Magnetic resonance elastography and proton density fat fraction predict adverse outcomes in hepatocellular carcinoma.

BACKGROUND: Magnetic resonance (MR) elastography and proton density fat fraction (PDFF) are emerging techniques for non-invasive assessment of liver stiffness and steatosis, respectively. We investigated the role of MR metrics in pre-treatment prognostication of hepatocellular carcinoma (HCC). METHODS: Patients with newly diagnosed HCC were prospectively recruited. Pre-treatment MR elastography and PDFF were performed on tumor and non-tumor regions. HCC treatment was categorized as potentially curative (resection/ablation) or non-curative (locoregional/systemic therapy). HCC recurrence, liver-related complications (ascites/ variceal bleeding/ hepatic encephalopathy) and mortality were monitored. RESULTS: Of the 158 recruited patients (mean age 62.9 years, 84.2% male, 82.9% viral hepatitis), 58.2% (n = 92) and 41.8% (n = 66) received potentially curative and non-curative therapy, respectively. Pre-treatment non-tumor liver stiffness independently predicted liver-related complications, regardless of treatment type (HR 1.384, 95% CI 1.067-1.796, p = 0.014). In the potentially curative therapy group, non-tumor stiffness and non-tumor PDFF were independently associated with HCC recurrence (HR 1.308, 95% CI 1.022-1.673 & HR 1.080, 95% CI 1.009-1.156 respectively, both p < 0.05); and non-tumor PDFF predicted mortality (HR 1.160, 95% CI 1.038-1.296, p = 0.009). In the non-curative group, tumor stiffness independently predicted liver-related complications (HR 1.299, 95% CI 1.023-1.651, p = 0.032), and a combination of tumor stiffness ≥ 5.7 kPa plus non-tumor stiffness ≥ 3.7 kPa was associated with a two-fold risk of liver-related complications (86.7% vs 40.0%, p < 0.001). CONCLUSION: Pre-treatment MR elastography and PDFF over tumor and non-tumor regions demonstrated prognosticating roles in HCC. Simultaneous measurements of both metrics during conventional MR liver should be considered in the diagnostic workup of HCC.

Diffusion-weighted magnetic resonance imaging of breast lesions: first experiences at 3 T.

PURPOSE: Dynamic contrast-enhanced magnetic resonance imaging (MRI) has been established as a valuable tool for the detection of breast cancer. There is evidence suggesting that diffusion-weighted imaging (DWI) may be useful to distinguish between malignant and benign breast lesions. We seek to evaluate the ability of DWI to differentiate between malignant and benign breast lesions at 3 T. METHODS: Dynamic contrast-enhanced MRI and DWI of the breasts were performed in 31 female patients (age: mean, 46 years; range, 34-69 years) with suspected breast lesions on mammography and ultrasound using a 3-T scanner (MAGNETOM Tim Trio; Siemens Medical Solutions, Erlangen, Germany). Each lesion was assigned as either malignant or benign, blinded to the results of mammography and ultrasound, according to their imaging characteristics on contrast-enhanced MRI, DWI, and apparent diffusion coefficient (ADC) measurements. Tissue samples were obtained from all lesions by either needle or excision biopsy. Using histological results as the gold standard, the diagnostic accuracies of the dynamic contrast-enhanced MRI, DWI, and ADC were calculated and compared. RESULTS: All breast lesions (n = 31) were identified on both the dynamic contrast-enhanced MRI and DWI scans. The threshold ADC value was determined to be 0.00121 mm2/s, below which a lesion was considered malignant. The sensitivities/specificities of the dynamic contrast-enhanced MRI, qualitative DWI, and quantitative ADC were 95%/91%, 95%/63.6%, and 90%/91%, respectively. The differences in sensitivities, specificities, positive and negative predictive values, and diagnostic accuracies between the 3 examinations were statistically insignificant. CONCLUSIONS: Diffusion-weighted imaging at 3 T is highly sensitive in the detection of malignant breast lesions even with qualitative assessment alone, whereas ADC measurement offers quantitative assessment and increases the specificity to more than 90%. Further studies involving a larger cohort size and a wider spectrum of breast lesions are indicated.

Magnetic resonance whole body imaging at 3 Tesla: feasibility and findings in a cohort of asymptomatic medical doctors.

