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Cancer, Obesity and Bariatric Surgery
Abstract
Cancer is the second leading cause of death globally and the leading cause in developed countries. Nearly four in ten cancers can be attributed to modifiable risk factors, with obesity having the second highest contribution after tobacco smoking. Based on current trends, it is predicted that by 2030 38% of the world’s adult population will be overweight, and 20% will be obese. In the United States of America (USA) and the United Kingdom (UK), this projection would translate to a combined additional 492,000–669,000 cases of cancer. The relationship between obesity and cancer is multimodal and complex. The mechanisms of carcinogenesis vary significantly between cancers and between populations, belying the notion of a “one size fits all” association with obesity. Understanding the obesity-linked mechanisms for specific cancers on a cellular level may explain the increased incidences of cancer and poor prognoses in obese patients. This may also help in the discovery of targeted therapies. This chapter reviews the mechanisms of carcinogenesis in the obese population, the clinical relationship between obesity and specific cancers, and the effect of non-surgical and bariatric surgery weight loss.
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Introduction:
Weight loss after bariatric surgery yields important health benefits. A multitude of observational studies have investigated the association of bariatric surgery for severe obesity with the risk of cancer. However, the results were debatable. The aim of the present study was to estimate the effect of bariatric surgery on overall cancer risk.
Methods:
A systematic literature search was performed to identify studies evaluating the association of bariatric surgery for severe obesity with the risk of cancer. Meta-analysis was performed to calculate combined prevalence.
Results:
Twenty-one cohort studies with 304,516 patients with obesity having under gone bariatric surgery and 8,492,408 patients with obesity as controls were included. Meta-analysis found decreased cancer risk to be associated with bariatric surgery (OR = 0.56, 95% CI = 0.48-0.66), both for the incidence of cancer (OR = 0.56, 95% CI = 0.46-0.68) and mortality of cancer (OR = 0.56, 95% CI = 0.41-0.75). In subgroup analysis, bariatric surgery was significantly associated with decreased breast cancer risk and endometrial cancer risk, but not associated with other cancer risk.
Conclusions:
Our meta-analysis indicated that bariatric surgery for severe obesity was associated with decreased cancer risk, both for cancer incidence and mortality. Moreover, further studies estimating the functional effect and side effects may eventually provide a better, comprehensive understanding.
Background
Epidemiologic studies regarding weight loss and subsequent cancer risk are sparse. The study aim was to evaluate the association between weight change by intentionality and obesity-related cancer incidence in the Women’s Health Initiative (WHI) Observational Study. Eleven cancers were considered obesity related: breast, ovary, endometrium, colon and rectum, esophagus, kidney, liver, multiple myeloma, pancreas, stomach and thyroid.
Methods
Postmenopausal women (n = 58,667) aged 50-79 years had body weight and waist circumference (WC) measured at baseline and year 3. Weight or WC change was categorized as: stable (change < ±5%), loss (≥5%) and gain (≥5%). Self-report at year 3 characterized weight loss as intentional or unintentional. During subsequent 12 years (mean) follow-up, 6,033 incident obesity-related cancers were identified. Relationships were evaluated using multivariable Cox proportional hazards regression models.
Results
Compared to women with stable weight, women with intentional weight loss had lower obesity-related cancer risk (HR = 0.88, 95% CI: 0.80-0.98). A similar result was observed for intentional WC reduction (HR = 0.88, 95% CI: 0.80-0.96). Among all cancers, intentional weight loss was most strongly associated with endometrial cancer (HR = 0.61, 95% CI: 0.42-0.88). Intentional WC loss was also associated with lower colorectal cancer risk (HR = 0.79, 95% CI: 0.63-0.99). Unintentional weight loss or weight gain was not associated with overall obesity-related cancer risk.
Conclusion
Intentional weight or WC loss in postmenopausal women was associated with lower risk of obesity-related cancer. These findings suggest that postmenopausal women who intentionally lose weight can reduce their obesity-related cancer risk.
