Contrast-Enhanced Ultrasound and Conventional Ultrasound Characteristics of Breast Cancer With Different Molecular Subtypes.

BACKGROUND: Identifying molecular subtypes of breast cancer (BC) is of great significance in selecting optimal treatment strategy. Different molecular subtypes of BC have various vascular distribution characteristics. Contrast-enhanced ultrasound (CEUS) can dynamically display the microcirculation of tumor. This study intends to explore the conventional ultrasound and CEUS characteristics of different molecular subtypes of BC. METHODS: During this prospective study, 86 patients with BC who were divided into Luminal A (LA), Luminal B (LB), HER2 over-expression (H2), and triple-negative (TN). The CEUS qualitative and quantitative characteristics of BC with different molecular subtypes was explored, as well as the conventional ultrasound features. In addition, the diagnostic efficiency of CEUS quantitative parameters in differentiating molecular subtypes of BC was analyzed. RESULTS: Our study found that the Adler grade differed significantly among 4 molecular subtypes (P < .05). The enhancement speed, enhancement degree and size after enhancement of 4 molecular subtypes were statistically different (P < .05). The wash in slope (WIS), peak intensity (PI), and wash-in area under the curve (WiAUC) differed significantly among 4 subtypes (P < .05). The diagnostic efficiency of PI was better for detecting LA and H2 subtype with the areas under the receiver operating characteristic curve was 0.778 and 0.734, respectively. CONCLUSION: Different molecular subtypes of BC have different CEUS and conventional ultrasound characteristics. CEUS can provide valuable imaging basis for precise clinical diagnosis and individualized therapy of BC with different molecular subtypes.

Effects of subanaesthetic S-ketamine on postoperative delirium and cognitive function in elderly patients undergoing non-cardiac thoracic surgery: a protocol for a randomised, double-blinded, placebo-controlled and positive-controlled, non-inferiority trial (SKED trial).

INTRODUCTION: Postoperative delirium (POD) is a common and distressing complication after thoracic surgery. S-ketamine has neuroprotective properties as a dissociative anaesthetic. Emerging literature has indicated that S-ketamine can reduce cognitive impairment in patients with depression. However, the role of S-ketamine in preventing POD remains unknown. Therefore, this study aims to evaluate the effect of intraoperative prophylactic S-ketamine compared with that of dexmedetomidine on the incidence of POD in elderly patients undergoing non-cardiac thoracic surgery. METHODS AND ANALYSIS: This will be a randomised, double-blinded, placebo-controlled, positive-controlled, non-inferiority trial that enrolled patients aged 60-90 years undergoing thoracic surgery. The patients will be randomly allocated in a ratio of 1:1:1 to S-ketamine, dexmedetomidine or normal saline placebo groups using computer-generated randomisation with a block size of six. The primary outcome will be the incidence of POD within 4 days after surgery and this will be assessed using a 3-Minute Diagnostic Confusion Assessment Method two times per day. The severity and duration of POD, the incidence of emergence delirium, postoperative pain, quality of sleep, cognitive function, and the plasma concentrations of acetylcholine, brain-derived neurotrophic factor, tumour necrosis factor-α and incidence of adverse events will be evaluated as secondary outcomes. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Institutional Review Board of the Cancer Hospital and the Institute of Guangzhou Medical University (ZN202119). At the end of the trial, we commit to making a public disclosure available, regardless of the outcome. The public disclosure will include a publication in an appropriate journal and an oral presentation at academic meetings. TRIAL REGISTRATION NUMBER: ChiCTR2100052750 (NCT05242692).

Deep learning radiomics for focal liver lesions diagnosis on long-range contrast-enhanced ultrasound and clinical factors.

