Papers by Antonia D'Errico
Ultrastructural Pathology, 2020
We present an unusual case of liver involvement in monoclonal gammopathy with generalized crystal... more We present an unusual case of liver involvement in monoclonal gammopathy with generalized crystal-storing histiocytosis (G-CSH). A bone marrow storage disease was diagnosed in a 79-year-old man with monoclonal gammopathy of uncertain significance (MGUS). The patient presented with pleural effusion, an osteolytic lesion of the humerus, and an increase of aspartate transaminase and cholestatic markers that raised the clinical suspect of liver disease. A second bone marrow biopsy confirmed the diagnosis of MGUS with a histiocytic component suggestive for G-CSH. Liver biopsy showed an unremarkable histology, no significant inflammatory infiltrates, and intrasinusoidal foamy histiocytes. PAS and Masson's trichrome stains, showed, in the cytoplasm of both histiocytes and hepatocytes, rod-shaped eosinophilic crystals, which were immunoreactive for kappa light chains. Transmission electron microscopy performed on reprocessed histological sections confirmed the presence of crystals in the hepatocyte cytoplasms. Immunogold labeling intensely stained crystals for kappa light chains. To the best of our knowledge, this is the second case in which an intrahepatocellular crystal storage is described during liver involvement in G-CSH. The present case also suggests that an increase in liver serum enzymes may support the clinical diagnosis of liver CSH in a patient with MGUS.
Liver Transplantation, 2018
Radiofrequency ablation (RFA) represents a potentially curative option for early‐stage hepatocell... more Radiofrequency ablation (RFA) represents a potentially curative option for early‐stage hepatocellular carcinoma (HCC). This study aims at evaluating the histologic response after RFA of small HCCs arising in cirrhosis. Data were reviewed from 78 patients with de novo HCCs who were treated with RFA and subsequently transplanted. The last radiological assessment before liver transplantation (LT) was used for comparison between modified Response Evaluation Criteria in Solid Tumors (mRECIST) and histological findings. A total of 125 de novo HCCs (median diameter, 20 mm) were treated with RFA only in 92 sessions. There were 98 nodules that did not show local recurrence during follow‐up (78.4%), and the remaining were retreated, except 1 because of subsequent LT. On explanted livers, complete pathological response (CPR) was observed in 61.6%, being 76.9% when <2 cm, 55.0% when 2‐3 cm, and 30.8% when >3 cm. Tumors near hepatic vessels had CPR in 50% of patients versus 69.3% for tumor...
BMC cancer, Jan 12, 2018
We report on a female patient who underwent primary radical resection for a stage 2B Her-2-positi... more We report on a female patient who underwent primary radical resection for a stage 2B Her-2-positive Barrett's-type esophageal adenocarcinoma (EAC). Despite Her-2 targeted therapy, her disease recurred and required repeated metastectomies. Digital cell sorting and targeted sequencing of cancer sub-clones from EAC and metastases revealed a completely mutated TP53, whereas the sorted stromal cells were wild-type. Her-2 amplification was significantly lower in the metastases when the patient became therapy-resistant. The mechanism of therapy resistance illustrated by this case could only be detected through accurate analysis of tumor sub-populations. Investigating tumor sub-populations of recurrent disease is important for adjusting therapy in recurrent EAC.
Oncotarget, Jan 3, 2018
The choice of surgical treatment for hepatocellular carcinoma (HCC) depends on several prognostic... more The choice of surgical treatment for hepatocellular carcinoma (HCC) depends on several prognostic variables, among which histological features, like microvascular invasion and tumor grade, are well established. This study aims to identify the tissue miRNAs predictive of recurrence after liver resection in "histologically advanced" HCC. We selected 54 patients: 15 retrospective resected patients without recurrence (group A), 19 retrospective resected patients with HCC recurrence (group B), and 20 prospective patients (group C), with 4 recurrence cases. All selected HCC were "histologically advanced" (high Edmondson grade and/or presence of microvascular invasion). A wide spectrum of miRNAs was studied with TaqMan Human microRNA Arrays; qRT-PCR assays were used to validate results on selected miRNAs; immunohistochemistry for IGF2 was applied to study the mechanism of miR-483-3p. As a result, a significant differential expression between group A and B was found for ...
