Patients undergoing liver resection for non-alcoholic fatty liver disease-related hepatocellular carcinoma and those for viral hepatitis-related hepatocellular carcinoma have similar survival outcomes.

Numerous studies have compared outcomes of liver resection (LR) of patients with non-alcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC) to those of patients with non-NAFLD-related HCC. However, results have been inconsistent. We aim to clarify this issue. We enrolled 801 patients with hepatitis B virus (HBV)-related HCC, 433 patients with hepatitis C virus (HCV)-related HCC, and 128 patients with NAFLD-related HCC undergoing LR. Overall survival (OS) and disease-free survival (DFS) of patients with different etiologies of chronic liver disease was compared using the Kaplan-Meier estimator and log-rank test after propensity score matching (PSM). After PSM, 83 patients remained in each group. The groups did not differ significantly in age, sex, the proportion of patients with pathological American Joint Committee on Cancer stage 1, tumor size > 50 mm, receipt of major resection, alpha-fetoprotein (AFP) ≥ 20 ng/ml, presence of cirrhosis, model for end-stage liver disease (MELD) score, and American Society of Anesthesiologists (ASA) classification. The five-year OS of patients with HBV-, HCV-, and NAFLD-related HCC was 78%, 75%, and 78%, respectively (p = 0.789). The five-year DFS of the HBV, HCV, and NAFLD groups was 60%, 45%, and 54%, respectively (p = 0.159). Perioperative morbidity was noted in 17 (20.5%) in the HBV group, 22 (26.5%) in the HCV group, and 15 (18.1%) in the NAFLD group (p = 0.398). The five-year OS, DFS, and perioperative morbidity of patients undergoing LR for NAFLD-related HCC and those for viral hepatitis-related HCC was similar.

Hepatitis B virus-related hepatocellular carcinoma has superior overall survival compared with other etiologies.

BACKGROUND: Whether the etiology of chronic liver disease (CLD) impacts the overall survival (OS) of patients with hepatocellular carcinoma (HCC) remains unclear. We aim to clarify this issue. MATERIALS AND METHODS: Between 2011 and 2020, 3941 patients who were newly diagnosed with HCC at our institution were enrolled in this study. In patients with multiple CLD etiologies, etiology was classified using the following hierarchy: hepatitis C virus (HCV) > hepatitis B virus (HBV) > alcohol-related > all negative. All negative was defined as negative for HCV, HBV, and alcohol use disorder. RESULTS: Among 3941 patients, 1407 patients were classified with HCV-related HCC, 1677 patients had HBV-related HCC, 145 patients had alcohol-related HCC, and 712 patients had all-negative HCC. Using the all-negative group as the reference group, multivariate analysis showed that HBV is an independent predictor of mortality (hazard ratio: 0.856; 95% confidence interval: 0.745-0.983; p = 0.027). Patients with HBV-related HCC had superior OS compared with patients with other CLD etiologies (p<0.001). Subgroup analyses were performed, for Barcelona Clinic Liver Cancer (BCLC) stages 0-A (p<0.001); serum alpha-fetoprotein (AFP) levels≧20 ng/ml (p<0.001); AFP levels < 20 ng/ml (p<0.001); age > 65 years (p<0.001); and the use of curative treatments (p = 0.002). No significant difference in OS between HBV and other etiologies was observed among patients aged ≤ 65 years (p = 0.304); with BCLC stages B-D (p = 0.973); or who underwent non-curative treatments (p = 0.1). CONCLUSION: Patients with HBV-related HCC had superior OS than patients with other HCC etiologies.

Tumor necrosis as a predictor of early tumor recurrence after resection in patients with hepatoma.

BACKGROUND: Tumor necrosis is a significant risk factor affecting patients' prognosis after liver resection (LR) for hepatocellular carcinoma (HCC). We aimed to develop a model with tumor necrosis as a variable to predict early tumor recurrence in HCC patients undergoing LR. MATERIALS AND METHODS: Patients who underwent LR between 2010 and 2018 for newly diagnosed HCC but did not receive neoadjuvant therapy were enrolled in this retrospective study. Six predictive factors based on pathological features-tumor size > 5 cm, multiple tumors, high-grade tumor differentiation, tumor necrosis, microvascular invasion, and cirrhosis-were chosen a priori based on clinical relevance to construct a multivariate logistic regression model. The variables were always retained in the model. The impact of each variable on early tumor recurrence within one year of LR was estimated and visualized using a nomogram. The nomogram's performance was evaluated using calibration plots with bootstrapping. RESULTS: Early tumor recurrence was observed in 161 (21.3%) patients. The concordance index of the proposed nomogram was 0.722. The calibration plots showed good agreement between nomogram predictions and actual observations of early recurrence. CONCLUSION: We developed a nomogram incorporating tumor necrosis to predict early recurrence of HCC after LR. Its predictive accuracy is satisfactory.