Background: Routine clinical factors play an important role in the clinical diagnosis of focal liver lesions (FLLs); however, they are rarely used in computer-assisted diagnosis. Therefore, we developed a deep learning (DL) radiomics model, and investigated its effectiveness in diagnosing FLLs using long-range contrast-enhanced ultrasound (CEUS) cines and clinical factors. Methods: Herein, 303 patients with pathologically confirmed FLLs after surgery at three hospitals were retrospectively enrolled and divided into a training cohort (n=203), internal validation (IV) cohort (n=50) from one hospital with the ratio of 4:1, and external validation (EV) cohort (n=50) from the other two hospitals. Four DL radiomics models, namely Four Stream 3D convolutional neural network (FS3DU) (trained with CEUS cines only), FS3DU+A (trained with CEUS cines and alpha fetoprotein), FS3DU+H (trained with CEUS cines and hepatitis), and FS3DU+A+H (trained with CEUS cines, alpha fetoprotein, and hepatitis), were formed based on 3D convolutional neural networks (CNNs). They used approximately 20-s preoperative CEUS cines and/or clinical factors to extract spatiotemporal features for the classification of FLLs and the location of the region of interest. The area under curve of the receiver operating characteristic and diagnosis speed were calculated to evaluate the models in the IV and EV cohorts, and they were compared with those of two radiologists. Two-sided Delong tests were used to calculate the statistical differences between the models and radiologists. Results: FS3DU+A+H, which incorporated CEUS cines, hepatitis, and alpha fetoprotein, achieved the highest area under curve of 0.969 (95% CI: 0.901-1.000) and 0.957 (95% CI: 0.894-1.000) among radiologists and other models in IV and EV cohorts, respectively. A significant difference was observed when comparing FS3DU and radiologist 2 (all P<0.05). The diagnosis speed of all the models was the same (10.76 s per patient), and it was two times faster than those of the radiologists (radiologist 1: 23.74 and 27.75 s; radiologist 2: 25.95 and 29.50 s in IV and EV cohorts, respectively). Conclusions: The proposed DL radiomics demonstrated excellent performance on the benign and malignant diagnosis of FLLs by combining CEUS cines and clinical factors. It could help the individualized characterization of FLLs, and enhance the accuracy of diagnosis in the future.

Comparison between spleen and liver stiffness measurements by sound touch elastography for diagnosing cirrhosis at different aminotransferase levels: a prospective multicenter study.

OBJECTIVES: To compare the performance of spleen stiffness measurement (SSM) and liver stiffness measurement (LSM) by sound touch elastography (STE) for the diagnosis of cirrhosis at different alanine aminotransferase (ALT) levels, and to compare the applicability and repeatability of SSM with LSM performed by STE, a new two-dimensional shear wave elastography technology. METHODS: This prospective multicenter study included 25 centers and recruited chronic hepatitis B (CHB) patients with liver biopsy between May 2018 and November 2019. All patients underwent LSM and SSM by STE. Success and reliability rates were calculated and compared. Intra-observer agreement was assessed using intraclass correlation coefficients (ICCs). Differences between areas under the receiver operating characteristic curves (AUCs) of LSMs and SSMs at different ALT levels were compared using the Delong test. RESULTS: Among 603 CHB patients, the success and reliability rates of SSM were 94.53% (570/603) and 85.74% (517/603), respectively, which were similar to those of LSM (p > 0.05), respectively. The ICC for intra-observer agreements of SSM was 0.964 (p < 0.001). In the total cohort, ALT ≤ 2 × upper limit of normal (ULN) group, and A0-1 group, the AUCs of SSMs were significantly lower than those of LSMs for the diagnosis of cirrhosis (p < 0.001). In the ALT > 2 × ULN group and A2-3 group, the AUC of SSM improved and was not significantly different from that of LSM (p = 0.342, p = 0.510, respectively). CONCLUSIONS: SSM by STE achieved applicability and repeatability equivalent to those of LSM. SSM might be a good substitute to LSM in patients with high ALT levels. KEY POINTS: • Spleen stiffness measurement performed by sound touch elastography was proven to have similar applicability and repeatability to liver stiffness measurement in this prospective multicenter study. • Spleen stiffness measurement demonstrated a poorer diagnostic performance for cirrhosis compared with liver stiffness measurement in the total cohort and low ALT level group, yet it showed a similar diagnostic performance to liver stiffness measurement in patients with high ALT levels.

Effect of general anesthesia with thoracic paravertebral block on postoperative delirium in elderly patients undergoing thoracoscopic lobectomy: a randomized-controlled trial.

