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1.  Effectiveness of lorazepam-assisted interviews in an adolescent with dissociative amnesia: A case report★ 
Neural Regeneration Research  2013;8(2):186-190.
To facilitate gathering information during a psychiatric interview, some psychiatrists advocate augmenting the interview using drugs. Rather than barbiturates, benzodiazepines have been used for drug-assisted interviews. Dissociative amnesia is one of the indications for these interviews. Herein, we present the case of a 15-year-old female who was diagnosed as having dissociative amnesia because of conflicts with her friends. She was administered a lorazepam-assisted interview to aid recovery of her memories. In this case, a small dose of lorazepam was sufficient to recover her memories without any adverse effects.
doi:10.3969/j.issn.1673-5374.2013.02.012
PMCID: PMC4107513  PMID: 25206490
neural regeneration; clinical practice; dissociative amnesia; dissociative disorder; dissociation; drug-assisted interview; amobarbital, lorazepam; benzodiazepine; adolescent; memory loss; emotional distress; distress; grant-supported paper; neuroregeneration
2.  Prognosis Prediction of Measurable Enhancing Lesion after Completion of Standard Concomitant Chemoradiotherapy and Adjuvant Temozolomide in Glioblastoma Patients: Application of Dynamic Susceptibility Contrast Perfusion and Diffusion-Weighted Imaging 
PLoS ONE  2014;9(11):e113587.
Purpose
To assess the prognosis predictability of a measurable enhancing lesion using histogram parameters produced by the normalized cerebral blood volume (nCBV) and normalized apparent diffusion coefficient (nADC) after completion of standard concomitant chemoradiotherapy (CCRT) and adjuvant temozolomide (TMZ) medication in glioblastoma multiforme (GBM) patients.
Materials and Methods
This study was approved by the institutional review board (IRB), and the requirement for informed consent was waived. A total of 59 patients with newly diagnosed GBM who received standard CCRT with TMZ and adjuvant TMZ for six cycles underwent perfusion-weighted and diffusion-weighted imaging. Twenty-seven patients had a measurable enhancing lesion and 32 patients lacked a measurable enhancing lesion based on the Response Assessment in Neuro-Oncology (RANO) criteria in the follow-up MRI, which was performed within 3 months after adjuvant TMZ therapy was completed. We measured the nCBV and nADC histogram parameters based on the measurable enhancing lesion. The progression free survival (PFS) was analyzed by the Kaplan-Meier method with the use of the log-rank test.
Results
The median PFS of patients lacking measurable enhancing lesion was longer than for those with measurable enhancing lesions (17.6 vs 3.3 months, P<.0001). There was a significant, positive correlation between the 99th percentile nCBV value of a measurable enhancing lesion and the PFS (P = .044, R2 = .152). In addition, the median PFS was longer in patients with a 99th percentile nCBV value ≧4.5 than it was in those with a value <4.5 (4.4 vs 3.1 months, P = .036).
Conclusion
We found that the nCBV value can be used for the prognosis prediction of a measurable enhancing lesion after the completion of standard treatment for GBM, wherein a high 99th percentile nCBV value (≧4.5) suggests a better PFS for GBM patients.
doi:10.1371/journal.pone.0113587
PMCID: PMC4242641  PMID: 25419975
3.  The control of blood pressure might be important in delaying progression of arterial aging in patients with type 2 diabetes mellitus 
Objective
Arterial stiffness, as assessed by the brachial-ankle pulse wave velocity (baPWV), is associated with arterial aging and has been consistently linked to cardiovascular disease. The factors involved in reducing the progression of arterial stiffness in patients with type 2 diabetes mellitus (DM) have not yet been fully established.
Methods
Of 478 patients who underwent two baPWV measurements (at baseline and 1 year later) at the Department of Internal Medicine, St Vincent’s Hospital, from November 2009 to June 2011, 341 subjects were enrolled in this study (male to female ratio =150:191; mean age, 62.1±7.7 years). The 341 subjects were over the age of 50 with type 2 DM, were diagnosed without peripheral artery disease, and 170 if the subjects (50%) had hypertension.
Results
baPWV at baseline increased in a linear manner along with age (β=22.8, t=10.855; P<0.0001, R2=0.258). After 1 year follow-up, the change in baPWV (ΔbaPWV) was variable (median 32.7 cm/s [approximate range, −557 to ∼745]). In multiple linear regression, the change in systolic blood pressure (β=7.142, 95% confidence interval =4.557–9.727; P<0.0001, R2=0.305) was associated with ΔbaPWV during follow-up. The change in glycated hemoglobin (HbA1c) and a glycemic control of keeping HbA1c levels below 7.0% were not associated with ΔbaPWV.
Conclusion
We found that the variation of blood pressure was associated with the progression of vascular aging of the large- to middle-sized arteries in patients with type 2 DM. Therefore, control of blood pressure might be important in reducing arterial aging or PWV in patients with type 2 DM.
doi:10.2147/CIA.S66019
PMCID: PMC4136951  PMID: 25143718
arterial aging; blood pressure; diabetes mellitus
4.  Ultrasound-guided sclerotherapy for benign non-thyroid cystic mass in the neck 
Ultrasonography  2014;33(2):83-90.
