Prognostic significance of MRI features in patients with solitary large hepatocellular carcinoma following surgical resection.

OBJECTIVE: To assess the prognostic impact of preoperative MRI features on outcomes for single large hepatocellular carcinoma (HCC) (≥ 8 cm) after surgical resection. MATERIAL AND METHODS: This retrospective study included 151 patients (mean age: 59.2 years; 126 men) with a single large HCC who underwent gadoxetic acid-enhanced MRI and surgical resection between 2008 and 2020. Clinical variables, including tumor markers and MRI features (tumor size, tumor margin, and the proportion of hypovascular component on hepatic arterial phase (AP) (≥ 50% vs. < 50% tumor volume) were evaluated. Cox proportional hazards model analyzed overall survival (OS), recurrence-free survival (RFS), and associated factors. RESULTS: Among 151 HCCs, 37.8% and 62.2% HCCs were classified as ≥ 50% and < 50% AP hypovascular groups, respectively. The 5- and 10-year OS and RFS rates in all patients were 62.0%, 52.6% and 41.4%, 38.5%, respectively. Multivariable analysis revealed that ≥ 50% AP hypovascular group (hazard ratio [HR] 1.7, p = 0.048), tumor size (HR 1.1, p = 0.006), and alpha-fetoprotein ≥ 400 ng/mL (HR 2.6, p = 0.001) correlated with poorer OS. ≥ 50% AP hypovascular group (HR 1.9, p = 0.003), tumor size (HR 1.1, p = 0.023), and non-smooth tumor margin (HR 2.1, p = 0.009) were linked to poorer RFS. One-year RFS rates were lower in the ≥ 50% AP hypovascular group than in the < 50% AP hypovascular group (47.4% vs 66.9%, p = 0.019). CONCLUSION: MRI with ≥ 50% AP hypovascular component and larger tumor size were significant factors associated with poorer OS and RFS after resection of single large HCC (≥ 8 cm). These patients require careful multidisciplinary management to determine optimal treatment strategies. CLINICAL RELEVANCE STATEMENT: Preoperative MRI showing a ≥ 50% arterial phase hypovascular component and larger tumor size can predict worse outcomes after resection of single large hepatocellular carcinomas (≥ 8 cm), underscoring the need for tailored, multidisciplinary treatment strategies. KEY POINTS: MRI features offer insights into the postoperative prognosis for large hepatocellular carcinoma. Hypovascular component on arterial phase ≥ 50% and tumor size predicted poorer overall survival and recurrence-free survival. These findings can assist in prioritizing aggressive and multidisciplinary approaches for patients at risk for poor outcomes.

Does high [18F]FDG uptake always mean poor prognosis? Colon cancer with high-level microsatellite instability is associated with high [18F]FDG uptake on PET/CT.

OBJECTIVES: High-level microsatellite instability (MSI-high) is generally associated with higher F-18 fluorodeoxyglucose ([18F]FDG) uptake than stable microsatellite (MSI-stable) tumors. However, MSI-high tumors have better prognosis, which is in contrast with general understanding that high [18F]FDG uptake correlates with poor prognosis. This study evaluated metastasis incidence with MSI status and [18F]FDG uptake. METHODS: We retrospectively reviewed 108 right-side colon cancer patients who underwent preoperative [18F]FDG PET/CT and postoperative MSI evaluations using a standard polymerase chain reaction at five Bethesda guidelines panel loci. The maximum standard uptake value (SUVmax), SUVmax tumor-to-liver ratio (TLR), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumor were measured using SUV 2.5 cut-off threshold. Student's t-test or Mann-Whitney U test was performed for continuous variables, and χ2 test or Fisher's exact test was performed for categorical variables (p value of < 0.05 for statistical significance). Medical records were reviewed for metastasis incidence. RESULTS: Our study population had 66 MSI-stable and 42 MSI-high tumors. [18F]FDG uptake was higher in MSI-high tumors than MSI-stable tumors (TLR, median (Q1, Q3): 7.95 (6.06, 10.54) vs. 6.08 (4.09, 8.82), p = 0.021). Multivariable subgroup analysis demonstrated that higher [18F]FDG uptake was associated with higher risks of distant metastasis in MSI-stable tumors (SUVmax: p = 0.025, MTV: p = 0.008, TLG: p = 0.019) but not in MSI-high tumors. CONCLUSION: MSI-high colon cancer is associated with high [18F]FDG uptake, but unlike MSI-stable tumors, the degree of [18F]FDG uptake does not correlate with the rate of distant metastasis. CLINICAL RELEVANCE STATEMENT: MSI status should be considered during PET/CT assessment of colon cancer patients, as the degree of [18F]FDG uptake might not reflect metastatic potential in MSI-high tumors. KEY POINTS: • High-level microsatellite instability (MSI-high) tumor is a prognostic factor for distant metastasis. • MSI-high colon cancers had a tendency of demonstrating higher [18F]FDG uptake compared to MSI-stable tumors. • Although higher [18F]FDG uptake is known to represent higher risks of distant metastasis, the degree of [18F]FDG uptake in MSI-high tumors did not correlate with the rate at which distant metastasis occurred.

