Prediction of Efficacy for Atezolizumab/Bevacizumab in Unresectable Hepatocellular Carcinoma with Hepatobiliary-Phase Gadolinium Ethoxybenzyl-Diethylenetriaminepentaacetic Acid MRI.

BACKGROUND: This study aimed to examine whether the coefficient of variation (CV) in the hepatobiliary-phase (HBP) of Gd-EOB-DTPA-MRI could be an independent predictive factor for tumor progression. METHODS: Patients who underwent Gd-EOB-DTPA-MRI before Atezolizumab/bevacizumab therapy at six affiliated institutions between 2018 and 2022 were included. CV for each patient was calculated as the mean value for up to five tumors larger than 10 mm, and CV of the whole tumor was calculated using LIFEx software. The tumor response was evaluated within 6-10 weeks. The primary endpoint was to investigate the predictive factors, including CV, related to tumor progression using logistic regression analysis. The secondary endpoints were tumor response rate and progression-free survival (PFS) based on CV. RESULTS: Of the 46 enrolled patients, 13 (28.3%) underwent early progressive disease. Multivariate analysis revealed that a high CV (≥0.22) was an independent predictive factor for tumor progression (p = 0.043). Patients with a high CV had significantly frequent PD than those with a low CV (43.5 vs. 13.0%, p = 0.047). Patients with a high CV tended to have shorter PFS than those with a low CV (3.5 vs. 6.7 months, p = 0.071). CONCLUSION: Quantitative analysis using CV in the HBP of Gd-EOB-DTPA-MRI may be useful for predicting tumor progression for atezolizumab/bevacizumab therapy.

Effects of Short-Term Lenvatinib Administration Prior to Transarterial Chemoembolization for Hepatocellular Carcinoma.

AIM: Transarterial chemoembolization (TACE) combined with lenvatinib, employing a 4-day lenvatinib administration followed by TACE without an interval (short-term LEN-TACE), was performed for hepatocellular carcinoma (HCC). The aim was to assess tumor hemodynamics following the 4-day lenvatinib and to evaluate the treatment outcomes after the short-term LEN-TACE. METHODS: 25 unresectable HCC patients received this combined therapy. Lenvatinib (4-12 mg) was administrated for 4 days prior to TACE. Perfusion CT scans were obtained before and after the lenvatinib administration. Either cTACE (76%) or DEB-TACE (24%) were performed. RESULTS: intra-tumor blood flow significantly decreased after the 4-day lenvatinib (p < 0.05). The TACE procedure was successful with no severe adverse events in all patients. The overall complete response (CR) rate was 75% (cTACE 84%, DEB-TACE 40%). The lipiodol-washout ratio between 1 week and 4 months after cTACE correlated with the arterial flow reduction ratio by lenvatinib prior to TACE (r = -0.55). The 12-month progression-free survival (PFS) rate was 75.0%. CONCLUSIONS: The short-term LEN-TACE is feasible and safe, demonstrating promising outcomes with a high CR ratio, contributing to lipiodol retention in the tumor after cTACE, and extended PFS. To confirm the advantages of this treatment protocol, a prospective clinical trial is mandatory.

Multimodality Imaging of Primary Hepatic Lymphoma: A Case Report and a Literature Review.

Primary hepatic lymphoma (PHL) is a rare form of non-Hodgkin lymphoma primarily affecting the liver. We present a case of an 84-year-old man diagnosed with PHL, incidentally detected during abdominal ultrasonography. The ultrasonography showed a hypoechoic nodule. When examined by CEUS, the nodule showed hyperenhancement in the arterial phase and hypoenhancement in the portal and late phases. Conversely, CECT demonstrated hypoenhancement through all the phases. The patient declined a tumor biopsy and opted for follow-up care. Ten months later, the lobular mass had increased from 15 mm to 65 mm, presenting as hypoechogenic and demonstrating the "vessel-penetrating sign" on color Doppler imaging. CEUS revealed reticulated enhancement, indicating intratumoral vessels. The mass displayed hypoattenuation on plain CT, hypointensity in T1-weighted images, and hyperintensity in T2-weighted images and exhibited significant restriction in diffusion-weighted images. Both CECT and contrast-enhanced MRI exhibited hypoenhancement. The patient underwent a partial hepatic segmentectomy, and the mass was pathologically diagnosed as a diffuse large B-cell lymphoma. Subsequent postoperative radiological examinations revealed no other lesions, confirming the diagnosis of PHL. Our report highlights specific ultrasonographic signs of PHL observed from an early stage and presents a review of the relevant literature.

