Value of Additional Ultrasound Examination in Patients with Equivocal Computed Tomography Findings of Acute Appendicitis: Comparison with Computed Tomography Reassessment.

OBJECTIVES: The objective of this study was to find the diagnostic values of additional ultrasound (US) in patients with equivocal computed tomography (CT) findings of acute appendicitis, compared to CT reassessment. MATERIALS AND METHODS: Patients with equivocal CT findings of acute appendicitis (n = 115), who underwent the US, were included in the study. Two abdominal radiologists reviewed CT scans independently. They analyzed CT findings and made a diagnosis of acute appendicitis. The patients were categorized into positive and negative appendicitis based on the previous US reports. The diagnostic performance, interobserver agreement of CT findings, and appendicitis likelihood were calculated. RESULTS: The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of US (100%, 92.1%, 79.5%, and 100%, respectively) were higher than those of CT reassessment (reviewer 1: 51.9%, 87.5%, 56.1%, and 85.6%; reviewer 2: 66.7%, 85.2%, 58.1%, and 89.3%, respectively). In the coexistent inflammation group, the sensitivity, specificity, PPV, and NPV of US (reviewer 1: 100%, 98%, 91.5%, and 100%; reviewer 2: 100%, 98%, 87.7%, and 100%, respectively) were higher than those of CT reassessment (reviewer 1: 27.3%, 94.1%, 49.9%, and 85.8%; reviewer 2: 14.3%, 98.0%, 50.5%, and 88.9%, respectively). CONCLUSION: In patients with equivocal CT findings of acute appendicitis, US shows better diagnostic performance than CT reassessment, and helps differentiate with periappendicitis.

Frequent silencing of popeye domain-containing genes, BVES and POPDC3, is associated with promoter hypermethylation in gastric cancer.

The Popeye domain-containing (POPDC) genes BVES, POPDC2 and POPDC3 encode proteins that regulate cell-cell adhesion and cell migration during development. Herein, we report the frequent downregulation of BVES and POPDC3 by promoter hypermethylation in gastric cancer. POPDC expression in 11 gastric cancer cell lines and 96 paired gastric tumor and normal adjacent tissues was analyzed with quantitative reverse transcription-polymerase chain reaction. The methylation status of BVES and POPDC3 was analyzed with methylated DNA immunoprecipitation sequencing, bisulfite sequencing and pyrosequencing. Expression of BVES and POPDC3 was downregulated in 73% of the gastric cancer cell lines and in 69% (BVES) and 87% (POPDC3) of the gastric cancer tissues. The BVES and POPDC3 promoter regions were hypermethylated in the gastric cancer cell lines in which they were silenced. Combined treatment with a DNA methylation inhibitor and a histone deacetylase inhibitor strongly induced BVES and POPDC3 expression. BVES and POPDC3 were hypermethylated in 69% (BVES) and 64% (POPDC3) of the gastric cancer tissues. We knocked down POPDC3 expression with short hairpin RNAs and examined the consequences on cell migration and invasion. Knockdown of POPDC3 in SNU-216 cells caused increased cell migration and invasion. Thus, epigenetic inactivation of BVES and POPDC3 occurs frequently in gastric tumors and may promote gastric cancer cell migration and invasion.

Epigenetic down-regulation and suppressive role of DCBLD2 in gastric cancer cell proliferation and invasion.

The promoter region of Discoidin, CUB and LCCL domain containing 2 (DCBLD2) was found to be aberrantly methylated in gastric cancer cell lines and in primary gastric cancers, as determined by restriction landmark genomic scanning. DCBLD2 expression was inversely correlated with DCBLD2 methylation in gastric cancer cell lines. Treatment with 5-aza-2'-deoxycytidine and trichostatin A partially reversed DCBLD2 methylation and restored gene expression in DCBLD2-silenced cell lines. In an independent series of 82 paired gastric cancers and adjacent normal tissues, DCBLD2 expression was down-regulated in 79% of gastric cancers as compared with normal tissues as measured by real-time reverse transcription-PCR. Pyrosequencing analysis of the DCBLD2 promoter region revealed abnormal hypermethylation in gastric cancers, and this hypermethylation was significantly correlated with down-regulation of DCBLD2 expression. Furthermore, ectopic expression of DCBLD2 in gastric cancer cell lines inhibited colony formation in both anchorage-dependent and anchorage-independent cultures and also inhibited invasion through the collagen matrix. These data suggest that down-regulation of DCBLD2, often associated with promoter hypermethylation, is a frequent event that may be related to the development of gastric cancer.