Using the hazard function to evaluate hepatocellular carcinoma recurrence risk after curative resection.

Predicting recurrence patterns of hepatocellular carcinoma (HCC) can be helpful in developing surveillance strategies. This study aimed to use the hazard function to investigate recurrence hazard and peak recurrence time transitions in patients with HCC undergoing liver resection (LR). We enrolled 1204 patients with HCC undergoing LR between 2007 and 2018 at our institution. Recurrence hazard, patterns, and peak rates were analyzed. The overall recurrence hazard peaked at 7.2 months (peak hazard rate [pHR]: 0.0197), but varied markedly. In subgroups analysis based on recurrence risk factors, patients with a high radiographic tumor burden score (pHR: 0.0521), alpha-fetoprotein level ≥ 400 ng/ml (pHR: 0.0427), and pT3-4 (pHR: 0.0656) showed a pronounced peak within the first year after LR. Patients with cirrhosis showed a pronounced peak within three years after LR (pHR: 0.0248), whereas those with Barcelona Clinic Liver Cancer stage B (pHR: 0.0609) and poor tumor differentiation (pHR: 0.0451) showed multiple peaks during the 5-year follow-up period. In contrast, patients without these recurrence risk factors had a relatively flat hazard function curve. HCC recurrence hazard, patterns, and peak rates varied substantially depending on different risk factors of HCC recurrence.

A simple preoperative model to predict overall survival of patients undergoing liver resection for hepatocellular carcinoma ≥10 cm.

BACKGROUND: Studies have rarely reported on preoperative predictors of prognosis of patients undergoing liver resection (LR) for HCC ≥10 cm. We developed a simple model to predict overall survival (OS) of these patients. METHODS: We enrolled 305 patients with HCC ≥10 cm undergoing LR. Cirrhosis and imaging-defined AJCC stage were used to develop a preoperative model. Patients were divided into three groups based on the Kaplan-Meier estimator. RESULTS: Group 1 included patients with AJCC stage 1 and no cirrhosis (n = 86), group 2 those with AJCC stage 1 and cirrhosis plus those with AJCC stage 2 or 3 and no cirrhosis (n = 166), and group 3 those with AJCC stage 2 or 3 and cirrhosis (n = 51). The five-year OS of group 1, 2, and 3 was 55%, 32%, and 25%, respectively (p < 0.001). With group 1 as the reference, multivariate analysis of OS showed that group 2 (HR = 2.043; 95% CI = 1.332-3.134; p = 0.001) and group 3 (HR = 2.740; 95% CI = 1.645-4.564; p < 0.001) were independent predictors of OS. CONCLUSION: We developed a simple model to predict OS of patients undergoing LR for HCC ≥10 cm.

Causes of Death among Patients with Hepatocellular Carcinoma According to Chronic Liver Disease Etiology.

This study was conducted to determine whether the causes of death among patients with hepatocellular carcinoma (HCC) differ according to chronic liver disease (CLD) etiology. Between 2011 and 2020, 3977 patients who were newly diagnosed with HCC at our institution were enrolled in this study. We determined whether the cause of death was HCC-related and non-HCC-related. For patients with multiple CLD etiologies, etiology was classified using the following hierarchy: hepatitis C virus (HCV) > hepatitis B virus (HBV) > alcohol-related causes > all negative. All negative was defined as negative for HCV, HBV, and alcohol-related causes. Among 3977 patients, 1415 patients were classified as HCV-related, 1691 patients were HBV-related, 145 patients were alcohol-related, and 725 patients were all negative. HCC-related mortality was the leading cause of death, irrespective of etiology. Among patients who underwent curative treatment, HCC-related mortality was the leading cause of death for patients in the HCV, HBV, and all-negative groups, but not for patients in the alcohol-related group. Among patients 75 years and older who underwent curative treatment, HCC-related mortality was the leading cause of death in the HCV but not HBV or all-negative groups. In conclusion, although most patients with HCC die due to HCC-related causes, non-HCC-related mortality represents a competing event in certain patient subgroups. The current study results underscore the importance of assessing and managing underlying comorbidities, particularly among patients with HCC at risk of non-HCC-related mortality.

