Gastrointestinal stromal tumors: a comprehensive radiological review.

Gastrointestinal stromal tumors (GISTs) originating from the interstitial cells of Cajal in the muscularis propria are the most common mesenchymal tumor of the gastrointestinal tract. Multiple modalities, including computed tomography (CT), magnetic resonance imaging (MRI), fluorodeoxyglucose positron emission tomography, ultrasonography, digital subtraction angiography, and endoscopy, have been performed to evaluate GISTs. CT is most frequently used for diagnosis, staging, surveillance, and response monitoring during molecularly targeted therapy in clinical practice. The diagnosis of GISTs is sometimes challenging because of the diverse imaging findings, such as anatomical location (esophagus, stomach, duodenum, small bowel, colorectum, appendix, and peritoneum), growth pattern, and enhancement pattern as well as the presence of necrosis, calcification, ulceration, early venous return, and metastasis. Imaging findings of GISTs treated with antineoplastic agents are quite different from those of other neoplasms (e.g. adenocarcinomas) because only subtle changes in size are seen even in responsive lesions. Furthermore, the recurrence pattern of GISTs is different from that of other neoplasms. This review discusses the advantages and disadvantages of each imaging modality, describes imaging findings obtained before and after treatment, presents a few cases of complicated GISTs, and discusses recent investigations performed using CT and MRI to predict histological risk grade, gene mutations, and patient outcomes.

Clinical impact of low tube voltage computed tomography during hepatic arteriography with low iodine to detect hepatocellular carcinoma before transarterial chemoembolization.

PURPOSE: This study aimed to evaluate the clinical impact of low tube voltage computed tomography (CT) during hepatic arteriography (CTHA) using low iodine contrast to detect hepatocellular carcinoma (HCC). MATERIALS AND METHODS: CTHA images were obtained using a dual-spin technique (80 kVp and 135 kVp) with 30 ml of low-dose iodine contrast (75 mgI/ml). Three radiologists reviewed 135 kVp and 80 kVp CTHA images to diagnose HCC, recording their confidence scores and evaluations of sharpness, noise, artifact, and overall image quality. Lesion-to-liver contrast ratios and objective noise were measured by a non-reader radiologist. RESULTS: We included 23 patients (body mass index, 23.6 ± 2.6 kg/m2) with 89 HCCs. The mean radiation dose index volume was 21.3 mGy at 135 kVp and 9.4 mGy at 80 kVp (P < 0.001). The overall sensitivity and positive predictive value for diagnosing HCCs at 80 kVp vs. 135 kVp were 0.787 vs. 0.730 and 0.712 vs. 0.756, respectively. The lesion-to-liver contrast ratio at 80 kVp was significantly higher than at 135 kVp in the first (3.1 vs. 2.0; P = 0.008) and second phase (3.1 vs. 2.3; P = 0.016). Objective noise was significantly higher at 80 kVp than at 135 kVp in the first (15. 6 ± 4.9 vs. 11.0 ± 3.1; P < 0.001) and second (16.9 ± 5.2 vs. 15.0 ± 7.3; P = 0.046) phases. CONCLUSION: An 80 kVp CTHA, with lower-dose iodine, improved the sensitivity and reduced the radiation dose, despite a decreased positive predictive value in comparison with a 135-kVp CTHA with the same iodine dose.

Effect of Portal Vein and Hepatic Artery Occlusion on Radiofrequency Ablation: Animal Experiment Comparing MR and Histology Measurements of the Ablation Zones.