BACKGROUND: Postoperative delirium (POD) is characterized by acute brain dysfunction, especially in elderly patients. Postoperative pain is an important factor in the development of delirium, and effective pain management can reduce the risk of POD. Thoracic paravertebral block (TPVB) can effectively relieve postoperative pain and inhibit the perioperative stress and inflammatory response. We investigated whether the combination of TPVB with general anesthesia reduced the occurrence of POD following thoracoscopic lobectomy. METHODS: A total of 338 elderly patients, aged 65-80 years, who underwent elective surgery for video-assisted thoracoscopic lobectomy (VATS) were randomly assigned to either a patient-controlled intravenous analgesia group (PIA) or a patient-controlled paravertebral-block analgesia group (PBA). POD was evaluated using the 3-min diagnostic confusion assessment method (3D-CAM). The postoperative quality of recovery (QoR) was assessed with Chinese version of QoR-40 scale. Pain intensity was measured using the visual analog scale (VAS) score. Tumor necrosis factor-α (TNF-α) and neurofilament light (NFL) levels were determined using enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: Delirium occurred in 47 (28%) of 168 cases in the PIA group and 28 (16.5%) of 170 cases in the PBA group (RR 1.7, p = 0.03). PBA was also associated with a higher rate of overall recovery quality at day 7 after surgery (27.1% vs. 17.3%, P = 0.013) compared with PIA. The incremental change in surgery-induced TNF-α and NFL was greater in the PIA group than PBA group (p < 0.05). CONCLUSION: Thoracic paravertebral block analgesia is associated with lower incidence of postoperative delirium, probably due to its anti-neuroinflammatory effects. Furthermore, as a component of multimodal analgesia, TPVB provides not only superior analgesic but also opioid-sparing effects. TRIAL REGISTRATION: The study was registered on the Chinese Clinical Trial Registry Center ( www.chictr.org.cn ; registration number: ChiCTR 2,000,033,238 ) on 25/05/2018.

The diagnostic value of contrast-enhanced ultrasound LI-RADS for hepatocellular carcinoma in patients with cirrhosis and chronic hepatitis B.

PURPOSE: To explore the diagnostic value of American College of Radiology Contrast-Enhanced Ultrasound-Liver Imaging Reporting and Data System (ACR-CEUS-LI-RADS) for hepatocellular carcinoma (HCC) in patients with cirrhosis and chronic hepatitis B. METHODS: A total of 205 patients at high risk of HCC with solitary hepatic nodule were enrolled and retrospectively analyzed. All patients were over 18 years old and had a single lesion with a diameter < 50 mm. Lesions were categorized according to size and contrast enhancement patterns in the arterial, portal venous and late phases. Diagnostic efficacy of CEUS LI-RADS for HCC, and the rate of non-HCC malignancies in the LR-M class were compared between patients with cirrhosis and chronic hepatitis B. RESULTS: Of all 205 nodules (median nodule size was 34 mm), 142 (69.3%) were HCC. Of the 127 (61.9%) LR-5 category nodules, 95.8% (92/96) nodules were corresponded to HCC in cirrhosis, while 61.3% (19/31) nodules were corresponded to HCC in chronic hepatitis B (P = 0.000). Positive predictive value (PPV) of LR-5 category for HCC was 95.8% in cirrhosis and 61.3% in chronic hepatitis B (P = 0.000). More category of LR-4 nodules were proved to be HCC in patients with cirrhosis than chronic hepatitis B (80.0% vs 8.3%, P = 0.000). Of 41 LR-M category nodules, more non-HCC malignancies were found in chronic hepatitis B (76.0%) than that in cirrhosis (25.0%, P = 0.001). CONCLUSIONS: The LR-5 category is highly specific for the diagnosis of HCC in patients with cirrhosis. However, LR-5 category nodules require further CT or MRI examination or histological confirmation in patients with chronic hepatitis B for its unsatisfactory PPV for HCC.

[Effects of different postoperative analgesic strategies on postoperative neurocognitive function and quality of recovery in elderly patients undergoing one lung ventilation].

OBJECTIVE: To evaluate the effects of different postoperative analgesic strategies on neurocognitive function and quality of recovery in elderly patients at 7 days after thoracic surgery with one lung ventilation. METHODS: Ninety elderly patients undergoing video-assisted thoracic surgery were randomized into 3 groups (n=30) to receive postoperative analgesia with thoracic paravertebral block analgesia (TA), epidural analgesia (EA) and intravenous analgesia (GA). Before and at 7 days after the surgery, the patients' cognitive function was assessed using Mini-Mental State Examination (MMSE), and their early recovery at 7 days postoperatively was evaluated using Quality of Recovery-40 items (QoR-40). RESULTS: The patients in TA and EA groups had significantly higher MMSE scores and lower incidence of postoperative neurocognitive dysfunction (PNCD) than those in GA group without significant difference between the former two groups. At 7 days after the surgery, serum levels of S100-ß and MMP-9 were significantly higher in GA group than in TA and EA group, and did not differ significantly between the latter two groups. QoR-40 scores were significantly higher in TA and EA groups than in GA group, and were higher in TA group than in EA group. The chest intubation time and length of hospital stay were significantly shorter in TA and EA groups than in GA group. CONCLUSIONS: In elderly patients undergoing surgeries with one lung ventilation, general anesthesia combined with either postoperative continuous thoracic paravertebral block or epidural analgesia can significantly improve postoperative neurocognitive function and quality of recovery, but continuous thoracic paravertebral block analgesia can be more advantageous for improving postoperative quality of recovery.