A preoperative model for predicting early recurrence in patients undergoing resection for single hepatocellular carcinoma.

BACKGROUND AND AIM: The updated Barcelona Clinic Liver Cancer guidelines recommend liver resection (LR) for patients with single hepatocellular carcinoma (HCC) of any size. This study developed a preoperative model for predicting early recurrence in patients undergoing LR for single HCC. MATERIALS AND METHODS: We identified 773 patients undergoing LR for single HCC between 2011 and 2017 from the cancer registry database of our institution. Multivariate Cox regression analyses were performed to construct a preoperative model for predicting early recurrence, i.e., recurrence within 2 years of LR. RESULTS: Early recurrence was identified in 219 patients (28.3%). The final model of early recurrence included four predictive factors-alpha-fetoprotein level of ≥20 ng/mL, tumor size of >30 mm, Model for End-Stage Liver Disease score of >8, and cirrhosis. Preoperative application of this model provided three risk strata for recurrence-free survival (RFS): low risk, with 2-year RFS of 79.8% (95% confidence interval [CI]: 75.7-84.2%); intermediate risk, with 2-year RFS of 66.6% (95% CI: 61.1-72.6%); and high risk, with 2-year RFS of 51.1% (95% CI: 43.0-60.8%). CONCLUSION: We developed a preoperative model for predicting early recurrence after LR for single HCC. This model provides useful information for clinical decision-making.

Alpha-Fetoprotein Combined with Radiographic Tumor Burden Score to Predict Overall Survival after Liver Resection in Hepatocellular Carcinoma.

We evaluated whether combining the radiographic tumor burden score (TBS) and alpha-fetoprotein (AFP) level could be used to stratify overall survival (OS) among hepatocellular carcinoma (HCC) patients after liver resection (LR). Patients who underwent LR for Barcelona Clinic Liver Cancer stage 0, A, or B HCC between 2011 and 2018 were enrolled. TBS scores were calculated using the following equation: TBS2 = (largest tumor size (in cm))2 + (tumor number)2. Among 743 patients, 193 (26.0%) patients had a low TBS (<2.6), 474 (63.8%) had a moderate TBS (2.6-7.9), and 75 (10.1%) had a high TBS (>7.9). Those with a TBS ≤ 7.9 and AFP < 400 ng/mL had a significantly better OS than those with a TBS > 7.9 and an AFP < 400 ng/mL (p = 0.003) or ≥ 400 ng/mL (p < 0.001). A multivariate analysis using TBS ≤ 7.9 and AFP < 400 ng/mL as the reference values showed that a TBS > 7.9 and an AFP < 400 ng/mL (hazard ratio (HR): 2.063; 95% confidence interval [CI]: 1.175-3.623; p = 0.012) or ≥ 400 ng/mL (HR: 6.570; 95% CI: 3.684-11.719; p < 0.001) were independent predictors of OS. In conclusion, combining radiographic TBSs and AFP levels could stratify OS among HCC patients undergoing LR.

Stationary Trend in Elevated Serum Alpha-Fetoprotein Level in Hepatocellular Carcinoma Patients.

A recent study from the US showed a decreasing trend in the elevated serum alpha-fetoprotein (AFP) level (i.e., ≥20 ng/mL) in hepatocellular carcinoma (HCC) patients at the time of diagnosis. Furthermore, advanced tumor stage and severe underlying liver disease were associated with elevated AFP levels. We aimed to evaluate this issue in an area endemic for hepatitis B virus (HBV). Between 2011 and 2020, 4031 patients were newly diagnosed with HCC at our institution. After excluding 54 patients with unknown AFP data, the remaining 3977 patients were enrolled in this study. Elevated AFP level was defined as ≥20 ng/mL. Overall, 51.2% of HCC patients had elevated AFP levels; this proportion remained stationary between 2011 and 2020 (51.8% vs. 51.1%). Multivariate analysis showed that female gender (odds ratio (OR) = 1.462; p < 0.001), tumor size per 10 mm increase (OR = 1.155; p < 0.001), multiple tumors (OR = 1.406; p < 0.001), Barcelona Clinic Liver Cancer stages B-D (OR = 1.247; p = 0.019), cirrhosis (OR = 1.288; p = 0.02), total bilirubin > 1.4 mg/dL (OR = 1.218; p = 0.030), and HBV- or hepatitis C virus (HCV)-positive status (OR = 1.720; p < 0.001) were associated with elevated AFP levels. In conclusion, a stationary trend in elevated serum AFP level in HCC patients has been noted in the past 10 years. Advanced tumor stage, severe underlying liver disease, viral etiology, and female gender are associated with elevated AFP levels in HCC patients.

