Upper gastrointestinal tract perforation assessed by contrast-enhanced ultrasonography after oral Sonazoid administration in a stomach leakage mouse model

Purpose@#The purpose of this study was to elucidate whether contrast-enhanced ultrasonography (CEUS) can visualize orally administered Sonazoid leaking into the peritoneal cavity in a postoperative stomach leakage mouse model. @*Methods@#Adult female mice (n=33, 9-10 weeks old) were used. Preoperative CEUS was performed after delivering Sonazoid via intraperitoneal injection and the per oral route. A gastric leakage model was then generated by making a surgical incision of about 0.5 cm at the stomach wall, and CEUS with per oral Sonazoid administration was performed. A region of interest was drawn on the CEUS images and the signal intensity was quantitatively measured. Statistical analysis was performed using a mixed model to compare the signal intensity sampled from the pre-contrast images with those of the post-contrast images obtained at different time points. @*Results@#CEUS after Sonazoid intraperitoneal injection in normal mice and after oral administration in mice with gastric perforation visualized the contrast medium spreading within the liver interlobar fissures continuous to the peritoneal cavity. A quantitative analysis showed that in the mice with gastric perforation, the orally delivered Sonazoid leaking into the peritoneal cavity induced a statistically significant (P<0.05) increase in signal intensity in all CEUS images obtained 10 seconds or longer after contrast delivery. However, enhancement was not observed before gastric perforation surgery (P=0.167). @*Conclusion@#CEUS with oral Sonazoid administration efficiently visualized the contrast medium spreading within the peritoneal cavity in a postoperative stomach leakage mouse model.

Expression of Organic Anion Transporting Polypeptides in an H-Ras 12V Transgenic Mouse Model of Spontaneous Hepatocellular Carcinoma

Purpose@#Expression of organic anion transporting polypeptides (OATPs) 1B1/1B3 in hepatocellular carcinoma (HCC) induces a paradoxical enhancement of gadoxetic acid on liver magnetic resonance imaging (MRI). We examined the expression profile of OATPs with regard to tumor differentiation in a genetically modified H-Ras 12V mouse model of spontaneous HCC that undergoes multistep hepatocarcinogenesis with minimal inter-individual variation. @*Materials and Methods@#Tumor nodules were harvested from transgenic H-Ras 12V mice. Hematoxylin and eosin-stained slides were examined for tumor differentiation and high-grade pathological components (tumor necrosis, thickened trabeculae, or vascular invasion). Immunohistochemistry of OATP 1B1/1B3 was performed, and OATP expression was assessed. @*Results@#We examined well-differentiated HCCs (n=59) in which high-grade pathological components were absent (n=49) or present (n=10). Among the well-differentiated HCCs without high-grade pathological components (n=49), OATP expression was negative, weak positive, and moderate positive in 23, 17, and nine cases, respectively. Among the well-differentiated HCCs with highgrade pathological components (n=10), OATP expression was negative, weak positive, and moderate positive in one, two, and seven cases, respectively. The ratio of positive OATP 1B1/1B3 expressing tumors was higher in HCCs with high-grade pathological components than in those without high-grade pathological components (p=0.004). @*Conclusion@#Our findings support those of previous clinical studies that have reported the frequent appearance of gadoxetic acidenhanced MRI in moderately differentiated HCC.

Expression of Organic Anion Transporting Polypeptides in an H-Ras 12V Transgenic Mouse Model of Spontaneous Hepatocellular Carcinoma