PURPOSE: This animal experimental study evaluated how hepatic artery and portal vein transient occlusion affects the ablation zone of hepatic radiofrequency ablation (RFA). MATERIAL AND METHODS: Twenty-one rabbits were divided into three groups of seven each: (1) control, (2) hepatic artery occlusion, and (3) portal vein occlusion by a balloon catheter. For each rabbit, two or three RFA sessions were performed using an electrode needle. Ablation time, temperature around the tip of RFA needle at the end of RFA, ablation volume on fat-suppressed T1-weighted image in the hepatobiliary phase, and coagulative necrosis area on histopathology were measured and compared between the three groups using the Kruskal-Wallis paired Mann-Whitney U tests. RESULTS: In 43 RFA sessions (group 1, 15; group 2, 14; group 3, 14), mean tissue temperature in group 3 (77.0 °C ± 7.7 °C) was significantly higher compared to groups 1 (59.2 °C ± 18.8 °C; P = 0.010) and 2 (67.5 °C ± 9.9 °C; P = 0.010). In addition, mean ablation volume and coagulative necrosis in group 3 (2.10 ± 1.37 mm3 and 0.86 ± 0.28 mm2, respectively) were larger compared to groups 1 (0.84 ± 0.30 mm3; P < 0.001 and 0.55 ± 0.26 mm2; P = 0.020, respectively) and 2 (0.89 ± 0.59 mm3; P = 0.002 and 0.60 ± 0.22 mm2; P = 0.024, respectively). CONCLUSION: Portal vein occlusion potentially boosts tissue temperature, ablation volume, and area of histopathologically proven coagulative necrosis during hepatic RFA in the non-cirrhotic liver.

Noncontrast MRI of acute abdominal pain caused by gastrointestinal lesions: indications, protocol, and image interpretation.

Gastrointestinal tract lesions are major causes of acute abdominal pain. A rapid, accurate, and reliable diagnosis is required to manage patients. Magnetic resonance imaging (MRI) is a nonionizing modality that is beneficial for pregnant women, children, and young adults who are sensitive to ionizing radiation. For patients with renal impairment who are not accurately diagnosed with noncontrast computed tomography, noncontrast MRI can serve as an alternative diagnostic modality. MRI protocols used for acute abdominal pain are supposed to be optimized and prioritized to shorten scanning times. Single-shot T2-weighted and fat-suppressed T2-weighted imaging are important pulse sequences that are used to reveal pathology and inflammation in the gastrointestinal tract. Diffusion-weighted imaging clearly depicts inflammation and abscesses as hyperintense lesions. Most acute gastrointestinal tract lesions, including inflammation, ischemia, obstruction, and perforation, demonstrate bowel wall thickening. Bowel obstruction and adynamic ileus present bowel dilatation, and perforation and penetration show bowel wall defects. MRI can be used to reveal these pathological findings with some characteristics depending on their underlying pathophysiology. This review article discusses imaging modalities for acute abdominal pain, describes a noncontrast MRI protocol for acute abdominal pain caused by gastrointestinal tract lesions, and reviews MRI findings of acute gastrointestinal tract lesions.

Foreign-body granulomas and abscesses caused by dropped gallstones after cholecystectomy: Four cases diagnosed with multimodality imaging.

Four cases (age range, 60-78 years, male:female = 1:3) who had undergone cholecystectomy presented with fever (n = 1), right abdominal pain with fever (n = 1), appetite loss with fever (n = 1), and absence of symptoms (n = 1). Computed tomography (CT) showed an irregular-shaped invasive mass or fluid collection in the right Morrison's pouch, right paracolic gutter, gallbladder fossa, subphrenic space, or abdominal wall. CT and ultrasound revealed gallstones in the granuloma in 3 cases and an abscess in one case. The inflammatory process induced by dropped gallstones may mimic peritoneal malignancies. Awareness of cholecystectomy and the detection of gallstones in the lesion are essential for the diagnosis of dropped gallstones.

Difference of computed tomographic characteristic findings between gastric and intestinal gastrointestinal stromal tumors.

PURPOSE: We aimed to compare the computed tomography (CT) imaging differences between gastric and intestinal gastrointestinal stromal tumors (GISTs). MATERIALS AND METHODS: Thirty-eight patients with 38 gastric GISTs and 27 with 31 intestinal GISTs were enrolled. Tumors were classified as small (< 5 cm) or large (≥ 5 cm). Qualitative and quantitative CT imaging characteristics on non-contrast and contrast-enhanced CT were evaluated by two radiologists independently and statistically compared. RESULTS: Early venous return and higher CT number of the draining vein in the arterial phase were more frequent in small-sized intestinal GISTs than in small-sized gastric GISTs (p < 0.001). Small-sized intestinal GISTs demonstrated a wash-out pattern, whereas small-sized gastric GISTs showed a plateau pattern. Contrast enhancement was higher in small-sized intestinal GISTs than in small-sized gastric GISTs (p < 0.001). CT number was inversely proportional to the diameter of intestinal GISTs in both arterial and venous phases but not to that of gastric GISTs. CONCLUSION: Strong enhancement with wash-out pattern and early venous return are characteristic findings of small-sized intestinal GISTs. Radiologists should be aware that CT findings of GISTs have a wide spectrum and may differ according to size and site of origin.