Profile of vascular markers and CT enhancement of hyaline vascular type Castleman's disease.

Blood vessels in lymph nodes (LNs) are unique in comprising both capillaries and high endothelial venules (HEVs). Hyaline vascular type Castleman's disease accompanies robust angiogenesis, but it is unclear how the capillaries and HEVs respond. We retrospectively examined surgical specimens of hyaline vascular type unicentric Castleman's disease patients (n = 24) and control LNs (n = 9). We performed immunohistochemistry of CD 31 for capillaries and MECA-79 for HEVs and calculated their microvascular density. We measured CT enhancement as the ratio of Hounsfield Units (HUs) of the target lesion against muscle compared with microvascular density. The microvascular density of Castleman's disease specimen were (CD 31+) 169.7 ± 77.6, (MECA-79+) 203.5 ± 96.7, and the microvascular density of control LNs were (CD 31+) 80.7 ± 20.1, (MECA-79+) 67.4 ± 23.7, respectively. The microvascular density of both CD 31+ (P < 0.001) and MECA-79+ (P < 0.001) was higher in Castleman's disease. A positive correlation existed between CT HU ratio and microvascular density for both markers (CD 31: r = 0.517, P = 0.002; MECA-79: r = 0.521, P = 0.002). Intra-nodal angiogenesis of Castleman's disease involves robust proliferation of not only CD 31+ capillaries, but also MECA-79+ HVEs, which each correlated with degree of CT enhancement.

A modified LI-RADS: targetoid tumors with enhancing capsule can be diagnosed as HCC instead of LR-M lesions.

OBJECTIVE: To elucidate whether the presence of enhancing capsule can be applied to establish a modified Liver Imaging Reporting and Data System (LI-RADS) to differentiate hepatocellular carcinoma (HCC) from non-HCC malignancies in extracellular contrast agent (ECA)-enhanced and hepatobiliary agent (HBA)-enhanced MRI. METHODS: We enrolled 198 participants (161 men; mean age, 56.3 years) with chronic liver disease who underwent ECA-MRI and HBA-MRI before surgery for de novo hepatic nodule(s). Two reviewers assigned LI-RADS categories (v2018). We defined a "modified LR-5 category, which emphasizes enhancing capsule (mLR-5C)" over targetoid features and classifies tumors with both targetoid appearance and enhancing capsule as HCC instead of LR-M. We compared the diagnostic performance of conventional LI-RADS and modified LI-RADS criteria for both MRIs. RESULTS: A total of 258 hepatic nodules (194 HCCs, 43 benign lesions, and 21 non-HCC malignancies; median size, 19 mm) were analyzed. By conventional LI-RADS, 47 (18.2%) nodules (31 HCCs and 16 non-HCC malignancies) were categorized as LR-M. The mLR-5C criterion showed superior sensitivity (ECA-MRI, 76.6% vs. 67.0%; HBA-MRI, 60.4% vs. 56.3%; both p < 0.05) while maintaining high specificity (ECA-MRI, 93.8% vs. 98.4%; HBA-MRI, 95.3% vs. 98.4%; both p > 0.05) compared with the LR-5 criterion. Using the mLR-5C criterion, ECA-MRI exhibited higher sensitivity than HBA-MRI (76.6% vs. 60.4%, p < 0.001) and similar specificity (93.8% vs. 95.3%, p > 0.99). CONCLUSION: Our modified LI-RADS achieved superior sensitivity for diagnosing HCC, without compromising specificity compared with LR-5. ECA-MRI showed higher sensitivity in diagnosing HCC than HBA-MRI by applying the mLR-5C for LR-M lesions. KEY POINTS: • By conventional LI-RADS, 31 (16.0%) of 194 HCCs were categorized as LR-M. • Among 31 HCCs categorized as LR-M, 19 HCCs or 8 HCCs were recategorized as HCC on ECA-MRI or HBA-MRI, respectively, after applying the modified LR-5 category, which allocates targetoid lesions with enhancing capsule as mLR-5C instead of LR-M. • The mLR-5C showed superior sensitivity compared with the LR-5 in both MRIs (ECA-MRI, 76.6% vs. 67.0%; HBA-MRI, 60.4% vs. 56.3%, both p < 0.05), while maintaining high specificity (ECA-MRI, 93.8% vs. 98.4%; HBA-MRI, 95.3% vs. 98.4%; both p > 0.05).