Epigenetic inactivation of protein kinase D1 in gastric cancer and its role in gastric cancer cell migration and invasion.

Protein kinase D (PKD) 1 influences cell migration by mediating both trans-Golgi vesicle fission and integrin recycling to the cell surface. Using restriction landmark genomic scanning methods, we found that the promoter region of PKD1 was aberrantly methylated in gastric cancer cell lines. Silencing of PKD1 expression was detected in 72.7% of gastric cancer cell lines examined, and the silencing was associated with CpG hypermethylation in the promoter region of PKD1. Treatment with 5-aza-2'-deoxycytidine and trichostatin A partially reversed PKD1 methylation and restored gene expression in PKD1-silenced cell lines. Real-time reverse transcription-polymerase chain reaction analysis of 96 paired clinical primary gastric cancer samples revealed that 59% of the analyzed tumors had a >2-fold decrease in PKD1 expression compared with each normal-appearing tissue and that this downregulation of PKD1 expression was significantly correlated with increased methylation. We also observed a gradual increase in the level of promoter methylation of PKD1 in aging, normal-appearing mucosal tissues, suggesting that PKD1 methylation may be one of the earliest events that predispose an individual to gastric cancer. PKD1 expression was required for directional migration of gastric cancer cells. Furthermore, knock down of PKD1 by RNA interference promoted the invasiveness of cell lines that expressed PKD1 at relatively high levels. Based on these results, we propose that PKD1 is frequently silenced by epigenetic regulation, which plays a role in cell migration and metastasis in gastric cancer.

Meta- and gene set analysis of stomach cancer gene expression data.

We generated gene expression data from the tissues of 50 gastric cancer patients, and applied meta-analysis and gene set analysis to this data and three other stomach cancer gene expression data sets to define the gene expression changes in gastric tumors. By meta-analysis we identified genes consistently changed in gastric carcinomas, while gene set analysis revealed consistently changed biological themes. Genes and gene sets involved in digestion, fatty acid metabolism, and ion transport were consistently down-regulated in gastric carcinomas, while those involved in cellular proliferation, cell cycle, and DNA replication were consistently up-regulated. We also found significant differences between the genes and gene sets expressed in diffuse and intestinal type gastric carcinoma. By gene set analysis of cytogenetic bands, we identified many chromosomal regions with possible gross chromosomal changes (amplifications or deletions). Similar analysis of transcription factor binding sites (TFBSs), revealed transcription factors that may have caused the observed gene expression changes in gastric carcinomas, and we confirmed the overexpression of one of these, E2F1, in many gastric carcinomas by tissue array and immunohistochemistry. We have incorporated the results of our meta- and gene set analyses into a web accessible database (http://human-genome.kribb.re.kr/stomach/).

Non-invasive Assessment of Liver Fibrosis with ElastPQ: Comparison with Transient Elastography and Serologic Fibrosis Marker Tests, and Correlation with Liver Pathology Results.

We investigated the feasibility of using ultrasound shear wave elastography point quantification (ElastPQ) for liver fibrosis staging and compared it with other non-invasive tools with respect to efficacy in liver stiffness measurement. A total of 106 patients who underwent liver stiffness measurements, using ElastPQ and biochemical investigations, before parenchymal liver biopsy or surgery were included. Among these, 51 also underwent transient elastography (TE). Correlations of ElastPQ, TE and aspartate aminotransferase-to-platelet ratio index (APRI) with histopathological findings (as the reference standard) were determined using Spearman's correlation coefficient. The diagnostic performance of ElastPQ, TE and APRI was evaluated using receiver operating characteristic (ROC) curve analysis. ElastPQ had good diagnostic accuracy in identifying each liver fibrosis stage, with an area under the ROC curve (AUC) of 0.810 to 0.864. Stiffness values obtained using ElastPQ, TE and APRI were significantly positively correlated (r = 0.686, r = 0.732 and r = 0.454, respectively) with histologic fibrosis staging (p < 0.001). According to the AUC for the diagnosis of significant fibrosis (≥F2) and cirrhosis (=F4), ElastPQ had better diagnostic accuracy (AUC = 0.929 and 0.834, respectively) than APRI (AUC = 0.656 and 0.618, respectively) (p < 0.05), and was similar to TE (AUC = 0.915 and 0.879, respectively). ElastPQ is a promising ultrasound-based imaging technique for evaluation of liver fibrosis, with a diagnostic accuracy comparable to that of TE.

