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Nutrient restriction-activated Fra-2 promotes tumor progression via IGF1R in miR-15a downmodulated pancreatic ductal adenocarcinoma

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1132-1146页

作者： Gian Luca Rampioni Vinciguerra Marina Capece Luca Reggiani Bonetti Giovanni Nigita Federica Calore Sydney Rentsch Paolo Magistri Roberto Ballarin fabrizio di benedetto Rosario distefano Roberto Cirombella Andrea Vecchione Barbara Belletti Gustavo Baldassarre Francesca Lovat Carlo M.Croce Department of Cancer Biology and Genetics and Comprehensive Cancer Center The Ohio State UniversityColumbus 43210 OHUSA Department of Clinical and Molecular Medicine Faculty of Medicine and PsychologySant’Andrea HospitalUniversity of Rome“Sapienza”Rome 00189Italy Department of diagnostic Clinic and Public Health MedicineUniversity of Modena and Reggio EmiliaModena 41100Italy Hepato-pancreato-biliary Surgery and Liver Transplantation Unit University of Modena and Reggio EmiliaModena 41100Italy division of Molecular Oncology Centro di Riferimento Oncologico di Aviano(CRO)Istituto di Ricovero e Cura a Carattere Scientifico(IRCCS)National Cancer InstituteAviano 33081Italy

Pancreatic ductal adenocarcinoma(PDAC)is a lethal disease,characterized by an intense desmoplastic reaction that compresses blood vessels and limits nutrient *** aggressiveness largely relies on its extraordinary capability to thrive and progress in a challenging tumor *** of the onco-suppressor miR-15a has been extensively documented in ***,we identified the transcription factor Fos-related antigen-2(Fra-2)as a miR-15a target mediating the adaptive mechanism of PDAC to nutrient *** report that the IGF1 signaling pathway was enhanced in nutrient deprived PDAC cells and that Fra-2 and IGF1R were significantly overexpressed in miR-15a downmodulated PDAC ***,we discovered that miR-15a repressed IGF1R expression via Fra-2 *** miR-15a-low context,IGF1R hyperactivated mTOR,modulated the autophagic flux and sustained PDAC growth in nutrient *** a genetic mouse model,Mir15aKO PDAC showed Fra-2 and Igf1r upregulation and mTOR activation in response to diet ***,nutrient restriction improved the efficacy of IGF1R inhibition in a Fra-2 dependent ***,our results point to a crucial role of Fra-2 in the cellular stress response due to nutrient restriction typical of pancreatic cancer and support IGF1R as a promising and vulnerable target in miR-15a downmodulated PDAC.

关键词： IGF1R Fra miR

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Perihilar-cholangiocarcinoma: what really matters?

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Hepatobiliary Surgery and Nutrition 2022年第4期11卷 616-619页

作者： fabrizio di benedetto Paolo Magistri Stefano di Sandro Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit University Hospital of Modena“Policlinico”University of Modena and Reggio EmiliaModenaItaly

Treatment of peri-hilar cholangiocarcinoma(PHC)is one of the most critical challenges in the modern era of liver surgery(1).In addition to the highly demanding technique and insidious diagnostic work-up,the procedure ... 详细信息

关键词： operative carcinoma liver

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Surgery in biliary lithiasis: from the traditional “open” approach to laparoscopy and the“rendezvous” technique

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Hepatobiliary & Pancreatic diseases International 2017年第6期16卷 595-601页

作者： Giuseppe Tarantino Paolo Magistri Roberto Ballarin Giacomo Assirati Antonio di Cataldo fabrizio di benedetto Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit University of Modena and Reggio Emilia 41124 ModenaItaly Department of General Surgery Sapienza-University of Rome 00189 Rome Italy Department of Surgical Sciences Organ Transplantation and Advanced Technologies University of Catania95124 Catania Italy

