Sphingosine-1-phosphate transporter spinster homolog 2 is essential for iron-regulated metastasis of hepatocellular carcinoma.

Iron dyshomeostasis is associated with hepatocellular carcinoma (HCC) development. However, the role of iron in HCC metastasis is unknown. This study aimed to elucidate the underlying mechanisms of iron's enhancement activity on HCC metastasis. In addition to the HCC cell lines and clinical samples in vitro, iron-deficient (ID) mouse models were generated using iron-free diet and transferrin receptor protein knockout, followed by administration of HCC tumors through either orthotopic or ectopic route. Clinical metastatic HCC samples showed significant ID status, accompanied by overexpression of sphingosine-1-phosphate transporter spinster homolog 2 (SPNS2). Mechanistically, ID increased SPNS2 expression, leading to HCC metastasis in both cell cultures and mouse models. ID not only altered the anti-tumor immunity, which was indicated by phenotypes of lymphatic subsets in the liver and lung of tumor-bearing mice, but also promoted HCC metastasis in a cancer cell autonomous manner through the SPNS2. Since germline knockout of globe SPNS2 showed significantly reduced HCC metastasis, we further developed hepatic-targeting recombinant adeno-associated virus vectors to knockdown SPNS2 expression and to inhibit iron-regulated HCC metastasis. Our observation indicates the role of iron in HCC pulmonary metastasis and suggests SPNS2 as a potential therapeutic target for the prevention of HCC pulmonary metastasis.

Diagnostic performance in T staging for patients with esophagogastric junction cancer using high-resolution MRI: a comparison with conventional MRI at 3 tesla.

BACKGROUND: To investigate and compare the diagnostic performance in T staging for patients with esophagogastric junction cancer using high-resolution magnetic resonance imaging (HR MRI), as compared with conventional MRI at 3 Tesla. METHODS: A total of 118 patients with pathologically confirmed esophagogastric junction cancer were included and underwent multiparameter HR MRI (Cohort 1, 62 patients) or conventional MRI (Cohort 2, 56 patients). T2-weighted, T1-weighted, diffusion-weighted and contrast-enhanced T1-weighted images of each patient were evaluated by two radiologists who determined the preoperative T staging by consensus. Using pathologic staging as the gold standard, the consistency between HR MRI and pathology and between conventional MRI and pathology in T staging was calculated and compared. The overall accuracy, overstatement and understatement of HR MRI and conventional MRI in T staging of patients with esophagogastric junction cancer were computed and compared. Moreover, the diagnostic performance of HR MRI and conventional MRI in T staging (≤ T1 and ≥ T4) of patients with esophagogastric junction cancer were evaluated. RESULTS: There were no significant differences in age (p = 0.465) and sex (p = 0.175) between Cohorts 1 and 2. Excellent agreement was observed in the T staging of patients with esophagogastric junction cancer between pathology and HR MRI (kappa = 0.813), while moderate agreement was observed between pathology and conventional MRI (kappa = 0.486). Significant differences were observed in overall accuracy (88.7% vs 64.3%, p = 0.002) and understatement (1.6% vs 26.8%, p < 0.001) but not for overstatement (9.7% vs 8.9%, p = 0.889) in T staging between HR MRI and conventional MRI techniques. For differentiating the T stages of ≤ T1 from ≥ T2 and the T stages of ≤ T3 from ≥ T4, no significant differences were observed between the imaging techniques. CONCLUSIONS: HR MRI has good diagnostic performance and may serve as an alternative technique in the T staging of patients with esophagogastric junction cancer in clinical practice.

Five-year follow-up of 23 asymmetrical Parkinson's disease patients treated with unilateral subthalamic nucleus stimulation.

In this study, 23 asymmetrical Parkinson's disease patients were treated with unilateral deep brain stimulation of the subthalamic nucleus and followed up for 5 years. At 5 years after stimulation treatment, Unified Parkinson's Disease Rating Scale II, III and axial symptom scores in the off-drug condition were significantly increased compared those at baseline. However, total Unified Parkinson's Disease Rating Scale II, III and axial symptom scores were significantly lower with stimulation-on compared with the synchronous stimulation-off state in off-drug condition, and the motor symptoms of contralateral side limbs were effectively controlled. Only low Hoehn-Yahr stage was correlated with good long-term postoperative improvement in motor symptoms. The mean levodopa-equivalent daily dose after stimulation treatment was significantly lower than that before treatment, but dyskinesias became worse. Our experimental findings indicate that unilateral deep brain stimulation of the subthalamic nucleus is an effective treatment for improving motor symptoms in well selected asymmetrical Parkinson's disease patients presenting no severe axial symptoms and dyskinesias.

