Background and Objectives:Comparative studies have demonstrated that EUS-guided liver biopsy (EUS-LB) is a useful and safe technique. However, there is not sufficient evidence information on their cost differences and potential applications. We aimed to investigate whether EUS-LB is a cost-effective alternative to traditional LB methods (percutaneous [PC-LB], transjugular [TJ-LB]) and determine its indications in clinical practice. Methods:In this observational, prospective, and multicenter study, patients who underwent EUS-LB at different tertiary centers (N = 52) were compared with a similar number of PC-LB (N = 50) and TJ-LB (N = 37) collected retrospectively. Diagnostic yield (percentage of conclusive histological diagnosis), specimen quality, adverse events, and cost-effectiveness were analyzed. Results:EUS-LB had 87% of diagnostic yield and 4% of mild adverse events, similar to traditional techniques (P = 0.097 and P = 0.252, respectively). Despite higher tissue fragmentation and lower longest specimen length in EUS-LB, no differences were found in the number of complete portal tracts, tissue adequacy (EUS-LB, 19%; PC-LB, 30%; TJ-LB, 36%; P = 0.164) or pathologist satisfaction, allowing adequate fibrosis stage assessment, particularly in metabolic dysfunction-associated steatotic liver disease. EUS-LB was more cost-effective when both LB and EUS were indicated (saving: €112.20 × 15% additional histological diagnosis [AHD]); in patients with cholestasis unsuitable for magnetic resonance cholangiopancreatography (MRCP) prior to LB; contraindication for the PC-LB, including cases of uncooperative individuals (saving: €234.75 × 15% AHD). Conclusions:EUS-LB is a useful alternative to traditional methods and the most cost-effective option when both LB and EUS are indicated, in cases of cholestasis as an alternative to MRCP and when the PC route is contraindicated.

The patient was a 57-year-old female with a 3.8 cm, solid, lobulated, and ill-defined pancreatic head lesion suspected to represent a primary pancreatic malignancy. An endoscopic ultrasound (EUS) was performed and EUS-guided fine needle aspiration (FNA) of the pancreatic mass was obtained with rapid on-site evaluation (ROSE). The direct smears showed the following [Figure 1].

E-cadherin, encoded by CDH1, is an essential molecule for epithelial homeostasis, whose loss or aberrant expression results in disturbed cell–cell adhesion, increased cell invasion and metastasis. Carriers of CDH1 germline mutations have a high risk of developing diffuse gastric cancer and lobular breast cancer, associated with the cancer syndrome Hereditary Diffuse Gastric Cancer (HDGC). The ubiquitous availability of cancer panels has led to the identification of an increasing amount of “incidental” CDH1 genetic variants that pose a serious clinical challenge. This has sparked intensive research aiming at an accurate classification of the variants and consequent validation of their clinical relevance. The present study addressed the significance of a novel CDH1 variant, G212E, identified in an unusually large pedigree displaying strong aggregation of diffuse gastric cancer. We undertook a comprehensive pipeline encompassing family data, in silico predictions, in vitro assays and in vivo strategies, which validated the deleterious phenotype induced by this genetic alteration. In particular, we demonstrated that the G212E variant affects the stability and localization, as well as the adhesive and anti-invasive functions of E-cadherin, triggering epithelial disruption and disorganization. Our findings illustrate the clinical implication of a complementary approach for effective variant categorization and patient management.

El importante y significativo incremento de la incidencia de la enfermedad inflamatoria intestinal (EII) en la población europea ha supuesto la creación de unidades clínicas multidisciplinarias y guías prácticas de manejo y estandarización de los informes anatomopatológicos. Recientemente hemos publicado una guía interpretativa de biopsias endoscópicas con sospecha de EII. Sin embargo, el apartado de diagnóstico de lesiones preneoplásicas quedó pendiente y lo abordamos en este documento. El riesgo de carcinoma de colon se halla aumentado en la EII, en la que la displasia epitelial (DE) constituye la manifestación histológica inicial del proceso neoplásico. Su diagnóstico, la gradación y el control determinan las pautas de cribado y manejo del paciente. En este artículo procedemos a revisar: las definiciones de DE, las clasificaciones macroscópicas y microscópicas así como su repercusión en el establecimiento del tratamiento, la distinción entre DE secundaria a EII y adenoma esporádico, la utilidad de la inmunohistoquímica en los estudios histopatológicos además de los protocolos de estudio macroscópico de piezas de colectomía y de disección submucosa endoscópica provenientes del tratamiento quirúrgico de la DE o del carcinoma asociado a EII.