Purpose@#Expression of organic anion transporting polypeptides (OATPs) 1B1/1B3 in hepatocellular carcinoma (HCC) induces a paradoxical enhancement of gadoxetic acid on liver magnetic resonance imaging (MRI). We examined the expression profile of OATPs with regard to tumor differentiation in a genetically modified H-Ras 12V mouse model of spontaneous HCC that undergoes multistep hepatocarcinogenesis with minimal inter-individual variation. @*Materials and Methods@#Tumor nodules were harvested from transgenic H-Ras 12V mice. Hematoxylin and eosin-stained slides were examined for tumor differentiation and high-grade pathological components (tumor necrosis, thickened trabeculae, or vascular invasion). Immunohistochemistry of OATP 1B1/1B3 was performed, and OATP expression was assessed. @*Results@#We examined well-differentiated HCCs (n=59) in which high-grade pathological components were absent (n=49) or present (n=10). Among the well-differentiated HCCs without high-grade pathological components (n=49), OATP expression was negative, weak positive, and moderate positive in 23, 17, and nine cases, respectively. Among the well-differentiated HCCs with highgrade pathological components (n=10), OATP expression was negative, weak positive, and moderate positive in one, two, and seven cases, respectively. The ratio of positive OATP 1B1/1B3 expressing tumors was higher in HCCs with high-grade pathological components than in those without high-grade pathological components (p=0.004). @*Conclusion@#Our findings support those of previous clinical studies that have reported the frequent appearance of gadoxetic acidenhanced MRI in moderately differentiated HCC.

Human Organic Anion Transporting Polypeptide 1B3 Applied as an MRI-Based Reporter Gene

Objective@#Recent innovations in biology are boosting gene and cell therapy, but monitoring the response to these treatments is difficult. The purpose of this study was to find an MRI-reporter gene that can be used to monitor gene or cell therapy and that can be delivered without a viral vector, as viral vector delivery methods can result in long-term complications. @*Materials and Methods@#CMV promoter-human organic anion transporting polypeptide 1B3 (CMV-hOATP1B3) cDNA or CMV-blank DNA (control) was transfected into HEK293 cells using Lipofectamine. OATP1B3 expression was confirmed by western blotting and confocal microscopy. In vitro cell phantoms were made using transfected HEK293 cells cultured in various concentrations of gadoxetic acid for 24 hours, and images of the phantoms were made with a 9.4T micro-MRI. In vivo xenograft tumors were made by implanting HEK293 cells transfected with CMV-hOATP1B3 (n = 4) or CMV-blank (n = 4) in 8-week-old male nude mice, and MRI was performed before and after intravenous injection of gadoxetic acid (1.2 μL/g). @*Results@#Western blot and confocal microscopy after immunofluorescence staining revealed that only CMV-hOATP1B3-transfected HEK293 cells produced abundant OATP1B3, which localized at the cell membrane. OATP1B3 expression levels remained high through the 25th subculture cycle, but decreased substantially by the 50th subculture cycle. MRI of cell phantoms showed that only the CMV-hOATP1B3-transfected cells produced a significant contrast enhancement effect. In vivo MRI of xenograft tumors revealed that only CMV-hOATP1B3-transfected HEK293 tumors demonstrated a T1 contrast effect, which lasted for at least 5 hours. @*Conclusion@#The human endogenous OATP1B3 gene can be non-virally delivered into cells to induce transient OATP1B3 expression, leading to gadoxetic acid-mediated enhancement on MRI. These results indicate that hOATP1B3 can serve as an MRI-reporter gene while minimizing the risk of long-term complications.

Preoperative Prediction for Early Recurrence Can Be as Accurate as Postoperative Assessment in Single Hepatocellular Carcinoma Patients