Surgical excision has traditionally been the treatment of choice for benign non-thyroid cystic neck masses, including lymphatic malformation, ranula, branchial cleft cyst, thyroglossal duct cyst, and parathyroid cyst. However, there is a tendency toward recurrence after surgery, and surgery may be accompanied by complications, including nerve injuries, vascular injuries, and scar formation. Ultrasound-guided sclerotherapy using various agents has been challenged and successfully applied as an alternative treatment for benign non-thyroid cystic neck masses. This report reviews the available sclerosing agents and describes the applications of sclerotherapy to the treatment of benign cystic masses in the neck.
doi:10.14366/usg.13026
PMCID: PMC4058977  PMID: 24936500
Neck; Cysts; Ultrasonography; Sclerotherapy; Picibanil
5.  The clinical usefulness of central hemodynamics to evaluate diastolic dysfunction in subjects without hypertension 
Objective
Diastolic dysfunction is associated with increased arterial stiffness in patients with hypertension. However, the role of arterial stiffness in diastolic dysfunction in subjects without hypertension has not been fully established.
Materials and methods
A total of 287 subjects (male:female ratio 121:166, mean age 53.0±14.4 years) without hypertension or any heart disease who simultaneously received transthoracic echocardiography and noninvasively semiautomated radial artery applanation tonometry (with an Omron HEM-9000AI) in the Department of Internal Medicine, St Vincent’s Hospital, from July 2011 to September 2012, were enrolled in this study.
Results
A total of 147 subjects (male:female ratio 59:88, mean age 61.7±9.9 years), representing 51.2% of the 287 subjects, had diastolic dysfunction (defined as abnormal relaxation pattern of mitral inflow). There were significant differences in systolic blood pressure (BP), pulse pressure, late systolic peak pressure (SBP2), and radial augmentation index (RaAIx) between normal diastolic function and diastolic dysfunction. ΔBP was defined as systolic BP minus SBP2, because of the difference in systolic BP between the two groups. ΔBP (odds ratio [OR] 1.059, 95% confidence interval [CI] 1.005–1.115; P=0.032) and RaAIx (odds ratio 1.027, 95% CI 1.009–1.044, P=0.003) were associated with diastolic dysfunction. A receiver operating-characteristic curve showed that ΔBP (area under the curve 0.875, 95% CI 0.832–0.911) and RaAIx (area under the curve 0.878, 95% CI 0.835–0.914) were associated with diastolic dysfunction.
Conclusion
We found that ΔBP and increased RaAIx were associated with diastolic dysfunction in subjects without hypertension after adjustment for age and sex. Therefore, it is suggested that noninvasive estimation of central BP may be useful to reflect diastolic dysfunction in subjects with normal peripheral BP.
doi:10.2147/CIA.S58810
PMCID: PMC3974697  PMID: 24729693
central blood pressure; augmentation index; diastolic dysfunction
7.  Hyperfunction Thyroid Nodules: Their Risk for Becoming or Being Associated with Thyroid Cancers 
Korean Journal of Radiology  2013;14(4):643-652.
Objective
To retrospectively evaluate the risk of thyroid cancer in patients with hyperfunctioning thyroid nodules through ultrasonographic-pathologic analysis.
Materials and Methods
Institutional review board approval was obtained and informed consent was waived. From 2003 to 2007, 107 patients consecutively presented with hot spots on thyroid scans and low serum thyroid-stimulating hormone levels. Among them, 32 patients who had undergone thyroid ultrasonography were analyzed in this study. Thyroid nodules depicted on ultrasonography were classified based on size and categorized as benign, indeterminate, or suspicious malignant nodules according to ultrasonographic findings. The thyroid nodules were determined as either hyperfunctioning or coexisting nodules and were then correlated with pathologic results.
Results
In 32 patients, 42 hyperfunctioning nodules (mean number per patient, 1.31; range, 1-6) were observed on thyroid scans and 68 coexisting nodules (mean, 2.13; range, 0-7) were observed on ultrasonography. Twenty-five patients (78.1%) had at least one hyperfunctioning (n = 17, 53.1%) or coexisting (n = 16, 50.0%) nodule that showed a suspicious malignant feature larger than 5 mm (n = 8, 25.0%), or an indeterminate feature 1 cm or greater (n = 20, 62.5%) in diameter, which could have been indicated by using fine needle aspiration (FNA). Seven patients were proven to have 11 thyroid cancers in 3 hyperfunctioning and 8 coexisting nodules. All of these had at least one thyroid cancer, which could have been indicated by using FNA. The estimated minimal risk of thyroid cancer was 6.5% (7/107).
Conclusion
Patients with hyperfunctioning nodules may not be safe from thyroid cancer because hyperfunctioning nodules can coexist with thyroid cancer nodules. To screen out these cancers, ultrasonography should be performed.
doi:10.3348/kjr.2013.14.4.643
PMCID: PMC3725360  PMID: 23901323
Hyperfunctioning nodule; Radionuclide imaging; Thyroid cancer; Ultrasonography; Guideline
8.  Usefulness of Integrated PET/MRI in Head and Neck Cancer: A Preliminary Study 
Purpose
The new modality of an integrated positron emission tomography/magnetic resonance imaging (PET/MRI) has recently been introduced but not validated. Our objective was to evaluate clinical performance of 18F-fluoro-2-deoxyglucose (18F-FDG) PET/MRI in patients with head and neck cancer.
Methods
This retrospective study was conducted between January 2013 and February 2013. Ten patients (eight men, two women; mean age, 61.4 ± 13.4 years) with histologically proven head and neck tumors were enrolled. Whole-body PET/MRI and regional positron emission tomography (PET) with dedicated MRI were sequentially obtained. Maximum standardized uptake value (SUVmax), SUVmean, metabolic tumor volume, total lesion glycolysis and contrast enhancement were analyzed. A total of ten whole-body positron emission tomography (PET), ten regional positron emission tomography (PET), ten dedicated MRI and ten regional PET/gadolinium-enhanced T1-weighted (Gd)-MRI images were analyzed for initial staging. Two nuclear medicine physicians analyzed positron emission tomography (PET) and PET/MRI with a consensus. One radiologist analyzed dedicated MRI. The primary lesions and number of metastatic lymph nodes analyzed from each image were compared.
