Association of body-shape phenotypes with imaging measures of body composition in the UK Biobank cohort: relevance to colon cancer risk.

BACKGROUND: Body mass index (BMI), waist and hip circumference are strongly correlated and do not reflect body composition. A Body Shape Index (ABSI) and Hip Index (HI) define waist and hip size among individuals with the same weight and height and would thus reflect body density. We examined differences in body composition between body-shape phenotypes defined with ABSI and HI and used this information to propose explanations for associations between body-shape phenotypes and colon cancer risk. METHODS: We used data from the UK Biobank Resource for 15,520 men, 16,548 women with dual-emission X-ray absorptiometry (DXA) measurements; 3997 men, 4402 women with magnetic resonance imaging (MRI) measurements; 200,289 men, 230,326 women followed-up for colon cancer. We defined body-shape phenotypes as: large-ABSI-small-HI ("apple"), small-ABSI-large-HI ("pear"), small-ABSI-small-HI ("slim"), large-ABSI-large-HI ("wide"). We evaluated differences in body composition in linear models and associations with colon cancer risk in Cox proportional hazards models adjusted for confounders and explored heterogeneity by BMI. RESULTS: Among individuals with the same height and weight, visceral adipose tissue (VAT) was lowest for "pear" and highest for "apple", while abdominal subcutaneous adipose tissue (ASAT) was lowest for "slim" and highest for "wide" phenotype. In the gynoid region, differences between "apple" and "pear" phenotypes were accounted for mainly by fat mass in women but by lean mass in men. In men, lean mass was inversely associated with waist size, while the pattern of gynoid fat resembled ASAT in women. Lean and fat mass were higher for higher BMI, but not hand grip strength. Compared to normal weight "pear", the risk of colon cancer in men (1029 cases) was higher for "apple" phenotype for normal weight (hazard ratio HR = 1.77; 95% confidence interval: 1.16-2.69) and comparably for overweight and obese, higher for "wide" phenotype for overweight (HR = 1.60; 1.14-2.24) and comparably for obese, but higher for "slim" phenotype only for obese (HR = 1.98; 1.35-2.88). Associations with colon cancer risk in women (889 cases) were weaker. CONCLUSIONS: ABSI-by-HI body-shape phenotypes provide information for body composition. Colon cancer risk in men appears related to ASAT quantity for "slim" and "wide" but to factors determining VAT accumulation for "apple" phenotype.

Beneficial impacts of fermented celery (Apium graveolens L.) juice on obesity prevention and gut microbiota modulation in high-fat diet fed mice.

Metabolic syndrome caused obesity has long been recognized as a risk of health. Celery and celery extracts have various medicinal properties, such as anti-diabetes and anti-inflammatory properties and blood glucose and serum lipid reduction. However, the effect of probiotic fermentation on celery juice and the association between fermented celery juice (FCJ) and obesity were unclear. This study aimed to evaluate the beneficial effects of FCJ on high-fat diet (HFD) induced obesity and related metabolic syndromes. C57BL/6 mice were randomly divided into six groups (n = 15 per group) fed either a normal diet (ND) or HFD with or without CJ/FCJ (10 g kg-1 day-1) by oral gavage for 12 weeks. Here we demonstrated that the probiotic fermentation of celery juice (CJ) could enhance the active ingredients in celery, such as total polyphenols, flavonoids, vitamin C and SOD. Compared to the slight improvement induced by CJ ingestion, FCJ intake significantly inhibited body weight gain, prevented dyslipidemia and hyperglycemia, and suppressed visceral fat accumulation. Furthermore, 16S rRNA sequencing analysis revealed that FCJ intake altered the composition of gut microbiota, increasing the ratio of Firmicutes/Bacteroidetes and the relative abundance of beneficial bacteria (Lactobacillus, Ruminococcaceae_UCG-014, Faecalibaculum and Blautia), and decreasing the relative abundance of harmful bacteria (Alloprevotella and Helicobacter). These findings suggest that FCJ can prevent HFD-induced obesity and become a novel gut microbiota modulator to prevent HFD-induced gut dysbiosis and obesity-related metabolic disorders.

Objectively Measured Physical Activity and Body Fatness: Associations with Total Body Fat, Visceral Fat, and Liver Fat.