Predictive Factors of Complete Response to Transarterial Chemoembolization in Intermediate Stage Hepatocellular Carcinoma beyond Up-To-7 Criteria.

AIM: To clarify the prognosis and identify predictors for obtaining a complete response (CR) by transarterial chemoembolization (TACE) in intermediate stage HCC beyond up-to-7 criteria. METHODS: Of the 120 patients with intermediate stage HCC who were treated by TACE as the initial treatment from February 2007 to January 2016, 72 finally matched the following inclusion criteria: beyond up-to-7 criteria; Child-Pugh score under 7; and no combined therapy within 4 weeks after the initial TACE. The CR rate and overall survival (OS) were evaluated. Logistic regression analysis was performed to identify predictors of CR. The deterioration of liver function after TACE was also evaluated. RESULTS: The CR rate was 56.9%, and the overall median survival time (MST) was 37.7 months. The MST was 38.7 months in the CR group and 28.0 months in the non-CR group (p = 0.018). HCC within up-to-11 criteria was the only predictor of CR. The CR rate and MST were 70.7% and 37.7 months, respectively, in patients with HCC within up-to-11 criteria and 38.7% and 32.7 months, respectively, in the patients beyond up-to-11 criteria. Deterioration of the Child-Pugh score after the initial TACE and the 2nd TACE occurred in 24.2% and 12.0%, respectively, and deterioration of the modified albumin-bilirubin (mALBI) grade occurred in 17.6% and 7.4%, respectively. CONCLUSION: TACE can achieve high CR rates with prolonged overall survival for intermediate stage HCC beyond up-to-7 criteria. The predictor of CR was within up-to-11 criteria. Deterioration of liver function was not severe, but requires caution. Multidisciplinary approach as additional treatment after TACE is important.

Vascular Normalization Caused by Short-Term Lenvatinib Could Enhance Transarterial Chemoembolization in Hepatocellular Carcinoma.

We describe the clinical effects of short-term lenvatinib administration prior to conventional transarterial chemoembolization (cTACE) on tumor vasculature. Two patients with unresectable hepatocellular carcinoma underwent high-resolution digital subtraction angiography (DSA) and perfusion four-dimensional computed tomography during hepatic arteriography (4D-CTHA) before and after administration of lenvatinib treatment. The doses and periods of lenvatinib administration were, respectively, 12 mg/day for 7 days and 8 mg/day for 4 days. In both cases, high-resolution DSA revealed a decrease in dilatation and tortuosity of the tumor vessels. Furthermore, the tumor staining became more refined, and newly formed tiny tumor vessels were observed. Perfusion 4D-CTHA revealed a decrease in arterial blood flow to the tumor by 28.6% (from 487.9 to 139.5 mL/min/100 mg) and 42.5% (from 288.2 to 122.6 mL/min/100 mg) in the two cases, respectively. The cTACE procedure resulted in good lipiodol accumulation and complete response. Patients have remained recurrence-free for 12 and 11 months after the cTACE procedure, respectively. The administration of short-term lenvatinib in these two cases resulted in the normalization of tumor vessels, which likely led to improved lipiodol accumulation and a favorable antitumor effect.

Quantitative Analysis of Signal Heterogeneity in the Hepatobiliary Phase of Pretreatment Gadoxetic Acid-Enhanced MRI as a Prognostic Imaging Biomarker in Transarterial Chemoembolization for Intermediate-Stage Hepatocellular Carcinoma.

