Porto-sinusoidal vascular disorder.

It is well established that portal hypertension can occur in the absence of cirrhosis, as reported in patients with immune disorders, infections and thrombophilia. However, similar histological abnormalities primarily affecting the hepatic sinusoidal and (peri)portal vasculature have also been observed in patients without portal hypertension. Thus, the term porto-sinusoidal vascular disorder (PSVD) has recently been introduced to describe a group of vascular diseases of the liver featuring lesions encompassing the portal venules and sinusoids, irrespective of the presence/absence of portal hypertension. Liver biopsy is fundamental for PSVD diagnosis. Specific histology findings include nodular regenerative hyperplasia, obliterative portal venopathy/portal vein stenosis and incomplete septal fibrosis/cirrhosis. Since other conditions including alcohol-related and non-alcoholic fatty liver disease, or viral hepatitis, or the presence of portal vein thrombosis may occur in patients with PSVD, their relative contribution to liver damage should be carefully assessed. In addition to histology and clinical diagnostic criteria, imaging and non-invasive tests such as liver and spleen stiffness measurements could aid in the diagnostic workup. The introduction of PSVD as a novel clinical entity will facilitate collaborative studies and investigations into the underlying molecular pathomechanisms encompassed by this term

Etiology, Pathogenesis, Diagnosis, and Practical Implications of Hepatocellular Neoplasms.

Hepatocellular carcinoma (HCC), a major global contributor of cancer death, usually arises in a background of chronic liver disease, as a result of molecular changes that deregulate important signal transduction pathways. Recent studies have shown that certain molecular changes of hepatocarcinogenesis are associated with clinicopathologic features and prognosis, suggesting that subclassification of HCC is practically useful. On the other hand, subclassification of hepatocellular adenomas (HCAs), a heterogenous group of neoplasms, has been well established on the basis of genotype-phenotype correlations. Histologic examination, aided by immunohistochemistry, is the gold standard for the diagnosis and subclassification of HCA and HCC, while clinicopathologic correlation is essential for best patient management. Advances in clinico-radio-pathologic correlation have introduced a new approach for the diagnostic assessment of lesions arising in advanced chronic liver disease by imaging (LI-RADS). The rapid expansion of knowledge concerning the molecular pathogenesis of HCC is now starting to produce new therapeutic approaches through precision oncology. This review summarizes the etiology and pathogenesis of HCA and HCC, provides practical information for their histologic diagnosis (including an algorithmic approach), and addresses a variety of frequently asked questions regarding the diagnosis and practical implications of these neoplasms

Autoimmune Gastritis in the Pediatric Age: An Underestimated Condition Report of Two Cases and Review.

<b>Background:</b> Diagnosis of pediatric autoimmune gastritis (AIG) in children is important due to poor outcome and risk of malignancy. This condition is often underestimated in the clinico-pathologic diagnostic work-up, leading to delayed time-to-diagnosis. To increase the awareness of this condition in the pediatric population, we present two cases encountered at our institution, discuss their clinical, biological, and histological presentations in relation with evidence from the literature, and propose an algorithm for diagnosis and follow-up of AIG in children. <b>Case presentation:</b> Two patients (12 and 17 years old) presented with iron deficiency anemia and negative family history for autoimmune disorders. In both cases, the final diagnosis of autoimmune gastritis was delayed until pathological examination of endoscopic gastric biopsies showed atrophy of oxyntic glands. <i>Helicobacter pylori</i> search was negative. Follow up biopsies revealed persistent disease. Literature review on this condition shows unclear etiology and poor long term outcome in some patients because of increased risk of malignancy. <b>Conclusions:</b> AIG should be considered in the differential diagnosis of iron deficiency anemia in the pediatric population.Standardized clinico-pathologic work-up is mandatory. Endoscopic follow-up should be performed due to the risk of malignancy

Rate of Freeze Impacts the Survival and Immune Responses Post Cryoablation of Melanoma.

The emergence of ablative therapies has revolutionized the treatment of inoperable solid tumors. Cryoablation stands out for its uniqueness of operation based on hypothermia, and for its ability to unleash the native tumor antigens, resulting in the generation of anti-tumor immune responses. It is not clearly understood how alterations in the rate of freeze impact the immune response outcomes. In this study, we tested fast freeze and slow freeze rates for their locoregional effectiveness and their ability to elicit immune responses in a B16F10 mouse model of melanoma. Tumor bearing mice treated with fast freeze protocol survived better than the ones treated with slow freeze protocol. Fast freeze resulted in a higher magnitude of CD4 <sup>+</sup> and CD8 <sup>+</sup> T-cell responses, and a significantly extended survival post re-challenge. Thus, fast freeze rate should be applied in any future studies employing cryoablation as an in vivo vaccination tool in conjunction with targeted immunotherapies

Synchronous tumors of the pancreas and the gallbladder: a case report with targeted NGS evaluation.

