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Hepatocellular carcinoma is the most common primary liver tumor, with 905 677 diagnosed cases and 830 180 deaths, in 2020 worldwide. In Argentina, it accounts for the 9th cause of death for cancer in men and the 10th in women. Unlike other highly-prevalent tumors, scientific evidence for most therapeutic options is limited mainly to small cohorts and retrospective studies. The aim of this study is to characterize and describe epidemiologically patients with diagnosis of hepatocellular carcinoma in the Italian Hospital of Buenos Aires during a 12-year period. Overall survival for our cohort was 58%, 46%, and 36% at 1, 3 and 5 years respectively. Average survival for patients receiving palliative treatment was 5 months, while for those who received either non-curative or curative treatment was 23 and 75 months respectively. Recurrence-free survival for those patients who underwent a curative treatment was 89%, 76% y 61% at 1, 3 and 5 years. A thorough analysis of etiology, risk factors, incidence, mortality and treatment was made. The study's importance lies in its large sample size, quantity and quality of data, and will most certainly stimulate the development of local studies in hepatocellular carcinoma.El carcinoma hepatocelular (HCC) es el tumor primario más frecuente del hígado, con 905 677 casos diagnosticados en 2020, en todo el mundo, y 830 180 muertes. Es responsable de la novena causa de muerte por cáncer en los hombres y la décima en mujeres en Argentina. A diferencia de otros tumores de alta prevalencia, la evidencia científica acerca del HCC se limita principalmente a pequeñas cohortes y estudios retrospectivos. El objetivo de este estudio fue describir epidemiológicamente a aquellos pacientes con diagnóstico de HCC en el Hospital Italiano de Buenos Aires en un periodo de 12 años. La supervivencia global para nuestra cohorte fue de 58, 46 y 36% a 1, 3 y 5 años respectivamente. El promedio de supervivencia en pacientes con tratamiento paliativo fue de 5 meses, 23 para aquellos que recibieron tratamientos no curativos y 75 meses para los que recibieron tratamientos curativos. El porcentaje de pacientes libres de enfermedad a 1, 3 y 5 años fue de 89%, 76% y 61% respectivamente. Se realizó un estudio minucioso de la etiología, factores de riesgo, incidencia, mortalidad y tratamientos realizados. Su importancia yace en su tamaño muestral, calidad y cantidad de información disponible.

The aim of this study was to determine the effect of hyperbilirubinemia in the sensitivity of percutaneous transluminal forceps biopsy (PTFB) in patients with suspected malignant biliary stricture. Ninety-three patients with suspicion of malignant biliary stricture underwent percutaneous transhepatic cholangiography followed by PTFB. Sensitivity, specificity and predictive values were analysed based on the presence or absence of hyperbilirubinemia, defined as total bilirubin equal to, or higher than 5 mg/dL. Variables included demographic and clinical features, laboratory, tumour type and localization, stricture length, therapeutic approach and histopathology. Additionally, major morbidity and mortality were assessed. The overall sensitivity, specificity, positive predictive value and accuracy of PTFB were 61.1%, 100%, 100%, and 62.4%, respectively. Hyperbilirubinemia affected 57% of patients at the time of PTFB. There were 35 (37%) false negative results, none of them related to tumour type or localization, stricture length, or previous biliary intervention (i.e. PBBD (percutaneous biliary balloon dilatation), ERCP (endoscopic retrograde cholangiopancreatography)) (p > 0.05). However, when bilirubin was

Background IgG4-related disease can manifest diversely, including autoimmune pancreatitis and IgG4-related cholangiopathy. We are reporting a very unusual cause of pancreatic cancer triggered in a previously unknown IgG4-related disease. Case summary A 75-year-old man was diagnosed with a 43 mm × 33 mm pancreatic head tumor after consulting for abdominal pain and jaundice. A pancreaticoduodenectomy was carried out uneventfully, and the histopathology report showed an early stage of acinar-cell pancreatic cancer. The patient reconsulted on the 30th postoperative day with fever, jaundice and asthenia. Magnetic resonance cholangiopancreatography evidenced an extense bile duct stricture. A percutaneous biliary drainage proved to be ineffective, even after exchanging it with larger bore drainage. Reviewing the surgical specimen, features compatible with IgG4-related disease were observed. Consequently, empiric treatment with steroids was initiated achieving excellent results. Conclusion IgG4-related disease may cause chronic inflammation of the pancreas and can condition pancreatic malignancies.

