Publications by authors named "Roberto Coppola"

109 Publications

Application of minimally invasive pancreatic surgery: an Italian survey.

Updates Surg 2019 Mar 16;71(1):97-103. Epub 2018 May 16.

Humanitas University, Rozzano, MI, Italy.

The value of minimally invasive pancreatic surgery (MIPS) is still debated. To assess the diffusion of MIPS in Italy and identify the barriers preventing wider implementation, a questionnaire was developed under the auspices of three Scientific Societies (AISP, It-IHPBA, SICE) and was sent to the largest possible number of Italian surgeons also using the mailing list of the two main Italian Surgical Societies (SIC and ACOI). The questionnaire consisted of 25 questions assessing: centre characteristics, facilities and technologies, type of MIPS performed, surgical techniques employed and opinions on the present and future value of MIPS. Only one reply per unit was considered. Fifty-five units answered the questionnaire. While 54 units (98.2%) declared to perform MIPS, the majority of responders were not dedicated to pancreatic surgery. Twenty-five units (45.5%) performed < 20 pancreatic resections/year and 39 (70.9%) < 10 MIPS per year. Forty-nine units (89.1%) performed at least one minimally invasive (MI) distal pancreatectomy (DP), and 10 (18.2%) at least one MI pancreatoduodenectomy (PD). Robotic assistance was used in 18 units (31.7%) (14 DP, 7 PD). The major constraints limiting the diffusion of MIPS were the intrinsic difficulty of the technique and the lack of specific training. The overall value of MIPS was highly rated. Our survey illustrates the current diffusion of MIPS in Italy and underlines the great interest for this approach. Further diffusion of MIPS requires the implementation of standardized protocols of training. Creation of a prospective National Registry should also be considered.
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http://dx.doi.org/10.1007/s13304-018-0535-3DOI Listing
March 2019

Neutrophil to lymphocyte ratio predicts risk of nodal involvement in T1 colorectal cancer patients.

Minerva Chir 2018 Oct 12;73(5):475-481. Epub 2018 Apr 12.

Department of Surgery, University Campus Bio-Medico of Rome, Rome, Italy.

Background: Risk of nodal involvement in T1 colorectal cancer is assessed by tumor histological features. In several tumors, the ratio between neutrophils and lymphocytes (NLR) or platelets and lymphocytes (PLR) have been applied to lymph-node metastases prediction. The aim of this study was to evaluate the role of NLR, derived NLR (dNLR) and PLR in predicting nodal involvement in T1 colorectal cancers.

Methods: NLR, dNLR and PLR in surgical resected T1 colorectal cancers were retrospectively calculated and analysed in nodal positive and negative cases.

Results: Data regarding 102 patients were considered. Nodal involvement rate was 10.8%. NLR values were higher in node positive patients (P=0.04). A trend toward significance (P=0.05) was found for higher dNLR values and positive nodal status. For NLR, ROC curve analysis allowed to choose a predictive cut-off value of 3.7 (AUC of 0.69; 95% CI: 0.48-0.89). Nodal positivity was reported in 71.5% of high NLR patients; only two N0 cases (28.5%) were registered in high NLR group (P<0.001). The logistic regression analysis aimed to evidence the predictive role of high NLR in node positivity resulted in a significant OR of 37.1 (P<0.0001; 95% CI: 0.48-0.89). NLR allowed to distinguish N0 from N1 patients in 99.4% of cases.

Conclusions: NLR<3.7 was associated with lower risk of lymph-node metastases in T1 colorectal cancer patients. NLR could be used with histopathological data to identify patients at lower risk of nodal metastases.
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http://dx.doi.org/10.23736/S0026-4733.18.07430-8DOI Listing
October 2018

The role of procalcitonin in the diagnosis of bacterial infection after major abdominal surgery: Advantage from daily measurement.

Medicine (Baltimore) 2018 Jan;97(3):e9496

Internal Medicine Department, University Campus Bio-Medico of Rome, Rome Internal Medicine Department, University G. D'Annunzio, Chieti Department of Surgery, University Campus Bio-Medico of Rome Department of Public Health and Infectious Diseases, Sapienza University of Rome Unit of Clinical Laboratory Science, University Campus Bio-Medico of Rome, Rome, Italy.

Postsurgical infections represent an important cause of morbidity after abdominal surgery. The microbiological diagnosis is not achieved in at least 30% of culture with consequent worsening of patient outcome. In this study, procalcitonin measurement, during the first 3 days after abdominal surgery, has been evaluated for the early diagnosis of postsurgical infection.Ninety consecutive patients subjected to major abdominal surgery at the University Campus Bio-Medico of Rome, have been included. PCT concentrations were measured by time-resolved amplified cryptate emission (TRACE) assay at admission and at the first, second, and third day after surgery. PCT levels were compared using the Mann-Whitney test and by ANOVA test for variance analysis. Receiver operating characteristic (ROC) analysis was performed to define the diagnostic ability of PCT in case of postsurgical infections.PCT values resulted significantly different between patients developing or not developing postsurgical infections. PCT >1.0 ng/mL at first or second day after surgery and >0.5 ng/mL at third day resulted diagnostic for infectious complication, whereas a value <0.5 ng/mL at the fifth day after surgery was useful for early and safety discharge of patients.In conclusion, PCT daily measurement could represent a useful diagnostic tool improving health care in the postsurgical period following major abdominal surgery and should be recommended.
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http://dx.doi.org/10.1097/MD.0000000000009496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5779742PMC
January 2018

Multi-drug resistant Klebsiella pneumoniae strains circulating in hospital setting: whole-genome sequencing and Bayesian phylogenetic analysis for outbreak investigations.

Sci Rep 2017 06 14;7(1):3534. Epub 2017 Jun 14.

Unit of Clinical Pathology and Microbiology, University Campus Bio-Medico of Rome, Rome, Italy.

