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Advanced hepatocellular carcinoma and sorafenib: Diagnosis, indications, clinical and radiological follow-up

World Journal of Hepatology 2015年第8期7卷 1041-1053页

作者： Stefano Colagrande Francesco Regini Gian Giacomo Taliani Cosimo Nardi Andrea Lorenzo Inghilesi Dipartimento di Scienze Biomediche Sperimentali e Cliniche Università degli Studi di Firenze-Azienda Ospedaliero-Universitaria Careggi Dipartimento di Medicina Speri-mentale e Clinica Università degli Studi di Firenze-Azienda Ospedaliero-Universitaria Careggi

Advanced stage hepatocellular carcinoma(HCC) is a category of disease defined by radiological, clinical and hepatic function parameters, comprehending a wide range of patients with different general conditions. The main therapeutic option is represented by sorafenibtreatment, a multi-kinase inhibitor with anti-proliferative and anti-angiogenic effect. Trans-arterial Radio Embolization also represents a promising new approach to intermediate/advanced HCC. Post-marketing clinical studies showed that only a portion of patients actually benefits from sorafenib treatment, and an even smaller percentage of patients treated shows partial/complete response on follow-up examinations, up against relevant costs and an incidence of drug related adverse effects. Although the treatment with sorafenib has shown a significant increase in mean overall survival in different studies, only a part of patients actually shows real benefits, while the incidence of drug related significant adverse effects and the economic costs are relatively high. Moreover, only a small percentage of patients also shows a response in terms of lesion dimensions reduction. Being able to properly differentiate patients who are responding to the therapy from non-responders as early as possible is then still difficult and could be a pivotal challenge for the future; in fact it could spare several patients a therapy often difficult to bear, directing them to other second line treatments(many of which are at the moment still under investigation). For this reason, some supplemental criteria to be added to the standard modified Response Evaluation Criteria in Solid Tumors evaluation are being searched for. In particular, finding some parameters(cellular density, perfusion grade and enhancement rate) able to predict the sensitivity of the lesions to anti-angiogenic agents could help in stratifying patients in terms of treatment responsiveness before the beginning of the therapy itself, or in the first weeks of sorafenib treatment. This would bring a strongly desi

关键词： Modified Response Evaluation Criteria inSolid Tumors Diffusion weighted imaging Barcelonaclinic liver cancer Advanced hepatocellular carcinoma Sorafenib Advanced hepatocellular carcinoma secondline therapies Perfusion weighted imaging Responseevaluation Hepatocellular carcinoma follow-up Response Evaluation Criteria in Solid Tumors

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challenges of advanced hepatocellular carcinoma

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World Journal of Gastroenterology 2016年第34期22卷 7645-7659页

作者： Stefano Colagrande Andrea L Inghilesi Sami Aburas Gian G Taliani Cosimo Nardi Fabio Marra Dipartimento di Scienze Biomediche Sperimentali e Cliniche University of Florence Dipartimento di Medicina Sperimentale e Clinica Centro di Ricerca DenotheUniversity of Florence

Hepatocellular carcinoma(HCC) is an aggressive malignancy,resulting as the third cause of death by cancer each year. The management of patients with HCC is complex,as both the tumour stage and any underlying liver disease must be considered conjointly. Although surveillance by imaging,clinical and biochemical parameters is routinely performed,a lot of patients suffering from cirrhosis have an advanced stage HCC at the first diagnosis. Advanced stage HCC includes heterogeneous groups of patients with different clinical condition and radiological features and sorafenib is the only approved treatment according to Barcelona Clinic Liver Cancer. Since the introduction of sorafenib in clinical practice,several phase Ⅲ clinical trials have failed to demonstrate any superiority over sorafenib in the frontline setting. Locoregional therapies have also been tested as first line treatment,but their role in advanced HCC is still matter of debate. No single agent or combination therapies have been shown to impact outcomes after sorafenib failure. Therefore this review will focus on the range of experimental therapeutics for patients with advanced HCC and highlights the successes and failures of these treatments as well as areas for future development. Specifics such as dose limiting toxicity and safety profile in patients with liver dysfunction related to the underlying chronic liver disease should be considered when developing therapies in HCC. Finally,robust validated and reproducible surrogate end-points as well as predictive biomarkers should be defined in future randomized trials.