Diffuse Infiltrative Splenic Lymphoma: Diagnostic Efficacy of Arterial-Phase CT.

OBJECTIVE: To evaluate the diagnostic performance of obliteration of normal heterogeneous enhancement of the spleen (ONHES) on arterial phase (AP) computed tomography (CT) images in diffuse infiltrative splenic lymphoma (DISL). MATERIALS AND METHODS: One hundred and thirty-six patients with lymphoma who had undergone two-phase (arterial and portal venous) abdominal CT were included in this study. We retrospectively evaluated the diagnostic performance of ONHES on AP CT in diagnosing DISL. Two observers evaluated ONHES on AP CT using the 5-point confidence level and assessed the presence or absence of subjective splenomegaly on axial CT images. Another two observers measured the splenic index as proposed by objective CT criteria. Statistical analysis included interobserver agreement and diagnostic performance of CT findings. RESULTS: Eleven of the 136 patients with lymphoma had DISL. The area under the receiver operating characteristic curve of ONHES (0.948 for observer 1 and 0.922 for observer 2) was superior to that of the splenic index (0.872 for observer 3 and 0.877 for observer 4), but the difference was not statistically significant (p > 0.05). The diagnostic performance of ONHES in conjunction with subjective splenomegaly showed higher diagnostic performance, as compared with subjective splenomegaly alone (accuracy: 100% and 85.3% for observer 1, 98.5% and 87.5% for observer 2; positive predictive value: 100% and 35.5% for observer 1, 90.9% and 39.3% for observer 2, respectively). CONCLUSION: Obliteration of normal heterogeneous enhancement of the spleen in conjunction with subjective splenomegaly can improve the diagnostic performance for DISL. Our results suggest that ONHES on AP CT images could be useful as an adjunctive diagnostic indicator of DISL in patients with lymphoma.

Right adrenal venography findings correlated with C-arm CT for selection during C-arm CT-assisted adrenal vein sampling in primary aldosteronism.

PURPOSE: This study was designed to evaluate retrospectively the efficacy of C-arm CT to confirm right adrenal vein catheterization during adrenal vein sampling (AVS) and to correlate adrenal venography findings with C-arm CT and/or biochemical results for right adrenal vein selection. METHODS: Forty-two consecutive primary aldosteronism patients (M:F = 21:21; age: 29-70 years) underwent C-arm CT assisted sequential AVS. After catheterization of right adrenal vein, C-arm CT was performed to confirm catheter position. Catheter was repositioned when right adrenal gland was not opacified. Radiological images, medical records, and biochemical results were reviewed for technical/biochemical success rates and complications. Right adrenal venography findings of pinnate pattern, visualization of renal capsular vein, and retroperitoneal vein other than renal capsular vein were correlated with C-arm CT and/or biochemical results for right adrenal vein selection. RESULTS: Both the technical and biochemical success of AVS was achieved in 40 patients (95.2%). C-arm CT failed due to catheter instability in one, and adrenal/vena cava cortisol gradient was <3 in one patient. Catheter was repositioned in four patients (9.5%) according to C-arm CT findings. Right adrenal venography finding of renal capsular vein significantly correlated with C-arm CT and/or biochemical results (100%) for right adrenal vein selection (p = 0.011, χ(2) test), whereas pinnate pattern (p = 0.099) and other retroperitoneal veins (p = 0.347) did not. There was no procedure-related complication. CONCLUSIONS: C-arm CT increases confidence of right adrenal vein catheterization during AVS. Visualization of renal capsular vein on adrenal venography suggests right adrenal vein catheterization and C-arm CT may not be required.

Comparison of internally cooled wet electrode and hepatic vascular inflow occlusion method for hepatic radiofrequency ablation.

BACKGROUND/AIMS: Various strategies to expand the ablation zone have been attempted using hepatic radiofrequency ablation (RFA). The optimal strategy, however, is unknown. We compared hepatic RFA with an internally cooled wet (ICW) electrode and vascular inflow occlusion. METHODS: EIGHT DOGS WERE ASSIGNED TO ONE OF THREE GROUPS: only RFA using an internally cooled electrode (group A), RFA using an ICW electrode (group B), and RFA using an internally cooled electrode with the Pringle maneuver (group C). The ablation zone diameters were measured on the gross specimens, and the volume of the ablation zone was calculated. RESULTS: The ablation zone volume was greatest in group B (1.82±1.23 cm(3)), followed by group C (1.22±0.47 cm(3)), and then group A (0.48±0.33 cm(3)). The volumes for group B were significantly larger than the volumes for group A (p=0.030). There was no significant difference in the volumes between groups A and C (p=0.079) and between groups B and C (p=0.827). CONCLUSIONS: Both the usage of an ICW electrode and hepatic vascular occlusion effectively expanded the ablation zone. The use of an ICW electrode induced a larger ablation zone with easy handling compared with using hepatic vascular occlusion, although this difference was not statistically significant.