Carbapenems resistant Enterobacteriaceae infections are increasing worldwide representing an emerging public health problem. The application of phylogenetic and phylodynamic analyses to bacterial whole genome sequencing (WGS) data have become essential in the epidemiological surveillance of multi-drug resistant nosocomial pathogens. Between January 2012 and February 2013, twenty-one multi-drug resistant K. pneumoniae strains, were collected from patients hospitalized among different wards of the University Hospital Campus Bio-Medico. Epidemiological contact tracing of patients and Bayesian phylogenetic analysis of bacterial WGS data were used to investigate the evolution and spatial dispersion of K. pneumoniae in support of hospital infection control. The epidemic curve of incident K. pneumoniae cases showed a bimodal distribution of cases with two peaks separated by 46 days between November 2012 and January 2013. The time-scaled phylogeny suggested that K. pneumoniae strains isolated during the study period may have been introduced into the hospital setting as early as 2007. Moreover, the phylogeny showed two different epidemic introductions in 2008 and 2009. Bayesian genomic epidemiology is a powerful tool that promises to improve the surveillance and control of multi-drug resistant pathogens in an effort to develop effective infection prevention in healthcare settings or constant strains reintroduction.
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http://dx.doi.org/10.1038/s41598-017-03581-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5471223PMC
June 2017

Endoscopic full-thickness resection of superficial colorectal neoplasms using a new over-the-scope clip system: A single-centre study.

Dig Liver Dis 2017 Sep 2;49(9):1009-1013. Epub 2017 May 2.

Digestive Endoscopy Unit, University Campus Bio-Medico, Rome, Italy.

Background And Aim: Endoscopic full-thickness resection (EFTR) provides complete en-bloc resection with a histopathological evaluation of submucosal, muscular, and serosal layers. The aim of this study was to investigate the efficacy and safety of a novel over-the-scope device for colorectal EFTR.

Material And Methods: In this retrospective, observational, open-label case study, a total of 20 patients with superficial colorectal neoplasms, underwent EFTR using a new endoscopic full-thickness resection device (FTRD; Ovesco Endoscopy, Tübingen, Germany). Endoscopic treatment outcomes (technical success, rate of EFTR, adverse events) and early follow-up at three months, were analyzed.

Results: We reported a 100% of technical success, defined as full-thickness resection. Among the R1 resections, histology was negative for neoplasm. Non-lifting adenomas had histology positive for adenocarcinoma: seven T1/G1/sm1; one T1/G1/sm2; one, who underwent a surgical resection, T1/G1/sm3. Mean size of the resected lesions was 26mm, ranging from 10 to 42mm. One (5%) patient developed abdominal pain, fever and leukocytosis and was treated conservatively with medical therapy. In all specimens, histological complete resection was confirmed.

Conclusions: EFTR is a feasible and effective technique that could become a valid alternative to EMR and ESD in the management of recurrent adenomas, no-lifting lesions and scars of R1 resections. However, prospective studies are needed to further evaluate the device and technique.
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http://dx.doi.org/10.1016/j.dld.2017.04.015DOI Listing
September 2017

Phase II study of induction chemotherapy followed by chemoradiotherapy in patients with borderline resectable and unresectable locally advanced pancreatic cancer.

Sci Rep 2017 04 5;7:45845. Epub 2017 Apr 5.

Department of General Surgery, Campus Bio-Medico University, Rome, Italy.

There is not a clear consensus regarding the optimal treatment of locally advanced pancreatic disease. There is a potential role for neoadjuvant therapy to treat micrometastatic disease with chemotherapy, as well as for the treatment of local disease with radiotherapy. We evaluated the safety and efficacy of induction chemotherapy with oxaliplatin and gemcitabine followed by a high weekly dose of gemcitabine concurrent to radiation therapy in patients with borderline resectable and unresectable locally advanced pancreatic cancer. In our study, 41 patients with pancreatic cancer were evaluated. In all cases an accurate pre-treatment staging was performed. Patients with evidence of metastatic disease were excluded, and thus a total of 34 patients were consequently enrolled. Of these, twenty-seven patients (80%) had locally advanced unresectable tumours, seven patients (20%) had borderline resectable disease. This protocol treatment represents a well-tolerated promising approach. Fifteen patients (55.5%) underwent surgical radical resection. With a median follow-up of 20 months, the median PFS and OS were 20 months and 19.2 months, respectively. The median OS for borderline resectable patients was 21.5 months compared with 14 months for unresectable patients (p = 0.3). Continued optimization in multimodality therapy and an accurate patient selection remain crucial points for the appropriate treatment of these patients.
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http://dx.doi.org/10.1038/srep45845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5381116PMC
April 2017

PD-L1/PD-1 check-point in gastric carcinoma with lymphoid stroma case report with immunochemical study.

Medicine (Baltimore) 2017 Feb;96(7):e5730

Pathology Unit Gastroenterology Unit Surgical Unit, University Hospital Campus Bio-Medico, Rome, Italy.

Introduction: Gastric carcinoma with lymphoid stroma is an unusual type of gastric tumor associated with a better prognosis than typical gastric carcinomas. The hallmark of this cancer is a prominent lymphoid infiltration of the stroma that represents an intense host lymphocytic response. The programmed death 1-programmed death-ligand 1 (PD-1/PD-L1) axis has recently emerged as a master immune checkpoint that controls antitumor immune responses against many neoplasms.

Patient's Concerns Case Study And Outcome: We report the case of a male patient with gastric carcinoma with lymphoid stroma with a large mass infiltrating the gastric wall without nodal metastasis. He is alive without disease 10 months after surgery. We focused the study on factors that potentially modulate the prognosis. In this setting we demonstrate, for the first time in this type of tumor, by immunohistochemistry a strong PD-L1 expression in neoplastic cell and the presence of PD-1 positive infiltrating lymphocytes.

Conclusion: The applied approach may contribute to the knowledge about host reaction in such tumor and it may also be used for tumor precise identification on the endoscopic biopsy time before excision surgery.
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http://dx.doi.org/10.1097/MD.0000000000005730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5319490PMC
February 2017

All that glitters are not gold! Reactive lymphoid hyperplasia mimicking colorectal liver metastases: description of a case and literature review.