OBJECTIVES: To evaluate the feasibility of whole body imaging using a 3 Tesla magnetic resonance scanner without a contrast agent, and to study the prevalence of abnormal findings among a cohort of asymptomatic doctors. DESIGN: Prospective study. SETTING: Private hospital, Hong Kong. PARTICIPANTS: A total of 132 asymptomatic medical doctors (111 men, 21 women), with a mean age of 56 (range, 38-82) years, volunteered for the study. They underwent corresponding whole body imaging at our hospital between October 2005 and February 2006. Imaging involved a 3 Tesla magnetic resonance scanner with 32 channels, parallel imaging, Total Imaging Matrix technology, a maximum gradient amplitude of 40 mT/m and a slew rate of 200 mT/m/ms (Magnetom Tim Trio, Siemens Medical Solution, Erlangen, Germany). The use of matrix coils enabled coverage of the whole body. No contrast agent was used. MAIN OUTCOME MEASURES: Detection of abnormalities in asymptomatic, apparently healthy adults. RESULTS: All examinations were completed successfully. The mean scan time per subject was 33 (standard deviation, 4) minutes. All subjects tolerated the examination well and overall imaging quality was satisfactory. A total of 124 (94%) subjects had positive findings, of whom 24 (18%) had further workup. Five (4%) subjects were found to have tumours, of which two (1.5%) were proven malignant. Our cancer detection rate was comparable to that of other reported whole body screening studies using contrast magnetic resonance imaging and positron emission tomography. CONCLUSION: We demonstrated the feasibility of performing whole body imaging in 30 minutes, using 32-channel magnetic resonance imaging at 3 Tesla without a contrast agent or any ionising radiation.

Effectiveness of radiofrequency ablation for hepatocellular carcinomas larger than 3 cm in diameter.

HYPOTHESIS: Radiofrequency ablation is a safe and effective treatment for hepatocellular carcinomas 3.1 to 8.0 cm in diameter. DESIGN: Case series with prospective data collection. SETTING: Tertiary referral center. PATIENTS: Eighty-six patients with hepatocellular carcinoma treated with radiofrequency ablation from May 1, 2001, to December 31, 2002, were placed into categories of those with tumors 3 cm or smaller (group 1, n = 51) and those with tumors 3.1 to 8.0 cm (group 2, n = 35) in diameter. INTERVENTIONS: Radiofrequency ablation was performed with a single or cluster cool-tip electrode. The choice of treatment route was based on tumor size and position. MAIN OUTCOME MEASURES: Complication, treatment mortality, and complete ablation rates. RESULTS: Radiofrequency ablation was performed percutaneously in 26 patients in group 1 and 9 patients in group 2, with laparoscopy in 2 patients in group 1 and 1 patient in group 2, and with open operation in 23 patients in group 1 and 25 patients in group 2. The complication rates were 12% and 17% in group 1 and group 2, respectively (P =.48); treatment mortality rates were 0% and 3%, respectively (P =.41). Complete ablation rates after a single session of ablation assessed by means of computed tomography 1 month after treatment were 94% and 91% in group 1 and group 2, respectively (P =.68). CONCLUSION: Radiofrequency ablation is a safe and effective treatment for patients with hepatocellular carcinomas 3.1 to 8.0 cm in diameter.

Radiofrequency ablation for subcapsular hepatocellular carcinoma.

BACKGROUND: Limited data from recent studies suggested an increased risk of bleeding complications, needle-track seeding, and local recurrence after radiofrequency ablation (RFA) of subcapsular hepatocellular carcinoma (HCC). METHODS: Between May 2001 and October 2002, 80 patients underwent RFA of 104 HCC nodules. Forty-eight patients had subcapsular HCC (group I), whereas the other 32 patients did not have subcapsular HCC (group II). RFA was performed via celiotomy, laparoscopy, or a percutaneous approach. Subcapsular HCCs were ablated by indirect puncture through nontumorous liver, and the needle track was thermocoagulated. RESULTS: There were no significant differences between groups in treatment morbidity (14.6% vs. 15.6%; P =.898), mortality (2.1% vs. 0%; P = 1.000), complete ablation rate after a single session (89.4% vs. 96.9%; P =.392), local recurrence rate (4.3% vs. 12.5%; P =.216), recurrence-free survival (1 year: 60.9% vs. 49.2%; P =.258), or overall survival (1 year: 88.3% vs. 79.4%; P =.441). After a median follow-up of 13 months, no needle-track seeding or intraperitoneal metastasis was observed. CONCLUSIONS: This study shows that the results of RFA for subcapsular HCCs are comparable to those of RFA for nonsubcapsular HCCs. Subcapsular HCC should not be considered a contraindication for RFA treatment.

