Faculty Bibliography

AIM: To determine the expression and clinical significance of transcriptional intermediary factor 1 gamma (TIF1gamma), Smad4 and transforming growth factor-beta (TGFbetaR) across a spectrum representing colorectal cancer (CRC) development. METHODS: Tissue microarrays were prepared from archival paraffin embedded tissue, including 51 colorectal carcinomas, 25 tubular adenomas (TA) and 26 HPs, each with matched normal colonic epithelium. Immunohistochemistry was performed using antibodies against TIF1gamma, Smad4 and TGFbetaRII. The levels of expression were scored semi-quantitatively (score 0-3 or loss and retention for Smad4). RESULTS: Overexpression of TIF1gamma was detected in 5/26 (19%) HP; however, it was seen in a significantly higher proportion of neoplasms, 15/25 (60%) TAs and 24/51 (47%) CRCs (P < 0.05). Normal colonic mucosa, HP, and TAs showed strong Smad4 expression, while its expression was absent in 22/51 (43%) CRCs. Overexpression of TGFbetaRII was more commonly seen in neoplasms, 13/25 (52%) TAs and 29/51 (57%) CRCs compared to 9/26 (35%) HP (P < 0.05). Furthermore, there was a correlation between TIF1gamma overexpression and Smad4 loss in CRC (Kendall tau rank correlation value = 0.35, P < 0.05). The levels of TIF1gamma overexpression were significantly higher in stage III than in stage I and II CRC (P < 0.05). CONCLUSION: The findings suggest that over-expression of TIF1gamma occurs in early stages of colorectal carcinogenesis, is inversely related with Smad4 loss, and may be a prognostic indicator for poor outcome

OBJECTIVE: The purpose of this article is to correlate clinicopathologic and MRI parameters with the presence of microvascular invasion at histopathologic examination in patients with hepatocellular carcinoma (HCC) who are undergoing liver transplantation. MATERIALS AND METHODS: In this retrospective single-center study, we assessed 60 patients (47 men and 13 women; mean age, 58 years) with HCC who underwent liver transplantation and pretransplant MRI (performed within 90 days before liver transplantation). Two observers analyzed the following tumor parameters in consensus: number, size, T1 and T2 signal intensity, margins, presence of capsule or pseudocapsule, distance to closest vessel, distance to liver capsule, and quantitative tumor enhancement. The size and number of HCCs, tumor differentiation, and the presence or absence of microvascular invasion were determined at histopathologic examination. Odds ratios (ORs) were calculated and logistic regression analysis was performed to assess the utility of these clinicopathologic and imaging parameters for predicting microvascular invasion. RESULTS: None of the clinical parameters or morphologic and enhancement MRI features of HCC was predictive of microvascular invasion. Tumor multifocality, on both MRI and pathologic examination, was the only variable that predicted microvascular invasion (OR = 2.43 and p = 0.013 for MRI; OR = 1.94 and p = 0.013 for pathologic examination). The presence of three or more tumors on MRI and four or more tumors at pathologic examination had high specificity (88.2% and 91.2%, respectively) for the prediction of microvascular invasion. CONCLUSION: Tumor multifocality on MRI was the only parameter that correlated significantly with microvascular invasion. All other MRI tumor characteristics failed to predict microvascular invasion

Liver involvement in genetic and metabolic disorders may result in intrahepatic accumulation of specific precursors or byproducts, which have distinctive features on light microscopy. The 'polyglucosan disorders' are diseases in which polyglucosan (abnormal glycogen with decreased branching) is formed and deposited in various tissues because of decreased or absent glycogen branching enzyme activity. These disorders include Lafora disease (myoclonus epilepsy) and type IV glycogen storage disease. Polyglucosan deposits in both conditions result in ground-glass hepatocellular inclusions resembling those seen in chronic hepatitis B virus infection. In the present report, we describe a case of the rare, adulthood form of glycogen branching enzyme deficiency, adult polyglucosan body disease (APBD), in which abnormal serum liver tests prompted a liver biopsy. The pathologic findings of periportal ground-glass hepatocellular inclusions, mild chronic portal inflammation, and periportal fibrosis are not well described in APBD, but resemble the chronic changes that have been reported in Lafora disease. The differential diagnosis of ground-glass hepatocytes and the genetic basis of APBD are discussed

Oncocytic adrenocortical neoplasm is a rare adrenal tumour that usually follows a benign clinical course. In some cases, however, these tumours have exhibited malignant behaviour. Here, we present the first published case showing bulk fat within an oncocytic adrenocortical neoplasm on CT and MRI, a finding that mimics fat within an adrenal myelolipoma. The distinction between these entities is important, as the current suggested management of an oncocytic adrenocortical neoplasm is resection with subsequent imaging surveillance