BACKGROUND: In the era of local and systemic therapies for intermediate-stage hepatocellular carcinoma (HCC), personalized therapy has become available. The aim of our study was to evaluate the usefulness of quantitative analysis of pretreatment gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) to predict prognosis following transarterial chemoembolization (TACE). METHODS: This retrospective study included patients with treatment-naïve intermediate-stage HCC who underwent EOB-MRI before the initial TACE and were treated by initial TACE between February 2007 and January 2016. Signal heterogeneity in the hepatobiliary phase (HBP) of EOB-MRI was quantitatively evaluated by the coefficient of variation (CV). The cutoff CV value was determined using the Classification and Regression Tree algorithm. RESULTS: A total of 64 patients were enrolled. In multivariate analysis, High CV (≥0.16) was significantly associated with poor prognosis (p = 0.038). In a subgroup analysis of patients within up-to-7 criteria, MST was significantly shorter in the High CV group than in the Low CV group (37.7 vs. 82.9 months, p = 0.024). In patients beyond up-to-7 criteria, MST was 18.0 and 38.3 months in the High CV and Low CV groups, respectively (p = 0.182). In both groups scanned at 1.5 T or 3.0 T, High CV was significantly associated with poor prognosis (p = 0.001 and 0.003, respectively). CONCLUSION: CV of the tumor in the HBP of EOB-MRI is a valuable prognostic factor of TACE.

The diagnostic challenge of non-traumatic bladder rupture: a pictorial essay.

Non-traumatic bladder rupture (NTBR) is relative rare pathology including spontaneous rupture and iatrogenic injury. As increasing the medical intervention for the pelvic malignancy or elderly population, NTBR will be encountered more frequently. There are few previous studies summarizing the imaging features of NTBR. We reviewed imaging characteristics of 18 previous cases of NTBR experienced. In addition, 3 presentative cases that can be a pitfall to differentiate from NTBR. The aim of this article is to clarify the key CT findings of NTBR and its pitfalls.

Schwannoma in and around the porta hepatis: radiological features in eight cases and literature review.

PURPOSE: Schwannomas in and around the porta hepatis (porta hepatic schwannomas) are rare benign tumors easily misdiagnosed as other pathologies, including malignancies. We aimed to evaluate their imaging features on ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), and 18F-fluorodeoxyglucose-positron emission tomography/CT (FDG-PET/CT). METHODS: We performed a multi-institutional retrospective study by reviewing the clinical and imaging findings of pathologically proven eight porta hepatic schwannomas (mean age, 55 years; range, 38-80 years; one male and seven females). Preoperative imaging included three ultrasonography, eight CT, eight MRI, and two FDG-PET/CT. RESULTS: All patients were asymptomatic. The mean tumor size was 61.9 mm (range, 30-180 mm), and all tumors demonstrated well-defined lesions on ultrasonography and their solid components showed soft tissue attenuation on non-contrast CT. MRI showed two distinct components in all cases: the component with T1-weighted hypointensities and T2-weighted hyperintensities with poor enhancement (suggestive of Antoni B histology); the component with T2-weighted hypointensities with gradually increasing enhancement (suggestive of Antoni A histology), resulting in a heterogeneous pattern on post-contrast CT or MRI (8/8, 100%). The separated deviation of surrounding bile ducts and vessels without obstruction allowed the recognition of extrahepatic localization and their benign nature. A ginger root-like morphology (2/8, 25%) seemed to be suggestive of extension along the Glisson's sheath, although this finding was not seen frequently. CONCLUSION: Recognizing imaging features such as extrahepatic location, benign nature with internal structures suggestive of Antoni A/B histology, and characteristic tumor extension may provide key diagnostic clues for porta hepatic schwannomas.

Staged surgical repair for extensive cardiovascular damage by syphilis.