Results
Eight patients were diagnosed with head and neck cancer (one tongue cancer, four tonsillar cancers, one nasopharyngeal cancer and two hypopharyngeal cancers) by histological diagnosis. Two benign tumors (pleomorphic adenoma and Warthin tumor) were diagnosed with surgical operation. Whole-body positron emission tomography (PET) and regional positron emission tomography (PET) attenuated by MRI showed good image quality for the lesion detection. Whole-body positron emission tomography (PET) and regional positron emission tomography (PET) detected ten primary sites and compensated for a missed lesion on dedicated MRI. A discordant number of suspicious lymph node metastases was noted according to the different images; 22, 16, 39 and 40 in the whole-body positron emission tomography (PET) only, dedicated MR, regional positron emission tomography (PET) only and regional PET/Gd-MRI, respectively. There was no distant metastasis based on analysis of whole-body positron emission tomography (PET) and whole-body PET/Dixon-volume interpolated breathhold examination (VIBE) MRI. Regional PET/Gd-MRI combined with whole-body PET/MRI modified staging in three patients. Lesions of primary tumor and suspicious metastasis were well detected on both value of SUVmax and visual analysis. The regional PET/Gd-MRI combined with whole-body PET/MRI showed convenient clinical staging performance compared with positron emission tomography (PET) and MRI alone.
Conclusion
In this preliminary study, PET attenuated by MRI showed good image quality to detect lesions. And whole-body PET/MRI as a single modality was feasible for staging in a clinical setting. Whole-body positron emission tomography (PET), regional positron emission tomography (PET), dedicated MRI and regional PET/Gd-MRI showed discordant results in lesion detection. These discordant results might be synergistic effect for accurate staging.
doi:10.1007/s13139-013-0252-2
PMCID: PMC4028474  PMID: 24900149
Head and neck cancer; Oncology; PET; MRI; Integrated PET/MRI
9.  Use of Surgical Sponge with Running Sutures for Securing Full-Thickness Skin Grafts 
ISRN Dermatology  2011;2011:470921.
One of the most common methods of skin defect repairing is the use of a skin graft. It is simple and reliable technique, although sometimes it is not totally successful due to hematoma and seroma formation between the skin graft and the recipient bed. Here in, we present a method to secure the skin grafts using a surgical sponge with two running sutures. This technique ensures high survival rate of the skin grafts, and in addition it is easy to be performed by the surgeon only.
doi:10.5402/2011/470921
PMCID: PMC3262541  PMID: 22363852
10.  How good is cola for dissolution of gastric phytobezoars? 
AIM: To evaluate the efficacy of cola treatment for gastric phytobezoars, including diospyrobezoars.
METHODS: A total of 17 patients (range: 48 to 78 years) with symptomatic gastric phytobezoars treated with cola and adjuvant endoscopic therapy were reviewed. Three liters of cola lavage (10 cases) or drink (7 cases) were initially used, and then endoscopic fragmentation was done for the remnant bezoars by using a lithotripsy basket or a polypectomy snare. The overall success of dissolving a gastric phytobezoars with using three liters of cola and the clinical and endoscopic findings were compared retrospectively between four cases of complete dissolution by using only cola and 13 cases of partial dissolution with cola.
RESULTS: After 3 L of cola lavage or drinking, a complete dissolution of bezoars was achieved in four patients (23.5%), while 13 cases (76.5%) were only partially dissolved. Phytobezoars (4 of 6 cases) were observed more frequently than diospyrobezoars (0 of 11) in the group that underwent complete dissolution (P = 0.006). Gender, symptom duration, size of bezoar and method of cola administration were not significantly different between the two groups. Twelve of 13 patients with residual bezoars were completely treated with a combination of cola and endoscopic fragmentation.
CONCLUSION: The rate of complete dissolution with three liters of cola was 23.5%, but no case of diospyrobezoar was completely dissolved using this method. However, pretreatment with cola may be helpful and facilitate endoscopic fragmentation of gastric phytobezoars.
doi:10.3748/wjg.15.2265
PMCID: PMC2682243  PMID: 19437568
Gastric phytobezoars; Diospyrobezoars; Cola; Dissolution; Clinical efficacy
11.  Antiviral efficacy of adefovir dipivoxil versus lamivudine in patients with chronic hepatitis B sequentially treated with lamivudine and adefovir due to lamivudine resistance 
AIM: To compare the antiviral efficacy of adefovir (ADV) in lamivudine (LMV)-resistant patients with LMV treatment in nucleoside-naïve patients, using serum samples collected sequentially during the course of treatment progressing from LMV to ADV.
METHODS: Forty-four patients with chronic hepatitis B (CHB) were included. The patients were initially treated with LMV and then switched to ADV when LMV resistance developed. Antiviral efficacy was assessed by measuring the following: reduction in serum HBV DNA from baseline, HBV DNA negative conversion (defined as HBV DNA being undectable by the hybridization assay), and HBV DNA response (either HBV DNA level ≤ 105 copies/mL or a ≥ 2 log10 reduction from baseline HBV DNA level).
RESULTS: After two and six months of treatment, HBV DNA reduction was greater with LMV compared to ADV treatment (P = 0.021). HBV DNA negative conversion rates were 64% and 27% after one month of LMV and ADV treatment respectively (P = 0.001). Similarly, HBV DNA response rates were 74% and 51% after two months of LMV and ADV treatment respectively (P = 0.026).
