapy combined with pembrolizumab in PD-L1-negative NSCLC and can support pemetrexed as one of the preferable chemotherapy partners for immunochemotherapy combination regimens.
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- 2020
38. Immunohistochemical over-expression of HER2 does not always match with gene amplification in invasive bladder cancer
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Francesco Massari, Francesca Giunchi, Riccardo Schiavina, Michelangelo Fiorentino, Elisa Capizzi, Tania Franceschini, Franceschini T., Capizzi E., Massari F., Schiavina R., Fiorentino M., and Giunchi F.
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0301 basic medicine ,Male ,Pathology ,medicine.medical_specialty ,Receptor, ErbB-2 ,In situ hybridization ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,FISH ,HER2 ,Gene duplication ,Biomarkers, Tumor ,Medicine ,Humans ,skin and connective tissue diseases ,CISH ,neoplasms ,Aged ,Aged, 80 and over ,Carcinoma, Transitional Cell ,Bladder cancer ,Tissue microarray ,business.industry ,Cell Biology ,Middle Aged ,medicine.disease ,Immunohistochemistry ,Up-Regulation ,030104 developmental biology ,Urinary Bladder Neoplasms ,030220 oncology & carcinogenesis ,Over expression ,%22">Fish ,Urothelial carcinoma ,Female ,business ,Nucleic Acid Amplification Techniques ,Chrmonogenic in situ hybridization - Abstract
Background HER2 is a potential target of therapy in urothelial cancer (UC). Pathological case stratification according to HER2 gene amplification or HER2 protein overexpression was critical for patients’ selection in previous unsuccessful clinical trial with HER2 targeting agents. Study design We evaluated the HER2 overexpression by immunohistochemistry (IHC) together with the amplification of the HER2 gene with chromogenic(CISH) and fluorescent (FISH) in situ hybridization in a cohort of 61 patients covering the whole spectrum of bladder UC variants, using a tissue microarray (TMA) approach. Results IHC was available in all the 61 cases while ISH in 37 and FISH in 42. At IHC, 2/61 cases (3%) were scored 3+; 2 (3%) scored 2+; 2 (3%) scored 1+; the remaining 55 (91%) scored 0. At CISH analysis 10/37 cases (27%) were amplified, 6 cases with HER2 amplification showed positive HER2 IHC (3+, 2+, 1+). Seven cases with IHC score 0 were amplified at CISH. FISH analysis revealed an amplification in 5/42 cases (12%). The total number of HER2amplified cases was different between chromogenic and fluorescent ISH with 5 cases amplified using FISH compared to 10 with CISH. Conclusions In clinical trials with HER2 targeting agents the candidate patients should be investigated not only by IHC but also by ISH, independently of the IHC results. Since also usual type UC can overexpress HER2 we recommend to extend the patients’ selection to all the histotypes of bladder cancer other than the micropapillary type.
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- 2020
39. Paratesticular Mesenchymal Malignancies: A Single-Center Case Series, Clinical Management, and Review of Literature
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Maria Abbondanza Pantaleo, Francesco Buia, Matteo Ravaioli, Annalisa Astolfi, Michelangelo Fiorentino, Lidia Gatto, Valerio Di Scioscio, Alessandro Franceschelli, Elisa Capizzi, Massimo Del Gaudio, Maria Giulia Pirini, Matteo Cescon, Valentina Indio, Margherita Nannini, Maristella Saponara, Fabio Niro, Maurizio Cervellera, Valeria Tonini, Gatto L., Del Gaudio M., Ravaioli M., Cescon M., Tonini V., Cervellera M., Franceschelli A., Pirini M.G., Di Scioscio V., Buia F., Niro F., Capizzi E., Fiorentino M., Astolfi A., Indio V., Nannini M., Pantaleo M.A., and Saponara M.