OBJECTIVE: To evaluate the performance of predicting early recurrence using preoperative factors only in comparison with using both pre-/postoperative factors.MATERIALS AND METHODS: We retrospectively reviewed 549 patients who had undergone curative resection for single hepatcellular carcinoma (HCC) within Milan criteria. Multivariable analysis was performed to identify pre-/postoperative high-risk factors of early recurrence after hepatic resection for HCC. Two prediction models for early HCC recurrence determined by stepwise variable selection methods based on Akaike information criterion were built, either based on preoperative factors alone or both pre-/postoperative factors. Area under the curve (AUC) for each receiver operating characteristic curve of the two models was calculated, and the two curves were compared for non-inferiority testing. The predictive models of early HCC recurrence were internally validated by bootstrap resampling method.RESULTS: Multivariable analysis on preoperative factors alone identified aspartate aminotransferase/platelet ratio index (OR, 1.632; 95% CI, 1.056–2.522; p = 0.027), tumor size (OR, 1.025; 95% CI, 0.002–1.049; p = 0.031), arterial rim enhancement of the tumor (OR, 2.350; 95% CI, 1.297–4.260; p = 0.005), and presence of nonhypervascular hepatobiliary hypointense nodules (OR, 1.983; 95% CI, 1.049–3.750; p = 0.035) on gadoxetic acid-enhanced magnetic resonance imaging as significant factors. After adding postoperative histopathologic factors, presence of microvascular invasion (OR, 1.868; 95% CI, 1.155–3.022; p = 0.011) became an additional significant factor, while tumor size became insignificant (p = 0.119). Comparison of the AUCs of the two models showed that the prediction model built on preoperative factors alone was not inferior to that including both pre-/postoperative factors {AUC for preoperative factors only, 0.673 (95% confidence interval [CI], 0.623–0.723) vs. AUC after adding postoperative factors, 0.691 (95% CI, 0.639–0.744); p = 0.0013}. Bootstrap resampling method showed that both the models were valid.CONCLUSION: Risk stratification solely based on preoperative imaging and laboratory factors was not inferior to that based on postoperative histopathologic risk factors in predicting early recurrence after curative resection in within Milan criteria single HCC patients.

Response Assessment with MRI after Chemoradiotherapy in Rectal Cancer: Current Evidences

Baseline magnetic resonance imaging (MRI) has become the primary staging modality for surgical plans and stratification of patient populations for more efficient neoadjuvant treatment. Patients who exhibit a complete response to chemoradiotherapy (CRT) may achieve excellent local tumor control and better quality of life with organ-preserving treatments such as local excision or even watch-and-wait management. Therefore, the evaluation of tumor response is a key factor for determining the appropriate treatment following CRT. Although post-CRT MRI is generally accepted as the first-choice method for evaluating treatment response after CRT, its application in the clinical decision process is not fully validated. In this review, we will discuss various oncologic treatment options from radical surgical technique to organ-preservation strategies for achieving better cancer control and improved quality of life following CRT. In addition, the current status of post-CRT MRI in restaging rectal cancer as well as the main imaging features that should be evaluated for treatment planning will also be described for the tailored treatment.

Extraosseous Ewing's Sarcoma Presented as a Rectal Subepithelial Tumor: Radiological and Pathological Features

PURPOSE: Extraosseous Ewing's sarcoma (EOE) of the rectum is extremely rare: only three cases have been reported in the literature and none of these reports described their imaging findings in detail. Herein, we describe the tumor imaging and pathological features in detail. MATERIALS AND METHODS: We report a case of rectal EOE in a 72-year-old female who received local excision and was provisionally diagnosed with a rectal submucosal spindle cell tumor. We used immunohistochemistry, histopathology, and fluorescence in situ hybridization to characterize the tumor and provide a definitive diagnosis of EOE. RESULTS: MRI revealed a well-demarcated submucosal tumor with heterogeneous enhancement and hemorrhagic foci in rectum. EOE was diagnosed by positive staining of tumor cells for CD99 and Fli-1 by immunohistochemistry and the presence of the EWSR1 gene translocation by fluorescence in situ hybridization. Although the patient underwent radiation treatment and surgery, the tumor recurred after 4 months as revealed by computed tomography and magnetic resonance imaging. CONCLUSION: Rectal EOE may present as a rectal submucosal tumor. The understanding of imaging and histological characteristics of this tumor are critical for accurate diagnosis and appropriate aggressive treatment.