Updates Surg 2017 03 11;69(1):113-115. Epub 2017 Jan 11.

Department of Surgery, University Campus Bio-Medico di Roma, via Alvaro del Portillo, 200, 00128, Rome, Italy.

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http://dx.doi.org/10.1007/s13304-017-0416-1DOI Listing
March 2017

Klebsiella pneumoniae blaKPC-3 nosocomial epidemic: Bayesian and evolutionary analysis.

Infect Genet Evol 2016 12 1;46:85-93. Epub 2016 Nov 1.

Unit of Clinical Pathology and Microbiology, University Campus Bio-Medico of Rome, Italy; Department of Infectious Parasitic and Immunomediated Diseases, National Institute of Health, Rome, Italy.

K. pneumoniae isolates carrying blaKPC-3 gene were collected to perform Bayesian phylogenetic and selective pressure analysis and to apply homology modeling to the KPC-3 protein. A dataset of 44 bla-3 gene sequences from clinical isolates of K. pneumoniae was used for Bayesian phylogenetic, selective pressure analysis and homology modeling. The mean evolutionary rate for bla-3 gene was 2.67×10 substitution/site/year (95% HPD: 3.4×105.59×10). The root of the Bayesian tree dated back to the year 2011 (95% HPD: 2007-2012). Two main clades (I and II) were identified. The population dynamics analysis showed an exponential growth from 2011 to 2013 and the reaching of a plateau. The phylogeographic reconstruction showed that the root of the tree had a probable common ancestor in the general surgery ward. Selective pressure analysis revealed twelve positively selected sites. Structural analysis of KPC-3 protein predicted that the amino acid mutations are destabilizing for the protein and could alter the substrate specificity. Phylogenetic analysis and homology modeling of blaKPC-3 gene could represent a useful tool to follow KPC spread in nosocomial setting and to evidence amino acid substitutions altering the substrate specificity.
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http://dx.doi.org/10.1016/j.meegid.2016.10.031DOI Listing
December 2016

Neutrophil to Lymphocyte Ratio (NLR) and Derived Neutrophil to Lymphocyte Ratio (d-NLR) Predict Non-Responders and Postoperative Complications in Patients Undergoing Radical Surgery After Neo-Adjuvant Radio-Chemotherapy for Rectal Adenocarcinoma.

Cancer Invest 2016 14;34(9):440-451. Epub 2016 Oct 14.

a Department of General Surgery , University Campus Bio-Medico di Roma , Rome , Italy.

In order to evaluate neutrophil-to-lymphocyte ratio (NLR) and derived neutrophil-to-lymphocyte ratio (d-NLR) in predicting response and complications in rectal cancer patients who underwent surgery after neo-adjuvant radio-chemotherapy, 87 patients were evaluated. Cutoffs before and after radio-chemotherapy were respectively 2.8 and 3.8 for NLR, and 1.4 and 2.3 for d-NLR. They were analyzed in relation to clinical and pathological outcomes. Patients with preoperative NLR and d-NLR higher than cutoffs had significantly higher rates of tumor regression grade response (TRG ≥ 4) and postoperative complications. Elevated NLR and d-NLR after radio-chemotherapy are associated with worse pathological and clinical outcome.
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http://dx.doi.org/10.1080/07357907.2016.1229332DOI Listing
October 2016

HER2 Status in Gastric Cancer: Comparison between Primary and Distant Metastatic Disease.

Pathol Oncol Res 2017 Jan 30;23(1):55-61. Epub 2016 Jun 30.

Department of Pathology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo, 200, Rome, Italy.

HER2 (human epidermal growth factor receptor-2) assessment in histological samples of gastric cancer is essential to determine which patients might benefit from trastuzumab therapy. HER2 is often evaluated in primary tumor even if trastuzumab therapy is used to treat metastatic disease. However, the exact relationship in terms of HER2 status between primary and metastatic tumors has not been fully clarified. We aimed to evaluate the HER2 status concordance between primary gastric cancer and corresponding distant metastasis. HER2 status was evaluated by IHC (immunohistochemistry) and/or FISH ( fluorescence in situ hybridization) in 41 patients in primary gastric cancer and in paired metastasis. HER2 was assessed according scoring criteria applied in clinical approach. HER2 positivity was found in 14,6 % primary tumors and in 24,4%corresponding metastasis. HER2 concordance rate between primary and metastasis was 80,5 % (K-value = 0,388). Eight/41 (19,5 %)cases resulted discordant: 6 patients with metastatic HER2 positive lesions were found HER2 negative in primary cancers while 2 patient HER2 positive in primary lesion showed a negative conversion in metastasis. Our results showed a good concordance in terms of HER2 status between primary and metastatic lesions, as well as in biopsy and surgical removed specimens. However, the higher rate of HER2 positive status found in metastatic lesions underlined the importance of HER2 assessment in all samples obtained from different sites of gastric cancer disease.
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http://dx.doi.org/10.1007/s12253-016-0082-5DOI Listing
January 2017

Non-sutureless minimally invasive aortic valve replacement: mini-sternotomy versus mini-thoracotomy: a series of 1130 patients.

Interact Cardiovasc Thorac Surg 2016 08 8;23(2):253-8. Epub 2016 May 8.

Department of Cardiac Surgery, GVM Care and Research, Anthea Hospital, Bari, Italy.

Objectives: Aortic valve replacement through conventional sternotomy still represents the gold-standard surgical approach for aortic valve disease. However, given the increasing number of patients with comorbidities, strategies that can improve operative results are always sought. Minimally invasive aortic valve surgery, although related to a steep learning curve, might be associated with improved postoperative outcomes. The main aim of this study was to assess whether significant differences exist in terms of operative and early results between a mini-sternotomy and a right mini-thoracotomy approach for isolated aortic valve replacement without sutureless technologies.