Alterations of Ocular Surface and Tear Film in Patients with Obstructive Sleep Apnea/Hypopnea Syndrome.

Purpose: Obstructive sleep apnea/hypopnea syndrome (OSA) results in repeated oxygen desaturation, repeated arousals, and episodic nocturnal activation of sympathetic nervous system during sleep. Untreated OSA is strongly associated with an increase of cardio- and cerebrovascular disorders, as well as the damages of ophthalmological microstructures. However, previous literature only simply studied the association between the ophthalmic disorders and OSA. In the present study, we first investigated the alterations of ocular surface and tear film non-invasively with the innovated corneal topographer in untreated OSA patients and normal control subjects. Furthermore, we analyzed in depth whether the correlations between OSA severity and ocular surface exams exist. Participants and Methods: Participants underwent a full-night polysomnography to determine OSA occurrence and severity. All participants subsequently received Ocular Surface Disease Index questionnaire and comprehensive ocular exams, including floppy eyelid syndrome (FES) assessment, oculus scan for tear meniscus height, non-invasive keratograph tear film breakup time (NIKBUT), and ocular surface redness, endothelial cell density, and corneal fluorescein staining. Results: One hundred eighty-one participants were prospectively enrolled in the study. FES was found in 11.5% of the normal control group and 60.0% of the severe OSA group (p=0.0005). There were significant differences in the first-NIKBUT (F-NIKBUT) (p < 0.0001), average-NIKBUT (A-NIKBUT) (p = 0.0007), and redness scores over the nasal bulbar (p = 0.032), temporal bulbar (p < 0.0001), nasal limbal (p = 0.014), and temporal limbal (p < 0.0001) areas among the four groups. F-NIKBUT and A-NIKBUT were significantly shorter in the moderate/severe OSA group (apnea/hypopnea index (AHI) ≥15) than in the normal/mild OSA group (AHI <15) (both p < 0.0001). The redness scores over the temporal bulbar (p < 0.0001) and temporal limbal (p < 0.0001) areas were also significantly different in these two OSA groups. Moreover, F-NIKBUT and A-NIKBUT negatively correlated with AHI. Nasal bulbar redness, temporal bulbar redness, nasal limbal redness, and temporal limbal redness positively correlated with AHI. Conclusion: OSA patients had higher occurrence of FES. The NIKBUT was significantly shorter, and the temporal conjunctival redness scores over bulbar and limbal areas were higher in the moderate/severe OSA group than in the normal/mild OSA group. NIKBUT and conjunctival hyperemia significantly correlated with the severity of untreated OSA.

Reappraisal of the roles of alpha-fetoprotein in hepatocellular carcinoma surveillance using large-scale nationwide database and hospital-based information.

BACKGROUND/PURPOSE: Controversies over the use of alpha-fetoprotein (AFP) for detection of hepatocellular carcinoma (HCC) existed from guidelines. Using large-scale database and hospital-based information, we aimed to reappraise the role of AFP in HCC surveillance, including proportion of AFP elevation by stage of HCC, additional benefit of AFP in combination of ultrasonography (US) in the detection of early HCC, and survival in early HCC with high AFP levels. METHODS: This retrospective study enrolled 43,437 patients from database of the Taiwan Cancer Registry (TCR) and 4250 patients from Kaohsiung Chang Gung Memorial Hospital (KCGMH) between January 2011 and December 2017. RESULTS: The HCC cases in KCGMH accounted for 9.8% of the total cases in the TCR. Among both nationwide database and hospital-based information, the proportion of early HCC patients with an AFP level of ≥20 ng/mL was approximately 40%. In KCGMH, the proportion of patients with an AFP level of ≥20 ng/mL and a virus-related (hepatitis B and C) etiology was around 41.7%; furthermore, among patients with early HCC, those with an AFP level of ≥20 ng/mL had 4.7 years of median survival and 48.3% of the 5-year overall survival rate. By hospital electronic medical records review of early HCC cohort in KCGMH, approximately 10.9% of patients with AFP levels ≥20 ng/mL had US-undetectable early HCC. CONCLUSION: This study suggested that AFP in combination with US would add an additional benefit as being a prompted role for detection of early HCC in patients with US-undetectable HCC.

