Francesco Vasuri | Università di Bologna (original) (raw)

Papers by Francesco Vasuri

Research paper thumbnail of Synchronous hepatocellular carcinoma and renal cell carcinoma in a liver transplant recipient: a case report

Transplantation, Jan 27, 2007

Research paper thumbnail of The role of peritumoral CD8 + /TIA1 + lymphocytes in hepatocellular carcinoma aggressiveness and recurrence after surgical resection

Pathology - Research and Practice

Research paper thumbnail of Automatically Extracted Machine Learning Features from Preoperative CT to Early Predict Microvascular Invasion in HCC: The Role of the Zone of Transition (ZOT)

Cancers

Background: Microvascular invasion (MVI) is a consolidated predictor of hepatocellular carcinoma ... more Background: Microvascular invasion (MVI) is a consolidated predictor of hepatocellular carcinoma (HCC) recurrence after treatments. No reliable radiological imaging findings are available for preoperatively diagnosing MVI, despite some progresses of radiomic analysis. Furthermore, current MVI radiomic studies have not been designed for small HCC nodules, for which a plethora of treatments exists. This study aimed to identify radiomic MVI predictors in nodules ≤3.0 cm by analysing the zone of transition (ZOT), crossing tumour and peritumour, automatically detected to face the uncertainties of radiologist’s tumour segmentation. Methods: The study considered 117 patients imaged by contrast-enhanced computed tomography; 78 patients were finally enrolled in the radiomic analysis. Radiomic features were extracted from the tumour and the ZOT, detected using an adaptive procedure based on local image contrast variations. After data oversampling, a support vector machine classifier was devel...

Research paper thumbnail of Molecular Characterization of Pancreatic Ductal Adenocarcinoma Using a Next-Generation Sequencing Custom-Designed Multigene Panel

Diagnostics

Despite the efforts made in the management of PDAC, the 5-year relative survival rate of pancreat... more Despite the efforts made in the management of PDAC, the 5-year relative survival rate of pancreatic ductal adenocarcinoma (PDAC) still remains very low (10%). To date, precision oncology is far from being ready to be applied in cases of PDAC, although studies exploring the molecular and genetic alterations have been conducted, and the genomic landscape of PDAC has been characterized. This study aimed to apply a next-generation sequencing (NGS) laboratory-developed multigene panel to PDAC samples to find molecular alterations that could be associated with histopathological features and clinical outcomes. A total of 68 PDACs were characterized by using a laboratory-developed multigene NGS panel. KRAS and TP53 mutations were the more frequent alterations in 75.0% and 44.6% of cases, respectively. In the majority (58.7%) of specimens, more than one mutation was detected, mainly in KRAS and TP53 genes. KRAS mutation was significantly associated with a shorter time in tumor recurrence com...

Research paper thumbnail of ETS-Related Gene Expression in Healthy Femoral Arteries With Focal Calcifications

Frontiers in Cell and Developmental Biology

Bone development-related genes are enriched in healthy femoral arteries, which are more prone to ... more Bone development-related genes are enriched in healthy femoral arteries, which are more prone to calcification, as documented by the predominance of fibrocalcific plaques at the femoral location. We undertook a prospective histological study on the presence of calcifications in normal femoral arteries collected from donors. Since endothelial-to-mesenchymal transition (EndMT) participates in vascular remodeling, immunohistochemical (IHC) and molecular markers of EndMT and chondro-osteogenic differentiation were assessed. Transmission electron microscopy (TEM) was used to describe calcification at its inception. Two hundred and fourteen femoral arteries were enrolled. The mean age of the donors was 39.9 ± 12.9 years; male gender prevailed (M: 128). Histology showed a normal architecture; calcifications were found in 52 (24.3%) cases, without correlations with cardiovascular risk factors. Calcifications were seen on or just beneath the inner elastic lamina (IEL). At IHC, SLUG was incre...

Research paper thumbnail of Adventitial Microcirculation Is a Major Target of SARS-CoV-2-Mediated Vascular Inflammation

Biomolecules

We report the case of a 77-year-old woman affected by coronavirus disease-19 (COVID-19) who devel... more We report the case of a 77-year-old woman affected by coronavirus disease-19 (COVID-19) who developed an occlusive arterial disease of the lower limb requiring a left leg amputation. We studied the mechanisms of vascular damage by SARS-CoV-2 by means of a comprehensive multi-technique in situ analysis on the diseased popliteal arterial district, including immunohistochemistry (IHC), transmission electron microscopy (TEM) and miRNA analysis. At histological analyses, we observed a lymphocytic inflammatory infiltrate, oedema and endothelialitis of adventitial vasa vasorum while the media was normal and the intima had only minor changes. The vasa vasorum expressed the ACE2 receptor and factor VIII; compared with the controls, VEGFR2 staining was reduced. TEM analyses showed endothelial injury and numerous Weibel–Palade bodies in the cytoplasm. No coronavirus particle was seen. IL-6 protein and mRNA, together with miR-155-5p and miRs-27a-5p, which can target IL-6, were significantly inc...