The risk of gastric and/or esophageal cancers after bariatric surgery has been previously discussed in literature. A systematic review was performed to identify articles published between June 2012 and December 2018 reporting new cases of esophageal or gastric cancer not included in previous systematic reviews. Ten gastric malignancies, 28 esophageal cancers, and 2 gastro-intestinal stromal tumors (GIST) were identified. Primary bariatric surgery was a restrictive procedure in 26 cases, a purely malabsorptive procedure in 1 subject, and a gastric bypass in 13 patients. Although the vast majority of bariatric procedures seem to present a negligible relationship with any esophagogastric (EG) malignancy, published data remain incomplete. It was however considered of interest to update the number of EG neoplasms arisen following bariatric surgery.
According to GLOBOCAN 2018 data, gallbladder cancer (GBC) accounts for 1.2% of all global cancer diagnoses, but 1.7% of all cancer deaths. Only 1 in 5 GBC cases in the United States is diagnosed at an early stage, and median survival for advanced stage cancer is no more than about a year. The incidence of the disease is increasing in the developed world. Gallstones, biliary cysts, carcinogen exposure, typhoid, and Helicobacter pylori infection, and abnormal pancreaticobiliary duct junctions are all risk factors, many of which account for its geographical, ethnic and sex distribution. Genetics also plays a strong role, as about a quarter of GBC cases are considered familial, and certain ethnicities, such as Native Americans, are at far higher risk for the neoplasm. Prevention includes weight loss, vaccination against and treatment of bacterial infections, early detection and elimination of polyps and cysts, and avoidance of oral estrogen replacement therapy.
Purpose of Review
Obesity is a recognized risk factor for the development of breast cancer and recurrence even when patients are treated appropriately. We reviewed the literature that addresses the impact of obesity on diagnosis and the individual therapeutic interventions, and present a summary of the findings.
Recent Findings
Compared to non-obese women with breast cancer, obese women with breast cancer have a worse disease-free and overall survival despite appropriate local and systemic therapies. In brief, obese breast cancer patients experience more complications related to surgery, radiation, and chemotherapy. Further, obese patients are at increased risk for local recurrence compared to normal-weight women. Similarly, systemic chemotherapy is less effective, even when dosed appropriately on the basis of actual weight. Overall, endocrine therapy is less effective in obese women, and there is a suggestion that aromatase inhibitors may be selectively less effective than tamoxifen. Obese women are less likely to undergo breast reconstruction than normal-weight women, and those who do have surgery experience more surgical complications.
Summary
The efficacy of cancer treatments is significantly lower in obese breast cancer survivors, posing greater challenges in patient care and disease management in this patient population. Further investigations are warranted to assess the effects on treatment outcomes and optimize therapeutic mechanisms in order to successfully target breast cancer associated with obesity.
Introduction
Bariatric surgery treats morbid obesity resulting in long-lasting weight loss. Elevated body mass index (BMI) increases breast cancer risk. We hypothesized that patients undergoing bariatric surgery would have decreased overall and estrogen receptor (ER)-positive breast cancer incidences compared to a propensity-matched non-surgical cohort.
Methods
The bariatric population included all female patients who underwent weight loss surgery at a single institution from 1985 to 2015. Patients from all outpatient visits were propensity score matched 1:1 with bariatric patients using BMI, comorbidities, demographics, and insurance status. The primary outcome was breast cancer incidence. Univariate analyses compared the groups.
Results
A total of 4860 patients were included, with 2430 in both groups. Median follow-up time from date of surgery or morbid obesity diagnosis was 5.7 years. There were no differences in age or comorbidities aside from gastroesophageal reflux disease. Seventeen (0.7%) patients in the surgery group were subsequently diagnosed with breast cancer versus 32 (1.3%) in the non-surgery group (p = 0.03). The non-surgery group had more ER-positive tumors [4 (36.4%) vs. 22 (71.0%); p = 0.04].