MR Imaging-based Evaluation of Mesenteric Ischemia Caused by Strangulated Small Bowel Obstruction and Mesenteric Venous Occlusion: An Experimental Study Using Rabbits.

PURPOSE: This study assessed the MRI findings of strangulated small bowel obstruction (SBO) and mesenteric venous occlusion (MVO) in a rabbit model using 3T MRI. MATERIALS AND METHODS: Twenty rabbits were included in this study. The strangulated SBO and MVO models were generated via surgical procedures in nine rabbits, and sham surgery was performed in two rabbits. The success of generating the models was confirmed via angiographic, macroscopic, and microscopic findings after the surgical procedure. MRI was performed before and 30 min after inducing mesenteric ischemia. T1-weighted images (T1WIs), T2-weighted images (T2WIs), and fat-suppressed T2WIs (FS-T2WIs) were obtained using the BLADE technique, and fat-suppressed T1WIs (FS-T1WIs) were obtained. The signal intensities of the affected bowel before and after the surgical procedures were visually categorized as high, iso, and low intense compared with the findings for the normal bowel wall on all sequences. Bowel wall thickness was measured, and the signal intensity ratio (SI ratio) was calculated using the signal intensities of the bowel wall and psoas muscle. RESULTS: Angiographic, macroscopic, and microscopic findings confirmed that all surgical procedures were successful. The ischemic bowel wall was thicker than the normal bowel. The bowel wall was thicker in the MVO model (3.17 ± 0.55 mm) than in the strangulated SBO model (2.26 ± 0.46 mm). The signal intensity and SI ratio of the bowel wall were significantly higher after the procedure than before the procedure on all sequences in both models. The mesentery adjacent to the ischemic bowel loop exhibited a high signal intensity in all animals on FS-T2WIs. CONCLUSION: Non-contrast MRI can be used to evaluate mesenteric ischemia caused by strangulated SBO and MVO. FS-T2WIs represented the best modality for depicting the high signal intensity in the bowel wall and mesentery caused by ischemia.

Change in hepatic hemodynamics assessed by hepatic arterial blood pressure and computed tomography during hepatic angiography with the double balloon technique.

PURPOSE: To assess the change in hepatic arterial blood pressure (HABP) and computed tomography during hepatic arteriography (CTHA) using the double balloon technique. MATERIALS AND METHODS: Nine patients with hepatocellular carcinoma (HCC) were enrolled. We inserted a 5.2-Fr balloon catheter into the common or proper hepatic artery and a 1.8-Fr microballoon catheter into the lobar or segmental artery feeding the HCC. HABPs were measured with the 1.8-Fr microballoon catheter (usual-HABP), with the 1.8-Fr balloon inflated (B-HABP), and with both the 5.2-Fr and 1.8-Fr balloons inflated (BB-HABP). CTHAs were performed via a 1.8-Fr microcatheter (usual-CTHA), with the 1.8-Fr balloon inflated (B-CTHA selective), with both the 5.2-Fr and 1.8-Fr balloons inflated (BB-CTHA selective), and via the 5.2-Fr catheter with the 1.8-Fr balloon inflated (B-CTHA whole) and with both the 5.2-Fr and 1.8-Fr balloons inflated (BB-CTHA whole). RESULTS: In all cases, B-HABP was lower than usual-HABP. There was a decrease in BB-HABP in comparison with B-HABP in cases with occlusion of the proper hepatic artery. The contrast effect of B-CTHA selective increased in four cases. The contrast effect on B-CTHA whole remained in all cases. CONCLUSION: This technique can be useful in decreasing HABP and collateral blood flow from the adjacent hepatic segment.