Digestive Diseases and Sciences, 2017
Background miRNA deregulation and vascular modifications constitute promising predictors in the s... more Background miRNA deregulation and vascular modifications constitute promising predictors in the study of hepatocellular carcinoma (HCC). In the literature, the relative miRNA abundance in HCC is usually determined using as control non-matched tumoral tissue, healthy liver, or cirrhotic liver. However, a common standard RNA control for the normalization toward the tissue gene expression was not settled yet. Aim To assess the differences existing in the quantitative miRNA gene expression in HCC on tissue according to two different liver controls. Methods A wide array of miRNAs was analyzed on 22 HCCs arisen in cirrhotic and non-cirrhotic livers by means of microfluidic cards. Control samples included total RNA extracted from healthy and cirrhotic livers.
Hepato-gastroenterology
Papillary-cystic neoplasm of the pancreas is a rare neoplasm principally effecting women in the 2... more Papillary-cystic neoplasm of the pancreas is a rare neoplasm principally effecting women in the 2nd and 3rd decades of life. It is considered a low grade malignancy due to it's favourable prognosis and the rarity of metastatic diffusion. Pre-operative diagnosis is rare due to the similarity with other cystic pancreatic lesions. It is for this reason that definitive diagnosis is made at histologic examination of the surgical specimen and total surgical excision represents the therapy of choice. The authors herein describe 2 cases of papillary-cystic neoplasm of the pancreas, thus bringing the total number of cases reported in the world literature to 294.
Pathology, 1993
We report the case of an intrapericardial lesion with the pathological features of a multilocular... more We report the case of an intrapericardial lesion with the pathological features of a multilocular cyst, found on the adventitia of an aortic aneurysm in a 62-yr-old man. Microscopically, it consisted of numerous cavities lined by flattened or cuboidal cells with the immunocytochemical and electron microscopical features of mesothelium, sometimes forming a hyperplastic pattern. Numerous nerve bundles and collections of inflammatory cells were present in the stroma. These features were consistent with a reactive lesion.
Human Pathology, 1995
We studied by immunohistochemistry 25 cases of focal nodular hyperplasia (FNH) to evaluate the co... more We studied by immunohistochemistry 25 cases of focal nodular hyperplasia (FNH) to evaluate the composition of the extracellular matrix and the expression and distribution of endothelial cell-cell adhesion molecules and integrin receptors. The extracellular matrix of FNH retained the overall organization of that of normal liver. The matrix of central scars resembled that of portal tracts. The main difference was the presence of large vitronectin deposits, which might indicate the existence of local hemodynamic disturbances. The matrix lining the sinusoid-like vessels running in the hyperplastic parenchyma retained characteristic features of the normal perisinusoidal matrix, such as the presence of tenascin. In the zone surrounding the central scars, it contained large amounts of laminin, von Willebrand factor, and thrombospondin, suggesting the development of perisinusoidal fibrosis. Laminin deposition was accompanied by the induction of cell-cell adhesion molecules on adjacent endothelial cells and by the up-regulation of specific integrin receptors on both hepatocytes and sinusoidal endothelial cells. In conclusion, our study: (1) reinforces the hypothesis that FNH is merely a hyperplastic response of liver parenchyma to local vascular abnormalities, and (2) shows that the lesions of perisinusoidal fibrosis associated with FNH are accompanied by the induction of integrin receptors on hepatocytes and sinusoidal endothelial cells.
Pancreatology, 2014
dependent. Interestingly, using this approach, we also found that the transcriptome analysis coul... more dependent. Interestingly, using this approach, we also found that the transcriptome analysis could predict the sensitivity or resistance to the anticancer drugs, with a very scarce number of common genes suggesting that the phenotype of the sensitivity or resistance is specific to each drug. Conclusion: We found that the transcriptome analysis made on xenogratfed PDAC could predict the sensitivity to some anticancer drugs and the clinical outcome of patients with a PDAC. T-062. Characterization of pancreatic ductal adenocarcinoma patients using whole-transcriptome sequencing and copy number analysis by SNPs array techniques.
