Comparison of contrast-enhanced ultrasonography and MRI results obtained by expert and novice radiologists indicating short-term response after transarterial chemoembolisation for hepatocellular carcinoma.

AIM: To evaluate inter-reader agreement between novice and expert radiologists in assessing contrast-enhanced ultrasonography (CEUS) and magnetic resonance imaging (MRI) images for detecting viable tumours with different sizes after conventional transarterial chemoembolisation (cTACE). MATERIALS AND METHODS: This prospective study included patients who had less than five hepatomas and who underwent cTACE. Hepatomas with one or two feeding arteries were selected as target lesions. CEUS and MRI were performed within 1 week after cTACE to evaluate viable tumours. RESULTS: The expert group had higher kappa values in evaluating all tumour sizes via CEUS compared with MRI. The novice group had similar kappa values. In patients with tumours measuring ≤3 cm, the expert group had higher kappa values in reading CEUS compared with MRI images; however, in the novice group, the kappa value was lower in evaluating CEUS compared with MRI images. In patients with tumours measuring >3 cm, the expert and novice groups had good to excellent kappa values. The confidence level of the two groups in reading MRI images was high; however, the novice group had a lower confidence level. CONCLUSION: CEUS is a convenient, cost-effective, and easy to apply imaging tool that can help interventionists perform early detection of viable hepatocellular carcinoma post-TACE. It has a higher inter-rater agreement in interpreting CEUS images compared with MRI images among expert radiologists even when they are extremely familiar with post-cTACE MRI images. In novice radiologists, there may be a learning curve to achieve good consistency in CEUS interpretation.

The Introduction of Human Heme Oxygenase-1 and Soluble Tumor Necrosis Factor-α Receptor Type I With Human IgG1 Fc in Porcine Islets Prolongs Islet Xenograft Survival in Humanized Mice.

Apoptosis during engraftment and inflammation induce poor islet xenograft survival. We aimed to determine whether overexpression of human heme oxygenase-1 (HO-1) or soluble tumor necrosis factor-α receptor type I with human IgG1 Fc (sTNF-αR-Fc) in porcine islets could improve islet xenograft survival. Adult porcine islets were transduced with adenovirus containing human HO-1, sTNF-αR-Fc, sTNF-αR-Fc/HO-1 or green fluorescent protein (control). Humanized mice were generated by injecting human cord blood-derived CD34(+) stem cells into NOD-scid-IL-2Rγ(null) mice. Both HO-1 and sTNF-αR-Fc reduced islet apoptosis under in vitro hypoxia or cytokine stimuli and suppressed RANTES induction without compromising insulin secretion. Introduction of either gene into islets prolonged islet xenograft survival in pig-to-humanized mice transplantation. The sTNF-αR-Fc/HO-1 group showed the best glucose tolerance. Target genes were successfully expressed in islet xenografts. Perigraft infiltration of macrophages and T cells was suppressed with decreased expression of RANTES, tumor necrosis factor-α and IL-6 in treatment groups; however, frequency of pig-specific interferon-γ-producing T cells was not decreased, and humoral response was not significant in any group. Early apoptosis of islet cells was suppressed in the treatment groups. In conclusion, overexpression of HO-1 or sTNF-αR-Fc in porcine islets improved islet xenograft survival by suppressing both apoptosis and inflammation. HO-1 or sTNF-αR-Fc transgenic pigs have potential for islet xenotransplantation.

Molecular interactions between poly(ADP-ribose) polymerase (PARP I) and topoisomerase I (Topo I): identification of topology of binding.

The molecular interactions of poly(ADP-ribose) polymerase I (PARP I) and topoisomerase I (Topo I) have been determined by the analysis of physical binding of the two proteins and some of their polypeptide components and by the effect of PARP I on the enzymatic catalysis of Topo I. Direct association of Topo I and PARP I as well as the binding of two Topo I polypeptides to PARP I are demonstrated. The effect of PARP I on the 'global' Topo I reaction (scission and religation), and the activation of Topo I by the 36 kDa polypeptide of PARP I and catalytic modifications by poly(ADP-ribosyl)ation are also shown. The covalent binding of Topo I to circular DNA is activated by PARP I similar to the degree of activation of the 'global' Topo I reaction, whereas the religation of DNA is unaffected by PARP I. The geometry of PARP I-Topo I interaction compared to automodified PARP I was reconstructed from direct binding assays between glutathione S-transferase fusion polypeptides of Topo I and PARP I demonstrating highly selective binding, which was correlated with amino acid sequences and with the 'C clamp' model derived from X-ray crystallography.

An anti-apoptotic protein human survivin is a direct inhibitor of caspase-3 and -7.

