Effectiveness and Complications of Ultrasound Guided Fine Needle Aspiration for Primary Liver Cancer in a Chinese Population with Serum α-Fetoprotein Levels ≤200 ng/ml - A Study Based on 4,312 Patients

Background

Hepatocellular carcinoma (HCC) can be diagnosed by noninvasive approaches with serum α-fetoprotein (AFP) levels >200 ng/ml and/or a radiological imaging study of tumor mass >2 cm in patients with chronic liver disease. Percutaneous fine needle aspiration (FNA) under ultrasound (US) guidance has a diagnostic specificity of 95% and is superior to radiological imaging studies.

Aim

The aim of this study is to elucidate the effectiveness and complications of fine needle aspiration in a Chinese population with primary liver cancer and AFP levels ≤200 ng/ml.

Materials and Methods

A retrospective study was conducted over a period of 28 years. This selection period included patients with a suspected diagnosis of primary liver cancer whose AFP levels were ≤200 ng/ml and who underwent US-FNA. This data was then analyzed with cytomorphological features correlating with medical history, radiological imaging, AFP, and follow-up information.

Results

Of the 1,929 cases with AFP ≤200 mg/ml, 1,756 underwent FNA. Of these, 1,590 cases were determined malignant and the remaining 166 were determined benign. Further, 1,478 malignant cases were diagnosed by FNA alone, and of these, 1,138 were diagnosed as PLC. The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of the diagnoses were 92.96%, 100%, 100%, 59.71%, and 93.62% respectively. There was no significant difference in the sensitivity, specificity, PPV and NPV between the subgroups with tumor size<2 cm and ≥2 cm. Major complications included implantation metastasis and hemorrhage.

Conclusion

Patients with PLC, especially those who present with an AFP ≤200 ng/ml, should undergo FNA. If negative results are obtained by FNA, it still could be HCC and repeated FNA procedure may be needed if highly suspicious of HCC on imaging study. The superiority of FNA in overall accuracy may outweigh its potential complications, such like hemorrhage and implantation metastasis.     

Analysis of Prognostic Factors for Survival after Hepatectomy for Hepatocellular Carcinoma Based on a Bayesian Network

Background

The prognosis of hepatocellular carcinoma (HCC) after hepatectomy involves many factors. Previous studies have evaluated the separate influences of single factors; few have considered the combined influence of various factors. This paper combines the Bayesian network (BN) with importance measures to identify key factors that have significant effects on survival time.

Methods

A dataset of 299 patients with HCC after hepatectomy was studied to establish a BN using a tree-augmented naïve Bayes algorithm that could mine relationships between factors. The composite importance measure was applied to rank the impact of factors on survival time.

Results

124 patients (>10 months) and 77 patients (≤10 months) were correctly classified. The accuracy of BN model was 67.2%. For patients with long survival time (>10 months), the true-positive rate of the model was 83.22% and the false-positive rate was 48.67%. According to the model, the preoperative alpha fetoprotein (AFP) level and postoperative performance of transcatheter arterial chemoembolization (TACE) were independent factors for survival of HCC patients. The grade of preoperative liver function reflected the tendency for postoperative complications. Intraoperative blood loss, tumor size, portal vein tumor thrombosis (PVTT), time of clamping the porta hepatis, tumor number, operative method, and metastasis were dependent variables in survival time prediction. PVTT was considered the most significant for the prognosis of survival time.

Conclusions

Using the BN and importance measures, PVTT was identified as the most significant predictor of survival time for patients with HCC after hepatectomy.     

Circulating microRNA-200 Family as Diagnostic Marker in Hepatocellular Carcinoma

Goals

In this clinical study, we aimed to evaluate the role of circulating microRNA-200 family as a non-invasive tool to identify patients with cirrhosis-associated hepatocellular carcinoma (HCC).

Background

Prognosis of HCC remains poor with increasing incidence worldwide, mainly related to liver cirrhosis. So far, no reliable molecular targets exist for early detection of HCC at surgically manageable stages. Recently, we identified members of the microRNA-200 family as potential diagnostic markers of cirrhosis-associated HCC in patient tissue samples. Their value as circulating biomarkers for HCC remained undefined.

Methods

Blood samples and clinicopathological data of consecutive patients with liver diseases were collected prospectively. Expression of the microRNA-200 family was investigated by qRT-PCR in blood serum samples of 22 HCC patients with and without cirrhosis. Serum samples of patients with non-cancerous chronic liver cirrhosis (n = 22) and of healthy volunteers (n = 15) served as controls.

