The metabolic syndrome and its components as prognostic factors in colorectal cancer: A meta-analysis and systematic review

Background and Aim

Metabolic syndrome (MetS) increases the risk of colorectal cancer (CRC), and the impact of MetS on CRC prognosis remains controversial after the diagnosis of CRC has been established. This study aimed to explore the impact of the individual components and synergies of MetS on the prognosis of patients with CRC.

Methods

We searched articles published before August 3, 2022, in four databases, including PubMed, Embase, Cochrane Library, and ScienceDirect. The random-effects model inverse variance method was used to estimate the summarized effect size.

Results

Patients with CRC with MetS were 1.342 times more likely to experience all-cause mortality than those without MetS, and the 95% confidence interval (CI) of hazard ratio (HR) was 1.107–1.627 (P = 0.003). CRC-specific mortality in patients with CRC with MetS was 2.122 times higher than in those without MetS, and the 95% CI of HR was 1.080–4.173 (P = 0.029). CRC-specific mortality exhibited an increasing trend of risk with increased metabolic risk factors. The HR of CRC-specific mortality for one, two, and three metabolic risk factors was 1.206 (95% CI, 1.034–1.407; P = 0.017), 1.881 (95% CI, 1.253–2.824; P = 0.002), and 2.327 (95% CI, 1.262–4.291; P = 0.007), respectively.

Conclusions

Metabolic syndrome increased all-cause and CRC-specific mortality in patients with CRC. As a single component of MetS, diabetes mellitus increased overall mortality in patients with CRC, while obesity increased CRC-specific mortality in patients with CRC, with a significant difference from non-MetS. Moreover, the risk of CRC-specific mortality increased with increasing number of metabolic risk factors.     

Visceral Obesity If Associated with Gallbladder Polyps

Background/Aims

Gallbladder polyps (GBP) are a common clinical finding and may possess malignant potential. We conducted this study to determine whether visceral obesity is a risk factor for GBP.

Methods

We retrospectively reviewed records of subjects who received both ultrasonography and computed tomography with measurements of the areas of visceral adipose tissue and total adipose tissue (TAT) on the same day as health checkups.

Results

Ninety-three of 1,615 subjects (5.8%) had GBP and were compared with 186 age- and sex-matched controls. VAT (odds ratio [OR], 2.941; 95% confidence interval [CI], 1.325 to 6.529; p=0.008 for the highest quartile vs the lowest quartile) and TAT (OR, 3.568; 95% CI, 1.625 to 7.833; p=0.002 for the highest quartile vs the lowest quartile) were independent risk factors together with hypertension (OR, 2.512; 95% CI, 1.381 to 4.569; p=0.003), diabetes mellitus (OR, 2.942; 95% CI, 1.061 to 8.158; p=0.038), hepatitis B virus positivity (OR, 3.548; 95% CI, 1.295 to 9.716; p=0.014), and a higher level of total cholesterol (OR, 2.232; 95% CI, 1.043 to 4.778; p=0.039 for <200 mg/dL vs ≥240 mg/dL). Body mass index and waist circumference were not meaningful variables.

Conclusions

Visceral obesity measured by VAT and TAT was associated with GBP irrespective of body mass index or waist circumference.     