Conclusion
Female patients who underwent bariatric surgery were less frequently diagnosed with any breast cancer and ER-positive breast cancer versus a propensity-matched cohort suggesting a possible oncologic benefit to weight loss surgery.
Continuously rising trends in obesity-related malignancies render this disease spectrum a public health priority. Worldwide, the burden of cancer attributable to obesity, expressed as population attributable fraction, is 11.9% in men and 13.1% in women. There is convincing evidence that excess body weight is associated with an increased risk for cancer of at least 13 anatomic sites, including endometrial, esophageal, renal and pancreatic adenocarcinomas; hepatocellular carcinoma; gastric cardia cancer; meningioma; multiple myeloma; colorectal, postmenopausal breast, ovarian, gallbladder and thyroid cancers. We first synopsize current epidemiologic evidence; the obesity paradox in cancer risk and mortality; the role of weight gain and weight loss in the modulation of cancer risk; reliable somatometric indicators for obesity and cancer research; and gender differences in obesity related cancers. We critically summarize emerging biological mechanisms linking obesity to cancer encompassing insulin resistance and abnormalities of the IGF-I system and signaling; sex hormones biosynthesis and pathway; subclinical chronic low-grade inflammation and oxidative stress; alterations in adipokine pathophysiology; factors deriving from ectopic fat deposition; microenvironment and cellular perturbations including vascular perturbations, epithelial-mesenchymal transition, endoplasmic reticulum stress and migrating adipose progenitor cells; disruption of circadian rhythms; dietary nutrients; factors with potential significance such as the altered intestinal microbiome; and mechanic factors in obesity and cancer. Future perspectives regarding prevention, diagnosis and therapeutics are discussed. The aim of this review is to investigate how the interplay of these main potential mechanisms and risk factors, exerts their effects on target tissues provoking them to acquire a cancerous phenotype.
Obesity is the strongest risk factor for endometrial cancer (EC). To inform targeted screening and prevention strategies, we assessed the impact of obesity and subsequent bariatric surgery-induced weight loss on endometrial morphology and molecular pathways implicated in endometrial carcinogenesis. Blood and endometrial tissue were obtained from women with class III-IV obesity (body mass index ≥40kg/m2 and ≥50kg/m2, respectively) immediately prior to gastric bypass or sleeve gastrectomy, and at two and 12 months’ follow up. The endometrium underwent pathological examination and immunohistochemistry was used to quantify proliferation (Ki-67), oncogenic signaling (PTEN, pAKT, pERK) and hormone receptor (ER, PR) expression status. Circulating biomarkers of insulin resistance, reproductive function and inflammation were also measured at each time point. Seventy-two women underwent bariatric surgery. At 12 months, the mean change in total and excess body weight was -32.7% and -62.8%, respectively. Baseline endometrial biopsies revealed neoplastic change in ten women (14%): four had EC, six had atypical hyperplasia (AH). Following bariatric surgery, most cases of AH resolved (5/6) without intervention (3/6) or with intrauterine progestin (2/6). Biomarkers of endometrial proliferation (Ki-67), oncogenic signaling (pAKT) and hormone receptor status (ER, PR) were significantly reduced, with restoration of glandular PTEN expression, at 2 and 12 months. There were reductions in circulating biomarkers of insulin resistance (HbA1c, HOMA-IR) and inflammation (hsCRP, IL-6), and increases in reproductive biomarkers (LH, FSH, SHBG). We found an unexpectedly high prevalence of occult neoplastic changes in the endometrium of women undergoing bariatric surgery. Their spontaneous reversal and accompanying down-regulation of PI3K-AKT-mTOR signaling with weight loss may have implications for screening, prevention and treatment of this disease.
Background:
The association between obesity and rising incidence of hepatocellular carcinoma (HCC) in the USA has been documented; however, the role of bariatric surgery remains less clear.
Aim:
To evaluate the cross-sectional association of prior-bariatric surgery and HCC.