PURPOSE: It remains unclear to what extent habitual physical activity and sedentary time (ST) are associated with visceral fat and liver fat. We studied the substitution of ST with time spent physically active and total body fat (TBF), visceral adipose tissue (VAT), and hepatic triglyceride content (HTGC) in middle-age men and women. DESIGN: In this cross-sectional analysis of the Netherlands Epidemiology of Obesity study, physical activity was assessed in 228 participants using a combined accelerometer and heart rate monitor. TBF was assessed by the Tanita bioelectrical impedance, VAT by magnetic resonance imaging, and HTGC by proton-MR spectroscopy. Behavioral intensity distribution was categorized as ST, time spent in light physical activity (LPA), and moderate to vigorous physical activity (MVPA). To estimate the effect of replacing 30 min·d-1 of ST with 30 min·d-1 LPA or MVPA, we performed isotemporal substitution analyses, adjusted for sex, age, ethnicity, education, the Dutch Healthy Diet index, and smoking. RESULTS: Included participants (41% men) had a mean ± SD age of 56 ± 6 yr and spent 88 ± 56 min in MVPA and 9.0 ± 2.1 h of ST. Replacing 30 min·d-1 of ST with 30 min of MVPA was associated with 1.3% less TBF (95% confidence interval = -2.0 to -0.7), 7.8 cm2 less VAT (-11.6 to -4.0), and 0.89 times HTGC (0.82-0.97). Replacement with LPA was not associated with TBF (-0.03%; -0.5 to 0.4), VAT (-1.7 cm2; -4.4 to 0.9), or HTGC (0.98 times; 0.92-1.04). CONCLUSIONS: Reallocation of time spent sedentary with time spent in MVPA, but not LPA, was associated with less TBF, visceral fat, and liver fat. These findings contribute to the development of more specified guidelines on ST and physical activity.

Choline and Folic Acid in Diets Consumed during Pregnancy Interact to Program Food Intake and Metabolic Regulation of Male Wistar Rat Offspring.

BACKGROUND: North American women consume high folic acid (FA), but most are not meeting the adequate intakes for choline. High-FA gestational diets induce an obesogenic phenotype in rat offspring. It is unclear if imbalances between FA and other methyl-nutrients (i.e., choline) account for these effects. OBJECTIVE: This study investigated the interaction of choline and FA in gestational diets on food intake, body weight, one-carbon metabolism, and hypothalamic gene expression in male Wistar rat offspring. METHODS: Pregnant Wistar rats were fed an AIN-93G diet with recommended choline and FA [RCRF; 1-fold, control] or high (5-fold) FA with choline at 0.5-fold [low choline and high folic acid (LCHF)], 1-fold [recommended choline and high folic acid (RCHF)], or 2.5-fold [high choline and high folic acid (HCHF)]. Male offspring were weaned to an RCRF diet for 20 wk. Food intake, weight gain, plasma energy-regulatory hormones, brain and plasma one-carbon metabolites, and RNA sequencing (RNA-seq) in pup hypothalamuses were assessed. RESULTS: Adult offspring from LCHF and RCHF, but not HCHF, gestational diets had 10% higher food intake and weight gain than controls (P < 0.01). HCHF newborn pups had lower plasma insulin and leptin compared with LCHF and RCHF pups (P < 0.05), respectively. Pup brain choline (P < 0.05) and betaine (P < 0.01) were 22-33% higher in HCHF pups compared with LCHF pups; methionine was ∼23% lower after all high FA diets compared with RCRF (P < 0.01). LCHF adult offspring had lower brain choline (P < 0.05) than all groups and lower plasma 5-methyltetrahydrofolate (P < 0.05) than RCRF and RCHF groups. HCHF adult offspring had lower plasma cystathionine (P < 0.05) than LCHF adult offspring and lower homocysteine (P < 0.01) than RCHF and RCRF adult offspring. RNA-seq identified 144 differentially expressed genes in the hypothalamus of HCHF newborns compared with controls. CONCLUSIONS: Increased choline in gestational diets modified the programming effects of high FA on long-term food intake regulation, plasma energy-regulatory hormones, one-carbon metabolism, and hypothalamic gene expression in male Wistar rat offspring, emphasizing a need for more attention to the choline and FA balance in maternal diets.

Visceral Fat and Anastomotic Leakage After Colon Cancer Resection.

