Tumor Growth Kinetics Based on Initial Tumor Volume Doubling Time in Active Surveillance of Low-Risk Papillary Thyroid Carcinoma.

BACKGROUND: During active surveillance (AS) of low-risk papillary thyroid carcinomas (PTCs), the majority remain stable, while some exhibit either increase or decrease in tumor diameter or tumor volume (TV). We aimed to evaluate the clinical outcomes and relevant parameters influencing tumor growth kinetics of low-risk PTCs. METHODS: This retrospective cohort study evaluated clinical parameters of 402 patients with low-risk PTC sized <2 cm, with a follow-up duration over 3 years. Changes in maximum tumor diameter, TV, and initial TV doubling time (i-TVDT) calculated within 3-year were assessed. A significant change in TV was defined as a change of 75% or more. RESULTS: Of the 402 patients with low-risk PTC, 93.3% (375/402) were diagnosed with papillary thyroid microcarcinoma. During a median follow-up of 5 years, 3.4% (14/402) of patients developed new cervical lymph node (LN) metastasis, and 8.2% (33/402) experienced maximal diameter increase of ≥3 mm. The i-TVDT of <5 years emerged as an independent risk factor for both maximal diameter growth and new LN metastasis (p<0.001 and p=0.04, respectively). Based on TV changes and i-TVDT during AS, we identified four statistically significant tumor kinetic patterns (p<0.001): Stable (±75% change in TV), Rapid growth (TV increase >75% and i- TVDT <5 years), Slow growth (TV increase >75% and i-TVDT ≥5 years), and Shrinkage (TV decrease >75%). Most of the PTCs remained stable (67.7%), but 17.2% were rapidly growing, with a median onset of growth of 2.0 years. Slowly growing PTCs, comprising 10.9%, grew at a median of 4.3 years. A minority, 4.2%, exhibited shrinkage. In total, 115 (28.6%) patients underwent delayed surgery >12 months after initiating AS. The reasons for delayed surgery included patient preference (51/115, 44.3%), disease progression (31/115, 27.0%), and suspected disease progression, which was referred to as tumor growth not meeting the criteria of an increase of ≥3 mm in maximal tumor diameter (17/115, 14.8%). CONCLUSION: An i-TVDT of <5 years serve as an important prognostic indicator for disease progression, including tumor growth and new LN metastasis. The four tumor kinetic patterns based on TV changes and i-TVDT assist in guiding personalized decisions early in AS.

High-resolution diffusion-weighted MRI plus mammography for detecting clinically occult breast cancers in women with dense breasts.

PURPOSE: To compare the performance of mammography, high-resolution DW-MRI, DCE-MRI, and their combinations in detecting clinically occult breast cancer in women with dense breasts. METHOD: 544 breasts from 281 consecutive asymptomatic women with dense breasts were retrospectively identified. They underwent breast MRI for preoperative evaluation of breast cancers (n = 214) or as supplemental screening (n = 67) including DCE-MRI and DW-MRI (b values, 0 and 1000 sec/mm2; in-plane resolution, 1.1 × 1.1 mm2 and 1.3 × 1.3 mm2; section thickness, 3 mm), in addition to mammography. Three readers independently reviewed each examination on a per-breast basis. Histopathology and at least two year of imaging follow-up served as the gold standard. The sensitivities and specificities of different imaging modalities were compared using McNemar test. RESULTS: 230 of 544 breasts (42 %) had malignant lesions. The sensitivity of DW-MRI was higher than that of mammography (77.0 % vs 57.9 %; adjusted p < 0.001), but lower than that of DCE-MRI (84.8 %; adjusted p = 0.014). The specificity of DW-MRI was comparable to those of mammography (98.1 % vs 99.1 %; adjusted p > 0.999) and DCE-MRI (97.1 %; adjusted p > 0.999). DW-MRI plus mammography had a comparable sensitivity and specificity to those of DCE-MRI plus mammography (88.6 % vs 90.9 % and 97.1 % vs 96.2 %; adjusted p > 0.999 for both). CONCLUSIONS: High-resolution DW-MRI had a sensitivity higher than mammography and lower than DCE-MRI. Nevertheless, DW-MRI plus mammography showed a comparable sensitivity and specificity to DCE-MRI plus mammography for detecting clinically occult cancers in women with dense breasts.