Relationship of visceral adipose tissue to recurrence of adenomatous polyps

OBJECTIVES:   Insulin is a growth factor for colorectal cancer. Visceral adipose tissue (VAT) is strongly associated with insulin levels, and insulin and visceral obesity have been associated in cohort studies with colorectal cancer. The aim of this investigation was to determine whether VAT is associated with recurrence of adenomatous polyps, the precursor to colorectal cancer.
METHODS:   As an ancillary study to the Polyp Prevention Trial, a randomized clinical trial that evaluated the effect of a low-fat, high-fiber, high vegetable and fruit diet on adenomatous polyp recurrence, subjects at one clinical center underwent measurement of VAT with a single-slice CT scan through the L4–L5 interspace. The scan was performed around the time of the subject's year 4 colonoscopy that determined adenoma recurrence.
RESULTS:   Of 119 subjects, 44 of 84 men (52%) and 16 of 35 women (46%) had a recurrent adenoma ( p = 0.51). Body mass index (BMI) and weight at baseline and at year 4 colonoscopy were unrelated to adenoma recurrence. In a multivariate model including visceral fat quartile, remote history of polyps, gender, age, and randomization group, only remote history of polyps was statistically significantly associated with recurrent adenoma with a relative risk of 4.6 (95% CI 1.7, 12.4, p = 0.001). There was no consistent monotonic trend of increased or decreased risk of recurrence as one ascended quartiles of adipose tissue for visceral, subcutaneous, or total abdominal fat.
CONCLUSION:   In this study, no association between visceral adipose tissue and adenomatous polyp recurrence was observed. Further study and exploration of the role of VAT in adenoma progression is required.     

Association of visceral obesity and early colorectal neoplasia

AIM:To examine whether visceral adipose tissue(VAT)serves as a risk factor for colorectal adenoma-early colorectal cancer(CRC)sequence.METHODS:A retrospective case-control study was conducted with 153 patients with stageⅠCRC,age/sex-matched 554 patients with colorectal adenoma and557 normal controls.All subjects underwent various laboratory tests,abdominal fat computed tomography(CT),and colonoscopy.VAT was defined as an intraabdominal adipose tissue area measured by CT scan.Adipose tissue area was measured at the level of the umbilicus from CT scan.We used the lowest quartile of VAT and subcutaneous adipose tissue area as a reference group.RESULTS:The body mass index(BMI),total cholesterol,fasting glucose and VAT areas were significantly different among normal,adenoma and CRC groups.The VAT area was 120.6±49.0 cm2in normal controls,130.6±58.4 cm2in adenoma group and 117.6±51.6cm2in CRC group(P=0.002).In univariate analysis,increased BMI was a risk factor for CRC compared to control(P=0.025).However,VAT area was not a risk factor for CRC compared to control.In multivariate analysis that adjusted for smoking,alcohol consumption and subcutaneous adipose tissue area,VAT area was inversely related to CRC,compared to the adenoma(OR=0.53,95%CI:0.31-0.92,highest quartile vs lowest quartile).CONCLUSION:Our study shows that visceral obesity is not a risk factor for early CRC.Visceral obesity might influence the normal-adenoma sequence but not the adenoma-early carcinoma sequence.     

Deep-Learning for Epicardial Adipose Tissue Assessment With Computed Tomography: Implications for Cardiovascular Risk Prediction

BackgroundEpicardial adipose tissue (EAT) volume is a marker of visceral obesity that can be measured in coronary computed tomography angiograms (CCTA). The clinical value of integrating this measurement in routine CCTA interpretation has not been documented.ObjectivesThis study sought to develop a deep-learning network for automated quantification of EAT volume from CCTA, test it in patients who are technically challenging, and validate its prognostic value in routine clinical care.MethodsThe deep-learning network was trained and validated to autosegment EAT volume in 3,720 CCTA scans from the ORFAN (Oxford Risk Factors and Noninvasive Imaging Study) cohort. The model was tested in patients with challenging anatomy and scan artifacts and applied to a longitudinal cohort of 253 patients post-cardiac surgery and 1,558 patients from the SCOT-HEART (Scottish Computed Tomography of the Heart) Trial, to investigate its prognostic value.ResultsExternal validation of the deep-learning network yielded a concordance correlation coefficient of 0.970 for machine vs human. EAT volume was associated with coronary artery disease (odds ratio [OR] per SD increase in EAT volume: 1.13 [95% CI: 1.04-1.30]; P = 0.01), and atrial fibrillation (OR: 1.25 [95% CI: 1.08-1.40]; P = 0.03), after correction for risk factors (including body mass index). EAT volume predicted all-cause mortality (HR per SD: 1.28 [95% CI: 1.10-1.37]; P = 0.02), myocardial infarction (HR: 1.26 [95% CI:1.09-1.38]; P = 0.001), and stroke (HR: 1.20 [95% CI: 1.09-1.38]; P = 0.02) independently of risk factors in SCOT-HEART (5-year follow-up). It also predicted in-hospital (HR: 2.67 [95% CI: 1.26-3.73]; P ≤ 0.01) and long-term post–cardiac surgery atrial fibrillation (7-year follow-up; HR: 2.14 [95% CI: 1.19-2.97]; P ≤ 0.01).ConclusionsAutomated assessment of EAT volume is possible in CCTA, including in patients who are technically challenging; it forms a powerful marker of metabolically unhealthy visceral obesity, which could be used for cardiovascular risk stratification.     