BACKGROUND: Visceral fat is considered a risk for postoperative complications in colon cancer surgery. However, the association with anastomotic leakage as the most worrisome complication is not clear mainly because of underpowered studies. OBJECTIVE: The purpose of this study was to analyze the effect of visceral fat as a continuous variable on anastomotic leakage in a large cohort of colon cancer resections. DESIGN: This was a retrospective, multicenter cohort study. SETTINGS: This study used data of the Dutch Surgical Colorectal Audit of the years 2011 through 2014 from 8 Dutch teaching hospitals. Visceral fat was assessed on the routine preoperative abdominal CT scan. PATIENTS: A total of 2370 patients underwent colon cancer resection with primary anastomosis. There were 2011 patients operated electively and 359 in an emergency setting. MAIN OUTCOME MEASURES: The effect of visceral fat on anastomotic leakage after multivariable analysis was measured. RESULTS: Visceral fat was associated with anastomotic leakage in the elective colon resection group (n = 2011) but not in emergency colon resections (n = 359). Significant confounding was found for type of resection, BMI, and sex. The association of male sex and BMI as previously reported risk factors for anastomotic leakage was explained by visceral fat. LIMITATIONS: The study was limited by its retrospective character and missing clinical data of known risk factors for anastomotic leakage, like smoking history and certain medication. CONCLUSIONS: The independent association of visceral fat with anastomotic leakage was confined to the elective colon cancer resection group. The previously reported associations of male sex and BMI with anastomotic leakage were explained by visceral fat. Visceral fat-associated comorbidities did not influence anastomotic leakage, suggesting that its effect on colon anastomotic healing is local rather than systemic. Future risk analysis for anastomotic leakage in colon cancer surgery should contain visceral fat values and consider subgroup differences. See Video Abstract at http://links.lww.com/DCR/B396. ADIPOSIDAD VISCERAL Y FUGA ANASTOMTICA EN CASOS DE RESECCIN DE CNCER DE COLON: ANTECEDENTES:La acumulación de grasa visceral se considera como un factor de riesgo en caso de complicaciones postoperatorias de cirugía de cáncer de colon. Sin embargo, la asociación con la fuga anastomótica como la complicación más preocupante no está clara principalmente debido a los estudios de bajo impacto disponibles.OBJETIVO:Analizar el efecto de la adiposidad visceral como una variable contínua sobre la fuga anastomótica en una gran cohorte de resecciones de cáncer de colon.DISEÑO:Estudio de cohorte multicéntrico retrospectivo.AJUSTES:Se utilizaron los datos de la Auditoría Colorrectal Quirúrgica Holandesa entre los años 2011 y 2014 en 8 hospitales de enseñanza de los Paises bajos. La grasa visceral fué evaluada por medio de la tomografía computada abdominal preoperatoria de rutina.PACIENTES:Un total de 2370 pacientes fueron sometidos a resección de cáncer de colon con anastomosis primaria. 2011 pacientes fueron operados electivamente y 359 en situación de emergencia.PRINCIPALES MEDIDAS DE RESULTADO:El efecto de la adiposidad visceral en la fuga anastomótica después del análisis multivariable.RESULTADOS:La grasa visceral se asoció con la fuga anastomótica en el grupo de resección electiva de colon (n = 2011) pero no en las resecciones de emergencia (n = 359). Se encontraron factores de confusión significativos para el tipo de resección, el índice de masa corporal y el género. La adiposidad visceral explica la asociación del género masculino y el índice de masa corporal como factores de riesgo reportados previamente en los casos de fugas anastomóticas.LIMITACIONES:Carácter retrospectivo del estudio y la falta de datos clínicos de factores de riesgo conocidos para la fuga anastomótica, como los antecedentes de tabaquismo y el consumo de ciertos medicamentos.CONCLUSIONES:La asociación independiente de la adiposidad visceral con la fuga anastomótica se limitó al grupo de resección electiva por cáncer de colon. Las asociaciones previamente reportadas de género masculino e índice de masa corporal con fuga anastomótica se explicaron por la grasa visceral. Las comorbilidades asociadas a la grasa visceral no influyeron en la fuga anastomótica, lo que sugiere que la cicatrisación anastomótica obedece más a un factor local que a un factor sistémico. Un análisis de riesgos previsibles para fugas anastomóticas en casos de resección de cáncer de colon deben involucrar los valores de la adiposidad visceral y considerar las diferencias entre subgrupos. Consulte Video Resumen en http://links.lww.com/DCR/B396. (Traducción-Dr Xavier Delgadillo).

Establishment of normative biometric data for body composition based on computed tomography in a North American cohort.

BACKGROUND & AIMS: Accurate and reproducible biomarkers are required to allow a more personalized approach to patient care. Body composition is one such biomarker affecting outcomes in a range of surgical and oncological conditions. The aim of this study is to determine the age and sex specific distribution of body composition data, based on information gathered from computed tomography (CT). METHODS: This prospective study used healthy subjects from the medical records linkage of the Rochester Epidemiology Project, based in Minnesota, USA. Each patient had a CT scan without intravenous contrast performed between 1999 and 2001. Quantification was performed using previously validated semi-automated in-house developed software for body composition analysis. Subcutaneous adipose tissue area, visceral adipose tissue area, intermuscular adipose tissue area and skeletal muscle area were measured and indexed to subject height. Generalized Additive Models for Location, Scale and Shape were used to assess the location, scale, and shape of each variable across age, stratified by sex. Z-scores specific to sex were assessed for each of the parameters analyzed. Age-specific z-scores were calculated using the formula: Z = (Index Variable - µ)/σ or Z = (√ (Index Variable) - µ)/σ. RESULTS: There were 692 subjects enrolled in the study. The fitted model equation was offered for each variable with values presented for µ and σ. Modelling with penalized splines was performed for VAT index, IMAT index and total adipose tissue index. Scatterplots of each variable were produced with lines of Z-scores as a visual representation. CONCLUSION: This study offers comparative data to allow comparison amongst multiple populations. This will form an important reference for future research and clinical practice.

Perirenal Fat Surface Area and Oncologic Outcome in Elective Colon Cancer Surgery.