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Leiomyosarcoma ,Male ,rare tumors management ,medicine.medical_specialty ,Tomography Scanners, X-Ray Computed ,Population ,030232 urology & nephrology ,paratesticular sarcoma ,Disease ,genitourinary cancer ,Liposarcoma ,lcsh:RC254-282 ,NO ,03 medical and health sciences ,0302 clinical medicine ,Case Studies ,Testicular Neoplasms ,paratesticular sarcoma, genitourinary cancer, soft tissue sarcoma, leiomyosarcoma, liposarcoma, rare tumors management, case report ,Testis ,medicine ,Humans ,case report ,education ,Herniorrhaphy ,Aged ,education.field_of_study ,business.industry ,Genitourinary system ,Soft tissue sarcoma ,Sarcoma ,Middle Aged ,leiomyosarcoma ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Abdominal Pain ,Treatment Outcome ,Complementary and alternative medicine ,Oncology ,liposarcoma ,030220 oncology & carcinogenesis ,Localized disease ,soft tissue sarcoma ,Lymph Node Excision ,Radiology ,business ,Orchiectomy - Abstract
Background: Primary soft tissue sarcomas arising from the male urinary and genital tract are rare tumors, only accounting for 1% to 2% of all malignancies of the genitourinary tract. Clinical management of advanced disease is lacking in standardized recommendations due to the rarity of the disease. To date, complete and extensive surgery represents the only curative and standardized approach for localized disease, while the impact of retroperitoneal lymphadenectomy and adjuvant treatments on clinical outcomes are still unclear. Similarly, a standardized systemic treatment for advanced metastatic disease is still missing. Cases Presentation: Four out of 274 patients have been identified in our sarcoma population. The mean age was 54 years (range = 45-73). The histotypes showed liposarcoma in 2 cases and leiomyosarcoma in the remaining 2 cases. In all 4 cases, the disease was localized at presentation, patients underwent complete surgery, and no adjuvant treatments were done. Three cases presented a recurrence of disease at a mean follow-up of 86 months (range = 60-106 months), more than 7 years. Two cases were treated with a second surgery and chemotherapy and 1 case only with chemotherapy. Discussion and Conclusions: Sharing data about clinical management of paratesticular mesenchymal tumors is a key issue due to the rarity of this tumor’s subtype. In this article, we report the clinical history of 4 patients affected by paratesticular mesenchymal tumor. In particular, main issues of interest are the decision of postoperative treatment and systemic treatment at time of disease recurrence.
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- 2020
40. Comparison of Sequential Testing and Next Generation Sequencing in advanced Lung Adenocarcinoma patients – A single centre experience
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Giacomo Nuvola, Daria Maria Filippini, Michelangelo Fiorentino, Giulio Rossi, Filippo Gustavo Dall'Olio, Andrea Ardizzoni, Giada Grilli, Annalisa Altimari, Elisa Gruppioni, Nicole Conci, Andrea De Giglio, Alessandro Federico, Dall'Olio F.G., Conci N., Rossi G., Fiorentino M., De Giglio A., Grilli G., Altimari A., Gruppioni E., Filippini D.M., Di Federico A., Nuvola G., and Ardizzoni A.
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0301 basic medicine ,Pulmonary and Respiratory Medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Adenocarcinoma of Lung ,Adenocarcinoma ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,Proto-Oncogene Proteins ,Internal medicine ,Carcinoma ,medicine ,ROS1 ,Humans ,Lung cancer ,Retrospective Studies ,Lung ,business.industry ,High-Throughput Nucleotide Sequencing ,Retrospective cohort study ,Protein-Tyrosine Kinases ,medicine.disease ,030104 developmental biology ,medicine.anatomical_structure ,Sequential analysis ,030220 oncology & carcinogenesis ,Mutation ,KRAS ,business ,NSCLC, NGS, molecular characterization - Abstract
Objectives Molecular diagnosis determines therapeutic strategies for patients with non-small-cell lung cancer – adenocarcinoma (NSCLC-A) but depends on resources availability. We compared a sequential single-gene testing algorithm to next generation sequencing in NSCLC-A to assess differences in terms of effectiveness, costs, tissue consumption and time. Materials and methods We analyzed a retrospective cohort of advanced NSCLC-A patients treated at the Sant'Orsola-Malpighi University Hospital. The sequential testing includes a first analysis of EGFR and KRAS status with further molecular testing physician driven. The available NGS panel detects 35 hotspot mutations,19 amplifications and 23 rearrangements. Results We included 1758 patients; 1221 characterized with the sequential algorithm between January 2014 to February 2019 and 537 with Next Generation Sequencing (NGS) until January 2020. The prevalence of EGFR, ALK and KRAS alterations was similar between the stepwise and NGS group (16.5% vs 14.3%, 6.3% vs 6.3% and 36% vs 33.5%, respectively). Differently, ROS-1 rearrangements prevalence was higher in stepwise respect to NGS group (4.7% vs 0.7%). Similarly, the stepwise group presented higher prevalence than NGS for MET amplification (11.2% vs 2.2%), MET mutations (9.0% vs 2.4%), HER2 amplification (3.3% vs 1.9%) and mutations (9.8% vs 3.0%), and BRAF mutations (4.5% vs 5.6%). Among the NGS group other mutations were found in 141 patients (26.3%) and the presence of concurrent mutations in 131 (24.4%). The stepwise algorithm presented a relevant dropout rate that increased at each step, with 11.4%, 16.4% and 49.3% respectively for ALK, ROS1 and other analysis. Sequential testing’s expenditure was 1375 € per patient, vs 770 € for NGS. Moreover, NGS testing can be performed with just a 25 μm slide respect to an estimated 33.3 μm slide for sequential strategy. Conclusion NGS offered a less expensive and more reliable model of diagnosis respect to sequential one for patients affected by NSCLC-A.
