26 results on '"Pucciarelli, S"'
Search Results
2. Tryptophan metabolism along the kynurenine and serotonin pathways reveals substantial differences in colon and rectal cancer
- Author
-
Crotti, S., D’Angelo, E., Bedin, C., Fassan, M., Pucciarelli, S., Nitti, D., Bertazzo, A., and Agostini, M.
- Published
- 2017
- Full Text
- View/download PDF
3. Proximal colon cancer in patients aged 51–60 years of age should be tested for microsatellites instability. A comment on the Revised Bethesda Guidelines
- Author
-
Urso, E., Pucciarelli, S., Agostini, M., Maretto, I., Mescoli, C., Bertorelle, R., Viel, A., Rugge, M., and Nitti, D.
- Published
- 2008
- Full Text
- View/download PDF
4. T1 colon cancer in the era of screening: risk factors and treatment
- Author
-
Bianco, F., De Franciscis, S., Belli, A., Falato, A., Fusco, R., Altomare, D. F., Amato, A., Asteria, C. R., Avallone, A., Binda, G. A., Boccia, L., Buzzo, P., Carvello, M., Coco, Claudio, Delrio, P., De Nardi, P., Di Lena, M., Failla, A., La Torre, F., La Torre, M., Lemma, M., Luffarelli, P., Manca, G., Maretto, I., Marino, F., Muratore, A., Pascariello, A., Pucciarelli, S., Rega, D., Ripetti, V., Rizzo, Gianluca, Serventi, A., Spinelli, A., Tatangelo, F., Urso, E. D. L., Romano, G. M., and on behalf of the Italian Society of Colo-Rectal Surgery (SICCR) Cancer Group, Null
- Subjects
Adult ,Male ,Oncology ,medicine.medical_specialty ,Lymphatic metastasis ,Multivariate analysis ,Colorectal cancer ,Settore MED/18 - CHIRURGIA GENERALE ,Medical Overuse ,Audit ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,medicine ,Humans ,Lymph node ,Early Detection of Cancer ,Aged ,Neoplasm Staging ,Retrospective Studies ,Early-stage colon cancer ,Medical Audit ,business.industry ,Gastroenterology ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Quality assurance ,Colorectal surgery ,Acs nsqip ,Logistic Models ,medicine.anatomical_structure ,Lymph node metastases ,Screening ,Colonic Neoplasms ,Female ,Lymph Node Excision ,Lymph Nodes ,Lymphatic Metastasis ,Multivariate Analysis ,Surgery ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,business - Abstract
The aim of this study was to identify risk factors for lymph node positivity in T1 colon cancer and to carry out a surgical quality assurance audit.The sample consisted of consecutive patients treated for early-stage colon lesions in 15 colorectal referral centres between 2011 and 2014. The study investigated 38 factors grouped into four categories: demographic information, preoperative data, indications for surgery and post-operative data. A univariate and multivariate logistic regression analysis was performed to analyze the significance of each factor both in terms of lymph node (LN) harvesting and LN metastases.Out of 507 patients enrolled, 394 patients were considered for analysis. Thirty-five (8.91%) patients had positive LN. Statistically significant differences related to total LN harvesting were found in relation to central vessel ligation and segmental resections. Cumulative distribution demonstrated that the rate of positive LN increased starting at 12 LN harvested and reached a plateau at 25 LN.Some factors associated with an increase in detection of positive LN were identified. However, further studies are needed to identify more sensitive markers and avoid surgical overtreatment. There is a need to raise the minimum LN count and to use the LN count as an indicator of surgical quality.
- Published
- 2017
5. In-hospital mortality, 30-day readmission, and length of hospital stay after surgery for primary colorectal cancer: A national population-based study.
- Author
-
Pucciarelli, S., Zorzi, M., Gennaro, N., Gagliardi, G., Restivo, A., Saugo, M., Barina, A., Rugge, M., Zuin, M., Maretto, I., and Nitti, D.
- Subjects
COLON cancer ,MORTALITY ,PATIENT readmissions ,MEDICAL care ,SURGICAL diagnosis - Abstract
Introduction The simultaneous assessment of multiple indicators for quality of care is essential for comparisons of performance between hospitals and health care systems. The aim of this study was to assess the rates of in-hospital mortality and 30-day readmission and length of hospital stay (LOS) in patients who underwent surgical procedures for colorectal cancer between 2005 and 2014 in Italy. Methods All patients in the National Italian Hospital Discharge Dataset who underwent a surgical procedure for colorectal cancer during the study period were included. The adjusted odd ratios for risk factors for in-hospital mortality, 30-day readmission, and LOS were calculated using multilevel multivariable logistic regression. Results Among the 353 941 patients, rates of in-hospital mortality and 30-day readmission were 2.5% and 6%, respectively, and the median LOS was 13 days. High comorbidity, emergent/urgent admission, male gender, creation of a stoma, and an open approach increased the risks of all the outcomes at multivariable analysis. Age, hospital volume, hospital geographic location, and discharge to home/non-home produced different effects depending on the outcome considered. The most frequent causes of readmission were infection (19%) and bowel obstruction (14.6%). Conclusions We assessed national averages for mortality, LOS and readmission and related trends over a 10-year time. Laparoscopic surgery was the only one that could be modified by improving surgical education. Higher hospital volume was associated with a LOS reduction, but our findings only partially support a policy of centralization for colorectal cancer procedures. Surgical site infection was identified as the most preventable cause of readmission. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
6. Colorectal polyposis: clinical presentation and surgical treatment.
- Author
-
Urso, E. D. L., Delaini, G. G., Campi, M., Bacchelli, C., and Pucciarelli, S.
- Subjects
COLON polyps ,POLYPS ,ADENOMATOUS polyposis coli ,TUMOR genetics ,SURGICAL anastomosis ,LAPAROSCOPIC surgery ,COLECTOMY ,THERAPEUTICS - Abstract
The article focuses on the aspects of genetic, clinical, and treatment of colorectal polyposis disorders such as familial adenomatous polyposis (FAP) and multiple colorectal adenomas (MCRAs) syndromes. Among the clinical aspects discussed are genetic cause, physiological manifestation, and pathological characteristics. Also discussed several surgical methods including total colectomy with ileo-rectal anastomosis (IRA), laparoscopic approach, and protocolectomy.
- Published
- 2015
- Full Text
- View/download PDF
7. Relationship between telomere shortening, genetic instability, and site of tumour origin in colorectal cancers.
- Author
-
Rampazzo, E., Bertorelle, R., Serra, L., Terrin, L., Candiotto, C., Pucciarelli, S., Del Bianco, P., Nitti, D., and De Rossi, A.
- Subjects
TELOMERES ,CHROMOSOMES ,CANCER treatment ,CANCER invasiveness ,MICROSATELLITE repeats ,RESEARCH ,GENETIC mutation ,RESEARCH methodology ,MEDICAL cooperation ,EVALUATION research ,COLORECTAL cancer ,COMPARATIVE studies ,TRANSFERASES ,INTESTINAL mucosa - Abstract
Background: Telomeres, located at chromosome ends, are progressively shortened during each cell cycle by replication-dependent loss of DNA termini. Although maintenance of telomere length is critical for cell-replicative potential and tumourigenesis, the erosion of telomeres can lead to genetic instability, a pivotal mechanism in the neoplastic process.Patients and Methods: A total of 118 colorectal cancer (CRC) samples (53 right-colon, 30 left-colon, and 35 rectal tumours) and corresponding adjacent non-cancerous tissues were evaluated for telomere length, p53 mutation, and microsatellite instability (MSI). Telomere length was estimated by real-time PCR.Results: Telomeres were significantly shorter in CRCs than in adjacent tissues, regardless of tumour stage and grade, site, or genetic alterations (P<0.0001). Moreover, in normal tissues, but not in tumours, telomere length inversely correlated with age (r=-0.24, P=0.017). Telomere length in CRCs did not differ with tumour progression or p53 status; however, in CRCs carrying the wild-type p53, telomeres were significantly shorter in tumours with MSI than in those with stable microsatellites (P=0.027). Furthermore, telomere length differed according to tumour location, being longer in rectal cancers (P=0.03).Conclusions: These findings suggest that telomere shortening is a key initial event in colorectal carcinogenesis. The extent of telomere erosion is related to tumour origin site and may be influenced by the mismatch repair pathway. [ABSTRACT FROM AUTHOR]- Published
- 2010
- Full Text
- View/download PDF
8. Mid-transverse colon cancer and extended versus transverse colectomy: Results of the Italian society of surgical oncology colorectal cancer network (SICO CCN) multicenter collaborative study
- Author
-
Maurizio Degiuli, Davide Cavaliere, G. Li Destri, Daniela Rega, M. Santarelli, Michela Mineccia, Leonardo Solaini, E. Urso, Gaetano Gallo, G. De Manzoni, Riccardo Rosati, Paolo Delrio, Marco E. Allaix, A. Di Leo, Monica Ortenzi, R. De Luca, Gianluca Rizzo, A. Di Cataldo, Michele De Simone, Domenico D'Ugo, Giulia Turri, Claudio Coco, Francesca Pecchini, L. Siragusa, Michele Manigrasso, F. Bianco, Mario Trompetto, M. De Rosa, A. Coratti, C. Bombardini, Fabio Rondelli, R. Longhin, Federica Saraceno, M. Zuin, A. Vignali, Marco Milone, S. Vertaldi, Stefano Scabini, Luigina Graziosi, Mario Morino, A. Fontana, G.D. De Palma, A. Tribuzi, Giuseppe Giuliani, V. Robustelli, Mario Guerrieri, Micaela Piccoli, P. De Nardi, S. Giannessi, Ugo Elmore, Paolo Bianchi, Gabriele Anania, S. Pollesel, M. Rigamonti, Silvia Sofia, F. Roviello, M. Monni, Annibale Donini, G.S. Sica, Andrea Belli, Andrea Barberis, Salvatore Pucciarelli, Corrado Pedrazzani, Sergio Gentilli, Rossella Reddavid, Pierpaolo Sileri, M. Zuolo, M. Burati, C.A. Ammirati, Milone M., Degiuli M., Allaix M.E., Ammirati C.A., Anania G., Barberis A., Belli A., Bianchi P.P., Bianco F., Bombardini C., Burati M., Cavaliere D., Coco C., Coratti A., De Luca R., De Manzoni G., De Nardi P., De Rosa M., Delrio P., Di Cataldo A., Di Leo A., Donini A., Elmore U., Fontana A., Gallo G., Gentilli S., Giannessi S., Giuliani G., Graziosi L., Guerrieri M., Li Destri G., Longhin R., Manigrasso M., Mineccia M., Monni M., Morino M., Ortenzi M., Pecchini F., Pedrazzani C., Piccoli M., Pollesel S., Pucciarelli S., Reddavid R., Rega D., Rigamonti M., Rizzo G., Robustelli V., Rondelli F., Rosati R., Roviello F., Santarelli M., Saraceno F., Scabini S., Sica G.S., Sileri P., Simone M., Siragusa L., Sofia S., Solaini L., Tribuzi A., Trompetto M., Turri G., Urso E.D.L., Vertaldi S., Vignali A., Zuin M., Zuolo M., D'Ugo D., De Palma G.D., Milone, M., Degiuli, M., Allaix, M. E., Ammirati, C. A., Anania, G., Barberis, A., Belli, A., Bianchi, P. P., Bianco, F., Bombardini, C., Burati, M., Cavaliere, D., Coco, C., Coratti, A., De Luca, R., De Manzoni, G., De Nardi, P., De Rosa, M., Delrio, P., Di Cataldo, A., Di Leo, A., Donini, A., Elmore, U., Fontana, A., Gallo, G., Gentilli, S., Giannessi, S., Giuliani, G., Graziosi, L., Guerrieri, M., Li Destri, G., Longhin, R., Manigrasso, M., Mineccia, M., Monni, M., Morino, M., Ortenzi, M., Pecchini, F., Pedrazzani, C., Piccoli, M., Pollesel, S., Pucciarelli, S., Reddavid, R., Rega, D., Rigamonti, M., Rizzo, G., Robustelli, V., Rondelli, F., Rosati, R., Roviello, F., Santarelli, M., Saraceno, F., Scabini, S., Sica, G. S., Sileri, P., Simone, M., Siragusa, L., Sofia, S., Solaini, L., Tribuzi, A., Trompetto, M., Turri, G., Urso, E. D. L., Vertaldi, S., Vignali, A., Zuin, M., Zuolo, M., D'Ugo, D., De Palma, G. D., and Giuliani, A.