Relationship between vaspin gene expression and abdominal fat distribution of Korean women

Visceral adipose tissue-derived serpin (vaspin) is a novel adipokine that is thought to have insulin-sensitizing effects. We investigated vaspin mRNA expression in abdominal adipose tissue and examined how gene expression related to abdominal fat distribution and metabolic parameters in Korean women. We measured anthropometric variables, metabolic parameters, serum vaspin concentration, and vaspin mRNA expression in abdominal adipose tissue obtained from women who underwent abdominal gynecological surgery and were aged 18-67 years (n = 85). Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) area were measured in 40 subjects using computed tomography (CT). Vaspin expression was analyzed by real-time quantitative RT-PCR according to abdominal fat distribution. Vaspin mRNA expression was greater in adipocytes than in stroma/vascular cells. In the total subjects, vaspin expression was significantly higher in SAT than in VAT. Vaspin expression in SAT in subcutaneous fat type (VSR ≤ 0.3) was significantly higher than in visceral fat type (VSR > 0.3), although vaspin expression in VAT was similar between subcutaneous and visceral fat type. There was a significant negative correlation between vaspin expression in SAT and VAT area (r = -0.55, p = 0.001). Serum vaspin concentration was significantly correlated with fasting insulin (r = 0.30, p = 0.02), HOMA-IR (r = 0.29, p = 0.02), and the ratio of vaspin expression in VAT to vaspin expression in SAT (r = 0.41, p = 0.04). Vaspin expression in abdominal adipose tissue was adipocyte-specific and vaspin expression in SAT decreased as VAT area increased.     

Abdominal obesity is an independent risk factor for chronic heart failure in older people

OBJECTIVES: To examine whether total and abdominal adiposity are risk factors for the development of chronic heart failure (CHF) in older men and women. DESIGN: Prospective, longitudinal cohort: The Health, Aging and Body Composition study. SETTING: Memphis, Tennessee, and Pittsburgh, Pennsylvania, metropolitan areas. PARTICIPANTS: Three thousand seventy-five well-functioning community-dwelling older adults aged 70 to 79. MEASUREMENTS: Body composition using dual energy X-ray absorptiometry, visceral adipose tissue area using computed tomography, adjudicated CHF. RESULTS: Of the remaining (640 participants excluded from original group of 3,075) 2,435 participants (1,081 men, 1,354 women) without coronary heart disease or CHF at baseline, there were 166 confirmed diagnoses of CHF during the median+/-standard deviation (SD) follow-up of 6.1+/-1.4 years. After adjustment for age, race, sex, site, education, smoking, and chronic obstructive pulmonary disorder, all adiposity variables (body mass index (BMI), adipose tissue mass, percentage body fat, waist-to-thigh ratio, waist circumference, and visceral and subcutaneous abdominal adipose tissue) were significant predictors of the development of CHF. In a model that included waist circumference and BMI, waist circumference was associated with incident CHF (hazard ratio (HR)=1.27, 95% confidence interval (CI)=1.04-1.54 per SD increase, P=.02), but BMI was not (HR=1.08, 95% CI=0.86-1.35). When waist circumference and percentage fat were included together, both variables were significant predictors of CHF (waist: HR=1.17, 95% CI=1.00-1.36 per SD increase, P=.05; percentage fat: HR=1.47, 95% CI=1.16-1.87 per SD increase, P=.002). Stepwise adjustment for inflammation, hypertension, insulin resistance, and diabetes mellitus did not decrease the relative risk of a greater waist circumference for the development of CHF (all HR=1.27-1.32, 95% CI=1.02-1.61 per SD increase). CONCLUSION: Abdominal body fat distribution may be a stronger risk factor for CHF than overall obesity.     