Beeswax Alcohol Prevents Low-Density Lipoprotein Oxidation and Demonstrates Antioxidant Activities in Zebrafish Embryos and Human Subjects: A Clinical Study.

Oxidative stress is one of the primary instigators of the onset of various human ailments, including cancers, cardiovascular diseases, and dementia. Particularly, oxidative stress severely affects low-density lipid & protein (LDL) oxidation, leading to several detrimental health effects. Therefore, in this study, the effect of beeswax alcohol (BWA) was evaluated in the prevention of LDL oxidation, enhancement of paraoxonase 1 (PON-1) activity of high-density lipid & protein (HDL), and zebrafish embryo survivability. Furthermore, the implication of BWA consumption on the oxidative plasma variables was assessed by a preliminary clinical study on middle-aged and older human subjects (n = 50). Results support BWA augmentation of PON-1 activity in a dose-dependent manner (10-30 µM), which was significantly better than the effect exerted by coenzyme Q10 (CoQ10). Moreover, BWA significantly curtails LDL/apo-B oxidation evoked by CuSO4 (final 0.5 µM) and a causes a marked reduction in lipid peroxidation in LDL. The transmission electron microscopy (TEM) analysis revealed a healing effect of BWA towards the restoration of LDL morphology and size impaired by the exposure of Cu2+ ions (final 0.5 µM). Additionally, BWA counters the toxicity induced by carboxymethyllysine (CML, 500 ng) and rescues zebrafish embryos from development deformities and apoptotic cell death. A completely randomized, double-blinded, placebo-controlled preliminary clinical study on middle- and older-aged human subjects (n = 50) showed that 12 weeks of BWA (100 mg/day) supplementation efficiently diminished serum malondialdehyde (MDA) and total hydroperoxides and enhanced total antioxidant status by 25%, 27%, and 22%, respectively, compared to the placebo-control and baseline values. Furthermore, the consumption of BWA did not exhibit any noteworthy changes in physical variables, lipid profile, glucose levels, and biomarkers pertinent to kidney and liver function, thus confirming the safety of BWA for consumption. Conclusively, in vitro, BWA prevents LDL oxidation, enhances PON-1 activity in HDL, and positively influences oxidative variables in human subjects.

Comparison of Policosanols via Incorporation into Reconstituted High-Density Lipoproteins: Cuban Policosanol (Raydel®) Exerts the Highest Antioxidant, Anti-Glycation, and Anti-Inflammatory Activity.

Reconstituted high-density lipoproteins (rHDL) containing each policosanol from Cuba (Raydel®), China (Shaanxi Pioneer), and the United States (Lesstanol®) were synthesized to compare the physiological properties of policosanol depending on sources and origin countries. After synthesis with apolipoproteinA-I (apoA-I) into rHDL, all policosanols bound well with phospholipid and apoA-I to form discoidal rHDL. An rHDL containing Cuban policosanol (rHDL-1) showed the largest rHDL particle size of around 83 ± 3 nm, while rHDL containing Chinese policosanol (rHDL-2) or American policosanol (rHDL-3) showed smaller particles around 63 ± 3 nm and 60 ± 2 nm in diameter, respectively. The rHDL-1 showed the strongest anti-glycation activity to protect the apoA-I degradation of HDL from fructose-mediated glycation: approximately 2.7-times higher ability to suppress glycation and 1.4-times higher protection ability of apoA-I than that of rHDL-2 and rHDL-3. The rHDL-1 showed the highest antioxidant ability to inhibit cupric ion-mediated LDL oxidation in electromobility and the quantification of oxidized species. A microinjection of each rHDL into a zebrafish embryo in the presence of carboxymethyllysine (CML) showed that rHDL-1 displayed the strongest anti-oxidant activity with the highest embryo survivability, whereas rHDL-2 and rHDL-3 showed much weaker protection ability, similar to rHDL alone (rHDL-0). An intraperitoneal injection of CML (250 µg) into adult zebrafish caused acute death and hyperinflammation with an elevation of infiltration of neutrophils and IL-6 production in the liver. On the other hand, a co-injection of rHDL-1 resulted in the highest survivability and the strongest anti-inflammatory ability to suppress IL-6 production with an improvement of the blood lipid profile, such as elevation of HDL-C and lowering of the total cholesterol, LDL-cholesterol, and triglyceride. In conclusion, Cuban policosanol exhibited the most desirable properties for the in vitro synthesis of rHDL with the stabilization of apoA-I, the largest particle size, anti-glycation against fructation, and antioxidant activities to prevent LDL oxidation. Cuban policosanol in rHDL also exhibited the strongest in vivo antioxidant and anti-inflammatory activities with the highest survivability in zebrafish embryos and adults via the prevention of hyperinflammation in the presence of CML.