EASL versus LI-RADS: Intra-individual comparison of MRI with extracellular contrast and gadoxetic acid for diagnosis of small HCC.

BACKGROUND & AIMS: Liver Imaging Reporting and Data System (LI-RADS) and European Association for the Study (EASL) criteria for hepatocellular carcinoma (HCC) diagnosis have been updated in 2018. We aimed to compare the HCC diagnostic performance of LI-RADS and EASL criteria with extracellular contrast agents-MRI (ECA-MRI) and hepatobiliary agents-MRI (HBA-MRI). METHODS: We prospectively evaluated 179 participants with cirrhosis (n = 105) or non-cirrhotic chronic hepatitis B (CHB) (n = 74) who underwent both ECA-MRI and HBA-MRI before surgery for de novo nodule(s) measuring 10-30 mm. We compared the HCC diagnostic performance of EASL and LR-5 in both MRIs. RESULTS: In an analysis of 215 observations (175 HCCs, 17 non-HCC malignancies and 23 benign lesions) identified from cirrhotic or non-cirrhotic CHB participants, LR-5 with ECA-MRI provided the highest sensitivity (80.7%), followed by EASL with ECA-MRI (76.2%), LR-5 with HBA-MRI (67.3%) and EASL with HBA-MRI (63.0%, all P < .05). The specificities were comparable (89.4%-91.5%). When the analysis is limited to participants with pathological cirrhosis (123 observations), the sensitivity of LR-5 with ECA-MRI was similar to that of EASL with ECA-MRI (82.7% vs 80.2%, P = .156), but higher than LR-5 with HBA-MRI (65.1%) or EASL with HBA-MRI (62.8%, both P < .001), with comparable specificities (87.5%-91.7%). CONCLUSIONS: The LR-5 with ECA-MRI yielded the highest sensitivity with a similar specificity for HCC diagnosis in cirrhosis and non-cirrhotic CHB participants, while the sensitivities of LR-5 and EASL with ECA-MRI are similar for cirrhosis participants. This indicates non-invasive diagnosis criteria can differ by contrast agents and presence of cirrhosis.

Intraductal papillary mucinous neoplasm of the pancreas: diagnostic performance of the 2017 international consensus guidelines using CT and MRI.

OBJECTIVES: To assess the diagnostic performance of the 2017 international consensus guidelines for intraductal papillary mucinous neoplasm (IPMN) of the pancreas and to compare the diagnostic performance and intermodality agreement between contrast-enhanced CT and MRI. METHODS: We retrospectively evaluated patients with surgical resection of IPMN of the pancreas who underwent preoperative CT and MRI between 2009 and 2019. Two radiologists evaluated the clinical and imaging features of IPMN of pancreas according to the 2017 international consensus guideline. Univariable and multivariable analyses were performed to identify significant predictors of malignancy in IPMN. The diagnostic abilities of CT and MRI were compared, and their intermodality agreement was determined. RESULTS: Of 175 patients (mean age, 64 years; 116 males), 88 (50.3%) had malignant IPMN. On multivariable analysis, all three high-risk stigmata (main pancreatic duct [MPD] ≥ 10 mm, mural nodule ≥ 5 mm, and obstructive jaundice) and two worrisome features (MPD 5-9 mm and elevated carbohydrate antigen 19-9) were associated with malignant IPMN on CT and MRI (p < 0.05). A mural nodule < 5 mm on MRI was also associated with malignant IPMN (OR 5.3, p = 0.009). The diagnostic accuracy of high-risk stigmata showed no difference between CT and MRI (73.7% vs. 75.4%, p = 0.505), with good to excellent intermodality agreement. CONCLUSIONS: Current high-risk stigmata had the strongest association with malignant IPMN on CT and MRI. Although MRI is superior to CT for identifying mural nodules, diagnostic performance for differentiating malignant from benign IPMNs was similar between CT and MRI. KEY POINTS: • The current high-risk stigmata in the 2017 International Consensus Guidelines had the strongest association with malignant IPMN on CT and MRI. • MRI is better than CT for identifying enhancing mural nodule. • Diagnostic performance for differentiating malignant from benign IPMNs was similar between CT and MRI.

Magnetic Resonance Imaging With Extracellular Contrast Detects Hepatocellular Carcinoma With Greater Accuracy Than With Gadoxetic Acid or Computed Tomography.