Learning curve for radiofrequency ablation of liver tumors: prospective analysis of initial 100 patients in a tertiary institution.

OBJECTIVE: This study aims to evaluate the effect of operator experience on the treatment outcomes of radiofrequency ablation (RFA) for malignant liver tumors. SUMMARY BACKGROUND DATA: RFA is gaining popularity as the ablative therapy of choice for liver tumors. It is generally considered a simple and safe technique, and little attention has been paid to the importance of operator experience in this treatment. A learning curve in this treatment modality has not been documented before. PATIENTS AND METHODS: The clinical data and treatment outcomes of the initial 100 patients undergoing RFA for liver tumors (hepatocellular carcinoma, n = 84; metastasis, n = 15; cholangiocarcinoma n = 1) were collected prospectively. All patients were managed by a single team of surgeons and interventional radiologists. The data of the first 50 patients (group I) and the second 50 patients (group II) were compared. RESULTS: RFA was performed by percutaneous (group I, n = 22; group II, n = 19), open (group I, n = 26; group II, n = 30) or laparoscopic (group I, n = 2; group II, n = 1) approach. In group I, 30 patients (60%) had a solitary tumor and 20 (40%) had multiple tumors; in group II, 35 patients (70%) had a solitary tumor and 15 (30%) had multiple tumors (P = 0.295). The size of the largest tumor was comparable between groups I and II (median, 2.8 cm in both groups; P = 0.508). Group II had significantly shorter hospital stay (median, 4.0 versus 5.5 days; P = 0.048), lower morbidity rate (4% versus 16%; P = 0.046) and higher complete ablation rate (100% versus 85.7%; P = 0.006) than group I. There was 1 hospital death (2%) in group I and 0 in group II. By multivariate analysis, treatment period (group I versus group II) was an independent significant factor affecting the morbidity rate and complete ablation rate. CONCLUSIONS: A low complication rate and a high complete ablation rate could be achieved with the accumulated experience from the first 50 cases of RFA for liver tumors by a specialized team. This study demonstrates that there is a significant learning curve in RFA for liver tumors.

Ultrasound measurement of lumbosacral spine in children.

The aim of this study was to establish normal ultrasound measurements of lumbosacral spine in children as a screening assessment of tethered cord or postoperative retethering of cord. Sonography of lumbosacral spine was performed in 108 neurologically normal children (mean age = 2.1 years) using 5- to 12-MHz linear transducer. M-mode was applied at the posterior and anterior subarachnoid spaces just below the conus medullaris and at the L(5)/S(1) dural sac to document cerebrospinal fluid pulsation of the cauda equina. The oscillation rate and amplitude were measured. Sixteen children with spinal cord anomalies (6 with low tethered cord and 10 postoperative cases of low tethered cord) were also examined. The mean posterior/anterior subarachnoid spaces of normal children were 2.6 mm/1.8 mm at the terminal dural sac. The mean oscillation amplitude and rate of the cauda equina were 0.52 mm and 121/min at the L(5)/S(1) dural sac. The oscillation amplitude at this level demonstrated a statistically significant difference between normal and abnormal groups. In conclusion, we recommend taking the fifth percentile of the normal oscillation amplitude at the L(5)/S(1) dural sac as a reference. Any oscillation amplitude of less than 0.3 mm in a symptomatic patient should alert the clinician to possible cord abnormality, cord tethering, or retethering in postoperative cases.

Thermal ablative therapy for malignant liver tumors: a critical appraisal.