The time taken to HBV DNA negative conversion and to HBV DNA response were both delayed in ADV treatment compared with LMV.
CONCLUSION: The antiviral efficacy of ADV in LMV-resistant patients is slower and less potent than that with LMV in nucleoside-naïve patients during the early course of treatment.
doi:10.3748/wjg.v13.i30.4072
PMCID: PMC4205307  PMID: 17696224
Chronic hepatitis B; Lamivudine; Adefovir; Treatment efficacy
12.  Removal of press-through-packs impacted in the upper esophagus using an overtube 
Foreign bodies in the upper esophagus should be removed as soon as possible to avoid serious complications. However, removals of foreign bodies in the upper esophagus are very difficult, especially if they have sharp edges, such as press-through-packs (PTPs). We experienced four cases of the impacted PTPs in the upper esophagus which was successfully extracted endoscopically with the overtube. Because two edges of PTPs were so firmly impacted in the esophageal wall in all cases, the PTPs were not movable in the upper esophagus. However, after insertion of the overtube, PTPs became movable and were successfully extracted and no serious complications occurred after extraction of PTPs. In one case, insertion of the overtube rapidly expanded the upper esophagus and PTP progressed to the gastric cavity and it could be extracted with the endoscopic protector hood. The endoscopic removal with the overtube was a simple, safe and effective technique for the removal of the impacted PTPs in upper esophagus.
doi:10.3748/wjg.v12.i36.5909
PMCID: PMC4100680  PMID: 17007065
Esophagus; Foreign body; Endoscopy
13.  Treatment of Patients with Refractory Atopic Dermatitis Sensitized to House Dust Mites by Using Sublingual Allergen Immunotherapy 
Annals of Dermatology  2015;27(1):82-86.
Even though atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases, its treatment remains a challenge in clinical practice, with most approaches limited to symptomatic, unspecific anti-inflammatory, or immunosuppressive treatments. Many studies have shown AD to have multiple causes that activate complex immunological and inflammatory pathways. However, aeroallergens, and especially the house dust mite (HDM), play a relevant role in the elicitation or exacerbation of eczematous lesions in many AD patients. Accordingly, allergen-specific immunotherapy has been used in AD patients with the aim of redirecting inappropriate immune responses. Here, we report three cases of refractory AD sensitized to HDM who were treated with sublingual immunotherapy.
doi:10.5021/ad.2015.27.1.82
PMCID: PMC4323609
Atopic dermatitis; Pyroglyphidae; Sublingual immunotherapy
14.  Genomic Predictors for Recurrence Patterns of Hepatocellular Carcinoma: Model Derivation and Validation 
PLoS Medicine  2014;11(12):e1001770.
In this study, Lee and colleagues develop a genomic predictor that can identify patients at high risk for late recurrence of hepatocellular carcinoma (HCC) and provided new biomarkers for risk stratification.
Background
Typically observed at 2 y after surgical resection, late recurrence is a major challenge in the management of hepatocellular carcinoma (HCC). We aimed to develop a genomic predictor that can identify patients at high risk for late recurrence and assess its clinical implications.
Methods and Findings
Systematic analysis of gene expression data from human liver undergoing hepatic injury and regeneration revealed a 233-gene signature that was significantly associated with late recurrence of HCC. Using this signature, we developed a prognostic predictor that can identify patients at high risk of late recurrence, and tested and validated the robustness of the predictor in patients (n = 396) who underwent surgery between 1990 and 2011 at four centers (210 recurrences during a median of 3.7 y of follow-up). In multivariate analysis, this signature was the strongest risk factor for late recurrence (hazard ratio, 2.2; 95% confidence interval, 1.3–3.7; p = 0.002). In contrast, our previously developed tumor-derived 65-gene risk score was significantly associated with early recurrence (p = 0.005) but not with late recurrence (p = 0.7). In multivariate analysis, the 65-gene risk score was the strongest risk factor for very early recurrence (<1 y after surgical resection) (hazard ratio, 1.7; 95% confidence interval, 1.1–2.6; p = 0.01). The potential significance of STAT3 activation in late recurrence was predicted by gene network analysis and validated later. We also developed and validated 4- and 20-gene predictors from the full 233-gene predictor. The main limitation of the study is that most of the patients in our study were hepatitis B virus–positive. Further investigations are needed to test our prediction models in patients with different etiologies of HCC, such as hepatitis C virus.
Conclusions
Two independently developed predictors reflected well the differences between early and late recurrence of HCC at the molecular level and provided new biomarkers for risk stratification.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Primary liver cancer—a tumor that starts when a liver cell acquires genetic changes that allow it to grow uncontrollably—is the second-leading cause of cancer-related deaths worldwide, killing more than 600,000 people annually. If hepatocellular cancer (HCC; the most common type of liver cancer) is diagnosed in its early stages, it can be treated by surgically removing part of the liver (resection), by liver transplantation, or by local ablation, which uses an electric current to destroy the cancer cells. Unfortunately, the symptoms of HCC, which include weight loss, tiredness, and jaundice (yellowing of the skin and eyes), are vague and rarely appear until the cancer has spread throughout the liver. Consequently, HCC is rarely diagnosed before the cancer is advanced and untreatable, and has a poor prognosis (likely outcome)—fewer than 5% of patients survive for five or more years after diagnosis. The exact cause of HCC is unclear, but chronic liver (hepatic) injury and inflammation (caused, for example, by infection with hepatitis B virus [HBV] or by alcohol abuse) promote tumor development.
Why Was This Study Done?