Results

MicroRNA-141 and microRNA-200a were significantly downregulated in blood serum of patients with HCC compared to liver cirrhosis (p<0.007) and healthy controls (p<0.002). MicroRNA-141 and microRNA-200a could well discriminate patients with cirrhosis-associated HCC from healthy volunteers with area under the receiver-operating characteristic curve (AUC) values of 0.85 and 0.82, respectively. Additionally, both microRNAs could differentiate between HCC and non-cancerous liver cirrhosis with a fair accuracy.

Conclusions

Circulating microRNA-200 family members are significantly deregulated in patients with HCC and liver cirrhosis. Further studies are necessary to confirm the diagnostic value of the microRNA-200 family as accurate serum marker for cirrhosis-associated HCC.     

The Survival Benefit of Liver Transplantation for Hepatocellular Carcinoma Patients with Hepatitis B Virus Infection and Cirrhosis

Background

A precise predictive survival model of liver transplantation (LT) with antiviral prophylaxis for hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) and cirrhosis has not been established. The aim of our study was to identify predictors of outcome after LT in these patients based on tumor staging systems, antitumor therapy pre-LT, and antiviral prophylaxis in patients considered to be unfit by Milan or UCSF criteria.

Methods

From 2002 to 2008, 917 LTs with antiviral prophylaxis were performed on patients with HBV-cirrhosis, and 313 had concurrent HCC.

Results

Stratified univariate and multivariate analyses demonstrated that independent predictors for poor survival were tumor size >7.5 cm (P = 0.001), tumor number >1 (P = 0.005), vascular invasion (P = 0.001), pre-LT serum alpha-fetoprotein (AFP) level ≥1000 ng/ml (P = 0.009), and pre-LT aspartate aminotransferase (AST) level ≥120 IU/L (P = 0.044). Pre-LT therapy for HCC was an independent predictor of better survival (P = 0.028). Based on CLIP and TNM tumor staging systems, HCC patients with HBV-cirrhosis who met the following criteria: solitary tumor ≤7.5 cm, or ≤4 multifocal nodules, the largest lesion ≤5 cm and total tumor diameter ≤10 cm, or more nodules with the largest lesion ≤3 cm, and pre-LT serum AFP level <1000 µg/L and AST level <120 IU/L without vascular invasion and lymph node metastasis who were unfit for UCSF, had survival rates of 89% at 5 years. There was a 47% 5-year survival rate for patients with HCC exceeding the revised criteria.

Conclusions

The current criteria for LT based on tumor size, number and levels of AFP and AST may be modestly expanded while still preserving excellent survival after LT. The expanded criteria combined with antiviral prophylaxis and pre-LT adjuvant therapy for HCC may be a rational strategy to prolong survival after LT for HCC patients with HBV-associated cirrhosis.     

Diagnostic Performance of Alpha-Fetoprotein,Protein Induced by Vitamin K Absence,Osteopontin, Dickkopf-1 and Its Combinations for Hepatocellular Carcinoma

Background & Aims

Alpha-fetoprotein (AFP) is the most widely used serum biomarker for hepatocellular carcinoma (HCC), despite its limitations. As complementary biomarkers, protein induced by vitamin K absence (PIVKA-II), osteopontin (OPN), and Dickkopf-1 (DKK-1) have been proposed. This study aimed to perform a head-to-head comparison of the diagnostic performance of AFP, PIVKA-II, OPN and DKK-1 as single or in combination to seek the best biomarker or panel, and to investigate the clinical factors affecting their performance.

Methods

Using 401 stored plasma samples obtained from 208 HCC patients and 193 liver cirrhosis control patients, plasma AFP, PIVKA-II, OPN and DKK-1 levels were measured by ELISA, and receiver operating characteristic curve analyses were performed for each biomarker and for every combination of two to four markers.

Results

Of the four biomarkers, AFP showed the highest area under the curve (0.786). The sensitivity and specificity for each single biomarker was 62% and 90.2% (AFP>20 ng/mL), 51.0% and 91.2% (PIVKA-II>10 ng/mL), 46.2% and 80.3% (OPN>100 ng/mL), and 50.0% and 80.8% (DKK-1>500 pg/mL), respectively. Among the combinations of two biomarkers, AFP>20 ng/mL or DKK-1>500 pg/mL showed the best diagnostic performance (sensitivity 78.4%, specificity 72.5%). Triple or quadruple combination did not improve the diagnostic performance further. The patient’s age, etiology and tumor invasiveness of HCC affected the performance of each marker.