Left Ventricular Diastolic Dysfunction in Peritoneal Dialysis: A Forgotten Risk Factor

Left ventricular diastolic dysfunction (LVDD) is common among patients undergoing peritoneal dialysis (PD). We examined the relationship between LVDD, major adverse cardiovascular events (MACE), and mortality in PD patients. A total of 149 patients undergoing PD with preserved left ventricular systolic function were included and followed for 3.5 years. LVDD was diagnosed (according to the European Society of Cardiology guidelines) by conventional and tissue Doppler echocardiography. Serum high-sensitivity C-reactive protein (hsCRP) was measured. The location and volume of adipose tissue were assessed by computed tomography (CT) at the level of the fourth lumbar vertebra. Subjects with LVDD had higher levels of hsCRP, and more visceral and peritoneal fat than controls. The relationship between adjusted visceral adipose tissue and LVDD became nonsignificant when hsCRP and baseline demographic data were introduced into the logistic regression model (odds ratio = 1.52, P = 0.07). Subsequent hierarchical multivariate Cox regression analysis showed that LVDD was one of the most powerful determinants of MACE and mortality after adjusting for all confounding factors (hazard ratio [HR]: 1.71, 95% confidence interval [CI]: 1.43–3.51, P = 0.02 and HR: 2.25, 95% CI: 1.45–2.91, P = 0.04, respectively). Systemic inflammation (hsCRP) was also significantly associated with MACE and mortality (HR: 2.03, P = 0.03 and HR: 2.16, P = 0.04, respectively). LVDD is associated with systemic inflammation and increased visceral fat in patients undergoing PD. LVDD is also a sensitive, independent indicator of future MACE and mortality in PD patients.     

Gender disparity in hepatocellular carcinoma recurrence after curative hepatectomy

Introduction and objectivesWhether there is gender disparity in the recurrence of hepatocellular carcinoma (HCC) has been not fully addressed. This study aimed to investigate the impact of gender on HCC recurrence following curative hepatectomy.Patients and methodsThis retrospective cohort study included 1087 patients with HCC (917 males, 170 females) who underwent curative hepatectomy. Cox regression models were constructed to estimate the hazard ratio (HR) and 95% confidence interval (CI) of the risk parameters associated with HCC recurrence. In the sensitivity analysis, subgroup analysis, and propensity score matching (PSM) analysis were used. Logistic regression models were used to assess the odds ratio (OR) and 95% CI of the risk parameters related to early and late recurrence.ResultsMale patients showed significantly higher risk for HCC recurrence than females, in both multivariate Cox regression analysis (HR [95% CI] = 1.480 [1.084–2.020], P = 0.014) and PSM analysis (HR [95% CI] = 1.589 [1.093–2.312], P = 0.015). Higher risk of HCC recurrence was again found in males in the subgroup analysis, but the effect of male versus female gender on HCC recurrence did not depend on any selected subgroups (all P for interaction > 0.05). Gender was an independent risk factor for early recurrence (OR [95% CI] = 1.864 [1.215–2.936], P = 0.006), but not for late recurrence.ConclusionsThere is gender disparity in the recurrence of patients with HCC after curative hepatectomy: males had a higher risk for HCC recurrence than females.     