- Subjects
Male ,Time Factors ,Colorectal cancer ,Settore MED/18 - CHIRURGIA GENERALE ,Anastomotic Leak ,Transverse ,0302 clinical medicine ,Postoperative Complications ,Retrospective Studie ,Surgical oncology ,extended hemicolectomy ,segmental colectomy ,transverse colon cancer ,transversectomy ,Transverse Colectomy ,80 and over ,Medicine ,Hemicolectomy ,Colectomy ,Aged, 80 and over ,Colonic Neoplasm ,General Medicine ,Middle Aged ,Colorectal surgery ,Survival Rate ,Surgical Oncology ,Oncology ,Italy ,030220 oncology & carcinogenesis ,Colonic Neoplasms ,Extended hemicolectomy ,Segmental colectomy ,Transverse colon cancer ,Transversectomy ,Aged ,Colon, Transverse ,Disease-Free Survival ,Female ,Humans ,Length of Stay ,Neoplasm Staging ,Retrospective Studies ,Surgical Wound Infection ,030211 gastroenterology & hepatology ,Segmental resection ,Human ,medicine.medical_specialty ,Colon ,Anastomosis ,NO ,03 medical and health sciences ,business.industry ,Retrospective cohort study ,medicine.disease ,Surgery ,Settore MED/18 ,Postoperative Complication ,business - Abstract
Introduction: Transverse colon cancer (TCC) is poorly studied, and TCC cases are often excluded from large prospective randomized trials because of their complexity and their potentially high complication rate. The best surgical approach for TCC has yet to be established. The aim of this large retrospective multicenter Italian series is to investigate the advantages and disadvantages of both hemicolectomy and transverse colectomy in order to identify the best surgical approach. Materials and methods: This was a retrospective cohort study of patients with mid-transverse colon cancer treated with a segmental colon resection or an extended hemicolectomy (right or left) between 2006 and 2016 in 28 high-volume (more than 70 procedures/year) Italian referral centers for colorectal surgery. Results: The study included 1529 patients, 388 of whom underwent a segmental resection while 1141 underwent an extended resection. A higher number of complications has been reported in the segmental group than in the extended group (30.1% versus 23.6%; p 0.010). In 42 cases the main complication was the anastomotic leak (4.4% versus 2.2%; p 0.020). Recovery outcomes also showed statistical differences: time to first flatus (p 0.014), time to first mobilization (p 0.040), and overall hospital stay (p < 0.001) were significantly shorter in the extended group. Even if overall survival were similar between the groups (95.1% versus 97%; p 0.384), 3-year disease-free survival worsened after segmental resection (78.1% versus 86.2%; p 0.001). Conclusions: According to our results, an extended right colon resection for TCC seems to be surgically safer and more oncologically valid.
- Published
- 2020
9. A nationwide audit of the use of radiotherapy for rectal cancer in Italy
- Author
-
M. Fiorino, E. Contessini-Avesani, I. Demma, M. Lambertini, Davide F. D'Amico, A. Fianchini, G. Gagliardi, G. Casula, G. D’Ambrosio, Claudio Coco, G. Ambrosino, F. Galeotti, C. Eccher, B. Cola, Giorgio Romano, P. De Nardi, C. R. Asteria, Salvatore Pucciarelli, A. Infantino, Francesco Selvaggi, M. Brulatti, Elio Jovine, L. M. Casentino, Gagliardi G, Pucciarelli S, Asteria CR, Infantino A, Romano G, Cola B, De Nardi P, Brulatti M, Lambertini M, Contessini-Avesani E, Casula G, Coco C, D'Amico D, Selvaggi FF, Eccher C, D'Ambrosio G, Galeotti F, Jovine E, Demma I, Fianchini A, Ambrosino G, Casentino LM, Fiorino M, Gagliardi, G, Pucciarelli, S, Asteria, Cr, Infantino, A, Romano, G, Cola, B, DE NARDI, P, Brulatti, M, Lambertini, M, CONTESSINI AVESANI, E, Casula, G, Coco, C, D'Amico, D, Selvaggi, Francesco, Eccher, C, D'Ambrosio, G, Galeotti, F, Jovine, E, Demma, I, Fianchini, A, Ambrosino, G, Casentino, Lm, and Fiorino, M.
- Subjects
Male ,medicine.medical_specialty ,Colorectal cancer ,Rectal cancer - Adjuvant radiotherapy - Neoadjuvant radiotherapy - Disparities ,medicine.medical_treatment ,Audit ,Risk Assessment ,Good evidence ,Odds Ratio ,Medicine ,Humans ,Medical physics ,Neoplasm Invasiveness ,Colectomy ,Aged ,Neoplasm Staging ,Retrospective Studies ,Adjuvant radiotherapy ,Analysis of Variance ,Medical Audit ,business.industry ,Rectal Neoplasms ,General surgery ,Gastroenterology ,Radiotherapy Dosage ,Middle Aged ,medicine.disease ,Survival Analysis ,Colorectal surgery ,Neoadjuvant Therapy ,Adjuvant chemotherapy ,Radiation therapy ,Logistic Models ,Treatment Outcome ,Italy ,Health Care Surveys ,Multivariate Analysis ,Surgery ,Female ,Radiotherapy, Adjuvant ,business ,Abdominal surgery ,Follow-Up Studies - Abstract
BACKGROUND: There is good evidence that radiotherapy is beneficial in advanced rectal cancer, but its application in Italy has not been investigated. METHODS: We conducted a nationwide survey among members of the Italian Society of Colo-Rectal Surgery (SICCR) on the use of radiation therapy for rectal cancer in the year 2005. Demographic, clinical and pathologic data were retrospectively collected with an online database. Italy was geographically divided into 3 regions: north, center and south which included the islands. Hospitals performing 30 or more surgeries per year were considered high volume. Factors related to radiotherapy delivery were identified with multivariate analysis. RESULTS: Of 108 centers, 44 (41%) responded to the audit. We collected data on 682 rectal cancer patients corresponding to 58% of rectal cancers operated by SICCR members in 2005. Radiotherapy was used in 307/682 (45.0%) patients. Preoperative radiotherapy was used in 236/682 (34.6%), postoperative radiotherapy in 71/682 (10.4%) cases and no radiotherapy in 375 (55.0%) cases. Of the 236 patients who underwent preoperative radiotherapy, only 24 (10.2%) received short-course radiotherapy, while 212 (89.8%) received long-course radiotherapy. Of the 339 stage II-III patients, 159 (47%) did not receive any radiotherapy. Radiotherapy was more frequently used in younger patients (P < 0.0001), in patients undergoing abdominoperineal resection (APR) (P < 0.01) and in the north and center of Italy (P < 0.001). Preoperative radiotherapy was more frequently used in younger patients (P < 0.001), in large volume centers (P < 0.05), in patients undergoing APR (P < 0.005) and in the north-center of Italy (P < 0.05). CONCLUSION: Our study first identified a treatment disparity among different geographic Italian regions. A more systematic audit is needed to confirm these results and plan adequate interventions.