Methods: This is an observational retrospective multicentre study from nine Italian cardiac centres that analyses prospectively collected data of patients who underwent isolated minimally invasive aortic valve replacement between January 2010 and December 2014. Two approaches are considered (mini-sternotomy and mini-thoracotomy) and compared in terms of operative and early outcomes.

Results: After interrogation of the centralized database, a total of 1130 patients were retrieved (854 mini-sternotomy and 276 mini-thoracotomy). Patients in the mini-sternotomy group had a higher risk profile. There was no difference in terms of early mortality; cardiopulmonary bypass and cross-clamp time did not differ significantly between the groups; and a significantly higher number of reoperations for bleeding was observed in the right mini-thoracotomy group.

Conclusions: Both mini-sternotomy and mini-thoracotomy could be performed safely, with low mortality and postoperative morbidity. The mini-thoracotomy approach was associated with a significantly higher rate of reoperation for bleeding. Uptake among cardiac centres was low. Sutureless technologies could potentially increase surgical volume by simplifying the mini-thoracotomy procedure.
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http://dx.doi.org/10.1093/icvts/ivw104DOI Listing
August 2016

Prospective study of cetuximab and gemcitabine in combination with radiation therapy: feasibility and efficacy in locally advanced pancreatic head cancer.

Radiat Oncol 2015 Dec 15;10:255. Epub 2015 Dec 15.

Department of General Surgery, Campus Bio-Medico University, Rome, Italy.

Background: Radio-chemotherapy is one of the steps of multidisciplinary management in locally advanced pancreatic cancer. The Epidermal Growth Factor Receptor (EGFR) plays an important role in the disease pathway. The purpose of this prospective study is to evaluate the feasibility and the efficacy of radiotherapy in combination with gemcitabine and EGFR targeting therapy for patients with locally advanced disease.

Materials And Methods: From November 2008 through January 2012, 34 patients were included in this study. In all cases an accurate pre-treatment staging including CT scan, Endoscopic Ultra-Sonography (EUS), 18F - fluorodeoxyglucose (18F-FDG) PET-CT and laparoscopy with peritoneal washing was performed. External beam radiation was delivered with a total dose of 50.4 Gy (1.8 Gy per fraction). Patients were treated using 3D- conformal radiotherapy, and the clinical target volume was the primary tumor and involved lymph nodes. Gemcitabine 300 mg/m(2) and Cetuximab were given weekly during radiation therapy.

Results: Ten patients (29.4 %) were excluded from the protocol because of the evidence of metastatic disease at the pre-treatment staging. Three patients refused radiochemotherapy. Twenty-one patients completed the therapy protocol. During the combined therapy grade 3-4 toxicities observed were only haematological (leukopenia 47,6 %, trombocytopenia 4.8 %, elevated gamma-GT 23.8 %, elevated alkaline phosphatase 4,8 %). Non-haematological toxicity grade 3-4 was never reported. Post-treatment workup showed partial response in five patients (24 %), stable disease in 11 patients (52 %) and disease progression in 5 patients (24 %). Two-year Local Control was 49 % (median, 18.6 months), 2-year Metastases Free Survival was 24 % (median, 10.8 months). One and two-year Overall Survival were 66 % and 28 % respectively, with a median survival time of 15.3 months.

Conclusions: The combination of cetuximab and gemcitabine with concurrent radiation therapy provides a feasible and well tolerated treatment for locally advanced pancreatic cancer. Patients' selection is crucial in order to treat patients appropriately.
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http://dx.doi.org/10.1186/s13014-015-0564-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4681028PMC
December 2015

Microscopic Residual Tumor After Pancreaticoduodenectomy: Is Standardization of Pathological Examination Worthwhile?

Pancreas 2016 May-Jun;45(5):748-54

From the *Department of General Surgery, †Unit of Pathology, and ‡Public Health and Statistics, Campus Bio-Medico University of Rome, Rome, Italy.

Objectives: R1 resection rate after pancreaticoduodenectomy (PD) for cancer is highly variable. The aim of this study was to verify if a standardized histopathological work-up of the specimen affects the rate of R1 resection after PD for cancer.

Methods: Two groups of specimens were managed with (standardized method [SM] group) or without (non-standardized method [NSM] group) a SM of histopathological work-up. Each group included 50 cases of PD for periampullary cancer. Differences in terms of R1 resection rate between the 2 groups were evaluated. Correlation between R1 status and local recurrence was also evaluated.

Results: The cohort of 100 patients consisted of 66 pancreatic ductal adenocarcinoma, 15 cholangiocarcinoma, and 19 ampullary cancer. The R1 resection rate resulted statistically higher in the SM group (66% vs 10%). Local recurrence was more frequently related to R1 resection in the SM group (34.3% of cases) than in NSM group (20% of cases).

Conclusions: The use of the SM of pathological evaluation of the specimen after PD for cancer determines a significant increase of R1 resection. This remarkable difference seems to be due to the different definition of minimum clearance. The SM seems to better discriminate patients in terms of risk of local recurrence.
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http://dx.doi.org/10.1097/MPA.0000000000000540DOI Listing
January 2017

Incidence and prognostic impact of para-aortic lymph nodes metastases during pancreaticoduodenectomy for peri-ampullary cancer.

HPB (Oxford) 2015 Nov 3;17(11):1001-8. Epub 2015 Sep 3.

Department of General Surgery, Campus Bio-Medico University of Rome, Rome, Italy.

Background: Standard lymphadenectomy during pancreaticoduodenectomy (PD) for peri-ampullary cancer does not include the routine removal of para-aortic lymph nodes (PALN) (station 16, according to the JPS staging system). The aim of this study was to report the incidence and the prognostic value of PALN metastases in patients undergoing PD for peri-ampullary cancer.

Materials And Methods: One hundred thirty-five consecutive patients who underwent PD and PALN dissection for peri-ampullary cancer were prospectively evaluated. The relationship between clinicopathological factors, including PALN metastases and survival was evaluated at univariate and multivariate analysis.