Immune inflammation indicators and ALBI score to predict liver cancer in HCV-patients treated with direct-acting antivirals

BackgroundUnexpectedly high occurrence or recurrence rate of hepatocellular carcinoma (HCC) has been observed in patients with chronic hepatitis C receiving direct-acting antivirals (DAAs) therapy.AimsWe evaluated the predictive value of albumin-bilirubin (ALBI) score and immune-inflammation indicators to identify the risk of occurrence or recurrence of HCC in patients treated with DAAs in a real life setting.MethodsIn this retrospective cohort study, we analysed data from 514 patients with cirrhosis who were prospectively enrolled for treatment with DAAs. We assessed baseline neutrophil to lymphocyte ratio (NLR), systemic immune-inflammation index (SII), platelet to lymphocyte ratio (PLR), aspartate aminotransferase-lymphocyte ratio (ALRI) index and ALBI score.ResultsIn patients with no history of HCC (N = 416), increased AST, bilirubin, ALRI, and ALBI score, and decreased albumin and platelets were significantly associated with an increased risk of HCC development, at univariate analysis. At multivariate analysis, increase in ALBI grade (p = 0.038, HR: 2.35, 95% CI: 1.05–5.25) and decrease in platelets (p = 0.048, HR: 0.92, 95% CI: 0.85–1.0) were independently associated with HCC development. In patients with previous HCC (N = 98), adjusting for the time from HCC treatment, increased ALRI (p = 0.008, HR: 1.05, 95% CI: 1.01–1.09) was significantly associated with a risk of recurrence.ConclusionALBI score, platelet count and ALRI are promising, easy to perform and inexpensive tools for identifying patients with higher risk of HCC after treatment with DAAs.     

The Role of the CpG Island Methylator Phenotype on Survival Outcome in Colon Cancer

Background/AimsCpG island methylator phenotype (CIMP)- high colorectal cancers (CRCs) have distinct clinicopathological features from their CIMP-low/negative CRC counterparts. However, controversy exists regarding the prognosis of CRC according to the CIMP status. Therefore, this study examined the prognosis of Korean patients with colon cancer according to the CIMP status.MethodsAmong a previous cohort population with CRC, a total of 154 patients with colon cancer who had available tissue for DNA extraction were included in the study. CIMP-high was defined as 3/5 methylated markers using the five-marker panel (CACNA1G, IGF2, NEUROG1, RUNX3, and SOCS1).ResultsCIMP-high and CIMP-low/negative cancers were observed in 27 patients (17.5%) and 127 patients (82.5%), respectively. Multivariate analysis adjusting for age, gender, tumor location, tumor stage and CIMP and microsatellite instability (MSI) statuses indicated that CIMP-high colon cancers were associated with a significant increase in colon cancer-specific mortality (hazard ratio [HR], 3.23; 95% confidence interval [CI], 1.20 to 8.69; p=0.02). In microsatellite stable cancers, CIMP-high cancer had a poor survival outcome compared to CIMP-low/negative cancer (HR, 2.91; 95% CI, 1.02 to 8.27; p=0.04).ConclusionsRegardless of the MSI status, CIMP-high cancers had poor survival outcomes in Korean patients.     

Characterising the impact of body composition change during neoadjuvant chemotherapy for pancreatic cancer

BackgroundPancreatic Cancer remains a lethal disease for the majority of patients. New chemotherapy agents such as Folfirinox offer therapeutic potential for patients who present with Borderline Resectable disease (BRPC). However, results to date are inconsistent, with factors such as malnutrition limiting successful drug delivery. We sought to determine the prevalence of sarcopenia in BRPC patients at diagnosis, and to quantify body composition change during chemotherapy.MethodsThe diagnostic/restaging CT scans of BRPC patients were analysed. Body composition was measured at L3 using Tomovision Slice-O-Matic?. Total muscle and adipose tissue mass were estimated using validated regression equations. Sarcopenia was defined as per gender- and body mass index (BMI)-specific lumbar skeletal muscle index (LSMI) and muscle attenuation reference values.ResultsSeventy-eight patients received neo-adjuvant chemotherapy, and 67 patients underwent restaging CT, at which point a third were deemed resectable. Half were sarcopenic at diagnosis, and sarcopenia was equally prevalent across all BMI categories.. Skeletal muscle and adipose tissue (intra-muscular, visceral and sub-cutaneous) area decreased during chemotherapy (p < 0.0001). Low muscle attenuation was observed in half of patients at diagnosis, and was associated with increased mortality risk. Loss of lean tissue parameters during chemotherapy was associated with an increased mortality risk; specifically fat-free mass, HR 1.1 (95% CI 1.03–1.17, p = 0.003) and skeletal muscle mass, HR 1.21 (95%CI 1.08–1.35, p = 0.001).ConclusionsSarcopenia was prevalent in half of patients at the time of diagnosis with BRPC. Low muscle attenuation at diagnosis, coupled with lean tissue loss during chemotherapy, independently increased mortality risk.     