Effects of TORS-OSA Surgery on Lower Urinary Tract Symptoms, Overactive Bladder Symptoms, and Nocturia in Male Patients with Obstructive Sleep Apnea/Hypopnea Syndrome.

Objective: To determine the presence of lower urinary tract symptoms (LUTS), and overactive bladder (OAB) symptoms in men with obstructive sleep apnea/hypopnea syndrome (OSA) and the effects of transoral robotic surgery (TORS) for the treatment of OSA on these conditions. Materials and Methods: One hundred twenty-three patients with a diagnosis of OSA were prospectively enrolled. The evaluations of LUTS and OAB symptoms were based on self-administered questionnaires containing international prostate symptom score (IPSS) and OAB symptom score (OABSS), respectively. Men with an OABSS urgency score of ≥2 and sum score of ≥3 were considered to have OAB. The therapeutic outcomes were assessed at baseline, and 12 weeks after TORS-OSA Surgery. Results: There were significant differences in IPSS, and OABSS according to OSA severity. After TORS-OSA surgery, significant improvements on OSA severity, daytime quality of life (QoL) and nighttime sleep quality were observed. TORS-OSA surgery was also associated with a statistically significant improvement of LUTS, LUTS QoL score, and OAB symptoms (IPSS 22.1% decrease; IPSS QoL score 21.1% decrease; OABSS17.4% decrease) at post-operative 3 months' follow-up. The presence of OAB, and severe nocturia was significantly reduced from 22.8% to 11.4% (p=0.001), 5.7% to 0.8% (p=0.031) after TORS-OSA surgery. There were no patients who had acute airway compromise or massive bleeding peri- or post-operatively. Conclusion: TORS upper airway surgery could improve LUTS and OAB symptoms on male patients with OSA in addition to improvement of major parameters of sleep study and sleep-related QoL.

Systematic review and updated meta-analysis of multi-level surgery for patients with OSA.

OBJECTIVES: To perform an updated systematic review for determining the surgical success rate of multilevel upper airway surgery for patients with obstructive sleep apnea/hypopnea syndrome (OSA). METHODS: A systematic review was performed to identify English-language studies that evaluated the treatment of adult OSA patients with multilevel OSA surgery up to January, 2018. We used polysomnography as a metric of treatment success. Articles were only included if the surgery intervention involved at least two of the frequently involved anatomic sites: nose, oropharynx and hypopharynx. Eighty-seven studies fit the inclusion criteria and a meta-analysis was performed to determine the overall success. RESULTS: The meta-analysis included 3931 subjects with a mean age of 46.1 years. The originally reported success rate in the included literature was 59.9%. A meta-analysis was performed to redefine the success rate to be consistent with the commonly agreed upon criteria - namely "a reduction in apnea/hypopnea index (AHI, /hr.) of 50% or more and an AHI of less than 20". The recalculated success rate was 60.2%. Standard meta-analytic techniques for combining p-values between studies after weighting for sample size found significant improvements in AHI, apnea index, % of rapid eye movement sleep, lowest saturation of oxygen (%), and Epworth Sleepiness Scale. CONCLUSION: This study shows the significant improvement of treatment outcomes with multilevel surgery for OSA patients.

Aristolochic acid-associated urinary tract cancers: an updated meta-analysis of risk and oncologic outcomes after surgery and systematic review of molecular alterations observed in human studies.

