Prognostic Factors for Risk Stratification of Patients with Recurrent or Metastatic Pancreatic Adenocarcinoma Who Were Treated with Gemcitabine-Based Chemotherapy / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The aim of this study was to verify prognostic factors including sarcopenia in patients with recurrent or metastatic pancreatic cancer receiving gemcitabine-based chemotherapy. MATERIALS AND METHODS: Medical records and computed tomography scan of consecutive patients treated with palliative gemcitabine-based chemotherapy from 2008 to 2014 were reviewed. The lumbar skeletal muscle index at third lumbar spine level was computed, and together with clinicolaboratory factors, univariate and multivariable analyses for overall survival (OS) were performed. RESULTS: A total of 88 patients were found. Median age was 65 years, and male patients were predominant (67.0%). Most patients had initially metastatic disease (72.7%), and gemcitabine monotherapy was administered in 29 patients (33.0%) while gemcitabine plus erlotinib was administered in 59 patients (67.0%). Seventy-six patients (86.3%) had sarcopenia. With a median follow-up period of 44.3 months (range, 0.6 to 44.3 months), median OS was 5.35 months (95% confidence interval [CI], 4.11 to 6.59). In univariate and multivariable analysis, high carcinoembryonic antigen level (hazard ratio [HR], 4.18; 95% CI, 1.95 to 8.97; p < 0.001), initially metastatic disease (HR, 3.37; 95% CI, 1.55 to 7.32; p=0.002), sarcopenia (HR, 2.97; 95% CI, 1.20 to 7.36; p=0.019), neutrophilia (HR, 2.94; 95% CI, 1.27 to 6.79; p=0.012), and high lactate dehydrogenase level (HR, 1.96; 95% CI, 1.07 to 3.58; p=0.029) were identified as independent prognostic factors for OS. CONCLUSION: Five independent prognostic factors in patients with recurrent or metastatic pancreatic cancer who received gemcitabine-based chemotherapy were identified. These findings may be helpful in prediction of prognosis in clinical practice and can be used as a stratification factor for clinical trials.

Impact of Visceral Fat on the Metabolic Syndrome and Nonalcoholic Fatty Liver Disease

Visceral fat has been reported to be associated with nonalcoholic fatty liver disease (NAFLD) and the metabolic syndrome (MetS). We assessed the prevalence of both NAFLD and the MetS, measured visceral fat thickness VFT), and estimated the physical activity indexes of 224 relatively healthy hospital workers. We also investigated the associations between both VFT and physical activity index and each of NAFLD and the MetS. The MetS was diagnosed according to the guidelines outlined by the Adult Treatment Panel III, and NAFLD was diagnosed by ultrasonography. Subjects with hepatitis B and C infections and those reporting moderate alcohol consumption were excluded from the study. The prevalence of the MetS was 11.6% and that of NAFLD was 41.5%. Many subjects with the MetS had NAFLD (73.1%), and some subjects with NAFLD (20.4%) also had several components of the MetS (p=0.001). VFT was significantly increased by both the addition of components of the MetS and the severity of NAFLD (p<0.001). In addition, VFT was independently associated with NAFLD (odds ratio [OR], 1.10; 95% confidence interval [CI], 1.02-1.19) in subjects with more than 2 components of the MetS. In contrast, habitual physical activity was reversely associated with NAFLD (OR, 0.29; 95% CI, 0.10-0.87). In conclusion, an increased visceral fat content and reduced physical activity could be not only biological markers but also therapeutic targets in the treatment of NAFLD and the MetS.

Preliminary Study on the Topological Characteristics of Carotid Intima-Media Thickness in Hypertensives

BACKGROUND: The present study was aimed at defining the topological characteristics of the carotid intima-media thickness (IMT) in hypertensives, and to delineate whether the characteristics were different from those of non-hypertensive vascular risk factors. METHODS: B-mode carotid ultrasonography was performed in 33 participants who were devoid of stroke, ischemic heart disease, and carotid plaques. Longitudinal carotid images were obtained at 6 angular sites, 0 degree indexed adjacent to the external carotid artery (ECA) side from axial image crossing both internal carotid artery (ICA) and ECA, and then 45 degrees, 90 degrees, 180 degrees, 225 degrees, and 270 degrees. From the level of the flow divider, with an interval of 5 mm, up to 15 mm proximally, all the carotid IMT was measured. The IMT was then analyzed according to the levels and angles and compared according to either of hypertension or non-hypertension vascular risk factors. RESULTS: The carotid IMT showed asymmetric distributions in both the hypertension and non-hypertension risk groups. The IMT difference according to hypertension was observed better in the right carotid artery than the left. The right carotid IMT in the hypertension group showed significantly higher values at the most levels, and especially at 0 degree and 180 degrees of angular sites. CONCLUSIONS: It is important to understand the different topological characteristics of the carotid IMT according to the presence of hypertension, for a better reproducibility and predictability of the ultrasonic carotid IMT measurement.