Enhancement Patterns of Intrahepatic Cholangiocarcinoma on Contrast-Enhanced Ultrasound: Correlation with Clinicopathologic Findings and Prognosis.

To evaluate the correlations between the enhancement pattern of intrahepatic cholangiocarcinoma (ICC) on contrast-enhanced ultrasound (CEUS) and clinicopathologic findings and prognosis, a retrospective study was performed on 197 patients with mass-forming ICC who underwent pre-operative CEUS and surgical resection. The contrast medium we employed in CEUS was SonoVue, which contains microbubbles consisting of sulfur hexafluoride bubbles within a phospholipid shell. This study was approved by the institutional review board with informed consent waived. Patients were classified into an arterial rim-like enhancement group or an arterial non-rim-like enhancement group, and arterial enhancement patterns were correlated with clinicopathologic factors. Overall survival (OS) times were calculated using the Kaplan-Meier method, and differences between groups were compared with the log-rank test. Univariate and multivariate Cox regression models for OS were used to evaluate the independent prognostic factors. The mean and range of ICC tumor size of the arterial rim-like group (59.41 ± 22.09 mm, 20-100 mm) were similar to those of the arterial non-rim-like group (59.82 ± 30.35 mm, 14-162 mm, p = 0.914). Arterial enhancement patterns were correlated with chronic viral hepatitis or cirrhosis, vascular invasion, lymph node metastasis and single/multiple tumors. A total of 78 patients (39.6%) exhibited arterial rim-like enhancement, and the other 119 patients (60.4%) exhibited arterial non-rim-like enhancement. Arterial enhancement pattern (p = 0.045), vascular invasion (p = 0.005), lymph node metastasis (p = 0.000) and number of tumors (p = 0.001) were independent prognostic factors for OS. The arterial non-rim-like enhancement pattern of ICC on CEUS is an independent prognostic factor for better OS and may offer new information for predicting the prognosis of ICC patients before surgical resection.

Choroid plexus papilloma presenting as an occipital mass with neck pain: Case report.

RATIONALE: Choroid plexus papillomas are rare benign central nervous system neoplasms arising from choroid plexus epithelium. They are most often located in the lateral ventricle, followed by the fourth and third ventricles and, rarely, in the cerebellopontine angle. PATIENT CONCERNS: We report an uncommon case of a 17-year-old boy who presented with neck pain that had lasted for more than 1 month, with accompanying pain and numbness in his upper extremities. His conditions included slight dizziness, nausea, diplopia, paresthesia, and an unsteady gait. Magnetic resonance imaging (MRI) showed huge cerebellopontine angle tumor that extended to the front medulla oblongata. DIAGNOSIS: Choroid plexus papilloma (WHO I) was diagnosed in this patient. INTERVENTIONS: The patient was referred for neurosurgical intervention. The very large neoplasm was subtotally resected. OUTCOMES: The symptoms of the patient were gradually alleviated after surgery and subsequent radiotherapy treatment, but unfortunately, follow-up of 2 years later revealed that the disease was recurrent and the young man passed away. LESSONS: Neck pain is related to many factors. The case provided an awareness of the origin of severe intracranial disease. It is mandatory to take a thorough clinical assessment with a holistic approach.

Perfusion Characteristics of Hepatocellular Carcinoma at Contrast-enhanced Ultrasound: Influence of the Cellular differentiation, the Tumor Size and the Underlying Hepatic Condition.