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- 2020
41. Frequency of somatic mutations in head and neck melanoma: A single-institution experience
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Barbara Melotti, Cosimo Misciali, Giulia Veronesi, Mattia Riefolo, Michelangelo Fiorentino, Emi Dika, Barbara Corti, Martina Lambertini, Annalisa Patrizi, Annalisa Altimari, Dika E., Lambertini M., Patrizi A., Misciali C., Altimari A., Fiorentino M., Melotti B., Corti B., Riefolo M., and Veronesi G.
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Oncology ,Male ,Proto-Oncogene Proteins B-raf ,medicine.medical_specialty ,Mutation rate ,Somatic cell ,Dermatology ,General Biochemistry, Genetics and Molecular Biology ,GTP Phosphohydrolases ,Mutation Rate ,Internal medicine ,medicine ,Humans ,Single institution ,Head and neck ,Melanoma ,Aged ,Aged, 80 and over ,business.industry ,Membrane Proteins ,Middle Aged ,medicine.disease ,Proto-Oncogene Proteins c-kit ,Head and Neck Neoplasms ,Mutation ,Female ,business - Published
- 2020
42. Pathological features and outcomes of incidental renal cell carcinoma in candidate solid organ donors
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Francesco Vasuri, Antonia D'Errico, Carlo de Cillia, Deborah Malvi, Matteo Ravaioli, Costantino Ricci, Massimo Cardillo, Michelangelo Fiorentino, Francesca Ambrosi, Ambrosi F., Ricci C., Malvi D., De Cillia C., Ravaioli M., Fiorentino M., Cardillo M., Vasuri F., and D'errico A.
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medicine.medical_specialty ,lcsh:Internal medicine ,lcsh:Specialties of internal medicine ,030232 urology & nephrology ,Chromophobe cell ,030204 cardiovascular system & hematology ,urologic and male genital diseases ,Kidney transplantation ,03 medical and health sciences ,0302 clinical medicine ,Renal cell carcinoma ,lcsh:RC581-951 ,medicine ,Stage (cooking) ,lcsh:RC31-1245 ,Risk assessment ,Frozen section procedure ,business.industry ,Papillary Adenoma ,Cancer ,General Medicine ,Cancer transmission ,medicine.disease ,Donor evaluation ,Original Article ,Radiology ,business ,Clear cell - Abstract
Background : We report the findings of a single Italian center in the evaluation of renal lesions in deceased donors from 2001 to 2017. In risk evaluation, we applied the current Italian guidelines, which include donors with small (< 4 cm, stage pT1a) renal carcinomas in the category of non-standard donors with a negligible risk of cancer transmission. Methods : From the revision of our registries, 2,406 donors were considered in the Emilia Romagna region of Italy; organs were accepted from 1,321 individuals for a total of 3,406 organs. Results : The evaluation of donor safety required frozen section analysis for 51 donors, in which a renal suspicious lesion was detected by ultrasound. Thirty-two primary renal tumors were finally diagnosed: 26 identified by frozen sections and 6 in discarded kidneys. The 32 tumors included 13 clear cell renal cell carcinomas (RCCs), 6 papillary RCCs, 6 angiomyolipomas, 5 oncocytomas, 1 chromophobe RCC, and 1 papillary adenoma. No cases of tumor transmission were recorded in follow-up of the recipients. Conclusion : Donors with small RCCs can be accepted to increase the donor pool. Collaboration in a multidisciplinary setting is fundamental to accurately evaluate donor candidate risk assessment and to improve standardized protocols for surgeons and pathologists.
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- 2020
43. Is There a Role for Immunotherapy in Prostate Cancer?
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Matteo Santoni, Rodolfo Montironi, Alessia Cimadamore, Veronica Mollica, Francesco Massari, Liang Cheng, Francesca Giunchi, Marina Scarpelli, Antonio Lopez-Beltran, Alessandro Rizzo, Michelangelo Fiorentino, Rizzo A., Mollica V., Cimadamore A., Santoni M., Scarpelli M., Giunchi F., Cheng L., Lopez-Beltran A., Fiorentino M., Montironi R., and Massari F.