Comparison of characteristic computed tomographic findings of gastrointestinal and non-gastrointestinal stromal tumors in the small intestine.

PURPOSE: We aimed to reveal specific findings of gastrointestinal stromal tumors (GISTs) in the small intestine on contrast-enhanced computed tomography (CT) by comparing GISTs with non-GISTs. METHODS: We enrolled 28 patients with 39 GISTs and 20 patients with 22 non-GISTs who underwent enterectomy with a preoperative diagnosis of small intestinal tumor. All lesions were diagnosed by histopathological examination. Two radiologists independently evaluated internal homogeneity, growth pattern, calcification, intratumoral hemorrhage, degeneration, ulceration, and lymphadenopathy and measured the maximum diameter of the tumor and contrast-enhanced CT (CECT) value of the solid portion as well as the diameter and CT value of the feeding artery and drainage vein on CECT in the arterial and venous phases. RESULTS: Intratumoral hemorrhage was seen in 15.4% and 25.6% of GISTs and in 0% and 0% of non-GISTs (p = 0.079 and 0.010), with good interobserver agreement (κ = 0.715). The drainage vein diameter correlated well with the maximum diameter of the tumor (r = 0.744, p < 0.001). The CT value of the solid tumor part in the arterial and venous phases (p < 0.01) and the CT value of the drainage vein in the arterial phase (p < 0.05) were higher for GISTs than for non-GISTs (p < 0.01). CONCLUSIONS: Strong parenchymal enhancement with the peak in the arterial phase and the CT value of the drainage vein in the arterial phase was characteristics findings of GIST compared with non-GISTs. The diameter of the drainage vein was proportional to the maximum diameter of GISTs.

Antiglycolytic therapy combined with an image-guided minimally invasive delivery strategy for the treatment of breast cancer.

PURPOSE: The antiglycolytic agent 3-bromopyruvate (3-BrPA) promotes anticancer effects in multiple tumor models. This study evaluated the therapeutic efficacy of ultrasound (US)-guided intratumoral delivery of 3-BrPA in an orthotopic tumor model of breast cancer. MATERIALS AND METHODS: Human breast cancer cell line MDA MB 231 was used for in vitro and in vivo studies. The anticancer effect of 3-BrPA was evaluated by viability assay, quantification of adenosine triphosphate (ATP) and lactate levels, and activity of matrix metalloproteinase (MMP)-9. In animal experiments, 15 nude mice with MDA MB 231 breast tumors were divided into three groups for US-guided intratumoral treatment with 1.75 mM 3-BrPA (group 1), 5 mM 3-BrPA (group 2), and saline solution (group 3). Tumor size was measured and subjected to histopathologic examination. RESULTS: In vitro, treatment with 3-BrPA resulted in a dose-dependent decrease in cell viability. A decrease in ATP and lactate levels, invasion, and MMP9 activity and expression was observed after treatment with concentrations of 3-BrPA that did not affect cell viability. In vivo, a significant difference in tumor volume was observed between 3-BrPA-treated and control animals. At the end of the study, tumor volumes in the 3-BrPA groups were 1,876 mm(3)±346 and 426 mm(3)±180 in the 1.75-mM and 5-mM 3-BrPA groups, respectively, versus 4,447 mm(3)±571 in the control group (P< .05). CONCLUSIONS: US-guided intratumoral injection of 3-BrPA effectively blocks breast cancer progression in an orthotopic mouse tumor model.

Ultrasound-guided direct delivery of 3-bromopyruvate blocks tumor progression in an orthotopic mouse model of human pancreatic cancer.