Conclusions

AFP was the most useful single biomarker for HCC diagnosis, and the combined measurement of AFP and DKK-1 could maximize the diagnostic yield. Clinical decision should be based on the consideration of various factors affecting the diagnostic performance of each biomarker. Efforts to seek novel HCC biomarkers should be continued.     

Cone-Beam Computed Tomography Correlates with Conventional Helical Computed Tomography in Evaluation of Lipiodol Accumulation in HCC after Chemoembolization

Background & Aims

The amount of drug-loaded lipiodol in an HCC tumor post-transarterial chemoembolization (TACE) correlates with the risk of local tumor recurrence. Lipiodol enhancement of a tumor on conventional CT, measured in Hounsfield units (HU), can predict tumor response. Here we investigate whether cone-beam CT (CBCT) can also be used to predict tumor response, providing the benefit of being able to optimize the patient’s treatment plan intra-procedurally.

Methods

A total of 82 HCC nodules (82 patients), ≤5 cm in diameter, were treated with balloon-occluded TACE using miriplatin between December 2013 and November 2014. For each patient, both CBCT and conventional CT images were obtained post-TACE. The degree of correlation between CBCT and conventional CT was determined by comparing identical regions of interest for each imaging modality using pixel values.

Results

The pixel values from conventional CT and CBCT were highly correlated, with a Pearson correlation coefficient of 0.912 (p<0.001). The location of the nodules within the liver did not affect the results; the correlation coefficient was 0.891 (p<0.001) for the left lobe and 0.926 (p<0.001) for the right lobe. The mean pixel value for conventional CT was 439 ± 279 HU, and the mean pixel value for CBCT was 416 ± 311 HU.

Conclusions

CBCT may be used as a substitute for conventional CT to quantitatively evaluate the amount of drug-loaded lipiodol within an HCC nodule and, hence, the efficacy of TACE treatment. The major benefit of using CBCT is the ability to predict the likelihood of local recurrence intra-procedurally, enabling subsequent treatment optimization.     

Effects of a Multidisciplinary Approach to Improve Volume of Diagnostic Material in CT-Guided Lung Biopsies

Background

Recent publications have emphasized the importance of a multidisciplinary strategy for maximum conservation and utilization of lung biopsy material for advanced testing, which may determine therapy. This paper quantifies the effect of a multidisciplinary strategy implemented to optimize and increase tissue volume in CT-guided transthoracic needle core lung biopsies. The strategy was three-pronged: (1) once there was confidence diagnostic tissue had been obtained and if safe for the patient, additional biopsy passes were performed to further increase volume of biopsy material, (2) biopsy material was placed in multiple cassettes for processing, and (3) all tissue ribbons were conserved when cutting blocks in the histology laboratory. This study quantifies the effects of strategies #1 and #2.

Design

This retrospective analysis comparing CT-guided lung biopsies from 2007 and 2012 (before and after multidisciplinary approach implementation) was performed at a single institution. Patient medical records were reviewed and main variables analyzed include biopsy sample size, radiologist, number of blocks submitted, diagnosis, and complications. The biopsy sample size measured was considered to be directly proportional to tissue volume in the block.

Results

Biopsy sample size increased 2.5 fold with the average total biopsy sample size increasing from 1.0 cm (0.9–1.1 cm) in 2007 to 2.5 cm (2.3–2.8 cm) in 2012 (P<0.0001). The improvement was statistically significant for each individual radiologist. During the same time, the rate of pneumothorax requiring chest tube placement decreased from 15% to 7% (P = 0.065). No other major complications were identified. The proportion of tumor within the biopsy material was similar at 28% (23%–33%) and 35% (30%–40%) for 2007 and 2012, respectively. The number of cases with at least two blocks available for testing increased from 10.7% to 96.4% (P<0.0001).

Conclusions

The effect of this multidisciplinary strategy to CT-guided lung biopsies was effective in significantly increasing tissue volume and number of blocks available for advanced diagnostic testing.     

Long-Term Outcomes of Percutaneous Cryoablation for Patients with Hepatocellular Carcinoma within Milan Criteria

Background

Accumulating evidences have suggested that percutaneous cryoablation could be a valuable alternative ablation therapy for HCC but there has been no large cohort-based analysis on its long-term outcomes.

Methods

A series of 866 patients with Child-Pugh class A-B cirrhosis and HCC within Milan criteria who underwent percutaneous cryoablation was long-term followed. The safety, efficacy, 5-year survival, and prognostic factors of percutaneous cryoablation in the treatment of HCC were analyzed.