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0301 basic medicine ,Oncology ,Male ,medicine.medical_specialty ,Combination therapy ,medicine.drug_class ,medicine.medical_treatment ,immune checkpoint inhibitor ,Review ,Monoclonal antibody ,combination therapy ,CTLA-4 ,immune checkpoint inhibitors ,immunotherapy ,pd-1 ,predictive biomarkers ,prostate cancer ,vaccines ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,predictive biomarker ,lcsh:QH301-705.5 ,business.industry ,Cancer ,Prostatic Neoplasms ,General Medicine ,Immunotherapy ,medicine.disease ,Immune checkpoint ,030104 developmental biology ,lcsh:Biology (General) ,030220 oncology & carcinogenesis ,Cancer vaccine ,business - Abstract
In the last decade, immunotherapy has revolutionized the treatment landscape of several hematological and solid malignancies, reporting unprecedented response rates. Unfortunately, this is not the case for metastatic castration-resistant prostate cancer (mCRPC), as several phase I and II trials assessing programmed death receptor 1 (PD-1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitors have shown limited benefits. Moreover, despite sipuleucel-T representing the only cancer vaccine approved by the Food and Drug Administration (FDA) for mCRPC following the results of the IMPACT trial, the use of this agent is relatively limited in everyday clinical practice. The identification of specific histological and molecular biomarkers that could predict response to immunotherapy represents one of the current challenges, with an aim to detect subgroups of mCRPC patients who may benefit from immune checkpoint monoclonal antibodies as monotherapy or in combination with other anticancer agents. Several unanswered questions remain, including the following: is there—or will there ever be—a role for immunotherapy in prostate cancer? In this review, we aim at underlining the failures and promises of immunotherapy in prostate cancer, summarizing the current state of art regarding cancer vaccines and immune checkpoint monoclonal antibodies, and discussing future research directions in this immunologically “cold” malignancy.
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- 2020
44. Current Strategies and Novel Therapeutic Approaches for Metastatic Urothelial Carcinoma
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Michelangelo Fiorentino, Antonio Lopez-Beltran, Matteo Santoni, Francesca Giunchi, Francesco Massari, Riccardo Schiavina, Rodolfo Montironi, Alessandro Rizzo, Liang Cheng, Eugenio Brunocilla, Giovanni Brandi, Veronica Mollica, Mollica V., Rizzo A., Montironi R., Cheng L., Giunchi F., Schiavina R., Santoni M., Fiorentino M., Lopez-Beltran A., Brunocilla E., Brandi G., and Massari F.
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0301 basic medicine ,Oncology ,Drug ,PD-L1 ,Cancer Research ,medicine.medical_specialty ,Metastatic Urothelial Carcinoma ,medicine.medical_treatment ,media_common.quotation_subject ,Review ,Immune checkpoint inhibitor ,lcsh:RC254-282 ,immune checkpoint inhibitors ,03 medical and health sciences ,Immune checkpoint inhibitors ,Antibody drug conjugates ,0302 clinical medicine ,Immune system ,Clinical trials ,Antibody drug conjugate ,Internal medicine ,PD-1 ,medicine ,Survival rate ,urothelial carcinoma ,media_common ,Chemotherapy ,clinical trials ,biology ,antibody drug conjugates ,business.industry ,FGFR ,Immunotherapy ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Clinical trial ,030104 developmental biology ,030220 oncology & carcinogenesis ,biology.protein ,Urothelial carcinoma ,immunotherapy ,business - Abstract
Urothelial carcinoma (UC) is a frequent cause of cancer-related deaths worldwide. Metastatic UC has been historically associated with poor prognosis, with a median overall survival of approximately 15 months and a 5-year survival rate of 18%. Although platinum-based chemotherapy remains the mainstay of medical treatment for patients with metastatic UC, chemotherapy clinical trials produced modest benefit with short-lived, disappointing responses. In recent years, the better understanding of the role of immune system in cancer control has led to the development and approval of several immunotherapeutic approaches in UC therapy, where immune checkpoint inhibitors have been revolutionizing the treatment of metastatic UC. Because of a better tumor molecular profiling, FGFR inhibitors, PARP inhibitors, anti-HER2 agents, and antibody drug conjugates targeting Nectin-4 are also emerging as new therapeutic options. Moreover, a wide number of trials is ongoing with the aim to evaluate several other alterations and pathways as new potential targets in metastatic UC. In this review, we will discuss the recent advances and highlight future directions of the medical treatment of UC, with a particular focus on recently published data and ongoing active and recruiting trials.
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- 2020
45. Reliability of programmed death ligand 1 (PD-L1) tumor proportion score (TPS) on cytological smears in advanced non-small cell lung cancer: a prospective validation study
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Francesco Gelsomino, Elisa Capizzi, Vanina Livi, Laura Casolari, Michelangelo Fiorentino, Filippo Natali, Karim Rihawi, Rocco Trisolini, Andrea Ardizzoni, Costantino Ricci, Francesca Giunchi, Ricci C., Capizzi E., Giunchi F., Casolari L., Gelsomino F., Rihawi K., Natali F., Livi V., Trisolini R., Fiorentino M., and Ardizzoni A.
