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The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that affects the function and development of immune cells. Here, we show that recipient mice receiving AhR -/- T cells have improved survival and decreased acute graft-versus-host disease (aGVHD) in 2 different murine allogeneic bone marrow transplant (BMT) models. We also show that CD4 + T cells lacking AhR demonstrate reduced accumulation in secondary lymphoid tissue because of low levels of proliferation 4 days after BMT. Additionally, we found a significant increase in the quantity of peripherally induced regulatory donor T (pT reg ) cells in the colon of recipients transplanted with AhR -/- T cells 14 days after transplant. Blockade of AhR using a clinically available AhR antagonist greatly enhanced the in vitro generation of inducible T reg (iT reg ) cells from naïve CD4 + human T cells. We have identified AhR as a novel target on donor T cells that is critical to the pathogenesis of aGVHD.

Background: Eosinophilic gastroenteritis is a rare condition where eosinophilic inflammation occurs in the gastrointestinal tract in the absence of secondary causes. Little is known regarding aetiology, pathogenesis, or natural history., Aims: To characterize the clinical, endoscopic, and histopathologic features of eosinophilic gastroenteritis and to summarize treatment outcomes., Methods: Pathology reports of all patients who had undergone upper endoscopy with biopsy between January 1, 2000 and June 20, 2013 were reviewed. Eosinophilic gastroenteritis was diagnosed if there were ≥20 eosinophils/hpf on either gastric of duodenal biopsy, symptoms attributable to the gastrointestinal tract, and no known secondary cause of eosinophilia. Descriptive statistics characterized patients diagnosed with eosinophilic gastroenteritis and bivariate analysis compared adults and children., Results: There were 44 patients diagnosed with eosinophilic gastrointestinal disease. The most common symptoms were vomiting (71%) and abdominal pain (62%). Of the eosinophilic gastroenteritis cases, 12 (30%) had esophageal involvement, and 11 (28%) had colonic involvement. For treatment, 36 (80%) received corticosteroids. Overall, 27 (60%) had symptom resolution and 23 (51%) had endoscopic resolution. Cases underwent a mean of five endoscopic procedures per year., Conclusion: Eosinophilic gastroenteritis presents with non-specific gastrointestinal symptoms and in almost one-third of cases has concomitant esophageal or colonic involvement. It remains difficult to treat, with high rates of endoscopic utilization., (Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Purpose: To evaluate magnetic resonance imaging (MRI) findings of nonalcoholic steatohepatitis (NASH) and to determine the correlation of MRI findings with histopathology and Mayo End-Stage Liver Disease (MELD) score., Materials and Methods: Thirty patients (18 males, 12 females; mean age: 57+/-8.9 years; age range: 35-71 years) with histopathologically proven NASH who underwent MRI examinations between January 2001 and October 2005 were included in the study. Two radiologists retrospectively reviewed all magnetic resonance (MR) examinations in consensus to evaluate the presence and extent of predetermined findings of NASH including liver steatosis, early patchy liver enhancement indicating inflammation and liver fibrosis. The findings detected on MRI were correlated and compared to histopathological findings and MELD score by using nonparametric Spearman correlation coefficient and Kruskal-Wallis analysis of variance., Results: Liver steatosis was observed in 10 of 30 patients; early patchy liver enhancement, in 8 of 30 patients and liver fibrosis in 19 of 30 patients on MR images. Liver fibrosis was reticular in all these patients. There were statistically significant moderate correlations between MRI findings of liver steatosis and histopathologic grades of steatosis (r=0.43; P<.05), and between MRI findings of fibrosis and histopathologic stages of fibrosis (r=0.61; P<.001). Early patchy enhancement did not demonstrate statistically significant correlation with inflammation (P=.28). There was no statistically significant overall correlation between MRI findings of NASH and MELD score., Conclusion: MRI findings of liver steatosis and fibrosis in NASH showed moderate correlations with histopathologic grades of steatosis and stages of fibrosis, but MRI findings of NASH did not demonstrate any significant correlations with MELD score.