LRRC3B, encoding a leucine-rich repeat-containing protein, is a putative tumor suppressor gene in gastric cancer.

Leucine-rich repeat-containing 3B (LRRC3B) is an evolutionarily highly conserved leucine-rich repeat-containing protein, but its biological significance is unknown. Using restriction landmark genomic scanning and pyrosequencing, we found that the promoter region of LRRC3B was aberrantly methylated in gastric cancer. Gastric cancer cell lines displayed epigenetic silencing of LRRC3B, but treatment with the DNA methylation inhibitor 5-aza-2'-deoxycytidine and/or the histone deacetylase inhibitor trichostatin A increased LRRC3B expression in gastric cancer cell lines. Real-time reverse transcription-PCR analysis of 96 paired primary gastric tumors and normal adjacent tissues showed that LRRC3B expression was reduced in 88.5% of gastric tumors compared with normal adjacent tissues. Pyrosequencing analysis of the promoter region revealed that LRRC3B was significantly hypermethylated in gastric tumors. Stable transfection of LRRC3B in SNU-601 cells, a gastric cancer cell line, inhibited anchorage-dependent and anchorage-independent colony formation, and LRRC3B expression suppressed tumorigenesis in nude mice. Microarray analysis of LRRC3B-expressing xenograft tumors showed induction of immune response-related genes and IFN signaling genes. H&E-stained sections of LRRC3B-expressing xenograft tumors showed lymphocyte infiltration in the region. We suggest that LRRC3B is a putative tumor suppressor gene that is silenced in gastric cancers by epigenetic mechanisms and that LRRC3B silencing in cancer may play an important role in tumor escape from immune surveillance.

New type of reconstruction method after subtotal gastrectomy (Noh's operation).

The aim of this study was to compare a new type of reconstruction method (Noh's operation) with Roux-en- Y operation after subtotal gastrectomy. Noh's operation described herein includes a jejunal occlusion, an end-to-side gastrojejunostomy, a side-to-end jejunoduodenostomy, and a side-to-side jejunojejunostomy after subtotal gastrectomy. A series of 43 patients who had the new operation were compared with 47 patients with the Roux-en- Y procedure. The postgastrectomy syndromes, and the mucosal change of the remnant stomach and esophagus were evaluated after surgery. In the new operation, the Roux stasis syndrome occurred in 34.9% at 3 months, in 23.3% at 6 months, in 14.0% at 12 months, and in 11.6% at 24 months. In patients undergoing the Roux-en- Y operation, the syndrome occurred in 42.6% at 3 months, in 34.0% at 6 months, in 31.9% at 12 months, and in 29.8% at 24 months. This study shows that the new type of operation (Noh's operation) can be a good option for reconstruction after subtotal gastrectomy.

Major complications after radio-frequency thermal ablation of hepatic tumors: spectrum of imaging findings.

Although radio-frequency (RF) ablation has been accepted as a promising and safe technique for treatment of unresectable hepatic tumors, investigation of its complications has been limited. According to the multicenter (1,139 patients in 11 institutions) survey data of the Korean Study Group of Radiofrequency Ablation, a spectrum of complications occurred after RF ablation of hepatic tumors. The prevalence of major complications was 2.43%. The most common complications were hepatic abscess (0.66%), peritoneal hemorrhage (0.46%), biloma (0.20%), ground pad burn (0.20%), pneumothorax (0.20%), and vasovagal reflex (0.13%). Other complications were biliary stricture, diaphragmatic injury, gastric ulcer, hemothorax, hepatic failure, hepatic infarction, renal infarction, sepsis, and transient ischemic attack. One procedure-related death (0.09%) occurred (due to peritoneal hemorrhage). Three important strategies for decreasing the rate of complications are prevention, early detection, and proper management. A physician who performs RF ablation of hepatic malignancies should be aware of the broad spectrum of major complications so that these strategies can be used.