The concept and diagnostic criteria for autoimmune pancreatitis have evolved since the first case reports published in the 1960s. The advances in knowledge during the past two decades have resulted in the recognition of several pancreatic conditions that show, on histological evaluation, variable combinations of inflammation and fibrosis. In fact, autoimmune pancreatitis comprises two distinct diseases: type 1 and type 2. Type 2 autoimmune pancreatitis is a particular pancreatic disease about which there is limited data; it differs from the ‘classic’ IgG4-related type 1 autoimmune pancreatitis in terms of epidemiology, pathological characteristics and natural evolution. There are patients with complex pancreatic conditions where an autoimmune component and good response to steroids are demonstrated, but they do not meet the suggested criteria for the diagnosis of type 1 or type 2 autoimmune pancreatitis. Although the term steroid-responsive pancreatitis may be interpreted as a synonym to type 1 and 2 autoimmune pancreatitis, these are not the only pancreatic conditions that improve with this type of treatment. Here, we present three clinical cases and a literature review related to the diagnosis and treatment of autoimmune pancreatitis and other less frequent pancreatic disorders that present a good response to steroid therapy.

BACKGROUND Hepatocellular adenoma (HCA) is a rare benign liver tumor usually affecting young women with a history of prolonged use of hormonal contraception. Although the majority is asymptomatic, a low proportion may have significant complications such as bleeding or malignancy. Despite responding to the hormonal stimulus, the desire for pregnancy in patients with small HCA is not contraindicated. However, through this work we demonstrate that intensive hormonal therapies such as those used in the treatment of infertility can trigger serious complications CASE SUMMARY A 33-year-old female with a 10-year history of oral contraceptive use was diagnosed with a hepatic tumor as an incidental finding in an abdominal ultrasound. The patient showed no symptoms and physical examination was unremarkable. Laboratory functional tests were within normal limits and tests for serum tumor markers were negative. An abdominal magnetic resonance imaging (MRI) was performed, showing a 30 mm × 29 mm focal lesion in segment VI of the liver compatible with HCA or Focal Nodular Hyperplasia with atypical behavior. After a total of six years of follow-up, the patient underwent ovulation induction treatment for infertility. On a following MRI, a suspected malignancy was warned and hence, surgery was decided. The surgical specimen revealed malignant transformation of HCA towards trabecular hepatocarcinoma with dedifferentiated areas. There was non-evidence of tumor recurrence after three years of clinical and imaging follow-up. CONCLUSION HCAs can be malignant regardless its size and low-risk appearance on MRI when an ovultation induction therapy is indicated.

In Chronic hepatitis B (CHB) infection, virus and immune response interplay is thought to be responsible for pathogenesis. Yet, the impact of each immune cell population and viral protein expression in liver damage is still unknown. Our aim was to study the interplay between intrahepatic immune response and viral activity in relation to CHB liver damage. Immunostaining was performed in 29 liver biopsies from untreated CHB patients to characterize liver infiltrate [Th (CD4+), CTL (CD8+), Treg (FoxP3+), Th17 (IL-17A+) and Th1 (T-bet+)] and viral antigen expression (HBsAg and HBcAg). Inflammatory activity and fibrosis were assessed using the HAI and METAVIR scoring system. All studied populations were identified in the portal-periportal (P-P) areas with a CD4+ lymphocyte predominance, while only CD8+ and FoxP3+ cells were observed in the intralobular area. Both P-P CD4+ and intralobular CD8+ cell frequencies were increased among severe hepatitis cases. Concerning HBsAg and HBcAg expression, a mutually exclusive pattern was observed. HBcAg was mainly detected among HBeAg-positive patients and was associated with hepatitis severity and higher frequency of P-P FoxP3+, intralobular CD8+ and FoxP3+ cells. HBsAg was identified among HBeAg-negative cases with less severe hepatitis grade and lower frequency of P-P CD4+ and intralobular FoxP3+ lymphocytes. In conclusion, the HBV antigen profile expression seen during CHB infection may be reflecting different stages of viral replication which impacts the host immune response and liver damage process. While HBcAg might be an inducer of a regulatory microenvironment, the intralobular CTL population seemed to have a key role in hepatitis severity.

Background Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease whose prevalence has been increasing constantly and linked to the global obesity epidemic. The NAFLD histologic spectrum ranges from simple steatosis to nonalcoholic steatohepatitis (NASH), which can progress to cirrhosis and hepatocellular carcinoma. Liver biopsy is the only reliable means to diagnose and stage NASH, but its invasive nature limits its use. Therefore, the prediction of hepatic injury by means of the development of new noninvasive tests represents a growing medical need. Our aim was to evaluate matrix deposition and cell-death markers, which correlate with liver injury in an NAFLD patient cohort. Patients and methods Liver biopsies and serum from 34 NAFLD adult patients were analyzed. Histological parameters were evaluated. Matrix deposition [hyaluronic acid (HA) and tissue inhibitor of matrix metalloproteinase inhibitor-1 (TIMP-1)] and cell-death markers [cytokeratin-18 (M65) and caspase-cleaved cytokeratin-18 (M30)] were measured in serum samples. Results HA showed an association with fibrosis severity (P=0.03) and M30 with steatosis (P=0.013), inflammation (P=0.004), and fibrosis severity (P=0.04). In contrast, TIMP-1 and M65 showed no association with any histological parameter of liver injury. The evaluation of diagnostic accuracy showed good performance as less invasive markers of significant fibrosis of both HA (area under the receiver operating characteristic curve: 0.928) and M30 (area under the receiver operating characteristic curve: 0.848). Conclusion Biomarkers are essential tools that may provide a quick and accurate diagnosis for patients with life-threatening NAFLD and NASH. HA and M30, together or determined sequentially, have been found to be straightforward tests that may be sufficient to predict significant fibrosis even in a primary care center of an underdeveloped country. Fil: Valva, Pamela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina Fil: Rios, Daniela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina Fil: Casciato, Paola. Hospital Italiano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Gadano, Adrián Carlos. Hospital Italiano; Argentina Fil: Galdame, Omar. Hospital Italiano; Argentina Fil: Mullen, Eduardo. Hospital Italiano; Argentina Fil: Bertot, Gustavo. Instituto Universidad de la Fundación "Héctor Barceló"; Argentina Fil: de Matteo, Elena Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina Fil: Preciado, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina

