Research

Liver cancer

Clinical oncology

The Hepatobiliary Surgery Unit of Padova is a Regional Referral Centre for liver cancer and has a proven expertise in surgical treatment for primitive and metastatic liver cancer. It represents the center with the highest volume of oncological interventions for liver tumors in Italy according to last reports AGENAS. The clinical activity is based on solid contributions in basic, translational and clinical research. The continuous collaboration with other research groups is based on a stron commitment to innovation and guarantees the sharing of clinical and research protocols useful for training fellows and for providing care for patients with oncological liver diseases.

Overview of the research lines:

Primary liver cancer
Metastatic liver cancer
Liver transplantation for oncologic indications
Biobanking and cell biology Prognostic tools and Molecular signature

Primitive liver cancer

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is the second leading cause of cancer-related death worldwide. The treatment of HCC is based on liver transplantation, liver resection, thermal ablation, locoregional therapies and pharmacological treatment. The center provided a relevant contribution in the most recent national clinical guideline production. Cholangiocarcinoma (CCA) is a rare malignancy of the biliary duct system that may originate within the liver or in extrahepatic bile ducts, which terminate at the ampulla of Vater. Three different kind of tumor are described: intrahepatic cholangiocarcinoma (iCCA), perihilar cholangiocarcinoma (pCCA) and distal cholangiocarcinoma (dCCA) with different clinical presentation, diagnosis, treatment and prognosis. We are focusing our attention on the realization of a biomarkers panel for the study of the tumor biology.  

Publications:

1: Lai Q, Vitale A, Rossi M, Cillo U, Lerut J; European Hepatocellular Cancer Liver Transplantation (EurHeCaLT) Study Group. Which Is the True Role of Bridging Therapies for HCC Patients Waiting for Liver Transplantation? Ann Surg. 2017 Oct 23.

2: Akamatsu N, Cillo U, Cucchetti A, Donadon M, Pinna AD, Torzilli G, Kokudo N.Surgery and Hepatocellular Carcinoma. Liver Cancer. 2016 Nov;6(1):44-50.

3: Notarpaolo A, Layese R, Magistri P, Gambato M, Colledan M, Magini G,Miglioresi L, Vitale A, Vennarecci G, Ambrosio CD, Burra P, Di Benedetto F,Fagiuoli S, Colasanti M, Maria Ettorre G, Andreoli A, Cillo U, Laurent A,Katsahian S, Audureau E, Roudot-Thoraval F, Duvoux C. Validation of the AFP modelas a predictor of HCC recurrence in patients with viral hepatitis-related cirrhosis who had received a liver transplant for HCC. J Hepatol. 2017Mar;66(3):552-559.

4: Vitale A, Moustafa M, Spolverato G, Gani F, Cillo U, Pawlik TM. Defining the possible therapeutic benefit of lymphadenectomy among patients undergoing hepatic resection for intrahepatic cholangiocarcinoma. J Surg Oncol. 2016 May;113(6):685-91. doi: 10.1002/jso.24213. Epub 2016 Mar 3. PubMed PMID:26936676.

5: Cillo U, Spolverato G, Vitale A, Ejaz A, Lonardi S, Cosgrove D, Pawlik TM.Liver Resection for Advanced Intrahepatic Cholangiocarcinoma: A Cost-UtilityAnalysis. World J Surg. 2015 Oct;39(10):2500-9. doi: 10.1007/s00268-015-3150-1.PubMed PMID: 26148521.

Funding:

Ordinary department funding.

People involved:

Umberto Cillo, Full Professor
Enrico Gringer, Associate Professor
Fabio Farinati, Full Professor
Luca Fabris,Associate Professor

Group members:
Domenico Bassi, Riccardo Boetto, Francesco D’Amico, Alessandro Vitale, Marina Polacco (Hepatobiliary Surgeons), Alessandra Bertacco, Michela Di Giunta (Hepatobiliary Surgery Fellows)


Metastatic liver cancer

A liver metastasis is a tumor that has spread to the liver from a cancer that started in another place in the body. The liver is commonly involved when the tumor arises from gastrointestinal tract (colon, rectum, stomach, esophagus), pancreas, breast, lung, uterus. The best treatment is based on surgical resection. Unfortunately only 10-20% of the patients are really resectable at diagnosis and the only possible treatment is based on systemic therapy. Our fields of interest are represented by minimally invasive liver surgery, ex situ-liver resection, new biomarkers identification, research on circulating tumor cells.