El reciente aumento en la incidencia de enfermedad inflamatoria intestinal (EII) entre la población europea ha dado lugar a la creación en hospitales de unidades multidisciplinares específicas con protocolos definidos que comprometen a los anatomopatólogos. El consiguiente aumento en el número de biopsias requiere establecer unas pautas, tanto sobre los criterios estándar como sobre la nomenclatura, para facilitar el diagnóstico y mejorar el informe. Dichas pautas tienen como finalidad la sistematización, paso a paso, de la interpretación de las biopsias con objetivos que evalúan la confianza diagnóstica a cada nivel. Los distintos pasos determinarán si existe enfermedad en la mucosa intestinal, si la enfermedad es crónica y/o activa y, si la presencia de una EII se considera probable, si se puede diagnosticar la enfermedad como un Crohn (EC) o bien como colitis ulcerosa (CU). Se considerarán los cambios en la arquitectura celular que indican la cronicidad de la enfermedad, los cambios inflamatorios que se pueden graduar en un índice de actividad, el diagnóstico diferencial con otros tipos de colitis y las características microscópicas necesarias para clasificar la colitis como EC o CU. Además, se proponen ejemplos de la comunicación del diagnóstico histopatológico y se analizan algunos de los frecuentes errores en la interpretación microscópica.

Fatty livers occur in up to 20% of potential liver donors and increase cellular injury during the ischemia/ reperfusion phase, so any intervention that could enable a better outcome of grafts for liver transplantation would be very useful. The effect of melatonin on liver ischemia/reperfusion injury in a rat model of obesity and hepatic steatosis has been investigated. Forty fa/fa Zucker rats were divided in 4 groups. 3 groups were subjected to 35 min of warm hepatic ischemia and 36 h of reperfusion. One experimental group remained untreated and 2 were given 10 mg/kg melatonin intraperitoneally or orally. Another group was sham-operated. Plasma ALT, AST and hepatic content of ATP, MDA, hydroxyalkenals, NOx metabolites, antioxidant enzyme activity, caspase-9 and DNA fragmentation were determined in the liver. The expression of iNOS, eNOS, Bcl2, Bax, Bad and AIF were determined by RT-PCR Melatonin was effective at decreasing liver injury by both ways as assessed by liver transaminases, markers of apoptosis, of oxidative stress and improved liver ATP content. Melatonin administration decreased the activities or levels of most of the parameters measured in a beneficial way, and our study identified also some of the mechanisms of protection. We conclude that administration of melatonin improved liver function, as well as markers of pro/antioxidant status and apoptosis following ischemia/reperfusion in obese rats with fatty liver. These data suggest that this substance could improve outcome in patients undergoing liver transplantation who receive a fatty liver implant and suggest the need of clinical trials with it in liver transplantation. & 2012 Elsevier B.V. All rights reserved.

Fatty livers occur in up to 20% of potential liver donors and increase cellular injury during the ischemia/reperfusion phase, so any intervention that could enable a better outcome of grafts for liver transplantation would be very useful. The effect of melatonin on liver ischemia/reperfusion injury in a rat model of obesity and hepatic steatosis has been investigated. Forty fa/fa Zucker rats were divided in 4 groups. 3 groups were subjected to 35 min of warm hepatic ischemia and 36 h of reperfusion. One experimental group remained untreated and 2 were given 10 mg/kg melatonin intraperitoneally or orally. Another group was sham-operated. Plasma ALT, AST and hepatic content of ATP, MDA, hydroxyalkenals, NOx metabolites, antioxidant enzyme activity, caspase-9 and DNA fragmentation were determined in the liver. The expression of iNOS, eNOS, Bcl2, Bax, Bad and AIF were determined by RT-PCR Melatonin was effective at decreasing liver injury by both ways as assessed by liver transaminases, markers of apoptosis, of oxidative stress and improved liver ATP content. Melatonin administration decreased the activities or levels of most of the parameters measured in a beneficial way, and our study identified also some of the mechanisms of protection. We conclude that administration of melatonin improved liver function, as well as markers of pro/antioxidant status and apoptosis following ischemia/reperfusion in obese rats with fatty liver. These data suggest that this substance could improve outcome in patients undergoing liver transplantation who receive a fatty liver implant and suggest the need of clinical trials with it in liver transplantation.