Virchows Archiv, 2011
The organic anion transporter peptides (OATP) 1B1 and 1B3 are hepatocytic-specific transporters d... more The organic anion transporter peptides (OATP) 1B1 and 1B3 are hepatocytic-specific transporters determinant for the uptake of the contrast media Gd-EOB-DTPA during magnetic resonance, but variably lost in hepatocellular carcinoma (HCC). Here, we studied a series of HCCs from livers that underwent liver transplantation (OLT) and correlated the expression of OATP 1B1/1B3 with HCC morphological features and the expression of the biliary-type keratins K7 and K19, the latter previously correlated with a worse prognosis after OLT. Seventy-five HCCs from 69 OLT patients were evaluated by histology and immunohistochemistry with monoclonal antibodies against OATP 1B1/1B3, K7, and K19. Histopathological and immunohistochemical features were therefore compared to recipient follow-up data. Thirty-four (45%) HCCs were completely OATP-, and 18 (24%) showed positivity for K7 and/or K19. We observed a significant inverse correlation between OATP and K7/19 expression (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001): all OATP+ cases were K7/19-, while all K7+ and/or K19+ cases were OATP-. Sixteen cases were negative for all antibodies. No correlation was found between histopathological features and immunohistochemistry. Twenty-five recipients experienced HCC recurrence, and ten died from neoplastic recurrence. Neither OATP nor keratin expressions were correlated with HCC recurrence, while OATP negativity significantly correlated with HCC-related death after recurrence (P = 0.036). In conclusion, HCCs show a progressive loss in OATP immunoreactivity that correlates with the gain of a biliary phenotype. Although further studies are required to define these findings better, our results support the idea that OATP could be used together with K7/19 to identify a phenotypical &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;spectrum&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; in HCC progression.
Transplantation Proceedings, 2010
Surgical approaches to complicated benign intestinal failure are accepted worldwide, especially i... more Surgical approaches to complicated benign intestinal failure are accepted worldwide, especially in the pediatric population. Intestinal transplant surgery is thought to rescue patients in whom complications of total parenteral nutrition (TPN) develop. To report our experience with surgical intestinal rescue in an adult population with intestinal failure. An intestinal rehabilitation program initiated at our institution included comprehensive medical rehabilitation, surgical bowel rescue, and transplantation. From 2000 to 2009, of 81 adult patients referred by our gastroenterologists for bowel rehabilitation, 42 (51,8%) underwent 43 transplantations (32 isolated intestinal grafts and 11 multivisceral grafts). Underlying diseases were primarily short-bowel syndrome, Gardner syndrome, and intestinal pseudo-obstruction. Thirty-nine patients (48,2%) underwent surgical rescue (40 cases) consisting of bowel resection, adhesiolysis, stricturoplasty, liver transplantation with portocaval hemitransposition (6 cases in 5 patients). Underlying diseases were primarily intestinal fistulas, stenosis, or perforations, short-bowel syndrome, cocoon syndrome, and complete portal thrombosis. After a mean (SD) follow-up of 1043 (1016) days, in the transplantation population, 21 patients (50%) are alive, with a 1-, 3-, 5-year patient survival of 76%, 59%, and 52%, respectively, and graft survival of 66%, 54%, and 48%, respectively. After 901 (404) days in the rescue population, 32 patients (82%) are alive (2 died, and 5 were lost to follow-up); in 75%, TPN 25% was discontinued, and are receiving oral feeding with TPN support. The 1- and 3-year survival rate was 100% and 83%, respectively. Deaths occurred primarily in the transplantation population. Intestinal surgical rescue, when possible, is optimal.
Transplantation Proceedings, 2003
In human heart and kidney transplantations, granzyme B (GrB) and perforin have both been shown to... more In human heart and kidney transplantations, granzyme B (GrB) and perforin have both been shown to be predictive markers for acute cellular rejection (ACR). We investigated the tissue expression and possible relationship of GrB and perforin to the clinical outcome, histopathology, and function of intestinal transplants. In 13 consecutive patients undergoing small intestine transplantation, histologic/immunohistochemical rejection monitoring was performed together with GrB and perforin immunostaining (score "0", 0%-10% positive lymphocytes; "1", 10%-25%; "2", 25%-50%; "3", Ͼ50%). Eleven patients are currently alive and well. All 11 had at least one episode of ACR: one patient had 6 episodes of severe ACR requiring retransplantation; the remaining 10 experienced only mild or moderate rejection. Both GrB and perforin were always co-expressed. A highly significant correlation was observed between GrB/perforin scores and histological severity of ACR (Pearson's coefficient, R Ͻ 0.0009). Interestingly, score 3 GrB/perforin immunostaining was recorded only in the context of severe ACR; all the histologically negative or "indeterminate" biopsies (n ϭ 6) taken from a single affected patient showed GrB/perforin scores of 1 or 2. By contrast, none of the other tested histologically negative/"indeterminate" biopsies (n ϭ 350), including those performed during graft stabilization, had raised GrB or perforin scores. We conclude that in intestinal transplantation recipients, a direct correlation seems to exist between histologically confirmed ACR and raised GrB/perforin immunohistochemical scores. Our findings suggest the need to investigate the possibility of predicting ACR by routine serum polymerase chain reaction (PCR) monitoring, which would reduce discomfort to patients.