Studies in animal models of cancer have demonstrated that targeting tumor metabolism can be an effective anticancer strategy. Previously, we showed that inhibition of glucose metabolism by the pyruvate analog, 3-bromopyruvate (3-BrPA), induces anticancer effects both in vitro and in vivo. We have also documented that intratumoral delivery of 3-BrPA affects tumor growth in a subcutaneous tumor model of human liver cancer. However, the efficacy of such an approach in a clinically relevant orthotopic tumor model has not been reported. Here, we investigated the feasibility of ultrasound (US) image-guided delivery of 3-BrPA in an orthotopic mouse model of human pancreatic cancer and evaluated its therapeutic efficacy. In vitro, treatment of Panc-1 cells with 3-BrPA resulted in a dose-dependent decrease in cell viability. The loss of viability correlated with a dose-dependent decrease in the intracellular ATP level and lactate production confirming that disruption of energy metabolism underlies these 3-BrPA-mediated effects. In vivo, US-guided delivery of 3-BrPA was feasible and effective as demonstrated by a marked decrease in tumor size on imaging. Further, the antitumor effect was confirmed by (1) a decrease in the proliferative potential by Ki-67 immunohistochemical staining and (2) the induction of apoptosis by terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphospate nick end labeling staining. We therefore demonstrate the technical feasibility of US-guided intratumoral injection of 3-BrPA in a mouse model of human pancreatic cancer as well as its therapeutic efficacy. Our data suggest that this new therapeutic approach consisting of a direct intratumoral injection of antiglycolytic agents may represent an exciting opportunity to treat patients with pancreas cancer.

Efficient derivation of multipotent neural stem/progenitor cells from non-human primate embryonic stem cells.

The common marmoset (Callithrix jacchus) is a small New World primate that has been used as a non-human primate model for various biomedical studies. We previously demonstrated that transplantation of neural stem/progenitor cells (NS/PCs) derived from mouse and human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) promote functional locomotor recovery of mouse spinal cord injury models. However, for the clinical application of such a therapeutic approach, we need to evaluate the efficacy and safety of pluripotent stem cell-derived NS/PCs not only by xenotransplantation, but also allotransplantation using non-human primate models to assess immunological rejection and tumorigenicity. In the present study, we established a culture method to efficiently derive NS/PCs as neurospheres from common marmoset ESCs. Marmoset ESC-derived neurospheres could be passaged repeatedly and showed sequential generation of neurons and astrocytes, similar to that of mouse ESC-derived NS/PCs, and gave rise to functional neurons as indicated by calcium imaging. Although marmoset ESC-derived NS/PCs could not differentiate into oligodendrocytes under default culture conditions, these cells could abundantly generate oligodendrocytes by incorporating additional signals that recapitulate in vivo neural development. Moreover, principal component analysis of microarray data demonstrated that marmoset ESC-derived NS/PCs acquired similar gene expression profiles to those of fetal brain-derived NS/PCs by repeated passaging. Therefore, marmoset ESC-derived NS/PCs may be useful not only for accurate evaluation by allotransplantation of NS/PCs into non-human primate models, but are also applicable to analysis of iPSCs established from transgenic disease model marmosets.

Spontaneous tumor regression in a syngeneic rat model of liver cancer: implications for survival studies.

PURPOSE: To characterize tumor growth of N1S1 cells implanted into the liver of Sprague-Dawley rats to determine if this model could be used for survival studies. These results were compared with tumor growth after implantation with McA-RH7777 cells. MATERIALS AND METHODS: N1S1 or McA-RH7777 cells were implanted into the liver of Sprague-Dawley rats (n = 20 and n = 12, respectively) using ultrasound (US) guidance, and tumor growth was followed by using US. Serum profiles of 19 cytokines were compared in naive versus tumor-bearing rats. RESULTS: Both types of tumors were visible on US 1 week after tumor implantation, but the mean tumor volume of N1S1 tumors was larger compared to McA-RH7777 tumors (231 mm(3) vs 82.3 mm(3), respectively). Tumor volumes in both groups continued to increase, reaching means of 289 mm(3) and 160 mm(3) in N1S1 and McA-RH7777 groups, respectively, 2 weeks after tumor implantation. By week 3, tumor volumes had decreased considerably, and six tumors (50%) in the McA-RH7777 had spontaneously regressed, versus two (10%) in the N1S1 group. Tumor volumes continued to decrease over the following 3 weeks, and complete tumor regression of all tumors was seen 5 weeks and 6 weeks after tumor implantation in the McA-RH7777 and N1S1 groups, respectively. In an N1S1-implanted rat, multiple cytokines that have been shown to correlate with the ability of the tumor to survive in a hostile environment were increased by as much as 50%, whereas the average increase in cytokine levels was 90%. These findings suggest that the net cytokine environment favors an antitumor immune response. A similar trend was observed in a rat with a McA-RH7777 tumor, and the increase in cytokine levels was considerably more pronounced, with an average increase of 320%. CONCLUSIONS: The model of N1S1 cell implantation in the liver of Sprague-Dawley rats is not ideal for survival studies and should only be used with great caution in short-term studies that involve cancer therapies.