Results

A total of 1197 HCC lesions were ablated with 1401 cryoablation sessions. Complete response (CR) was achieved in 1163 (97.2%) lesions and 832 (96.1%) patients with 34 (2.8%) major complications, but no treatment-related mortality. After a median of 30.9 months follow-up, 502 (60.3%) patients who achieved CR developed different types of recurrence. The cumulative local tumor recurrence rate was 24.2% at 5-years. Multiple tumor lesions, tumor size > 3 cm, and repeated ablation of same lesion were independent risk factors associated with local recurrence. The 5-year overall survival (OS) rates were 59.5%. Age < 36 years, HCC family history, baseline hepatitis B virus DNA >10⁶ copies/ml, and three HCC lesions were independently and significantly negative predictors to the post-cryoablation OS.

Conclusions

Percutaneous cryoablation is an effective therapy for patients with HCC within Milan criteria, with comparable efficacy, safety and long-term survival to the reported outcomes of radiofrequency ablation.     

Importance of Simultaneous Evaluation of Multiple Risk Factors for Hemodialysis Patients’ Mortality and Development of a Novel Index: Dialysis Outcomes and Practice Patterns Study

Background

For hemodialysis (HD) patients, many risk factors for death are associated with each other intricately. However, they are often considered separately in clinical settings. We evaluated the maintenance HD patients’ risk of death within one year from multiple risk factors simultaneously considering their interrelationships using a novel index (survival index, SI) for HD patients in the United States developed using data from the Dialysis Outcomes and Practice Patterns Study (DOPPS).

Methods

We analyzed data from 3899 and 3765 patients to develop and validate SI, respectively. To predict death within one year, candidate models were developed using logistic regression models. The final model was determined by comparing the accuracy among the models for the prediction of deaths.

Results

The model included age; body mass index; serum creatinine, albumin, total cholesterol and phosphorus levels; history of cardiovascular diseases; and arteriovenous fistula use. SI showed a higher accuracy in predicting death (c-statistic, 0.739) than geriatric nutritional risk index (0.647) and serum albumin level (0.637). The probability of death predicted on the basis of SI matched the observed number of deaths. Cox proportional hazard models for time-dependent SI showed that patients with low SI had a higher risk of death than patients with high SI [reference, Group 4 (26.1≤SI)]; Group 1 (SI<12.7), adjusted hazard ratio, 7.97 (95% CI, 5.02, 12.65); Group 2 (12.7≤SI<19.0), 3.18 (95% CI, 1.96, 5.16); Group 3 (19.0≤SI<26.1), 2.20 (95% CI, 1.33, 3.66).

Conclusion

Results of this study suggest that the simultaneous evaluation of multiple risk factors can more accurately assess patients’ prognosis and identify patients at an increased risk of death than single factors.     

Prediction of Post-Weaning Fibrinogen Status during Cardiopulmonary Bypass: An Observational Study in 110 Patients

Background

After cardiac surgery with cardiopulmonary bypass (CPB), acquired coagulopathy often leads to post-CPB bleeding. Though multifactorial in origin, this coagulopathy is often aggravated by deficient fibrinogen levels.

Objective

To assess whether laboratory and thrombelastometric testing on CPB can predict plasma fibrinogen immediately after CPB weaning.

Patients / Methods

This prospective study in 110 patients undergoing major cardiovascular surgery at risk of post-CPB bleeding compares fibrinogen level (Clauss method) and function (fibrin-specific thrombelastometry) in order to study the predictability of their course early after termination of CPB. Linear regression analysis and receiver operating characteristics were used to determine correlations and predictive accuracy.

Results

Quantitative estimation of post-CPB Clauss fibrinogen from on-CPB fibrinogen was feasible with small bias (+0.19 g/l), but with poor precision and a percentage of error >30%. A clinically useful alternative approach was developed by using on-CPB A10 to predict a Clauss fibrinogen range of interest instead of a discrete level. An on-CPB A10 ≤10 mm identified patients with a post-CPB Clauss fibrinogen of ≤1.5 g/l with a sensitivity of 0.99 and a positive predictive value of 0.60; it also identified those without a post-CPB Clauss fibrinogen <2.0 g/l with a specificity of 0.83.

Conclusions

When measured on CPB prior to weaning, a FIBTEM A10 ≤10 mm is an early alert for post-CPB fibrinogen levels below or within the substitution range (1.5–2.0 g/l) recommended in case of post-CPB coagulopathic bleeding. This helps to minimize the delay to data-based hemostatic management after weaning from CPB.     

Radiofrequency Ablation Is Superior to Ethanol Injection in Early-Stage Hepatocellular Carcinoma Irrespective of Tumor Size

Background

Randomized trials suggest that radiofrequency ablation (RFA) may be more effective than percutaneous ethanol injection (PEI) in the treatment of hepatocellular carcinoma (HCC). However, the survival advantage of RFA needs confirmation in daily practice.