关键词： Barcelona Clinic Liver Cancer Portal vein thrombosis Modified Response Evaluation Criteria in Solid Tumors Advanced hepatocellular carcinoma management Advanced hepatocellular carcinoma second line therapies Sorafenib

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Imaging of the chemotherapy-induced hepatic damage:Yellow liver,blue liver,and pseudocirrhosis

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World Journal of Gastroenterology 2021年第46期27卷 7866-7893页

作者： Linda Calistri Vieri Rastrelli Cosimo Nardi Davide Maraghelli Sofia Vidali Michele Pietragalla Stefano Colagrande Department of Experimental and Clinical Biomedical Sciences Mario Serio University of FlorenceAzienda Ospedaliera Universitaria CareggiFlorence 50134Italy

The liver is the major drug-metabolizing and drug-detoxifying organ.Many drugs can cause liver damage through various mechanisms;however,the liver response to injury includes a relatively narrow spectrum of alterations that,regardless of the cause,are represented by phlogosis,oxidative stress and necrosis.The combination of these alterations mainly results in three radiological findings:vascular alterations,structural changes and metabolic function reduction.Chemotherapy has changed in recent decades in terms of the drugs,protocols and duration,allowing patients a longer life expectancy.As a consequence,we are currently observing an increase in chemotherapy-associated liver injury patterns once considered unusual.Recognizing this form of damage in an early stage is crucial for reconsidering the therapy regimen and thus avoiding severe complications.In this frontier article,we analyze the role of imaging in detecting some of these pathological patterns,such as pseudocirrhosis,“yellow liver”due to chemotherapy-associated steatosis-steatohepatitis,and“blue liver”,including sinusoidal obstruction syndrome,veno-occlusive disease and peliosis.

关键词： Hepatic damage Yellow liver Chemotherapy-associated steatohepatitis Blue liver Sinusoidal obstruction syndrome Veno-occlusive disease Peliosis Pseudocirrhosis

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Pancreatic fistula:A proposed percutaneous procedure

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World Journal of Hepatology 2013年第1期5卷 33-37页

作者： Silvia Pradella Ernesto Mazza Francesco Mondaini Stefano Colagrande Department of Experimental and Clinical Biomedical Sciences Section of RadiodiagnosticsUniversity of Florence Azienda OspedalieroUniversitaria Careggi 50134 FlorenceItaly Department of Diagnostic Imaging Section of Interventional RadiologyAzienda Ospedaliero-Universitaria Careggi50134 FlorenceItaly

AIM:To propose a percutaneous treatment for otherwise intractable pancreatic fistula (PF).METHODS:From 2005 to 2011,12 patients (9 men and 3 women,mean age 59 years,median 63 years,range 33-78 years) underwent radiological treatment for high-output PF associated with peripancreatic fluid collection.The percutaneous procedures were performed after at least 4 wk of unsuccessful conservative treatments.We chose either a one or two step procedure,depending on the size and characteristics of the fistula and the fluid collection (with an arbitrary cut-off of 2 cm).Initially,2 to 6 pigtail drainages of variable size from 8.3 (8.3-Pig Duan Cook,Bloomington,Indiana,United States) to 14 Fr (Flexima,Boston Scientific,Natick,United States) were positioned inside the collection using a transgastric approach.In a second procedure,after 7-10 d,two or more endoprostheses (cystogastrostomic 8 Fr double-pigtail,Cook,Bloomington,Indiana,United States in 10 patients;covered Niti-S stent,TaeWoong Medical Co,Seoul,South Korea in 2 patients) were placed between the collection and the gastric lumen.In all cases the metal or plastic pros-theses were removed within one year after positioning.RESULTS:Four out of 12 high-output fistulas fistulas were external while 8/12 were internal.The origin of the fistulous tract was visualised by computer tomography (CT) imaging studies:in 11 patients it was at the body,and in 1 patient at the tail of the pancreas.Single or multiple drainages were positioned under CT guidance.The catheters were left in place for a varying period (0 to 40 d-median 10 and 25 th-75 th percentile 0-14).In one case external transgastric drainages were left in place for a prolonged time (40 d) due to the presence of vancomycin-resistant bacteria (Staphylococcus) and fluconazole-resistant fungi (Candida) in the drained fluid.In this latter case systemic and local antibiotic therapy was administered.In both single and two-step techniques,when infection was present,we carried out additional washing with antibiotics to improve t

关键词： Pancreas Pancreatic fistula Interventional radiology Pancreatic surgery Complications

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Doege-Potter syndrome by malignant solitary fibrous tumor of the liver: A case report and review of literature

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World Journal of Gastrointestinal Surgery 2019年第8期11卷 348-357页