Results: PALN metastases (N16+) were found in 11.1% of cases. At univariate analysis, R1 resection, metastatic nodes different from para aortic (N1) and N16+ significantly affected patients' prognosis. Compared with N16+, the median overall survival (OS) of N0 patients was significantly longer (32 versus 69 months, respectively; P < 0.05), whereas no difference was found between N16+ and N1 patients (32 versus 34 months, respectively) (P > 0.05). At multivariate analysis, only R1 resection reached statistical significance and was confirmed an independent prognostic factor.

Conclusions: Neoplastic involvement of PALN in peri-ampullary cancer is frequent and, so, their removal during PD could be justified. Moreover, PALN metastases should be not considered an absolute contraindication to radical surgery.
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http://dx.doi.org/10.1111/hpb.12497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4605339PMC
November 2015

Melena as presentation of primary small intestine inflammatory myofibroblastic tumor in an adult woman. A case report.

Ann Ital Chir 2015 Jul 29;86(ePub). Epub 2015 Jul 29.

Introduction: Inflammatory myofibroblastic tumor (IMT), also known as inflammatory pseudotumor, plasma cell granuloma or inflammatory myofibroblastoma, is characterized histopathologically by myofibroblastic spindle cells with inflammatory cell infiltrates ( plasma cell, lymphocytes and eosinophils). Inflammatory myofibroblastic tumor is tipically seen in children or young adults and is most commonly localized in the lung, but it can occur anywhere in the body.

Case Report: We present a case in a young woman with severe acute G.I. bleeding, an uncommon presentation of IMT in adults. The patient was admitted to the emergency department for melena. MRI showed a distal jejunum hypervascular mass. Other exams were negative. Surgical excision was recommended, so the patient underwent surgery with complete removal of the tumoral mass. No adjuvant therapy was employed and the patient is asymptomatic after 6 months of follow-up.

Discussion: IMT is an rare lesion that mimics malignancy and is accompanied by various clinical manifestations. The treatment of choice is believed to be complete surgical excision and long term follow up.

Key Words: Anemia, Inflammatory myofibroblastic tumor (IMT), Small intestine, Surgery.
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July 2015

Role of c-mesenchymal-epithelial transition pathway in gastric cancer.

Expert Opin Pharmacother 2015 Jun 16;16(8):1195-207. Epub 2015 Apr 16.

University Campus Bio-Medico Rome - Medical Oncology, via Alvaro del Portillo , 200, 00128, Rome , Italy

Introduction: Gastric cancer is the fourth most common cancer burden worldwide; many patients show incurable disease at the time of diagnosis and prognosis remains unfavorable. Recently, new findings on gastric cancer biology led to the preclinical and clinical development of new compounds aiming to improve the overall survival and to preserve quality of life and reducing chemotherapy-related toxicities. Patients with human epidermal growth factor receptor 2 (HER2) overexpression/amplification have experienced benefit from the integration of trastuzumab to the standard chemotherapy. Ramucirumab has been recently approved in second line for treatment of gastric cancer.

Areas Covered: Drugs targeting molecules such as anti c-mesenchymal-epithelial transition (MET), mammalian target of rapamycin inhibitors, polo-like kinase 1 inhibitors are under investigation or in preclinical or early clinical development. Approximately 10 - 20% of gastric cancer presented an increased MET gene copy numbers; inappropriate activation of MET promotes cellular proliferation, cell motility, invasiveness and angiogenesis and is associated with more aggressive phenotype and with a lower survival.

Expert Opinion: The role of c-MET has been extensively evaluated both in Asian and Western population, even if data are far from being conclusive. The activation of MET/hepatocyte growth factor pathway is a negative prognostic factor, and it could partially explain the resistance to EGFR/HER2 inhibitors acting as a rescue pathway likewise in other tumors.
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http://dx.doi.org/10.1517/14656566.2015.1037739DOI Listing
June 2015

Size and charge of nanoparticles following incubation with human plasma of healthy and pancreatic cancer patients.

Colloids Surf B Biointerfaces 2014 Nov 16;123:673-8. Epub 2014 Oct 16.

University Campus Bio-Medico di Roma, General Surgery, Via Álvaro del Portillo 200, 00128 Rome, Italy.

When nanoparticles (NPs) enter a biological environment, proteins bind to their surface forming a protein coating, which alters NP features giving it a biological identity, which controls its physiological response. The NP biological identity (size, charge and aggregation state) does strictly correlate with its physicochemical properties and the nature of the biological environment. While the former relationship has been extensively investigated, whether and how alterations in the physiological environment affect the biological identity of the NPs remains unclear. In this work we enrolled healthy and histologically proven pancreatic cancer patients. A statistically significant reduction in the level of clinically relevant proteins in cancer patients occurred. Positively and negatively charged lipid nanoparticles with two different surface chemistries (plain and PEGylated) were incubated with human plasma from both groups and characterized thoroughly by dynamic light scattering and zeta potential measurements. Only when plain positively charged NPs were tested, significant difference in zeta-potential between healthy and pancreatic cancer groups was found. This result implies that pooling human plasma from healthy volunteers might lead to a bias and thus unpredictable consequences in regard to previously optimized targeting profile.
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http://dx.doi.org/10.1016/j.colsurfb.2014.10.008DOI Listing
November 2014

Serum lactate dehydrogenase alone is not a helpful prognostic factor in resected colorectal cancer patients.

Updates Surg 2014 Sep 8;66(3):211-5. Epub 2014 Aug 8.