Methods

We conducted a population-based cohort study using the Taiwan Cancer Registry, National Health Insurance claim database and National Death Registry data from 2004 through 2009. Patients receiving PEI or RFA as first-line treatment for newly-diagnosed stage I-II HCC were enrolled.

Results

A total of 658 patients receiving RFA and 378 patients receiving PEI treatment were included for final analysis. The overall survival (OS) rates of patients in the RFA and PEI groups at 5-year were 55% and 42%, respectively (p < 0.01). Compared to patients that received PEI, those that received RFA had lower risks of overall mortality and first-line treatment failure (FTF), with adjusted hazard ratios (HRs) [95% confidence interval (CI)] of 0.60 (0.50-0.73) for OS and 0.54 (0.46-0.64) for FTF. The favorable outcomes for the RFA group were consistently significant for patients with tumors > 2 cm as well as for those with tumors < 2 cm. Consistent results were also observed in other subgroup analyses defined by gender, age, tumor stage, and co-morbidity status.

Conclusion

RFA provides better survival benefits than PEI for patients with unresectable stage I-II HCC, irrespective of tumors > 2 cm or ≤ 2 cm, in contemporary clinical practice.     

Surgical Strategy for Hepatocellular Carcinoma Patients with Portal/Hepatic Vein Tumor Thrombosis

Background

Portal/hepatic vein tumor thrombosis (PVTT/HVTT) in hepatocellular carcinoma (HCC) is a sign of advanced stage disease and is associated with poor prognosis. This study investigated the surgical outcomes of patients with HCC and PVTT/HVTT to determine the most appropriate surgical treatment strategy for these patients.

Materials and Methods

The study population included 77 HCC patients from January 2004 to June 2009 who underwent hepatectomy in our department and were diagnosed with PVTT/HVTT based on pathological examination. The patients were divided into two groups: in group 1, PVTT/HVTT was located in the hepatic resection area and removed with the tumor en bloc (38 cases); in group 2, PVTT/HVTT was beyond the resection line and removed by suction or thrombectomy (39 cases). Concerning the factor of surgical margins, the patients were further divided into four subgroups: group 1A: patients in group 1 with surgical margins ≤1 cm (28 cases); group 1B: patients in group 1 with surgical margins >1 cm (9 cases); group 2A: patients in group 2 with surgical margins ≤1 cm (28 cases); and group 2B: patients in group 2 with surgical margins >1 cm (9 cases).

Results

Most of the characteristics of groups 1 and 2 were similar. Patients in group 2 had significantly higher median blood loss (p=0.002) and higher blood transfusion rate (p=0.002) during the operation, which were not considered prognostic factors (p=0.323 and 0.571, respectively). The median overall survival (OS) duration in group 1 was significantly longer than that in group 2 (14.3 vs. 10.4 months, p=0.047). The median OS durations in groups 1A, 1B, 2A, and 2B were 14.3, 42.7, 7.5, and 18.0 months, respectively, which were significantly different(p=0.018).

Conclusions

When PVTT/HVTT is located in the hepatic resection area and removed with the tumor en bloc, the median OS duration is longer. Based on this finding, widening the surgical margins when technically possible may increase OS.     

Near Work Related Parameters and Myopia in Chinese Children: the Anyang Childhood Eye Study

Purpose

To examine the associations of near work related parameters with spherical equivalent refraction and axial length in Chinese children.

Methods

A total of 1770 grade 7 students with mean age of 12.7 years were examined with cycloplegic autorefraction and axial length. Questions were asked regarding time spent in near work and outdoors per day, and near work related parameters.

Results

Multivariate models revealed the following associations with greater odds of myopia: continuous reading (> 45min), odds ratio [OR], 1.4; 95% confidence interval [CI], 1.1-1.8; close television viewing distance (≤ 3m), OR, 1.7; 95% CI, 1.2-2.3; head tilt when writing, OR, 1.3; 95% CI, 1.1-1.7, and desk lighting using fluorescent vs. incandescent lamp, OR, 1.5; 95% CI, 1.2-2.0. These factors, together with close reading distance and close nib-to-fingertip distance were significantly associated with greater myopia (P<0.01). Among near work activities, only reading more books for pleasure was significantly associated with greater myopia (P=0.03). Television viewing distance (≤ 3 m), fluorescent desk light, close reading distance (≤20 cm) and close nib-to-fingertip distance (≤ 2 cm) were significantly associated with longer axial length (P<0.01). Reading distance, desk light, and reading books for pleasure had significant interaction effects with parental myopia.