Chronic Hepatitis C Virus (HCV) infection is a major risk for hepatocellular carcinoma (HCC) development. HCV Core protein has been associated with the modulation of potentially oncogenic cellular processes and E2 protein has been useful in evolutive studies to analyze the diversity of HCV. Thus, the aim of this study was to evaluate HCV compartmentalization in tumoral, non-tumoral liver tissue and serum and to identify viral mutations potentially involved in carcinogenesis. Samples were obtained from four patients with HCC who underwent liver transplantation. Core and E2 were amplified, cloned and sequenced. Phylogenies and BaTS Test were performed to analyze viral compartmentalization and a signature sequence analysis was conducted by VESPA. The likelihood and Bayesian phylogenies showed a wide degree of compartmentalization in the different patients, ranging from total clustering to a more scattered pattern with small groups. Nevertheless, the association test showed compartmentalization for the three compartments and both viral regions tested in all the patients. Signature amino acid pattern supported the compartmentalization in three of the cases for E2 protein and in two of them for Core. Changes observed in Core included polymorphism R70Q/H previously associated with HCC. In conclusion, evidence of HCV compartmentalization in the liver of HCC patients was provided and further biological characterization of these variants may contribute to the understanding of carcinogenesis mediated by HCV infection. © 2016 Wiley Periodicals, Inc.

A double-blind randomized controlled trial was performed to compare the safety and efficacy of α-lipoic acid (ALA) in liver transplantation (LT). The grafts were randomized to receive ALA or placebo before the cold ischemia time. Furthermore, patients transplanted with the ALA-perfused graft received 600 mg of intravenous ALA, while patients with the nonperfused graft received the placebo just before graft reperfusion. Hepatic biopsy was performed 2 h postreperfusion. Blood samples were collected before, during and 1 and 2 days after reperfusion. Quantitative polymerase chain reaction (qPCR) analysis was performed on biopsies to assess genes involved in the response to hypoxia, apoptosis, cell growth, survival and proliferation, cytokine production and tissue damage protection. Nine of 40 patients developed postreperfusion syndrome (PRS), but seven of them belonged to the control group. There was a decrease in PHD2 and an increase in alpha subunit of hypoxia-inducible factor-1 (HIF-1α) and baculoviral IAP repeat containing 2 (Birc2) transcript levels in the biopsies from the ALA-treated versus the control group of patients. Additionally, plasma levels of alarmins were lower in ALA-treated patients than control patients, which suggests that ALA-treated grafts are less inflammatory than untreated grafts. These results showed that ALA is safe for use in LT, induces gene changes that protect against hypoxia and oxidative stress and reduces the appearance of PRS. Fil: Casciato, Paola. Instituto Universitario del Hospital Italiano de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Ambrosi, Nella Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina Fil: Caro, Fiorella Yanina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina Fil: Vazquez, Mónica. Instituto Universitario del Hospital Italiano de Buenos Aires; Argentina Fil: Müllen, Eduardo. Instituto Universitario del Hospital Italiano de Buenos Aires; Argentina Fil: Gadano, Adrián Carlos. Instituto Universitario del Hospital Italiano de Buenos Aires; Argentina Fil: de Santibanes, Eduardo. Instituto Universitario del Hospital Italiano de Buenos Aires; Argentina Fil: de Santibañes, Martin. Instituto Universitario del Hospital Italiano de Buenos Aires; Argentina Fil: Zandomeni, Marcos. Instituto Universitario del Hospital Italiano de Buenos Aires; Argentina Fil: Chahdi, Magali. Instituto Universitario del Hospital Italiano de Buenos Aires; Argentina Fil: Lazarte, Julio C.. Instituto Universitario del Hospital Italiano de Buenos Aires; Argentina Fil: Biagiola, David A.. Instituto Universitario del Hospital Italiano de Buenos Aires; Argentina Fil: Iaquinandi, Juan Cruz. Instituto Universitario del Hospital Italiano de Buenos Aires; Argentina Fil: Santofimia-Castaño, Patricia. Centre de Recherche En Cancerologie de Marseille; Francia Fil: Iovanna, Juan Lucio. Centre de Recherche En Cancerologie de Marseille; Francia Fil: Incardona, Claudio. Instituto Universitario del Hospital Italiano de Buenos Aires; Argentina. Fundación Gador; Argentina Fil: Chuluyan, Hector Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina

The role of the different lymphocyte populations in liver microenvironment of chronic hepatitis C (CHC) patients is still matter of debate. Since Th17 and Treg have opposite functions, their balance could affect disease progression. The aim was to explore liver microenvironment and its peripheral blood counterpart in adult CHC patients. CD4+ lymphocytes were predominant in the liver, with high Foxp3+ but low IL-17A+ frequency. IL-17A+ lymphocytes and IL-17A+/Foxp3+ ratio displayed association with advanced fibrosis (p = 0.0130; p = 0.0236, respectively), while Foxp3+ lymphocytes and IL-10 expression level inversely correlated with fibrosis severity (p = 0.0381, p = 0.0398, respectively). TGF-β/IL-6 ratio correlated with IL-17A+/Foxp3+ ratio (p = 0.0036, r = 0.5944) and with IL-17A+ lymphocytes (p = 0.0093; r = 0.5203). TNF-α and TGF-β were associated with hepatitis severity (p = 0.0409, p = 0.0321). Peripheral blood lymphocyte frequency was not associated with liver damage. There are functionally different immune cell populations actively involved in liver damage, but the liver cytokine milieu actually drives the pathogenesis. The intrahepatic Foxp3+ lymphocytes predominance beside the low IL-17A+ lymphocytes frequency, delineate a skewed IL-17A+/Foxp3+ balance towards Foxp3+ lymphocytes. However, the IL-17A+ lymphocytes association with advanced fibrosis denotes their role in the pathogenesis. Therefore, the interplay between Th17 and Treg conditions liver fibrogenesis. Fil: Rios, Daniela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Anatomía Patológica; Argentina. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina Fil: Valva, Pamela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Anatomía Patológica; Argentina. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina Fil: Casciato, Paola Cecilia. Hospital Italiano; Argentina Fil: Frias, Silvia. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina Fil: Soledad Caldirola, María. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Área de Inmunología; Argentina Fil: Gaillard, María Isabel. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Área de Inmunología; Argentina Fil: Bezrodnik, Liliana. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Área de Inmunología; Argentina Fil: Bandi, Juan. Hospital Italiano; Argentina Fil: Galdame, Omar. Hospital Ramos Mejia; Argentina Fil: Ameigeiras, Beatriz. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina Fil: Krasniansky, Diana. Hospital General de Agudos “Carlos G. Durand”. Unidad de Hepatología; Argentina Fil: Brodersen, Carlos. Hospital General de Agudos “Carlos G. Durand”. Unidad de Hepatología; Argentina Fil: Mullen, Eduardo. Hospital Italiano; Argentina Fil: de Matteo, Elena Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Anatomía Patológica; Argentina Fil: Preciado, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Anatomía Patológica; Argentina. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina

In January 2015, a 20-month-old child and her family took part in recreational activities at Carrasco and Malvín beaches (Montevideo, Uruguay). An intense harmful algae bloom (HAB) was developing along the coast at that time. A few hours after the last recreational exposure episode, the family suffered gastrointestinal symptoms which were self-limited except in the child’s case, who was admitted to hospital in Uruguay with diarrhea, vomiting, fatigue, and jaundice. The patient had increased serum levels of liver enzymes and bilirubin and five days later presented acute liver failure. She was referred to the Italian Hospital in Buenos Aires, being admitted with grade II–III encephalopathy and hepatomegaly and requiring mechanical respiratory assistance. Serology tests for hepatitis A, B, and C, Epstein-Barr virus, and cytomegalovirus were negative. Laboratory features showed anemia, coagulopathy, and increased serum levels of ammonium, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin. Autoimmune Hepatitis Type-II (AH-II) was the initial diagnosis based on a liver kidney microsomal type 1 antibodies (LKM-1) positive result, and twenty days later a liver transplant was performed. The liver histopathology had indicated hemorrhagic necrosis in zone 3, and cholestasis and nodular regeneration, which were not characteristic of AH-II. LC/ESI-HRMS (liquid chromatography electrospray ionization high-resolution mass spectrometry) analysis of MCs in the explanted liver revealed the presence of Microsytin-LR (MC-LR) (2.4 ng·gr−1 tissue) and [D-Leu1]MC-LR (75.4 ng·gr−1 tissue), which constitute a toxicological nexus and indicate a preponderant role of microcystins in the development of fulminant hepatitis., This study was supported by the National Council of Scientific and Technical Research (CONICET) PIP No. 112 201101 00959 res 1672, Ministry of Science and Technology PICT No. 2013-0861, and National University of La Plata PPID/X024.