BACKGROUND & AIMS: Computed tomography (CT) and magnetic resonance imaging (MRI) are used to detect hepatocellular carcinoma (HCC). We performed a prospective study to compare the diagnostic performance of CT, MRI with extracellular contrast agents (ECA-MRI), and MRI with hepatobiliary agents (HBA-MRI) in the detection of HCC using the liver imaging reporting and data system (LI-RADS). METHODS: We studied 125 participants (102 men; mean age, 55.3 years) with chronic liver disease who underwent CT, ECA-MRI, or HBA-MRI (with gadoxetic acid) before surgery for a nodule initially detected by ultrasound at a tertiary center in Korea, from November 2016 through February 2019. We collected data on major features and assigned LI-RADS categories (v2018) from CT and MRI examinations. We then compared the diagnostic performance for LR-5 for each modality alone, and in combination. RESULTS: In total, 163 observations (124 HCCs, 13 non-HCC malignancies, and 26 benign lesions; mean size, 20.7 mm) were identified. ECA-MRI detected HCC with 83.1% sensitivity and 86.6% accuracy, compared to 64.4% sensitivity and 71.8% accuracy for CT (P < .001) and 71.2% sensitivity (P = .005) and 76.5% accuracy for HBA-MRI (P = .005); all technologies detected HCC with 97.4% specificity. Adding CT to either ECA-MRI (89.2% sensitivity, 91.4% accuracy; both P < .05) or HBA-MRI (82.8% sensitivity, 86.5% accuracy; both P < .05) significantly increased its diagnostic performance in detection of HCC compared with the MRI technologies alone. ECA-MRI identified arterial phase hyperenhancement in a significantly higher proportion of patients (97.6%) than CT (81.5%; P < .001) or HBA-MRI (89.5%; P = .002). ECA-MRI identified non-peripheral washout in 79.8% of patients, vs 74.2% of patients for CT and 73.4% of patients for HBA-MRI (differences not significant). ECA-MRI identified enhancing capsules in 85.5% of patients, vs 33.9% for CT (P < .001) and 41.4% for HBA-MRI (P < .001). CONCLUSION: In a prospective study of patients with chronic liver disease and a nodule detected by ultrasound, ECA-MRI detected HCC with higher levels of sensitivity and accuracy than CT or HBA-MRI, based on LI-RADS. Diagnostic performance was best when CT was used in combination with MRI compared with MRI alone.

T lymphocytes negatively regulate lymph node lymphatic vessel formation.

Lymph node lymphatic vessels (LNLVs) serve as a conduit to drain antigens from peripheral tissues to within the lymph nodes. LNLV density is known to be positively regulated by vascular endothelial growth factors secreted by B cells, macrophages, and dendritic cells (DCs). Here, we show that LNLV formation was negatively regulated by T cells. In both steady and inflammatory states, the density of LNLVs was increased in the absence of T cells but decreased when T cells were restored. Interferon-γ secretion by T cells suppressed lymphatic-specific genes in lymphatic endothelial cells and consequently caused marked reduction in LNLV formation. When T cells were depleted, recruitment of antigen-carrying DCs to LNs was augmented, reflecting a compensatory mechanism for antigen presentation to T cells through increased LNLVs. Thus, T cells maintain the homeostatic balance of LNLV density through a negative paracrine action of interferon-γ.

Optimisation of the MR protocol in pregnant women with suspected acute appendicitis.

PURPOSE: To investigate the optimal magnetic resonance (MR) imaging protocol in pregnant women suspected of having acute appendicitis. MATERIALS AND METHODS: One hundred and forty-six pregnant women with suspected appendicitis were included. MR images were reviewed by two radiologists in three separate sessions. In session 1, only axial single-shot turbo spin echo (SSH-TSE) T2-weighted images (WI) were included with other routine sequences. In sessions 2 and 3, coronal and sagittal T2WI were sequentially added. The visibility of the appendix and diagnostic confidence of appendicitis were evaluated in each session using a 5-point grading scale. If diseases other than appendicitis were suspected, specific diagnosis with a 5-point confidence scale was recorded. Diagnostic performance for appendicitis and other diseases were evaluated. RESULTS: Twenty-five patients (17.1%) were diagnosed with appendicitis. Among the patients with normal appendix, 28 were diagnosed with other disease. Diagnostic performance including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve values for diagnosing appendicitis and other diseases showed no significant difference among sets for both reviewers (p>0.05). CONCLUSION: Diagnostic performance of MR in pregnant patients with suspected appendicitis can be preserved with omission of sagittal or both coronal and sagittal SSH-T2WI. KEY POINTS: • Diagnostic performance of appendicitis is preserved with omission of sagittal/coronal T2WIs. • Diagnosis of other disease may be sufficient with axial T2WIs only. • Careful serial omission of sagittal and coronal T2WIs can be considered.