Conclusions

Continuous reading, close distances of reading, television viewing and nib-to-fingertip, head tilt when writing, reading more books for pleasure and use of fluorescent desk light were significantly associated with myopia in 12-year-old Chinese children, which indicates that visual behaviors and environments may be important factors mediating the effects of near work on myopia.     

Dietary Intervention for Overweight and Obese Adults: Comparison of Low-Carbohydrate and Low-Fat Diets. A Meta-Analysis

Background

Reduced calorie, low fat diet is currently recommended diet for overweight and obese adults. Prior data suggest that low carbohydrate diets may also be a viable option for those who are overweight and obese.

Purpose

Compare the effects of low carbohydrate versus low fats diet on weight and atherosclerotic cardiovascular disease risk in overweight and obese patients.

Data Sources

Systematic literature review via PubMed (1966–2014).

Study Selection

Randomized controlled trials with ≥8 weeks follow up, comparing low carbohydrate (≤120gm carbohydrates/day) and low fat diet (≤30% energy from fat/day).

Data Extraction

Data were extracted and prepared for analysis using double data entry. Prior to identification of candidate publications, the outcomes of change in weight and metabolic factors were selected as defined by Cochrane Collaboration. Assessment of the effects of diets on predicted risk of atherosclerotic cardiovascular disease risk was added during the data collection phase.

Data Synthesis

1797 patients were included from 17 trials with <1 year follow up in 12. Compared with low fat diet, low carbohydrate was associated with significantly greater reduction in weight (Δ = -2.0 kg, 95% CI: -3.1, -0.9) and significantly lower predicted risk of atherosclerotic cardiovascular disease events (p<0.03). Frequentist and Bayesian results were concordant. The probability of greater weight loss associated with low carbohydrate was >99% while the reduction in predicted risk favoring low carbohydrate was >98%.

Limitations

Lack of patient-level data and heterogeneity in dropout rates and outcomes reported.

Conclusions

This trial-level meta-analysis of randomized controlled trials comparing LoCHO diets with LoFAT diets in strictly adherent populations demonstrates that each diet was associated with significant weight loss and reduction in predicted risk of ASCVD events. However, LoCHO diet was associated with modest but significantly greater improvements in weight loss and predicted ASCVD risk in studies from 8 weeks to 24 months in duration. These results suggest that future evaluations of dietary guidelines should consider low carbohydrate diets as effective and safe intervention for weight management in the overweight and obese, although long-term effects require further investigation.     

Sonographic and Clinical Features of Papillary Thyroid Microcarcinoma Less than or Equal to Five Millimeters: A Retrospective Study

Objective

To retrospectively compare the sonographic and clinical features of papillary thyroid microcarcinoma (PTMC) ≤5 mm and PTMC >5 mm to improve the diagnostic value of ultrasonography.

Methods

A total of 367 cases of PTMC between January 2013 and December 2014 was included in this study. The patients were classified into group A (≤5 mm, n = 181) or group B (>5 mm, n = 186), and the sonographic and clinical features were reviewed and compared between the two groups.

Results

There was no significant difference in the shape, ratio of length/width, boundary, peripheral halo ring, echogenicity, cystic change and accompanying Hashimoto''s thyroiditis between these two groups. However, the calcification (61.3% vs. 72.6%) and hypervascularity (13.8% vs. 24.7%) were more frequent in group B (p = 0.026 and 0.008, respectively). The patients were younger, and more patients were aged less than 45 years (41.4% vs. 57.0%) in group B. Capsular invasion (7.2% vs. 34.4%), multifocality (21.5% vs. 48.9%), bilaterality (17.1% vs. 39.8%), central lymph node metastasis (13.8% vs. 38.2%) and lateral lymph node metastasis (1.1% vs. 5.4%) were more frequent in group B. No clinical or sonographic feature was related to cervical lymph node metastasis in group A, while less than 45 years in age (p = 0.010), male gender (p = 0.040), capsular invasion (p<0.001), multifocality (p = 0.016) and calcification (p = 0.042) were related to cervical lymph node metastasis in group B.

Conclusions

The sonographic features of PTMC ≤5 mm were similar to those of PTMC >5 mm, including an irregular shape, a length/width ratio of ≥1, an unclear boundary, no peripheral halo ring, hypoechogenicity, no cystic change, calcification, no hypervascularity and no accompanying Hashimoto''s thyroiditis. The clinical features of PTMC ≤5 mm were less aggressive than those of PTMC >5 mm.     