Background. Incidental hepatocellular carcinoma (iHCC) generates uncertainty over risk of recurrence after liver transplantation (LT). Aim. To compare recurrence between iHCC and confirmed HCC diagnosed prior to transplant based on imaging criteria (cHCC). Material and methods. Fifty-four HCC patients were analyzed from a series of 309 consecutive adult transplanted patients. We developed a recurrence predicting score (RPS) applying ORs based on pathologic risk variables. Results. Incidence of iHCC was 4.8% (n = 15) and overall recurrence 12.9% (cHCC 15.4% and iHCC 7%; P = 0.39). Variables included in the RPS were: microvascular invasion OR 17.8 (1.78-178.97; P = 0.014: 2 points), neural invasion OR 15.5 (1.13-212.17; P = 0.04: 1.5 points), nuclear grade > II OR 9.3 (1.17-74.84; P = 0.035: 1 point), and beyond Up-to 7 criteria OR 13.1 (1.66-103.67; P = 0.015: 1.5 points). Two risk groups were identified: low risk for recurrence (0-1 point) and intermediate-high risk groups (2-6 points). Low risk category remained an independent predictor of recurrence: OR 0.11 (0.01-0.67; P = 0.017); AUROC of 0.75 (0.54-0.96). A tendency towards more patients categorized as low risk group among iHCC patients was observed (69.2%; P = 0.13). Conclusions. In this series iHCC was not associated to lower risk of recurrence when compared to cHCC. We propose application of an RPS as a clinical tool for recurrence risk estimation.

PURPOSE: Current American Joint Committee on Cancer and the Union Internationale Contre le Cancer TNM classification disregards location of positive nodes, discontinuing N3 category, which constitutes a major modification to 1987 version. This study was designed to assess the impact of the recategorization of former N3 cases and the reliability of the current N1-N2 subcategorization of Stage III patients. METHODS: Prospectively collected data from 1,391 patients (55.8 percent males; median age, 64 (range, 21–97) years), operated on with curative intent between 1980 and 1999, were analyzed. The median follow-up was 60 (interquartile range, 27–97) months with 129 cases lost to follow-up. RESULTS: Of positive node cases, 25.3 percent were former N3. Among them, 30.5 percent migrated to the N1 group and 69.5 percent to the N2 group. The proportions of former N3 cases in N1 and N2 groups were 12.5 percent and 46.1 percent, respectively (P < 0.001). Node-positive patients had an actuarial five-year survival rate of 56.7 percent (95 percent confidence interval, 53–59), with a significant difference between N1/N2 categories (63.6 vs. 44.1 percent, respectively; P < 0.001). Although apical node involvement and more than three positive nodes were associated with poorer outcomes in univariate analysis, only the number of positive nodes had independent association (hazard ratio, 1.6 (range, 1.2–2.2); P < 0.001). Integration of former N3 cases did not modify outcomes. CONCLUSIONS: The recategorization of former N3 involved a high proportion of positive node cases. Current N1/N2 categories clearly defined different outcomes and were not modified by the integration of former N3.

Mechanisms leading to liver damage in chronic hepatitis C (CHC) are being discussed, but both the immune system and the virus are involved. The aim of this study was to evaluate intrahepatic viral infection, apoptosis and portal and periportal/interface infiltrate in paediatric and adult patients to elucidate the pathogenesis of chronic hepatitis C. HCV-infected, activated caspase-3+ and TUNEL+ hepatocytes, as well as total, CD4+, CD8+, Foxp3+ and CD20+ lymphocytes infiltrating portal and periportal/interface tracts were evaluated in 27 paediatric and 32 adult liver samples by immunohistochemistry or immunofluorescence. The number of infected hepatocytes was higher in paediatric than in adult samples (p 0.0078). In children, they correlated with apoptotic hepatocytes (activated caspase-3+r = 0.74, p < 0.0001; TUNEL+r = 0.606, p 0.0017). Also, infected (p = 0.026) and apoptotic hepatocytes (p = 0.03) were associated with the severity of fibrosis. In adults, activated caspase-3+ cell count was increased in severe hepatitis (p = 0.009). Total, CD4+, CD8+ and Foxp3+ lymphocyte count was higher in adult samples (p < 0.05). Paediatric CD8+ cells correlated with infected (r = 0.495, p 0.04) and TUNEL+ hepatocytes (r = 0.474, p = 0.047), while adult ones correlated with activated caspase-3+ hepatocytes (r = 0.387, p 0.04). In adults, CD8+ was associated with hepatitis severity (p < 0.0001) and correlated with inflammatory activity (CD8+ r = 0.639, p 0.0003). HCV, apoptosis and immune response proved to be involved in CHC pathogenesis of both paediatric and adult patients. However, liver injury in paediatric CHC would be largely associated with a viral cytopathic effect mediated by apoptosis, while in adults it would be mainly associated with an exacerbated immune response. Fil: Valva, Pamela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Anatomía Patológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Gismondi, Maria Ines. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Casciato, Paola C.. Hospital Italiano; Argentina Fil: Galoppo, Marcela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina Fil: Lezama, Carol. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina Fil: Galdame, Omar. Hospital Italiano; Argentina Fil: Gadano, Adrián Carlos. Hospital Italiano; Argentina Fil: Galoppo, María Cristina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina Fil: Mullen, Eduardo. Hospital Italiano; Argentina Fil: de Matteo, Elena Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Anatomía Patológica; Argentina Fil: Preciado, María Victoria. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Anatomía Patológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