Methods:
The United States Nationwide Inpatient Sample (NIS) database was queried from 2004 to 2014 for discharges with a diagnosis of morbid obesity. Primary outcomes of interest were HCC and in-hospital mortality rate. Secondary outcomes were length of stay and cost. Baseline characteristics were balanced using propensity score matching (PSM). Using Poisson and logistic regressions, adjusted HCC prevalence ratio (PR) and mortality odds ratio (OR) were derived in patients with prior-bariatric surgery compared to those without bariatric surgery.
Results:
Of the 2,881,414 patients included in our study, 267,082 (9.3%) underwent bariatric surgery. From 2004 to 2014, there was a threefold increase in age-adjusted prevalence of HCC from 27 per 100,000 to 72 per 100,000 (PTrend < 0.001). After PSM, 230,956 patients with prior-bariatric surgery were matched with 230,956 patients without bariatric surgery. Prior-bariatric surgery was associated with lower prevalence of HCC (PR 0.11; 95% CI, 0.03-0.48; P < 0.001). In-hospital mortality was also lower for patients with surgery (OR 0.22; 95% CI, 0.20-0.26; P < 0.001). The occurrence of HCC added $18,840 extra cost, increased mean length of stay by 2 (95% CI; 1-3) days, and increased risk of death by 65% (aOR 1.65; 95% CI 1.18-2.29).
Conclusion:
In this nationwide study of morbidly obese patients, prior-bariatric surgery was associated with a lower prevalence of HCC and lower in-patient mortality.
Background
Obesity increases the risk of several types of cancer. Whether bariatric surgery influences the risk of obesity‐related cancer is not clear. This study aimed to uncover the risk of hormone‐related (breast, endometrial and prostate), colorectal and oesophageal cancers following obesity surgery.
Methods
This national population‐based cohort study used data from the Hospital Episode Statistics database in England collected between 1997 and 2012. Propensity matching on sex, age, co‐morbidity and duration of follow‐up was used to compare cancer risk among obese individuals undergoing bariatric surgery (gastric bypass, gastric banding or sleeve gastrectomy) and obese individuals not undergoing such surgery. Conditional logistic regression provided odds ratios (ORs) with 95 per cent confidence intervals.
Results
In the study period, from a cohort of 716 960 patients diagnosed with obesity, 8794 patients who underwent bariatric surgery were matched exactly with 8794 obese patients who did not have surgery. Compared with the no‐surgery group, patients who had bariatric surgery exhibited a decreased risk of hormone‐related cancers (OR 0·23, 95 per cent c.i. 0·18 to 0·30). This decrease was consistent for breast (OR 0·25, 0·19 to 0·33), endometrium (OR 0·21, 0·13 to 0·35) and prostate (OR 0·37, 0·17 to 0·76) cancer. Gastric bypass resulted in the largest risk reduction for hormone‐related cancers (OR 0·16, 0·11 to 0·24). Gastric bypass, but not gastric banding or sleeve gastrectomy, was associated with an increased risk of colorectal cancer (OR 2·63, 1·17 to 5·95). Longer follow‐up after bariatric surgery strengthened these diverging associations.
Conclusion
Bariatric surgery is associated with decreased risk of hormone‐related cancers, whereas gastric bypass might increase the risk of colorectal cancer.
It is unclear whether weight change during adulthood affects the risk of obesity‐related cancers such as those of the esophagus, colorectum, pancreas, breast, endometrium, and kidney among Japanese, where obesity is less frequent and less severe. We examined the association between weight change during adulthood and the risk of obesity‐related cancer among Japanese by conducting a pooled analysis of two prospective studies of residents in Miyagi Prefecture, Japan. A total of 78,743 persons (40,422 women and 38,321 men) aged 40‐79 years participated in the Miyagi Cohort Study in 1990 and in the Ohsaki Cohort Study in 1994. Weight change since age 20 was divided into four categories (weight loss; stable weight; moderate weight gain; high weight gain). Cox proportional hazards regression analysis was used to estimate the multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) for obesity‐related cancer incidence. During 1,057,899 person‐years of follow up, 4,467 cases of obesity‐related cancer (women; 1,916 cases, men; 2,551cases) were identified. In women, compared with the stable weight, weight gain was associated with an increased risk of obesity‐related cancer (moderate weight gain; HRs = 1.10, 95%CIs: 0.97‐1.26, high weight gain; HRs = 1.29, 95%CIs: 1.14‐1.47). The results indicate that weight gain since age 20 was associated with a significantly increased risk of obesity‐related cancer among Japanese women. By contrast, in men, our study found that weight change is not associated with the incidence of obesity‐related cancer. This article is protected by copyright. All rights reserved.