作者： Delvecchio Antonella Duda Loren Conticchio Maria Fiore Felicia Lafranceschina stefano Riccelli Umberto Cristofano Antonella Pascazio Bianca colagrande Anna Resta Leonardo Memeo Riccardo Department of Emergency and Organ Transplantation General Surgery Unit “M. Rubino” University of Bari Bari 70124 Italy Department of Pathology University of Bari Bari 70124 Italy Department of Oncology Ente Ecclesiastico Ospedale F. Miulli Acquaviva delle Fonti 70021 Italy Department of General Surgery Ospedale San Paolo Bari 70123 Italy

BACKGROUND Solitary fibrous tumor of the liver (SFTL) is a rare occurrence with a low number of cases reported in literature. SFTL is usually benign but, 10%-20% cases are reported to be malignant with a tendency to metastasize. The majority of malignant SFTL cases are associated with a paraneoplastic hypoglycaemia defined as Doege-Potter syndrome. Surgery is the best therapeutic treatment, however, long- life follow-up is recommended. CASE SUMMARY A 74-year-old man, was admitted to the emergency department after a syncopal episode with detection of hypoglycaemia resistant to medical treatment. The computed tomography revealed a solid mass measuring 15 cm of the left liver. An open left hepatectomy was performed with complete resection of tumor. Histopathological analyses confirmed a malignant SFTL. CONCLUSION Large series with long-term follow-up have not been published neither have clinical trials been undertaken. Consequently, the methodical long-term followup of surgically treated SFTLs is strongly recommended.

关键词： Solitary fibrous tumor Malignant solitary fibrous tumor of the liver Mesenchymal tumor Hepatic tumor Doege-Potter syndrome

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Predictors of survival in patients with established cirrhosis and hepatocellular carcinoma treated with sorafenib

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World Journal of Gastroenterology 2014年第3期20卷 786-794页

作者： Andrea L Inghilesi Donatella Gallori Lorenzo Antonuzzo Paolo Forte Daniela Tomcikova Umberto Arena Stefano Colagrande Silvia Pradella Bernardo Fani Elena Gianni Luca Boni Giacomo Laffi Francesco Di Costanzo Fabio Marra Dipartimento di Medicina Sperimentale e Clinica Università degli Studi di Firenze Oncologia Medica Azienda Ospedaliero-Universitaria Careggi Gastroenterologia 2 Azienda Ospedaliero-Universitaria Careggi Centro per il Coordinamento delle Sperimentazioni Cliniche Istituto Toscano Tumoriand Azienda Ospedaliero-Universitaria Careggi Dipartimento di Scienze Biomediche Sperimentali e ClinicheUniversità degli Studi di Firenze

AIM:To investigate in greater detail the efficacy and safety of sorafenib for the treatment of hepatocellular carcinoma(HCC)in patients with established cirrhosis.METHODS:From October 2009 to July 2012 patients with an established diagnosis of cirrhosis and HCC treated with sorafenib were consecutively enrolled.According to the Barcelona Clinic Liver Cancer(BCLC)classification,patients were in the advanced stage(BCLC-C)or in the intermediate stage(BCLC-B)but unfit or unresponsive to other therapeutic strategies.Treatment was evaluated performing a 4-phase computed tomography or magnetic resonance imaging scan every 2-3 mo,and analyzed according to the modified Response Evaluation Criteria in Solid Tumors.Sorafenib was administered at 800 mg/d,until radiological progression or occurrence of unacceptable adverse events(AEs).Univariate and multivariate analyses identified predictors of 16-wk clinical benefit and overall survival.RESULTS:Forty-four patients were enrolled,15 had intermediate HCC and 14 a Child-Pugh score of B7.AEs caused treatment interruption in 19 patients(43%),and median treatment duration was shorter in this subset(5 wk vs 19 wk,P<0.001)and in the BCLC-C subgroup(13 wk vs 40 wk,P=0.015).No significant differences in the reason for treatment interruption or in treatment duration were found comparing patients in Child-Pugh class A vs B or in patients older or younger than 70 years.After 16 wk of treatment,18 patients(41%)had stable disease or partial response.Patients with viral infection or BCLC-C were at higher risk of disease progression.ECOG,extrahepatic spread,macrovascular invasion,alpha-fetoprotein or alkaline phosphatase levels at admission were independent predictors of overall survival.CONCLUSION:In patients with cirrhosis and HCC treated with sorafenib,AEs are a common cause of early treatment withdrawal.Vascular invasion and extrahepatic spread condition early response to treatment and survival.Baseline biochemical parameters may be helpful to identify patients at higher risk of shorter

关键词： Hepatocellular carcinoma Sorafenib Cirrhosis Adver

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