Publications:

1: Cremolini C, Casagrande M, Loupakis F, Aprile G, Bergamo F, Masi G, Moretto R R, Pietrantonio F, Marmorino F, Zucchelli G, Tomasello G, Tonini G, Allegrini G, Granetto C, Ferrari L, Urbani L, Cillo U, Pilati P, Sensi E, Pellegrinelli A,Milione M, Fontanini G, Falcone A. Efficacy of FOLFOXIRI plus bevacizumab inliver-limited metastatic colorectal cancer: A pooled analysis of clinical studiesby Gruppo Oncologico del Nord Ovest. Eur J Cancer. 2017 Mar;73:74-84.

2: Spolverato G, Vitale A, Ejaz A, Cosgrove D, Cowzer D, Cillo U, Pawlik TM.Hepatic Resection for Disappearing Liver Metastasis: a Cost-Utility Analysis. JGastrointest Surg. 2015 Sep;19(9):1668-75

3: Spampinato MG, Arvanitakis M, Puleo F, Mandala L, Quarta G, Traisci D, PlaiaA, Di Bartolomeo N, Baldazzi G, Cillo U. Totally laparoscopic liver resections for primary and metastatic cancer in the elderly: safety, feasibility and short-term outcomes. Surg Endosc. 2013 Jun;27(6):1881-6.

4: Gringeri E, Polacco M, D'Amico FE, Bassi D, Boetto R, Tuci F, Bonsignore P,Noaro G, D'Amico F, Vitale A, Feltracco P, Barbieri S, Neri D, Zanus G, Cillo U. Liver autotransplantation for the treatment of unresectable hepatic metastasis:an uncommon indication-a case report. Transplant Proc. 2012 Sep;44(7):1930-3.

5: Romano M, DE Francesco F, Zarantonello L, Ruffolo C, Ferraro GA, Zanus G,Giordano A, Bassi N, Cillo U. From Inflammation to Cancer in Inflammatory BowelDisease: Molecular Perspectives. Anticancer Res. 2016 Apr;36(4):1447-60. Review.

Funding:

Ordinary department funding.

People involved:
Umberto Cillo, Full Professor
Enrico Gringeri, Associate Professor
Fabio Farinati (Full Professor

Group members:
Domenico Bassi, Riccardo Boetto, Francesco D’Amico, Alessandro Vitale, Marina Polacco (Hepatobiliary Surgeons), Alessandra Bertacco, Michela Di Giunta (Hepatobiliary Surgery Fellows)


Liver transplantation for oncologic indications

The efficacy of Direct-Acting Antiviral (DAA) for the eradication of hepatitis C infection (HCV) is significantly changing the scenario of liver transplantation. In the immediate future more and more donors will be available for new oncological indications. Liver transplantation for Hepatocarcinoma (HCC) represents one of the most frequent indication for liver transplantation. Recently, in Italy, well selected cases of patients with oncological diagnosis are considered for liver transplantation: colo-rectal liver metastases, perihilar cholangiocarcinoma (pCCA), hepitelioid hemangioendotelioma and neuroendocrine tumor liver metastases. We are focusing our research area in the improvement of liver transplantation protocol for oncological indication and surveillance after transplantation

Publications:

1: Lai Q, Vitale A, Iesari S, Finkenstedt A, Mennini G, Spoletini G, Hoppe-Lotichius M, Vennarecci G, Manzia TM, Nicolini D, Avolio AW, Frigo AC, Graziadei I, Rossi M, Tsochatzis E, Otto G, Ettorre GM, Tisone G, Vivarelli M,Agnes S, Cillo U, Lerut J; European Hepatocellular Cancer Liver Transplant Study Group. Intention-to-treat survival benefit of liver transplantation in patientswith hepatocellular cancer. Hepatology. 2017 Dec;66(6):1910-1919.

2: Zanetto A, Shalaby S, Vitale A, Mescoli C, Ferrarese A, Gambato M, Franceschet E, Germani G, Senzolo M, Romano A, Angeli P, Rugge M, Farinati F, Forton DM,Cillo U, Burra P, Russo FP. Dropout rate from the liver transplant waiting list because of hepatocellular carcinoma progression in hepatitis C virus-infected patients treated with direct-acting antivirals. Liver Transpl. 2017 Sep;23(9):1103-1112.