- Published
- 2010
10. Definition and management of colorectal polyposis not associated with APC/MUTYH germline pathogenic variants: AIFEG consensus statement
- Author
-
Emanuele Damiano Luca Urso, Maurizio Ponz de Leon, Marco Vitellaro, Guglielmo Niccolò Piozzi, Quoc Riccardo Bao, Aline Martayan, Andrea Remo, Vittoria Stigliano, Cristina Oliani, Emanuela Lucci Cordisco, Salvatore Pucciarelli, Guglielmina Nadia Ranzani, Alessandra Viel, Francesca Adami, Elisa Alducci, Lucia Amadori, Valentina Arcangeli, Luisa Balestrino, Daniela Barana, Lucio Bertario, Bernardo Bonanni, Stefania Boni, Pierluigi Bullian, Fiorella Carbonardi, Ileana Carnevali, Paola Castelli, Francesco Celotto, Giulia Cini, Gino Crivellari, Duilio Della Libera, Anastasia Dell'elice, Maria Digennaro, Alessandra D'urso, Antonella Fabretto, Daniele Fanale, Irene Feroce, Daniela Furlan, Paola Ghiorzo, Mara Giacché, Milena Gusella, Barbara Liserre, Isabella Mammi, Stefania Massuras, Daniela Mazzà, Eleonora Mollica, Alberto Morabito, Giorgia Nardo, Flavia Palermo, Elena Panizza, Margherita Patruno, Monica Pedroni, Valeria Grazia Maria Pensotti, Guglielmo Niccolo Piozzi, Simonetta Pozzi, Silvia Presi, Marta Puzzono, Mila Ravegnani, Maria Teresa Ricci, Luca Roncucci, Giovanni Battsita Rossi, Elena Maria Sala, Lupe Sanchez Mete, Daniele Sandonà, Stefania Sciallero, Davide Serrano, Stefano Signoroni, Francesca Spina, Monica Taborelli, Gianluca Tedaldi, Maria Grazia Tibiletti, Silvia Tognazzo, Gianluca Tolva, Cristina Maria Concetta Trovato, Daniela Turchetti, Dora Varvara, Caterina Vivanet, Stefania Zovato, Raffaella Alessia Zuppardo, Urso E.D.L., Ponz de Leon M., Vitellaro M., Piozzi G.N., Bao Q.R., Martayan A., Remo A., Stigliano V., Oliani C., Lucci Cordisco E., Pucciarelli S., Ranzani G.N., Viel A., Adami F., Alducci E., Amadori L., Arcangeli V., Balestrino L., Barana D., Bertario L., Bonanni B., Boni S., Bullian P., Carbonardi F., Carnevali I., Castelli P., Celotto F., Cini G., Crivellari G., Libera D.D., Dell'elice A., Digennaro M., D'urso A., Fabretto A., Fanale D., Feroce I., Furlan D., Ghiorzo P., Giacche M., Gusella M., Liserre B., Mammi I., Massuras S., Mazza D., Mollica E., Morabito A., Nardo G., Palermo F., Panizza E., Patruno M., Pedroni M., Pensotti V.G.M., Pozzi S., Presi S., Puzzono M., Ravegnani M., Ricci M.T., Roncucci L., Rossi G.B., Sala E.M., Mete L.S., Sandona D., Sciallero S., Serrano D., Signoroni S., Spina F., Taborelli M., Tedaldi G., Tibiletti M.G., Tognazzo S., Tolva G., Trovato C.M.C., Turchetti D., Varvara D., Vivanet C., Zovato S., and Zuppardo R.A.
- Subjects
Oncology ,medicine.medical_specialty ,Gastrointestinal tumors ,Colorectal cancer ,Surgical Management ,Colorectal polyposis ,Germline ,03 medical and health sciences ,Cancer Genetic ,0302 clinical medicine ,MUTYH ,Internal medicine ,medicine ,Cancer Genetics ,Polyposis coli ,Hepatology ,Pathogenic mutation ,business.industry ,Colorectal polyposis not associated with APC/MUTYH mutation ,Polyposis management guideline ,Gastroenterology ,Expert consensus ,Endoscopic surveillance ,medicine.disease ,Consensus development conference ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,business - Abstract
An expert consensus panel convened by the Italian Association for Inherited and Familial Gastrointestinal Tumors (Associazione Italiana per lo Studio della Familiarita ed Ereditarieta dei Tumori Gastrointestinali, AIFEG) reviewed the literature and agreed on a number of position statements regarding the definition and management of polyposis coli without an identified pathogenic mutation on the APC or MUTYH genes, defined in the document as NAMP (non-APC/MUTYH polyposis).
- Published
- 2021
11. Colonic J-pouch or straight colorectal reconstruction after low anterior resection for rectal cancer: Impact on quality of life and bowel function: A multicenter prospective randomized study
- Author
-
Daniela Rega, Silvia De Franciscis, Giuseppe La Torre, C. R. Asteria, Dajana Cuicchi, Salvatore Pucciarelli, Francesco Marchegiani, Emilio Morpurgo, Ugo Pace, Paola Del Bianco, Elio Jovine, Paolo Delrio, Gianluca Pellino, Luigi Boccia, Luigi Zorcolo, Lorella Lotto, Francesca Giandomenico, A. Amato, Gian Luca De Salvo, Angelo Restivo, Teresa Gavaruzzi, Gaya Spolverato, Antonio Chiappa, Diego Coletta, Francesco Selvaggi, Francesco Bianco, Gavaruzzi, T., Pace, U., Giandomenico, F., Pucciarelli, S., Bianco, F., Selvaggi, F., Restivo, A., Asteria, C. R., Morpurgo, E., Cuicchi, D., Jovine, E., Coletta, D., La Torre, G., Amato, A., Chiappa, A., Marchegiani, F., Rega, D., De Franciscis, S., Pellino, G., Zorcolo, L., Lotto, L., Boccia, L., Spolverato, G., De Salvo, G. L., Delrio, P., and Del Bianco, P.
- Subjects
Quality of life ,Male ,Reconstructive surgery ,medicine.medical_specialty ,Colonic Pouche ,Constipation ,Low anterior resection ,Patient Reported Outcome Measure ,Colorectal cancer ,Colon ,Colonic Pouches ,Anastomosis ,03 medical and health sciences ,Postoperative Complications ,0302 clinical medicine ,medicine ,Humans ,Reconstructive Surgical Procedure ,Patient Reported Outcome Measures ,Bowel function ,Rectal cancer ,Patient-reported outcome ,Gynecology ,Patient-reported outcomes ,Proctectomy ,business.industry ,Rectal Neoplasms ,Anastomosis, Surgical ,Gastroenterology ,Postoperative complication ,General Medicine ,J-pouch reconstruction ,Plastic Surgery Procedures ,Middle Aged ,medicine.disease ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,Female ,Postoperative Complication ,medicine.symptom ,Pouch ,business ,Colorectal Surgery ,Human - Abstract
BACKGROUND Patient-reported outcomes associated with different bowel reconstruction techniques following anterior resection for rectal cancer are still a matter of debate. OBJECTIVE This study aimed to assess quality of life and bowel function in patients who underwent colonic J-pouch or straight colorectal anastomosis reconstruction after low anterior resection. DESIGN Bowel function and quality of life were assessed within a multicenter randomized trial. Questionnaires were administered before the surgery (baseline) and at 6, 12, and 24 months after surgery. SETTINGS Patients were enrolled by 19 centers. The enrollment started in October 2009 and was stopped in February 2016. The study was registered at www.clinicaltrials.gov (Identifier: NCT01110798). PATIENTS Patients who underwent low anterior resection for primary mid-low rectal cancer and who were randomly assigned in a 1:1 ratio to receive either stapled colonic J-pouch or straight colorectal anastomosis were selected. MAIN OUTCOME MEASURES The primary outcomes measured were quality of life and bowel function. RESULTS Of the 379 patients who were evaluable, 312 (82.3%) completed the baseline, 259 (68.3%) the 6-month, 242 (63.9%) the 12-month, and 199 (52.5%) the 24-month assessment. Bowel functioning and quality of life did not significantly differ between arms for almost all domains. The total bowel function score, the urgency, and the stool fractionation scores significantly worsened after surgery and remained impaired over time in both arms (p < 0.0032), whereas constipation improved after surgery but recovered to baseline levels from 1 year onward (p < 0.0036). All patients showed a significant and continuous improvement in emotional functioning (p < 0.0013) and future perspective (p < 0.0001) from baseline to the end of the study. LIMITATIONS Limitations of the study include missing data, which increased over time; the possibility that some treatments have slightly changed since the study was conducted; and investigators not blind to treatment allocation. CONCLUSION The findings of this study do not support the routine use of colonic J-pouch reconstruction in patients with rectal cancer who undergo a low anterior resection. See Video Abstract at http://links.lww.com/DCR/B328. BOLSA J COLONICA O RECONSTRUCCION COLORRECTAL RECTA DESPUES DE RESECCION ANTERIOR BAJA PARA CANCER RECTAL: IMPACTO EN LA CALIDAD DE VIDA Y LA FUNCION INTESTINAL: UN ESTUDIO ALEATORIZADO PROSPECTIVO MULTICENTRICO: Los resultados informados por el paciente asociados con diferentes tecnicas de reconstruccion intestinal despues de la reseccion anterior para el cancer de recto aun son tema de debate.Evaluar la calidad de vida y la funcion intestinal en pacientes que se sometieron a una bolsa en J colonica o reconstruccion de anastomosis colorrectal recta despues de una reseccion anterior baja.La funcion intestinal y la calidad de vida se evaluaron en un ensayo aleatorizado multicentrico. Los cuestionarios se administraron antes de la cirugia (basal) y a los 6, 12 y 24 meses despues de la cirugia.Los pacientes fueron incluidos en 19 centros. La inscripcion comenzo en Octubre de 2009 y se detuvo en Febrero de 2016. El estudio se registro en www.clinicaltrials.gov (Identificador: NCT01110798).Pacientes que se sometieron a reseccion anterior baja por cancer rectal primario medio-bajo y que fueron aleatorizados en una proporcion de 1: 1 para recibir bolsa J colonica con grapas o anastomosis colorrectal recta.calidad de vida y funcion intestinal.De los 379 pacientes que fueron evaluables, 312 (82.3%) completaron la evaluacion inicial, 259 (68.3%) a los 6 meses, 242 (63.9%) a los 12 meses y 199 (52.5%) a los 24 meses. . El funcionamiento intestinal y la calidad de vida no difirieron significativamente entre los dos grupos en casi todos los dominios. La puntuacion total de la funcion intestinal, la urgencia y las puntuaciones de fraccionamiento de las heces empeoraron significativamente despues de la cirugia y continuaron con el tiempo extra en ambos grupos (p
- Published
- 2020
12. miR-27a is a master regulator of metabolic reprogramming and chemoresistance in colorectal cancer
- Author
-
Gianluigi Mazzoccoli, Matteo Fassan, Maria Letizia Taddei, Sara Bruzzaniti, Vittorio Colantuoni, Giovannina Barisciano, Livio Muccillo, Francesca Bergamo, Tommaso Colangelo, Annalucia Carbone, Marco Agostini, Valeria Rosato, Fabrizio Bianchi, Giuseppe Matarese, Lina Sabatino, Salvatore Pucciarelli, Mario Galgani, Luigi Ippolito, Paola Chiarugi, Barisciano, G., Colangelo, T., Rosato, V., Muccillo, L., Taddei, M. L., Ippolito, L., Chiarugi, P., Galgani, M., Bruzzaniti, S., Matarese, G., Fassan, M., Agostini, M., Bergamo, F., Pucciarelli, S., Carbone, A., Mazzoccoli, G., Colantuoni, V., Bianchi, F., and Sabatino, L.