Elevated Serum Osteoprotegerin Levels in Systemic Lupus Erythematosus / 대한류마티스학회지

OBJECTIVE: To determine the serum levels of soluble osteoprotegerin (OPG), decoy receptor of receptor activator of nuclear factor kB ligand (RANKL), in patients with systemic lupus erythematosus (SLE) and to assess the its relationships with certain clinical manifestations. METHODS: Serum levels of OPG in 60 patients with SLE and 30 healthy controls were determined by enzyme-linked immunosorbent assay. At the time of serum sampling, clinical manifestations and lupus disease activity index (SLEDAI) were assessed. RESULTS: Serum levels of OPG in 60 patients with SLE were significantly higher than in 30 healthy controls (1,058+/-699 versus 806+/-113 pg/mL, p=0.008). Patients with active disease had higher levels of OPG levels than those with inactive disease (1,355+/-837 versus 760+/-113 pg/mL, p<0.001). Serum OPG levels correlated with SLEDAI (gamma=0.588, p<0.0001), anti-dsDNA antibody titers (gamma=0.337, p=0.009) and serum MCP-1 levels (gamma=0.485, p<0.0001). In particular, serum OPG levels were found to be significantly increased in patients with neurological manifestation compared to those without (1,504+/-1,152 versus 918+/-376 pg/mL, p=0.004). CONCLUSION: The results of this study suggest that serum OPG levels are increased in patients with SLE. Serum OPG has a role as marker for disease activity and its increased levels reflect the involvement of neurological manifestation.

Hepatitis Viral Infection and Carotid Intima-Media Thickness

BACKGROUND: Carotid atherosclerosis has been known to be associated with systemic inflammatory status. The present study aimed to investigate the relationship between hepatitis viral infection or vaccination and carotid atherosclerosis in a relatively healthy population. METHODS: A cross-sectional study was performed in 281 subjects (mean age+/-SD, y; 43.8+/-7.2) in the Chonbuk national university hospital. All the participants were examined for the carotid intima-media thickness (IMT) in both common carotid, carotid bulb, and internal carotid arteries. Hepatitis B surface antigen (HBsAg) and IgG antibodies against hepatitis B and C virus (anti-HBs and anti-HCV) were determined by enzyme linked immunosorbent assays. RESULTS: Twelve subjects (4.3%) were HBsAg seropositive and 6 (2.1%) were anti-HCV positive but the positivity did not affect the mean carotid IMT. However, the hepatitis B-exposure group including both the HBsAg positive and anti-HBs positive without vaccination history showed a significantly higher carotid IMT (mean+/-SD, mm; 0.757+/-0.107 vs. 0.728+/-0.105, P=0.031), even after adjusting for the potential confounders. And, in the subgroup having anti-HBs, the carotid IMT was lower in the hepatitis B vaccinated subjects than in the others (0.725+/-0.103 vs. 0.760+/-0.111, P=0.019). CONCLUSIONS: Subjects exposed to the hepatitis B pathogen, even though they had anti-HBs, showed the higher carotid IMT, and the participants with a vaccination history demonstrated the lower IMT values. Subsequent study in a large representative population might be needed to further delineate the characteristic associations.

Association between the Serum Osteoprotegerin Level and Target Lesion Calcium in Coronary Artery Disease

BACKGROUND AND OBJECTIVES: Osteoprotegerin (OPG) is a decoy receptor for receptor nuclear factor-kB ligand (RANKL). We sought to evaluate the association between the serum OPG level and the target lesion calcium (TLC) in those patients suffering with coronary artery disease (CAD). SUBJECTS AND METHODS: We assayed the serum OPG levels in 65 CAD patients (mean age: 62+/-10 yrs, M : F=46 : 19) with using enzyme immunoassay, and these patient underwent intravascular ultrasound (IVUS) examinations of their target lesions. The degree of TLC was estimated by the maximum arc of calcium and also the calcified plaque surface area that was calculated from the serial cross-section IVUS images. RESULTS: The median serum OPG levels were greater in the subjects with TLC than in the subjects without TLC (1.36 vs 0.95 ng/mL, respectively, p<0.05). Significant correlation was noted between the serum OPG levels and the maximum arc of calcium (r=0.274, p=0.027). The median serum OPG levels were significantly increased more in the subjects who had a maximum arc of calcium ranging from 90 to 180 degrees than in those subjects who had a maximum arc of calcium less than 90 degrees (1.63 vs 1.14 ng/mL, respectively, p<0.05) and the median serum OPG levels were also increased more in the subjects who fell within the second tertile of the calcified plaque surface area than that in those subjects who fell within the first and third tertile (0.96, 1.53, 1.40 ng/mL for the first, second, third tertile, respectively, p<0.05). On the stepwise multivariate logistic regression analysis, the serum OPG level remained a risk factor for TLC after adjustment was made for the other risk factors such as age, diabetes mellitus, HbA1C and a smoking history (p=0.019, odds ratio 5.208 [95% confidence interval: 1.308-20.744]). CONCLUSION: In patients with CAD, an increased serum OPG level is associated with target lesion calcification.