An Overview of the Korean Intermittent Exotropia Multicenter Study by the Korean Association for Pediatric Ophthalmology and Strabismus.

The Korean Intermittent Exotropia Multicenter Study (KIEMS), which was initiated by the Korean Association of Pediatric Ophthalmology and Strabismus, is a collaborative multicenter study on intermittent exotropia in Korea. The KIEMS was designed to provide comprehensive information, including subjective and objective findings of intermittent exotropia in a large study population. A total of 65 strabismus specialists in 53 institutions contributed to this study, which, to date, is one of the largest clinical studies on intermittent exotropia. In this article, we provide a detailed methodology of the KIEMS to help future investigations that may use the KIEMS data.

Cigarette Smoking Preferentially Affects Intracranial Vessels in Young Males: A Propensity-Score Matching Analysis.

PURPOSE: Cigarette smoking (CS) is one of the major risk factors of cerebral atherosclerotic disease, however, its level of contribution to extracranial and intracranial atherosclerotic stenosis (ECAS and ICAS) was not fully revealed yet. The purpose of our study was to assess the association of CS to cerebral atherosclerosis along with other risk factors. MATERIALS AND METHODS: All consecutive patients who were angiographically confirmed with severe symptomatic cerebral atherosclerotic disease between January 2002 and December 2012 were included in this study. Multivariate logistic regression analyses were performed to identify risk factors for ECAS and ICAS. Thereafter, CS group were compared to non-CS group in the entire study population and in a propensity-score matched population with two different age-subgroups. RESULTS: Of 1709 enrolled patients, 794 (46.5%) had extracranial (EC) lesions and the other 915 (53.5%) had intracranial (IC) lesions. CS group had more EC lesions (55.8% vs. 35.3%, P<0.001) whereas young age group (<50 years) had more IC lesion (84.5% vs. 47.6%, P<0.001). In multivariate analysis, seven variables including CS, male, old age, coronary heart disease, higher erythrocyte sedimentation rate, multiple lesions, and anterior lesion were independently associated with ECAS. In the propensity-score matched CS group had significant more EC lesion compared to non-CS group (65.7% vs. 47.9%) only in the old age subgroup. CONCLUSION: In contrast to a significant association between CS and severe symptomatic ECAS shown in old population, young patients did not show this association and showed relatively higher preference of ICAS.

Risk factors for developing Mycobacterium kansasii lung disease: A case-control study in Korea.

Previous studies have suggested that development of Mycobacterium kansasii lung disease (MKLD) was associated with COPD, pneumoconiosis, aging, male, immunosuppression, alcohol, malignancy, and certain occupations such as mining and sandblasting. However, previous studies were outdated and used non-comparative statistical methods. We aimed to determine the current risk factors for developing MKLD in Korea by using appropriate statistical techniques.Eighty-six MKLD patients were identified through a search of the Ulsan University Hospital database between January 2010 and December 2014. These cases were matched with 172 controls who had normal respiratory systems in a health examination during the same period (matching variables, age and sex; case: control ratio of 1:2). Clinical and demographic characteristics were gathered by reviewing the medical record and telephone survey. Multivariate logistic regression analyses were performed to evaluate risk factors for developing MKLD.Multivariate analysis showed that occupation in heavy industries (adjusted odds ratio (aOR) 6.41, 95% confidence interval (CI) 2.19-18.74, P = .001) and low body mass index (BMI) (aOR [per kg/m] 0.73, 95% CI 0.63-0.85, P < .001) were independent risk factors for development of MKLD. Educational attainment more than high school was associated with a lower risk of MKLD development (aOR 0.22, 95% CI 0.08-0.63, P = .005).Employees in heavy industry and low BMI are independent risk factors for development of MKLD in Korea.