- Subjects
EXPRESSION ,Cancer Research ,PROMOTES ,Colorectal cancer ,MICRORNAS ,Cell ,Biology ,Article ,CELL-PROLIFERATION ,MECHANISMS ,CHEMORADIOTHERAPY ,03 medical and health sciences ,miR-27a, chemoresistance, colorectal cancer, metabolism ,0302 clinical medicine ,TARGETS ,microRNA ,medicine ,PI3K/AKT/mTOR pathway ,030304 developmental biology ,0303 health sciences ,Cell growth ,MTOR ,Cancer ,GROWTH ,medicine.disease ,Cancer metabolism ,medicine.anatomical_structure ,Oncology ,Anaerobic glycolysis ,030220 oncology & carcinogenesis ,miRNAs ,Cancer research ,Reprogramming - Abstract
BackgroundMetabolic reprogramming towards aerobic glycolysis in cancer supports unrestricted cell proliferation, survival and chemoresistance. The molecular bases of these processes are still undefined. Recent reports suggest crucial roles for microRNAs. Here, we provide new evidence of the implication of miR-27a in modulating colorectal cancer (CRC) metabolism and chemoresistance.MethodsA survey of miR-27a expression profile in TCGA-COAD dataset revealed that miR-27a-overexpressing CRCs are enriched in gene signatures of mitochondrial dysfunction, deregulated oxidative phosphorylation, mTOR activation and reduced chemosensitivity. The same pathways were analysed in cell lines in which we modified miR-27a levels. The response to chemotherapy was investigated in an independent cohort and cell lines.ResultsmiR-27a upregulation in vitro associated with impaired oxidative phosphorylation, overall mitochondrial activities and slight influence on glycolysis. miR-27a hampered AMPK, enhanced mTOR signalling and acted in concert with oncogenes and tumour cell metabolic regulators to force an aerobic glycolytic metabolism supporting biomass production, unrestricted growth and chemoresistance. This latter association was confirmed in our cohort of patients and cell lines.ConclusionsWe disclose an unprecedented role for miR-27a as a master regulator of cancer metabolism reprogramming that impinges on CRC response to chemotherapy, underscoring its theragnostic properties.
- Published
- 2020
13. Non-Operative Management Versus Total Mesorectal Excision for Locally Advanced Rectal Cancer with Clinical Complete Response After Neoadjuvant Chemoradiotherapy: a GRADE Approach by the Rectal Cancer Guidelines Writing Group of the Italian Association of Medical Oncology (AIOM)
- Author
-
Domenico Corsi, Michela Cinquini, Federica Grillo, Marco Messina, Chiara Carlomagno, Renato Cannizzaro, Carlo Aschele, Angelo Restivo, Irene De Simone, Brunella Barbaro, Gianluca Masi, Alessandro Pastorino, Gabriele Luppi, Ivan Moschetti, Giulia Capelli, Maria Antonietta Gambacorta, Francesca Valvo, Salvatore Pucciarelli, Gaya Spolverato, Sara Lonardi, Capelli, G., De Simone, I., Spolverato, G., Cinquini, M., Moschetti, I., Lonardi, S., Masi, G., Carlomagno, C., Corsi, D., Luppi, G., Gambacorta, M. A., Valvo, F., Cannizzaro, R., Grillo, F., Barbaro, B., Restivo, A., Messina, M., Pastorino, A., Aschele, C., and Pucciarelli, S.
- Subjects
Oncology ,medicine.medical_specialty ,Metanalysis ,Colorectal cancer ,Writing ,medicine.medical_treatment ,Locally advanced ,Disease ,Medical Oncology ,Neoadjuvant chemotherapy ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Metanalysi ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,GRADE Approach ,Rectal cancer ,Grading (education) ,Neoplasm Staging ,Settore MED/36 - DIAGNOSTICA PER IMMAGINI E RADIOTERAPIA ,GRADE ,Surgery ,Rectal Neoplasms ,business.industry ,Gastroenterology ,Colostomy ,Chemoradiotherapy ,medicine.disease ,Total mesorectal excision ,Neoadjuvant Therapy ,Clinical trial ,Treatment Outcome ,Neoplasm Recurrence ,Italy ,Local ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,Neoplasm Recurrence, Local ,business ,Neoadjuvant chemoradiotherapy - Abstract
Background: The standard approach for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME). After nCRT 20% of patients achieve a clinical complete response (pCR) and could be treated with a non-operative management (NOM). Methods: The panel of the Italian Association of Medical Oncology (AIOM) Guidelines on rectal cancer applied the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach addressing the following question: Should NOM vs. TME be used for patients with rectal cancer with clinical complete response after nCRT? Five outcomes were identified: disease-free survival (DFS), mortality, local recurrence, colostomy rate, and functional outcomes. Results: Nine studies were included in the analysis. A higher risk of disease recurrence was observed in the NOM group compared to the TME group (RR = 1.69, 95% CI 1.08, 2.64) on the other hand, we observed a slightly positive but not significant effect on mortality of NOM (RR = 0.82, 95% CI 0.46, 1.45). Patients in the NOM group were more likely to experience local recurrence (RR = 5.37, 95% CI 2.56, 11.27) and patients in the TME group were more likely to have a permanent colostomy (RR = 0.15, 95% CI 0.08, 0.29). Only one study evaluated functional outcomes. The overall certainty of evidence was rated as very low. Conclusions: NOM was found to correlate with a higher risk of local recurrence which did not translate in worse OS and a lower colostomy rate. Due to the paucity of evidences, no recommendations are possible. NOM remains an experimental treatment; thus, patients managed with NOM should be enrolled in clinical trials with a dedicated follow-up schedule.
- Published
- 2020
14. Long-Term Outcomes of Local Excision Following Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer
- Author
-
Antonino De Paoli, Gaya Spolverato, Lucrezia D’Alimonte, Paola Del Bianco, Giovanna Mantello, Laura Albertoni, Giulia Capelli, Mario Guerrieri, Maria Antonietta Gambacorta, Vincenzo Canzonieri, Quoc Riccardo Bao, Vincenzo Valentini, Salvatore Pucciarelli, Claudio Coco, D'Alimonte, L., Bao, Q. R., Spolverato, G., Capelli, G., Del Bianco, P., Albertoni, L., De Paoli, A., Guerrieri, M., Mantello, G., Gambacorta, M. A., Canzonieri, V., Valentini, V., Coco, C., and Pucciarelli, S.
- Subjects
Male ,medicine.medical_specialty ,Colorectal cancer ,Locally advanced ,Rectum ,Disease-Free Survival ,chemoradiotherapy ,Stoma ,Surgical oncology ,80 and over ,medicine ,Rectal Adenocarcinoma ,Humans ,Prospective Studies ,rectal cancer ,Settore MED/36 - DIAGNOSTICA PER IMMAGINI E RADIOTERAPIA ,Aged ,Neoplasm Staging ,Colorectal Cancer ,Aged, 80 and over ,Rectal Neoplasms ,business.industry ,Correction ,Chemoradiotherapy ,Middle Aged ,medicine.disease ,Total mesorectal excision ,Neoadjuvant Therapy ,Surgery ,Neoplasm Recurrence ,Treatment Outcome ,medicine.anatomical_structure ,Local ,Oncology ,Female ,Neoplasm Recurrence, Local ,business - Abstract
Background Local excision might represent an alternative to total mesorectal excision for patients with locally advanced rectal cancer who achieve a major or complete clinical response after neoadjuvant chemoradiotherapy. Methods Between August 2005 and July 2011, 63 patients with mid-low rectal adenocarcinoma who had a major/complete clinical response after neoadjuvant chemoradiotherapy were enrolled in a multicenter prospective phase 2 trial and underwent transanal full thickness local excision. The main endpoint of this study was to evaluate the 5- and 10-year overall, relapse-free, local, and distant relapse-free survival, which were calculated by applying the Kaplan–Meier method. The rate of patients with rectum preserved and without stoma were also calculated. Results Of 63 patients, 38 (60%) were male and 25 (40%) were female, with a median (range) age of 64 (25–82) years. At baseline, the following clinical stages were found: cT2, n = 21 (33.3%); cT3, n = 42 (66.6%), 39 (61.9%) patients were cN+. At a median (range) follow-up of 108 (32–166) months, the estimated cumulative 5- and 10-year overall survival, relapse-free survival, local recurrence-free survival, and distant recurrence-free survival were 87% (95% CI 76–93) and 79% (95% CI 66–87), 89% (95% CI 78–94) and 82% (95% CI 66–91), both 91% (95% CI 81–96), and 90% (95% CI 80–95) and 86% (95% CI 73–93), respectively. Overall, 49 (77.8%) patients had their rectum preserved, and 54 (84.1%) were stoma-free. Conclusion In highly selected patients, the local excision approach after neoadjuvant chemoradiotherapy is associated with excellent long-term outcomes, high rates of rectum preservation and absence of permanent stoma.