Transplantation, 2011
Background. Systemic inflammation markers, such as neutrophil-to-lymphocyte ratio (NLR), have rec... more Background. Systemic inflammation markers, such as neutrophil-to-lymphocyte ratio (NLR), have recently emerged as the prognostic factors for recurrence of liver tumors. Methods. We assessed the ability of NLR and of other variables to predict the outcomes of orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC). A retrospective analysis was performed in 219 patients with HCC who underwent OLT between 1997 and 2009, with a median follow-up of 40 months. Results. Overall 3-and 5-year patient survival rates were 76.6% and 70.7%, respectively. Overall 3-and 5-year recurrence-free survival (RFS) rates were 83.8% and 82.1%, respectively. On univariate analysis, the factors affecting overall survival were ␣-fetoprotein more than 30 ng/mL (Pϭ0.006), NLR more than or equal to 5 (PϽ0.0001), hepatitis C infection (Pϭ0.043), and presence of microvascular invasion (MVI; Pϭ0.006). Preoperative treatments (Pϭ0.006), ␣-fetoprotein more than 30 ng/mL (Pϭ0.003), NLR more than or equal to 5 (PϽ0.0001), exceeding Milan criteria at final histology (Pϭ0.001), poor tumor differentiation (Pϭ0.02), and presence of MVI (PϽ0.0001) predicted a lower RFS. Cox's proportional hazard model showed that only increased NLR and presence of MVI independently predicted overall survival and RFS. Conclusions. NLR is an important predictor of outcome after OLT for HCC and should be used to identify OLT candidates at high risk of recurrence.
Transplantation, 2007
Analysis of intraoperative changes of metabolic, hemodynamic, and coagulative parameters is usefu... more Analysis of intraoperative changes of metabolic, hemodynamic, and coagulative parameters is useful to detect early ischemia-reperfusion damage after intestinal transplant. The objective of our study is to correlate the histological damage at the end of transplant in relation to the intraoperative changes after reperfusion. The histological aspect was graded according to Park&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s classification at the end of the surgical procedure with biopsies of the graft. Patients were divided into two groups according to the presence or absence of histological damage of the small bowel wall: group A (normal mucosa/minimal damage: Park&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s grades 0-1) and group B (mucosal damage: Park&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s grades 2-8). Significant hemodynamic, metabolic, and coagulative disorders were observed in group B. Consequently, these disorders are thought to be early indicators of graft damage. Actual monitoring procedures used for postoperative graft surveillance remain paramount in detecting postoperative intestinal dysfunction, but the indicators described in this paper could represent a further help in intraoperative and postoperative management.
Pathology - Research and Practice, 2010
Malignant mixed tumors of the liver in adults are extremely rare. To our knowledge, only a few ca... more Malignant mixed tumors of the liver in adults are extremely rare. To our knowledge, only a few cases have been reported in the literature. Nested stromal-epithelial tumors (NSET) of the liver are characterized by non-hepatocytic, non-biliary tumors with nests of epithelial and spindle cells, an associated myofibroblastic stroma, as well as variable calcifications and ossifications. We report a case of NSET of the liver affecting a young woman and provide detailed histological and clinical follow-up data, adding an additional case of this extremely rare pathology to the literature.
Liver Transplantation, 2006
The aim of this study was to evaluate how the immunohistochemical detection of liver hepatitis C ... more The aim of this study was to evaluate how the immunohistochemical detection of liver hepatitis C virus (HCV) antigens (HCV-Ag) could support the histologic diagnosis and influence the clinical management of post-liver transplantation (LT) liver disease. A total of 215 liver specimens from 152 HCV-positive patients with post-LT liver disease were studied. Histologic coding was: hepatitis (126), rejection (34), undefined (24; coexisting rejection grade I and hepatitis), or other (31). The percentage of HCV-Ag infected hepatocytes were evaluated, on frozen sections, by an immunoperoxidase technique. HCV-Ag were detectable early in 57% of cases within 30 days post-LT, 92% of cases between 31 and 180 days, and 74% of cases after more than 180 days. Overall, HCV-Ag were detected more frequently in histologic hepatitis as compared to rejection (P Ͻ 0.0001) with a higher percentage of positive hepatocytes (P Ͻ 0.00001). In 16 patients with a high number of HCV-Ag-positive hepatocytes (65%; range 40-90%) a clinical diagnosis of recurrent hepatitis (RHC) was made despite inconclusive histopathologic diagnosis. Multivariate analysis identified the percentage of HCV-Ag-positive hepatocytes and the time post-LT as independent predictors for RHC (P ϭ 0.008 and P ϭ 0.041, respectively) and the number of HCV-Ag-positive hepatocytes Ն50% as the only independent predictor for nonresponse (P Ͻ 0.001) in 26 patients treated with ␣-interferon plus ribavirin. In conclusion, HCV reinfection occurs early post-LT, reaching its peak within 6 months. Immunohistochemical detection of post-LT HCV reinfection support the diagnosis of hepatitis when the histologic features are not conclusive. A high number of infected cells, independently from the genotype, represents a negative predictive factor of response to antiviral treatment.