BACKGROUND:According to the current literature, biliary lithiasis is a worldwide-diffused condition that affects almost 20% of the general population. The rate of common bile duct stones(CBDS) in patients with symptomatic cholelithiasis is estimated to be 10% to 33%, depending on patient’s *** to stones in the gallbladder, the natural history of secondary CBDS is still not completely understood. It is not clear whether an asymptomatic choledocholithiasis requires treatment or not. For many years, open cholecystectomy with choledochotomy and/or surgical sphincterotomy and cleaning of the bile duct were the gold standard to treat both pathologies. Development of both endoscopic retrograde cholangiopancreatography(ERCP) and laparoscopic surgery,together with improvements in diagnostic procedures, influenced new approaches to the management of CBDS in association with *** SOURCES:We decided to systematically review the literature in order to identify all the current therapeutic options for CBDS. A systematic literature search was performed independently by two authors using Pub Med, EMBASE, Scopus and the Cochrane Library ***:The therapeutic approach nowadays varies greatly according to the availability of experience and expertise in each center, and includes open or laparoscopic common bile duct exploration, various combinations of laparoscopic cholecystectomy and ERCP and combined laparoendoscopic ***:Although ERCP followed by laparoscopic cholecystectomy is currently preferred in the majority of hospitals worldwide, the optimal treatment for concomitant gallstones and CBDS is still under debate, and greatly varies among different centers.

关键词： biliary obstruction bile duct stones gallstones endoscopic retrograde cholangiopancreatography laparoscopic cholecystectomy

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Chasing the right path: tips, tricks and challenges of robotic approach to posterior segments

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Hepatobiliary Surgery and Nutrition 2019年第5期8卷 512-514页

作者： fabrizio di benedetto Giuseppe Tarantino Paolo Magistri Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit University of Modena and Reggio EmiliaModenaMOItaly

The advent of minimally invasive technologies to approachliver diseases changed some paradigms of liver surgeryduring the last two *** allow to safely treatpatients with poor liver function,portal hypertension andcirrhosis,reducing the risk of decompensation(1).However,those potential benefits resulted to be in contrast with theactual application of such technologies in the real-life(2,3).

关键词： liver diseases surgery

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Use of robotics in liver donor right hepatectomy

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Hepatobiliary Surgery and Nutrition 2018年第3期7卷 231-232页

作者： fabrizio di benedetto Paolo Magistri Karim JHalazun Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit University of Modena and Reggio EmiliaModenaMOItaly Department of Medical and Surgical Sciences and Translational Medicine Faculty of Medicine and PsychologySapienza University of RomeRomeRMItaly division of Liver Transplantation and Hepatobiliary Surgery Department of SurgeryWeill Cornell Medical CollegeNew YorkNYUSA

We read with great interest the paper by Chen and colleagues entitled "Use of robotics in liver donor right hepatectomy" (1). The authors currently represent the leading group performing robotic living donor liver pro... 详细信息

关键词： donor liver hepatectomy

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Robotic distal pancreatectomy: can results overcome cost-effectiveness prejudices?

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Hepatobiliary Surgery and Nutrition 2019年第3期8卷 304-306页

作者： fabrizio di benedetto Roberto Ballarin Paolo Magistri Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit University of Modena and Reggio EmiliaModenaMOItaly

Pancreas surgery was historically considered the most challenging type of surgery for surgeons all over the *** is related to higher morbidity and mortality rates as compared to other surgical procedures and survival ... 详细信息

关键词： surgery mortality overcome

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Modern surgical approach to hepatocellular carcinoma

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Hepatobiliary Surgery and Nutrition 2023年第6期12卷 953-955页

作者： Paolo Magistri Gian Piero Guerrini Stefano di Sandro fabrizio di benedetto Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit University Hospital of Modena“Policlinico”University of Modena and Reggio EmiliaModenaItaly

We are glad to contribute with an editorial on the important topic of therapeutic opportunities for hepatocellular carcinoma(HCC).The increasing diffusion of minimally invasive approaches to the liver and the growing experience worldwide have progressively changed our curative strategies for patients affected by primary and metastatic liver tumors(1).

关键词： Robotic surgery minimally invasive liver surgery(MILS) surgical oncology liver transplant living donor liver transplantation(LDLT)

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Hepatocellular carcinoma and liver transplant: beyond the Milan criteria and the risk of "short-blanket" syndrome

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Hepatobiliary Surgery and Nutrition 2020年第4期9卷 518-521页

作者： Stefano Gitto Stefano di Sandro Paolo Magistri Pietro Andreone fabrizio di benedetto Department of Experimental and Clinical Medicine University of FlorenceFlorenceItaly Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit AOU di Modena and University of Modena and Reggio EmiliaModenaItaly Internal and Metabolic Medicine AOU di Modena and University of Modena and Reggio EmiliaModenaItaly

Liver transplant(LT)is considered the best option for patients with hepatocellular carcinoma(HCC)confined into the liver and generally associated with liver cirrhosis(1).The Milan criteria(MC)represent a milestone in the selection of these patients(2).Therefore,basing on MC,the 5-year survival rate after LT could increase to 70%,with a HCC recurrence rate lower than 10%(2).Despite that,too many patients affected by HCC may not benefit from LT due to a tumor stage beyond the selection *** the last two decades,authors and physicians tried to overcome the MC exploring the opportunity to safely transplant patients beyond(3).Notably,the donor shortage and the competition between patients listed due to HCC and those listed for other indications,force physicians in selecting candidates with the best transplant benefit(3).