Hepatitis B e Antigen Status and Hepatitis B DNA Levels in Women of Childbearing Age with Chronic Hepatitis B Infection Screening for Clinical Trials

Background

Perinatal or mother-to-child transmission of hepatitis B virus (HBV) results in a high frequency of chronic infection. Risk of mother-to-child transmission is associated with maternal viral factors including hepatitis B e antigen (HBeAg) positivity and viral load.

Aim

To investigate associations between age, HBeAg status, HBV DNA levels and genotype in female patients screened for inclusion into two contemporary, randomized HBV trials.

Methods

Retrospective analyses focused on differences between women of childbearing age (≤44 years) and older women. Female patients (N = 355; 18–69 years) were included in the analysis: 41.7% of patients were Asian. In total, 44.4% were HBeAg-positive.

Results

Significantly more women aged ≤44 years were HBeAg-positive compared to women ≥45 years (57.2% versus 27.5%, respectively, p<0.0001), this proportion declined with increasing age. Younger women were significantly more likely to have high HBV viral load (HBV DNA>10⁸ copies mL: ≤44 years 46.0% vs ≥45 years 25.5%, respectively; p<0.0001), and this declined with increasing age. HBeAg positivity was slightly higher in Asian women, associated with a higher proportion of HBV genotypes B and C in this population. There was no obvious relationship between genotype and viral load.

Conclusions

Women of childbearing age with CHB are more likely to have high HBV viral load and HBeAg positivity than older women; this likelihood decreases with age. Maternal serological and virological status should therefore be established early in pregnancy, taking into account age and genotype, and a risk-reducing strategy implemented in any patient who is HBeAg positive and has a high viral load.     

Quantitative Evaluation of Diffusion and Dynamic Contrast-Enhanced MR in Tumor Parenchyma and Peritumoral Area for Distinction of Brain Tumors

Purpose

To quantitatively evaluate the diagnostic efficiency of parameters from diffusion and dynamic contrast-enhanced MR which based on tumor parenchyma (TP) and peritumoral (PT) area in classification of brain tumors.

Methods

45 patients (male: 23, female: 22; mean age: 46 y) were prospectively recruited and they underwent conventional, DCE-MR and DWI examination. With each tumor, 10–15 regions of interest (ROIs) were manually placed on TP and PT area. ADC and permeability parameters (K^trans, Ve, Kep and iAUC) were calculated and their diagnostic efficiency was assessed.

Results

In TP, all permeability parameters and ADC value could significantly discriminate Low- from High grade gliomas (HGG) (p<0.001); among theses parameters, Ve demonstrated the highest diagnostic power (iAUC: 0.79, cut-off point: 0.15); the most sensitive and specific index for gliomas grading were K^trans (84%) and Kep (89%). While, in PT area, only K^trans could help in gliomas grading (P = 0.009, cut-off point: 0.03 min^-1). Moreover, in TP, mean Ve and iAUC of primary central nervous system lymphoma (PCNSL) and metastases were significantly higher than that in HGG (p<0.003). Further, in PT area, mean K^trans (p≤0.004) could discriminate PCNSL from HGG and ADC (p≤0.003) could differentiate metastases with HGG.

Conclusions

Quantitative ADC and permeability parameters from Diffusion and DCE-MR in TP and PT area, especially DCE-MR, can aid in gliomas grading and brain tumors discrimination. Their combined application is strongly recommended in the differential diagnosis of these tumor entities.     

Non-Contrast Enhanced MR Angiography (NCE-MRA) of the Calf: A Direct Comparison between Flow-Sensitive Dephasing (FSD) Prepared Steady-State Free Precession (SSFP) and Quiescent-Interval Single-Shot (QISS) in Patients with Diabetes

Objectives

To compare the image quality and diagnostic performance of two non-contrast enhanced MR angiography (NCE-MRA) techniques using flow-sensitive dephasing (FSD) prepared steady-state free precession (SSFP) and quiescent-interval single-shot (QISS) for the calf arteries in patients with diabetes.

Materials and Methods

Twenty six patients underwent the two NCE-MRA techniques followed by contrast-enhanced MRA (CE-MRA) of lower extremity on a 1.5T MR system. Image quality scores, arterial stenosis scores, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), vessel sharpness, and diagnostic accuracy for detecting more than 50% arterial stenosis were evaluated and statistically compared using CE-MRA as the reference standard.