Avoidance and management of surgical and hardware-related complications of deep brain stimulation.

OBJECTIVE: Although deep brain stimulation (DBS) is nonablative, it may give rise to many complications. In order to identify and reduce factors contributing to the complications, we performed a retrospective analysis of patients who received DBS in our institution over a 9-year period from March 2000 to December 2008. METHODS: Included in this study were 161 patients (85 male and 76 female). Data from these patients were collected and analyzed with respect to the complications and factors potentially related to these complications. RESULTS: A total of 25 surgical and hardware-related complications occurred in 24 patients, including confusion in 11 cases (6.83%), asymptomatic intracranial hemorrhage in 1 case (0.62%), electrode misplacement in 2 cases (1.24%), infection of the subcutaneous pocket receiving the pulse generator in 1 case (0.62%), skin erosion in 2 cases (1.24%), pulse generator seroma formation in 6 cases (3.72%), and device malfunction in 1 case (0.62%). There was no permanent neurological deficit. CONCLUSION: Confusion is the most common complication in simultaneous bilateral DBS targeting the subthalamic nucleus, especially in patients with severe Parkinson's disease. With increasing experience of surgeons, complete obedience to intraoperative surgical routines and reasonable application of the microelectrode recording technique, other complications could also be reduced.

[Natural history of small hepatocellular carcinoma: studied by MRI].

OBJECTIVE: To study natural history of small hepatocellular carcinoma (sHCC) and value of MRI in this research. METHODS: From 1999 to 2002, serial MR imagings were performed in 192 patients with cirrhosis no less than twice in order to detect sHCC focus. Characteristic MRI findings of focus were analysed. Diameters of focus (D) were measured. Tumorigenesis detected time (T) was counted; T and D were analysed by statistics and tumor volume doubling time (T(d)) was calculated. RESULTS: Fifty-eight new tumor foci in 33 patients were found, including 31 foci in 23 patients developed on the basis of cirrhosis, with a 12.0% cumulative tumorigenic rate of three years. The tumorigenesis detected time (T) was 386.9 +/- 256.4 days and the maximum diameter (D) was 2.258 +/- 1.074 cm. T was statistical correlated with D(3) (P < 0.01) and regressive formulas were established: D(3) = -2.69 + 0.058T (P = 0.0007), D(3) = -72.13 + 16.04lnT (P = 0.0064). Tumor volume doubling time was 20 approximately 279 days (mean: 104 days). CONCLUSION: The percentage of tumorigenesis is high in patients with cirrhosis. Regular MRI examinations are necessary to detect sHCC early. The optimal interval time is 3 approximately 6 months.

[Clinical value of MR cholangiopancreatography combining with dynamic enhanced MRI in the detection of cholangiocarcinoma].

OBJECTIVES: To evaluate the clinical value of breath-hold magnetic resonance cholangiopancreatography (MRCP) combining with dynamic enhanced MRI in the diagnosis of cholangiocarcinoma. METHODS: MRCP findings of 88 cholangiocarcinoma patients proved surgically and pathologically were analyzed retrospectively. RESULTS: MRCP examination succeeded in all the 88 patients and the pancreaticobiliary ducts were shown satisfactorily. The accuracy of MRCP in the location of both hilar and extrahepatic cholangiocarcinoma was 100%, and the accuracy of detecting hilar and extrahepatic cholangiocarcinoma were 100% and 52.2%, respectively. Combining with dynamic enhanced MRI, the detecting accuracy of extrahepatic cholangiocarcinoma improved to 91.3%. CONCLUSIONS: MRCP examination has a high successful rate and can accurately determine the location of hilar and extrahepatic cholangiocarcinoma, and the accuracy of qualitative diagnosis for the former two is high. Combining with dynamic enhanced MRI, the specificity of determining extrahepatic cholangiocarcinoma is also high.