关键词： beyond listed overcome

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Heavily calcified gastrointestinal stromal tumors:Pathophysiology and implications of a rare clinicopathologic entity

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World Journal of Gastrointestinal Oncology 2017年第3期9卷 135-141页

作者： Massimiliano Salati Giulia Orsi Luca Reggiani Bonetti fabrizio di benedetto Giuseppe Longo Stefano Cascinu Department of Medical and Surgical Sciences for Children and Adults Division of Medical OncologyUniversity Hospital of Modena and Reggio Emilia Department of diagnostic Medicine and Public Health Division of PathologyUniversity Hospital of Modena and Reggio Emilia Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit University Hospital of Modena and Reggio Emilia Azienda Ospedaliero-Universitaria Policlinico di Modena

Gastrointestinal stromal tumors(GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract, and are characterized by a broad spectrum of clinical, histological and molecular features at presentation. Although focal and scattered calcifications are not uncommon within the primary tumor mass, heavy calcification within a GIST is rarely described in the literature and the clinical-biological meaning of this feature remains unclear. Cases with such an atypical presentation are challenging and may be associated with diagnostic pitfalls. Herein, we report a gastric GIST with the unusual presentation of prominent calcifications that was identified incidentally on imaging during a post-trauma diagnostic work-up. The patient underwent laparoscopic surgery with a radical resection of the mass, which was subsequently characterized by histological analysis as spindle-shaped tumor cells, positive for CD117/c-KIT, CD34 and DOG1, and with calcified areas. Given the intermediate risk of recurrence, no adjuvant therapy was recommended andthe patient underwent regular follow-up for 22 mo, with no evidence of relapse. Our case can be considered of interest because of the rarity of clinical presentation and the uniquely large size of the GIST at diagnosis(longest diameter exceeding 9 cm). In closing, we discuss the pathophysiology and clinical implications of calcifications in GISTs by reviewing the most up-to-date relevant literature.

关键词： Gastrointestinal stromal tumor Calcification Stomach Atypical presentation Computed tomography

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Robotic liver surgery is the optimal approach as bridge to transplantation

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World Journal of Hepatology 2017年第4期9卷 224-226页

作者： Paolo Magistri Giuseppe Tarantino Roberto Ballarin Andrea Coratti fabrizio di benedetto Department of Medical and Surgical Sciences and Translational Medicine Sapienza - University of Rome Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit University of Modena and Reggio Emilia Department of Oncology Division of Oncological and Robotic General Surgery Careggi University Hospital

The role of minimally invasive liver surgery as a bridge to transplantation is very promising but still underestimated. However, it should be noted that surgical approach for hepatocellular carcinomas(HCC) is not merely a technical or technological issue. Nowadays, the epidemiology of HCC is evolving due to the increasing role of non-alcoholic fatty-liver-disease, and the emerging concerns on direct-acting antivirals against hepatitis C virus in terms of HCC incidence. Therefore, a fully multidisciplinary study of the cirrhotic patient is currently more important than ever before, and the management of those patients should be reserved to tertiary referral hepatobiliary centers. In particular, minimally invasive approach to the liver showed several advantages compared to the classical open procedure, in terms of:(1) the small impact on abdominal wall;(2) the gentle manipulation on the liver;(3) the limited surgical trauma; and(4) the respect of venous shunts. Therefore, more direct indications should be outlined also in the Barcelona Clinic Liver Cancer model. We believe that treatment of HCC in cirrhotic patients should be reserved to tertiary referral hepatobiliary centers, that should offer patient-tailored approaches to the liver disease, in order to provide the best care for each case, according to the individual comorbidities, risk factors, and personal quality of life expectations.

关键词： Hepatocellular carcinomas Liver transplant Robotic surgery Bridge to transplantation Da vinci Barcelona Clinic Liver Cancer Patient safety

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