BACKGROUND: Central obesity is associated with surgical difficulties, but few studies explore the relationship with long-term results after colon cancer surgery. OBJECTIVE: The purpose of this study was to investigate the association between perirenal fat surface area, a proxy for total visceral fat, and oncologic outcome after intestinal resection for colon cancer. DESIGN: We investigated the association between perirenal fat surface area (exposure) on recurrence and death (outcome) in patients undergoing surgery with curative intent for colon cancer. SETTINGS: The study was conducted at Stockholm South General Hospital, serving a population of 600,000. PATIENTS: Patients (N = 733) without metastases at diagnosis who had a preoperative CT and had undergone elective colon resection between 2006 and 2016 were included. MAIN OUTCOME MEASURES: We compared overall survival, recurrence-free survival, and cause-specific survival by perirenal fat surface area. RESULTS: Patients with high perirenal fat surface area (fourth quartile) had more often left-sided tumors (45% vs 32% in the first quartile) and experienced more postoperative complications (29% vs 13%), but there were no differences in pathologic T and N stage, radicality of surgery, or adjuvant chemotherapy treatment. Overall survival decreased by increasing cancer stage but was not different between perirenal fat surface area categories. The HR for recurrence-free survival per centimeter squared increase in perirenal fat surface area was 1.00 (95% CI, 0.99-1.01) adjusted for age, sex, ASA category, tumor location, and postoperative complication Clavien-Dindo ≥2. The cumulative incidence of recurrence with death as a competing risk was not statistically different between perirenal fat surface area categories (p = 0.06). Subgroup analyses showed a nonsignificant tendency for men with low perirenal fat surface area to have a lower risk of recurrence and women a higher risk. LIMITATIONS: In all register-based studies there can be randomly distributed errors. The results can only be generalized to colon resections. Our cohort ranged over a large year span. CONCLUSIONS: We found no association between perirenal fat surface area and overall survival, recurrence-free survival, or cause-specific cumulative incidence of recurrence in patients undergoing colon resection for cancer. See Video Abstract at http://links.lww.com/DCR/B326. LA SUPERFICIE DE GRASA PERIRRENAL Y EL RESULTADO ONCOLGICO EN CIRUGA ELECTIVA DE CNCER DE COLON: ANTECEDENTES:La obesidad central está asociada con dificultades quirúrgicas, pero pocos estudios exploran la relación de los resultados a largo plazo después de cirugía de cáncer de colon.OBJETIVO:Investigar la asociación entre la superficie de la grasa perirrenal, como un indicador de la grasa visceral total y el resultado oncológico después de una resección intestinal por cáncer de colon.DISEÑO:Se estudió la asociación entre el área de la superficie de la grasa perirrenal (expuesta) con la recurrencia y la muerte (resultado) de pacientes sometidos a cirugía con intención curativa por cáncer de colon.AJUSTES:Atención brindada por el Hospital General del Sur de Estocolmo a una población de 600,000 habitantes.PACIENTES:Aquellos pacientes sin metástasis (n = 733) en el momento del diagnóstico que tuvieron una tomografía computada preoperatoria y que se sometieron a una resección electiva de colon entre 2006-2016.PRINCIPALES MEDIDAS DE RESULTADO:Comparamos la sobrevida general, la sobrevida libre de recurrencia y la sobrevida específica de la causa, por área de superficie de grasa perirrenal.RESULTADOS:Los pacientes con una mayor área de superficie de grasa perirrenal (cuarto cuartil) tuvieron más frecuentemente tumores del lado izquierdo (45% frente a 32% en el primer cuartil) y sufrieron más complicaciones postoperatorias (29% frente a 13%), pero no hubieron diferencias en el Estadío patológico T y N, ni en lo radical de la cirugía o del tratamiento de quimioterapia adyuvante. La supervivencia general disminuyó al aumentar el estadio del cáncer, pero no fue diferente entre las categorías de área de superficie grasa perirrenal. La razón de riesgo para la sobrevida libre de recurrencia por aumento de cm2 en el área de la superficie grasa perirrenal fue de 1.00 (intervalo de confianza del 95%: 0.99-1.01) ajustada por edad, sexo, categoría de la Sociedad Americana de Anestesiólogos, ubicación del tumor y complicación postoperatoria según Clavien-Dindo ≥ 2) La incidencia acumulada de recurrencia con muerte como un riesgo competitivo no fue estadísticamente diferente entre las categorías de área de superficie grasa perirrenal (p = 0.06). Los análisis de subgrupos mostraron una tendencia no significativa para que los hombres con un área de superficie menor en grasa perirrenal tengan un menor riesgo de recurrencia y las mujeres un mayor riesgo.LIMITACIONES:En todos los estudios basados en registros puede haber errores distribuidos aleatoriamente. Los resultados solo pueden generalizarse a resecciones de colon. Nuestra cohorte osciló durante un gran lapso de años.CONCLUSIONES:No se encontró asociación entre el área de superficie de la grasa perirrenal y la sobrevida general, ni con la sobrevida libre de recurrencia o la incidencia acumulada de recurrencia específica de la causa en pacientes sometidos a resección de colon por cáncer. Consulte Video Resumen en http://links.lww.com/DCR/B326. (Traducción-Dr Xavier Delgadillo).

Murinometric measurements and retroperitoneal adipose tissue in young rats exposed to the high-fat diet: Is there correlation? / Medidas murinométricas e tecido adiposo retroperitoneal em ratos jovens expostos à dieta hiperlipídica: existe correlação?