Research paper thumbnail of Aflatoxin B1 DNA-Adducts in Hepatocellular Carcinoma from a Low Exposure Area

Nutrients

Aflatoxin B1 (AFB1) is a class 1 carcinogen with an ascertained role in the development of hepato... more Aflatoxin B1 (AFB1) is a class 1 carcinogen with an ascertained role in the development of hepatocellular carcinoma (HCC) in high exposure areas. Instead, this study aimed to assay whether chronic/intermittent, low-dose AFB1 consumption might occur in low-exposure geographical areas, ultimately accumulating in the liver and possibly contributing to liver cancer. AFB1-DNA adducts were assayed by immunostaining in liver tissues from three Italian series of twenty cirrhosis without HCC, 131 HCC, and 45 cholangiocarcinoma, and in an AFB1-induced HCC rat model. CD68, TP53 immunostaining, and TP53 RFLP analysis of R249S transversion were used to characterize cell populations displaying AFB1-DNA adducts. Twenty-five HCCs displayed AFB1-adducts both in neoplastic hepatocytes and in cells infiltrating the tumor and non-tumor tissues. Nuclear immunostaining was observed in a few cases, while most cases showed cytoplasmic immunostaining, especially in CD68-positive tumor-infiltrating cells, su...

Research paper thumbnail of Research Article Diffuse Calcifications Protect Carotid Plaques regardless of the Amount of Neoangiogenesis and Related Histological Complications

Copyright © 2015 Francesco Vasuri et al. This is an open access article distributed under the Cre... more Copyright © 2015 Francesco Vasuri et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. Neoangiogenesis is crucial in plaque progression and instability. Previous data from our group showed that Nestin-positive intraplaque neovessels correlatedwith histological complications.The aimof the present work is to evaluate the relationship between neoangiogenesis, plaque morphology, and clinical instability of the plaque.Materials and Methods. Seventy-three patients (53 males and 20 females, mean age 71 years) were consecutively enrolled. Clinical data and 14 histological variables, including intraplaque hemorrhage and calcifications, were collected. Immunohistochemistry for CD34 and Nestin was performed. RT-PCR was performed to evaluate Nestin mRNA (including 5 healthy arteries as controls). Results. Diffusely c...

Research paper thumbnail of Venous outflow in partial heterotopic liver transplantation with spleen replacement: Evidence of no chronic venous hypertension

American Journal of Transplantation, 2021

We recently described the first case of partial heterotopic liver transplantation replacing the s... more We recently described the first case of partial heterotopic liver transplantation replacing the spleen with delayed recipient hepatectomy to overcome the problem of organ shortage and to make possible debated indications for liver transplantation.1,2 The surgical technique of the RAVAS procedure was described in different steps: before planning the operation1 and after the first procedure performed, with a case report and video of the technique.

Research paper thumbnail of MicroRNA expression profiling with a droplet digital PCR assay enables molecular diagnosis and prognosis of cancers of unknown primary

Research paper thumbnail of MicroRNA profiles of human peripheral arteries and abdominal aorta in normal conditions: MicroRNAs-27a-5p, -139-5p and -155-5p emerge and in atheroma too

Mechanisms of Ageing and Development, 2021

Atherosclerosis may starts early in life and each artery has peculiar characteristics likely affe... more Atherosclerosis may starts early in life and each artery has peculiar characteristics likely affecting atherogenesis. The primary objective of the work was to underpin the microRNA (miR)-profiling differences in human normal femoral, abdominal aortic, and carotid arteries. The secondary aim was to investigate if those identified miRs, differently expressed in normal conditions, may also have a role in atherosclerotic arteries at adult ages. MiR-profiles were performed on normal tissues, revealing that aorta and carotid arteries are more similar than femoral arteries. MiRs emerged from profiling comparisons, i.e., miR-155-5p, -27a-5p, and -139-5p, were tested for validation by RT-qPCR in normal arteries and also in pathological/atheroma counterparts, considering all the available 20 artery specimens. The three miRs were confirmed to be differently expressed in normal femoral vs aorta/carotid arteries. A different expression of those miRs was also observed in atherosclerotic arteries, together with some miR-target proteins, such as vimentin, CD44, E-cadherin and an additional marker SLUG. The different expression of miRs and targets/markers suggests that aorta/carotid and femoral arteries differently activate molecular drivers of pathological condition, thus conditioning the morphology of atheroma in adult life and likely suggesting the application of artery-specific treatment to counteract atherosclerosis.