A 45-year-old man had aortic regurgitation with a syphilitic true aneurysm of the ascending to transverse arch aorta and a descending aortic aneurysm from chronic Stanford type B aortic dissection. After antibiotic therapy, two-staged surgical repair was performed and there has been no evidence of recurrence in 12 months since the second stage. We describe the successful management of extensive cardiovascular syphilitic damage.

Ratio of early transmitral velocity to lateral mitral annular early diastolic velocity has the best correlation with wedge pressure following cardiac surgery.

BACKGROUND: Although previous investigators reported that mitral annular velocity predicts mean pulmonary capillary wedge pressure (PCWP), it is unknown whether the lateral or septal mitral annular velocity more faithfully predicts PCWP after cardiac surgery. METHODS AND RESULTS: To assess the effect of cardiac surgery on the predictive values for PCWP by measuring mitral annular velocity, 52 consecutive patients undergoing cardiac surgery were studied. All patients underwent transthoracic echocardiography and right-sided cardiac catheterization both before and after surgery. The peak early diastolic velocity of transmitral flow (E) was measured by pulsed-wave Doppler and the peak early diastolic velocities of the lateral (LEa) and septal (SEa) mitral annulus by pulsed-wave tissue Doppler imaging. The ratios of E to LEa (E/LEa) and SEa (E/SEa) were calculated. Immediately after echocardiography, PCWP was measured using a balloon-tipped pulmonary artery catheter. After surgery, LEa was significantly increased (6.4+/-2.7 vs 8.6+/-3.3 cm/s, p<0.001), but SEa was unchanged (6.0+/-2.5 vs 5.5+/-2.3 cm/s, p=0.09). E/LEa correlated well with PCWP both before and after surgery (r=0.79 and r=0.69, respectively, p<0.001). Although E/SEa correlated well before surgery (r=0.67, p<0.001), it correlated only weakly after surgery (r=0.44, p<0.01). CONCLUSIONS: E/LEa has the best correlation with PCWP both before and after cardiac surgery and may be more useful than E/SEa in the noninvasive estimation of PCWP.

Augmentation of left ventricular apical endocardial rotation with inotropic stimulation contributes to increased left ventricular torsion and radial strain in normal subjects: quantitative assessment utilizing a novel automated tissue tracking technique.

BACKGROUND: The difference in the left ventricular (LV) torsion of the endo- and epicardium (Endo, Epi) with inotropic stimulation and its relation to radial strain (RS) remain unclear. METHODS AND RESULTS: LV basal and apical short-axis images were recorded in 13 normal subjects at rest and during dobutamine infusion (5, 10 microg x kg (-1) x min(-1)). A total of 8 points (anterior, lateral, posterior and septum in both Endo and Epi) were manually placed by 2-dimensional tissue tracking technique and the movement of these points during a cardiac cycle was tracked, after which the rotation angles and RS were calculated. LV torsion was defined as the net difference between the basal and apical rotations. In the LV apex, Endo-rotation increased (7.8+/-2.7 to 14.1+/-4.6 degrees, p<0.01), whereas Epi-rotation was unchanged, with dobutamine. The apical Endo-rotation was significantly greater than the Epi-rotation, although no difference was seen between the Endo and Epi in the LV base throughout the study. During dobutamine infusion, the LV Endo-torsion increased (9.5+/-2.8 to 19.3+/-4.8 degrees, p<0.01) and these values were greater than those for Epi. The apical RS increased with the dobutamine dose (39.0+/-9.3 to 61.9+/-15.5%, p<0.01), whereas basal RS initially increased at 5 microg x kg(-1) x min(-1), but thereafter showed no further increase at 10 microg x kg(-1) x min(-1) of dobutamine. CONCLUSIONS: Augmentation of LV rotation with inotropism was clearly observed in the apical Endo, thus causing increased LV endo-torsion and apical RS.

Usefulness of mitral annular velocity in predicting exercise tolerance in patients with impaired left ventricular systolic function.