Synchronous tumors of the pancreas and gallbladder are rare and often attributed to an abnormal pancreato-biliary junction, which results in a persistent reflux of pancreatic secretions leading to chronic biliary inflammation. We present the case of a 73-year-old woman with synchronous lesions of the pancreas and gallbladder initially considered as two primary localized cancers and treated with curative intent. At relapse, targeted next generation sequencing (NGS), performed in search of potential therapeutic targets, uncovered the fact that the two lesions appeared to be clonally related. This case illustrates the problem of synchronous lesions of the pancreas and gallbladder. New pathologic assessments with comparative molecular analysis of mutational profiles may be helpful in this context

Comparison of different biopsy forceps models for tissue sampling in eosinophilic esophagitis.

Background and aims: Eosinophilic esophagitis (EoE) is a mixed inflammatory and fibrostenotic disease. Unlike superficial inflammatory changes, subepithelial fibrosis is not routinely sampled in esophageal biopsies. This study aimed to evaluate the efficacy and safety of deep esophageal sampling with four different types of biopsy forceps. Patients and methods: In this cross-sectional study, esophageal biopsies were taken in 30 adult patients by one expert endoscopist. Biopsies sampled from distal esophagus using a static jaw forceps (Olympus, FB-11K-1) were compared with proximal biopsies sampled with static jaw (Olympus, FB-45Q-1), alligator jaw (Olympus, FB-210K), and large-capacity forceps (Boston Scientific, Radial Jaw 4). One pathologist calculated the surface area of epithelial and subepithelial layers in hematoxylin and eosin (H&E)-stained biopsies. Results: Subepithelial tissue was acquired in 97 % (static jaw FB-11K-1), 93 % (static jaw FB-45Q-1), 80 % (alligator jaw), and 55 % (large-capacity) of samples. Median (interquartile [IQR]) ratios of surface area of epithelial to subepithelial tissue were: static jaw FB-45Q-1, 1.07 (0.65 - 4.465); static jaw FB-11K-1, 1.184 (0.608 - 2.545); alligator jaw, 2.353 (1.312 - 4.465); and large-capacity, 2.71 (1.611 - 4.858). The static jaw models obtained a larger surface area of subepithelial tissue compared with the alligator jaw (P < 0.001 and P = 0.037, for FB-11K-1 and FB-45Q-1, respectively) and the large-capacity forceps (P < 0.001, for both static jaw models). No esophageal perforations occurred. Conclusions: The static jaw forceps models allowed sampling of subepithelial tissue in > 90 % of biopsies and appear to be superior to alligator or large-capacity forceps in sampling larger amounts of subepithelial tissue

Invasive Ductular Reaction Operates Hepatobiliary Junctions upon Hepatocellular Injury in Rodents and Humans.

Ductular reaction (DR) is observed in virtually all liver diseases in both humans and rodents. Depending on the injury, DR is confined within the periportal area or invades the parenchyma. On severe hepatocellular injury, invasive DR has been proposed to arise for supplying the liver with new hepatocytes. However, experimental data evidenced that DR contribution to hepatocyte repopulation is at the most modest, unless replicative capacity of hepatocytes is abrogated. Herein, we proposed that invasive DR could contribute to operating hepatobiliary junctions on hepatocellular injury. The choline-deficient ethionine-supplemented mouse model of hepatocellular injury and human liver samples were used to evaluate the hepatobiliary junctional role of the invasive form of DR. Choline-deficient ethionine-supplemented-induced DR expanded as biliary epithelium into the lobule and established new junctions with the canaliculi. By contrast, no new ductular-canalicular junctions were observed in mouse models of biliary obstructive injury exhibiting noninvasive DR. Similarly, in humans, an increased number of hepatobiliary junctions were observed in hepatocellular diseases (viral, drug induced, or metabolic) in which DR invaded the lobule but not in biliary diseases (obstruction or cholangitis) in which DR was contained within the portal mesenchyme. In conclusion, our data in rodents and humans support that invasive DR plays a hepatobiliary junctional role to maintain structural continuity between hepatocytes and ducts in disorders affecting hepatocytes