Research paper thumbnail of Non-alcoholic steatohepatitis is a risk factor for intrahepatic cholangiocarcinoma and affects its long-time outcome: results from a multicenter international case-control study

Journal of Hepatology, 2020

Research paper thumbnail of Periostin, tenascin, osteopontin isoforms in long- and non-long survival patients with pancreatic cancer: a pilot study

Molecular Biology Reports, 2020

Pancreatic adenocarcinoma (PDAC) is the most frequent histological type of malignancy in the panc... more Pancreatic adenocarcinoma (PDAC) is the most frequent histological type of malignancy in the pancreas. Extracellular matrix (ECM), plays a critical role during the process of human carcinogenesis and the possible diversity in matricellular proteins composition of ECM may have a significant impact on the clinical course of PDAC. Aim of this paper was to evaluate the expression of three matricellular proteins, including Periostin (POSTN), Tenascin (TNS) and Osteopontin (OPN), in PDAC from long-survival (LS) and non-long survival (NLS) patients. A total of 30 PDAC were analyzed, 15 from patients that survived more than 60 months after surgery (LS) and 15 that died from the disease within 24 (NLS). RNA was extracted and OPN, TNS and POSTN mRNA levels were evaluated by qRT-PCR. LS and NLS samples showed the same type of POSTN and TN isoforms. On the contrary, OPN seems to be preferentially expressed in NLS PDAC. Moreover, OPNb and OPNc isoforms were expressed exclusively in NLS samples. In conclusion, Our data led to hypothesize a possible relationship between the expression of different isoforms of each of these proteins and the clinical outcome of patients with PDAC.

Research paper thumbnail of Hypothermic Oxygenated New Machine Perfusion System in Liver and Kidney Transplantation of Extended Criteria Donors:First Italian Clinical Trial

Scientific Reports, 2020

With the aim to explore innovative tools for organ preservation, especially in marginal organs, w... more With the aim to explore innovative tools for organ preservation, especially in marginal organs, we hereby describe a clinical trial of ex-vivo hypothermic oxygenated perfusion (HOPE) in the field of liver (LT) and kidney transplantation (KT) from Extended Criteria Donors (ECD) after brain death. A matched-case analysis of donor and recipient variables was developed: 10 HOPE-ECD livers and kidneys (HOPE-L and HOPE-K) were matched 1:3 with livers and kidneys preserved with static cold storage (SCS-L and SCS-K). HOPE and SCS groups resulted with similar basal characteristics, both for recipients and donors. Cumulative liver and kidney graft dysfunction were 10% (HOPE L-K) vs. 31.7%, in SCS group (p = 0.05). Primary non-function was 3.3% for SCS-L vs. 0% for HOPE-L. No primary non-function was reported in HOPE-K and SCS-K. Median peak aspartate aminotransferase within 7-days post-LT was significantly higher in SCS-L when compared to HOPE-L (637 vs.344 U/L, p = 0.007). Graft survival at ...

Research paper thumbnail of Dual Kidney Transplantation after Hypothermic Oxygenated Perfusion from Marginal Donor after Circulatory Death with Acute Kidney Injury: A Case Report

OBM Transplantation, 2020

Donation after circulatory death (DCD) is an increasingly used resource to alleviate chronic rena... more Donation after circulatory death (DCD) is an increasingly used resource to alleviate chronic renal graft shortages. Organs from donors with progressively increased creatinine levels due to acute kidney injury are used, but the effects of this condition on kidney transplantation are still unclear. Ex-situ machine perfusion is emerging as a potential tool to preserve and resuscitate vulnerable grafts. We report a case of DCD kidneys discarded due to severe acute kidney injury with favorable histological Karpinski score and transplanted after in-situ normothermic regional perfusion (NRP) and ex-vivo hypothermic oxygenated perfusion (HOPE). Kidneys from a 57-years-old man with circulatory death were discarded by other Italian transplant centers due to high serum creatinine level (3.66 mg/dL) at the beginning of

Research paper thumbnail of Pd-ligand 1 is expressed in inflammatory cells but not in neoplastic cells in hepatocellular carcinoma: An immunohistochemical study