Coronary CT angiography characteristics of OCT-defined thin-cap fibroatheroma: a section-to-section comparison study.

OBJECTIVES: To evaluate whether plaque characteristics as assessed by coronary computed tomography angiography (CCTA) were associated with the presence of a thin-cap fibroatheroma (TCFA)-a precursor of plaque rupture-defined by optical coherence tomography (OCT) in a section-to-section-level comparison. METHODS: From 28 symptomatic patients, 31 coronary lesions were evaluated on 727 cross-sections co-registered by both CCTA and OCT. CCTA plaque characteristics included low attenuation plaque (LAP, <30 HU), napkin ring sign (NRS), positive remodelling (PR, remodelling index ≥1.10), and spotty calcification and plaque area and plaque burden. By OCT, presence of TCFA, lumen area and arc of lipid were determined. RESULTS: OCT revealed a TCFA in 69 (9.4%) sections from 19 (61.2 %) lesions. In per-section analysis, OCT-TCFA showed higher frequency of CCTA-detected LAP (58.0% vs. 18.5%), NRS (31.9% vs. 8.8%) and PR (68.1% vs. 48.0%) and greater plaque burden (70.6% vs. 61.9%) as compared to sections without OCT-TCFA (all p < 0.05). In multivariable analysis, LAP (odds ratio [OR] 4.05, p < 0.001) and NRS (OR 2.47, p = 0.005) were associated with OCT-TCFA. CCTA-measured lumen area correlated well with OCT-measured lumen area (R = 0.859, limits of agreement -0.5 ± 3.7 mm2). CONCLUSIONS: LAP and NRS in CCTA were associated with the presence of OCT-defined TCFA in a section-to-section comparison. KEY POINTS: • CT-defined LAP and NRS were associated with OCT-defined TCFA • OCT-TCFA showed higher frequency of LAP, NRS, PR and greater plaque burden • Non-calcified plaque area was correlated with OCT-measured lipid arc.

Usefulness of argon plasma coagulation ablation subsequent to endoscopic snare papillectomy for ampullary adenoma.

BACKGROUND AND AIM: Endoscopic snare papillectomy (ESP) is an effective treatment for ampullary adenoma. Argon plasma coagulation (APC) is widely used as an additional method to control bleeding or ablate the residual tumor. However, the efficacy of this procedure has not yet been fully evaluated. This study aimed to evaluate the usefulness of APC as an additional method to ESP. METHODS: Patients who underwent ESP for ampullary adenoma between September 2005 and September 2015 were retrospectively reviewed. Using propensity score matching, we compared short- and long-term outcomes between the ESP-with-additional-APC group (ESP + APC group) and the ESP-only group. Primary outcome was early post-ESP adverse events (AE), and secondary outcomes were late AE and recurrence. RESULTS: Among 109 patients, additional APC was carried out in 59 (54.1%) patients. After matching, 41 patients were included in both groups, respectively. Bleeding rate was significantly lower in the ESP + APC group than in the ESP-only group (7.3% vs 31.7%, odds ratio = 0.180, P < 0.01). However, there were no significant differences in other procedure-related early AE such as pancreatitis (12.2% vs 19.5%, P = 0.365), cholangitis (2.4% vs 9.8%, P = 0.198), and perforation (2.4% vs 2.4%, P = 1.000) between the ESP + APC group and the ESP-only group. During the follow-up period (mean 904 ± 868 days), papillary stricture (9.8% vs 4.9%, P = 0.405) and recurrence rates (24.4% vs 24.4%, P = 0.797) were not significantly different between the ESP + APC group and the ESP-only group. CONCLUSION: Additional APC during ESP may have a beneficial effect by decreasing bleeding rate without harmful effects.

Initial surgery versus conservative management of symptomatic severe mitral regurgitation in the elderly.