Obesity has been linked to an increased prevalence in multiple cancers. Studies have suggested a reduction in the overall risk of cancer after bariatric surgery. We reviewed the evidence for bariatric surgery reducing the risk of endometrial cancer. Data was extracted from PubMed, EMBASE, and Medline to perform a systematic review. Thirty-one full text articles were identified from 265 abstracts. Nine observational studies were relevant to endometrial cancer. In the five controlled studies, 462 of 113,032 (0.4%) patients receiving bariatric surgery versus 11,997 of 848,864 (1.4%) controls developed endometrial cancer, odds ratio of 0.317 (95% CI 0.161 to 0.627) using random effects model (P < 0.001). Bariatric surgery seems to reduce the risk of endometrial cancer; however, more research is required.
There is currently insufficient high-quality evidence to determine the effect of combined lifestyle and behavioural interventions on survival, quality of life, or significant weight loss in women with a history of endometrial cancer compared to those receiving usual care.
The limited evidence suggests that there is little or no serious or life-threatening adverse effects due to these interventions, although musculoskeletal problems were increased, presumably due to increased activity levels. Our conclusion is based on low- and very low quality evidence from a small number of trials and very few patients. We therefore have very little confidence in the evidence: the true effect of weight-loss interventions in obese women with endometrial cancer is currently not known.
Excess body weight is a poor prognostic factor in women with early breast cancer, but the effect of weight loss on the risk of breast cancer recurrence and mortality in women who are overweight or obese at the time of breast cancer diagnosis has not been evaluated. The Alliance for Clinical Trials in Oncology Breast Cancer Weight Loss trial, also known as A011401, is testing the impact of a telephone-based weight loss program on invasive disease-free survival in 3136 women with a body mass index ≥27 kg/m² who have recently been diagnosed with stage II-III, HER-2 negative breast cancer. Secondary outcomes of the trial include the impact of the weight loss intervention on overall survival, body weight, physical activity, dietary intakes, incidence of comorbidities, serum biomarkers and patient reported outcomes. Participants are randomized 1:1 to a 2-year, telephone-based weight loss intervention or to an education control group. The intervention is delivered through 42 telephone calls, delivered by health coaches based at the Dana-Farber Cancer Institute. Calls are supplemented by an intervention workbook, as well as a number of tools to help facilitate weight loss. Intervention goals include loss of 10% of baseline body weight, achieved through caloric restriction and increased physical activity. This large-scale study testing the impact of purposeful weight loss after cancer diagnosis on the risk of breast cancer recurrence and mortality has the potential to make weight loss programs a standard part of breast cancer treatment.
Objective:
Bariatric surgery is recommended for patients with obesity and type 2 diabetes. Recent evidence suggested a strong connection between gut microbiota and bariatric surgery.
Design:
Systematic review.
Methods:
The PubMed and OVID Embase were used and articles concerning bariatric surgery and gut microbiota were screened. The main outcome measures were alterations of gut microbiota after bariatric surgery and correlations between gut microbiota and host metabolism. We applied the system of evidence level to evaluate the alteration of microbiota. Modulation of short-chain fatty acid and gut genetic content was also investigated.