Acta Histochemica, 2019

Nowadays, the major limit to the immunohistochemical (IHC) analysis of tissue PD-L1 is the high v... more Nowadays, the major limit to the immunohistochemical (IHC) analysis of tissue PD-L1 is the high variability of the monoclonal antibodies commercially available. Aims of the present paper are to assess the best clone and the most suitable scoring for PD-L1 IHC determination on human hepatocellular carcinoma (HCC) among three commercially available clones, and to evaluate which PD-L1 clone is the best in predicting HCC aggressiveness in vivo. We built a tissue microarray (TMA) with 60 retrospective HCC cases, including the correspondent nontumoral tissue. IHC was automatically performed using the following anti-PD-L1 clones: 28.8, SP142, and SP263. As results, we did not find any immunoreactivity for PD-L1 in both neoplastic and normal hepatocytes included in the TMA using the three antibodies. Positivity for PD-L1 was exclusively seen in inflammatory cells within the HCC tissue and in cirrhotic parenchyma. When a gold standard was assessed, the sensitivity of SP142, 28.8 and SP263 was 46 %, 54 % and 85 % respectively. Using the SP263 clone, the absolute number of PD-L1positive inflammatory cells in the HCC cores was paired with the number of PD-L1-positive inflammatory cells in the corresponding non-tumoral tissue (P = 0.001). Finally, using SP263, the mean number of PD-L1-positive cells was 11.3 ± 12.6 in HCC from deceased patients, versus 4.7 ± 5.2 in alive patients (p = 0.039). SP263 is the most sensitive clone for PD-L1 IHC tissue determination in HCC, as well as the best antibody for the assessment of its biological behavior.

Research paper thumbnail of Pathobiological and Radiological Approach For Hepatocellular Carcinoma Subclassification

Scientific Reports, 2019

Many advances have been made in the imaging diagnosis and in the histopathological evaluation of ... more Many advances have been made in the imaging diagnosis and in the histopathological evaluation of HCC. However, the classic imaging and histopathological features of HCC are still inadequate to define patient’s prognosis. We aimed to find the link between new proposed morphovascular patterns of hepatocellular carcinoma (HCC) and magnetic resonance imaging (MRI) features to identify pre-operatory markers of biologically aggressive HCC. Thirty-nine liver nodules in 22 patients were consecutively identified. Histopathological analysis and immunohistochemistry for CD34 and Nestin were performed to identify the four different HCC morphovascular patterns. MRI was performed using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid. Three out of four morphovascular HCC patterns showed peculiar MRI features: in particular Pattern D (solid aggressive HCCs with CD34+/Nestin+ new-formed arteries) were isointense on T1-WI in 83% of cases and hyperintense on T2-WI in 50%. Five histological...

Research paper thumbnail of SAT-459-NASH as a risk factor for intrahepatic cholangiocarcinoma and its prognostic role: Case-control study

Journal of Hepatology, 2019

Research paper thumbnail of Brivanib in combination with Notch3 silencing shows potent activity in tumour models

British Journal of Cancer, 2019

BACKGROUND: Sorafenib is the first targeted agent proven to improve survival of patients with adv... more BACKGROUND: Sorafenib is the first targeted agent proven to improve survival of patients with advanced hepatocellular carcinoma (HCC) and it has been used in first line treatments with heterogeneous response across patients. Most of the promising agents evaluated in first-line or second-line phase III trials for HCC failed to improve patient survival. The absence of molecular characterisation, including the identification of pathways driving resistance might be responsible for these disappointing results. METHODS: 2D DIGE and MS analyses were used to reveal proteomic signatures resulting from Notch3 inhibition in HepG2 cells, combined with brivanib treatment. The therapeutic potential of Notch3 inhibition combined with brivanib treatment was also demonstrated in a rat model of HCC and in cell lines derived from different human cancers. RESULTS: Using a proteomic approach, we have shown that Notch3 is strongly involved in brivanib resistance through a p53dependent regulation of enzymes of the tricarboxylic acid (TCA), both in vitro and in vivo. CONCLUSION: We have demonstrated that regulation of the TCA cycle is a common mechanism in different human cancers, suggesting that Notch3 inhibitors combined with brivanib treatment may represent a strong formulation for the treatment of HCC as well as Notch3-driven cancers.

Research paper thumbnail of Unusual metastatic localization to the kidney of basaloid squamous cell carcinoma of the oropharynx

Urologia Journal, 2018

Case presentation: A 55-year-old man with a history of basaloid squamous cell carcinoma of the or... more Case presentation: A 55-year-old man with a history of basaloid squamous cell carcinoma of the oropharynx with laterocervical lymph node metastases 6 years before (and treated with chemoradiation) presented with flank pain and hematuria. Computed tomography scan found a renal lesion, with radiological features more suspicious for primitive renal neoplasia. Histopathological and immunohistochemical examination after surgical excision revealed a basaloid squamous cell carcinoma involving renal parenchyma. Conclusion: Basaloid squamous cell carcinoma is a rare tumor but with a high percentage of distant metastasis, and it is mandatory, also for a general pathologist, to know this disease. Moreover, in a patient with renal metastases, any type of cancer should be taken into account, and this case is emblematic of why the previous medical history is crucial for differential diagnosis.