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0301 basic medicine ,Oncology ,PD-L1 ,medicine.medical_specialty ,Validation study ,Pembrolizumab ,lcsh:RC254-282 ,cytological smear ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Single agent ,Lung cancer ,non-small cell lung cancer ,Original Research ,biology ,business.industry ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,cytological smears ,030104 developmental biology ,030220 oncology & carcinogenesis ,immunohistochemistry ,biology.protein ,Immunohistochemistry ,Non small cell ,business ,Programmed death - Abstract
Introduction: Programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) assessment is mandatory for the single agent pembrolizumab treatment of patients with advanced non-small cell lung cancer (NSCLC). PD-L1 testing has been validated and is currently certified only on formalin-fixed paraffin-embedded materials but not on cytological smears. Unfortunately, a significant proportion of patients, having only cytological material available, cannot be tested for PD-L1 and treated with pembrolizumab. In this study, we aimed to validate PD-L1 IHC on cytological smears prospectively by comparing clone SP263 staining in 150 paired histological samples and cytological smears of NSCLC patients. Methods: We prospectively enrolled 150 consecutive advanced NSCLC patients. The clone SP263 was selected as, in a previous study of our group, it showed higher accuracy compared with clones 28-8 and 22-C3, with good cyto-histological agreement using a cut-off of 50%. For cyto-histological concordance, we calculated the kappa coefficient using two different cut-offs according to the percentage of PD-L1 positive neoplastic cells (Results: The overall agreement between histological samples and cytological smears was moderate (kappa = 0.537). However, when the cyto-histological concordance was calculated using the cut-off of 50%, the agreement was good (kappa = 0.740). With the same cut-off, and assuming as gold-standard the results on formalin-fixed paraffin-embedded materials, PD-L1 evaluation on smears showed specificity and negative predictive values of 98.1% and 93.9%, respectively. Conclusion: Cytological smears can be used in routine clinical practice for PD-L1 assessment with a cut-off of 50%, expanding the potential pool of NSCLC patients as candidates for first-line single agent pembrolizumab therapy.
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- 2020
46. Indications for renal biopsy in patients with diabetes. Joint position statement of the Italian Society of Nephrology and the Italian Diabetes Society
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Salvatore Di Paolo, Marco Fiorentino, Gianpaolo Reboldi, Luca De Nicola, Paola Fioretto, Loreto Gesualdo, Giuseppe Pugliese, Andrea Natali, Giuseppe Penno, Federica Barutta, Di Paolo, S., Fiorentino, M., De Nicola, L., Reboldi, G., Gesualdo, L., Barutta, F., Natali, A., Penno, G., Fioretto, P., and Pugliese, G.
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Nephrology ,medicine.medical_specialty ,Consensus ,Diabetic kidney disease (DKD) ,Diabetic nephropathy (DN) ,DKD phenotypes ,Non-diabetic renal disease (NDRD) ,Renal biopsy ,Biopsy ,Endocrinology, Diabetes and Metabolism ,Medicine (miscellaneous) ,030209 endocrinology & metabolism ,030204 cardiovascular system & hematology ,Kidney ,urologic and male genital diseases ,Severity of Illness Index ,Diabetic nephropathy ,03 medical and health sciences ,0302 clinical medicine ,Predictive Value of Tests ,Internal medicine ,Diabetes mellitus ,Diabetes Mellitus ,medicine ,Humans ,Hypoglycemic Agents ,Diabetic Nephropathies ,Type 1 diabetes ,Nutrition and Dietetics ,medicine.diagnostic_test ,business.industry ,Diabetes Mellitus, Type 1 ,Prognosis ,medicine.disease ,DKD phenotype ,Albuminuria ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Nephrotic syndrome ,Type 1 ,Retinopathy - Abstract
Aims This joint document of the Italian Society of Nephrology and the Italian Diabetes Society reviews the main indications to perform a renal biopsy in diabetic patients, according to the recommendations of a panel of experts based on all available scientific evidence. Data synthesis Renal biopsy has a pivotal role in assessing the nature and severity of renal injury in patients with diabetic kidney disease (DKD). The procedure is mandatory in the presence of one of more of the following features: rapid onset or progression of albuminuria or sudden onset of nephrotic syndrome, rapid GFR decline with or without albuminuria, hematuria, active urine sediment, clinical and/or laboratory suspicion of other systemic diseases, and, in patients with type 1 diabetes, short diabetes duration and absence of retinopathy. Indeed, ~40% of diabetic individuals with kidney injury undergoing renal biopsy are affected by a non-diabetic renal disease (NDRD). Furthermore, the histological evaluation of patients with suspected classical diabetic nephropathy allows to define the extent of glomerular, tubulo-interstitial and vascular lesions, thus providing important prognostic (and potentially therapeutic) data. In the future, the indications for renal biopsy might be extended to the definition of the histological lesions underlying the “nonalbuminuric” DKD phenotypes, as well as to the evaluation of the response to treatment with the new anti-hyperglycemic drugs that provide cardiorenal protection. Conclusions In view of the heterogeneous clinical presentation and course of DKD and of the related heterogeneous histopathological patterns, a more extensive use of renal biopsy may be crucial to provide valuable information with important pathogenic, diagnostic, prognostic, and therapeutic implications.