OBJECTIVE: The purpose of this study is to compare the diagnostic accuracy of liver apparent diffusion coefficient (ADC) versus normalized liver ADC using the spleen as a reference organ for the diagnosis of liver fibrosis and cirrhosis. MATERIALS AND METHODS: Fifty-six patients, 34 with liver disease and 22 control subjects, were assessed with breath-hold single-shot echo-planar diffusion-weighted imaging using b values of 0, 50, and 500 s/mm(2). Liver ADC and normalized liver ADC (defined as the ratio of liver ADC to spleen ADC) were compared between patients stratified by fibrosis stage. Receiver operating characteristic (ROC) analysis was used to determine the performance of ADC and normalized liver ADC for prediction of liver fibrosis and cirrhosis. Reproducibility was assessed by measuring coefficient of variation (n = 7). RESULTS: Liver ADC failed to distinguish individual stages of fibrosis, except between stages 0 and 4. There were significant differences in normalized liver ADC between control livers and intermediate stages of fibrosis (stages 2-3) and cirrhosis (stage 4) and between stages 1 and 4, and there was a trend toward significance between stages 0 and 1 (p = 0.051) and stages 1 and 3 (p = 0.06). ROC analysis showed that normalized liver ADC was superior to liver ADC for detection of stage >/= 2 (area under the ROC curve, 0.864 vs 0.655; p = 0.013) and stage >/=3 (0.805 vs 0.689; p = 0.015), without a difference for diagnosing cirrhosis (0.935 vs 0.720; p = 0.185). Normalized liver ADC had higher reproducibility than ADC (mean coefficient of variation, 3.5% vs 12.6%). CONCLUSION: Our results suggest that normalizing liver ADC with spleen ADC improves diagnostic accuracy for detection of liver fibrosis and cirrhosis when using breath-hold diffusion-weighted imaging, with better reproducibility

AIM: To evaluate circulating endothelial lineage cells (ELCs) as biomarkers of tumor neovascularization in patients with pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: ELCs were isolated from the peripheral blood of patients with PDAC (n=14) or controls (n=17) before and after tumor resection/surgery and quantified using flow cytometry. Vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) were detected in tumor using immunohistochemistry and in plasma using an ELISA technique. RESULTS: Circulating ELC levels were increased in patients with PDAC compared to controls. After PDAC resection, ELC levels declined. ELC level increases were associated with cancer recurrence. VEGF and PlGF were identified in cancer cells and exocrine pancreas cells. Only PlGF was detected in tumor-associated inflammatory cells. Plasma levels of PlGF were higher in patients with PDAC compared to controls. CONCLUSION: Circulating ELCs are a potential biomarker of PDAC neovascularization, and PlGF may be an important target in treatment of PDAC

OBJECTIVE: The purpose of this study was to determine the diagnostic performance of chemical shift imaging, compared with that of single-echo T2*-weighted imaging, for hepatic iron quantification in patients with liver disease, and to examine the confounding effect of steatosis. MATERIALS AND METHODS: Sixty-three patients who underwent liver MRI and who had concomitant liver histopathologic analysis were retrospectively assessed. Chemical shift imaging and T2*-weighted imaging (n = 49) of the liver were reviewed by two independent observers. An iron index for each sequence (I(Fe-CSI) and I(Fe-T2*), respectively) was correlated with pathologic iron grade (0-4). Receiver operating characteristic curve analysis was performed to assess the accuracy of both sequences for the diagnosis of iron deposition (grades >or= 1, >or= 2, and >or= 3), and the impact of steatosis on accuracy was evaluated. RESULTS: Forty-seven (74.6%) patients had hepatic siderosis. There was a significant correlation between both I(Fe-CSI) and I(Fe-T2*) with pathologic iron grade (r = 0.65 and -0.61, respectively; p < 0.0001 for both). I(Fe-CSI) and I(Fe-T2*) were significantly higher or lower in iron grades 2-4 versus grades 0-1 and in grades 3-4 versus grades 0-2 (p < 0.001). Area under the curve values for detecting iron grade >or= 1, >or= 2, and >or= 3 were 0.75, 0.88, and 0.90 for I(Fe-CSI) and 0.72, 0.81, and 0.98 for I(Fe-T2*). Accuracy was lower for both sequences in steatotic patients for detection of iron grades >or= 1 and >or= 2, without reaching significance. CONCLUSION: Routine chemical shift imaging and single-echo T2*-weighted imaging have excellent diagnostic performance for detection of significant hepatic siderosis (grade >or= 2). Concomitant steatosis lowers the diagnostic performance of both sequences without reaching significance