Rectal Mucinous Adenocarcinoma: MR Imaging Assessment of Response to Concurrent Chemotherapy and Radiation Therapy-A Hypothesis-generating Study.

Purpose To develop a system for assessment of tumor regression grade (TRG) with magnetic resonance (MR) imaging that is applicable to rectal mucinous adenocarcinoma (RMAC) and to obtain a preliminary evaluation of the association of MR imaging assessment of TRG with response to preoperative concurrent chemotherapy and radiation therapy (CCRT). Materials and Methods This retrospective study was approved by the institutional review board, and informed consent was waived. Pre- and post-CCRT MR images of 59 patients with RMAC (median age, 59 years; range, 29-80 years; 42 men [median age, 59 years; range, 36-80 years] and 17 women [median age, 57 years; range, 29-79 years]) who underwent CCRT and subsequent elective resection from July 2005 to June 2015 were analyzed. Two experienced gastrointestinal radiologists independently analyzed imaging parameters such as T stage, mesorectal fascia status, extramural vascular invasion status, and TRG by using modified criteria developed for assessment of RMAC. Interobserver variability was calculated with weighted κ analysis, and disagreement was settled in consensus. MR imaging TRG results were compared with those from pathologic TRG analysis (Mandard grade). Logistic regression analyses were performed to evaluate associations between imaging parameters and pathologic TRG. Results There was moderate to substantial agreement for imaging parameters (post-CCRT T stage-weighted κ, 0.7134; post-CCRT mesorectal fascia status, 0.618; TRG, 0.5023). Modified MR imaging TRG results were significantly associated with pathologic responsiveness (responsive group, Mandard grade 1 or 2; nonresponsive group, Mandard grades 3-5; P = .023). Results of univariate and multivariate logistic regression analyses indicated that MR imaging TRG was the only factor significantly associated with CCRT responsiveness (univariate analysis, P = .023; multivariate analysis, P = .0261). Conclusion The modified MR imaging assessment of TRG was associated with treatment response to CCRT in patients with RMAC. © RSNA, 2017 Online supplemental material is available for this article.

Use of Imaging to Predict Complete Response of Colorectal Liver Metastases after Chemotherapy: MR Imaging versus CT Imaging.

Purpose To compare the diagnostic performances of contrast agent-enhanced computed tomography (CT) and gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced liver magnetic resonance (MR) imaging (referred to as EOB MR imaging) in the evaluation of disappearing colorectal liver metastases (CRLMs) after chemotherapy. Materials and Methods The eight institutional review boards approved this retrospective study and waived the requirement for informed consent. On the basis of retrospective searches in eight hospitals, 87 patients with 393 CRLMs, each patient with one or more CRLM that later disappeared on contrast-enhanced CT scans after chemotherapy, and subsequently underwent surgery for the CRLMs, were enrolled. The anonymized imaging data and case report forms were sent to the central review system and independently reviewed by four radiologists. All anonymized data were randomly allocated into two groups (groups A and B), which were read by two independent readers. True absence of tumor was defined as pathologic absence of tumor for resected lesions and no in situ recurrence within 1 year after surgery for lesions left unresected at each 3-month follow-up contrast-enhanced CT. Positive predictive values for absence of tumor and for residual tumor on contrast-enhanced CT and EOB MR images were compared by using a generalized estimating equation. Results Among 393 CRLMs, the positive predictive value for absence of tumor on EOB MR images (78.0%; 95% confidence interval [CI]: 63.68%, 87.74%) was significantly higher than that on contrast-enhanced CT scans (35.2%; 95% CI: 25.11%, 46.79%; P < .001). The positive predictive value for residual tumor on CT scans (86.0%; 95% CI: 78.61%, 91.16%) was higher than that on EOB MR images (83.8%; 95% CI: 77.50%, 88.67%) without statistical significance (P = .330). Conclusion EOB MR imaging was superior to contrast-enhanced CT imaging for assessment of disappearing CRLMs after chemotherapy. © RSNA, 2017 Online supplemental material is available for this article.

Feasibility of 3D navigator-triggered magnetic resonance cholangiopancreatography with combined parallel imaging and compressed sensing reconstruction at 3T.