Effect of longitudinal changes of body fat on the incidence and regression of nonalcoholic fatty liver disease

AimsTo investigate the longitudinal association between changes in body fat amount and the incidence and regression of nonalcoholic fatty liver disease (NAFLD).MethodsWe performed a cohort study of 2017 subjects without liver disease or significant alcohol consumption from 2007 to 2008 and participated in a voluntary follow-up between 2011 and 2013. Of the 2017 subjects, we enrolled 956 (47.4%) subjects who had available abdominal fat data in both 2007–2008 and 2011–2013. NAFLD was diagnosed on the basis of ultrasonographic findings. Adipose tissue area was evaluated by computed tomography.ResultsWe observed 145 incident cases of NAFLD (22.6% of 642), and 79 subjects experienced a regression of NAFLD (25.2% of 314) during a median of 4.64 years. An increasing change in visceral adipose tissue (VAT) area was associated with a higher incidence of NAFLD (highest tertile vs. lowest tertile of VAT hazard ratio [HR] 2.45, 95% confidence interval [CI] 1.56–3.85, P for trend <0.001) in the multivariable analysis. An increasing change in VAT area was inversely associated with the regression of NAFLD (highest tertile vs. lowest tertile of VAT HR 0.40, 95% CI 0.20–0.80, P for trend = 0.008).ConclusionsAn increasing change in VAT area was longitudinally associated with a higher risk of incident NAFLD and inversely associated with the regression of NAFLD.     

18F-FDG PET/CT predicts microvascular invasion and early recurrence after liver resection for hepatocellular carcinoma: A prospective observational study

BackgroundThis study assessed the prognostic value of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) in the prediction of MVI and early recurrence following resection.MethodThis prospective study (ClinicalTrials.gov ID: NCT02145013) included 78 consecutive HCC patients who underwent 18F-FDG PET/CT before curative-intent resection from 2014 to 2017. Prognostic factors available before surgery for predicting MVI and early recurrence (≤2 years) were identified by univariate and multivariate analyses.ResultsThe 18F-FDG PET/CT result was positive in 30 (38%) patients. MVI was present in 33% (26/78) of specimens. Early recurrence occurred in 19% (14/74) of surviving patients. PET/CT positivity was the sole independent predictor of MVI (odds ratio [OR] = 3.6, 95% confidence interval [CI] = 1.1–11.2; p = 0.03), with a specificity and sensitivity for predicting MVI of 73% and 62%, respectively. Analysis of variables available before surgery showed that PET/CT positivity (hazard ratio [HR] = 5.8, 95% CI = 1.6–20.4; p = 0.006) and the male sex (HR = 6.6; 95% CI = 1.8–24.2; p = 0.005) were independent predictors of early recurrence.Conclusion18F-FDG PET/CT predicts MVI and early recurrence after surgery for HCC and could be used to select patients for neoadjuvant treatment.     

Greater beneficial effects of visceral fat reduction compared with subcutaneous fat reduction on parameters of the metabolic syndrome: a study of weight reduction programmes in subjects with visceral and subcutaneous obesity.