Aim: This study aimed to verify the correlation between murine measurements and retroperitoneal adipose tissue in rats exposed to the high-fat diet. Material and methods: Wistar male adult rats, descendants of mothers who consumed a high-fat diet during pregnancy and lactation and fed the same diet after weaning were used. At 60 days of life, body weight, longitudinal axis and waist circumference (WC) were measured. The Body Mass Index (BMI) and the Lee Index were calculated for a posterior analysis of the correlation with the amount of retroperitoneal adipose tissue dissected on the same day. For analysis of the data, the Pearson correlation test was used, considering statistical significance for p<0.05. Results: Body weight had a weak correlation (r= 0.31; p= 0.38) with retroperitoneal adipose tissue. While the longitudinal correlated moderately and negative (r= -0.40; p= 0.25). Abdominal circumference (r= 0.62; p= 0.05), body mass index (r= 0.61; p= 0.03) and Lee (r= 0.69; p= 0.03) correlated moderately and positively with adipose tissue. Conclusion: Among the measured murine measurements, weight and longitudinal axis were not good indicators to represent accumulation of retroperitoneal adipose tissue in rats. However, Lee's index seems to be the best murine marker to diagnose the accumulation of retroperitoneal fat. BMI, CA and Lee index were murine parameters with higher correlation.

Objetivo: Este estudo teve como objetivo verificar a correlação entre medidas murinométricas e tecido adiposo retroperitoneal em ratos expostos à dieta hiperlipídica. Material e métodos: Foram utilizados ratos Wistar machos adultos, descendentes de mães que consumiram dieta hiperlipídica durante a gestação e lactação e alimentados com a mesma dieta após o desmame. Aos 60 dias de vida, foram medidos o peso corporal, o eixo longitudinal e a circunferência da cintura (CC). O Índice de Massa Corporal (IMC) e o Índice de Lee foram calculados para posterior análise da correlação com a quantidade de tecido adiposo retroperitoneal dissecado no mesmo dia. Para análise dos dados, utilizou se o teste de correlação de Pearson, considerando significância estatística para p<0.05. Resultados: O peso corporal apresentou uma correlação fraca (r= 0,31; p= 0,38) com o tecido adiposo retroperitoneal. Enquanto o longitudinal correlacionou moderadamente e negativo (r= -0,40; p= 0,25). A circunferência abdominal (r = 0,62; p = 0,05), índice de massa corporal (r= 0,61; p= 0,03) e Lee (r= 0,69; p= 0,03) correlacionaram-se moderada e positivamente com o tecido adiposo. Conclusão: Entre as medidas murinométricas, o peso e o eixo longitudinal não foram bons indicadores para representar o acúmulo de tecido adiposo retroperitoneal em ratos. No entanto, o índice de Lee parece ser o melhor indicador murinométrico para diagnosticar o acúmulo de gordura retroperitoneal. O IMC, índice de Lee e CA foram parâmetros murinométricos com maior correlação.

Impact of skeletal muscle mass on complications following expander breast reconstruction.

Sarcopenia is characterized by skeletal muscle mass (SMM) depletion and decreased muscle power. In two-stage breast reconstruction using a tissue expander, obesity is the main risk factor for postoperative complications. Obese patients with breast cancer and sarcopenia have a hidden lower SMM with a larger body mass index (BMI). This study aimed to investigate the impact of decreased SMM on complications after tissue expander surgery. In this nonrandomized, retrospective cohort study, 157 patients underwent 169 expander indwelling surgeries. Cross-sectional areas (cm2) of skeletal muscles at the third lumbar vertebra were measured on computed tomography (CT) and normalized for height (cm2/m2) to determine the skeletal muscle index (SMI). Subcutaneous and visceral adipose tissue areas were measured in the same slice and normalized for height (cm2/m2) to determine the total adipose tissue index (TATI). The SMI/TATI ratio was calculated as an index of sarcopenic obesity. Postoperative complications occurred in 40 cases (23.7%). In multivariate analysis, a lower SMI/TATI ratio was identified as a significant independent risk factor for complications (P < 0.001, adjusted odds ratio (OR) = 2.28 per 10% decrease). Delayed wound healing was significantly associated with lower SMI/TATI ratio (P = 0.003, OR = 6.33 per 10% decrease) and diabetes (P = 0.044, OR = 7.36). Seroma was significantly associated with high BMI (P < 0.001, OR = 8.00 per 5-kg/m2 increase) and blood loss (P = 0.003, OR = 1.18 per 10 g increase). These results show that patients with a large adipose tissue volume and lower SMM (sarcopenic obesity) have more complications after expander surgery than those with high BMI, or TATI alone.

Morphomic Factors Associated With Complete Response to Neoadjuvant Therapy in Esophageal Carcinoma.

