Hedgehog Signaling: Implications in Liver Pathophysiology.

The purpose of this review is to summarize current knowledge about the role of the Hedgehog signaling pathway in liver homeostasis and disease. Hedgehog is a morphogenic signaling pathway that is active in development. In most healthy tissues, pathway activity is restricted to stem and/or stromal cell compartments, where it enables stem cell self-renewal and tissue homeostasis. Aberrant over-activation of Hedgehog signaling occurs in many cancers, including hepatocellular and cholangio-carcinoma. The pathway is also activated transiently in stromal cells of injured tissues and orchestrates normal wound healing responses, including inflammation, vascular remodeling, and fibrogenesis. In liver, sustained Hedgehog signaling in stromal cells plays a major role in the pathogenesis of cirrhosis. Hedgehog signaling was thought to be silenced in healthy hepatocytes. However, recent studies show that targeted disruption of the pathway in hepatocytes dysregulates lipid, cholesterol, and bile acid metabolism, and promotes hepatic lipotoxicity, insulin resistance, and senescence. Hepatocytes that lack Hedgehog activity also produce a secretome that activates Hedgehog signaling in cholangiocytes and neighboring stromal cells to induce inflammatory and fibrogenic wound healing responses that drive progressive fibrosis. In conclusion, Hedgehog signaling must be precisely controlled in adult liver cells to maintain liver health.

Prevalence and Predictors of Sustained Smoking after a Cancer Diagnosis in Korean Men.

PURPOSE: Although smoking has a significant impact on mortality and morbidity of cancer patients, many patients continue to smoke post-diagnosis. The purpose of this study was to investigate prevalence and predictors of sustained smoking among male cancer survivors. MATERIALS AND METHODS: The Korean National Health Insurance Service-National Health Screening Cohort database was used for this population-based, retrospective study. Study subjects were 15,141 men who were diagnosed with their first incident cancer between 2004 and 2011. Changes in smoking status before and after a cancer diagnosis were investigated. For patients who were current smokers pre-diagnosis, association between post-diagnosis sustained smoking and demographic, socioeconomic, and clinical variables were examined. RESULTS: Of the 4,657 pre-diagnosis smokers, 2,255 (48%) had quit after cancer diagnosis, while 2,402 (51.6%) continued to smoke. In a multivariate logistic regression analysis, younger age at cancer diagnosis (adjusted odds ratio [aOR], 1.37; 95% confidence interval [CI], 1.21 to 1.55; p < 0.001), low socioeconomic status (aOR, 1.29; 95% CI, 1.15 to 1.45; p ≤ 0.001), pre-diagnosis heavy smoking (aOR, 1.24; 95% CI, 1.09 to 1.41; p=0.001), diagnosis of non-smoking- related cancer (aOR, 1.67; 95% CI, 1.42 to 1.96; p < 0.001), and high serum glucose level (aOR, 1.23; 95% CI, 1.03 to 1.46; p=0.019) were associated with sustained smoking after a cancer diagnosis. CONCLUSION: Almost half of the male smokers continue to smoke after a cancer diagnosis. Targeted interventions for smoking cessation should be considered for patients with younger age, low socioeconomic status, heavy smoking history, non-smoking-related cancer, and high blood glucose levels.

Risk Factors of Cardiovascular Disease according to Alcohol Behavioral Change after Cancer Diagnosis.

BACKGROUND: Problem drinking increases the incidence of all-cause mortality and specific cancers, and persistent drinking is associated with cardiovascular disease in certain cancer survivors. This study analyzed the cardiovascular risk factors before and after diagnosis in Korean cancer survivors. METHODS: Data for the period between 2002 and 2013 were collected from the National Health Insurance Service Health-Examinee Cohort Database. Among the 27,835 patients included, those with moderate alcohol consumption before and after cancer diagnosis were excluded. Problem drinking was defined as males under 65 years consuming over 14 glasses a week, and males over 65 years or females consuming over seven glasses a week. A t-test, chi-square test, and linear regression analysis were performed for differences in cardiovascular risk factors and differences according to cancer types. RESULTS: There was a difference in the body mass index, systolic and diastolic blood pressure, and total cholesterol among patients who became moderate drinkers after diagnosis, but fasting blood glucose did not show any significant changes. Risk factors for cardiovascular disease were analyzed in patients with liver, stomach, rectal, and breast cancer with improved drinking behavior, and there were significant differences in body mass index, systolic and diastolic blood pressure, fasting blood glucose, and total cholesterol in stomach cancer patients. CONCLUSION: Moderate drinking can lower cardiovascular risk in cancer survivors, and among the many drinking-related cancers, stomach cancer patients demonstrated significantly reduced cardiovascular risk factors.

Factors associated with continued smoking after the diagnosis of type 2 diabetes: a retrospective study in the Korean cohort.