Hypoxia Induces the Expression of Connective Tissue Growth Factor in Dermal Fibroblasts / 대한류마티스학회지

OBJECTIVE: Connective tissue growth factor (CTGF) has been proposed to play a role in fibrotic process of systemic sclerosis. Since hypoxia was known to be associated with fibrosis in several profibrogenic conditions, we investigated whether CTGF expression in dermal fibroblast is regulated by hypoxia caused by microvascular loss. METHODS: Dermal fribroblasts from patient with systemic sclerosis and normal controls were cultured in the presence of cobalt chloride (CoCl2), a chemical inducer of HIF-1alpha or hypoxic culture conditions. Expression of HIF-1alpha, VEGF and CTGF was evaluated by semiquantitative reverse transcription-polymerase chain reaction and Western blotting. RESULTS: Scleroderma fibroblasts expressed increased levels of HIF-1alpha, VEGF and CTGF compared to normal dermal fibroblasts. Dermal fibroblasts exposed to various concentration of CoCl2 (1~100microM) enhanced the expression of CTGF mRNA in dose-dependent fashion. Actinomycin D significantly blocked the hypoxia-mediated up-regulation of CTGF mRNA expression, whereas cycloheximide did not block the up-regulation. Up-regulation of CTGF by hypoxia was not mediated by endogenous production of transforming growth factor (TGF)-beta. In time-kinetics study, dermal fibroblasts from scleroderma patients exhibited earlier peak expression of CTGF mRNA than those from normal dermal fibroblasts. In addition, simultaneous treatment of suboptimal concentration of CoCl2 and TGF-beta exhibited the up-regulation of CTGF mRNA in additive fashion. Interferon-gamma did not modulate the expression of CTGF mRNA induced by CoCl2, while the up-regulation of CTGF by TGF-beta was downregulated by Interferon-gamma in a dose-dependent fashion. CONCLUSION: These data indicate that hypoxia up-regulates the expression of CTGF in dermal fibroblasts and provide the evidence that hypoxia caused by microvascular alterations contributes the progression of fibrosis in systemic sclerosis by up-regulation of CTGF.

A Successful Endoscopic Therapy for Uncontrolled Duodenal Varix after Transjugular Intrahepatic Portosystemic Shunt / 대한소화기내시경학회지

Duodenal varix is a rare site of bleeding in patient with portal hypertension and frequently causes massive bleeding. Treatment modalities are endoscopic sclerotherapy, endoscopic ligation, transjugular intrahepatic portosystemic shunt (TIPS), and shunt operation. A patient with duodenal varix was hemodynamically unstable and an emergent salvage transjugular intrahepatic portosystemic shunt was performed. In spite of TIPS procedure, varix bleeding was not controlled and endoscopic band ligation and endoscopic sclerotherapy were performed with successful hemostasis and eradication of duodenal varix.

A case of gastric adenocarcinoma presented as internal jugular vein thrombosis / 대한내과학회지

The migratory thrombophlebitis and thromboembolic disorders of the venous and arterial systems in the setting of malignancy are termed Trousseau's syndrome. The overall incidence of clinical thromboembolic events in patients with cancer has been reported to vary between 1~11%. Pancreatic carcinoma has been associated with the greatest risk of thromboembolic events. Other tumor type also prone to an increased risk of thromboembolic events, including lung, prostate, stomach, acute leukemia and colon cancer. Hypercoagulability associated cancer may result from activation of coagulation, injury to the endothelium, or alteration of blood flow. Unlike other coagulopathies, Trousseau's syndrome may manifest with thromboses in unusal areas, including the upper extremities, face and visceral organs. Neck vein thrombosis associated with distant cancers have been rarely reported. Jugular vein thrombosis associated with gastrc cancer is very rare. We report one case of gastic adenocarcinoma presented as internal jugular vein thrombosis.