BACKGROUND: The risk of primary aristolochic acid (AA)-associated urothelial carcinoma (AA-UC) has been summarized by a 2013-published meta-analysis. Given that additional evidence has been continuously reported by original studies, an updated meta-analysis is needed. Meanwhile, to complete the whole picture, a systematic review of molecular alterations observed in AA-urinary tract cancers (AA-UTC) was also performed. METHODS: We searched PubMed, Embase and four Chinese databases up to October 2020. Observational studies comparing risk or oncologic outcomes of UTC between patients with and without AA exposure were eligible for systematic review and meta-analysis. Studies investigating molecular alterations in AA-UTC using human tissue samples were eligible for systematic review. RESULTS: In total, 38 and 20 studies were included in the systematic review and meta-analysis, respectively. Exposure to AA led to an overall increased risks of primary UTC [UC and renal cell carcinoma (RCC)] (OR 6.085, 95% CI 3.045-12.160) and postoperatively recurrent UC (RR 1.831, 95% CI 1.528-2.194). Subgroup analysis of postoperative primary AA-upper tract UC (AA-UTUC) showed increased risks of bladder recurrence (adjusted RR 1.949, 95% CI 1.462-2.597) and contralateral UTUC recurrence (crude RR 3.760, 95% CI 2.225-6.353), worse overall survival (adjusted HR 2.025, 95% CI 1.432-2.865) and worse disease-specific survival (adjusted HR 3.061, 95% CI 1.190-7.872), but no effect on cancer-specific survival (adjusted HR 0.772, 95% CI 0.269-2.215). High mutation load with AA mutational signature presenting largely in the putative driver genes was observed in AA-UTUC. In contrast, AA mutational signature is rarely found in the mutated RCC driver genes and the mutation load in AA-RCC is low. Therefore, AA has different roles in the genesis of UTUC and RCC. CONCLUSIONS: Implementing effective strategies to completely protect people from exposure to AA is urgently needed. Additionally, more effort should be made in identifying the precise carcinogenic mechanisms of AA to determine the future treatment strategies. PLAIN LANGUAGE SUMMARY: Risk, recurrence and survival outcomes after surgery and molecular changes possibly involved in the genesis of aristolochic acid-associated urinary tract cancers Background: The association between aristolochic acid (AA) and primary urothelial carcinoma (UC) has been summarized by a 2013-published meta-analysis. Given that additional evidence has been reported in the past 7 years, an updated meta-analysis is needed. Meanwhile, to complete the whole picture, a systematic review of molecular changes possibly involved in AA-mediated urinary tract carcinogenesis was also performed. Methods: We searched PubMed, Embase and four Chinese databases for human studies up to October 2020. Studies comparing the risk of urinary tract cancer (UTC) between patients with and without AA exposure and studies investigating the molecular changes in AA-associated UTC (AA-UTC) using human tissue samples were eligible for inclusion. Thirty-eight studies were finally included. Results: The results showed that exposure to AA was associated with a 6-fold increased risk of primary UTC (UC and renal cell carcinoma, RCC) and a 1.8-fold increased risk of postoperatively recurrent UC. After studies reporting primary AA-upper tract UC (AA-UTUC) were analyzed, a 1.9-fold increased risk of bladder recurrence and a 3.8-fold increased risk of contralateral UTUC recurrence was observed. Additionally, exposure to AA worsened the postoperative survival of patients with UTUC by a 2-fold increased risk of overall death and a 3-fold increased risk of death from other diseases and recurrences. However, there was no effect on death due to cancer. Lastly, AA seemed to play different roles in the etiology of UTUC and RCC based on the observations of different mutation loads and different distributions of AA-induced mutations in AA-UTUC and AA-RCC samples. Conclusions: Implementing effective strategies to completely protect people from exposure to AA is urgently needed. Moreover, more effort should be made in identifying the precise carcinogenic mechanisms of AA-UTC to determine the future treatment strategies.

Identifying endemic areas and estimating the prevalence of hyperlipidemia in Taiwan's townships.

BACKGROUND/PURPOSE: This study aimed to evaluate geographic variations and differences in the prevalence of hypertriglyceridemia and hypercholesterolemia between Taiwan's townships. METHODS: The prevalence of hypertriglyceridemia and hypercholesterolemia was evaluated according to the geographic characteristics of the people in the Adult Preventive Service Program from 2009 to 2010. The prevalence of hypertriglyceridemia and hypercholesterolemia in 2009 and 2010 was used and divided into three groups. Then, all townships were classed as having a significantly high prevalence, low prevalence, or an undetermined prevalence. RESULTS: The mean prevalence of hypertriglyceridemia and hypercholesterolemia was 29.26% and 43.96%, respectively. Geographic variations were observed: 125 townships had a high prevalence of hypertriglyceridemia, 122 townships had a low prevalence of hypertriglyceridemia, 142 townships had a high prevalence of hypercholesterolemia, and 159 townships had a low prevalence. A higher prevalence of hypertriglyceridemia was noted in the aboriginal areas. CONCLUSION: Geographic variations exist in the prevalence of hypertriglyceridemia, and hypercholesterolemia. Our findings indicate that the prevention and treatment services in these high prevalence areas should be a priority.