Background: Liver biopsy represents the gold standard for evaluating damage and progression in patients with chronic hepatitis C (CHC); however, developing noninvasive tests that can predict liver injury represents a growing medical need. Considering that hepatocyte apoptosis plays a role in CHC pathogenesis; the aim of our study was to evaluate the presence of different apoptosis markers that correlate with liver injury in a cohort of pediatric and adult patients with CHC. Methods: Liver biopsies and concomitant serum samples from 22 pediatric and 22 adult patients with CHC were analyzed. Histological parameters were evaluated. In serum samples soluble Fas (sFas), caspase activity and caspase-generated neoepitope of the CK-18 proteolytic fragment (M30) were measured. Results: sFas was associated with fibrosis severity in pediatric (significant fibrosis p=0.03, advanced fibrosis p=0.01) and adult patients (advanced fibrosis p=0.02). M30 levels were elevated in pediatric patients with severe steatosis (p=0.01) while in adults no relation with any histological variable was observed. Caspase activity levels were higher in pediatric samples with significant fibrosis (p=0.03) and they were associated with hepatitis severity (p=0.04) in adult patients. The diagnostic accuracy evaluation demonstrated only a good performance for sFas to evaluate advanced fibrosis both in children (AUROC: 0.812) and adults (AUROC: 0.800) as well as for M30 to determine steatosis severity in children (AUROC: 0.833). Conclusions: Serum sFas could be considered a possible marker of advanced fibrosis both in pediatric and adult patient with CHC as well as M30 might be a good predictor of steatosis severity in children. Fil: Valva, Pamela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Anatomía Patológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Casciato, Paola. Hospital Italiano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Lezama, Carol. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina Fil: Galoppo, Marcela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina Fil: Gadano, Adrián Carlos. Hospital Italiano; Argentina Fil: Galdame, Omar. Hospital Italiano; Argentina Fil: Galoppo, María Cristina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina Fil: Mullen, Eduardo. Hospital Italiano; Argentina Fil: de Matteo, Elena Noemí. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Anatomía Patológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Preciado, María Victoria. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Anatomía Patológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

Nodular regenerative hyperplasia of the liver is a rare condition. We describe here the case of a patient with HIV who presented with a clinical syndrome of portal hypertension. After multiple evaluations the diagnosis was recognized by the histology. The findings were attributed to the prolonged use of didanosine.

BACKGROUND/AIMS: Liver biopsy represents the gold standard for damage evaluation, but noninvasive serum markers that mirror liver fibrosis progression are actual goals both in adults and especially in children. The aim was to determine specific serum markers that correlate with liver fibrosis progression during chronic HCV infection. METHODS: Liver biopsies and concomitant serum samples from 22 pediatric and 22 adult HCV patients were analyzed. Histological parameters were evaluated. On serum TGF-ß1, tissue inhibitor of matrix metalloprotein inhibitor-1 (TIMP-1), hyaluronic acid (HA) and aminoterminal peptide of procollagen type III (PIIINP) were tested. RESULTS: Significant fibrosis (F≥2) and advanced fibrosis (F≥3) represented 64% and 20%, respectively in children; while 54% F≥2 and 23% F≥3 in adults. Hyaluronic acid (p = 0.011) and PIIINP (p = 0.016) were related to worse fibrosis stages only in adults, along with TIMP-1 (p = 0.039) just in children; but TGF-ß1 was associated with mild fibrosis (p = 0.022) in adults. The AUROC of TIMP-1 in children to discriminate advanced fibrosis was 0.800 (95%IC 0.598-0.932). In adults, the best AUROCs were that of HA, PIIINP and TGF-ß1 [0.929 (IC95% 0.736-0.994), 0.894 (IC95% 0.689-0.984) and 0.835 (IC95% 0.617-0.957)], respectively. In children, according to the cut off (165.7 ng/mL) value for TIMP-1, biopsies could have been avoided in 72% (18/25). Considering the cut off for HA (109.7 ng/mL), PIIINP (9.1 µg/L), and TGF-ß1 (10,848.3 pg/mL), biopsies could have been avoided in 87% (19/22) of adult patients by using HA and 73% (16/22) using PIIINP or TGF-ß1. CONCLUSIONS: In adults given the diagnostic accuracy of HA, PIIINP, TGF-ß1, their combination may provide a potential useful tool to assess liver fibrosis. This first pediatric study suggests that TIMP-1 is clinically useful for predicting liver fibrosis in HCV patients.