BACKGROUND: In patients undergoing neoadjuvant chemoradiotherapy (nCRT) followed by surgery for locally advanced esophageal squamous cell carcinoma (ESCC), patients with a pathologic complete response (pCR) have the greatest benefit. The purpose of this study was to identify morphomic factors obtained from pretreatment computed tomography scans associated with a pCR in ESCC. METHODS: We retrospectively analyzed patients with ESCC treated with nCRT who underwent esophagectomy between 2006 and 2016. Clinical and morphomic characteristics pre-nCRT were analyzed to identify factors associated with pCR using univariate and multivariable analyses. RESULTS: There were 183 patients with ESCC included in this study, and 45 (24.6%) patients achieved pCR. The overall survival in patients with pCR was better than that in patients without pCR (5.8 years vs 1.2 years; P < .001). On univariate analysis, increased age, radiation dose greater than or equal to 4000 cGy, and larger subcutaneous adipose tissue area were correlated with pCR. On multivariable logistic regression, increased age (odds ratio, 1.53; P = .03), radiation dose greater than or equal to 4000 cGy (odds ratio, 2.19; P = .04), and larger dorsal muscle group normal-density area (odds ratio, 1.59; P = .03) were independently associated with pCR. CONCLUSIONS: Increased age, radiation dose greater than or equal to 4000 cGy, and larger dorsal muscle group normal-density area were significantly associated with pCR. These factors may be useful in determining which patients are most likely to benefit from nCRT followed by esophagectomy.

Exercise-Induced Changes in Visceral Adipose Tissue Mass Are Regulated by IL-6 Signaling: A Randomized Controlled Trial.

Visceral adipose tissue is harmful to metabolic health. Exercise training reduces visceral adipose tissue mass, but the underlying mechanisms are not known. Interleukin-6 (IL-6) stimulates lipolysis and is released from skeletal muscle during exercise. We hypothesized that exercise-induced reductions in visceral adipose tissue mass are mediated by IL-6. In this randomized placebo-controlled trial, we assigned abdominally obese adults to tocilizumab (IL-6 receptor antibody) or placebo during a 12-week intervention with either bicycle exercise or no exercise. While exercise reduced visceral adipose tissue mass, this effect of exercise was abolished in the presence of IL-6 blockade. Changes in body weight and total adipose tissue mass showed similar tendencies, whereas lean body mass did not differ between groups. Also, IL-6 blockade increased cholesterol levels, an effect not reversed by exercise. Thus, IL-6 is required for exercise to reduce visceral adipose tissue mass and emphasizes a potentially important metabolic consequence of IL-6 blockade.

Analysis of the Correlation Between Central Obesity and Abdominal Aortic Diseases.

BACKGROUND: Atherosclerosis and abdominal aortic aneurysms (AAAs) have several similar risk factors but different pathogenesis. Inflammation of the arteries is common to both. Central obesity can act as an endocrine organ through the secretion of inflammatory cytokines, and the perivascular fat has a local effect that could contribute to diseases of the abdominal aorta. Although the relation between central obesity and atherosclerosis occlusive arterial disease has been demonstrated, the correlation with AAA has conflicting results. The aim of this study was to analyze the correlation between central obesity and the presence of abdominal aortic diseases using computed tomography. METHODS: Six hundred thirty-nine consecutive patients classified into 3 groups (AAA, aortic atherosclerotic occlusive disease (AAOD), and without aortic disease [control group]) who underwent computed tomography had the aorta diameter, the visceral fat area (VFA), and the subcutaneous fat area (SFA) measured at the level of third and fourth lumbar vertebrae. RESULTS: VFA showed no difference between the groups. SFA was lower in atherosclerotic group (AAOD) than control (P < 0.01 in general and P < 0.04 in male). In AAA group, we found in men that the first tertile of aorta diameter had higher VFA than third tertile (P = 0.02). CONCLUSIONS: There was no difference in VFA between patients in AAA, AAOD, and without aortic disease groups. In men with aneurysm, there was an inverse relationship between VFA and aortic diameter. In AAOD, visceral to subcutaneous ratio is higher due to lower SFA.

Influence of Visceral Fat in the Outcomes of Colorectal Cancer.

AIM: To determine the relationship of visceral fat (VF) with the surgical outcome of the patients with colorectal cancer (CRC) submitted to curative surgery. METHODS: Retrospective analysis of all patients submitted to CRC surgery during 3 years with a minimum of 5 years of follow-up. We assessed the length of hospital stay, complications, pathologic reports, surgical re-interventions and hospital re-admissions, relapses, survival time and disease-free time. VF was calculated based on patients' pre-operative CT-scan. The patients were divided into quartiles according to the VF area. Linear regression models and logistic regression models were used to establish a relationship between VF and all data collected. RESULTS: The study included 199 patients (129 with colon cancer [CC] and 70 with rectal cancer). The average area of VF was 115.7 cm2. Patients with CRC revealed a direct relationship between VF and postoperative complications (p = 0.043), anastomotic leakage (p = 0.009) and re-operation (p = 0.005). The subgroup of patients with CC had an inverse association between VF and lymph nodes harvested (p = 0.027). Survival analyses did not reveal significant differences. CONCLUSION: VF has an influence on postoperative complications, anastomotic leakage and re-operation. A negative influence of VF on lymph nodes harvested was observed on CC patients.

Physical exercise alters hepatic morphology of low-density lipoprotein receptor knockout ovariectomized mice.