This study aimed to analyze the influence of the cellular differentiation, the tumor size and the underlying hepatic condition on the enhancement pattern of hepatocellular carcinoma (HCC) on contrast-enhanced ultrasound (CEUS). 276 patients with single lesion ≤ 5 cm who underwent CEUS exam and were pathologically confirmed as HCC were retrospectively enrolled. Enhancement patterns, washout patterns, wash-in time and washout time were observed and recorded. During the arterial phase, more poorly differentiated HCCs (42.5%) and lesions > 3 cm (35.2%) performed inhomogeneous enhancement (p < 0.05). More well differentiated HCCs (63.4%) performed late washout or no washout while compared with moderately (37.8%) or poorly (24.1%) differentiated HCCs (p < 0.05). Poorly differentiated HCCs showed the shortest washout time (83.0 ± 39.8 s), moderately differentiated HCCs showed the moderate washout time (100.4 ± 52.1 s), and well differentiated HCCs showed the longest washout time (132.3 ± 54.2 s) (p < 0.05). Lesions > 3 cm (97.2 ± 51.3 s) washed out more rapidly than lesions ≤ 3 cm (113.9 ± 53.5 s) (p < 0.05). The dynamic enhancement procedure of HCC was influenced by the cellular differentiation and the tumor size. While, hepatic background showed no influence on the dynamic enhancement of HCC.

Primary hepatic neuroendocrine tumors: clinical characteristics and imaging features on contrast-enhanced ultrasound and computed tomography.

OBJECTIVE: Primary hepatic neuroendocrine tumor (PHNET) is an extremely rare liver neoplasm, and its clinical characteristics and imaging features are not well understood. The aim of this study was to analyze the clinical profiles and imaging features of PHNETs on contrast-enhanced ultrasound (CEUS) and computed tomography (CT) METHODS: Patients with PHNET between January 2008 and December 2015 were retrospectively identified, and their demographics, laboratory data, and imaging characteristics on CEUS and CT analyzed. RESULTS: Ten consecutive patients with PHNETs were included (including one G1, seven G2, and two G3 of tumor grades).The median age of patient was 45 years (range: 27-72 years), and 60.0% of patients were male. The most common symptom was abdominal pain (60.0%), and cirrhosis was found in 40.0% of patients. Tumors were confined within the liver in 60.0% of patients, while the remaining patients had extra-hepatic metastasis. The tumors revealed hyperechoic in 60% of patients and mixed echoic in 30% of patients on conventional US, displaying intense arterial enhancement followed by washout in the portal and/or the late phases in 80.0% of patients on CEUS and 60% at CT. CONCLUSIONS: Although PHNET is a very rare liver tumor, it should be considered as a possible differential diagnosis in the management of hepatic tumors. Most PHNETs were hyperechoic or mixed echoic on conventional US, showing similar enhancement patterns to that of hepatocellular carcinoma on CEUS.

Combined hepatocellular carcinoma and cholangiocarcinoma (biphenotypic) tumors: clinical characteristics, imaging features of contrast-enhanced ultrasound and computed tomography.

BACKGROUND: Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is an uncommon primary liver malignancy and little known about the clinical and imaging characteristics of cHCC-CC. We aim to define the demographics, imaging features of cHCC-CC on contrast-enhanced ultrasound (CEUS) and contrast-enhanced computed tomography (CT) in this study. METHODS: From January 2005 to December 2014, 45 patients with pathologically proven cHCC-CC who underwent preoperative CEUS and 43 patients who had additional CT scan in our institution were included. A retrospective review of the imaging studies and clinical data in these patients was conducted. RESULTS: In our series, cHCC-CC accounted for 1.6 % of all primary liver malignancy. Mean age of patient with cHCC-CC was 52.8 year (range: 28-74 year) and 88.9 % (40/45) of patients were male. Thirty of forty five patients (66.7 %) had cirrhosis and 20 % (9/45) of patients had chronic hepatitis B without cirrhosis. Alpha--fetoprotein (AFP) was elevated in 62.2 % (28/45) of patients and carbohydrate antigen 19-9 (CA19-9) elevated in 22.2 % (10/45) of patients). Both AFP and CA19-9 were simultaneously elevated in 15.6 % (7/45) of patients. Enhancement pattern resembling cholangiocarcinoma (CC) was noted in 53.3 % (24/45) of patients (on CEUS and in 30.2 % (13/43) of patients at CT. Enhancement pattern resembling hepatocellular carcinoma (HCC) was observed in 42.2 % (19/45) of patients on CEUS and in 58.1 % (25/43) of patients at CT. The percentage of tumors showing CC enhancement pattern (27.9 %, 12/43) was comparable with that of tumors showing HCC enhancement pattern (44.2 %, 19/43) on both CEUS and CT (p = 0.116). Simultaneous elevation of tumor markers (AFP and CA19-9) or tumor marker elevation (AFP or CA19-9) in discordance with enhancement pattern on CEUS was demonstrated in 51.1 % (23/45) of patients and on CT in 53.5 % (23/43) of patients, which was significantly more than simultaneous elevation of tumor markers (AFP and CA19-9) alone (p = 0.000). CONCLUSIONS: The clinical characteristics of cHCC-CC are similar to those of HCC. The cHCC-CC tumors display enhancement patterns resembling CC or HCC in comparable proportion on both CEUS and CT. Combination of simultaneous elevation of tumor makers (AFP and CA19-9) and tumor mark elevation (AFP or CA19-9) in discordance with presumptive imaging findings on CEUS or CT may lead significantly more patients to be suspicious of the diagnosis of cHCC-CC.