Survivin, an apoptosis inhibitor/cell-cycle regulator, is critically required for suppression of apoptosis and ensuring normal cell division in the G2/M phase of the cell cycle. It is highly expressed in a cell cycle-regulated manner and localizes together with caspase-3 on microtubules within centrosomes. Whether survivin is a physiologically relevant caspase inhibitor has been unclear due to the difficulties with obtaining correctly folded survivin and finding the right conditions for inhibition assay. In this study, recombinant, active human survivin was expressed in Escherichia coli and purified to homogeneity. The protein, existing as a homodimer in solution, binds caspase-3 and -7 tightly with dissociation constants of 20.9 and 11.5 nM, respectively, when evaluated by surface plasmon resonance spectroscopy. Consistently, survivin potently inhibits the cleavage of a physiological substrate poly(ADP-ribose) polymerase and an artificial tetrapeptide by caspase-3 and -7 in vitro with apparent inhibition constants of 36.0 and 16.5 nM, respectively. The data suggest that sequestering caspase-3 and -7 in inhibited states on microtubules is at least one mechanism of survivin in the suppression of default apoptosis in the G2/M phase. The localization of survivin on microtubules, which is essential for its function, should increase the protective activity at the action site.

Direct interaction of SOS1 Ras exchange protein with the SH3 domain of phospholipase C-gamma1.

A recent report that microinjection of the SH3 domain of PLC-gamma1 could induce DNA synthesis raised the functional importance of the SH3 domain of PLC-gamma1 in mitogenic signaling. In this report, we provide evidence that SOS1, a p21Ras-specific guanine nucleotide exchange factor, directly binds to the SH3 domain of PLC-gamma1, and that the SH3 domain of PLC-gamma1 is involved in SOS1-mediated p21Ras activation. SOS1 was coprecipitated with the GST-fused SH3 domain of PLC-gamma1 in vitro. The interaction between SOS1 and the PLC-gamma1 SH3 domain is mediated by direct physical interaction. The carboxyl-terminal proline-rich domain of SOS1 is involved in the interaction with the PLC-gamma1 SH3 domain. Moreover, PLC-gamma1 could be co-immunoprecipitated with SOS1 antibody in cell lysates. From transient expression studies, we could demonstrate that the SH3 domain of PLC-gamma1 is necessary for the association with SOS1 in vivo. Intriguingly, overexpression of the SH3 domain of PLC-gamma1, lipase-inactive PLC-gamma1, or wild-type PLC-gamma1 elevated p21Ras activity and ERK activity when compared with vector transfected cells. The PLC-gamma1 mutant lacking the SH3 domain could not activate p21Ras. p21Ras activities in cell lines overexpressing either PLC-gamma1 or the SH2-SH2-SH3 domain of PLC-gamma1 were elevated about 2-fold compared to vector transfected cells. This study is the first to demonstrate that the PLC-gamma1 SH3 domain enhances p21Ras activity, and that the SH3 domain of PLC-gamma1 may be involved in the SOS1-mediated signaling pathway.

Dynamic helical biphasic CT emerges as a potential tool for the diagnosis of proximal arterioportal shunting.

BACKGROUND/AIMS: This article reports our preliminary observation regarding the diagnostic ability of dynamic helical biphasic computed tomography (CT) for proximal arterioportal shunting in hepatoma patients as compared with that of conventional angiography. METHODOLOGY: Three hundred and sixty patients with clinically-suspected liver lesions received both dynamic helical biphasic CT scan and conventional angiography of the liver. The criteria for diagnosis of proximal arterioportal (AP) shunting in dynamic helical biphasic CT included early and strong enhancement of main portal vein or its major branches approaching the density of the aorta, or enhancement of the portal vein earlier than opacification of the splenic vein and superior mesenteric vein in the arterial phase. The angiographic diagnosis of proximal AP shunting was made if there was early opacification of the main portal vein or its major branches in the arterial phase. Peripheral subsegmental small AP shunting was excluded from our study. The existence and extent of AP shunting were compared in these two imaging modalities. RESULTS: Dynamic helical biphasic CT scan demonstrated proximal AP shunting in 23 patients. All of these patients harbored hepatoma. Conventional angiography showed proximal AP shunting in 20 patients, which were all positive on dynamic helical CT. Dynamic helical biphasic CT demonstrated the presence of proximal AP shunting in 3 more patients than conventional angiography did. The extent of AP shunting was well correlated between these two imaging modalities in 17 patients. CONCLUSIONS: From our preliminary experience, the diagnostic accuracy of dynamic helical biphasic CT for proximal AP shunting in patients with hepatoma seemed to be comparable to, or even surpassed that of conventional angiography. It seems that faint AP shunting in patients with large hepatoma might be missed by conventional angiography.

Pictorial review: Radiological diagnosis of duodenal abnormalities.

This article depicts the radiological findings of many common gastrointestinal entities. Specifically, examples of disease processes that affect the stomach, gall bladder, small intestine, pancreas and colon are shown. In most cases there is correlation between ultrasound, computed tomography (CT) and fluoroscopic imaging. The major emphasis of the article, however, is to demonstrate classic barium imaging of a large number of gastrointestinal disease processes.

Radiologic and pathologic correlation of adenomyomatosis of the gallbladder.