PURPOSE: To assess the feasibility of 3D navigator-triggered magnetic resonance cholangiopancreatography (MRCP) with combined parallel imaging (PI) and compressed sensing (CS). MATERIALS AND METHODS: With Institutional Review Board approval, 30 consecutive patients who underwent MRCP for suspected pancreaticobiliary disease were prospectively recruited. All patients underwent 3D navigator-triggered MRCP with conventional PI alone, and with combined PI and CS using a 3T machine. The acquisition time and relative duct-to-periductal contrast ratios (RCs) at three biliary segments were quantitatively compared between the two MRCP methods. Qualitative image parameters were independently evaluated by two blinded radiologists, and were compared between two methods using the Wilcoxon signed-rank test. RESULTS: The mean acquisition time of MRCP with combined PI and CS (131.87 ± 33.60 sec) was significantly shorter compared with that of MRCP with PI (253.63 ± 56.08 sec; P < 0.001). The RC obtained using MRCP with combined PI and CS at two segments was slightly lower compared to that obtained using MRCP with PI (P = 0.007 and 0.002). Both reviewers found no significant differences in duct visualization, overall image quality, and degree of artifacts between the two methods (P ≥ 0.063; P = 0.637; and P = 0.752, respectively). Lesion conspicuity and confidence in duct abnormalities were comparable between two MRCP methods in both readers (P = 0.564 and P > 0.999). CONCLUSION: Combined PI and CS reconstruction is feasible for 3D navigator-triggered MRCP, providing image quality comparable to that of MRCP with PI alone, in about half the acquisition time. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1289-1297.

Lack of anti-tumor activity by anti-VEGF treatments in hepatic hemangiomas.

Recently, anti-vascular endothelial growth factor (anti-VEGF) agents have been described in the literature as a valid treatment option for symptomatic liver hemangiomas, but only limited evidence supports this notion. The purpose of this study was to elucidate whether or not the administration of anti-VEGF agents can reliably achieve a size reduction in liver hemangiomas. We examined patients with incidental hemangiomas who received anti-angiogenic agents for the treatment of other malignancies. Our study population consisted of 17 colorectal cancer patients and one lung cancer patient carrying 21 hemangiomas who received bevacizumab, and seven renal cell carcinoma patients carrying nine hepatic hemangiomas who received sunitinib. We have measured the liver hemangioma volume on both the pre-treatment and post-treatment computed tomography images and then calculated the volume alteration rates. No statistically significant difference (P = 0.365) in the volume of the liver hemangiomas was observed before (1.1-168.8 cm(3); mean ± SD 19.8 ± 39.7 cm(3)) or after (1.2-163.6 cm(3); 19.3 ± 38.0 cm(3)) bevacizumab treatment. The volume reduction rate ranged from -35.0 to 11.2 % (mean ± SD -1.3 ± 10.8 %). The sunitinib treatment group also showed no statistically significant difference (P = 0.889) in hemangioma volume before (1.2-6.5 cm(3); 3.0 ± 1.8 cm(3)) or after (1.2-6.0 cm(3); 3.0-1.7 cm(3)) treatment. The volume reduction rate ranged from -13.3 to 7.7 % (median: mean ± SD -2.5 ± 6.6 %). We did not observe liver hemangioma shrinkage after bevacizumab or sunitinib treatment. Our data do not support the application of anti-VEGF agents for the treatment of hepatic hemangiomas.

Antiangiogenic Therapy Induces Hepatic Tumor Vascular Network Rearrangement to Receive Perfusion via the Portal Vein and Hepatic Artery.

PURPOSE: Hepatic malignancies can easily develop resistance to antiangiogenic therapy, but the underlying mechanism remains poorly understood. This study explores whether antiangiogenic therapy influences the tumor vascular network and/or the vessels feeding the hepatic tumor. METHODS: Mice implanted with Lewis lung carcinoma (LLC) cells were subcutaneously injected 3 times (once every other day starting 1 week after LLC implantation) with either an antiangiogenic agent [vascular endothelial growth factor (VEGF)-Trap] or control agent (bovine serum albumin) at a dose of 25 mg/kg before performing angiography. Hepatic arteriography and portography were performed using a vascular cast method with vascular latex. RESULTS: Arteriography of the control-treated LLC-implanted mice showed marked staining of the mass with a prominent feeding artery, suggesting that the tumor is supplied by arterial perfusion. No significant staining was observed on portography. By contrast, 33% (n = 3/9) of the LLC-implanted mice treated with the antiangiogenic agent VEGF-Trap showed intratumoral staining during portography, indicating that these tumors received perfusion via the portal vein. CONCLUSION: Antiangiogenic treatment can induce rearrangement of the hepatic tumor vascular network to establish communication with the portal vein. This implies that hepatic tumors can develop resistance to antiangiogenic therapy by maintaining perfusion through portal venous perfusion.