Department of General Surgery, University Campus Bio-Medico di Roma, Via Alvaro del Portillo, 200, 00128, Rome, Italy,

Several studies showed how serum levels of lactate dehydrogenase (LDH) are related with a worse prognosis and response to therapy. Its role in colorectal cancer is not still assessed. The aim of this study was to assess the prognostic role of serum level of LDH in non-metastatic, previously untreated, T2-T3-T4 colorectal tumours undergoing surgery. Data regarding preoperative serum levels of LDH have been retrospectively collected. A group with normal levels of serum LDH (group A) and a group with high levels of serum LDH (group B) have been identified and compared in relation with disease staging and outcome. A series of 96 cases have been analysed. Only age was significantly associated with increased LDH serum level (p 0.001). No significant differences between serum LDH levels, staging pT (p 0.721), pN (p 0.080) and grading (0.849) have been found. Test's sensitivity and specificity were 76 and 46.5%, respectively. Preoperative serum levels of LDH alone failed to demonstrate a prognostic role in a selected series of colorectal cancer patients. Low rates of sensitivity and specificity have been found.
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http://dx.doi.org/10.1007/s13304-014-0260-5DOI Listing
September 2014

Conversion in mini-invasive colorectal surgery: the effect of timing on short term outcome.

Int J Surg 2014 7;12(8):805-9. Epub 2014 Jul 7.

Department of General Surgery, University Campus Bio-Medico di Roma, Via Alvaro del Portillo, 200, 00128 Rome, Italy.

Introduction: Different results have been reported about postoperative outcomes of conversion during laparoscopic colorectal surgery. We aimed to detect the effect of conversion on postoperative outcome and to identify features associated to better outcome after conversion.

Methods: Two hundred-fourteen mini-invasive left colonic and rectal resections were retrospectively analysed. Two groups were identified: mini-invasive colorectal surgery (MI) that includes both laparoscopic and robotic resections, and conversion to open surgery.

Results: Among 214 colorectal procedures, 189 were MI. Conversion rate was 11.7%. Operating time was shorter for MI at overall analysis (p 0.003) and sub-analysis of left colectomies (p 0.001). MI procedures had shorter hospital stay (p 0.000) both in left colectomy and rectal resection (p 0.008 and p 0.001 respectively). A shorter time to first flatus emission was detected in MI group in both overall analysis (p 0.003) and procedure's sub-analysis (left colectomy p 0.032; anterior rectal resection p 0.040). Oral feeding was resumed earlier after mini-invasive rectal resections (p 0.014). Converted procedures required more blood transfusions (p 0.000) and grade II complication rate was lower after MI procedures (p 0.013). Conversion presented higher anastomotic leakage and reoperation rates (p 0.035 and p 0.006 respectively). Conversion before 105 min (early conversion) had a significant lower number of blood transfusions (p 0.047).

Conclusions: Conversion is associated to higher rate of blood transfusions, grade II complication and slower recovery. Earlier conversion has better outcomes. Colorectal surgeons should identify any critical aspects that could avoid late conversion allowing reducing negative effects of conversion.
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http://dx.doi.org/10.1016/j.ijsu.2014.06.010DOI Listing
July 2015

Continuous glucose monitoring and robot surgery of an insulinoma: a case report and review of the literature.

Pancreas 2014 Apr;43(3):483-5

Department of General Surgery University Campus Bio-Medico of Rome Rome, Italy Department of Endocrinology and Diabetes University Campus Bio-Medico of Rome Rome, Italy Department of Endoscopic Ultrasound University Campus Bio-Medico of Rome Rome, Italy Department of RadiologyUniversity Campus Bio-Medico of Rome Rome, Italy Department of General Surgery University Campus Bio-Medico of Rome Rome, Italy Department of Endocrinology and Diabetes University Campus Bio-Medico of Rome Rome, Italy.

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http://dx.doi.org/10.1097/MPA.0000000000000040DOI Listing
April 2014

Reply to 'Hospital volume, margin status, and long-term survival after pancreaticoduodenectomy for pancreatic adenocarcinoma' (Am Surg 2012;78:225-9).

Am Surg 2014 Jan;80(1):87-8

Department of General Surgery, Campus Bio-Medico University of Rome, Rome, Italy.

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January 2014

T1 colorectal cancer: poor histological grading is predictive of lymph-node metastases.

Int J Surg 2014 27;12(3):209-12. Epub 2013 Dec 27.

Department of General Surgery, University Campus Bio-Medico di Roma, Via Alvaro del Portillo, 200, 00128 Rome, Italy.

Introduction: After complete local excision of pT1 colorectal cancers, prediction of the absence of lymph-node involvement represents an interesting perspective in order to avoid unnecessary additional radical surgery, reducing morbidity, mortality and costs of care. We aimed to identify independent risk factors predictive of nodal involvement in pT1 colorectal cancer patients.

Methods: Data regarding depth of submucosal invasion, histological grading, tumour budding and lymphovascular invasion in a consecutive series of 48 pT1 surgically resected colorectal cancers have been retrospectively collected and related to the nodal status.

Results: A 12.5% rate of nodal involvement has been found. The poor differentiation was found as the only independent predictor of nodal metastases in pT1 colorectal cancer (p = 0.01).

Conclusions: Poor differentiation was the only independent significant predictor of nodal involvement in pT1 colorectal tumours. Our and literature's data confirm that risk factors must be prospectively collected and reported; further genetic and epigenetic predictive factors have to be investigated in order to carefully evaluate the needing of major surgery for pT1 colorectal cancer.
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http://dx.doi.org/10.1016/j.ijsu.2013.12.012DOI Listing
December 2014

US-guided application of Nd:YAG laser in porcine pancreatic tissue: an ex vivo study and numerical simulation.

Gastrointest Endosc 2013 Nov 13;78(5):750-5. Epub 2013 May 13.

Digestive Endoscopy Unit Campus Bio-Medico, University of Rome, Rome, Italy.

Background: Laser ablation (LA) with a neodymium-doped yttrium aluminum garnet (Nd:YAG) laser is a minimally invasive approach able to achieve a high rate of complete tissue necrosis. In a previous study we described the feasibility of EUS-guided Nd:YAG pancreas LA performed in vivo in a porcine model.