BACKGROUND: To demonstrate the radiologic-pathologic correlation of adenomyomatosis of gallbladder (GBA) and emphasize the role of high-resolution real-time ultrasound (RTUS) in the diagnosis of GBA. METHODS: Ten (four male and six female, mean age = 49 years) patients with proven GBA (three diffuse, three segmental, and four fundal) diagnosed by histopathology or confirmed by oral cholecystography (OCG) were reviewed. Radiologic studies included OCG (n = 8), RTUS (n = 8), and computed tomography (CT; n = 4). Six patients subsequently underwent cholecystectomy. RESULTS: Histopathologic correlation between pathologic specimens and OCG, RTUS, and CT was possible in six patients. The diagnostic criteria with ultrasound included numerous tiny intramural cysts containing echogenic foci with reverberation artifacts and associated segmental or diffuse gallbladder wall thickening. OCG with fatty meal demonstrated intramural diverticula. Localized fundal GBA was better visualized on RTUS and CT scan than on OCG. CONCLUSION: Accurate diagnosis of GBA may be made by either OCG or high-resolution RTUS preoperatively. CT scan may used as an alternative method to help make the diagnosis in equivocal cases.

Selective intra-arterial calcium injection in the investigation of adult nesidioblastosis: a case report.

A 69-year-old man with recurrent hypoglycaemia had inappropriately elevated plasma insulin level during a symptomatic hypoglycaemia, but had a negative prolonged fast. Computerized tomography (CT) of the abdomen revealed a nodular lesion over the body of pancreas, whereas pancreatic arteriography failed to show tumour blush. Hence, arterial stimulation (with calcium) and venous sampling (ASVS) was performed and a brisk response of plasma insulin level was found when calcium was injected both into the splenic and the superior mesenteric arteries. Since no tumour was found during the operation, the patient received subtotal distal pancreatectomy. Pathological examination of the resected tissue disclosed a typical finding of nesidioblastosis. We suggest that selective intra-arterial calcium injection with hepatic venous sampling for insulin gradients is useful for the diagnosis of adult nesidioblastosis.

Significance of isolated gastric varices among Chinese patients.

BACKGROUND: Isolated gastric varices rarely occurs, and was considered as a hint of pancreatic disease rather than liver cirrhosis. Recently, the frequency of acute gastrointestinal bleeding secondary to isolated gastric varices tended to increase among cirrhotic patients. We therefore conducted this retrospective study to analyze its possible etiologies. METHODS: Thirty-six cases of isolated gastric varices were found in an extensive review of the endoscopic records at our hospital from 1984 to 1993. Gastric varices developed after injection sclerotherapy of esophageal varices were excluded. Medical records were reviewed to determine their etiologies. RESULTS: The underlying disorders of these 36 patients included liver cirrhosis in 26 patients (72.2%), pancreatic diseases in 7 patients (19.4%), myelofibrosis in 1 patient (2.7%), and unknown cause in 2 patients (5.5%). Among those with liver cirrhosis, portal hemodynamic study conducted in 5 patients to find all with a high level of portal venous pressure; angiography conducted in 5 patients also found all with gastric varices. Among those with pancreatic diseases, angiography and/or splenoportography was conducted in 5 patients to evidence all with gastric varices, splenic vein obstruction and splenomegaly. CONCLUSIONS: Isolated gastric varices identified in endoscopy can first strongly suggests the presence of liver cirrhosis with portal hypertension. Pancreatic diseases complicating with splenic vein obstruction is the second possible underlying etiology.

Intraductal mucin-hypersecreting papillary adenocarcinoma of the pancreas: a case report.

A 68-year-old male was admitted with jaundice and abdominal fullness. Abdominal ultrasonography and computed tomography (CT) scan showed a diffusely dilated main pancreatic duct (MPD) with microcystic lesions over the pancreatic head and dilatation of the biliary tract. Duodenoscopy revealed mucin secretion at the orifice of the papilla of Vater. Findings of endoscopic retrograde cholangiopancreatography (ERCP) were compatible with a mucinous tumor of pancreas invading the common bile duct. The patient was treated with a modified Whipple's operation. Pathological diagnosis was papillomatosis with papillary adenocarcinoma of the pancreas.

[Computed tomography for evaluation of hepatocellular carcinoma after treatment with transarterial chemoembolization].

Totally 135 series of computed tomography (CT) and angiographic examination were performed in 53 patients with proved hepatoma treated by TAE. CT examination was performed four to six weeks after TAE, and a comparative angiographic examination was performed within three weeks after CT examination. The pictures of CT scanning were read to determine 1). the grading of lipiodol retention inside the tumor, 2). the presence/absence of filling defect in the tumor margins coated by lipiodol, 3). the presence/absence of residual tumor tissue within or surrounding the main tumor, and 4). the presence/absence of developed satellite nodules. In comparison with angiographic findings, CT demonstrated 96.3% specificity and 58.2% sensitivity in the grading of lipiodol filling, and 96.3% specificity and 65.7% sensitivity in the tumor margins of lipiodol coating. However, it was difficult for CT to detect small nodules, especially those less than 1 cm in diameter. We find no statistically significant association between newly developed satellite nodules and grading of lipiodol retention inside the tumor or tumor margins of lipiodol coating. Therefore, when CT pictures reveal filling defect over the margins of the tumor coated by lipiodol or less-than-50% lipiodol filling inside the tumor, repeated angiography and further treatment with TAE are suggested.