OBJECTIVE: To investigate the factors associated with continued smoking in patients newly diagnosed with type 2 diabetes. DESIGN: Retrospective study using the Korean National Health Insurance Service-National Health Screening Cohort (2002-2013) database. PARTICIPANTS: Male patients newly diagnosed with type 2 diabetes between 1 January 2004 and 31 December 2011. MEASUREMENT: Change in smoking behaviour after the diabetes diagnosis was assessed using a self-reported questionnaire, which was administered before and after the diagnosis. To identify the factors associated with continued smoking after diabetes diagnosis, a multivariate-adjusted logistic regression was conducted using only the variables with statistical significance from the univariate analyses. RESULTS: Younger age, lower economic status, heavier smoking habit, lower Charlson Comorbidity Index and comorbid hypertension were identified as factors associated with continued smoking after the diagnosis of type 2 diabetes. Older patients (adjusted OR (aOR) 0.71, 95% CI 0.63 to 0.79) and patients with longer diabetic duration (1-2 years OR 0.88, 95% CI 0.80 to 0.98, ≥3 years OR 0.63, 95% CI 0.55 to 0.73) were more likely to quit smoking. Contrastingly, smokers in the lower economic status (aOR 1.29, 95% CI 1.18 to 1.42) and heavier smoking habit (moderate: aOR 1.53, 95% CI 1.35 to 1.72; heavy: aOR 1.90, 95% CI 1.67 to 2.17) categories were more likely to continue smoking after the diagnosis. CONCLUSIONS: It is important to identify the factors associated with smoking behaviour in patients with type 2 diabetes. Recognising the factors that contribute to the vulnerability of patients to continued smoking will be helpful in developing policies and intervention strategies in future. Vulnerable patients may require intensive education and encouragement to quit smoking. We recommend physicians to take a more proactive approach, such as encouraging frequent clinical sessions for behavioural counselling and even early pharmacological interventions, when they encounter patients with the factors outlined in this study.

Effects of smoking habit change on all-cause mortality and cardiovascular diseases among patients with newly diagnosed diabetes in Korea.

This study aimed to investigate the effects of smoking habit change on the risks of all-cause mortality and cardiovascular diseases (CVDs) among patients with newly diagnosed diabetes using the Korean National Sample Cohort data. Survival regression analyses for the risks of all-cause mortality and CVDs were performed. Quitters without body mass index (BMI) change (adjusted hazard ratio [aHR], 0.68; 95% confidence interval [CI], 0.46-1.00) and quitters with BMI loss (aHR, 1.76; 95% CI, 1.13-2.73) showed significantly reduced and substantially the increased risk of all-cause mortality, respectively, compared with sustained smokers. Smoking reduction after diabetes diagnosis may have potential positive effects. However, definite benefits on the health outcomes were not identified in this study. Participants who started smoking after diabetes diagnosis had higher risks of all-cause mortality and CVDs than those who were never smokers or ex-smokers, although not statistically significant. In conclusion, smoking cessation after diabetes diagnosis could reduce the risks of all-cause mortality and cardiovascular events among patients with newly diagnosed diabetes when accompanied by proper weight management. Therefore, physicians should advice patients with newly diagnosed type 2 diabetes on the importance of smoking cessation in combination with long-term weight management to maximize the benefits of smoking cessation.

Effect of post-cessation hyperglycemia on cardiovascular disease and mortality among middle-aged men: an eight-year longitudinal study.

Smoking cessation reduces the risk of cardiovascular disease (CVD), but also elevates fasting serum glucose (FSG) levels. The effect of post-cessation hyperglycemia on cardiovascular disease is unknown. The study population consisted of 127,066 men without type 2 diabetes from the Korean National Health Insurance System - Health Screening Cohort database. Change in smoking habits and FSG was determined by the difference in smoking status and FSG levels from the first (2002 and 2003) and second (2004 and 2005) health examinations. Continual smokers, quitters, ex-smokers, and never smokers were stratified according to FSG elevation. The study participants were followed-up for CVD and CVD-related death from 2006 to 2013. Compared to continual smokers, quitters had decreased risk of CVD among those without FSG elevation (hazard ratio, HR, 0.76, 95% confidence interval, CI, 0.66-0.86) and with FSG elevation (HR 0.83, 95% CI 0.72-0.96). Similarly, quitters had a tendency towards reduced risk of CVD-related death among those without FSG elevation (HR 0.74, 95% CI 0.51-1.09) and with FSG elevation (HR 0.68, 95% CI 0.46-1.03). Post-cessation hyperglycemia did not attenuate the beneficiary risk-reducing effects of quitting on CVD and CVD-related death.

Anemia after gastrectomy in long-term survivors of gastric cancer: A retrospective cohort study.

INTRODUCTION: The prevalence of gastric cancer in Korea is increasing, and anemia is one of the most common complications of a gastrectomy. The purpose of this study was to estimate the incidence of anemia and assess its associated factors in long-term gastric cancer survivors. METHODS: This study was a retrospective cohort study of gastric cancer patients who visited a single medical center from January 2009 to December 2014 in Korea. We included 385 patients who survived for at least five years after gastrectomy with no recurrence or metastasis. Anemia was defined by World Health Organization criteria (Hb < 12 g/dL in women and <13 g/dL in men). RESULTS: Hemoglobin levels decreased from 14.24 ± 1.23 mg/dL before surgery to 13.60 ± 1.57 mg/dL one year after surgery (P < 0.001). The cumulative incidence rate of anemia after surgery increased linearly from 18.7% in the first year to 39.5% in the fifth year. The risk of anemia was higher in females (RR, 2.00; 95% CI, 1.26-3.18), patients that received total gastrectomy (RR, 3.00; 95% CI, 2.09-4.30) and patient with diabetes (RR, 1.87; 95% CI, 1.05-3.22). A higher postoperative BMI decreased the risk of anemia (RR, 0.38; 95% CI, 0.22-0.67). CONCLUSIONS: During five years of follow-up after gastrectomy, the incidence of anemia steadily increased, and the risk of anemia was higher in females, total gastrectomy patients, patients with diabetes, low BMI patients.