To explore the effects of physical exercise on the liver of animals in menopause, we analyzed the histomorphometric parameters of the hepatic tissue in ovariectomized and dyslipidemic female mice. The animals were distributed in six groups (n = 5): sedentary control (SC), sedentary ovariectomized control (SOC), trained ovariectomized control (TOC), sedentary LDL knockout (LDL-S), sedentary ovariectomized LDL knockout (LDL-SO), and trained ovariectomized LDL knockout (LDL-TO). At the end of the experiment, the liver and the visceral adipose tissue (VAT) of animals were removed for morphometric and stereological studies. In the LDL-S and LDL-SO animals, both sedentary, results showed reduction in the area (µm2) and major and minor diameters (µm) of hepatocytes and reduction in the portions of large hepatocytes, and increase in the percentage of Kupffer cells. The trained group showed a tendency of increase in the area and diameter and in the percentage of hepatocytes, as well significant reduction in the percentage of Kupffer cells and interstitial tissue. We suggested that training can prevent cell and tissue damage caused by the process of increase in hepatic fat, lipoperoxidation, and tissue inflammation in animals with privation of estrogen and dyslipidemia, apparently reflecting a better metabolic response of the hepatic tissue in organisms undergoing training.

Impact of adipose tissue on prostate cancer aggressiveness - analysis of a high-risk population.

Background We investigated whether visceral adiposity is associated with more aggressive disease at prostatectomy. Materials and methods Four hundred and seventy-four patients referred for postoperative adjuvant or salvage radiotherapy were included in this study. Primary endpoints were positive surgical margins (pSM) or extracapsular extension (ECE). Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were manually contoured. Univariate and multivariate logistic regression was performed. Results In univariate analysis, VAT volume (p = 0.006), adipose tissue ratio (VAT/SAT, p = 0.003), density of the SAT (p = 0.04), as well as age (p < 0.001) were associated with pSM. In the univariate analysis, SAT density was associated with a trend towards a higher rate of ECE (p = 0.051) but visceral fat volume (p = 0.01), as well as the adipose tissue ratio (p = 0.03) were both protective factors. None of the adipose tissue measurements or BMI had an influence on biochemical recurrence or overall survival (all p ≥ 0.5). Conclusions SAT-volume and increased SAT-density were generally associated with more aggressive prostate cancers whereas VAT as a protective factor. These findings emphasize a possible mechanism for the association between obesity and prostate cancer aggressiveness.

Deep learning-based quantification of abdominal fat on magnetic resonance images.

Obesity is increasingly prevalent and associated with increased risk of developing type 2 diabetes, cardiovascular diseases, and cancer. Magnetic resonance imaging (MRI) is an accurate method for determination of body fat volume and distribution. However, quantifying body fat from numerous MRI slices is tedious and time-consuming. Here we developed a deep learning-based method for measuring visceral and subcutaneous fat in the abdominal region of mice. Congenic mice only differ from C57BL/6 (B6) Apoe knockout (Apoe-/-) mice in chromosome 9 that is replaced by C3H/HeJ genome. Male congenic mice had lighter body weight than B6-Apoe-/- mice after being fed 14 weeks of Western diet. Axial and coronal T1-weighted sequencing at 1-mm-thickness and 1-mm-gap was acquired with a 7T Bruker ClinScan scanner. A deep learning approach was developed for segmenting visceral and subcutaneous fat based on the U-net architecture made publicly available through the open-source ANTsRNet library-a growing repository of well-known neural networks. The volumes of subcutaneous and visceral fat measured through our approach were highly comparable with those from manual measurements. The Dice score, root-mean-square error (RMSE), and correlation analysis demonstrated the similarity between two methods in quantifying visceral and subcutaneous fat. Analysis with the automated method showed significant reductions in volumes of visceral and subcutaneous fat but not non-fat tissues in congenic mice compared to B6 mice. These results demonstrate the accuracy of deep learning in quantification of abdominal fat and its significance in determining body weight.

Design and validation of a novel estimator of visceral adipose tissue area and comparison to existing adiposity surrogates.

AIMS: Visceral adiposity measured by computed tomography (CT) as intra-abdominal fat area (IAFA) predicts metabolic diseases. Existing adiposity surrogates have not been systematically compared to a regression-based model derived in individuals of Japanese ancestry. We developed and validated a method to estimate IAFA in individuals of Japanese ancestry and compared it to existing adiposity surrogates. METHODS: We assessed age, BMI, waist circumference (WC), fasting lipids, glucose, smoking status, grip strength, mid-thigh circumference (MTC), humeral length, leg length, and IAFA by single-slice CT at the umbilicus for 622 Japanese Americans. We used stepwise linear regression to predict IAFA and termed the predicted value the Estimate of Visceral Adipose Tissue Area (EVA). For men, the final model included age, BMI, WC, high-density lipoprotein cholesterol (HDLc), glucose, and MTC; for women, age, BMI, WC, HDLc, low-density lipoprotein cholesterol, glucose, and MTC. We compared goodness-of-fit (R2) from linear regression models and mean-squared errors (MSE) from k-fold cross-validation to compare the ability of EVA to estimate IAFA compared to an estimate by Després et al., waist-to-height ratio, WC, deep abdominal adipose tissue index, BMI, lipid accumulation product, and visceral adiposity index (VAI). We classified low/high IAFA using area under receiver-operating characteristic curves (AUROC) for IAFA dichotomized at the 75th percentile. RESULTS: EVA gave the least MSE and greatest R2 (men: 1244, 0.61; women: 581, 0.72). VAI gave the greatest MSE and smallest R2 (mean 2888, 0.08; women 1734, 0.14). CONCLUSIONS: EVA better predicts IAFA in Japanese-American men and women compared to existing surrogates for adiposity.