The Lancet, 2011
... Activate your free trial. a Department of Digestive Disease and Internal Medicine, StOrsola-M... more ... Activate your free trial. a Department of Digestive Disease and Internal Medicine, StOrsola-Malpighi University Hospital, Bologna, Italy. b Department of Hematology, Oncology and Laboratory Medicine, St Orsola-Malpighi University Hospital, Bologna, Italy. ...
Journal of Hepatology, 1998
Acute hepatitis caused by recurrent or de novo hepatitis B virus (HBV) infection after liver tran... more Acute hepatitis caused by recurrent or de novo hepatitis B virus (HBV) infection after liver transplantation frequently induces aggressive disease leading to liver failure. The aim of this study was to determine the efficacy and safety of lamivudine treatment in post-transplant acute hepatitis B. Twelve patients with acute hepatitis B were started on lamivudine 100 mg p.o. daily within 8 weeks of the appearance of HBsAg. One patient was excluded after 1 month because of hepatocellular carcinoma recurrence. Patients were followed for an average of 68.6 weeks (range 32-108), and were clinically and biochemically evaluated on a monthly basis. They had a histological assessment at baseline, after at least 6 months, and whenever clinically indicated. Basal HBV-DNA ranged between 13 and 1288 pg/ml and serum alanine aminotransferase between 97 and 1036 U/l. HBV-DNA became undetectable within 8 weeks and transaminases normalized within 24 weeks in all cases. At the last visit, eight patients (73%) remained HBV-DNA negative by liquid hybridization and had normal or close to normal alanine aminotransferase. Five patients (45%) were also HBsAg negative and HBV-DNA negative by polymerase chain reaction. HBV-DNA and transaminase breakthrough occurred in three patients (27%). Histology after 6-9 months showed chronic hepatitis in seven patients. Lamivudine was well tolerated without serious adverse reactions. These results indicate that lamivudine treatment induces sustained inhibition of viral replication and normalization of transaminases in the majority of post-transplant patients with acute hepatitis B. HBsAg loss may be achieved in a considerable number of cases. Although viral resistance is relatively frequent, early initiation of lamivudine appears to be effective and safe.
Journal of Hepatology, 2003
Journal of Hepatology, 1998
The hepatitis C virus (HCV) genome consists of quasispecies populations of heterogeneous variants... more The hepatitis C virus (HCV) genome consists of quasispecies populations of heterogeneous variants, especially in the hypervariable region. To assess the profiles of viral quasispecies in HCV-related hepatocellular carcinoma, we studied the viral population patterns in serum and liver tissues of 13 HCV-positive patients with hepatocellular carcinoma developed on cirrhotic and non-cirrhotic livers (5 and 8 cases, respectively). HCV genome heterogeneity was analyzed by polymerase chain reaction-mediated single-strand conformation polymorphism analysis, which showed multiple DNA bands representing different hypervariable region sequences. The HCV populations were different between tumorous and nontumorous tissues in 3/5 hepatocellular carcinomas with cirrhosis and in 6/8 without cirrhosis. At least one or more than one common band was detected in both compartments in all but one case. No significant differences in the complexity of HCV quasispecies were found in hepatocellular carcinoma with or without underlying cirrhosis. Comparison of the HCV quasispecies profiles in serum and liver tissues showed a different distribution of HCV variants between these two compartments in 6/7 patients. In four cases, both common and compartmentalized sequences were detected, whereas in two cases, both without cirrhosis, the HCV population in serum was completely different from that found in the liver. These results suggest that the complexity of HCV populations is influenced by the presence of hepatocellular carcinoma rather than by the severity of the underlying chronic liver disease. The different quasispecies patterns found in serum and liver may reflect different biological properties of circulating and intrahepatic HCV particles or the existence of extrahepatic sites of replication.
Uploads
Papers by Antonia D'Errico