Research paper thumbnail of Synchronous hepatocellular carcinoma and renal cell carcinoma in a liver transplant recipient: a case report

Transplantation, Jan 27, 2007

Research paper thumbnail of The role of peritumoral CD8 + /TIA1 + lymphocytes in hepatocellular carcinoma aggressiveness and recurrence after surgical resection

Pathology - Research and Practice

Research paper thumbnail of Automatically Extracted Machine Learning Features from Preoperative CT to Early Predict Microvascular Invasion in HCC: The Role of the Zone of Transition (ZOT)

Cancers

Background: Microvascular invasion (MVI) is a consolidated predictor of hepatocellular carcinoma ... more Background: Microvascular invasion (MVI) is a consolidated predictor of hepatocellular carcinoma (HCC) recurrence after treatments. No reliable radiological imaging findings are available for preoperatively diagnosing MVI, despite some progresses of radiomic analysis. Furthermore, current MVI radiomic studies have not been designed for small HCC nodules, for which a plethora of treatments exists. This study aimed to identify radiomic MVI predictors in nodules ≤3.0 cm by analysing the zone of transition (ZOT), crossing tumour and peritumour, automatically detected to face the uncertainties of radiologist’s tumour segmentation. Methods: The study considered 117 patients imaged by contrast-enhanced computed tomography; 78 patients were finally enrolled in the radiomic analysis. Radiomic features were extracted from the tumour and the ZOT, detected using an adaptive procedure based on local image contrast variations. After data oversampling, a support vector machine classifier was devel...

Research paper thumbnail of Molecular Characterization of Pancreatic Ductal Adenocarcinoma Using a Next-Generation Sequencing Custom-Designed Multigene Panel

Diagnostics

Despite the efforts made in the management of PDAC, the 5-year relative survival rate of pancreat... more Despite the efforts made in the management of PDAC, the 5-year relative survival rate of pancreatic ductal adenocarcinoma (PDAC) still remains very low (10%). To date, precision oncology is far from being ready to be applied in cases of PDAC, although studies exploring the molecular and genetic alterations have been conducted, and the genomic landscape of PDAC has been characterized. This study aimed to apply a next-generation sequencing (NGS) laboratory-developed multigene panel to PDAC samples to find molecular alterations that could be associated with histopathological features and clinical outcomes. A total of 68 PDACs were characterized by using a laboratory-developed multigene NGS panel. KRAS and TP53 mutations were the more frequent alterations in 75.0% and 44.6% of cases, respectively. In the majority (58.7%) of specimens, more than one mutation was detected, mainly in KRAS and TP53 genes. KRAS mutation was significantly associated with a shorter time in tumor recurrence com...

Research paper thumbnail of ETS-Related Gene Expression in Healthy Femoral Arteries With Focal Calcifications

Frontiers in Cell and Developmental Biology

Bone development-related genes are enriched in healthy femoral arteries, which are more prone to ... more Bone development-related genes are enriched in healthy femoral arteries, which are more prone to calcification, as documented by the predominance of fibrocalcific plaques at the femoral location. We undertook a prospective histological study on the presence of calcifications in normal femoral arteries collected from donors. Since endothelial-to-mesenchymal transition (EndMT) participates in vascular remodeling, immunohistochemical (IHC) and molecular markers of EndMT and chondro-osteogenic differentiation were assessed. Transmission electron microscopy (TEM) was used to describe calcification at its inception. Two hundred and fourteen femoral arteries were enrolled. The mean age of the donors was 39.9 ± 12.9 years; male gender prevailed (M: 128). Histology showed a normal architecture; calcifications were found in 52 (24.3%) cases, without correlations with cardiovascular risk factors. Calcifications were seen on or just beneath the inner elastic lamina (IEL). At IHC, SLUG was incre...

Research paper thumbnail of Adventitial Microcirculation Is a Major Target of SARS-CoV-2-Mediated Vascular Inflammation

Biomolecules

We report the case of a 77-year-old woman affected by coronavirus disease-19 (COVID-19) who devel... more We report the case of a 77-year-old woman affected by coronavirus disease-19 (COVID-19) who developed an occlusive arterial disease of the lower limb requiring a left leg amputation. We studied the mechanisms of vascular damage by SARS-CoV-2 by means of a comprehensive multi-technique in situ analysis on the diseased popliteal arterial district, including immunohistochemistry (IHC), transmission electron microscopy (TEM) and miRNA analysis. At histological analyses, we observed a lymphocytic inflammatory infiltrate, oedema and endothelialitis of adventitial vasa vasorum while the media was normal and the intima had only minor changes. The vasa vasorum expressed the ACE2 receptor and factor VIII; compared with the controls, VEGFR2 staining was reduced. TEM analyses showed endothelial injury and numerous Weibel–Palade bodies in the cytoplasm. No coronavirus particle was seen. IL-6 protein and mRNA, together with miR-155-5p and miRs-27a-5p, which can target IL-6, were significantly inc...