OBJECTIVE: In elderly patients, the benefit of surgical correction of severe mitral regurgitation (MR) may not be greater than the operative risk. This study sought to compare the long-term clinical outcomes between initial surgery and conservative management in elderly patients (≥70 years of age) with severe MR. METHODS: We prospectively evaluated 157 consecutive patients (75 men, 74±4 years of age) with severe degenerative MR and mild symptoms. Mitral valve surgery was performed on 79 (initial surgery group), whereas the conservative strategy was chosen for 78 patients (conservative management group). We compared the overall and cardiac mortality and cardiac event between strategies in the overall and propensity-matched cohort (46 pairs). RESULTS: During the median follow-up of 5.4 years, overall death occurred less in the initial surgery group (16 vs 37 patients). This group showed reduced cardiac mortality (HR 0.31; 95% CI 0.13 to 0.73; p=0.007), overall mortality (HR 0.39; 95% CI 0.21 to 0.74; p=0.004) and cardiac event (HR 0.26; 95% CI 0.13 to 0.53; p<0.001). A significant reduction in cardiac mortality (HR 0.18; 95% CI 0.05 to 0.63; p=0.007), overall mortality (HR 0.36; 95% CI 0.15 to 0.86; p=0.022) and cardiac event (HR 0.20; 95% CI 0.07 to 0.52; p=0.001) in the initial surgery group was also observed in the propensity-matched cohort. CONCLUSIONS: In elderly patients with severe degenerative MR and mild symptoms, initial surgical strategy was associated with significant long-term reductions in cardiac and overall mortality compared with conservative management.

Comparison of the effect of spinal anesthesia and general anesthesia on 5-year tumor recurrence rates after transurethral resection of bladder tumors.

Non-muscle invasive bladder tumors are early-stage tumors with high recurrence rates. Transurethral resection of bladder tumor (TURB) is performed under spinal or general anesthesia; however, the effect of the two anesthetic techniques on non-muscle invasive bladder tumor recurrence is unknown. Thus, we compared their effects on tumor recurrence rates five years after TURB. Data from 876 patients who underwent TURB from 2000 to 2007 was reviewed. Patients received spinal or general anesthesia based on their choice or the clinician's preference. Tumor recurrence five years after TURB was assessed using multivariate Cox regression model, propensity score analysis (matching and inverse probability of treatment weighting), and Kaplan-Meier method. The five-year tumor recurrence rate after TURB was 42% and 53% for spinal and general anesthesia groups, respectively (P = 0.013). Hazard ratios for tumor recurrence in the spinal anesthesia group compared to that in the general anesthesia group were 0.619 (P <0.001), 0.642 (P = 0.001), and 0.636 (P <0.001) in the Cox regression model, Cox regression model with propensity score matching, and adjusted analysis with inverse probability of treatment weighting, respectively. The five-year tumor recurrence rate was significantly lower in the spinal anesthesia group than in the general anesthesia group in both the unadjusted (P = 0.002) and adjusted Kaplan-Meier curves (P <0.001). Therefore, spinal anesthesia for non-muscle invasive bladder tumor resection was associated with a lower five-year tumor recurrence rate than general anesthesia. This finding provides useful information for an appropriate selection of anesthetic technique for TURB.

Extranodal extension status is a powerful prognostic factor in stage III colorectal cancer.

PURPOSE: The present study aimed to evaluate the clinicopathologic characteristics of patients with extranodal extension (ENE) and the prognostic implications of ENE in stage III colorectal cancer (CRC). RESULTS: ENE was more frequent in younger patients and those with rectal cancer, higher T stage, higher N stage, lymphovascular invasion (LVI), and perineural invasion (PNI). Five-year disease-free survival (DFS) and overall survival (OS) were lower in patients with ENE-positive than in those with ENE-negative tumors (DFS, 66.4% vs. 80.1%; and OS, 74.8% vs. 85.6%, respectively; P < 0.001 both). In multivariate analysis, pathologic stage, the presence of ENE, LVI, PNI, and no adjuvant chemotherapy were significant independent prognostic factors for DFS and OS. There were no statistically significant differences in DFS and OS between ENE-positive stage IIIB tumors and ENE-negative stage IIIC tumors. MATERIALS AND METHODS: The records of 1,948 stage III CRC patients who underwent curative surgery between January 2003 and December 2010 were retrospectively reviewed. CONCLUSIONS: The presence of ENE is independently and significantly associated with lower DFS and OS rates after curative resection for stage III CRC. ENE status should be considered in both the pathologic report and CRC staging system.