Results

All examinations were performed successfully. Of the total 153 calf arterial segments obtained in the 26 patients, FSD and QISS showed no significant difference in the number of diagnostic arterial segments (151 [98%] vs. 147 [96%], respectively, P>0.05). The image quality of FSD was higher than that of QISS in the peroneal artery and posterior tibial artery (P<0.05), but no significant difference in the anterior tibial artery (P>0.05). SNR and CNR of FSD were higher than those of QISS (P<0.01), while FSD showed comparable vessel sharpness compared with QISS (P>0.05). The time efficiency of SNR and CNR between FSD and QISS showed no significant difference when taking into account the times for FSD-related scout scans. There was no difference in sensitivity (95% vs. 93%, P>0.05) and negative predictive value (98% vs. 97%, P>0.05) between FSD and QISS for detecting stenosis greater than 50%. However, FSD showed higher specificities (99% vs. 92%, P<0.05) and diagnostic accuracy (98% vs. 92%, P<0.05) compared to QISS.

Conclusion

Both FSD and QISS had similar high sensitivity and negative predictive value for detecting calf arteries with over 50% stenosis, but FSD showed slightly higher diagnostic specificity and better depiction of arterial lesions due to its isotropic submillimeter spatial resolution. QISS, being an easier to use and less time-consuming technique, could be a method of choice for rapid screening of arterial disease of the lower extremity.     

Stereotactic Body Radiation Therapy as an Alternative Treatment for Small Hepatocellular Carcinoma

Background

Even with early stage hepatocellular carcinoma (HCC), patients are often ineligible for surgical resection, transplantation, or local ablation due to advanced cirrhosis, donor shortage, or difficult location. Stereotactic body radiation therapy (SBRT) has been established as a standard treatment option for patients with stage I lung cancer, who are not eligible for surgery, and may be a promising alternative treatment for patients with small HCC who are not eligible for curative treatment.

Materials and Methods

A registry database of 93 patients who were treated with SBRT for HCC between 2007 and 2009 was analyzed. A dose of 10-20 Gy per fraction was given over 3-4 consecutive days, resulting in a total dose of 30-60 Gy. The tumor response was determined using dynamic computed tomography or magnetic resonance imaging, which was performed 3 months after completion of SBRT.

Results

The median follow-up period was 25.6 months. Median size of tumors was 2 cm (range: 1-6 cm). Overall patients’ survival rates at 1 and 3 years were 86.0% and 53.8%, respectively. Complete and partial tumor response were achieved in 15.5% and 45.7% of patients, respectively. Local recurrence-free survival rate was 92.1% at 3 years. Most local failures were found in patients with HCCs > 3 cm, and local control rate at 3 years was 76.3% in patients with HCC > 3 cm, 93.3% in patients with tumors between 2.1-3 cm, and 100% in patients with tumors ≤ 2 cm, respectively. Out-of-field intrahepatic recurrence-free survival rates at 1 and 3 years were 51.9% and 32.4%, respectively. Grade ≥ 3 hepatic toxicity was observed in 6 (6.5%).

Conclusions

SBRT was effective in local control of small HCC. SBRT may be a promising alternative treatment for patients with small HCC which is unsuitable for other curative therapy.     

Risk of Developing Depressive Disorders following Hepatocellular Carcinoma: A Nationwide Population-Based Study

Background & Aims

To evaluate the risk of depressive disorders among patients with Hepatocellular Carcinoma (HCC) using the National Health Insurance Research Database (NHIRD) in Taiwan.

Methods

We conducted a retrospective study of a newly diagnosed HCC cohort of 55,973 participants who were selected from the NHIRD. Patients were observed for a maximum of 6 years to determine the rates of newly onset depressive disorders, and Cox regression was used to identify the risk factors associated with depressive disorders in HCC patients.

Results

Of the total 55,973 HCC patients, 1,041 patients (1.86%) were diagnosed with depressive disorders during a mean (SD) follow-up period of 1.1 (1.2) years. The Cox multivariate proportional hazards analysis showed that age of 40–59 (HR 1.376, 95% CI 1.049–1.805, p = 0.021), age of 60–79 (HR 1.341, 95% CI 1.025–1.753, p = 0.032), women (HR 1.474 95% CI 1.301–1.669, p < 0.001), metastasis (HR 1.916, 95% CI 1.243–2.953, p = 0.003), and HCV (HR 1.445, 95% CI 1.231–1.697, p < 0.001) were independent risk factors for developing depressive disorders.

Conclusions

Our study indicated a subsequent risk of depressive disorders in patients with HCC, and the risk increased for those with female gender, aged 40 to 59, aged 60 to 79, with metastasis, or with HCV. Psychological evaluation and support are two critical issues in these HCC patients with the risk factors.