Visceral Obesity May Affect Oncologic Outcome in Patients with Colorectal Cancer
ABSTRACT Obesity is closely related to the development of colorectal cancer as well as other metabolic complications. We investigated the prognostic significance of visceral obesity and body mass index (BMI) in 161 resectable colorectal cancer patients.
Ratios of visceral fat area (VFA) to subcutaneous fat area (SFA) were measured from the digital images of patients' computed tomography taken before the surgery, and patients were divided into those with high and those with low VFA/SFA ratio according to the degree of proportional visceral adiposity, and into an overweight and a normal-weight group according to their preoperative BMI.
The overweight group showed a borderline decrease in cumulative disease-free survival compared to the normal-weight group (P = 0.064). Patients with high VFA/SFA ratio (more than 50 percentiles) had significantly lower cumulative disease-free survival rate compared to patients with low VFA/SFA ratio (P = 0.008). BMI and visceral adiposity showed no influence on overall survival of patients.
Increased visceral adiposity was a significant predictor of disease-free survival in patients with resectable colorectal cancer. The prognostic significance of visceral adiposity should further be determined in a larger set of patients.
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ABSTRACT: The molecular mechanisms responsible for the association of obesity with adverse colon cancer outcomes are poorly understood. We investigated the effects of a high-energy diet on growth of an in vivo colon cancer model. Seventeen days following the injection of 5x10(5) MC38 colon carcinoma cells, tumors from mice on the high-energy diet were approximately twice the volume of those of mice on the control diet. These findings were correlated with the observation that the high-energy diet led to elevated insulin levels, phosphorylated AKT, and increased expression of fatty acid synthase (FASN) by the tumor cells. Metformin, an antidiabetic drug, leads to the activation of AMPK and is currently under investigation for its antineoplastic activity. We observed that metformin blocked the effect of the high-energy diet on tumor growth, reduced insulin levels, and attenuated the effect of diet on phosphorylation of AKT and expression of FASN. Furthermore, the administration of metformin led to the activation of AMPK, the inhibitory phosphorylation of acetyl-CoA carboxylase, the upregulation of BNIP3 and increased apoptosis as estimated by poly (ADP-ribose) polymerase (PARP) cleavage. Prior work showed that activating mutations of PI3K are associated with increased AKT activation and adverse outcome in colon cancer; our results demonstrate that the aggressive tumor behavior associated with a high-energy diet has similar effects on this signaling pathway. Furthermore, metformin is demonstrated to reverse the effects of the high-energy diet, thus suggesting a potential role for this agent in the management of a metabolically defined subset of colon cancers.Endocrine Related Cancer 03/2010; 17(2):351-60. DOI:10.1677/ERC-09-0252 · 4.91 Impact Factor
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ABSTRACT: The association between obesity and the risk of colorectal cancer (CRC) cannot be easily evaluated because CRC itself is associated with a gradual loss of bodyweight. Aberrant crypt foci (ACF) can be classified as dysplastic ACF or non-dysplastic ACF by magnifying colonoscopy, and dysplastic ACF are thought to be a biomarker of CRC. Ninety-four participants who underwent colonoscopy at Yokohama City University Hospital, Japan, were enrolled in the current study. We detected 557 ACF, including 67 dysplastic ACF (12.0%). Univariate regression analysis was conducted to determine correlations between the number of dysplastic ACF and various potential risk factors, including patient age, waist circumference, body mass index, visceral fat area (VFA), and plasma adiponectin level. The results of multiple regression analysis revealed that the number of dysplastic ACF correlated with age (correlation coefficient r=0.212, P=0.0383) and plasma adiponectin level (r=-0.201, P=0.0371), even after adjustments for sex, waist circumference, body mass index, and VFA. Our univariate correlation analysis data showed a significant correlation with the number of dysplastic ACF with VFA (r=0.238, P=0.0209), no correlation with subcutaneous fat area, and an inverse correlation with the plasma level of adiponectin (r=-0.258, P=0.0118). Thus, our results suggest that aging and visceral fat accumulation could correlate moderately with colorectal carcinogenesis. The novelty of our study lies in the finding that visceral fat accumulation and a low plasma adiponectin level may promote colorectal carcinogenesis; therefore, these obesity-related parameters may serve as novel targets for CRC prevention.Cancer Science 11/2008; 100(1):29-32. DOI:10.1111/j.1349-7006.2008.00994.x · 3.53 Impact Factor
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ABSTRACT: Westernization of lifestyle and diet has resulted in an increase in overweight patients in Japan. Although the adverse effects of higher body mass index (BMI) on early surgical outcomes are known, the relationship between BMI and long-term outcome is unclear. Clinicopathological characteristics and 5-year survival rate of overweight (BMI >or= 25 kg/m2; H-BMI; n = 1126) and nonoverweight (BMI < 25 kg/m2; N-BMI; n = 6799) patients who underwent gastrectomy with curative intent at the Cancer Institute Hospital between 1970 and 2004 were compared. Patients in the H-BMI group tended to have earlier-stage disease. The 5-year survival rate was significantly better in the H-BMI than N-BMI group (81.5% vs 74.1%, respectively; P < .001). Postoperative mortality was 1% in both groups (P = .482), whereas postoperative morbidity was 22% and 19% in the H-BMI and N-BMI groups, respectively (P = .007). Multivariate analysis indicated overweight, age, gender, surgical procedure, histology, operation year, pT, and pN as independent prognostic factors. Subset analyses of pT and pN stages revealed overweight as an independent prognostic factor in patients with pT1 and pN0. The 5-year survival rate following curative gastrectomy is better in overweight than nonoverweight Japanese patients, especially for early-stage gastric cancer. Further studies are needed to determine whether these results apply to other countries where morbidity and mortality for gastric cancer are higher than in Asian countries.Annals of Surgical Oncology 07/2009; 16(12):3245-51. DOI:10.1245/s10434-009-0645-8 · 3.94 Impact Factor