Association of Carbonic Anhydrase 9 Polymorphism and the Epithelial Growth Factor Receptor Mutations in Lung Adenocarcinoma Patients.

Carbonic anhydrase 9 (CA9) plays a vital role in lung cancer progression. The current study explored the effect of CA9 gene polymorphisms and the epidermal growth factor receptor (EGFR) mutations on the clinicopathological characters of lung adenocarcinoma. In this study, three loci of CA9 single nucleotide polymorphism (SNP) (rs2071676 A>G, rs3829078 A>G, and rs1048638 C>A) were genotyped using the TaqMan allelic discrimination method in 193 EGFR wild type individuals and 281 EGFR mutation subjects. After adjusting for age, gender, and cigarette smoking status in logistic regression, all three CA9 SNPs illustrated a non-significant difference for the distribution between the EGFR wild type group and EGFR mutation group. Nevertheless, a significantly lower rate of CA9 SNP rs2071676 AG (adjusted odds ratio (AOR): 0.40, 95% confidence interval (CI): 0.16-0.95, p = 0.039) and AG+GG (AOR: 0.43, 95% CI: 0.18-0.98, p = 0.046) were found in the male population with L858R EGFR mutation compared to men with EGFR wild type. In addition, the CA9 SNP rs2071676 AG+GG genotype were significantly correlated to the lower tumor stage of lung adenocarcinoma in the whole study population (p = 0.044) and EGFR wild type individuals (p = 0.033). For the male population, the presence of CA9 SNP rs2071676 AG+GG genotype was also correlated to a lower tumor stage (p = 0.037) and fewer lymph node invasion (p = 0.003) in those with EGFR wild type. In conclusion, the existence of CA9 SNP rs2071676 is associated with the rate of EGFR L858R mutation in males. Furthermore, the CA9 SNP rs2071676 is correlated to lower tumor stage and lower risk for developing lymph node metastasis in lung adenocarcinoma, mainly in the EGFR wild type.

Intranasal Administration of a Polyethylenimine-Conjugated Scavenger Peptide Reduces Amyloid-ß Accumulation in a Mouse Model of Alzheimer's Disease.

Amyloid-ß (Aß) aggregation in the brain plays a central and initiatory role in pathogenesis and/or progression of Alzheimer's disease (AD). Inhibiting Aß aggregation is a potential strategy in the prevention of AD. A scavenger peptide, V24P(10-40), designed to decrease Aß accumulation in the brain, was conjugated to polyethylenimine (PEI) and tested as a preventive/therapeutic strategy for AD in this study. This PEI-conjugated V24P(10-40) peptide was delivered intranasally, as nasal drops, to four-month-old APP/PS1 double transgenic mice for four or eight months. Compared with control values, peptide treatment for four months significantly reduced the amount of GdnHCl-extracted Aß40 and Aß42 in the mice's hippocampus and cortex. After treatment for eight months, amyloid load, as quantified by Pittsburgh compound B microPET imaging, was significantly decreased in the mice's hippocampus, cortex, amygdala, and olfactory bulb. Our data suggest that this intranasally delivered scavenger peptide is effective in decreasing Aß accumulation in the brain of AD transgenic mice. Nasal application of peptide drops is easy to use and could be further developed to prevent and treat AD.

Circulating microRNAs as biomarkers for diagnosis of early hepatocellular carcinoma associated with hepatitis B virus.