Portal venous perfusion steal causing graft dysfunction after orthotopic liver transplantation: serial imaging findings in a successfully treated patient

A 53-year-old male with hepatocellular carcinoma underwent orthotopic liver transplantation. Preoperative computed tomography revealed main portal vein luminal narrowing by flat thrombi and the development of cavernous transformation. On post-transplantation day 1, thrombotic portal venous occlusion occurred, and emergency thrombectomy was performed. Subsequent Doppler ultrasonography and contrast-enhanced ultrasonography confirmed the restoration of normal portal venous flow. The next day, however, decreased portal venous velocity was observed via Doppler ultrasonography, and serum liver enzymes and bilirubin levels remained persistently elevated. Direct portography identified massive perfusion steal through prominent splenorenal collateral veins. Stent insertion and balloon angioplasty of the portal vein were performed, and subsequent Doppler ultrasonography demonstrated normalized portal flow parameters. Afterwards, the serum liver enzymes and bilirubin levels rapidly normalized.

Necrotic lymphoma in a patient with post-transplantation lymphoproliferative disorder: ultrasonography and CT findings with pathologic correlation

Seventeen months after kidney transplantation for the treatment of nephrotic syndrome, a retroperitoneal mass was incidentally detected in a 30-year-old man during routine follow-up. Ultrasonography revealed a mass measuring 5.5 cmx4.3 cm located between the liver and the atrophic right kidney, which showed markedly heterogeneous internal echogenicity. Contrast-enhanced computed tomography displayed a mild degree of enhancement only at the periphery of the mass, while the center lacked perceivable intensification. The patient underwent surgical resection. The final pathological diagnosis was non-Hodgkin lymphoma (diffuse large B-cell lymphoma), and extensive necrosis was observed on microscopic examination. We found that the prominent heterogeneous echogenicity of the mass (an unusual finding of lymphoma) demonstrated on ultrasonography is a result of extensive necrosis, which may sometimes occur in patients with post-transplantation lymphoproliferative disorder.

Histogram Analysis of Hepatobiliary Phase MR Imaging as a Quantitative Value for Liver Cirrhosis: Preliminary Observations

PURPOSE: To investigate whether histogram analysis of the hepatobiliary phase on gadoxetate enhanced-MRI could be used as a quantitative index for determination of liver cirrhosis. MATERIALS AND METHODS: A total of 63 patients [26 in a normal liver function (NLF) group and 37 in a cirrhotic group] underwent gadoxetate-enhanced MRI, and hepatobiliary phase images were obtained at 20 minutes after contrast injection. The signal intensity of the hepatic parenchyma was measured at four different regions of interest (ROI) of the liver, avoiding vessels and bile ducts. Standard deviation (SD), coefficient of variation (CV), and corrected CV were calculated on the histograms at the ROIs. The distributions of CVs calculated from the ROI histogram were examined and statistical analysis was carried out. RESULTS: The CV value was 0.041+/-0.009 (mean CV+/-SD) in the NLF group, while that of cirrhotic group was 0.071+/-0.020. There were statistically significant differences in the CVs and corrected CV values between the NLF and cirrhotic groups (p<0.001). The most accurate cut-off value among CVs for distinguishing normal from cirrhotic group was 0.052 (sensitivity 83.8% and specificity 88.5%). There was no statistically significant differences in SD between NLF and cirrhotic groups (p=0.307). CONCLUSION: The CV of histograms of the hepatobiliary phase on gadoxetate-enhanced MRI may be useful as a quantitative value for determining the presence of liver cirrhosis.

MRI Findings of Rectal Submucosal Tumors

Rectal submucosal lesions encompass a wide variety of benign and malignant tumors involving the rectum. With optical colonoscopy, any mass-like protrusion covered by normal mucosa, whether the underlying process is intramural or extramural in origin, may be reported as a submucosal lesion. Whereas the assessment of submucosal lesions may be limited with performing optical colonoscopy, cross-sectional imaging such as CT, transrectal ultrasonography and MRI allows the evaluation of perirectal tissues and pelvic organs in addition to the entire thickness of the rectum, and so this is advantageous for the assessment of rectal submucosal tumors. Among these, MRI is the best investigative modality for soft tissue characterization. Therefore, knowledge of the MRI features of rectal submucosal tumors can help achieve accurate preoperative diagnoses and facilitate the appropriate management.