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- 2020
47. Pulmonary adenocarcinoma with psammoma bodies is associated with a specific endobronchial ultrasound pattern and a high prevalence of actionable driver mutations
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Alessandra Cancellieri, Rocco Trisolini, Michelangelo Fiorentino, Daniela Paioli, Filippo Natali, Marco Ferrari, Jouke T. Annema, Andrea Ardizzoni, Annalisa Altimari, Vanina Livi, Nicole Conci, Trisolini R., Cancellieri A., Livi V., Annema J.T., Ferrari M., Natali F., Paioli D., Conci N., Altimari A., Fiorentino M., Ardizzoni A., Pulmonology, and CCA - Imaging and biomarkers
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0301 basic medicine ,Pulmonary and Respiratory Medicine ,Cancer Research ,Pathology ,medicine.medical_specialty ,Lung Neoplasms ,Psammoma body ,Pulmonary adenocarcinoma ,Adenocarcinoma of Lung ,Malignancy ,03 medical and health sciences ,Molecular profiling ,0302 clinical medicine ,Next generation sequencing ,Prevalence ,Medicine ,Humans ,Endobronchial ultrasound ,ALK Rearrangement ,Pathological ,Endoscopic Ultrasound-Guided Fine Needle Aspiration ,business.industry ,medicine.disease ,030104 developmental biology ,BRAF mutation ,Oncology ,030220 oncology & carcinogenesis ,Mutation ,Molecular Profile ,Female ,business ,Breast carcinoma - Abstract
Introduction Pulmonary adenocarcinoma with psammoma bodies (PAPBs) is a rare histological variant whose association with a high prevalence of targetable mutations has been suggested by scant literature reports describing small series. We aim to describe the endobronchial ultrasound (EBUS) pattern and the molecular profile by next-generation sequencing of an Italian series of patients with PAPBs. Material and methods Over a 8-year period (2012–2019), we identified 15 patients with a very uncommon endobronchial ultrasound (EBUS) heterogeneity pattern characterized by the presence of multiple to countless, punctate non-shadowing foci (“starry sky” sign) which were not evident at CT and corresponded to psammoma bodies at pathological examination. The clinical, radiological, pathological and molecular findings of these patients were retrieved and analyzed. Results Pathological examination of the EBUS-TBNA specimens revealed malignancy (12 pulmonary adenocarcinoma, 2 breast carcinoma, 1 colonic carcinoma) and showed the presence of psammoma bodies in all of the 15 patients with the starry sky sign. Among the 12 patients with pulmonary adenocarcinoma with psammoma bodies, female sex (8/12, 66.7 %) and never-smoking habit (6/12, 50 %) were prevalent. Molecular tumor profiling using the Oncomine™ Focus DNA and RNA fusion panels was successfully performed in 11/12 patients and revealed 10 genetic alterations (BRAF mutation, 4; EGFR mutation, 2; ALK rearrangement, RET rearrangement, PIK3CA mutation, CDK4 amplification 1) in 7 patients (63.6 %). Conclusion The present series suggests that pulmonary adenocarcinoma with psammoma bodies is associated with a readily identifiable EBUS pattern and with a high prevalence of different, often uncommon and actionable, driver mutations.
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- 2020
48. PD-L1 Expression is Associated with Poor Prognosis in Renal Cell Carcinoma
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Michelangelo Fiorentino, Pernilla Sundqvist, Anna Fält, Vezira Kosuta, Sabina Davidsson, Jessica Carlsson, Francesca Giunchi, Carlsson J., Sundqvist P., Kosuta V., Falt A., Giunchi F., Fiorentino M., and Davidsson S.