Objective: To assess by MR imaging the frequency of hepatic nodules in patients waiting on the liver transplant list and to determine whether certain underlying hepatic diseases were more often associated with the development of such hepatic nodules., Material and Methods: We reviewed the MR and clinical records in all patients seen by the liver transplant service at our center since its inception in January 1998 until September 2002. A total of 371 patients (207 men and 164 women, age range 18-68 years, mean 45 years) were included in the study. The presence of hepatic nodules, size, number and underlying hepatic diseases were determined in all patients. Magnetic resonance imaging was performed on a 1.5-T MR imager using T1-weighted, T2-weighted and multi-phase gadolinium-enhanced sequences. Odds ratio (OR) and 95% confidence intervals (CIs) were computed to evaluate the association between the underlying hepatic disease and the development of hepatic nodule., Results: Among 371 liver transplantation candidates, the most common underlying hepatic disease was hepatitis C virus (HCV) infection, either alone (n=93; 25%) or associated with other hepatic diseases (n=40; 10.8%). Of all patients, 33 (8.9%) had regenerative nodules (RNs), 40 (10.7%) dysplastic nodules (DNs) and 57 (15.3%) hepatocellular carcinomas (HCCs). Hepatocellular carcinoma was observed in 35.3% of patients with HCV infection and alcohol abuse combined, 24.5% with cryptogenic cirrhosis, 25% with hemochromatosis and 19% with alcohol abuse. Patients who had either DNs or HCC were 2.5 times more likely to have either alcohol abuse or HCV, alone or combined, as the substrate of their liver disease (OR 2.54, 95% CI 1.56-4.13). Our data suggest a supra-additive interaction between HCV infection and ethanol in their association with MR imaging detected lesions., Conclusion: Patients with cryptogenic cirrhosis, alcohol abuse, HCV infection (alone or combined) and hemochromatosis had the greatest likelihood of having HCC, with the combination of HCV infection and alcohol abuse having the highest of all.

We report the MRI findings of primary small-cell carcinoma of the kidney (PSCCK) in a 59-year-old female. This tumor appeared as a 16-cm mass that arose from the right kidney. This lesion had diminished signal on T1-weighted images and heterogeneous mixed signal on T2-weighted images. The tumor primarily involved the renal medulla with persistent thin renal cortex. Despite the tumors' large size, no substantial central necrosis was present. The predominant medullary location and the lack of central necrosis in this large tumor were features unusual for renal cell carcinoma and should raise the suspicion of another malignancy, the differential diagnosis of which should contain extrapulmonary small-cell carcinoma of the kidney.

We describe the MR appearance of breast cancer metastases to the stomach. The stomach wall was diffusely thickened with loss of the regular fold pattern best shown on the single shot T2-weighted images and enhanced with moderate mural enhancement on early and late post gadolinium images. The combination of gastric wall thickening and abnormal enhancement should suggest the diagnosis of diffuse mural metastases in a woman with a history of breast cancer.

We report the magnetic resonance (MR) appearance of a large B-cell lymphoma in the peripancreatic head region, in a 38-year-old male who presented with a 1-month history of pruritus and jaundice. Routine laboratory examination at presentation revealed an elevated bilirubin. The tumor was a large, solitary well-defined mass with no evidence of necrosis, which showed mild diffuse heterogeneous enhancement. The tumor was closely applied to the lateral margin of the head of the pancreas. The constellation of MR findings was interpreted as consistent with the correct eventual diagnosis of lymphoma.

We report the MR appearance of undifferentiated (embryonal) sarcoma of the liver (USL) in a 13-year-old female who presented with a 1-year history of intermittent abdominal pain, weight loss, and fatigue. The tumor was a large, solitary, well-defined focal mass lesion with multiple cystic spaces, septations, and substantial central necrosis.

The purpose of our study was to assess the difference in magnetic resonance imaging (MRI) features of cavernous hemangiomas in patients with chronic liver disease compared them with hemangiomas in normal livers. We retrospectively searched our records of MRI of the liver between October 1998 and June 2002, and identified 76 hemangiomas in 49 patients (18 men and 31 women; age range 29-81 years [mean, 57 years]). Hemangiomas were classified into 3 groups: patients with cirrhosis [group 1, 8 lesions in 8 patients], patients with chronic hepatitis [group 2, 6 lesions in 5 patients], and patients without underlying liver disease [group 3, 62 lesions in 36 patients]. Four radiologists, blinded to clinical information, retrospectively reviewed in consensus the MRI findings of hemangiomas for number, size, signal intensities on T1- and T2-weighted images, and enhancement patterns on early- and late-phase postcontrast images. The mean lesion numbers and sizes were 1.0 and 16.2 +/- 9.6 mm, 1.2 and 15.3 +/- 7.1 mm, and 1.7 and 26.1 +/- 24.7 mm in groups 1-3, respectively. There was a correlation (p < 0.05, coefficient: 0.35) between lesion number and severity of liver disease. Although there was no significant difference in lesion size among the 3 groups, all of 11 lesions larger than 4 cm in diameter belonged to group 3. Almost all lesions appeared moderately hypointense on T1-weighted images and moderately hyperintense on T2-weighted images. Twenty-seven lesions showed immediate homogeneous enhancement (pattern 1), and 49 showed peripheral nodular enhancement with centripetal enhancement progression (pattern 2). There was no difference in frequency of enhancement patterns among the 3 groups. Hemangiomas were more often solitary in livers with chronic liver disease, large lesions were exclusively seen in livers without chronic liver disease, and there was a trend for small lesions in patients with chronic liver disease.