High perirenal fat thickness predicts a poor progression-free survival in patients with localized clear cell renal cell carcinoma.

OBJECTIVES: The aim of the study was to assess the association between the progression-free survival (PFS) and perirenal fat thickness (PFT) in a population of histopathologically confirmed, localized clear cell renal cell carcinoma (ccRCC) patients. METHODS: We retrospectively enrolled 174 patients with localized ccRCC at our center between December 2009 and December 2015. The preoperative visceral fat area (VFA), PFT, and subcutaneous fat area (SFA) were evaluated. Kaplan-Meier curves were used to assess the differences in PFS between the high and the low PFT groups within sexes. Potential independent prognostic factors of PFS were identified by univariable and multivariable Cox analyses. RESULTS: During the follow-up period (median, 38 months), 27 patients (21 with high PFT and 6 with low PFT) experienced tumor progression. Kaplan-Meier curves revealed that high PFT was associated with a worse PFS than low PFT (P = 0.005). In the univariable Cox analyses, high VFA, high PFT, T stage, and the presence of sarcomatoid differentiation were significantly associated with a poor PFS. Moreover, both high PFT and VFA retained significance in the multivariable analysis. CONCLUSION: We first report the evidence that high PFT presents as an independent risk factor of tumor progression in localized ccRCC. We suggest that this noninvasive and readily available preoperative parameter may help in the risk stratification of ccRCC patients before surgery.

Decreased visceral fat area correlates with improved total testosterone levels after Roux-en-Y gastric bypass in obese Chinese males with type 2 diabetes: a 12-month follow-up.

BACKGROUND: Obesity and type 2 diabetes (T2D) are recognized as risk factors for hypogonadism in males. Serum sex hormone profiles have not been assessed adequately in obese Chinese males with T2D who have undergone Roux-en-Y gastric bypass (RYGB). OBJECTIVE: This study was conducted to examine the changes in sex hormone profiles, anthropometric parameters, and metabolic indexes before and after RYGB. SETTING: University Hospital, China. METHODS: There were 45 obese males with T2D who had undergone RYGB enrolled in this retrospective study, focusing on anthropometric parameters, metabolic indexes, and sex hormone profiles before and after surgery. RESULTS: The baseline prevalence of hypogonadism (defined by total testosterone [TT] levels<8 nM) was 33.33%. After surgery, both the levels of TT and sex hormone-binding globulin increased, while the levels of estradiol decreased. However, the calculated free testosterone, follicle-stimulating hormone, and luteinizing hormone levels remained unchanged. Multiple linear regression analysis showed that the visceral fat area was the only significant and independent parameter associated with TT levels at baseline (ß = -.479, P = .001). After surgery, decreases in the visceral fat area continued to be negatively associated with increases in TT (r = -.411, P = .024). CONCLUSION: These preliminary results demonstrated that TT could be significantly increased in obese Chinese males with T2D after RYGB; this occurs in part via a reduction in adipose tissue, especially visceral fat. Therefore, RYGB might be a promising therapy to treat hypogonadism in obese men with T2D.

Change in visceral adiposity is an independent predictor of future arterial pulse pressure.

OBJECTIVES: Pulse pressure (PP), a marker of arterial stiffness, and body composition are both risk factors for cardiovascular disease. Little is known about whether changes in body composition may be linked to future PP. We sought to determine whether change in amount of abdominal and thigh fat over 5 years predicted PP at 10 years. METHODS: Visceral fat as well as abdominal and thigh subcutaneous fat areas were measured by computed tomography at baseline and 5 years later in 284 Japanese Americans (mean age 49.3 years; 50.4% men) without hypertension, heart disease, and glucose-lowering medication use at baseline. PP at 10 years was calculated as the difference between SBP and DBP measured with a mercury sphygmomanometer. The association between change in fat at 5 years and arterial PP at 10 years, adjusted for baseline PP, was examined using linear regression analysis. MAIN RESULTS: Change in abdominal visceral fat area at 5 years was positively associated with 10-year PP independent of sex, 5-year change in BMI, and baseline age, BMI, PP, abdominal visceral fat, smoking status, alcohol consumption, physical activity, homeostasis model assessment insulin resistance, and fasting plasma glucose. There were no significant associations between baseline amounts or change in abdominal or thigh subcutaneous fat areas and future PP. CONCLUSION: The accumulation of abdominal visceral fat over time independently predicted future PP in Japanese Americans.