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Adult ,Male ,0301 basic medicine ,Poor prognosis ,Histology ,antitumor immunity ,urologic and male genital diseases ,B7-H1 Antigen ,Disease-Free Survival ,World health ,Pathology and Forensic Medicine ,Negative regulator ,03 medical and health sciences ,Lymphocytes, Tumor-Infiltrating ,0302 clinical medicine ,Immune system ,Renal cell carcinoma ,medicine ,Humans ,Receptor ,Carcinoma, Renal Cell ,Aged ,Aged, 80 and over ,business.industry ,Cancer ,Middle Aged ,TIICs ,medicine.disease ,RCC ,Kidney Neoplasms ,Neoplasm Proteins ,Gene Expression Regulation, Neoplastic ,Survival Rate ,Medical Laboratory Technology ,030104 developmental biology ,programmed death ligand 1 ,030220 oncology & carcinogenesis ,Cancer research ,Female ,Pd l1 expression ,business ,prognostic marker ,Follow-Up Studies - Abstract
Programmed death ligand 1 (PD-L1) is a protein which, when interacting with its receptor programmed death 1, acts as a negative regulator of the antitumor T-cell-mediated immune response. The prognostic value of PD-L1 expression in renal cell carcinoma (RCC) has been controversial. In this study, the prognostic value of PD-L1 expression in RCC was evaluated by analyzing PD-L1 immunoreactivity in tumor cells and tumor-infiltrating immune cells (TIICs) in 346 RCC patients with long-term follow-up. PD-L1 positivity in tumor cells was associated with higher World Health Organization nucleolar grade (P
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- 2020
49. Infiltration of M2 Macrophages and Regulatory T Cells Plays a Role in Recurrence of Renal Cell Carcinoma
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Pernilla Sundqvist, Margareta Eriksson, Francesca Giunchi, Sabina Davidsson, Jessica Carlsson, Michelangelo Fiorentino, Ann Erlandsson, Davidsson S., Fiorentino M., Giunchi F., Eriksson M., Erlandsson A., Sundqvist P., and Carlsson J.
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regulatory T cell ,cell infiltration ,CD163+ M2 macrophages ,clinical outcome ,nephron sparing surgery ,lcsh:RC870-923 ,regulatory T lymphocyte ,Renal cell carcinoma ,CD163 antigen ,Biologiska vetenskaper ,Tissue microarray ,FOXP3 ,hemic and immune systems ,Hälsovetenskaper ,Biological Sciences ,Kidney Cancer ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Immunohistochemistry ,FOXP3+ regulatory T cells ,female ,priority journal ,Infiltration (medical) ,immunoreactivity ,radical nephrectomy ,Cell type ,Urology ,transcription factor FOXP3 ,chemical and pharmacologic phenomena ,macrophage ,+ ,lcsh:RC254-282 ,Article ,M2 macrophage ,male ,Health Sciences ,medicine ,human ,CD4+ T lymphocyte ,tissue microarray ,business.industry ,cancer staging ,human cell ,lcsh:Diseases of the genitourinary system. Urology ,medicine.disease ,major clinical study ,human tissue ,cancer recurrence ,Tumor progression ,Cancer research ,CD163 ,business - Abstract
Background It has been hypothesized that M2 macrophages and regulatory T cells (Tregs) may contribute to tumor progression by suppression of antitumor immunity. Objective To investigate the association between infiltration of CD163+ M2 macrophages and CD4+FOXP3+ Tregs with clinical outcomes in renal cell carcinoma patients. Design, setting, and participants A cohort of 346 patients diagnosed with renal cell carcinoma at Örebro University Hospital between 1986 and 2011 was evaluated for CD163+ M2 macrophage and CD4+FOXP3+ Treg infiltration by immunohistochemistry. Outcome measurements and statistical analysis Associations between clinicopathological features and infiltration of CD163+ M2 macrophages and/or CD4+FOXP3+ Tregs were estimated with chi-square or Fisher's exact tests. For survival analyses, Kaplan-Meier curves with log-rank tests and multivariate Cox proportional hazards regression models were used. Results and limitations We found that infiltration of CD163+ M2 macrophages and CD4+FOXP3+ Tregs were associated with adverse clinical outcomes. Our data further demonstrate that CD163+ M2 macrophages and CD4+FOXP3+ Tregs colocalize in tumor and normal tissue, and that this colocalization may have synergistic effects on tumor aggressiveness. The use of tissue microarrays rather than whole sections may be viewed as a limitation. Conclusions Infiltration of CD163+ M2 macrophages and CD4+FOXP3+ Tregs is associated with recurrence of renal cell carcinoma, and colocalization of these cell types may have an association with clinical outcome. Patient summary The aim of this study was to investigate the association between infiltration of M2 macrophages and regulatory T cells with clinical outcomes in renal cell carcinoma. We demonstrated that renal cell carcinoma patients with high infiltration of both these cell types are at an increased risk of poor clinical outcomes., Take Home Message Regulatory T cells (Tregs) and M2 macrophages have been hypothesized to contribute to tumor progression. We found that M2 macrophages and Tregs are associated with more aggressive renal cell carcinoma, and that they have a synergistic effect on clinical outcome.