Research paper thumbnail of Aflatoxin B1 DNA-Adducts in Hepatocellular Carcinoma from a Low Exposure Area

Nutrients

Aflatoxin B1 (AFB1) is a class 1 carcinogen with an ascertained role in the development of hepato... more Aflatoxin B1 (AFB1) is a class 1 carcinogen with an ascertained role in the development of hepatocellular carcinoma (HCC) in high exposure areas. Instead, this study aimed to assay whether chronic/intermittent, low-dose AFB1 consumption might occur in low-exposure geographical areas, ultimately accumulating in the liver and possibly contributing to liver cancer. AFB1-DNA adducts were assayed by immunostaining in liver tissues from three Italian series of twenty cirrhosis without HCC, 131 HCC, and 45 cholangiocarcinoma, and in an AFB1-induced HCC rat model. CD68, TP53 immunostaining, and TP53 RFLP analysis of R249S transversion were used to characterize cell populations displaying AFB1-DNA adducts. Twenty-five HCCs displayed AFB1-adducts both in neoplastic hepatocytes and in cells infiltrating the tumor and non-tumor tissues. Nuclear immunostaining was observed in a few cases, while most cases showed cytoplasmic immunostaining, especially in CD68-positive tumor-infiltrating cells, su...

Research paper thumbnail of Research Article Diffuse Calcifications Protect Carotid Plaques regardless of the Amount of Neoangiogenesis and Related Histological Complications

Copyright © 2015 Francesco Vasuri et al. This is an open access article distributed under the Cre... more Copyright © 2015 Francesco Vasuri et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. Neoangiogenesis is crucial in plaque progression and instability. Previous data from our group showed that Nestin-positive intraplaque neovessels correlatedwith histological complications.The aimof the present work is to evaluate the relationship between neoangiogenesis, plaque morphology, and clinical instability of the plaque.Materials and Methods. Seventy-three patients (53 males and 20 females, mean age 71 years) were consecutively enrolled. Clinical data and 14 histological variables, including intraplaque hemorrhage and calcifications, were collected. Immunohistochemistry for CD34 and Nestin was performed. RT-PCR was performed to evaluate Nestin mRNA (including 5 healthy arteries as controls). Results. Diffusely c...

Research paper thumbnail of Venous outflow in partial heterotopic liver transplantation with spleen replacement: Evidence of no chronic venous hypertension

American Journal of Transplantation, 2021

We recently described the first case of partial heterotopic liver transplantation replacing the s... more We recently described the first case of partial heterotopic liver transplantation replacing the spleen with delayed recipient hepatectomy to overcome the problem of organ shortage and to make possible debated indications for liver transplantation.1,2 The surgical technique of the RAVAS procedure was described in different steps: before planning the operation1 and after the first procedure performed, with a case report and video of the technique.

Research paper thumbnail of MicroRNA expression profiling with a droplet digital PCR assay enables molecular diagnosis and prognosis of cancers of unknown primary

Research paper thumbnail of MicroRNA profiles of human peripheral arteries and abdominal aorta in normal conditions: MicroRNAs-27a-5p, -139-5p and -155-5p emerge and in atheroma too

Mechanisms of Ageing and Development, 2021

Atherosclerosis may starts early in life and each artery has peculiar characteristics likely affe... more Atherosclerosis may starts early in life and each artery has peculiar characteristics likely affecting atherogenesis. The primary objective of the work was to underpin the microRNA (miR)-profiling differences in human normal femoral, abdominal aortic, and carotid arteries. The secondary aim was to investigate if those identified miRs, differently expressed in normal conditions, may also have a role in atherosclerotic arteries at adult ages. MiR-profiles were performed on normal tissues, revealing that aorta and carotid arteries are more similar than femoral arteries. MiRs emerged from profiling comparisons, i.e., miR-155-5p, -27a-5p, and -139-5p, were tested for validation by RT-qPCR in normal arteries and also in pathological/atheroma counterparts, considering all the available 20 artery specimens. The three miRs were confirmed to be differently expressed in normal femoral vs aorta/carotid arteries. A different expression of those miRs was also observed in atherosclerotic arteries, together with some miR-target proteins, such as vimentin, CD44, E-cadherin and an additional marker SLUG. The different expression of miRs and targets/markers suggests that aorta/carotid and femoral arteries differently activate molecular drivers of pathological condition, thus conditioning the morphology of atheroma in adult life and likely suggesting the application of artery-specific treatment to counteract atherosclerosis.