Comparison of CT and contrast-enhanced ultrasound findings in hepatic angiomyolipoma with pathological correlations.

OBJECTIVE: To compare imaging findings of CT and contrast-enhanced US (CEUS) in hepatic angiomyolipoma (HAML) and investigate their pathological correlations. METHODS: Imaging findings and preoperative diagnosis of CT and CEUS were retrospectively compared head to head in 46 patients with 54 histologically proven HAMLs. Correlations between imaging features and preoperative diagnosis with pathological types of HAMLs were analyzed. RESULTS: Fat was detected in 100% of lipomatous type, 84.6% of mixed type, and 7.1% of myomatous type (p = 0.000) of HAML at unenhanced CT. Well-defined hyper-echogenicity was displayed in 100% of lipomatous type, 88.5% of mixed type, 50% of myomatous type, and 66.7% of angiomatous type of HAMLs at unenhanced US. More arterial hyper-enhancement was noted on CEUS (100%) than on CT (73.1%) in mixed type (p = 0.015) and in lipomatous type (90.9% vs. 9.1%, p = 0.000) of HAMLs. Washout was present in more HAMLs on CT than on CEUS (42.6% vs. 18.5%, p = 0.007). Correct preoperative diagnosis was suggested in more HAMLs of myomatous type on CEUS than on CT (42.9% vs. 0%, p = 0.016) but showed no difference in other types of HAMLs. CONCLUSION: There are considerable discrepancies between CT and CEUS findings of HAMLs, and the imaging appearance and preoperative diagnosis of HAMLs on CT and CEUS are significantly affected by pathological types of HAMLs.

Diagnosis of Hepatic Angiomyolipoma by Combination of Baseline and Contrast-Enhanced Ultrasound--A Prospective Study in Non-Cirrhotic Patients.

OBJECTIVES: Hepatic angiomyolipoma (HAML) is a rare, benign mesenchymal tumor of the liver and its diagnosis has been considered challenging. The aim of this study was to investigate prospectively the diagnostic efficacy of the incorporation of both baseline ultrasound (US) and contrast-enhanced ultrasound (CEUS) features of HAML in patients without cirrhosis. MATERIALS AND METHODS: Consecutive 1748 non-cirrhotic patients with focal liver lesions (FLLs) were prospectively enrolled. Baseline US and CEUS were performed before resection or biopsy. Ultrasound imaging diagnosis of FLLs was compared with the pathological results. RESULTS: Final diagnoses were established in 41 patients with HAML (2.3%) with normal alpha fetal protein (AFP) level and in 1707 patients with FLL other than HAML. Diagnostic criteria for HAML was based on the combination of baseline US and CEUS appearance of the nodule: (1) Well-defined, marked hyper-echoic nodule without surrounding hypo-echoic halo on baseline US; (2) hyper-enhancement in the arterial phase (exclude initial peripheral nodular enhancement and spoke-wheel arteries) and remains hyper-enhancement or iso-enhancement in the late phase. The diagnostic criteria were fulfilled in 31 HAMLs, 1 hepatocellular adenoma and 1 hemangioma. Ten HAMLs were misdiagnosed as other liver tumors because they did not meet the diagnostic criteria mentioned above and consequently yielded a sensitivity, specificity, positive predictive values, negative predictive values and Youden index of 75.61%, 99.88%, 93.94%, 99.42%, and 0.75 respectively. CONCLUSION: The combination of baseline US and CEUS may lead to the correct diagnosis noninvasively in the majority of HAMLs in non-cirrhotic patients with normal AFP level.