Left ventricular (LV) diastolic function is 1 of the determinants of exercise tolerance. However, the relation between early diastolic velocity of the mitral annulus (Ea) obtained by tissue Doppler imaging and exercise tolerance is unknown in patients with impaired LV systolic function. To investigate the feasibility of evaluating exercise tolerance using tissue Doppler imaging, we studied 53 consecutive patients (mean age 58 +/- 14 years) with a LV ejection fraction of <50% (mean 37 +/- 9%). We measured the peak early diastolic velocity of transmitral flow (E) and Ea at the lateral border of the mitral annulus and then calculated the E/Ea ratio. After echocardiography, we measured the peak oxygen consumption and anaerobic threshold (AT) by cardiopulmonary exercise testing. Of all the echocardiographic parameters, the best correlation for AT was the E/Ea ratio (r = -0.74, p <0.001). Peak oxygen consumption correlated well with Ea and the E/Ea ratio (r = 0.64 and r = -0.68, respectively, p <0.001). The AT and peak oxygen consumption did not correlate with conventional Doppler indexes. Using an AT of 8 ml/min/kg as the cutoff to separate severe exercise intolerance from normal, mild, or moderate exercise intolerance, a receiver-operating characteristic curve showed that an E/Ea ratio of >11.3 had the best combination of sensitivity (88%) and specificity (86%). Exercise tolerance correlated with the E/Ea ratio in patients with impaired LV systolic function. In conclusion, the evaluation of LV diastolic function using tissue Doppler imaging is useful for predicting exercise tolerance in patients with heart failure.

Aging and transmitral flow pattern in patients with systemic hypertension.

PURPOSE: Currently, the transmitral flow (TMF) pattern is routinely recorded as the first step in the assessment of left ventricular diastolic function. In young, healthy subjects, it is known that the early diastolic flow (E wave) of TMF is larger than the late diastolic flow (A wave). The E/A ratio then gradually decreases with age. This change in the pattern of TMF can be expected to occur earlier in patients with systemic hypertension than in healthy subjects. However, data pertaining to this matter are limited for Japanese patients. The purpose of this study was to investigate the changing pattern of TMF with age in Japanese patients with systemic hypertension. METHODS: A database of echocardiographic examination reports was surveyed. A total of 553 patients with systemic hypertension (HT group) and 394 patients without hypertension or organic heart disease (control group) were included in this study. The patients were subdivided according to age, after which the E/A ratio was compared for different patient categories and age groups. RESULTS: The E/A ratio gradually decreased with age in the control group, and the mean value of E/A was <1 in the sixth decade. On the other hand, the E/A ratio rapidly decreased and was <1 in the fifth decade in the HT group. CONCLUSION: In patients in the HT group, the E/A ratio decreased about a decade earlier compared with patients in the control group.

Bosentan inhibits transient receptor potential channel expression in pulmonary vascular myocytes.

Bosentan, a dual endothelin receptor blocker, has been used clinically to treat idiopathic pulmonary arterial hypertension (IPAH). However, the mechanism of its antiproliferative effect on pulmonary artery smooth muscle cells (PASMCs) remains unclear. A rise in cytoplasmic Ca2+ stimulates PASMC proliferation and the canonical transient receptor potential (TRPC) channels are an important pathway for Ca2+ entry during PASMC proliferation. Bosentan (20-50 microM) significantly inhibited endothelin-1- or platelet-derived growth factor (PDGF)-mediated PASMC growth and [3H]thymidine uptake. In PASMCs, endothelin-1 (1 microM) and PDGF (10 ng/ml) both upregulated protein expression of TRPC6, whereas bosentan markedly downregulated TRPC6 protein levels. Furthermore, TRPC6 expression in PASMCs from patients with IPAH was greater than in normal PASMCs, and the antiproliferative effect of bosentan was significantly enhanced in IPAH-PASMCs in comparison with normal PASMCs. These observations demonstrate that the antiproliferative effect of bosentan on PASMCs involves the downregulation of TRPC6 channels via a mechanism possibly independent of endothelin receptor blockade. The greater effect of bosentan on IPAH-PASMCs than on normal PASMCs suggests that increased TRPC6 expression and function may be involved in the overgrowth of PASMCs in patients with IPAH.