Fluorescent iodized emulsion for pre- and intraoperative sentinel lymph node imaging: validation in a preclinical model.

PURPOSE: To validate the usefulness of a newly developed tracer for preoperative gastric sentinel lymph node (LN) (SLN) mapping and intraoperative navigation after a single preoperative submucosal injection in rat and beagle models. MATERIALS AND METHODS: This study was approved by the Experimental Animal Ethical Committee of Yonsei University College of Medicine according to the eighth edition of the Guide for the Care and Use of Laboratory Animals published in 2011. An emulsion was developed that contained indocyanine green in iodized oil, which can be visualized with both computed tomography (CT) and near-infrared (NIR) optical imaging and has the property of delayed washout. This emulsion was injected into the footpad of rats (n = 6) and the gastric submucosa of beagles (n = 8). CT lymphography was performed. The degree of enhancement of popliteal LNs was measured in rats, and the enhancing LNs were identified and the degree of enhancement of the enhancing LNs was measured in beagles. Next, NIR imaging was performed in beagles during open, laparoscopic, and robotic surgery to identify LNs containing the fluorescent signals of indocyanine green. The enhanced LNs detected with CT lymphography and NIR imaging were matched to see if they corresponded. RESULTS: Preoperative CT lymphography facilitated SLN mapping, and 26 SLNs were identified in eight beagles. NIR imaging enabled high-spatial-resolution visualization of both SLNs and the intervening lymphatic vessels and was useful for intraoperative SLN navigation. CONCLUSION: SLN mapping with fluorescent iodized oil emulsion is effective and feasible for both CT and NIR imaging.

Regulation and implications of inflammatory lymphangiogenesis.

Lymphatic vessels (LVs) are highly dynamic structures that intimately interact with their surrounding microenvironment. They have a profound influence on the immune system and therefore can manipulate inflammatory processes. Inflammation is a major cause of adulthood lymphangiogenesis and LV remodeling. In turn, LVs can reciprocally manipulate inflammatory processes. For instance, LV growth and/or activation regulate antigen presentation and inflammatory cell recruitment to lymph nodes (LNs), and therefore critically affect adaptive immunity. The vascular endothelial growth factor (VEGF)-C-VEGF receptor-3 and VEGF-A-VEGF receptor-2 signaling pathways are particularly important in inflammatory lymphangiogenesis. LVs contribute to the pathophysiology of various inflammatory conditions. Knowledge of lymphatic biology can be applied to manipulate inflammatory disorders and divert immune responses. This review summarizes basic concepts of inflammation-relevant lymphatic biology, and describes recent progress and practical implications.

MRI-detected extramural vascular invasion is an independent prognostic factor for synchronous metastasis in patients with rectal cancer.

OBJECTIVES: To determine whether magnetic resonance imaging (MRI)-detected extramural vascular invasion (EMVI) could predict synchronous distant metastases in rectal cancer. METHODS: Patients who underwent rectal MRI between July 2011 and December 2012 were screened. This study included 447 patients with pathologically confirmed rectal adenocarcinoma who had undergone MRI without previous treatment. Distant metastases were recorded at the initial work-up and over a 6-month follow-up. Univariate/multivariate logistic regression models were used to determine the risk of metastasis. The diagnostic performance was calculated using pathologic lymphovascular invasion (LVI) as a gold standard. RESULTS: Among 447 patients, 79 patients (17.7 %) were confirmed to have distant metastases. Three MRI features are significantly associated with a high risk of distant metastasis: positive EMVI (odds ratio 3.02), high T stage (odds ratio 2.10) and positive regional lymph node metastasis (odds ratio 6.01). EMVI in a large vessel (≥3 mm) had a higher risk for metastasis than EMVI in a small vessel (<3 mm). Sensitivity, specificity and accuracy of MRI-detected EMVI were 28.2 %, 94.0 % and 80.3 %, respectively. CONCLUSIONS: MRI-detected EMVI is an independent risk factor for synchronous metastasis in rectal cancer. EMVI in large vessels is a stronger risk factor for distant metastasis than EMVI in small vessels. KEY POINTS: • EMVI, LN metastasis and T staging on MRI are risk factors for metastasis. • EMVI in large vessels has greater risk for metastasis than in small vessels. • Regional LN metastasis on MRI has highest risk for predicting metastasis. • MR findings could be helpful for selecting patients at high risk for metastasis.

Use of Preoperative MRI to Select Candidates for Local Excision of MRI-Staged T1 and T2 Rectal Cancer: Can MRI Select Patients With N0 Tumors?