Results:
Totally 12 animal experiments and 9 clinical studies were included. Based on strong evidence, 4 phyla (Bacteroidetes, Fusobacteria, Verrucomicrobia and Proteobacteria) increased after surgery; within the phylum Firmicutes, Lactobacillales, and Enterococcus increased; and within the phylum Proteobacteria, Gammaproteobacteria, Enterobacteriales, Enterobacteriaceae and several genera and species increased. Decreased microbial groups were Firmicutes, Clostridiales, Clostridiaceae, Blautia and Dorea. However, the change in microbial diversity is still under debate. Faecalibacterium prausnitzii, Lactobacillus and Coprococcus comes are implicated in many of the outcomes, including body composition and glucose homeostasis.
Conclusions:
There is strong evidence to support a considerable alteration of the gut microbiome after bariatric surgery. Deeper investigations are required to confirm the mechanisms that link the gut microbiome and metabolic alterations in human metabolism.
Hepatocellular carcinoma (HCC) is the third leading cause of worldwide cancer mortality. HCC almost exclusively develops in patients with chronic liver disease, driven by a vicious cycle of liver injury, inflammation and regeneration that typically spans decades. Increasing evidence points towards a key role of the bacterial microbiome in promoting the progression of liver disease and the development of HCC. Here, we will review mechanisms by which the gut microbiota promotes hepatocarcinogenesis, focusing on the leaky gut, bacterial dysbiosis, microbe-associated molecular patterns and bacterial metabolites as key pathways that drive cancer-promoting liver inflammation, fibrosis and genotoxicity. On the basis of accumulating evidence from preclinical studies, we propose the intestinal-microbiota–liver axis as a promising target for the simultaneous prevention of chronic liver disease progression and HCC development in patients with advanced liver disease. We will review in detail therapeutic modalities and discuss clinical settings in which targeting the gut-microbiota–liver axis for the prevention of disease progression and HCC development seems promising.
Adiponectin is the most abundant peptide secreted by adipocytes, whose reduction plays a central role in obesity-related diseases, including insulin resistance/type 2 diabetes and cardiovascular disease. In addition to adipocytes, other cell types, such as skeletal and cardiac myocytes and endothelial cells, can also produce this adipocytokine. Adiponectin effects are mediated by adiponectin receptors, which occur as two isoforms (AdipoR1 and AdipoR2). Adiponectin has direct actions in liver, skeletal muscle, and the vasculature.Adiponectin exists in the circulation as varying molecular weight forms, produced by multimerization. Several endoplasmic reticulum ER-associated proteins, including ER oxidoreductase 1-α (Ero1-α), ER resident protein 44 (ERp44), disulfide-bond A oxidoreductase-like protein (DsbA-L), and glucose-regulated protein 94 (GPR94), have recently been found to be involved in the assembly and secretion of higher-order adiponectin complexes. Recent data indicate that the high-molecular weight (HMW) complexes have the predominant action in metabolic tissues. Studies have shown that adiponectin administration in humans and rodents has insulin-sensitizing, anti-atherogenic, and anti-inflammatory effects, and, in certain settings, also decreases body weight. Therefore, adiponectin replacement therapy in humans may suggest potential versatile therapeutic targets in the treatment of obesity, insulin resistance/type 2 diabetes, and atherosclerosis. The current knowledge on regulation and function of adiponectin in obesity, insulin resistance, and cardiovascular disease is summarized in this review.
The International Agency for Research on Cancer convened a workshop on the relationship between body fatness and cancer, from which an IARC handbook on the topic will appear. An executive summary of the evidence is presented.
Esophageal and gastric cancer (GC) are related to obesity and bariatric surgery. Risk factors, such as gastroesophageal reflux and Helicobacter pylori, must be investigated and treated in obese population. After surgery, GC reports are anecdotal and treatment is not standardized. This review aims to discuss GC related to obesity before and after bariatric surgery.