BACKGROUND:Ischemia/reperfusion (I/R) causes functional and structural damage to liver cells, this being more pronounced with increasing age of the tissue. Melatonin is a pineal indole that has been shown to play an important role as a free radical scavenger and anti-inflammatory molecule.MATERIAL AND METHODS:The age-dependent responses to I/R were compared in 2-mo-old and 14-mo-old male Wistar rats. After 35 min of hepatic ischemia followed by 36 h of reperfusion, rats were sacrificed. Sham-operated control rats underwent the same protocol without real vascular occlusion. Animals were intraperitoneally injected with 10 mg/kg melatonin 24 h before the operation, at the time of surgery, and 12 and 24 h after it. The tissues were submitted to histopathologic evaluation. The levels of ALT and AST were analyzed in plasma. The expression of TNF-α, IL-1β, IL-10, MCP-1, IFN-γ, iNOS, eNOS, Bad, Bax, Bcl2, AIF, PCNA, and NFKB1 genes were detected by RT-PCR in hepatic tissue.RESULTS:I/R was associated with significant increases in the expression of pro-inflammatory and pro-apoptotic genes in liver. Older rats submitted to I/R were found to respond with increased liver damage as compared with young rats, with serum ALT and AST levels significantly higher than in young animals. Mature rats also showed more evident increases in expression of pro-inflammatory cytokines (IL-1β, MCP-1, and IFN-γ) as well as a decrease in the mRNA expression of IL-10 as compared with young animals. Pro-apoptotic genes (Bax, Bad, and AIF) were significantly enhanced in liver after I/R, without differences between young and mature animals. However, the expression of Bcl2 gene did not show any change. Melatonin treatment was able to lower the expression of pro-inflammatory cytokines and pro-apoptotic genes and to improve liver function, as indicated by normalization of plasma AST and ALT levels and by reduction of necrosis and microsteatosis areas.CONCLUSIONS:Melatonin treatment was able to reduce the I/R-stimulated pro-inflammatory and pro-apoptotic genes in the rat liver. Since older animals showed a more marked increase in inflammation and in liver injury, the treatment was more effective in those subjects.

A rare case of pancreatic neuroendocrine neoplasm in a patient with tuberous sclerosis complex is described. The patient was a 31-year-old man who had multiple congenital subependymal nodules, bilateral cortical tubers, and seizures of difficult control. A 2.3 cm × 2 cm well-delimitated solid tumor in the tail of the pancreas was discovered during a monitoring abdominal computed tomography. A distal pancreatectomy was performed. Histologically, the tumor was formed by uniform cells with moderated cytoplasm arranged in a combined trabecular and nested pattern. The nuclear features were bland, and mitosis was infrequent. There was no vascular invasion. Immunoreactivity for cytokeratine AE1/AE3, chromogranin A, and synaptophysin confirmed the neuroendocrine nature of this neoplasia. Pancreatic hormones were negatives. One of the 5 lymph nodes isolated from the peripancreatic adipose tissue was positive for metastases. Small series and case reports have documented that in tuberous sclerosis many endocrine system alterations might occur, affecting the function of the pituitary, parathyroid, and other neuroendocrine tissue, including islet cells of the pancreas. However, the true association of these pathological conditions remains uncertain. As far as we know, there are 10 cases reported of pancreatic neuroendocrine tumors in a setting of tuberous sclerosis complex, in which 2 cases resulted in malignant, nonfunctioning pancreatic neuroendocrine tumors.

This report describes a 31-week stillborn female infant with placental mesen-chymal dysplasia (PMD) in association with hepatic mesenchymal hamartoma (HMH) and pulmonary hamartoma. Placental mesenchymal dysplasia was initially misdiagnosed as a partial mole. However, histologically, no trophoblastic proliferation or inclusions were observed. Differential diagnosis of the hepatic mass with similar tumors is discussed. To our knowledge, this is the first case of lung hamartoma reported in a fetus and the first case related to PMD and HMH. A common anomalous development of the mesoderm, a reparative post-injury process and a genetic mechanism, have been proposed to explain their pathogenesis.