Negatively charged superparamagnetic iron oxide nanoparticles: a new blood-pooling magnetic resonance contrast agent.

PURPOSE: Our purpose was to investigate the utility of superparamagnetic iron-oxide nanoparticles (SPIO) as a blood-pooling contrast agent at magnetic resonance imaging (MRI). MATERIALS AND METHODS: We studied four contrast agents: carboxymethyl-diethylaminoethyl dextran magnetite SPIO (CMEADM-S, diameter 54 nm), negatively charged CMEADM ultrasmall SPIO (CMEADM-U, 32 nm), alkali-treated dextran magnetite SPIO (ATDM-S, 55 nm), and ATDM ultrasmall SPIO (ATDM-U, 28 nm) carrying a neutral charge. Each contrast agent (80 µmol/kg) was injected intraperitoneally into apolipoprotein E (apoE) mice and the tissue iron concentration was measured 30-, 60-, 180-, and 300-min later by nuclear MR. For MR angiographic (MRA) evaluation, we injected the agents into the auricular vein of four groups of 15 rabbits. Immediately and 30-, 60-, 180-, and 300-min later, three rabbits from each group were subjected to MRI. The organ/background signal ratio (SR) was calculated. Statistical analyses were performed with Tukey's honestly significant difference (HSD) test. RESULTS: At 60 and 180 min, blood-iron concentration of CMEADM-U was significantly different from other contrast agents. In the abdominal aorta and inferior vena cava, SR of CMEADM-U was higher at 180 and 300 min than of the other contrast agents. In the thoracic aorta, there was no difference in SR at 300 min between CMEADM-U and CMEADM-S. CONCLUSION: Negatively charged SPIO nanoparticles may be useful as a blood-pooling contrast agent.

Transcatheter arterial embolization in patients with kidney diseases: an overview of the technical aspects and clinical indications.

Therapeutic embolization is defined as the voluntary occlusion of one or several vessels, and this is achieved by inserting material into the lumen to obtain transient or permanent thrombosis in the downstream vascular bed. There are a number of indications for this approach in urological practice, in particular for the patients with parenchymatous or vascular kidney disease. In this review, we present the different embolization techniques and the principally employed occluding agents, and then we present the principal clinical indications and we discuss other pathologies that may benefit from this non-invasive therapy. The complications, side effects and main precautions associated with this approach are also described.

3-Bromopyruvate induces endoplasmic reticulum stress, overcomes autophagy and causes apoptosis in human HCC cell lines.

BACKGROUND: Autophagy, a cellular response to stress, plays a role in resistance to chemotherapy in cancer cells. Resistance renders systemic chemotherapy generally ineffective against human hepatocellular carcinoma (HCC). Recently, we reported that the pyruvate analog 3-bromopyruvate (3-BrPA) promoted tumor cell death by targeting GAPDH. In continuance, we investigated the intracellular response of two human HCC cell lines (Hep3B and SK-Hep1) that differ in their status of key apoptotic regulators, p53 and Fas. METHODS AND RESULTS: 3-BrPA treatment induced endoplasmic reticulum (ER) stress, translation inhibition and apoptosis based on Western blot and qPCR, pulse labeling, Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and active caspase-3 in both the cell lines. However, electron microscopy revealed that 3-BrPA treated SK-Hep1 cells underwent classical apoptotic cell death while Hep3B cells initially responded with the protective autophagy that failed to prevent eventual apoptosis. CONCLUSION: 3-BrPA treatment promotes apoptosis in human HCC cell lines, irrespective of the intracellular response.

Embolization of acute nonvariceal upper gastrointestinal hemorrhage resistant to endoscopic treatment: results and predictors of recurrent bleeding.