PURPOSE: To assess the diagnostic accuracy of image subtraction compared with nonsubtracted images obtained with contrast-enhanced T1-weighted imaging (CE T1WI) for the diagnosis of hepatocellular carcinoma (HCC) necrosis after transarterial chemoembolization (TACE), using liver explant as the reference standard. MATERIALS AND METHODS: Thirty-four patients who underwent TACE within 90 days of liver transplantation and CE MRI scans were assessed by two independent observers who determined the percentage of tumor necrosis using nonsubtracted and subtracted postcontrast phases. Histopathologic percentage of necrosis was retrospectively determined by an experienced pathologist. Spearman rank correlation test was used to correlate the percentages of necrosis from MR evaluation and from pathology. Receiver operating characteristics curve analysis was performed to determine the performance of subtracted versus nonsubtracted datasets for the diagnosis of complete tumor necrosis. RESULTS: There were 57 HCCs (mean size, 2.4 cm; range, 1.2-4.2 cm) diagnosed at explant and identified on MRI, including 16 completely necrotic HCCs. Subtraction demonstrated better interobserver agreement than nonsubtraction dataset for the diagnosis of tumor necrosis. There was a strong correlation between image subtraction and histopathologic assessment of necrosis (r = 0.80-0.86, depending on the phase, P < 0.0001). Subtraction demonstrated significantly higher sensitivity and accuracy for the diagnosis of complete tumor necrosis compared with nonsubtracted dataset. CONCLUSION: Image subtraction enables accurate assessment of necrosis of HCC after TACE with the best accuracy observed at the arterial phase

Purpose: To determine the frequency of intraductal papillary mucinous neoplasm (IPMN) in patients with and without invasive ductal adenocarcinoma (IDAC). Methods: 82 patients underwent pancreatectomy for pancreas adenocarcinoma. 68/82 subjects underwent at least one preoperative imaging study including CT (n = 43), MRI (n = 25), or both (n = 12). Imaging studies were retrospectively evaluated to determine if IPMN was present in the gland at a location distant from IDAC. In 183 different adult patients undergoing MRI for renal mass, images were evaluated to determine the frequency of IPMN. Fisher's exact test was used to test whether the prevalence of IPMN was greater among patients with pancreas cancer than those without. Results: Five of 68 (7.3%) patients who underwent pancreatic resection for IDAC had IPMN at a site distant from the cancer. Two of 182 (1.1%) patients undergoing MRI for renal cancer had imaging evidence of IPMN. There was a significant difference (p = 0.017) in the prevalence of IPMN between patients with and without IDAC. The odds ratio for IPMN as a predictor of pancreas cancer was estimated as 7.18. Conclusion: IPMN occurs with increased frequency in patients with pancreas cancer as opposed to those without pancreas cancer. and IAP

OBJECTIVE: The purpose of this study was to conduct, using histopathologic examination as the reference standard, a preliminary evaluation of the use of a breath-hold multiecho T2(*)-weighted MRI sequence in the detection and quantification of hepatic iron deposition in patients with liver disease. MATERIALS AND METHODS: The images of 43 patients with liver disease who underwent 1.5-T MRI of the liver that included a multiecho T2(*)-weighted sequence who also underwent concomitant liver biopsy or liver transplantation were assessed. Two independent observers measured hepatic T2(*) by placing regions of interest in the hepatic parenchyma. Hepatic T2(*) values were compared between patients stratified by hepatic iron grade and were correlated with histopathologic iron grade. Receiver operating characteristics analysis was performed to assess the accuracy of images obtained with the hepatic T2(*)-weighted sequence in the diagnosis of iron deposition. RESULTS: Patients with iron deposition had shorter hepatic T2(*) values than did patients without iron deposition (mean T2(*), 17.7 vs 32.3 milliseconds with pooled data from both observers; p < 0.0001). Patients with iron grade 3 or greater had shorter T2(*) values than those with iron grade 2 or less (10.1 vs 20.8 milliseconds; p < 0.0001). There was a strong negative correlation between hepatic T2(*) and histopathologic iron grade (r = -0.849; p < 0.0001). For the prediction of iron grades 1 or greater and 3 or greater, area under the curve, sensitivity, and specificity were 0.968-0.982, 90.5-100%, and 100-97.3% at T2(*) cutoffs of less than 24 and less than 14 milliseconds, respectively. CONCLUSION: Hepatic iron overload in patients with liver disease can be assessed rapidly and accurately with MRI performed with a breath-hold T2(*)-weighted sequence