Subtraction Images of Gadoxetic Acid-Enhanced MRI: Effect on the Diagnostic Performance for Focal Hepatic Lesions in Patients at Risk for Hepatocellular Carcinoma.

OBJECTIVE: The purpose of this study is to evaluate the effect of subtraction images of gadoxetic acid-enhanced MRI on the image interpretation of focal hepatic lesions in patients at risk for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: We retrospectively analyzed 255 malignant nodules from 233 patients with chronic hepatitis or liver cirrhosis (187 men and 46 women; mean age, 55.2 years) who underwent preoperative gadoxetic acid-enhanced MRI and surgical resection. We compared the detection rate of arterial hypervascularity on visual assessment with that of subtraction images. Subgroup analysis was performed according to the pathologic profile of the lesion (HCC vs non-HCC), the lesion size (≤ 3 vs > 3 cm), and the MRI technique (1.5 vs 3 T). We assessed the effect of subtraction images in diagnosing HCC according to the American Association for the Study of Liver Diseases guidelines compared with that of visual assessment. RESULTS: After excluding six patients whose images were not of nondiagnostic quality, 249 nodules (215 HCCs, 27 cholangiocarcinomas, and seven combined HCC and cholangiocarcinomas) from 227 patients were analyzed. Subtraction images more sensitively detected the arterial hypervascularity of all of the hepatic lesions than did visual assessment (sensitivity, 89.2% vs 72.4%; p < 0.001). In all of the subgroup analyses, the same tendency was observed (p = 0.001-0.145). Compared with visual assessment only, arterial hypervascularity determined by both subtraction images and the visual enhancement patterns increased sensitivity from 76.5% to 87.5% (p < 0.001) in diagnosing HCCs, with a minimal decrease in specificity from 80.9% to 78.1% (p = 0.332). CONCLUSION: Adding subtraction images with consideration of visual enhancement patterns can enhance the sensitivity in diagnosing HCC by enhancing the detection of arterial hypervascularity.

Elevated C-reactive protein level during clinical remission can predict poor outcomes in patients with Crohn's disease.

Intestinal inflammation and mucosal damage in Crohn's disease (CD) are believed to progress even during clinical remission. We investigated the long-term prognosis of CD patients in clinical remission according to serum C-reactive protein (CRP) levels. This study included 339 CD patients in clinical remission (Crohn's disease activity index < 150) for more than 6 months between January 2008 and December 2010. Clinical outcomes were compared between patients with normal and elevated CRP levels during clinical remission. During clinical remission, 150 patients had normal CRP consistently and 189 had elevated CRP at least once. During follow-up (median, 7.9 years [interquartile range, 6.8-8.0]), the Kaplan-Meier analysis with the log-rank test showed that normal CRP group had a longer CD-related hospitalization-free survival (P = 0.007) and a longer CD-related intestinal resection-free survival (P = 0.046) than elevated CRP group. In multivariate analysis, elevated CRP was significantly and independently associated with an increased risk of subsequent CD-related hospitalization (adjusted hazard ratio [aHR] 1.787, 95% confidence interval [CI]: 1.245-2.565, P = 0.002) and of subsequent CD-related intestinal resection (aHR 1.726, 95% CI: 1.003-2.969, P = 0.049). The most common reason for CD-related hospitalization was penetrating complications (35.6%). Even when CD patients are in clinical remission, elevated CRP is significantly associated with subsequent CD-related hospitalization and CD-related intestinal resection during follow-up. CD patients in clinical remission but elevated CRP should receive more careful attention and timely interventions to improve long-term outcomes.

Comparison of Outcomes of Coronary Artery Bypass Grafting Versus Drug-Eluting Stent Implantation in Patients With Severe Left Ventricular Dysfunction.