The Budd-Chiari syndrome is a low-prevalence disease due to an hepatic outflow obstruction. It is associated with procoagulant status and liver transplantation is one of the therapeutic tools for the treatment.To evaluate the etiology, presenting form, treatment and evolution of patients with Budd-Chiari syndrome.Ten consecutive adult patients with Budd-Chiari syndrome evaluated from January 1998 to June 2009 were prospectively included. The median follow up was 32.4 months (4-108 months).The mean age of patients was 34 +/- 12 years old. Presentation was acute in 1 patient, chronic in 2 and subacute in 7. The mean time from consultation to diagnosis was 4 +/- 2 days. Clinical manifestations were splenomegaly in 8 patients, malnutrition in 7, ascites in 6 and encephalopathy in 4. Diagnosis was confirmed by angiography in all cases. Initial prothrombin concentration was30% in 3 patients, 31% to 50% in 5, and50% in 2; hematocrit was45% in 5 patients and platelet count was400.000/mm3 in 6. MELD distribution at diagnosis wasor = 13 points in 4 patients, between 14 and 16 points in 5 andor = 17 points in 1. Policytemia vera was detected in 7 patients, essential thrombocythemia in 1 and positive lupus inhibitor in 4. Nine patients were anticoagulated after diagnosis. Angioplasthy was required in 1 patient and 6 were treated with a transjugular intrahepatic portosystemic shunt. Death occurred in 1 patient due to gastrointestinal bleeding. Two patients were transplanted.In our experience all patients with Budd-Chiari syndrome have a procoagulant status. The transjugular intrahepatic portosystemic shunt is effective in treating this syndrome and liver transplantation should be reserved for patients who are refractory to other therapeutics.

The first Argentine experience with epidemiologic, molecular, and genetic counseling data is reported. We analyzed 43 families fulfilling Amsterdam criteria identified from a prospective database with data from 779 relatives. Eleven families (25.6 percent) presented as Lynch I, 29 (67.4 percent) as Lynch II, and 3 (7 percent) as Muir-Torre syndrome. Among the 306 affected members, 197 cases of colorectal cancer were identified (mean age at diagnosis, 52.1 (range, 21–90) years). The most frequent extracolonic tumors were gastric adenocarcinoma in males and endometrium adenocarcinoma in females. A high incidence of breast cancer was observed (16 cases among 155 females, crude rate: 11,594.20/100,000). Twenty-seven patients (8.8 percent) developed more than one tumor. These patients were younger than those with only one tumor (45 vs. 51 years; P = 0.001). In 5 of 11 patients who underwent molecular sequencing, a pathologic mutation was found. A novel C deletion at 1910 nucleotide, codon 637, exon 12 of MSH2 gene was identified in a family with a strong aggregation of breast cancer with lack of MSH2 immunohistochemical staining. For 78.2 percent of counseled individuals, this session represented the first time they received information, and 73.9 percent stated that their physicians were unaware of their family background. Argentine families presented a high incidence of stomach cancer. The elevated incidence of breast cancer and its association with a novel hMSH2 mutation bring to consideration the inclusion of this malignancy as part of the syndrome. A lack of awareness by both physicians and persons at risk was observed.

Mutation of the mismatch repair genes MLH1 and MSH2 account for the majority of the genetic abnormalities in Lynch syndrome. Immunohistochemical detection of their protein products is becoming an increasingly common method to detect these mutations. The aim of this study was to compare the expression of MLH1 and MSH2 by immunohistochemistry and its relationship with a group of clinical and histological variables in patients with known Lynch syndrome (n=16) and in cohort of young patients (less than 50 years) who did not meet Amsterdam criteria (n=25). The mean age was 40.7 and 64% were women. Conclusive results were obtained in 40 cases (97.6%). Eighteen cases (45%) showed abnormal expression of either MLH1 (11 cases) or MSH2 (6 cases) and both stains (1 case). Alteration of the normal staining pattern was seen more commonly in patients with Lynch syndrome than in the sporadic group (68.7% vs 28%, p=0.01). A significant correlation was obtained between abnormal protein expression and microsatellite instability (MSI): normal expression: 5.9%, lack of expression: 92.3%, p0.0001. The sensitivity and specificity of the immunohistochemical to predict MSI were 92.3% and 94.1% respectively. Immunohistochemistry and MSI results did not correlate with any histopathological parameter. In conclusion, in our experience abnormal staining of MLH and MSH correlates strongly with the presence of MSI. In addition it appears that in our population a significant proportion of young patients (50 years old) demonstrate alterations in the mismatch repair gene products suggesting an important role of these molecules in tumorigenesis.