The management of primary and secondary malignant liver tumors poses a great challenge to clinicians. Although surgical resection is the gold-standard treatment, most patients have unresectable malignant liver tumors. Over the past decade, various modalities of loco-regional therapy have gained much interest. Among them, thermal ablative therapy, including cryotherapy, microwave coagulation, interstitial laser therapy, and radiofrequency ablation (RFA), have been proven to be safe and effective. Despite the effective tumor eradication achieved within cryotherapy, the underlying freeze/thaw mechanism has resulted in serious complications that include bleeding from liver cracking and the 'cryoshock' phenomenon. Thermal ablation using microwave and laser therapy for malignant liver tumors is curative and is associated with minimal complications. However, this treatment modality is effective only for tumors <3 cm diameter. Radiofrequency ablation seems to be the most promising form of thermal ablative therapy in terms of a lower complication rate and a larger volume of ablation. However, its use is restricted by the difficulty encountered when using imaging studies to monitor the areas of ablation during and after the procedure. Moreover, the techniques of RFA need to be refined in order to achieve the same oncological radicality of malignant liver tumors as achieved by surgical resection. As each of the loco-regional therapies has its own advantages and limitations, a multidisciplinary approach using a combination of therapies will be the future trend for the management of malignant liver tumors.

Advanced glycation end products and endothelial dysfunction in type 2 diabetes.

OBJECTIVE: Data from experimental studies have suggested that the increased formation of advanced glycation end products (AGEs) is one of the causes of endothelial dysfunction in diabetes. This study was performed to investigate whether changes in endothelium-dependent vasodilation, a marker of endothelial function, were related to serum AGEs concentrations in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: For this study, 170 patients with type 2 diabetes and 83 healthy nondiabetic control subjects of similar age were recruited. Serum AGEs were assayed by competitive enzyme-linked immunosorbent assay. Endothelium-dependent and -independent vasodilation of the brachial artery was measured by high-resolution vascular ultrasound. RESULTS: Serum AGEs were increased in diabetic patients compared with control subjects (4.6 +/- 0.7 vs. 3.1 +/- 0.8 unit/ml; P < 0.01), and both endothelium-dependent (5.1 +/- 2.5 vs. 9.1 +/- 4.1%; P < 0.01) and endothelium-independent vasodilation (13.2 +/- 4.6 vs. 16.4 +/- 5.5%; P < 0.01) were impaired. On univariate analysis of all subjects, serum AGEs correlated with endothelium-dependent vasodilation (r = -0.51, P < 0.01); a weaker association was found with endothelium-independent vasodilation (r = -0.24, P < 0.01). On multiple regression analyses including age, sex, smoking status, and plasma lipids, only serum AGEs remained a significant independent determinant of endothelium-dependent vasodilation (r(2) = 0.34, P < 0.01). CONCLUSIONS: Increased serum concentrations of AGEs in patients with type 2 diabetes is associated with endothelial dysfunction, independent of other cardiovascular risk factors. Further studies to determine whether treatment targeting AGEs will lead to an amelioration of endothelial dysfunction are warranted.

Effects of angiotensin II receptor antagonist on endothelial vasomotor function and urinary albumin excretion in type 2 diabetic patients with microalbuminuria.

BACKGROUND: Microalbuminuria is associated with dysfunction of the vascular endothelium in patients with diabetes mellitus. The objective of the present study was to determine whether treatment with losartan at a dose sufficient to lower urinary albumin excretion was accompanied by an improvement in endothelial function in type 2 diabetic patients with microalbuminuria. METHODS: Endothelial function was measured in 80 type 2 diabetic patients with microalbuminuria and 68 non-diabetic controls using high-resolution vascular ultrasound. The diabetic patients were randomised to receive either losartan 50 mg daily or placebo in a 6-month double-blind study. Urinary albumin excretion and endothelial function were assessed at baseline, 3 and 6 months. RESULTS: Both endothelium-dependent (p<0.01) and -independent vasodilation (p<0.01) were significantly impaired in diabetic patients with or without history of hypertension compared to the non-diabetic controls. At baseline, the losartan- and placebo-treated groups were comparable in their clinical characteristics. Blood pressure did not change significantly in either group throughout the study. Urinary mean albumin excretion rate (MAER) decreased in the losartan-treated group (p<0.01) whereas an increase was observed in the placebo group (p<0.05). At 6 months, the losartan-treated group had significantly lower MAER than the placebo-treated group [54.5 (58.3) vs 78.5 (100.5) microg/min, p<0.05; median (interquartile range)]. No significant differences were found in endothelium-dependent or -independent vasodilation. CONCLUSIONS: Type 2 diabetic patients with microalbuminuria have impaired endothelium-dependent and -independent vasodilation. Treatment with low-dose losartan is sufficient to reduce microalbuminuria in these patients without alteration in endothelial function and systemic blood pressure.