- Published
- 2020
15. Immunogenetic markers in IL17F predict the risk of metastases spread and overall survival in rectal cancer patients treated with neoadjuvant chemoradiotherapy
- Author
-
Francesca Bergamo, Marcella Montico, Giuseppe Toffoli, Luca Quartuccio, Eva Dreussi, Erika Cecchin, Chiara Zanusso, F. Navarria, E. Palazzari, Elena De Mattia, Salvatore De Vita, Claudio Belluco, Antonino De Paoli, Salvatore Pucciarelli, Angela Buonadonna, Sara Gagno, Vincenzo Canzonieri, Cecchin, E., De Mattia, E., Dreussi, E., Montico, M., Palazzari, E., Navarria, F., Bergamo, F., Belluco, C., Quartuccio, L., De Vita, S., Canzonieri, V., Gagno, S., Zanusso, C., Buonadonna, A., Pucciarelli, S., De Paoli, A., and Toffoli, G.
- Subjects
Oncology ,medicine.medical_specialty ,Colorectal cancer ,Fluoropyrimidines ,IL17F ,Immunogenetics ,Neo-adjuvant chemo-radiotherapy ,Polymorphisms ,Rectal cancer ,030218 nuclear medicine & medical imaging ,Metastasis ,Capecitabine ,Immunogenetic ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Genetic model ,medicine ,Adjuvant therapy ,Humans ,Radiology, Nuclear Medicine and imaging ,Prospective Studies ,Polymorphism ,Survival rate ,Tumor Regression Grade ,business.industry ,Rectal Neoplasms ,Interleukin-17 ,Retrospective cohort study ,Hematology ,Chemoradiotherapy ,Chemoradiotherapy, Adjuvant ,medicine.disease ,Prognosis ,Neoadjuvant Therapy ,Treatment Outcome ,030220 oncology & carcinogenesis ,Neoplasm Recurrence, Local ,business ,Fluoropyrimidine ,medicine.drug - Abstract
Background and purpose: The role of the immune system in tumor response to chemo-radiotherapy (CRT) is an emerging issue. This work aimed at identifying predictive and prognostic immunogenetic variants in LARC patients after preoperative (po)-CRT and surgery. Materials and methods: A set of 192 polymorphisms in 34 candidate genes involved in the regulation of the immune response signalling network, was selected and analyzed in 370 LARC patients treated with po-CRT and surgery, split into a Test Set (n = 233) and a Validation Set (n = 137). Immunogenetic markers were selected based on a concordant significant effect on 2-year relapse-free survival (2-yrRFS) (bootstrapped P < 0.05) in both patients Sets. The effect of the selected immunogenetic variants on 5-year metastases-free (5yrMFS), 5-year disease-free (5yrDFS), and 10-year overall (10yrOS) survival was tested in the entire Set of 370 patients. Results: Two immunogenetic IL17F (IL17F-rs641701 and IL17F-rs9463772) markers predictive of 2yrRFS, 5yrDFS, 5yrMFS, and 10yrOS were identified. The combination of tumor regression grade (TRG) and patients genotype for IL17F-rs641701 and IL17F-rs9463772 allowed the identification of subgroups of patients with differential prognosis in term of both 5yrDFS (HR 11.29, P-value
- Published
- 2020
16. BTK inhibitors synergise with 5-FU to treat drug-resistant TP53-null colon cancers
- Author
-
Fabio Pisano, Marialuisa Lavitrano, Gian-Luca Ferri, Filomena D'Amato, Emile E. Voest, Marco Agostini, Sara Bonomo, Annamaria Cialdella, Carola Missaglia, Gabriele Romano, Maria Grazia Cerrito, Kristian Helin, Roberto Giovannoni, Emanuela Grassilli, Vincenzo Canzonieri, Biagio Eugenio Leone, Barbara Noli, Leonarda Ianzano, Salvatore Pucciarelli, Chelsea M. McLean, Lavitrano, M, Ianzano, L, Bonomo, S, Cialdella, A, Cerrito, M, Pisano, F, Missaglia, C, Giovannoni, R, Romano, G, Mclean, C, Voest, E, D'Amato, F, Noli, B, Ferri, G, Agostini, M, Pucciarelli, S, Helin, K, Leone, B, Canzonieri, V, Grassilli, E, Lavitrano, Marialuisa, Ianzano, Leonarda, Bonomo, Sara, Cialdella, Annamaria, Cerrito, Maria Grazia, Pisano, Fabio, Missaglia, Carola, Giovannoni, Roberto, Romano, Gabriele, Mclean, Chelsea M, Voest, Emile E, D'Amato, Filomena, Noli, Barbara, Ferri, Gian Luca, Agostini, Marco, Pucciarelli, Salvatore, Helin, Kristian, Leone, Biagio E, Canzonieri, Vincenzo, and Grassilli, Emanuela
- Subjects
0301 basic medicine ,Colorectal cancer ,medicine.medical_treatment ,Mice, Nude ,Apoptosis ,Drug resistance ,Pathology and Forensic Medicine ,Transforming Growth Factor beta1 ,03 medical and health sciences ,0302 clinical medicine ,drug-resistance ,Antineoplastic Combined Chemotherapy Protocols ,Agammaglobulinaemia Tyrosine Kinase ,Tumor Cells, Cultured ,Gene silencing ,Medicine ,Animals ,Humans ,Protein Isoforms ,Molecular Targeted Therapy ,TP53 ,Protein Kinase Inhibitors ,Neoplasm Staging ,Chemotherapy ,business.industry ,BTK inhibitor ,Cancer ,Drug Synergism ,medicine.disease ,Genes, p53 ,Xenograft Model Antitumor Assays ,E2F Transcription Factors ,Organoids ,BTK inhibitors ,030104 developmental biology ,colon cancer ,Cell culture ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Colonic Neoplasms ,Cancer research ,Disease Progression ,Fluorouracil ,p65BTK ,business ,Tyrosine kinase ,Colon cancer - Abstract
Colorectal cancer (CRC) is the fourth cause of death from cancer worldwide mainly due to the high incidence of drug-resistance. During a screen for new actionable targets in drug-resistant tumours we recently identified p65BTK–a novel oncogenic isoform of Bruton's tyrosine kinase. Studying three different cohorts of patients here we show that p65BTK expression correlates with histotype and cancer progression. Using drug-resistant TP53-null colon cancer cells as a model we demonstrated that p65BTK silencing or chemical inhibition overcame the 5-fluorouracil resistance of CRC cell lines and patient-derived organoids and significantly reduced the growth of xenografted tumours. Mechanistically, we show that blocking p65BTK in drug-resistant cells abolished a 5-FU-elicited TGFB1 protective response and triggered E2F-dependent apoptosis. Taken together, our data demonstrated that targeting p65BTK restores the apoptotic response to chemotherapy of drug-resistant CRCs and gives a proof-of-concept for suggesting the use of BTK inhibitors in combination with 5-FU as a novel therapeutic approach in CRC patients. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
- Published
- 2020
17. The INTERACT Trial: Long-term results of a randomised trial on preoperative capecitabine-based radiochemotherapy intensified by concomitant boost or oxaliplatin, for cT2 (distal)–cT3 rectal cancer
- Author
-
Francesco Cellini, Sara Lonardi, Brunella Barbaro, Giuseppe La Torre, Angela Buonadonna, F. Navarria, Antonino De Paoli, Fabio Maria Vecchio, M.C. Barba, Giovanna Mantello, Domenico D'Ugo, Roberto Persiani, Alessio G. Morganti, Francesco Deodato, Claudio Belluco, Ernesto Maranzano, Domenico Genovesi, Sergio Alfieri, Maria Antonietta Gambacorta, Giovanni Battista Doglietto, Cynthia Aristei, Antonio Crucitti, Marco Lupattelli, Vincenzo Valentini, Luciana Caravatta, Claudio Coco, Caterina Boso, Salvatore Pucciarelli, Valentini V., Gambacorta M.A., Cellini F., Aristei C., Coco C., Barbaro B., Alfieri S., D'Ugo D., Persiani R., Deodato F., Crucitti A., Lupattelli M., Mantello G., Navarria F., Belluco C., Buonadonna A., Boso C., Lonardi S., Caravatta L., Barba M.C., Vecchio F.M., Maranzano E., Genovesi D., Doglietto G.B., Morganti A.G., La Torre G., Pucciarelli S., and De Paoli A.