AIMS: To evaluate the effect of weight reduction on parameters of the metabolic syndrome in obese patients according to their pattern of abdominal fat distribution. METHODS: A longitudinal intervention study, consisting of a 12-week weight reduction programme, including lifestyle modification and adjuvant appetite suppressant, in 38 subjects with visceral obesity and 47 subjects with subcutaneous obesity. Visceral, subcutaneous and total adipose tissue areas were determined by CT scan at the level of L4-L5. Parameters for components of the metabolic syndrome were measured before and after weight reduction. RESULTS: Reductions in body weight, BMI and subcutaneous adipose tissue area were greater in the subcutaneous than in the visceral obesity group. In contrast, changes in fasting plasma glucose, insulin, and HOMA score were higher in the visceral than in the subcutaneous obesity group. Changes in visceral adipose tissue area were significantly related to changes in fasting plasma glucose, triglycerides and HOMA score. CONCLUSIONS: Visceral fat reduction induced greater beneficial effects on parameters of the metabolic syndrome than subcutaneous fat reduction. Evaluation of changes in abdominal fat distribution is necessary when obese subjects enter a weight reduction programme.     

Sex-dependent difference in the effect of metformin on colorectal cancer-specific mortality of diabetic colorectal cancer patients

AIM To assess factors associated with the higher effect of metformin on mortality in diabetic colorectal cancer(CRC) patients,since the factors related to the effectiveness of metformin have not been identified yet.METHODS Between January 2000 and December 2010,413 patients diagnosed with both stage 3/4 CRC and diabetes mellitus were identified. Patients' demographics and clinical characteristics were analyzed. The effect of metformin on CRC-specific mortality and the interactions between metformin and each adjusted factor were evaluated.RESULTS Total follow-up duration was median 50 mo(range: 1-218 mo). There were 85 deaths(45.9%) and 72 CRC-specific deaths(38.9%) among 185 patients who used metformin,compared to 130 total deaths(57.0%) and 107 CRC-specific deaths(46.9%) among 228 patients who did not use metformin. In multivariate analysis,survival benefit associated with metformin administration was identified(HR = 0.985,95%CI: 0.974-0.997,P = 0.012). Interaction test between metformin and sex after adjustment for relevant factors revealed that female CRC patients taking metformin exhibited a significantly lower CRC-specific mortality rate than male CRC patients taking metformin(HR = 0.369,95%CI: 0.155-0.881,P = 0.025). Furthermore,subgroup analysis revealed significant differences in CRC-specific mortality between the metformin and non-metformin groups in female patients(HR = 0.501,95%CI: 0.286-0.879,P = 0.013) but not male patients(HR = 0.848,95%CI: 0.594-1.211,P = 0.365). There were no significant interactions between metformin and other adjusted factors on CRC-specific mortality.CONCLUSION We showed a strong sex-dependent difference in the effect of metformin on CRC-specific mortality in advanced stage CRC patients with diabetes.     

Clinical usefulness of electrophysiologic testing in patients with ventricular tachycardia and chronic chagasic cardiomyopathy treated with amiodarone or sotalol

INTRODUCTION: This study assessed the role of electrophysiologic testing to identify therapeutic strategies for the treatment of patients with sustained ventricular tachycardia (VT) and chronic chagasic cardiomyopathy treated with amiodarone or sotalol. METHODS AND RESULTS: One hundred fifteen patients [69 men (60%); mean age 52 +/- 10 years] with chagasic cardiomyopathy presenting with symptomatic VT were studied after loading with Class III antiarrhythmic drugs; 78 had a history of sustained VT, and 37 with symptomatic nonsustained VT had sustained VT induced at baseline electrophysiologic study. All but 12 patients also underwent baseline electrophysiologic study. Mean left ventricular ejection fraction was 0.49 +/- 0.14. Based on results of electrophysiologic study after loading with Class III drugs, patients were divided into three groups: group 1 (n = 23) had no sustained VT induced; group 2 (n = 45) had only tolerated sustained VT induced; and group 3 (n = 47) had hemodynamically unstable sustained VT induced. After a mean follow-up of 52 +/- 32 months, total mortality rate was 39.1%; it was significantly higher in group 3 than in groups 2 and 1 [69%, 22.2%, and 26%, respectively, P < 0.0001, hazard ratio (HR) 10.4, 95% confidence interval (CI) 3.8, 21.8]. There was no significant difference in total mortality rate between groups 1 and 2 (P = 0.40, HR 1.5, 95% CI 0.75, 4.58). Cardiac mortality and sudden cardiac death rates also were higher in group 3 patients. CONCLUSION: In patients with chagasic cardiomyopathy and sustained VT, electrophysiologic testing can predict long-term efficacy of Class III antiarrhythmic drugs. This may help in the selection of patients for implantable cardioverter defibrillator therapy.     