Objective: To establish the best laser setting of Nd:YAG lasers for pancreatic tissue ablation. A secondary aim was to investigate the prediction capability of a mathematical model on ablation volume.

Design: Ex vivo animal study.

Setting: Hospital animal laboratory.

Subjects: Explanted pancreatic glands from 60 healthy farm pigs.

Intervention: Laser output powers (OP) of 1.5, 3, 6, 10, 15, and 20 W were supplied. Ten trials for each OP were performed under US guidance on ex vivo healthy porcine pancreatic tissue.

Main Outcome Measurements: Ablation volume (Va) and central carbonization volume (Vc) were measured on histologic specimens as the sum of the lesion areas multiplied by the thickness of each slide. The theoretical model of the laser-tissue interaction was based on the Pennes equation.

Results: A circumscribed ablation zone was observed in all histologic specimens. Va values grow with the increase of the OP up to 10 W and reach a plateau between 10 and 20 W. The trend of Vc values rises constantly until 20 W. The theoretical model shows a good agreement with experimental Va and Vc for OP between 1.5 and 10 W.

Limitations: Ex vivo study.

Conclusion: Volumes recorded suggest that the best laser OP could be the lowest one to obtain similar Va with smaller Vc in order to avoid the risk of thermal injury to the surrounding tissue. The good agreement between the two models demonstrates the prediction capability of the theoretical model on laser-induced ablation volume in an ex vivo animal model and supports its potential use for estimating the ablation size at different laser OPs.
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http://dx.doi.org/10.1016/j.gie.2013.04.178DOI Listing
November 2013

Infusion of bevacizumab increases the risk of intestinal perforation: results on a series of 143 patients consecutively treated.

Updates Surg 2013 Jun 27;65(2):121-4. Epub 2013 Mar 27.

Department of General Surgery, Campus Bio-Medico University of Rome, Rome, Italy.

Bevacizumab is largely used in colorectal cancer patients. Postsurgical healing complications have been described for patients following treatment with Bevacizumab. We report three cases of spontaneous intestinal perforation following infusion of Bevacizumab. From January 2002 through October 2010, Bevacizumab was delivered in 143 patients. Spontaneous intestinal perforation occurred in 3 cases (2.1 %). Bevacizumab may result in severe complications. Therefore, it is important to consider every patient treated with Bevacizumab at risk for life-threatening gastro-intestinal complications.
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http://dx.doi.org/10.1007/s13304-013-0207-2DOI Listing
June 2013

Efficacy of an absorbable fibrin sealant patch (TachoSil) after distal pancreatectomy: a multicenter, randomized, controlled trial.

Ann Surg 2012 Nov;256(5):853-9; discussion 859-60

Department of General Surgery, University of Milan, Istituto Clinico Humanitas IRCCS, Via Manzoni 56, Rozzano, Milan, Italy.

Objective: To evaluate the role of an absorbable fibrin sealant patch (TachoSil) in reducing postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP).

Background: POPF remains the main complication after DP.

Methods: This was a prospective, open, randomized, study in which patients undergoing elective DP were randomized to standard surgical suturing or stapling with or without TachoSil. The primary end point was the incidence of POPF according to International Study Group on Pancreatic Fistula criteria. Amylase level in drainage fluid, number of days until removal of drain, and duration of hospital stay were secondary end points.

Results: A total of 275 patients were enrolled at 19 centers over a 2-year period (TachoSil, n = 145; standard, n = 130). Twenty percent of procedures were laparoscopic and 21% were spleen-preserving resections. The incidence of POPF was not significantly different between groups (TachoSil, 62%; standard 68%; P = 0.267). Grade A fistula rate was similar in both groups (TachoSil 54%; standard 55%), whereas the grade B + C fistula rate was 8% with TachoSil versus 14% without (P = 0.139). Amylase drainage level on postoperative day 1 was significantly reduced with TachoSil (P = 0.025). Median number of days until drainage removal and length of hospital stay were similar in both groups (7 and 10 days, respectively).

Conclusions: The POPF rate was higher than expected when International Study Group on Pancreatic Fistula criteria were strictly applied, although the majority were biochemical fistulas. TachoSil had no significant effect on the rate of POPF, although there was a significant reduction of amylase level in drainage fluid on postoperative day 1.
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http://dx.doi.org/10.1097/SLA.0b013e318272dec0DOI Listing
November 2012

In situ identification of CD44+/CD24- cancer cells in primary human breast carcinomas.

PLoS One 2012 13;7(9):e43110. Epub 2012 Sep 13.

Department of Pathology, Campus Bio-Medico University of Rome, Rome, Italy.

Breast cancer cells with the CD44+/CD24- phenotype have been reported to be tumourigenic due to their enhanced capacity for cancer development and their self-renewal potential. The identification of human tumourigenic breast cancer cells in surgical samples has recently received increased attention due to the implications for prognosis and treatment, although limitations exist in the interpretation of these studies. To better identify the CD44+/CD24- cells in routine surgical specimens, 56 primary breast carcinoma cases were analysed by immunofluorescence and confocal microscopy, and the results were compared using flow cytometry analysis to correlate the amount and distribution of the CD44+/CD24- population with clinicopathological features. Using these methods, we showed that the breast carcinoma cells displayed four distinct sub-populations based on the expression pattern of CD44 and CD24. The CD44+/CD24- cells were found in 91% of breast tumours and constituted an average of 6.12% (range, 0.11%-21.23%) of the tumour. A strong correlation was found between the percentage of CD44+/CD24- cells in primary tumours and distant metastasis development (p = 0.0001); in addition, there was an inverse significant association with ER and PGR status (p = 0.002 and p = 0.001, respectively). No relationship was evident with tumour size (T) and regional lymph node (N) status, differentiation grade, proliferative index or HER2 status. In a multivariate analysis, the percentage of CD44+/CD24- cancer cells was an independent factor related to metastasis development (p = 0.004). Our results indicate that confocal analysis of fluorescence-labelled breast cancer samples obtained at surgery is a reliable method to identify the CD44+/CD24- tumourigenic cell population, allowing for the stratification of breast cancer patients into two groups with substantially different relapse rates on the basis of CD44+/CD24- cell percentage.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0043110PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3441535PMC
March 2013

Aberrant promoter methylation of beta-1,4 galactosyltransferase 1 as potential cancer-specific biomarker of colorectal tumors.