- Subjects
Male ,Oxaloacetates ,Colorectal cancer ,medicine.medical_treatment ,030218 nuclear medicine & medical imaging ,law.invention ,0302 clinical medicine ,Randomized controlled trial ,law ,Nuclear Medicine and Imaging ,Antineoplastic Combined Chemotherapy Protocols ,Pathologic complete response ,Prospective Studies ,Rectal cancer ,Boost ,Chemoradiation ,Oxaliplatin ,Preoperative radiochemotherapy ,Settore MED/36 - DIAGNOSTICA PER IMMAGINI E RADIOTERAPIA ,Aged, 80 and over ,Chemoradiotherapy ,Hematology ,Middle Aged ,Oncology ,030220 oncology & carcinogenesis ,Toxicity ,Female ,Radiology, Nuclear Medicine and Imaging ,Radiology ,medicine.drug ,Adult ,medicine.medical_specialty ,Capecitabine ,03 medical and health sciences ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Aged ,Chemotherapy ,Rectal Neoplasms ,business.industry ,medicine.disease ,Surgery ,Radiation therapy ,Concomitant ,business - Abstract
Background and purpose: Capecitabine-based radiochemotherapy (cbRCT) is standard for preoperative long-course radiochemotherapy of locally advanced rectal cancer. This prospective, parallel-group, randomised controlled trial investigated two intensification regimens. cT4 lesions were excluded. Primary objective: pathological outcome (TRG 1-2) among arms.Materials and methods: Low-located cT2N0-2M0, cT3N0-2M0 (up to 12 cm from anal verge) presentations were treated with cbRCT randomly intensified by either radiotherapy boost (Xelac arm) or multidrug concomitant chemotherapy (Xelox arm). Xelac: concomitant boost to bulky site (45 Gy/1.8 Gy/die, 5 sessions/week to the pelvis, + 10 Gy at 1 Gy twice/week to the bulky) plus concurrent capecitabine (1650 mg/mq/die). Xelox: 45 Gy to the pelvis + 5.4 Gy/1.8 Gy/die, 5 sessions/week to the bulky site + concurrent capecitabine (1300 mg/mq/die) and oxaliplatin (130 mg/mq on days 1,19,38). Surgery was planned 7-9 weeks after radiochemotherapy.Results: From June 2005 to September 2013, 534 patients were analysed: 280 in Xelac, 254 in Xelox arm. Xelox arm presented higher G >= 3 haematologic (p = 0.01) and neurologic toxicity (p < 0.001). Overall, 98.5% patients received curative surgery. The tumour regression grade distribution did not differ between arms (p = 0.102). TRG 1+2 rate significantly differed: Xelac arm 61.7% vs. Xelox 52.3% (p = 0.039). Pathological complete response (ypT0N0) rates were 24.4 and 23.8%, respectively (p non-significant). Median follow-up: 5.62 years. Five-year disease-free survival rate were 74.7% (Xelac) and 73.8% (Xelox), respectively (p = 0.444). Five-year overall survival rate were 80.4% (Xelac) and 85.5% (Xelox), respectively (p = 0.155).Conclusion: Xelac arm significantly obtained higher TRG1-2 rates. No differences were found about clinical outcome. Because of efficacy on TRG, inferior toxicity and good compliance, Xelac schedules or similar radiotherapy dose intensification schemes could be considered as reference treatments for cT3 lesions. (C) 2018 Published by Elsevier B.V.
- Published
- 2019
18. Assessment of intratumor immune-microenvironment in colorectal cancers with extranodal extension of nodal metastases
- Author
-
Edoardo D'Angelo, Fotios Loupakis, Giuseppe Nicolò Fanelli, Giada Munari, Nicola Veronese, Diana Sacchi, Claudia Mescoli, Matteo Fassan, Sara Lonardi, Massimo Rugge, Luca Vianello, Salvatore Pucciarelli, Marco Agostini, Nicola Valeri, Marco Scarpa, Cristiano Lanza, Claudio Luchini, Rocco Cappellesso, Roberta Salmaso, Fassan, M., Vianello, L., Sacchi, D., Fanelli, G.N., Munari, G., Scarpa, M., Cappellesso, R., Loupakis, F., Lanza, C., Salmaso, R., Mescoli, C., Valeri, N., Agostini, M., D'Angelo, E., Lonardi, S., Pucciarelli, S., Veronese, N., Luchini, C., and Rugge, M.
- Subjects
0301 basic medicine ,Neuroblastoma RAS viral oncogene homolog ,Cancer Research ,Colorectal cancer ,Biomarkers ,Extranodal extension ,Metastasis ,Oncology ,Genetics ,PDGFRA ,medicine.disease_cause ,lcsh:RC254-282 ,not known ,03 medical and health sciences ,0302 clinical medicine ,medicine ,PTEN ,lcsh:QH573-671 ,neoplasms ,biology ,business.industry ,lcsh:Cytology ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Primary tumor ,digestive system diseases ,030104 developmental biology ,030220 oncology & carcinogenesis ,biology.protein ,Cancer research ,Immunohistochemistry ,KRAS ,business ,Primary Research - Abstract
Background: No data is available on the molecular background of the extra-nodal extension (ENE) of lymph node metastasis (LN) in colorectal cancer (CRC). Methods: A series of 22 ENE-positive CRCs was considered and three samples per case were selected (the primary CRC, an ENE-negative and an ENE-positive metastatic LN). Samples (n=66) were analysed by immunohistochemistry for PD-L1, CD4, CD8, CD68 and CD80. Fifteen out of twenty-two cases were further profiled through a hotspot multigene mutational custom panel, including 164 hotspot regions of AKT1, APC, BRAF, CTNNB1, KIT, KRAS, NRAS, PDGFRA, PIK3CA, PTEN and TP53 genes. Results: A significantly higher percentage of CD4-, CD8- and CD68-positive cells was observed at the invasive front of both CRCs and in ENE in contrast with what observed at the core of both CRCs and their matched nodal metastases. ENE was also characterized by a significantly higher number of CD80-positive cells. No significant difference was observed in PD-L1 distribution among the different specimens. Fourteen out of 15 CRCs (93%) showed at least a driver mutation. The most frequently mutated gene was TP53 (n=8 tumors), followed by APC (n=6), BRAF (n=4), KRAS, NRAS and PIK3CA (n=2). In 11 out of 15 CRCs (73%) the mutational profiling of the primary tumor was consistent with what obtained from the two matched LNs. Conclusions: A heterogeneous intratumor immune-microenvironment has been observed in ENE-positive CRCs, which are characterized by an increased leukocytic infiltration at the ENE invasive front. © 2018 The Author(s).
- Published
- 2018
19. A functional biological network centered on XRCC3: a new possible marker of chemoradiotherapy resistance in rectal cancer patients
- Author
-
Marco Agostini, Maura Digito, Claudia Mescoli, Andrea Zangrando, Chiara Bedin, Carlo Zanon, Igor Jurisica, Marialuisa Lavitrano, Giovanni Esposito, Roberto Giovannoni, Edoardo D'Angelo, Donato Nitti, Chiara Pastrello, Marco Giordan, Salvatore Pucciarelli, Flavio Rizzolio, Gabriele Romano, Antonio Giordano, Isacco Maretto, Agostini, M, Zangrando, A, Pastrello, C, D'Angelo, E, Romano, G, Giovannoni, R, Giordan, M, Maretto, I, Bedin, C, Zanon, C, Digito, M, Esposito, G, Mescoli, C, Lavitrano, M, Rizzolio, F, Jurisica, I, Giordano, A, Pucciarelli, S, and Nitti, D
- Subjects
Oncology ,Male ,Pathology ,Cancer Research ,Colorectal cancer ,Drug Resistance ,RC, Rectal cancer ,Preoperative chemoradiotherapy ,DSB ,HT ,CRT, Chemoradiotherapy ,Carcinoembryonic antigen ,CEA ,Protein-protein interaction ,XRCC3 ,Tumor Cells, Cultured ,High throughput ,Rectal cancer ,pCRT ,Gy ,SNP, Single nucleotide polymorphism ,Tumor Regression Grade ,biological network ,Single-strand breaks ,Tumor ,Cultured ,biology ,Chemoradiotherapy ,Small interfering RNA ,Middle Aged ,DSB, Double-strand break ,integrated approach ,Tumor Cells ,HT, High throughput ,Gene Expression Regulation, Neoplastic ,DNA-Binding Proteins ,Treatment Outcome ,Gene Knockdown Techniques ,siRNA, Small interfering RNA ,Adenocarcinoma ,Molecular Medicine ,CRT ,Female ,Biological network ,Integrated approach ,Microarray ,Treatment response ,microarray ,Adult ,PPI, Protein-protein interaction ,RIN, RNA integrity number ,medicine.medical_specialty ,Double-strand breaks ,PPI ,mRNA ,SNP ,Settore BIO/11 - Biologia Molecolare ,Young Adult ,Internal medicine ,medicine ,Biomarkers, Tumor ,Humans ,SSB ,Aged ,Pharmacology ,CEA, carcinoembryonic antigen ,DSB, Double-strand breaks ,Gy, Gray ,SSB, Single-strand breaks ,mRNA, mRNA ,pCRT, Preoperative chemoradiotherapy ,preoperative chemoradiotherapy ,rectal cancer ,treatment response ,Drug Resistance, Neoplasm ,Gene Expression Profiling ,Multivariate Analysis ,Rectal Neoplasms ,Neoplastic ,carcinoembryonic antigen ,RIN ,medicine.disease ,Molecular medicine ,Gray ,RC ,RNA integrity number ,Single nucleotide polymorphism ,siRNA ,Gene expression profiling ,Gene Expression Regulation ,SSB, Single-strand break ,biology.protein ,Clinical Study ,Neoplasm ,Biomarkers - Abstract
Preoperative chemoradiotherapy is widely used to improve local control of disease, sphincter preservation and to improve survival in patients with locally advanced rectal cancer. Patients enrolled in the present study underwent preoperative chemoradiotherapy, followed by surgical excision. Response to chemoradiotherapy was evaluated according to Mandard’s Tumor Regression Grade (TRG). TRG 3, 4 and 5 were considered as partial or no response while TRG 1 and 2 as complete response. From pretherapeutic biopsies of 84 locally advanced rectal carcinomas available for the analysis, only 42 of them showed 70% cancer cellularity at least. By determining gene expression profiles, responders and non-responders showed significantly different expression levels for 19 genes (P < 0.001). We fitted a logistic model selected with a stepwise procedure optimizing the Akaike Information Criterion (AIC) and then validated by means of leave one out cross validation (LOOCV, accuracy D 95%). Four genes were retained in the achieved model: ZNF160, XRCC3, HFM1 and ASXL2. Real time PCR confirmed that XRCC3 is overexpressed in responders group and HFM1 and ASXL2 showed a positive trend. In vitro test on colon cancer resistant/susceptible to chemoradioterapy cells, finally prove that XRCC3 deregulation is extensively involved in the chemoresistance mechanisms. Protein-protein interactions (PPI) analysis involving the predictive classifier revealed a network of 45 interacting nodes (proteins) with TRAF6 gene playing a keystone role in the network. The present study confirmed the possibility that gene expression profiling combined with integrative computational biology is useful to predict complete responses to preoperative chemoradiotherapy in patients with advanced rectal cancer.