Acute nonvariceal upper gastrointestinal (UGI) hemorrhage is a frequent complication associated with significant morbidity and mortality. The most common cause of UGI bleeding is peptic ulcer disease, but the differential diagnosis is diverse and includes tumors; ischemia; gastritis; arteriovenous malformations, such as Dieulafoy lesions; Mallory-Weiss tears; trauma; and iatrogenic causes. Aggressive treatment with early endoscopic hemostasis is essential for a favorable outcome. However, severe bleeding despite conservative medical treatment or endoscopic intervention occurs in 5-10% of patients, requiring surgery or transcatheter arterial embolization. Surgical intervention is usually an expeditious and gratifying endeavor, but it can be associated with high operative mortality rates. Endovascular management using superselective catheterization of the culprit vessel, «sandwich¼ occlusion, or blind embolization has emerged as an alternative to emergent operative intervention for high-risk patients and is now considered the first-line therapy for massive UGI bleeding refractory to endoscopic treatment. Indeed, many published studies have confirmed the feasibility of this approach and its high technical and clinical success rates, which range from 69 to 100% and from 63 to 97%, respectively, even if the choice of the best embolic agent among coils, cyanaocrylate glue, gelatin sponge, or calibrated particles remains a matter of debate. However, factors influencing clinical outcome, especially predictors of early rebleeding, are poorly understood, and few studies have addressed this issue. This review of the literature will attempt to define the role of embolotherapy for acute nonvariceal UGI hemorrhage that fails to respond to endoscopic hemostasis and to summarize data on factors predicting angiographic and embolization failure.

The pyruvic acid analog 3-bromopyruvate interferes with the tetrazolium reagent MTS in the evaluation of cytotoxicity.

3-Bromopyruvate (3BrPA) is a pyruvate analog known for its alkylating property. Recently, several reports have documented the antiglycolytic and anticancer effects of 3BrPA and its potential for therapeutic applications. 3BrPA-mediated cytotoxicity has been evaluated in vitro by various methods including tetrazolium salt (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide)-based assays such as MTT, MTS, and so on. However, growing body of evidences has shown that tetrazolium reagent may interfere with the test compounds. In this study, we investigated whether the tetrazolium reagent interferes with the assessment of 3BrPA cytotoxicity. The results of the tetrazolium-based MTS assay were compared with 3 distinct cell viability detection methods, that is, Trypan Blue staining, ATP depletion, and Annexin V staining in 2 different cell lines, Vx-2 and HepG2. The MTS assay data showed false positive results by indicating increased cell viability at 1 mM and 2 mM 3BrPA whereas the other cell viability assays demonstrated that both Vx-2 and HepG2 cells are not viable at the same treatment conditions. In order to validate the direct interaction of 3BrPA with MTS reagent, we tested cell-free media incubated with different concentrations of 3BrPA. The results of cell-free media showed an increase in absorbance in a dose-dependent manner confirming the interaction of MTS with 3BrPA. Thus, our data clearly demonstrate that 3BrPA interferes with the accuracy of MTS-based cytotoxicity evaluation. Hence, we suggest that employing multiple methods of biochemical as well as morphological cytotoxicity assays is critical to evaluate 3BrPA-mediated cell death.

Metformin suppresses glucose-6-phosphatase expression by a complex I inhibition and AMPK activation-independent mechanism.

Metformin is widely used as a hypoglycemic agent for the treatment of type 2 diabetes. Both metformin and rotenone, an inhibitor of respiratory chain complex I, suppressed glucose-6-phosphatase (G6pc), a rate limiting enzyme of liver glucose production, mRNA expression in a rat hepatoma cell line accompanied by a reduction of intracellular ATP concentration and an activation of AMP-activated protein kinase (AMPK). When yeast NADH-quinone oxidoreductase 1 (NDI1) gene was introduced into the cells, neither inhibition of ATP synthesis nor activation of AMPK was induced by these agents. Interestingly, in contrast to rotenone treatment, G6pc mRNA down-regulation was observed in the NDI1 expressing cells after metformin treatment. Since NDI1 can functionally complement the complex I under the presence of metformin or rotenone, our results indicate that metformin induces down-regulation of G6pc expression through an inhibition of complex I and an activation of AMPK-independent mechanism.