BACKGROUND: To minimize the recurrence rate after local excision of rectal cancer, the false-negative rate of nodal staging should be minimized. OBJECTIVE: The purpose of this study was to develop a set of criteria using preoperative MRI that would minimize the false-negative rate for the diagnosis of regional lymph node metastasis. DESIGN: A prospectively maintained colorectal cancer database and MRI images were retrospectively reviewed. SETTINGS: This study was conducted at a multidisciplinary tertiary center. PATIENTS: A total of 246 consecutive patients who underwent MRI and curative-intent surgery for MRI-staged T1/T2 rectal cancer from January 2008 to July 2012 were included. MAIN OUTCOME MEASURES: MRI features significantly associated with lymph node metastasis were identified using a χ test. Five diagnostic criteria for lymph node metastasis were created based on these predictive MRI features, and their false-negative rates were compared using the generalized estimating equation method. RESULTS: Small size/homogeneity of lymph nodes and no visible tumor/partially involved muscular layer were significantly associated with lower risks of lymph node metastasis. When tumor invasion depth was not considered, the false-negative rate did not decrease below 10%, even when the strictest criterion for morphologic evaluation of lymph nodes (not visible or <3 mm) was used. Adding invasion depth to the diagnostic criteria significantly decreased the false-negative rate as low as 1.8%. LIMITATIONS: This study is limited by its small sample size and retrospective nature. CONCLUSIONS: Assessing both the depth of tumor invasion and lymph node morphology may reduce the false-negative rate and can be helpful to better identify candidates suitable for local excision of early stage rectal cancer. However, strict MRI criteria for oncologic safety might result in considerable false-positive cases and limit the application of local excision.

The spatiotemporal development of adipose tissue.

Adipose tissue is a structure highly specialized in energy storage. The adipocyte is the parenchymal component of adipose tissue and is known to be mesoderm or neuroectoderm in origin; however, adipocyte development remains poorly understood. Here, we investigated the development of adipose tissue by analyzing postnatal epididymal adipose tissue (EAT) in mouse. EAT was found to be generated from non-adipose structure during the first 14 postnatal days. From postnatal day 1 (P1) to P4, EAT is composed of multipotent progenitor cells that lack adipogenic differentiation capacity in vitro, and can be regarded as being in the 'undetermined' state. However, the progenitor cells isolated from P4 EAT obtain their adipogenic differentiation capacity by physical interaction generated by cell-to-matrix and cell-to-cell contact both in vitro and in vivo. In addition, we show that impaired angiogenesis caused by either VEGFA blockade or macrophage depletion in postnatal mice interferes with adipose tissue development. We conclude that appropriate interaction between the cellular and matrix components along with proper angiogenesis are mandatory for the development of adipose tissue.

Dynamic enhancement pattern of HCC smaller than 3 cm in diameter on gadoxetic acid-enhanced MRI: comparison with multiphasic MDCT.

BACKGROUND & AIMS: The dynamic enhancement pattern of HCCs smaller than 3 cm in diameter on gadoxetic acid-enhanced magnetic resonance imaging (MRI) have not been extensively investigated. We aimed to evaluate the dynamic enhancement patterns of small HCCs (≤3 cm) on gadoxetic acid-enhanced magnetic resonance imaging (MRI) and compare enhancement patterns with multiphasic multidetector computed tomography (MDCT) based on tumour cellular differentiation and size. METHODS: We retrospectively included 55 patients with 67 surgically confirmed small HCCs (≤3 cm) who underwent multiphasic MDCT and gadoxetic acid-enhanced MRI. Dynamic enhancement patterns were analysed according to tumour cellular differentiation and size. Hepatobiliary phase images were also analysed to assess their additional value. RESULTS: The proportion of small HCCs demonstrating the typical enhancement pattern differed depending on tumour cellular differentiation on both MRI (P = 0.001) and MDCT (P = 0.001), but differed depending on tumour size only on CT (P = 0.008). Gadoxetic acid-enhanced MRI more sensitively depicted the typical enhancement pattern than CT for all tumours (P = 0.001), for moderately or poorly differentiated HCCs (P = 0.021) and for HCCs ≤2 cm (P = 0.001). 80% of tumours with atypical enhancement could be diagnosed as HCC based on tumour size and hepatobiliary phase images. CONCLUSIONS: On both gadoxetic acid-enhanced MRI and multiphasic CT, the dynamic enhancement patterns of small HCCs (≤3 cm) differed according to tumour cellular differentiation. Gadoxetic acid-enhanced MRI more frequently demonstrated the typical HCC enhancement pattern than CT in small HCCs.