- Published
- 2015
20. Outcome and prognostic factors of local recurrent rectal cancer: a pooled analysis of 150 patients
- Author
-
F. Caminati, Guido Sciaudone, C. Fucini, Gianluca Pellino, Salvatore Pucciarelli, Isabella Mondi, N. Bartolini, Francesco Selvaggi, Isacco Maretto, Selvaggi, Francesco, Fucini, C, Pellino, Gianluca, Sciaudone, Guido, Maretto, I, Mondi, I, Bartolini, N, Caminati, F, and Pucciarelli, S.
- Subjects
Adult ,Male ,medicine.medical_specialty ,Survival ,Colorectal cancer ,medicine.medical_treatment ,Kaplan-Meier Estimate ,recurrent rectal cancer ,Local recurrence ,Humans ,Medicine ,Local recurrence, PET, Rectal cancer, Surgery for local recurrence, Survival ,Stage (cooking) ,Rectal cancer ,Surgery for local recurrence ,Colectomy ,Survival analysis ,Aged ,Neoplasm Staging ,Retrospective Studies ,Aged, 80 and over ,medicine.diagnostic_test ,Rectal Neoplasms ,business.industry ,Gastroenterology ,Middle Aged ,Prognosis ,medicine.disease ,Combined Modality Therapy ,Colorectal surgery ,Surgery ,Radiation therapy ,Logistic Models ,Treatment Outcome ,PET ,Italy ,Positron emission tomography ,Positron-Emission Tomography ,Resection margin ,Female ,Neoplasm Recurrence, Local ,business ,Abdominal surgery - Abstract
Surgery is the only curative treatment in patients with locally recurrent rectal cancer (LRRC). The aim of this study was to evaluate the outcome and the prognostic factors of tumour-free resection margin (R0) and overall survival (OS) in LRRC. METHODS: Consecutive LRRC patients observed between 1987 and 2005 in three Italian university hospitals were evaluated. Survival curves were estimated using the Kaplan-Meier method and compared with the log-rank test. In order to identify factors associated with both R0 resection and OS, a logistic regression analysis was performed in patients who underwent surgery with curative intent. RESULTS: Out of 150 patients with LRRC, 107 underwent surgery, but since 7 were found to have unresectable disease only 100 underwent surgical resection. Of them, 51 underwent radical and 49 extended resection. Sixty of the 107 patients underwent multimodality treatment. In 61 patients, R0 resection was achieved. Median OS after surgery was 43.4 months. In patients, who had surgery with curative intent, independent variables associated with R0 resection were: surgery for the primary tumour performed in other hospitals (p = 0.042) extended resection (p = 0.025) and use of positron emission tomography (PET) as a staging modality (p = 0.03). Independent variables associated with OS were: post-operative radiotherapy (p = 0.004), stage of the primary tumour (p = 0.004), R0 resection (p = 0.00001), and use of PET (0.02). CONCLUSIONS: Resection for LRRC results in improved survival. Other than the well-known prognostic factors R0 resection and OS, PET scan has an independent impact both on OS and R0 resection. It should therefore be included in routine clinical practice when staging LRRC.
- Published
- 2015
21. Multiplexed protein signal pathway mapping identifies patients with rectal cancer that responds to neoadjuvant treatment
- Author
-
Antonino De Paoli, Pierluigi Pilati, Enzo Mammano, Vincenzo Canzonieri, Claudio Belluco, Emanuela Tessari, Francesca Galdi, Emanuel F. Petricoin, Donato Nitti, Jianghong Deng, Mariaelena Pierobon, Lance A. Liotta, Francesco De Marchi, Salvatore Pucciarelli, Marco Agostini, Mammano, E, Galdi, F, Pierobon, M, Tessari, E, Deng, J, Pucciarelli, S, Agostini, M, De Marchi, F, Canzonieri, V, De Paoli, A, Belluco, C, Liotta, L, Petricoin, E, Pilati, P, and Nitti, D.
- Subjects
neoadjuvant treatment ,Adult ,Male ,Oncology ,Pathology ,medicine.medical_specialty ,Predictive marker ,protein kinase ,Rectal cancer ,Colorectal cancer ,Population ,Protein Array Analysis ,Protein Serine-Threonine Kinases ,Article ,law.invention ,Glycogen Synthase Kinase 3 ,Text mining ,Randomized controlled trial ,law ,Internal medicine ,Biomarkers, Tumor ,Humans ,Medicine ,Phosphorylation ,education ,beta Catenin ,Aged ,Laser capture microdissection ,education.field_of_study ,Rectal Neoplasms ,business.industry ,Gastroenterology ,Pyruvate Dehydrogenase Acetyl-Transferring Kinase ,Middle Aged ,Prognosis ,medicine.disease ,Neoadjuvant Therapy ,Checkpoint Kinase 2 ,Protein microarray ,Female ,Neoplasm Grading ,Signal transduction ,business ,Proto-Oncogene Proteins c-akt ,Follow-Up Studies ,Signal Transduction - Abstract
Currently there is no reliable technique for predicting clinical or pathologic complete tumor response after radiochemotherapy (RCT) in patients with rectal cancer. We applied reverse phase protein microarray (RPMA) technology to find a signal pathway that may predict the response to preoperative treatment.Fifteen rectal cancer samples were collected during preoperative RCT. Seven patients had a good response to preoperative therapy (Mandard grade I-II) and 8 patients had a poor response (Mandard grade III-V). Using laser capture microdissection (LCM) and RPMA analysis, we measured the phosphorylation level of nearly 80 end points and analyzed the signaling pathways.We identified 4 signaling proteins whose phosphorylation levels were significantly different (P.05) between the good vs. poor responders; CHK2 and β-catenin were more highly phosphorylated in poor responders, whereas PDK1 and glycogen synthase kinase (GSK)-3α/β had lower phosphorylation levels in poor responders. Interestingly GSK-3α/β, β-catenin, and PDK1 are all present in the phosphatidylinositol-3-kinase (PI3K)-AKT signaling pathway.Based on our results, we hypothesize that the activating state of the PI3K-AKT pathway can stratify patients who could benefit most from neoadjuvant treatment. Moreover, identification of theranostic targets has the potential to pinpoint new therapeutic strategies for the nonresponsive population.
- Published
- 2012
22. Tumor response is predicted by patient genetic profile in rectal cancer patients treated with neo-adjuvant chemo-radiotherapy
- Author
-
Erika Cecchin, Donato Nitti, Maria Luisa Friso, Salvatore Pucciarelli, Giuseppe Toffoli, Vincenzo Canzonieri, E. De Mattia, Paola Biason, A. De Paoli, Michele Visentin, Marco Agostini, Roberto Sigon, Cecchin, E, Agostini, M, Pucciarelli, S, De Paoli, A, Canzonieri, V, Sigon, R, De Mattia, E, Friso, Ml, Biason, P, Visentin, M, Nitti, D, and Toffoli, G
- Subjects
Adult ,Male ,Oncology ,medicine.medical_specialty ,Genotype ,Colorectal cancer ,Rectum ,Thiophenes ,Neo adjuvant ,chemo-radiotherapy ,Bioinformatics ,Tumor response ,Polymorphism, Single Nucleotide ,Genetic profile ,polymorphism ,pharmacogenetics ,5-fluorouracil ,hemic and lymphatic diseases ,Internal medicine ,Genetics ,medicine ,Humans ,neoplasms ,Genetic Association Studies ,Aged ,Neoplasm Staging ,Pharmacology ,Chemo-radiotherapy ,Rectal Neoplasms ,business.industry ,Gene Expression Profiling ,Middle Aged ,medicine.disease ,Multidrug Resistance-Associated Protein 2 ,Neoadjuvant Therapy ,stomatognathic diseases ,Treatment Outcome ,medicine.anatomical_structure ,Quinazolines ,Molecular Medicine ,Female ,Fluorouracil ,business ,Pharmacogenetics - Abstract
The aim of the study was the identification of a pharmacogenetic profile predictive of the tumor regression grade (TRG), considered as tumor response parameter, after neo-adjuvant treatment in rectal cancer patients. A total of 238 rectal cancer patients treated in a neo-adjuvant setting by a fluoropyrimidines-based chemo-radiotherapy (RT) were genotyped for 25 genetic polymorphisms in 16 genes relevant for treatment-associated pathways. Two polymorphisms were associated with TRG in a multivariate analysis: hOGG1-1245C>G, which can affect radiosensitivity and MTHFR-677C>T, which is involved in fluoropyrimidines action. Patients bearing at least one variant allele had a lower chance to get TRG T, which is responsible for the multi-drug resistance (odds ratio (OR)=1.96, 95% confidence interval (CI) 0.98-3.95, P=0.057). Exploratory classification and regression tree (CART) analysis highlighted high-order gene-gene and gene-environment interactions and a genetic signature associated with differential response, with hOGG1-1245C>G as the most predictive factor. Other significant variables were: ABCB1-3435C>T, MTHFR-677C>T, ERCC1-8092C>A, ABCC2-1249G>A, XRCC1-28152G>A, XRCC3-4541A>G and patients gender. On the basis of CART results, patients were categorized into three groups according to tumor response probability: intermediate and high profiles had a higher probability to get TRG G and MTHFR-677C>T polymorphisms in the tumor response of rectal cancer patients treated with chemo-RT in neo-adjuvant setting, and shows the relevance of gene-gene and gene-environment interactions for complex phenotypes as tumor response. The Pharmacogenomics Journal (2011) 11, 214-226; doi:10.1038/tpj.2010.25; published online 6 April 2010
- Published
- 2011
23. A ten markers panel provides a more accurate and complete microsatellite instability analysis in mismatch repair-deficient colorectal tumors
- Author
-
Claudia Mescoli, Emanuele Damiano Luca Urso, Donato Nitti, Luca Morandi, Silvia Pizzini, Salvatore Pucciarelli, Marco Agostini, Roberta Bertorelle, Maria Vittoria Enzo, Silvia Mason, Chiara Bedin, Mario Lise, Agostini, M, Enzo, Mv, Morandi, L, Bedin, C, Pizzini, S, Mason, S, Bertorelle, R, Urso, E, Mescoli, C, Lise, M, Pucciarelli, S, and Nitti, D.