Detailed analysis of temporal features on contrast enhanced ultrasound may help differentiate intrahepatic cholangiocarcinoma from hepatocellular carcinoma in cirrhosis.

AIM: To verify if detailed analysis of temporal enhancement patterns on contrast enhanced ultrasound (CEUS) may help differentiate intrahepatic cholangiocarcinoma (ICC) from hepatocellular carcinoma (HCC) in cirrhosis. METHODS: Thirty three ICC and fifty HCC in cirrhosis were enrolled in this study. The contrast kinetics of ICC and HCC was analyzed and compared. RESULTS: Statistical analysis did not reveal significant difference between ICC and HCC in the time of contrast first appearance and arterial peak maximum time. ICC displayed much earlier washout than that of HCC (47.93±26.45 seconds vs 90.86±31.26 seconds) in the portal phase, and most ICC (87.9%) showed washout before 60 seconds than HCC (16.0%). Much more ICC (78.8%) revealed marked washout than HCC (12.0%) while most HCC (88.0%) showed mild washout or no washout in late part of the portal phase (90-120 seconds). Twenty six out of thirty three ICC (78.8%) demonstrated both early washout(<60 seconds) and marked washout in late part of the portal phase, whereas, only six of fifty HCC (12.0%)showed these temporal enhancement features (p = 0.000).When both early washout and marked washout in the portal phase are taken as diagnostic criterion for ICC, the diagnostic sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 78.8%,88.0%,81.3%,86.3%,and 84.3% respectively by CEUS. CONCLUSIONS: Analysis of detailed temporal enhancement features on CEUS is helpful differentiate ICC from HCC in cirrhosis.If a nodule in cirrhotic liver displays hyper-enhancement in the arterial phase followed by early and marked washout in the portal phase, the nodule is highly suspicious of ICC rather than HCC.

Dynamic enhancing vascular pattern of intrahepatic peripheral cholangiocarcinoma on contrast-enhanced ultrasound: the influence of chronic hepatitis and cirrhosis.

PURPOSE: To analyse the dynamic enhancing features by real-time contrast-enhanced ultrasound (CEUS) of intrahepatic peripheral cholangiocarcinoma (ICC) in patients with chronic hepatitis and cirrhosis. MATERIALS AND METHODS: CEUS was performed by using contrast pulse sequencing (CPS) imaging with mechanical index of <0.2 after injection of 2.4 mL of contrast agent. CEUS images of histologically confirmed ICC in 54 patents (15 patents with chronic hepatitis B, 16 patents with cirrhosis, and 23 patents with normal underlying liver) were analyzed. RESULTS: Heterogeneous hyperenhancement was more frequently identified in ICC with chronic hepatitis (9 of 15, 60.0%, p = 0.000) and cirrhosis (8 of 16, 50.0%, p = 0.010) than in patients with normal liver (6 of 23, 26.1%) during arterial phase. The majority of ICC in patients with normal liver displayed peripheral hyperenhancement (13 of 23, 56.5%), than in patients with chronic hepatitis (4 of 15, 26.7%, p = 0.000) and cirrhosis (5 of 16, 31.3%, p = 0.001). Intense contrast uptake during the arterial phase (heterogeneous hyperenhancement or global hyperenhancement) followed by washout in venous phases was more frequently displayed in ICC patients with chronic hepatitis (11 of 15, 73.3%, p = 0.000) and in patients with cirrhosis (11 of 16, 68.8%, p = 0.000) than in ICC patients with normal underlying liver (8 of 23, 34.8%). CONCLUSION: The enhancing vascular pattern of ICC on CEUS in patients with chronic hepatitis and cirrhosis is different from that in ICC without underlying liver disease. The enhancing vascular pattern is indistinguishable from HCC on CEUS in most ICC patients with chronic hepatitis or cirrhosis.

Palliative care education in China: insight into one medical university.