The optimal revascularization strategy for patients with significant coronary artery disease (CAD) and severe left ventricular (LV) dysfunction (ejection fraction ≤35%) remains unclear. We compared the effects of coronary artery bypass surgery (CABG, n = 442) versus percutaneous coronary intervention (PCI) with drug-eluting stents (n = 469) on long-term mortality in 911 patients with significant CAD and severe LV dysfunction using large real-world registry data. Databases of 3 real-world registries were merged for a patient-level meta-analysis. Primary outcome was death from any cause; secondary outcomes were death from cardiac causes, myocardial infarction, stroke, or repeat revascularization. At a median follow-up of 37.3 months, the risk of all-cause death (adjusted hazard ratio [HR] 0.43; 95% confidence interval [CI] 0.31 to 0.61; p <0.001) was significantly lower in the CABG group than in the PCI group after adjustment. Similar findings were observed with regard to the risks of death from cardiac cause (adjusted HR 0.49; 95% CI 0.33 to 0.73; p <0.001) and repeat revascularization (adjusted HR 0.08; 95% CI 0.03 to 0.20; p <0.001). However, there were no significant differences in the risks of myocardial infarction and stroke between the 2 groups. The superiority of CABG over PCI was particularly pronounced in patients receiving ß blockers and angiotensin-converting enzyme inhibitor or angiotensin receptor blockers than those who are not. In conclusion, among patients with significant CAD and severe LV dysfunction, CABG showed a lower risk of all-cause death, cardiac-cause death, and repeat revascularization compared with PCI with drug-eluting stents.

Development of a scoring system for differentiating IgG4-related sclerosing cholangitis from primary sclerosing cholangitis.

BACKGROUND: Recent research has shown that a substantial number of patients with primary sclerosing cholangitis (PSC) can also have elevated serum/tissue IgG4. The aim of our study was to develop a simple scoring system for the discrimination of IgG4-related sclerosing cholangits (IgG4-SC) from PSC. METHODS: Patients with IgG4-SC (n = 39) and PSC (n = 76) who had intrahepatic/hilar strictures were included. Candidate-differentiating variables included patient age, other organ involvement (OOI), inflammatory bowel disease, serum IgG4, and cholangiographic features. A scoring system was developed on the basis of these variables, and its performance was internally validated using a bootstrapping-based method. RESULTS: The scoring system in the final model included age (<30 years, 0 points; 30-39 years, 1 point; 40-49 years, 2 points; 50-59 years, 3 points; ≥60 years, 4 points), OOI (no, 0 points; yes, 3 points), and beaded appearance (yes, 0 points; no, 2 points). The patients were classified according to their total score into three categories: 0-4 points, probable PSC; 5-6 points, indicating diagnostic steroid trial; 7-9 points, probable IgG4-SC. The discrimination between IgG4-SC and PSC using the scoring system was excellent (area under the receiver operating characteristic curve, 0.986). CONCLUSIONS: A reliable differentiation of IgG4-SC from PSC can be made using the scoring system presented here. We suggest the diagnosis of IgG4-SC at a cutoff of 7 points or higher and the indication of diagnostic steroid trial at 5 or 6 points. External validation of our scoring system is warranted.

Lymph node standardized uptake values at pre-treatment 18F-fluorodeoxyglucose positron emission tomography as a valuable prognostic factor for distant metastasis in nasopharyngeal carcinoma.

OBJECTIVE: The aim of the present study was to evaluate prognostic values of pre-treatment fluorine-18 fludeoxyglucose (18F-FDG) positron emission tomography (PET) parameters for predicting the distant metastasis (DM) of nasopharyngeal cancer. METHODS: 73 patients diagnosed with nasopharyngeal cancer with regional lymph node (LN) involvement, who underwent pre-treatment 18F-FDG PET evaluation between January 2005 and December 2012, were retrospectively reviewed. We assessed the 18F-FDG PET parameters of the primary tumours (T-) and regional LNs (N-). For patients with bilateral retropharyngeal, bilateral neck and/or supraclavicular LN involvement, we also assessed the 18F-FDG PET parameters of the farthest LN station [N(f)-]. The following 18F-FDG PET parameters were evaluated: maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), peak standardized uptake value (SUVpeak), metabolic tumour volumes (MTVs) (MTV30-MTV70, which were calculated as the tumour volume with 30%, 40%, 50%, 60% and 70% of the SUVmax as the threshold, respectively) and total lesion glycolysis (TLG) (TLG30-TLG70, which were determined by the product of each MTV and the corresponding SUVmean within that MTV). Distant metastasis-free survival (DMFS) rates were estimated from the date of the start of radiotherapy to the date of DM or last follow-up by the Kaplan-Meier method. Univariate and multivariate analyses were performed to identify prognostic factors for DMFS. The median follow-up period was 53 months (range 12-110 months). RESULTS: Most patients (95%) received concurrent chemoradiotherapy. The major failure pattern was DM (15 of all patients, 21%) and the 5-year DMFS was 79%. In univariate analysis, the T-SUVmax, T-SUVmean, T-SUVpeak, N-SUVmax, N-SUVpeak, N(f)-SUVmax and N(f)-SUVpeak were significant prognostic factors for DMFS. In multivariate analysis, the T-SUVmax, T-SUVpeak, N(f)-SUVmax and N(f)-SUVpeak were significant prognostic factors for DMFS. Of these parameters, the N(f)-SUVmax (hazard ratio = 6.524; p = 0.001) and N(f)-SUVpeak (hazard ratio = 5.399; p = 0.001) were the strongest prognostic factors for DMFS. CONCLUSION: In patients with nasopharyngeal cancer with LN involvement, the standardized uptake value parameter of the farthest LN station seems to be an important 18F-FDG PET parameter for predicting DM. Further studies are needed to validate its clinical significance. Advances in knowledge: We found that pre-treatment 18F-FDG PET parameters of primary tumours and regional LNs (the SUVmax and SUVpeak of the primary tumour and the farthest LN station) were significant prognostic factors for DMFS in patients with nasopharyngeal carcinoma with LN involvement.