- Subjects
congenital, hereditary, and neonatal diseases and abnormalities ,Cancer Research ,Colorectal cancer ,DNA Mutational Analysis ,mononuclotide repeats ,Biology ,MLH1 ,DNA Mismatch Repair ,Polymerase Chain Reaction ,Multiplex polymerase chain reaction ,Biomarkers, Tumor ,medicine ,Genetics ,Humans ,neoplasms ,Adaptor Proteins, Signal Transducing ,Mononuclotide repeat ,Nuclear Proteins ,Microsatellite instability ,nutritional and metabolic diseases ,colorectal cancer ,General Medicine ,DNA Methylation ,medicine.disease ,Colorectal Neoplasms, Hereditary Nonpolyposis ,Immunohistochemistry ,digestive system diseases ,DNA-Binding Proteins ,MutS Homolog 2 Protein ,Oncology ,Cancer research ,Microsatellite ,DNA mismatch repair ,Microsatellite Instability Analysis ,MutL Protein Homolog 1 - Abstract
UNLABELLED Tumour microsatellite instability (MSI) is useful in identifying patients with hereditary non-polyposis colorectal cancer (HNPCC) with defective DNA mismatch repair (MMR) genes. A reference Bethesda panel has limitations resulting from the inclusion of dinucleotide markers, which are less sensitive and specific for detection of tumours with MMR deficiencies. We developed a multiplex PCR assay with additional four mononucleotide markers and one dinucleotide marker (NR-21, NR-24, BAT-40, TGF-BetaR and D18S58) for a rapid and proper classification of MSI-H, MSI-L and MSS colorectal cancers. Two tetranucleotide markers were added to identify sample mix-ups and/or contamination. RESULTS all the 44 cases test cases were in agreement with previous classification except for three cases: one case MSI-H-Bethesda unstable only for dinucleotides markers shifted to MSI-L category and two cases MSI-L-Bethesda unstable for mononucleotide markers shifted to MSI-H category. Immunohistochemistry analysis revealed that these two MSI-H cases did not expressed hMLH1 and they were found to be methylated at the MLH1 promoter, while the first one that shifted to MSI-L showed MMR protein expression. CONCLUSION a complete panel of ten markers including four dinucleotide and six mononucleotide microsatellites allows accurate evaluation of tumor MSI status.
- Published
- 2009
24. Prediction of rectal lymph node metastasis by pelvic computed tomography measurement
- Author
-
Pier Carlo Muzzio, Alessandro Ambrosi, Isacco Maretto, E. Urso, Massimo Rugge, S Burzi, M. Zandonà, Fabio Pomerri, Salvatore Pucciarelli, Donato Nitti, Pomerri, F, Maretto, I, Pucciarelli, S, Rugge, M, Burzi, S, Zandona, M, Ambrosi, Alessandro, Urso, E, Muzzio, Pc, and Nitti, D.
- Subjects
Adult ,Male ,medicine.medical_specialty ,Colorectal cancer ,ENDORECTAL ULTRASOUND ,PREOPERATIVE CHEMORADIATION ,Adenocarcinoma ,Metastasis ,CHEMORADIOTHERAPY ,Predictive Value of Tests ,LOCAL EXCISION ,Abdomen ,Rectal cancer staging ,Lymph node status ,medicine ,Rectal Adenocarcinoma ,Humans ,Lymph node ,Aged ,Neoplasm Staging ,Retrospective Studies ,Aged, 80 and over ,Rectal Neoplasms ,business.industry ,TOTAL MESORECTAL EXCISION ,Reproducibility of Results ,General Medicine ,Middle Aged ,medicine.disease ,CANCER ,RANDOMIZED-TRIAL ,COMBINED-MODALITY THERAPY ,medicine.anatomical_structure ,Oncology ,Lymphatic Metastasis ,Predictive value of tests ,COMPLETE PATHOLOGICAL RESPONSE ,Female ,Surgery ,Lymph Nodes ,Radiology ,Lymph ,Tomography, X-Ray Computed ,business ,Chemoradiotherapy ,Follow-Up Studies ,RADIOTHERAPY - Abstract
Aim Rectal cancer staging represents a crucial step to select the best treatment for this tumour. Particularly after neo-adjuvant chemoradiotherapy (CRT), it may influence the surgical procedure (e.g. radical resection vs. local excision). The aim of this study was to determine the best lymph node size cut-off at computed tomography (CT) to predict nodal metastasis in rectal cancer patients with and without preoperative CRT. Methods A consecutive series of patients operated on for primary mid–low rectal adenocarcinoma, all staged with pelvic CT scan, were subdivided as follows: those who underwent surgery alone treatment without CRT (Group A) and those who underwent preoperative CRT (Group B). All CT scans were re-viewed by a single radiologist and, based on the lymph node size, findings were compared with pathologic lymph node status (pN). At each lymph node size cut-off value, the following were calculated: accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). The best cut-off value was defined as having an accuracy ≥70% with the highest NPV. Results The study population consisted of 162 patients: Group A ( n = 52) and Group B ( n = 110). Patients classified as pN-positive ( n = 45) had a higher number of and larger sized lymph nodes by CT scan than patients classified as pN-negative ( n = 117). The cut-off values with an accuracy ≥70% ranged between 7 and 11 mm in Group A and between 9 and 14 mm in Group B. The cut-off with the best NPV was 7 mm for Group A and 10 mm for Group B. Conclusions Acknowledging the limitations of the dimensional criterion, lymph node size cut-off values found in our study may be useful for planning rectal cancer treatment using CT scan.
- Published
- 2009
25. A haplotype of the methylenetetrahydrofolate reductase gene predicts poor tumor response in rectal cancer patients receiving preoperative chemoradiation
- Author
-
Donato Nitti, Veronica Lisi, Mario Lise, Salvatore Pucciarelli, Maria Luisa Friso, Salvatore Terrazzino, Alberta Leon, Alessandro Ambrosi, Marco Agostini, Lara Maria Pasetto, Terrazzino, S, Agostini, M, Pucciarelli, S, Pasetto, Lm, Friso, Ml, Ambrosi, Alessandro, Lisi, V, Leon, A, Lise, M, and Nitti, D.
- Subjects
Adult ,Male ,Antimetabolites, Antineoplastic ,medicine.medical_specialty ,Genotype ,Colorectal cancer ,tumor regression grade ,Single-nucleotide polymorphism ,Adenocarcinoma ,Radiation Dosage ,germline polymorphism ,MTHFR haplotype ,preoperative chemoradiation ,rectal cancer ,Gastroenterology ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Genetics ,medicine ,Humans ,General Pharmacology, Toxicology and Pharmaceutics ,Molecular Biology ,Methylenetetrahydrofolate Reductase (NADPH2) ,Genetics (clinical) ,Aged ,Neoplasm Staging ,Tumor Regression Grade ,Polymorphism, Genetic ,Predictive marker ,biology ,Rectal Neoplasms ,Remission Induction ,Haplotype ,Cancer ,Middle Aged ,Prognosis ,medicine.disease ,Combined Modality Therapy ,Variable number tandem repeat ,Haplotypes ,Chemotherapy, Adjuvant ,Methylenetetrahydrofolate reductase ,biology.protein ,Molecular Medicine ,Female ,Radiotherapy, Adjuvant ,Fluorouracil - Abstract
OBJECTIVE: The objective of the present study was to evaluate whether germline methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms as well as polymorphisms in the thymidylate synthase gene promoter, namely the variable number tandem repeat polymorphism (TS VNTR) and the intrarepeat G to C single nucleotide polymorphism (TS SNP), are predictive markers of tumor regression in rectal cancer patients following preoperative chemoradiotherapy. BASIC METHODS: Blood samples from 125 patients with primary adenocarcinoma of the mid-low rectum who received 5-fluorouracil-based chemotherapy and external beam radiotherapy (median dose 48.4 Gy), 125 patients (women n=45, men n=80; median age 60 years, range 31-79 years) were genotyped. Response to preoperative treatment was evaluated employing the Tumor Regression Grade criteria. On the basis of the pathologic response, patients were classified as responders (TRG 1-2, n=48) and non-responders (TRG 3-5, n=74). Three patients were excluded because of insufficient data. MAIN RESULTS: Among the polymorphic variants examined, the MTHFR 677T-1298A haplotype was, upon univariate analysis, the only variable found associated with tumor regression (P=0.004). Moreover, at multivariate analysis, the MTHFR 677T-1298A haplotype was an independent predictor of tumor regression. Patients not carrying the MTHFR 677T-1298A haplotype (odds ratio 0.29, 95% confidence interval 0.13-0.64, P=0.002) displayed a higher response rate than patients with the MTHFR 677T-1298A haplotype. CONCLUSIONS: Unlike TS VNTR and SNP polymorphisms, MTHFR 677T-1298A haplotype in genomic DNA has the potential to be a predictive marker of tumor response in rectal cancer patients submitted to preoperative chemoradiotherapy.
- Published
- 2006
26. Preoperative chemoradiation and local excision for selected T2-T3 rectal cancer patients
- Author
-
A. De Paoli, Giovanni Boz, Roberto Innocente, Maria Luisa Friso, Roberto Sigon, Carlo Riccardo Rossi, Donato Nitti, Vincenzo Canzonieri, Marco Trovo, Salvatore Pucciarelli, De Paoli, A, Sigon, R, Pucciarelli, S, Innocente, R, Friso, M, Boz, G, Canzonieri, V, Nitti, D, Trovo, M, and Rossi, C
- Subjects
Cancer Research ,Local excision ,medicine.medical_specialty ,Preoperative chemoradiotherapy ,Radiation ,Oncology ,Colorectal cancer ,business.industry ,medicine ,Radiology, Nuclear Medicine and imaging ,Radiology ,medicine.disease ,business - Published
- 2005
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.