Research paper thumbnail of Non-alcoholic steatohepatitis is a risk factor for intrahepatic cholangiocarcinoma and affects its long-time outcome: results from a multicenter international case-control study

Journal of Hepatology, 2020

Research paper thumbnail of Periostin, tenascin, osteopontin isoforms in long- and non-long survival patients with pancreatic cancer: a pilot study

Molecular Biology Reports, 2020

Pancreatic adenocarcinoma (PDAC) is the most frequent histological type of malignancy in the panc... more Pancreatic adenocarcinoma (PDAC) is the most frequent histological type of malignancy in the pancreas. Extracellular matrix (ECM), plays a critical role during the process of human carcinogenesis and the possible diversity in matricellular proteins composition of ECM may have a significant impact on the clinical course of PDAC. Aim of this paper was to evaluate the expression of three matricellular proteins, including Periostin (POSTN), Tenascin (TNS) and Osteopontin (OPN), in PDAC from long-survival (LS) and non-long survival (NLS) patients. A total of 30 PDAC were analyzed, 15 from patients that survived more than 60 months after surgery (LS) and 15 that died from the disease within 24 (NLS). RNA was extracted and OPN, TNS and POSTN mRNA levels were evaluated by qRT-PCR. LS and NLS samples showed the same type of POSTN and TN isoforms. On the contrary, OPN seems to be preferentially expressed in NLS PDAC. Moreover, OPNb and OPNc isoforms were expressed exclusively in NLS samples. In conclusion, Our data led to hypothesize a possible relationship between the expression of different isoforms of each of these proteins and the clinical outcome of patients with PDAC.

Research paper thumbnail of Hypothermic Oxygenated New Machine Perfusion System in Liver and Kidney Transplantation of Extended Criteria Donors:First Italian Clinical Trial

Scientific Reports, 2020

With the aim to explore innovative tools for organ preservation, especially in marginal organs, w... more With the aim to explore innovative tools for organ preservation, especially in marginal organs, we hereby describe a clinical trial of ex-vivo hypothermic oxygenated perfusion (HOPE) in the field of liver (LT) and kidney transplantation (KT) from Extended Criteria Donors (ECD) after brain death. A matched-case analysis of donor and recipient variables was developed: 10 HOPE-ECD livers and kidneys (HOPE-L and HOPE-K) were matched 1:3 with livers and kidneys preserved with static cold storage (SCS-L and SCS-K). HOPE and SCS groups resulted with similar basal characteristics, both for recipients and donors. Cumulative liver and kidney graft dysfunction were 10% (HOPE L-K) vs. 31.7%, in SCS group (p = 0.05). Primary non-function was 3.3% for SCS-L vs. 0% for HOPE-L. No primary non-function was reported in HOPE-K and SCS-K. Median peak aspartate aminotransferase within 7-days post-LT was significantly higher in SCS-L when compared to HOPE-L (637 vs.344 U/L, p = 0.007). Graft survival at ...

Research paper thumbnail of Dual Kidney Transplantation after Hypothermic Oxygenated Perfusion from Marginal Donor after Circulatory Death with Acute Kidney Injury: A Case Report

OBM Transplantation, 2020

Donation after circulatory death (DCD) is an increasingly used resource to alleviate chronic rena... more Donation after circulatory death (DCD) is an increasingly used resource to alleviate chronic renal graft shortages. Organs from donors with progressively increased creatinine levels due to acute kidney injury are used, but the effects of this condition on kidney transplantation are still unclear. Ex-situ machine perfusion is emerging as a potential tool to preserve and resuscitate vulnerable grafts. We report a case of DCD kidneys discarded due to severe acute kidney injury with favorable histological Karpinski score and transplanted after in-situ normothermic regional perfusion (NRP) and ex-vivo hypothermic oxygenated perfusion (HOPE). Kidneys from a 57-years-old man with circulatory death were discarded by other Italian transplant centers due to high serum creatinine level (3.66 mg/dL) at the beginning of

Research paper thumbnail of Pd-ligand 1 is expressed in inflammatory cells but not in neoplastic cells in hepatocellular carcinoma: An immunohistochemical study