Even when it is diagnosed early, HCC has a poor prognosis because it often recurs. Patients treated for HCC can experience two distinct types of tumor recurrence. Early recurrence, which usually happens within the first two years after surgery, arises from the spread of primary cancer cells into the surrounding liver that left behind during surgery. Late recurrence, which typically happens more than two years after surgery, involves the development of completely new tumors and seems to be the result of chronic liver damage. Because early and late recurrence have different clinical courses, it would be useful to be able to predict which patients are at high risk of which type of recurrence. Given that injury, inflammation, and regeneration seem to prime the liver for HCC development, might the gene expression patterns associated with these conditions serve as predictive markers for the identification of patients at risk of late recurrence of HCC? Here, the researchers develop a genomic predictor for the late recurrence of HCC by examining gene expression patterns in tissue samples from livers that were undergoing injury and regeneration.
What Did the Researchers Do and Find?
By comparing gene expression data obtained from liver biopsies taken before and after liver transplantation or resection and recorded in the US National Center for Biotechnology Information Gene Expression Omnibus database, the researchers identified 233 genes whose expression in liver differed before and after liver injury (the hepatic injury and regeneration, or HIR, signature). Statistical analyses indicate that the expression of the HIR signature in archived tissue samples was significantly associated with late recurrence of HCC in three independent groups of patients, but not with early recurrence (a significant association between two variables is one that is unlikely to have arisen by chance). By contrast, a tumor-derived 65-gene signature previously developed by the researchers was significantly associated with early recurrence but not with late recurrence. Notably, as few as four genes from the HIR signature were sufficient to construct a reliable predictor for late recurrence of HCC. Finally, the researchers report that many of the genes in the HIR signature encode proteins involved in inflammation and cell death, but that others encode proteins involved in cellular growth and proliferation such as STAT3, a protein with a well-known role in liver regeneration.
What Do These Findings Mean?
These findings identify a gene expression signature that was significantly associated with late recurrence of HCC in three independent groups of patients. Because most of these patients were infected with HBV, the ability of the HIR signature to predict late occurrence of HCC may be limited to HBV-related HCC and may not be generalizable to HCC related to other causes. Moreover, the predictive ability of the HIR signature needs to be tested in a prospective study in which samples are taken and analyzed at baseline and patients are followed to see whether their HCC recurs; the current retrospective study analyzed stored tissue samples. Importantly, however, the HIR signature associated with late recurrence and the 65-gene signature associated with early recurrence provide new insights into the biological differences between late and early recurrence of HCC at the molecular level. Knowing about these differences may lead to new treatments for HCC and may help clinicians choose the most appropriate treatments for their patients.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001770.
The US National Cancer Institute provides information about all aspects of cancer, including detailed information for patients and professionals about primary liver cancer (in English and Spanish)
The American Cancer Society also provides information about liver cancer (including information on support programs and services; available in several languages)
The UK National Health Service Choices website provides information about primary liver cancer (including a video about coping with cancer)
Cancer Research UK (a not-for-profit organization) also provides detailed information about primary liver cancer (including information about living with primary liver cancer)
MD Anderson Cancer Center provides information about symptoms, diagnosis, treatment, and prevention of primary liver cancer
MedlinePlus provides links to further resources about liver cancer (in English and Spanish)
doi:10.1371/journal.pmed.1001770
PMCID: PMC4275163  PMID: 25536056
16.  Primary percutaneous coronary intervention ameliorates complete atrioventricular block complicating acute inferior myocardial infarction 
Objective
Complete atrioventricular block (CAVB) in acute inferior ST-segment elevation myocardial infarction (STEMI) is associated with poor clinical outcomes after noninvasive treatment. This study was designed to determine the effect of primary percutaneous coronary intervention (PCI) in patients with CAVB complicating acute inferior STEMI, at a single center.
Methods
We enrolled 138 consecutive patients diagnosed with STEMI involving the inferior wall; of these, 27 patients had CAVB. All patients received primary PCI. The clinical characteristics, procedural data, and clinical outcomes were compared in patients with versus without CAVB.
Results
Baseline clinical characteristics were similar between patients with and without CAVB. Patients with CAVB were more likely to present with cardiogenic shock, and CAVB was caused primarily by right coronary artery occlusion. Door-to-balloon time was similar between those two groups. After primary PCI, CAVB was reversed in all patients. The peak creatinine phosphokinase level, left ventricular ejection fraction and in-hospital mortality rate were similar between the two groups. After a median follow up of 318 days, major adverse cardiac events did not differ between the groups (8.1% in patients without CAVB; 11.1% in patients with CAVB) (P=0.702).
Conclusion
We conclude that primary PCI can ameliorate CAVB-complicated acute inferior STEMI, with an acceptable rate of major adverse cardiac events, and suggest that primary PCI should be the preferred reperfusion therapy in patients with CAVB complicating acute inferior myocardial infarction.
doi:10.2147/CIA.S74088
PMCID: PMC4246926  PMID: 25473274
major adverse cardiac events; PCI-capable hospital
17.  Delay in the Recovery of Normal Sleep-Wake Cycle after Disruption of the Light-Dark Cycle in Mice: A Bipolar Disorder-Prone Animal Model? 
Psychiatry Investigation  2014;11(4):487-491.
Objective
Disruption of the circadian rhythm is known as a provoking factor for manic episodes. Individual differences exist in the recovery rate from disruption in the general population. To develop a screening method to detect individuals vulnerable to bipolar disorder, the authors observed the relationship between the recovery of the normal sleep-wake cycle after switching the light-dark (LD) cycle and quinpirole-induced hyperactivity in mice.