Solitary Drain-Site Recurrence after Lumpectomy for Breast Cancer

Locoregional recurrence after breast conservative surgery is not a rare event. However, a metastatic nodule solely at the surgical drain site seems to be extremely unusual. In this report, we present a patient who received a lumpectomy for breast cancer but a metastatic nodule developed at the drain site more than two years after her surgery.

Preoperative Radiologic and Postoperative Pathologic Risk Factors for Early Intra-Hepatic Recurrence in Hepatocellular Carcinoma Patients Who Underwent Curative Resection

PURPOSE: The risk of hepatocellular carcinoma (HCC) recurrence must be considered ahead of surgery. This study was undertaken to identify pre-operative risk factors for early intrahepatic recurrence of HCC after curative resection in a large-scale. MATERIALS AND METHODS: We retrospectively reviewed the preoperative three-phase multi-detector CT (MDCT) and laboratory data for 240 HCC patients who underwent curative resection; tumor size, number, gross shape, capsule integrity, distinctiveness of tumor margin, portal vein thrombosis (PVT), alpha-fetoprotein level (AFP), and protein induced by vitamin K absence-II (PIVKA-II) levels were assessed. Surgical pathology was reviewed; tumor differentiation, capsule, necrosis, and micro-vessel invasion were recorded. RESULTS: HCC recurred in 61 patients within six months (early recurrence group), but not in 179 patients (control group). In univariate analysis, large tumor size (p = 0.018), shape (p = 0.028), poor capsule integrity (p = 0.046), elevated AFP (p = 0.015), and PIVKA-II (p = 0.008) were significant preoperative risk factors. Among the pathologic features, PVT (p = 0.023), Glisson's capsule penetration (p = 0.033), microvascular invasion (p < 0.001), and poor differentiation (p = 0.001) showed statistical significance. In multivariate analysis, only the histopathologic parameters of microvascular invasion and poor differentiation achieved statistical significance. CONCLUSION: Preoperative CT and laboratory parameters showed limited value, while the presence of microscopic vascular tumor invasion and poorly differentiated HCC correlated with higher risk of early recurrence after curative resection.

The Influence of Training on Breast Ultrasound Expertise

PURPOSE: This study was designed to evaluate the effectiveness of the training experience to develop expertise for breast ultrasound. The same group of radiology residents was evaluated before and after training on the use of the Breast Imaging Reporting and Data System (BI-RADS) to develop breast imaging expertise. MATERIALS AND METHODS: An evaluation set of breast ultrasonography images of pathologically confirmed lesions that consisted of 100 masses (54 benign and 46 malignant masses) without clinical information was developed. Two experienced breast radiologists independently reviewed cases to reach a consensus. Six radiology residents (four second-year residents and two third-year residents) trained one month to interpret breast ultrasound examinations, and to read and to review teaching files with expertise. The residents evaluated the examination set according to BI-RADS for shape, orientation, margin, lesion-boundary, echo pattern, posterior echo features, surrounding tissue, calcification and final assessment before and after the training. Training performance was measured by means of agreement (k) and diagnostic performance. RESULTS: After training, the second-year residents showed statistically significant increased agreement as compared to the experts for 15 of the total 36 BI-RADS descriptors. The third-year residents showed increased agreement for three of the 18 descriptors. The mean sensitivity for the residents was 94.2% (range, 89.1-100%) before training and the mean sensitivity increased to 97.8% (range, 95.7-100%) after training. The mean specificity was 50.6% (range, 40.7-59.3%) before training and the mean specificity decreased to 42.0% (range, 31.5-51.9%) after training. CONCLUSION: In this study, the use of breast ultrasonography training improved the ability of residents to determine lesion description, final assessment and coherence.