Hepatocarcinogenesis is a multistep process that evolves from cirrhosis or dysplastic nodule (DN), and eventually leads to overt hepatocellular carcinoma (HCC). Differentiation between early HCC and DN is an important issue in the clinical setting. This study aims to investigate the potential of circulating microRNA (miRNA) levels in the diagnosis of early HCC. RNA was extracted from sera of 30 chronic hepatitis B patients with pathologically proven DN and 120 age- and sex-matched patients with early HCC. Paired samples were collected from ten patients with DN who developed overt HCC in the follow-up. A panel of ten cancer-associated miRNAs was analyzed by quantitative real-time reverse-transcription polymerase chain reaction. Serum levels of miR-16, miR-122, miR-221, let-7b and miR-15b were significantly lower in patients with DN than in the HCC group. When DN progressed to overt HCC, serum miR-122, miR-let-7b and miR-15b levels increased significantly (p = 0.046, 0.043 and 0.044, respectively). As a single marker, α-fetoprotein (AFP) and miR-122 as well as let-7b had the similar performance for differentiate HCC from DN. As limited to subjects with normal AFP, let-7b resulted in a sensitivity of 84.8% and a specificity of 50% in separating HCC and DN with a cutoff value of 3.5 (p = 0.001). In conclusion, miR-122 and let-7b, which are upregulated in the serum of early-HCC patients, can be useful markers for differentiating early HCC from DN in chronic hepatitis B patients.

Prognostic Factors of Survival From Intractable Oronasal Bleeding After Successful Transarterial Embolization.

PURPOSE: To evaluate the prognostic factors that influence the survival of patients with traumatic intractable oronasal bleeding treated by transarterial embolization (TAE). MATERIALS AND METHODS: Patients who received TAE for intractable oronasal bleeding in the National Taiwan University Hospital from 2002 through 2013 were included in the study. Retrospective reviews were undertaken to collect relevant clinical and neuroradiologic data that might be correlated with patients' survival. The Wilcoxon rank-sum test or Fisher exact test was adopted to analyze differences between the survival group and the mortality group. Odds ratios were estimated by univariate logistic regression. RESULTS: TAE successfully controlled the bleeding in 24 of 26 patients (92.3%) who had severe craniofacial injury in the 12-year period. Of the 24 patients with successful TAE, 13 patients were discharged alive from the hospital. The overall survival rate was 50% (13 of 26). Significantly higher initial Glasgow Coma Scale (GCS) score (P = .01) and lower Injury Severity Score (ISS; P < .01) were present in the survival group than in the mortality group by the Wilcoxon rank-sum test. Moreover, patients with an ISS of at least 30, a GCS score lower than 9, initial hemoglobin level lower than 10 g/dL, and computed tomographic (CT) findings of a brain midline shift had statistically higher odds ratios predicting mortality than their counterparts as estimated by univariate logistic regression. CONCLUSIONS: The results of this study showed that the combination of diagnostic angiography and therapeutic embolization is effective treatment for intractable oronasal bleeding in patients with severe craniofacial injury. The prognosis in patients who were rescued with successful TAE was statistically correlated with the severity of trauma and concomitant brain injury. An ISS of at least 30, a GCS score lower than 9, an initial hemoglobin level lower than 10, and CT findings of a brain midline shift were strong predictors for mortality.

Validation and modification of a proposed substaging system for patients with intermediate hepatocellular carcinoma.

BACKGROUND AND AIM: Based on up-to-seven criteria and Child-Pugh score, four substages of Barcelona Clinic Liver Cancer (BCLC) intermediate hepatocellular carcinoma (HCC) were proposed. The purpose of this study was to validate and modify this proposal. METHODS: Between January 2002 and February 2011, newly diagnosed intermediate HCC patients underwent transarterial embolization (TAE) were enrolled. Patients were stratified into four (B1-B4) substages and followed up until death or end of 2012. Patients' survivals and discriminatory ability of substaging systems were compared. RESULTS: Five-hundred and eighty patients were enrolled. There were 56.6%, 33.8%, 7.4%, and 2.2% in substage B1, B2, B3, and B4. The 5-year survival rate was 21.4%, 13.9%, 7.4%, and 7.7% with median survival time of 2.4, 1.3, 0.5, and 0.8 years (P < 0.001). In addition to substage B1-B4, α-fetoprotein (AFP) level was an independent factor associated with survival in multivariate analysis. According to AFP < or > 200 ng/mL, B1 was classified into B1a and B1b, and B2 into B2a and B2b. There were no differences in survivals between B1b and B2a (P = 0.174), and B2b and B3 (P = 0.785). Patients were re-classified into modified (m)B1 (B1a), mB2 (B1b + B2a), mB3 (B2b + B3). The modified substages (mB1-mB3) showed a more desirable substaging system. CONCLUSIONS: For BCLC intermediate HCC patients, substages B1-B4 were useful in predicting survival after TAE. However, modified substaging system provided better prognostic prediction.