Methods
Sixteen male mice (age of 5 weeks, weight 28-29 gm) were subjected to a circadian rhythm disruption protocol. Sleep-wake behaviors were checked every 5 min for a total duration of 15 days, i.e., 2 days of baseline observations, 3 days of LD cycle changes, and 10 days of recovery. During the dark cycle on the 16th experimental day, their general locomotor activities were measured in an open field for 120 minutes after an injection of quinpirole (0.5 mg/kg, s.c.).
Results
The individual differences in the recovery rate of the baseline sleep-wake cycle were noted after 3 days of switching the LD cycle. Fifty percent (n=8) of the mice returned to the baseline cycle within 6 days after normalizing the LD cycle (early recovery group). The locomotor activities of mice that failed to recover within 6 days (delayed recovery group) were significantly higher (mean rank=12.25) than those of the early recovery group (mean rank=4.75, u=62.0, p=0.001, Mann-Whitney U test).
Conclusion
Given that the quinpirole-induced hyperactivity is an animal model of bipolar disorder, our results suggest individuals who have difficulties in recovery from circadian rhythm disruption may be vulnerable to bipolar disorder.
doi:10.4306/pi.2014.11.4.487
PMCID: PMC4225215  PMID: 25395982
Bipolar disorder; Circadian rhythm; Quinpirole; Locomotor activity; Open field test; Animal model
18.  Glioma: Application of Whole-Tumor Texture Analysis of Diffusion-Weighted Imaging for the Evaluation of Tumor Heterogeneity 
PLoS ONE  2014;9(9):e108335.
Background and Purpose
To apply a texture analysis of apparent diffusion coefficient (ADC) maps to evaluate glioma heterogeneity, which was correlated with tumor grade.
Materials and Methods
Forty patients with glioma (WHO grade II (n = 8), grade III (n = 10) and grade IV (n = 22)) underwent diffusion-weighted imaging (DWI), and the corresponding ADC maps were obtained. Regions of interest containing the lesions were drawn on every section of the ADC map containing the tumor, and volume-based data of the entire tumor were constructed. Texture and first order features including entropy, skewness and kurtosis were derived from the ADC map using in-house software. A histogram analysis of the ADC map was also performed. The texture and histogram parameters were compared between low-grade and high-grade gliomas using an unpaired student’s t-test. Additionally, a one-way analysis of variance analysis with a post-hoc test was performed to compare the parameters of each grade.
Results
Entropy was observed to be significantly higher in high-grade gliomas than low-grade tumors (6.861±0.539 vs. 6.261±0.412, P  = 0.006). The fifth percentiles of the ADC cumulative histogram also showed a significant difference between high and low grade gliomas (836±235 vs. 1030±185, P = 0.037). Only entropy proved to be significantly different between grades III and IV (6.295±0.4963 vs. 7.119±0.3165, P<0.001). The diagnostic accuracy of ADC entropy was significantly higher than that of the fifth percentile of the ADC histogram (P = 0.0034) in distinguishing high- from low-grade glioma.
Conclusion
A texture analysis of the ADC map based on the entire tumor volume can be useful for evaluating glioma grade, which provides tumor heterogeneity.
doi:10.1371/journal.pone.0108335
PMCID: PMC4182447  PMID: 25268588
19.  2’f-OMe-phosphorodithioate modified siRNAs show increased loading into the RISC complex and enhanced anti-tumour activity 
Nature communications  2014;5:3459.
Improving small interfering RNA (siRNA) efficacy in target cell populations remains a challenge to its clinical implementation. Here, we report a chemical modification, consisting of phosphorodithioate (PS2) and 2’-O-Methyl (2’-OMe) MePS2 on one nucleotide that significantly enhances potency and resistance to degradation for various siRNAs. We find enhanced potency stems from an unforeseen increase in siRNA loading to the RNA-induced silencing complex, likely due to the unique interaction mediated by 2’-OMe and PS2. We demonstrate the therapeutic utility of MePS2 siRNAs in chemoresistant ovarian cancer mouse models via targeting GRAM Domain Containing 1B (GRAMD1B), a protein involved in chemoresistance. GRAMD1B silencing is achieved in tumors following MePS2-modified siRNA treatment, leading to a synergistic anti-tumor effect in combination with paclitaxel. Given the previously limited success in enhancing siRNA potency with chemically modified siRNAs, our findings represent an important advance in siRNA design with the potential for application in numerous cancer types.
doi:10.1038/ncomms4459
PMCID: PMC4112501  PMID: 24619206
20.  Magnetic Resonance Imaging Diagnosis of Metastatic Lymph Nodes in a Rabbit Model: Efficacy of PJY10, a New Ultrasmall Superparamagnetic Iron Oxide Agent, with Monodisperse Iron Oxide Core and Multiple-Interaction Ligands 
PLoS ONE  2014;9(9):e107583.
Background
Accurate diagnosis of lymph node metastasis is crucial in treatment planning for cancer patients. Despite the use of various parameters, making correct diagnosis of a small metastatic or a hyperplastic benign node is still a challenge. In this study, we evaluated the feasibility of detecting lymph node metastasis using a new ultrasmall superparamagnetic iron oxide particle, PJY10, in a rabbit model.
Methods
To make metastatic and benign lymph nodes, either VX2 carcinoma or fecal material suspension was inoculated into thighs of 56 rabbits three weeks or three days before magnetic resonance (MR) imaging, respectively. T2*-weighted 3T MR imaging was performed before and 24 hours after PJY10 injection (5.2 [n = 15], 7.8 [n = 17], and 10.4 [n = 24] mg Fe/kg). MR images were correlated with pathologic results to calculate sensitivity and specificity. Quantitative analysis of the signal intensity (SI) – number of voxels[low] (the fraction of the number of voxels with the normalized SI on the postcontrast image lower than that on the precontrast image) and mean SI ratio – was also performed for each lymph node.