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- 2020
50. Comprehensive analysis of 34 MiT family translocation renal cell carcinomas and review of the literature: investigating prognostic markers and therapy targets
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Pedram Argani, Cosimo Sacco, Enrico Bollito, Francesco Pierconti, Camillo Porta, Cathryn Scott, Anna Caliò, Alessandra Mosca, Guido Martignoni, Angelo Sidoni, Michele Milella, Serena Ammendola, Matteo Brunelli, Michelangelo Fiorentino, Steno Sentinelli, Luisa Canu, Serena Pedron, Simona Fisogni, Diego Segala, Anna Paola Fraccon, Enrico Munari, Andrea Remo, Calio A., Brunelli M., Segala D., Pedron S., Remo A., Ammendola S., Munari E., Pierconti F., Mosca A., Bollito E., Sidoni A., Fisogni S., Sacco C., Canu L., Sentinelli S., Fraccon A.P., Fiorentino M., Scott C., Milella M., Porta C., Argani P., and Martignoni G.
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0301 basic medicine ,Male ,Cell ,Cathepsin K ,kidney carcinoma ,TFE3 ,cabozantinib ,cathepsin K ,FISH ,immunohistochemistry ,predictive markers ,prognosis ,target therapy ,Translocation renal cell carcinoma ,Tyrosine-kinase inhibitor ,Translocation, Genetic ,chemistry.chemical_compound ,0302 clinical medicine ,Renal cell carcinoma ,Medicine ,Child ,Middle Aged ,Proto-Oncogene Proteins c-met ,Prognosis ,Kidney Neoplasms ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Immunohistochemistry ,Female ,predictive marker ,prognosi ,Adult ,Cabozantinib ,Adolescent ,medicine.drug_class ,Pathology and Forensic Medicine ,03 medical and health sciences ,Young Adult ,Proto-Oncogene Proteins ,Humans ,Carcinoma, Renal Cell ,Aged ,Chromosomes, Human, X ,Settore MED/08 - ANATOMIA PATOLOGICA ,business.industry ,Receptor Protein-Tyrosine Kinases ,medicine.disease ,Axl Receptor Tyrosine Kinase ,030104 developmental biology ,chemistry ,Cancer research ,INGLESE ,PAX8 ,business ,Biomarkers - Abstract
Summary Recently cabozantinib, a tyrosine kinase inhibitor with activity against VEGF, MET, AXL, and downregulating cathepsin K in vitro, has been proposed for the treatment of advanced clear and non-clear renal cell carcinomas. Since it is well known that cathepsin K is expressed in the majority of MiT family translocation renal cell carcinomas, we investigated cathepsin K, MET, AXL, and VEGF in a large series of those tumours, looking for possible predictive markers. We collected the clinicopathological features of 34 genetically confirmed MiT family translocation renal cell carcinomas [26 Xp11 and 8 t(6;11) renal cell carcinomas] and studied them using an immunohistochemical panel including PAX8, cathepsin K, HMB45, Melan-A, CD68 (PG-M1), CK7, CA9, MET, AXL and by FISH for VEGFA and MET. Cathepsin K was expressed in 14 of 26, HMB45 in 8 of 25, and Melan-A in 4 of 23 Xp11 renal cell carcinomas, whereas labelling for CK7 and CA9 was minimal. In t(6;11) renal cell carcinoma, cathepsin K and melanogenesis markers were constantly positive, whereas CK7 and CA9 were negative. None of the 34 carcinomas showed CD68 (PG-M1) and AXL expression. One aggressive Xp11 renal cell carcinoma showed increased VEGFA gene copy number (4–5 copies) with concurrent gains of TFE3 and TFEB. None of the 34 carcinomas showed MET gene amplification, whereas staining for MET was found in 7 of 8 t(6;11) and in 16 of 24 Xp11 renal cell carcinomas, and in the latter cases, when the expression was >50%, correlated with aggressiveness (p=0.0049). In Xp11 renal cell carcinomas, the aggressiveness was also correlated with larger tumour size (p=0.0008) and the presence of necrosis (p=0.027) but not nucleolar grading (p=1). Interestingly, in patients with tumours exhibiting two of three parameters (necrosis, larger tumour size and MET immunolabelling >50%) an aggressive clinical behaviour was observed in 88% of cases. In conclusion, cathepsin K, CD68 (PG-M1), CK7, CA9, and PAX8 is a useful panel for the diagnosis. Larger tumour size, the presence of necrosis and MET immunohistochemical expression correlate with aggressive behaviour in Xp11 renal cell carcinomas, especially in combination. VEGF, MET, cathepsin K but not AXL may be potential predictive markers for targeted therapy in MiT family translocation renal cell carcinomas.
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- 2020
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