Left Main Coronary Artery Disease: Secular Trends in Patient Characteristics, Treatments, and Outcomes.

Left main coronary artery (LMCA) disease is the highest-risk lesion subset of ischemic heart disease, and has traditionally been an indication for coronary artery bypass grafting (CABG). Recent evidence suggests comparable clinical outcomes between percutaneous coronary intervention (PCI) and CABG for LMCA disease, with similar rates of mortality and serious composite outcomes, a higher rate of stroke with CABG, and a higher rate of repeat revascularization with PCI. These results have been translated to the current guideline recommendation that PCI is a reasonable alternative to CABG in patients with low to intermediate anatomic complexity. However, how the characteristics, treatment, and clinical outcomes of patients with unprotected LMCA disease have evolved over time has not yet been fully evaluated. We therefore described secular trends in the characteristics and long-term outcomes of unprotected LMCA disease using "real-world" clinical experience from the IRIS-MAIN (Interventional Research Incorporation Society-Left MAIN Revascularization) registry together with a broad review of this topic.

Tumor apparent diffusion coefficient as an imaging biomarker to predict tumor aggressiveness in patients with estrogen-receptor-positive breast cancer.

The purpose of this retrospective study was to evaluate whether tumor apparent diffusion coefficient (ADC) was correlated with pathologic biomarkers such as tumor cellularity, Ki67, tumor-infiltrating lymphocytes (TILs), and peritumoral lymphocytic infiltrate (PLI) in patients with estrogen receptor (ER)-positive breast cancer. The study was approved by the institutional review board and informed consent was waived. From July 2014 to December 2014, we reviewed 140 ER-positive tumors in 138 consecutive patients (range, 28-77 years; mean, 52 years) who underwent preoperative breast MRI and definitive surgery. All patients underwent diffusion-weighted imaging with a 3T scanner. Two radiologists drew the region of interest of the entire tumor and obtained the mean and pixel-based histogram of ADC. On pathology, two pathologists reviewed tumor cellularity, Ki67, TILs, and PLI. Multiple linear regression analysis was used to determine pathologic variables independently associated with ADC. Tumors with high tumor cellularity and high Ki67 had significantly lower ADCs than those with low tumor cellularity and low Ki67 (P < 0.05 for all). Tumors without PLI had significantly higher standard deviation than those with PLI (0.23 ± 0.08 versus 0.18 ± 0.05; P < 0.001). Median ADC was negatively correlated with tumor cellularity (r = -0.441), and Ki67 (r = -0.382). The standard deviation of ADC was also negatively correlated with the degree of PLI (r = -0.319). On multivariate linear regression analysis, tumor cellularity and Ki67 were independently associated with tumor ADC. Tumor ADC would be an MRI biomarker for the prediction of tumor aggressiveness indicators such as Ki67, tumor cellularity, and PLI in ER-positive breast cancer. Copyright © 2016 John Wiley & Sons, Ltd.