3: Vitale A, Huo TL, Cucchetti A, Lee YH, Volk M, Frigo AC, Cescon M, Tuci F,Pinna AD, Cillo U. Survival Benefit of Liver Transplantation Versus Resection for Hepatocellular Carcinoma: Impact of MELD Score. Ann Surg Oncol. 2015;22(6):1901-7.

5: Gringeri E, Bassi D, D'Amico FE, Boetto R, Polacco M, Lodo E, D'Amico F,Vitale A, Boccagni P, Zanus G, Cillo U. Neoadjuvant therapy protocol and liver transplantation in combination with pancreatoduodenectomy for the treatment of hilar cholangiocarcinoma occurring in a case of primary sclerosing cholangitis:case report with a more than 8-year disease-free survival. Transplant Proc. 2011 May;43(4):1187-9.

Funding:

Ordinary department funding.

People involved:
Umberto Cillo, Full Professor
Enrico Gringeri, Associate Professor
Fabio Farinati, full Professor

Group members:
Domenico Bassi, Riccardo Boetto, Francesco D’Amico, Alessandro Vitale, Marina Polacco (Hepatobiliary Surgeons), Alessandra Bertacco, Michela Di Giunta (Hepatobiliary Surgery Fellows)


Biobanking and cell biology - Molecular signature

A biobank is essentially a collection of biospecimens that have been ethically collected, well-annotated, and stored using standard operating procedures (SOPs). The field of biobanking has grown tremendously in size and complexity over the last couple of decades, and is now considered an essential part of the healthcare infrastructure. In this era of precision (sometimes termed “personalized”) oncology, biobanks represent a highly valuable resource for biomarker translational research and cancer drug discovery. We are particularly interested in this new and promising research area. Our department has recently submitted a research program regarding the preparation of a biobank.

Publications:

1: Fasolato S, Trevellin E, Ruvoletto M, Granzotto M, Zanus G, Boscaro E, Babetto E, Terrin L, Battocchio MA, Ciscato F, Turato C, Quarta S, Cillo U, Pontisso P,Vettor R. SerpinB3 induces dipeptidyl-peptidase IV/CD26 expression and its metabolic effects in hepatocellular carcinoma. Life Sci. 2018 May 1;200:134-141.

2: Turato C, Cannito S, Simonato D, Villano G, Morello E, Terrin L, Quarta S, Biasiolo A, Ruvoletto M, Martini A, Fasolato S, Zanus G, Cillo U, Gatta A, Parola M, Pontisso P. SerpinB3 and Yap Interplay Increases Myc Oncogenic Activity. Sci Rep. 2015 Dec 4;5:17701.

3: Pozzan C, Cardin R, Piciocchi M, Cazzagon N, Maddalo G, Vanin V, Giacomin A,Pontisso P, Cillo U, Farinati F. Diagnostic and prognostic role of SCCA-IgM serumlevels in hepatocellular carcinoma (HCC). J Gastroenterol Hepatol. 2014 Aug;29(8):1637-44.

4: Piciocchi M, Cardin R, Vitale A, Vanin V, Giacomin A, Pozzan C, Maddalo G,Cillo U, Guido M, Farinati F. Circulating free DNA in the progression of liver damage to hepatocellular carcinoma. Hepatol Int. 2013 Oct;7(4):1050-7. doi:10.1007/s12072-013-9481-9. Epub 2013 Nov 2.

5: Romano M, De Francesco F, Pirozzi G, Gringeri E, Boetto R, Di Domenico M,Zavan B, Ferraro GA, Cillo U. Expression of cancer stem cell biomarkers as a tool for a correct therapeutic approach to hepatocellular carcinoma. Oncoscience. 2015 May 15;2(5):443-456. eCollection 2015. Review.

Funding:

Ordinary department funding.

People involved:
Umberto Cillo, Full Professor
Enrico Gringeri, Associate Professor
Fabio Farinati, Full Professor

Group members:
Domenico Bassi, Riccardo Boetto, Francesco D’Amico, Alessandro Vitale, Marina Polacco (Hepatobiliary Surgeons), Alessandra Bertacco, Michela Di Giunta (Hepatobiliary Surgery Fellows).