Hepatic involvement by tuberculosis is a rare type of manifestation of the disease. There are several forms of clinical presentations. One of them is the hepatic tuberculoma in which we base our presentation. Given that hepatic tuberculoma is a rare entity and generally shows inespecific symptoms, it is rarely suspected by the clinical picture. The diagnosis of hepatic tuberculosis is generally done in the intraoperative or postoperative period by analyzing a specimen taken by laparoscopy or laparotomy during the study of a hepatic mass. Laboratory tests or image studies do not give pathognomonic information to conform the diagnosis. The cornerstone in the treatment of this pathology is the antituberculous therapy. Surgical or endoscopic interventions are occasionally required. The role of surgery in the treatment of this pathology is reserved for a few solitary lesions. Once the correct treatment is performed the outcome is favorable. We present 4 cases of hepatic tuberculoma with different imaging and clinical presentations.

BACKGROUND: Colorectal cancer (CRC) is the second most frequent cancer and the second cause of mortality related to cancer in Argentina. The detection of premalignant lesions (PML) through colonoscopy has been demonstrated to be effective in the prevention of CRC. It is important to be aware of the prevalence of these lesions to estimate their impact on the prevention of CRC in our population. The aim of this study was to assess the prevalence of PML in asymptomatic subjects with different levels of risk of CRC. METHODS: A cross-sectional analysis was performed based on the colonoscopy records of asymptomatic subjects screened for CRC in a General Hospital of Buenos Aires City, Argentina, between July 2004 and March 2007. The prevalence of PML was assessed in 2 groups: 1) average risk and 2) first-degree relatives with CRC. Patients with incomplete colonoscopy, poor preparation or second-degree relatives with CRCwere excluded. PMLwas defined as polyps or flat adenomaswith low or high-grade dysplasia.Multivariate logistic analysis was performed to establish the association between individual characteristics and PML. RESULTS: Data from 1233 subjects was collected (female= 733, mean age= 67.6 years SD= ±11.2). We found a global prevalence of 24.1% for PML and 1.1% for CRC. Average risk group (n=476; female= 246; mean age=61.8 years SD= ±9,06) showed a prevalence of 22.1% for PML (CI 95%= 18.3-25.8), in which 19.2% had low-grade and 2.5% high-grade dysplasia. The prevalence of CRC was 1.05%. First-degree relatives group (n=757; female =487; mean age= 54.9 years SD= ±11.53) showed a prevalence of 25.2% (CI 95%=22.1-28.3), in which 20% had lowgrade and 4.8% high-grade dysplasia. The prevalence of CRC in this group was 1.2%. In the validation set a logistic regressionmodel showed that family history of CRCwas independently associated with increased risk of PML (odds ratio=1.54; CI 95%= 1.15-2.05; P=0.004). This difference was greater in younger subjects (table 1). Male sex was also independently associated with an increased risk of PML (odds ratio=1.50; IC 95%= 1.15-1.97; P=0.003). CONCLUSION: Approximately a quarter of this population presented at least one PML and a significantly increased risk in first-degree relatives with CRC and male sex was observed. These results may contribute to issue local guidelines for CRC prevention. Table 1. Prevalence in different age groups

A placental lesion, characterized by fibrinoid and trophoblastic necrosis with massive infiltration of the intervillous space by mononuclear cells (massive chronic intervillositis, MCI), was observed in six cases, five with intrauterine growth retardation (IUGR) and one with sudden intrauterine fetal death. Four out of six had chronic villitis of unknown etiology (CVUE) associated with this lesion, and five had lesions of anchoring villitis. In three cases, acute atherosislike lesions in spiral arteries of parietal and/or basal decidua were observed. Massive deposits of IgM, a smaller amount of C3 and Clq, and slight deposits of IgG and IgA were found in these vessels. Neither mothers nor infants had any clinical or serological evidence of infection. Cases with MCI were compared with those having CVUE without intervillositis. Patients with MCI showed lower values of infant weight, infant length, and ponderal index than controls. However, cases with MCI group showed a higher incidence of IUGR. Placentas from the MCI group had a greater number of acute atherosislike lesions than controls. Massive chronic intervillositis may represent an extreme variant of villitis of unknown etiology. A maternal immunological aggression toward fetal tissues is proposed as pathophysiological mechanism, although a nondetermined placental infection cannot be excluded.

We have investigated the presence and clinical implications of maternal vascular lesions and chronic villitis of unknown etiology (CVUE) in 18 placentas of 15 mothers with several autoimmune diseases (AD), including, for the first time, idiopathic thrombocytopenic purpura, autoimmune thyroid diseases, and multiple sclerosis. The group with AD had significantly more maternal vascular lesions and CVUE than the control group. We did not find lesions that could be attributed to any of the diseases in particular. The histopathologic picture was similar in these diseases, although there appears to be a spectrum in severity. Placental vascular damage with deposits of IgM, C3, and C1q was more prominent in systemic lupus erythematosus and in a patient with systemic sclerosis. In both of these diseases but not in the other conditions, these lesions were related to poor fetal outcome. Although the precise role of each of these autoimmune diseases in pregnancy and fetal outcome remains to be established, there appears to be at least one link between them represented by the presence of severe acute atherosis and heavy granular vascular deposits of IgM, C3, and C1q associated in some with poor fetal outcome. The role of CVUE remains speculative.