Acta Histochemica, 2019

Nowadays, the major limit to the immunohistochemical (IHC) analysis of tissue PD-L1 is the high v... more Nowadays, the major limit to the immunohistochemical (IHC) analysis of tissue PD-L1 is the high variability of the monoclonal antibodies commercially available. Aims of the present paper are to assess the best clone and the most suitable scoring for PD-L1 IHC determination on human hepatocellular carcinoma (HCC) among three commercially available clones, and to evaluate which PD-L1 clone is the best in predicting HCC aggressiveness in vivo. We built a tissue microarray (TMA) with 60 retrospective HCC cases, including the correspondent nontumoral tissue. IHC was automatically performed using the following anti-PD-L1 clones: 28.8, SP142, and SP263. As results, we did not find any immunoreactivity for PD-L1 in both neoplastic and normal hepatocytes included in the TMA using the three antibodies. Positivity for PD-L1 was exclusively seen in inflammatory cells within the HCC tissue and in cirrhotic parenchyma. When a gold standard was assessed, the sensitivity of SP142, 28.8 and SP263 was 46 %, 54 % and 85 % respectively. Using the SP263 clone, the absolute number of PD-L1positive inflammatory cells in the HCC cores was paired with the number of PD-L1-positive inflammatory cells in the corresponding non-tumoral tissue (P = 0.001). Finally, using SP263, the mean number of PD-L1-positive cells was 11.3 ± 12.6 in HCC from deceased patients, versus 4.7 ± 5.2 in alive patients (p = 0.039). SP263 is the most sensitive clone for PD-L1 IHC tissue determination in HCC, as well as the best antibody for the assessment of its biological behavior.

Research paper thumbnail of Pathobiological and Radiological Approach For Hepatocellular Carcinoma Subclassification

Scientific Reports, 2019

Many advances have been made in the imaging diagnosis and in the histopathological evaluation of ... more Many advances have been made in the imaging diagnosis and in the histopathological evaluation of HCC. However, the classic imaging and histopathological features of HCC are still inadequate to define patient’s prognosis. We aimed to find the link between new proposed morphovascular patterns of hepatocellular carcinoma (HCC) and magnetic resonance imaging (MRI) features to identify pre-operatory markers of biologically aggressive HCC. Thirty-nine liver nodules in 22 patients were consecutively identified. Histopathological analysis and immunohistochemistry for CD34 and Nestin were performed to identify the four different HCC morphovascular patterns. MRI was performed using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid. Three out of four morphovascular HCC patterns showed peculiar MRI features: in particular Pattern D (solid aggressive HCCs with CD34+/Nestin+ new-formed arteries) were isointense on T1-WI in 83% of cases and hyperintense on T2-WI in 50%. Five histological...

Research paper thumbnail of SAT-459-NASH as a risk factor for intrahepatic cholangiocarcinoma and its prognostic role: Case-control study

Journal of Hepatology, 2019

Research paper thumbnail of Brivanib in combination with Notch3 silencing shows potent activity in tumour models

British Journal of Cancer, 2019

BACKGROUND: Sorafenib is the first targeted agent proven to improve survival of patients with adv... more BACKGROUND: Sorafenib is the first targeted agent proven to improve survival of patients with advanced hepatocellular carcinoma (HCC) and it has been used in first line treatments with heterogeneous response across patients. Most of the promising agents evaluated in first-line or second-line phase III trials for HCC failed to improve patient survival. The absence of molecular characterisation, including the identification of pathways driving resistance might be responsible for these disappointing results. METHODS: 2D DIGE and MS analyses were used to reveal proteomic signatures resulting from Notch3 inhibition in HepG2 cells, combined with brivanib treatment. The therapeutic potential of Notch3 inhibition combined with brivanib treatment was also demonstrated in a rat model of HCC and in cell lines derived from different human cancers. RESULTS: Using a proteomic approach, we have shown that Notch3 is strongly involved in brivanib resistance through a p53dependent regulation of enzymes of the tricarboxylic acid (TCA), both in vitro and in vivo. CONCLUSION: We have demonstrated that regulation of the TCA cycle is a common mechanism in different human cancers, suggesting that Notch3 inhibitors combined with brivanib treatment may represent a strong formulation for the treatment of HCC as well as Notch3-driven cancers.

Research paper thumbnail of Unusual metastatic localization to the kidney of basaloid squamous cell carcinoma of the oropharynx

Urologia Journal, 2018

Case presentation: A 55-year-old man with a history of basaloid squamous cell carcinoma of the or... more Case presentation: A 55-year-old man with a history of basaloid squamous cell carcinoma of the oropharynx with laterocervical lymph node metastases 6 years before (and treated with chemoradiation) presented with flank pain and hematuria. Computed tomography scan found a renal lesion, with radiological features more suspicious for primitive renal neoplasia. Histopathological and immunohistochemical examination after surgical excision revealed a basaloid squamous cell carcinoma involving renal parenchyma. Conclusion: Basaloid squamous cell carcinoma is a rare tumor but with a high percentage of distant metastasis, and it is mandatory, also for a general pathologist, to know this disease. Moreover, in a patient with renal metastases, any type of cancer should be taken into account, and this case is emblematic of why the previous medical history is crucial for differential diagnosis.