Biliary sphincterotomy reduces the risk of acute gallstone pancreatitis recurrence in non-candidates for cholecystectomy

BackgroundPopulation aging and comorbidity are leading to an increase in patients unfit for cholecystectomy.AimsTo evaluate whether endoscopic biliary sphincterotomy after a first episode of acute gallstone pancreatitis reduces the risk of pancreatitis recurrence and gallstone-related events in non-surgical candidates.MethodsRetrospective study of patients admitted for a first episode of acute gallstone pancreatitis rejected for cholecystectomy between 2013–2018. The role of endoscopic sphincterotomy was evaluated by adjusting for age, severity of pancreatitis, and presence of choledocholithiasis.ResultsWe included 247 patients (mean age 80 ± 12 years; Charlson index: 5; severity of pancreatitis: 72% mild). Sphincterotomy was performed in 23.9%. Recurrence of pancreatitis occurred in 17.4% patients (median follow-up: 426 days). The one-year cumulative incidence of a new episode of pancreatitis was 1.8% (95% confidence interval [CI]: 0.2–12%) and 23% (95% CI: 17–31%) in patients with and without sphincterotomy, respectively (p = 0.006). In multivariate analysis, sphincterotomy showed a protective role for recurrence of pancreatitis (adjusted hazard ratio [HR]: 0.29, 95% CI: 0.08–0.92, p = 0.037) and for any gallstone-related event (HR 0.46, 95% CI: 0.21–0.98, p = 0.043).ConclusionsEndoscopic biliary sphincterotomy reduced the risk of gallstone pancreatitis recurrence and other biliary-related disorders in patients with a first episode of pancreatitis non-candidates for cholecystectomy.     

Visceral adipose tissue and metabolic complications of obesity are reduced in Prader-Willi syndrome female adults: evidence for novel influences on body fat distribution

Visceral obesity is detrimental to health, but the mechanisms controlling body fat distribution are not fully understood. In premenopausal adult females (30 nonobese, 14 obese [body mass index >30 kg/m(2)]), variance in fasting insulin, glucose, insulin/glucose ratio, C-peptide/insulin ratio, triglycerides, and high-density lipoprotein/low-density lipoprotein-cholesterol ratio, were independently influenced by visceral but not total sc or abdominal sc adipose tissue, as measured by whole-body magnetic resonance imaging. Adult females with Prader-Willi syndrome (n = 13) had significantly reduced visceral adiposity, compared with obese controls (visceral/total sc adipose tissue ratio: 0.067 +/- 0.017 vs. 0.108 +/- 0.021), independent of their total adiposity (P < 0.001), or use of exogenous sex steroids. This is in contrast to that expected by their physical inactivity, hypogonadism, adult GH deficiency, and psychiatric problems. Females with Prader-Willi syndrome not receiving sex steroids (n = 8) had significantly reduced fasting insulin, insulin/glucose ratio, and triglycerides and increased C-peptide/insulin ratio, compared with obese controls, adjusting for total (P < 0.05) but not visceral adiposity (P = 0.3-0.6), supporting their association. The cause of the reduced visceral adiposity in Prader-Willi syndrome may reflect novel hormonal, hypothalamic, and/or genetic influences on body fat distribution.