Effects of glycoprotein IIb/IIIa inhibition on microvascular flow after coronary reperfusion. A quantitative myocardial contrast echocardiography study.

OBJECTIVES: We assessed the effect of glycoprotein IIb/IIIa inhibition (GPI) on microvascular flow after coronary occlusion/reperfusion using quantitative myocardial contrast echocardiography (QMCE). BACKGROUND: Platelets may play a major role in the dissociation of epicardial artery recanalization and tissue-level reperfusion, referred to as the "no-reflow phenomenon." Therefore, GPI might improve myocardial reperfusion, distinct from its effects on epicardial patency.T METHOD: hree-hour occlusion of the left anterior descending coronary artery (LAD) was followed by 3-h reperfusion in 16 open-chest dogs: 8 controls and 8 given a continuous infusion of the GPI tirofiban, starting 45 min before LAD reopening. Perfusion of the LAD bed was quantified by the rate of intensity rise (b) by QMCE; myocardial blood flow (MBF) was assessed by fluorescent microspheres. RESULTS: No differences in b or MBF were observed within the risk area between the control and GPI groups at baseline or occlusion. However, b and MBF were higher in GPI dogs than in controls during reperfusion, despite similar epicardial flow (p < 0.05 at 30, 60, and 90 min; p = NS at 180 min). Infarct area size was significantly reduced in GPI dogs compared with non-treated dogs (26.9 +/- 10.5% vs. 49.0 +/- 11.1% of at-risk area, respectively). CONCLUSIONS: As demonstrated by QMCE, GPI improves microvascular flow and reduces the infarct area after coronary occlusion/reperfusion, independent of epicardial flow. These data demonstrate the usefulness of QMCE in assessing microvascular flow, provide novel evidence for the role of platelets in the early phase of reperfusion injury, and show that GPI is of value in preserving microvascular perfusion after coronary reperfusion.

Visualization of risk-area myocardium as a high-intensity, hyperenhanced "hot spot" by myocardial contrast echocardiography following coronary reperfusion: quantitative analysis.

OBJECTIVES: We examined whether delayed post-injection imaging of a new ultrasound contrast agent (BR-14) could produce prolonged opacification and hyperenhancement of myocardium subjected to coronary occlusion/reperfusion. BACKGROUND: We hypothesized that ultrasound exposure destroyed BR-14 and eliminated visualization of sustained myocardial opacification from retained microbubbles. METHODS: We studied eight open-chest dogs with 3 h of left anterior descending coronary artery (LAD) occlusion followed by 3 h of reperfusion. Myocardial contrast echocardiography (MCE) was performed before occlusion and 120 min after the onset of both occlusion and reperfusion. Ultrasound imaging was initiated 15 min after injection. Myocardial blood flow (MBF) was assessed by microspheres. RESULTS: Pre-occlusion images revealed uniform opacification of left ventricular myocardium greater than that of the cavity, with a mean intensity of the LAD bed of 8.66 +/- 1.38 dB. During occlusion, MCE resulted in the appearance of a perfusion defect in the LAD risk area (intensity 2.08 +/- 1.10 dB). After 120 min of reperfusion, the LAD risk-area myocardium manifested dense opacification of a higher intensity ("hot spot") than baseline (13.7 vs. 8.7 dB), but with reduced MBF consistent with accumulation of a high concentration of microbubbles. Increased MCE intensity was associated with a greater myeloperoxidase score. CONCLUSIONS: These data establish that contrast opacification by BR-14 may be selectively retained within the perfusion bed of a coronary artery subjected to occlusion/reperfusion. Such opacification exhibits defects with occlusion, manifests hyperenhanced intensity (hot spot) with reperfusion, is associated with the level of myeloperoxidase activity, and conforms to the area of myocardium subjected to altered flow.