We report the MR imaging findings of a primary malignant mesothelioma of the liver arising from Glisson's capsule. A 54-year-old woman, presenting with acute abdominal pain and a large liver mass previously shown on CT, underwent MR imaging to characterize the lesion. The tumor was a greater than 12 cm tumor located in the right lobe of the liver, which was sharply marginated, with heterogeneous internal signal, septations and central necrosis. The tumor was considered a hepatocellular carcinoma. The diagnosis of malignant mesothelioma was established by immunohistochemical staining and electron microscopy of the resected tumor.

To demonstrate the MR imaging features of liver metastases in patients with the clinical and histologic diagnosis of tumors of unknown primary tumors, a retrospective 7-year study was performed that included a total of 14 consecutive patients (7 men and 7 women; age range, 39-82 years; mean age, 60.6 years) with liver metastases from unknown primary site who had undergone MR imaging. The following lesion features were evaluated: a) number, b) diameter, c) signal intensity on T1 and T(2)-weighted images, and d) pattern of enhancement on immediate, 45 s and 90 s post gadolinium images. Lesions were classified as hypovascular, hypervascular and nearly isovascular relative to liver parenchyma as shown on immediate post gadolinium images. Patients were separated into four major groups, related to the histologic diagnosis of the lesions: (I) poorly differentiated neoplasms; (II) well-differentiated and moderately differentiated adenocarcinoma; (III) squamous cell carcinoma; (IV) combined poorly differentiated carcinoma and poorly differentiated adenocarcinoma. MRI findings were correlated with histologic information obtained by chart review and confirmed by retrospective histopathology review. All patients had the histologic diagnosis of adenocarcinoma: 8 patients belonged to group II (1 patient with the subtype well-differentiated and 7 patients with the subtype moderately differentiated) and 6 patients to group IV. Eleven patients (79%) presented with multiple lesions distributed throughout both hepatic lobes; 3 patients exhibited solitary lesions. All solitary metastases possessed a diameter equal or larger than 5 cm. Patients with multiple metastases demonstrated a wide range of diameter, ranging from less than 1.5 cm to more than 5 cm. Regarding lesion vascularity, 4 of 13 of the patients had hypovascular metastases and 9 of 13 of the patients had hypervascular lesions. One patient demonstrated both types of lesions. Five of six patients with the histopathologic diagnosis of poorly differentiated adenocarcinoma demonstrated hypervascular metastases. Solitary metastases were most often hypovascular (2 of 3); however no correlation with the histologic subtype was possible. Liver metastases from unknown primary site are often multiple and often hypervascular. Poorly differentiated tumors are the most common histologic type. Metastases are not uncommonly hypovascular, and these are often solitary.

We report the MR findings of a 42-year-old man who developed renal cell carcinoma in an allograft kidney, 10 years after transplantation. The lower pole of the transplant kidney showed a solid lesion which was well shown on the post gadolinium fat suppressed images as a heterogeneously enhancing 2 cm mass lesion.

We retrospectively reviewed the magnetic resonance imaging (MRI) of giant hemangiomas in 24 patients. MRI studies comprised T1-weighted, T2-weighted and serial gadolinium-enhanced spoiled gradient echo (SGE) images. Morphologic features, signal characteristics and enhancement patterns were assessed. Histopathologic evaluation was obtained in nine patients. On T2-weighted images all lesions (size 5.7-24 cm) were hyperintense relative to the spleen and two dominant patterns of heterogeneity were demonstrated: a central heterogeneous area of either bright, dark, or mixed signal intensity, and a network of multiple fibrous septa of low signal intensity. Histopathologic evaluation of two lesions with a central bright area demonstrated the presence of hypocellular myxoid tissue. Central enhancement (9 lesions) and an irregular flame-shaped peripheral pattern of enhancement (12 lesions) were present in lesions with a mean diameter greater than 10 cm. Although giant hemangiomas show greater variability in their MR imaging appearance, an accurate diagnosis can be made through still characteristic features of high signal intensity on T2-weighted images and discontinuous peripheral enhancement.

We report the MR appearance of epithelioid hemangioendothelioma (EHE) in a 51 year old man, who presented with a 14-month history of fatigue and anemia to his physician. The tumor showed massive replacement of the liver and had an unusual appearance of multiple high fluid content focal lesions with diminished vascularity.