Results
Sensitivities were 100% at all three dosages, whereas specificity increased with increasing dosage (89% at 10.4 mg Fe/kg). The benign nodes had a significantly higher number of voxels[low] and a lower mean SI ratio than the metastatic nodes at the dosage of 10.4 mg Fe/kg (P<.001). Az values were 0.905 for the number of voxels[low] and 0.952 for the mean SI ratio. The number of voxels[low] (P = .019) and the mean SI ratio (P = .034) had significant correlations with the histopathologic area ratio of metastatic foci in the metastatic nodes at 10.4 mg Fe/kg.
Conclusions
PJY10 enabled clear demonstration of lymph node metastasis with high sensitivity and specificity at its optimal dosage of 10.4 mg Fe/kg.
doi:10.1371/journal.pone.0107583
PMCID: PMC4162649  PMID: 25216040
21.  Contrast-Enhanced FLAIR (Fluid-Attenuated Inversion Recovery) for Evaluating Mild Traumatic Brain Injury 
PLoS ONE  2014;9(7):e102229.
Purpose
To evaluate whether adding a contrast-enhanced fluid-attenuated inversion recovery (FLAIR) sequence to routine magnetic resonance imaging (MRI) can detect additional abnormalities in the brains of symptomatic patients with mild traumatic brain injury.
Materials and Methods
Fifty-four patients with persistent symptoms following mild closed head injury were included in our retrospective study (M∶F = 32∶22, mean age: 59.8±16.4, age range: 26–84 years). All MRI examinations were obtained within 14 days after head trauma (mean: 3.2±4.1 days, range: 0.2–14 days). Two neuroradiologists recorded (1) the presence of traumatic brain lesions on MR images with and without contrast-enhanced FLAIR images and (2) the pattern and location of meningeal enhancement depicted on contrast-enhanced FLAIR images. The number of additional traumatic brain lesions diagnosed with contrast-enhanced FLAIR was recorded. Correlations between meningeal enhancement and clinical findings were also evaluated.
Results
Traumatic brain lesions were detected on routine image sequences in 25 patients. Three additional cases of brain abnormality were detected with the contrast-enhanced FLAIR images. Meningeal enhancement was identified on contrast-enhanced FLAIR images in 9 cases while the other routine image sequences showed no findings of traumatic brain injury. Overall, the additional contrast-enhanced FLAIR images revealed more extensive abnormalities than routine imaging in 37 cases (p<0.001). In multivariate logistic regression analysis, subdural hematoma and posttraumatic loss of consciousness showed a significant association with meningeal enhancement on contrast-enhanced FLAIR images, with odds ratios 13.068 (95% confidence interval 2.037 to 83.852), and 15.487 (95% confidence interval 2.545 to 94.228), respectively.
Conclusion
Meningeal enhancement on contrast-enhanced FLAIR images can help detect traumatic brain lesions as well as additional abnormalities not identified on routine unenhanced MRI. Therefore contrast-enhanced FLAIR MR imaging is recommended when a contrast MR study is indicated in a patient with a symptomatic prior closed mild head injury.
doi:10.1371/journal.pone.0102229
PMCID: PMC4100883  PMID: 25028975
22.  Usefulness of Integrated PET/MRI in Head and Neck Cancer: A Preliminary Study 
Purpose
The new modality of an integrated positron emission tomography/magnetic resonance imaging (PET/MRI) has recently been introduced but not validated. Our objective was to evaluate clinical performance of 18F-fluoro-2-deoxyglucose (18F-FDG) PET/MRI in patients with head and neck cancer.
Methods
This retrospective study was conducted between January 2013 and February 2013. Ten patients (eight men, two women; mean age, 61.4 ± 13.4 years) with histologically proven head and neck tumors were enrolled. Whole-body PET/MRI and regional positron emission tomography (PET) with dedicated MRI were sequentially obtained. Maximum standardized uptake value (SUVmax), SUVmean, metabolic tumor volume, total lesion glycolysis and contrast enhancement were analyzed. A total of ten whole-body positron emission tomography (PET), ten regional positron emission tomography (PET), ten dedicated MRI and ten regional PET/gadolinium-enhanced T1-weighted (Gd)-MRI images were analyzed for initial staging. Two nuclear medicine physicians analyzed positron emission tomography (PET) and PET/MRI with a consensus. One radiologist analyzed dedicated MRI. The primary lesions and number of metastatic lymph nodes analyzed from each image were compared.
Results
Eight patients were diagnosed with head and neck cancer (one tongue cancer, four tonsillar cancers, one nasopharyngeal cancer and two hypopharyngeal cancers) by histological diagnosis. Two benign tumors (pleomorphic adenoma and Warthin tumor) were diagnosed with surgical operation. Whole-body positron emission tomography (PET) and regional positron emission tomography (PET) attenuated by MRI showed good image quality for the lesion detection. Whole-body positron emission tomography (PET) and regional positron emission tomography (PET) detected ten primary sites and compensated for a missed lesion on dedicated MRI. A discordant number of suspicious lymph node metastases was noted according to the different images; 22, 16, 39 and 40 in the whole-body positron emission tomography (PET) only, dedicated MR, regional positron emission tomography (PET) only and regional PET/Gd-MRI, respectively. There was no distant metastasis based on analysis of whole-body positron emission tomography (PET) and whole-body PET/Dixon-volume interpolated breathhold examination (VIBE) MRI. Regional PET/Gd-MRI combined with whole-body PET/MRI modified staging in three patients. Lesions of primary tumor and suspicious metastasis were well detected on both value of SUVmax and visual analysis. The regional PET/Gd-MRI combined with whole-body PET/MRI showed convenient clinical staging performance compared with positron emission tomography (PET) and MRI alone.