CONTEXT: There has been an increase in the amount of palliative care available in developing countries, including in China. However, palliative care is still very limited, and it is not mandatory to teach courses on palliative care in Chinese medical universities. OBJECTIVES: To assess Chinese interns' awareness of palliative care concepts. METHODS: Using a questionnaire selected from an earlier Austrian study, interns in a Chinese medical university were surveyed. All those surveyed had already been interns for at least six months. RESULTS: Four hundred interns from a Chinese medical university (response rate 99.5%) were surveyed. Twenty-one percent were female (84 of 400), and the average age was 23 years. Approximately one-third (34.5%) of interns were familiar with the pain scale, and 31% of interns were familiar with the concept of pain management. Only 7.5% of interns felt adequately trained in basic pain management, and 13% felt adequately trained to manage symptoms of dying patients. Seventy-seven percent of interns reported inadequate education regarding discussion of death with patients and family members. More than 80% of interns felt that more education about palliative care should be included in the basic medical curriculum and clinical intern training. CONCLUSION: Palliative care education is inadequate from the perspective of the Chinese medical interns. An improvement in the medical school curriculum is needed.

Oral decitabine reactivates expression of the methylated gamma-globin gene in Papio anubis.

The silencing of tumor suppressor genes associated with increased DNA methylation of the promoter regions is a frequent observation in many forms of cancer. Reactivation of these genes using pharmacological inhibitors of DNA methyltransferase such as 5-aza-2'-deoxycytidine (decitabine) is a worthwhile therapeutic goal. The effectiveness and tolerability of low-dose intravenous and subcutaneous decitabine regimens to demethylate and reactivate expression of the methylated gamma-globin gene in baboons and in patients with sickle cell disease led to successful trials of low-dose regimens of this drug in patients with myelodysplastic syndrome. Since these low-dose regimens are well-tolerated with minimal toxicity, they are suitable for chronic dosing to maintain promoter hypomethylation and expression of target genes. The development of an orally administered therapy using DNA methyltransferase inhibitors would facilitate such chronic approaches to therapy. We tested the ability of decitabine and a new salt derivative, decitabine mesylate, to reactivate the methylated gamma-globin gene in baboons when administered orally. Our results demonstrate that oral administration of these drugs at doses 17-34 times optimal subcutaneous doses of decitabine reactivates fetal hemoglobin, demethylates the epsilon- and gamma-globin gene promoters, and increases histone acetylation of these promoters in baboons (Papio anubis).

Delivery of 5-aza-2'-deoxycytidine to cells using oligodeoxynucleotides.

The major goal of epigenetic therapy is to reverse aberrant promoter hypermethylation and restore normal function of tumor suppressor genes by the use of chromatin-modifying drugs. Decitabine, or 5-aza-2'-deoxycytidine (5-aza-CdR), is a well-characterized drug that is now Food and Drug Administration approved for the treatment of myelodysplastic syndrome. Although 5-aza-CdR is an extremely potent inhibitor of DNA methylation, it is subject to degradation by hydrolytic cleavage and deamination by cytidine deaminase. We show that short oligonucleotides containing a 5-aza-CdR can also inhibit DNA methylation in cancer cells at concentrations comparable with 5-aza-CdR. Detailed studies with S110, a dinucleotide, showed that it works via a mechanism similar to that of 5-aza-CdR after incorporation of its aza-moiety into DNA. Stability of the triazine ring in aqueous solution was not improved in the S110 dinucleotide; however, deamination by cytidine deaminase was dramatically decreased. This is the first demonstration of the use of short oligonucleotides to provide effective delivery and cellular uptake of a nucleotide drug and protection from enzymatic degradation. This approach may pave the way for more stable and potent inhibitors of DNA methylation as well as provide means for improving existing therapeutics.

Recombinant adeno-associated virus: formulation challenges and strategies for a gene therapy vector.

Recombinant adeno-associated virus (AAV)-based vectors capable of expressing therapeutic gene products in vivo have shown significant promise for human gene therapy. One challenge facing the field is the development of vector formulations to achieve optimal vector safety, stability and efficacy. Formulation challenges for AAV vectors can be divided into those relating to maintaining vector activity during purification and storage, and those relating to efficient target tissue transduction in vivo. AAV vectors are potentially susceptible to loss of activity through aggregation, proteolysis and oxidation, as well as through non-specific binding to product contact materials used for vector purification and storage. These deleterious changes need to be thoroughly characterized, and the conditions and excipients to prevent them need to be identified. For in vivo administration, major vector formulation challenges include optimization of efficiency and specificity of target tissue transduction, and the ability to overcome host immune responses.