Genes Chromosomes Cancer 2012 Dec 25;51(12):1133-43. Epub 2012 Aug 25.

Department of Bioscience, Biotechnology and Pharmacological Sciences, University of Bari, Italy.

Epigenetic alterations, such as CpG islands methylation and histone modifications, are recognized key characteristics of cancer. Glycogenes are a group of genes which epigenetic status was found to be changed in several tumors. In this study, we determined promoter methylation status of the glycogene beta-1,4-galactosyltransferase 1 (B4GALT1) in colorectal cancer patients. Methylation status of B4GALT1 was assessed in 130 colorectal adenocarcinomas, 13 adenomas, and in paired normal tissue using quantitative methylation specific PCR (QMSP). B4GALT1 mRNA expression was evaluated in methylated/unmethylated tumor and normal specimens. We also investigated microsatellite stability and microsatellite instability status and KRAS/BRAF mutations. Discriminatory power of QMSP was assessed by receiving operating curve (ROC) analysis on a training set of 24 colorectal cancers and paired mucosa. The area under the ROC curve (AUC) was 0.737 (95% confidence interval [CI]:0.591-0.881, P = 0.005) with an optimal cutoff value of 2.07 yielding a 54% sensitivity (95% CI: 35.1%-72.1%) and a specificity of 91.7% (95% CI: 74.1%-97.7%). These results were confirmed in an independent validation set where B4GALT1 methylation was detected in 52/106 patients. An inverse correlation was observed between methylation and B4GALT1 mRNA expression levels (r = -0.482, P = 0.037). Significant differences in methylation levels and frequencies was demonstrated in invasive lesions as compared with normal mucosa (P = 0.0001) and in carcinoma samples as compared with adenoma (P = 0.009). B4GALT1 methylation is a frequent and specific event in colorectal cancer and correlates with downregulation of mRNA expression. These results suggest that the glycogene B4GALT1 represent a valuable candidate biomarker of invasive phenotype of colorectal cancer.
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http://dx.doi.org/10.1002/gcc.21998DOI Listing
December 2012

Carcinoma of the ampulla of Vater: morphological and immunophenotypical classification predicts overall survival.

Pancreas 2013 Jan;42(1):60-6

Unit of Human Anatomy, CIR, Campus Bio-Medico University of Rome, Rome, Italy.

Objectives: The objective of the study was to verify if histopathological differentiation of ampullary carcinoma after surgical resection may be related to survival.

Methods: The prognostic role of an accurate histological and immunohistochemical classification has been investigated in a multicentric series of carcinoma of the ampulla of Vater. Immunohistochemical expression of cytokeratin 7 (CK7) and CK20 were analyzed in the different morphological histotypes of ampullary cancers, and results were compared with overall survival.

Results: Of 72 ampullary cancers, 48.6% were classified as pancreaticobiliary-type carcinomas, 43.1% were classified as intestinal-type carcinomas, and 8.3% were classified as "unusual"-type carcinomas. Cytokeratin 20 was expressed in 28 (90.3%) of the 31 intestinal-type carcinomas, whereas it was always negative in the pancreaticobiliary histotype; CK7 was expressed in 32 (91.4%) of the 35 pancreaticobiliary-type carcinomas and in 18 (58.1%) of the 31 intestinal-type carcinomas. By univariate analysis, overall survival was influenced significantly by pathological T factor, lymph node involvement, and histological/immunohistochemical subtyping. Furthermore, using a multivariate Cox regression model, lymph node metastasis and CK20 were identified as significant independent factors related to prognosis.

Conclusion: Our results prove the clinical use of ampullary cancer subclassification based on different histotypes and indicate the useful role of the CK7/CK20 expression profile for consistent histopathological classification and prognostic relevance.
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http://dx.doi.org/10.1097/MPA.0b013e318258fda8DOI Listing
January 2013

Impact of arterial revascularization in patients undergoing coronary bypass.

J Card Surg 2012 Jul 12;27(4):427-33. Epub 2012 Jun 12.

Department of Cardiac Surgery, Anthea Hospital, GVM Care & Research, Bari, Italy.

Background And Aim: A debate over alternative therapeutic strategies for multivessel coronary disease is currently ongoing. We aimed at analyzing the results of myocardial revascularization with arterial conduits.

Methods: We retrospectively reviewed 10,752 patients undergoing isolated coronary bypass surgery within our hospital's group. Average follow-up was 37.2 months. Through propensity-matching, we generated three groups (3584 patients each) on the basis of the revascularization strategy: use of one mammary artery plus venous grafts, use of two mammary arteries plus venous graft, and total arterial revascularization.

Results: Overall operative mortality was 2.8%. Patient-related factors (renal failure, advanced age, recent myocardial infarction, depressed LVEF, diabetes) were identified as predictors of mortality (logistic regression). Although mortality was not statistically different among groups, patients receiving more than one arterial conduit displayed in the long-term better freedom from cardiac death and from adverse cardiac events (repeat revascularization, myocardial infarction, recurrent angina) (Kaplan-Meier analysis). Use of only one arterial conduit, diabetes and depressed LVEF predicted cardiac mortality, and adverse events (Cox regression). No differences in any endpoint emerged among patients receiving two arterial conduit plus venous grafts or total arterial revascularization.

Conclusions: These data strongly support the practice of using two arterial conduits rather than one. The operative and late results of coronary surgery with arterial conduits are optimal and should serve as a current benchmark for the comparison with state-of-the-art percutaneous interventions.
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http://dx.doi.org/10.1111/j.1540-8191.2012.01481.xDOI Listing
July 2012
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