Conclusion
In this preliminary study, PET attenuated by MRI showed good image quality to detect lesions. And whole-body PET/MRI as a single modality was feasible for staging in a clinical setting. Whole-body positron emission tomography (PET), regional positron emission tomography (PET), dedicated MRI and regional PET/Gd-MRI showed discordant results in lesion detection. These discordant results might be synergistic effect for accurate staging.
doi:10.1007/s13139-013-0252-2
PMCID: PMC4028474  PMID: 24900149
Head and neck cancer; Oncology; PET; MRI; Integrated PET/MRI
23.  TARDBP regulates glycolysis in hepatocellular carcinoma by regulating PFKP through miR-520 
Hepatology (Baltimore, Md.)  2013;58(1):182-191.
Metabolic changes are common features of many cancer cells and are frequently associated with the clinical outcome of patients with various cancers including hepatocellular carcinoma (HCC). Thus, aberrant metabolic pathways in cancer cells are attractive targets for cancer therapy. However, our understanding of cancer-specific regulatory mechanisms of cell metabolism is still very limited. We found that Tat activating regulatory DNA-binding protein (TARDBP) is a novel regulator of glycolysis in HCC cells. TARDBP regulates expression of the platelet isoform of phosphofructokinase (PFKP), the rate-limiting enzyme of glycolysis that catalyzes the irreversible conversion of fructose-6-phosphate to fructose-1,6-bisphosphate. Silencing of TARDBP expression in multiple HCC cell lines leads to impaired glucose metabolism and inhibition of in vitro and in vivo growth of HCC cells. Notably, the miR-520 family is an intermediate regulator of TARDBP-mediated regulation of glycolysis. Mechanistically, TARDBP suppressed expression of the miR-520 family, which in turn inhibited expression of PFKP. We further showed that expression of TARDBP is significantly associated with the overall survival of patients with HCC.
Conclusion
Our study provides new mechanistic insights into the regulation of glycolysis in HCC cells and reveals TARDBP as a potential therapeutic target for HCC.
doi:10.1002/hep.26310
PMCID: PMC3923572  PMID: 23389994
TARDBP; PFKP; Glycolysis; miR-520; Hepatocellular carcinoma
24.  Development of a Model to Predict the Primary Infection Date of Bacterial Spot (Xanthomonas campestris pv. vesicatoria) on Hot Pepper 
The Plant Pathology Journal  2014;30(2):125-135.
A population model of bacterial spot caused by Xanthomonas campestris pv. vesicatoria on hot pepper was developed to predict the primary disease infection date. The model estimated the pathogen population on the surface and within the leaf of the host based on the wetness period and temperature. For successful infection, at least 5,000 cells/ml of the bacterial population were required. Also, wind and rain were necessary according to regression analyses of the monitored data. Bacterial spot on the model is initiated when the pathogen population exceeds 1015 cells/g within the leaf. The developed model was validated using 94 assessed samples from 2000 to 2007 obtained from monitored fields. Based on the validation study, the predicted initial infection dates varied based on the year rather than the location. Differences in initial infection dates between the model predictions and the monitored data in the field were minimal. For example, predicted infection dates for 7 locations were within the same month as the actual infection dates, 11 locations were within 1 month of the actual infection, and only 3 locations were more than 2 months apart from the actual infection. The predicted infection dates were mapped from 2009 to 2012; 2011 was the most severe year. Although the model was not sensitive enough to predict disease severity of less than 0.1% in the field, our model predicted bacterial spot severity of 1% or more. Therefore, this model can be applied in the field to determine when bacterial spot control is required.
doi:10.5423/PPJ.OA.09.2013.0090
PMCID: PMC4174847  PMID: 25288995
initial infection date; population density; validation
25.  Difference of the Naltrexone's Effects in Social Drinkers by Spicy Food Preference 
Journal of Korean Medical Science  2014;29(5):714-718.
The purpose of this study was to investigate the differences in subjective acute effects of alcohol and naltrexone among those who prefer spicy food to varying degrees. Acute biphasic alcohol effects scale (BAES), visual analogue scale for craving (VAS-C), blood alcohol concentration (BAC) and food preference scale were measured in 26 men. Repeated measures ANOVA (2 preference groups×4 time blocks) on the stimulative subscale of BAES revealed a significant group by block interaction in naltrexone condition (N+) (P<0.001), but not in non-naltrexone condition (N-). Furthermore, repeated measures ANOVA (2 drug groups×4 time blocks) on the stimulative subscale of BAES revealed a significant group by block interaction in strong preference for spicy food (SP) (P<0.001), but not in lesser preference for spicy food (LP). The paired t-test revealed that significant suppression of the stimulative subscale of BAES was observed at 15 min (P<0.001) and 30 min (P<0.001) after drinking when N+ compared with N- in SP. For those who prefer spicy food, the stimulative effect of acute alcohol administration was suppressed by naltrexone. This result suggests that the effect of naltrexone may vary according to spicy food preference.
Graphical Abstract
doi:10.3346/jkms.2014.29.5.714
PMCID: PMC4024942  PMID: 24851030
Spicy Food Preference; Capsaicin; Naltrexone; Alcohols

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