Barbara Muz, Pilar de la Puente, Feda Azab, Abdel Kareem Azab Department of Radiation Oncology, Cancer Biology Division, Washington University School of Medicine in St Louis, MO, USA Abstract: Hypoxia is a non-physiological level of oxygen tension, a phenomenon common in a majority of malignant tumors. Tumor-hypoxia leads to advanced but dysfunctional vascularization and acquisition of epithelial-to-mesenchymal transition phenotype resulting in cell mobility and metastasis. Hypoxia alters cancer cell metabolism and contributes to therapy resistance by inducing cell quiescence. Hypoxia stimulates a complex cell signaling network in cancer cells, including the HIF, PI3K, MAPK, and NFκB pathways, which interact with each other causing positive and negative feedback loops and enhancing or diminishing hypoxic effects. This review provides background knowledge on the role of tumor hypoxia and the role of the HIF cell signaling involved in tumor blood vessel formation, metastasis, and development of the resistance to therapy. Better understanding of the role of hypoxia in cancer progression will open new windows for the discovery of new therapeutics targeting hypoxic tumor cells and hypoxic microenvironment. Keywords: hypoxia, cancer, metastasis, angiogenesis, treatment resistance
Background:
Obesity is strongly associated with esophageal adenocarcinoma (EAC), yet it is unclear whether weight loss reduces the risk of EAC.
Objectives:
To test the hypothesis that the risk of EAC decreases after weight reduction achieved by obesity surgery.
Setting:
Nationwide register-based cohort study.
Methods:
This study included a majority of individuals who underwent obesity surgery in Sweden in 1980 to 2012. The incidence of EAC after obesity surgery was compared with the incidence in the corresponding background population of Sweden by means of calculation of standardized incidence ratios (SIRs) with 95% confidence intervals (CIs). The risk of EAC after obesity surgery also was compared with the risk in obese individuals who did not undergo obesity surgery by means of multivariable Cox regression, providing hazard ratios with 95% CIs, adjusted for potential confounders.
Results:
Among 34,437 study participants undergoing obesity surgery and 239,775 person-years of follow-up, 8 cases of EAC occurred (SIR 1.6; 95% CI .7-3.2). No clear trend of decreased SIRs was observed in relation to increased follow-up time after surgery. The SIR of EACs (n = 53) among 123,695 obese individuals who did not undergo obesity surgery (673,238 person-years) was increased to a similar extent as in the obesity surgery cohort (SIR = 1.9, 95% CI 1.4-2.5). Cox regression demonstrated no difference in risk of EAC between participants who underwent obesity surgery and those who did not (adjusted hazard ratio = .9, 95% CI .4-1.9).
Conclusion:
The risk of EAC might not decrease after obesity surgery, but larger studies with longer follow-up are needed to establish this association.
This meta-analysis aims to examine the association between being overweight/obese and risk of meningiomas and gliomas as well as overall brain/central nervous system (CNS) tumors.
Potentially eligible publications were sought in PubMed up to June 30, 2014. Random-effects meta-analysis and dose-response meta-regression analysis was conducted. Cochran Q statistic, I-squared and tau-squared were used for the assessment of between-study heterogeneity. The analysis was performed using Stata/SE version 13 statistical software.
A total of 22 studies were eligible, namely 14 cohort studies (10,219 incident brain/CNS tumor cases, 1,319 meningioma and 2,418 glioma cases in a total cohort size of 10,143,803 subjects) and eight case-control studies (1,009 brain/CNS cases, 1,977 meningioma cases, 1,265 glioma cases and 8,316 controls). In females, overweight status/obesity was associated with increased risk for overall brain/CNS tumors (pooled RR = 1.12, 95%CI: 1.03-1.21, 10 study arms), meningiomas (pooled RR = 1.27, 95%CI: 1.13-1.43, 16 study arms) and gliomas (pooled RR = 1.17, 95%CI: 1.03-1.32, six arms). Obese (BMI>30 kg/m2) females seemed particularly aggravated in terms of brain/CNS tumor (pooled RR = 1.19, 95%CI: 1.05-1.36, six study arms) and meningioma risk (pooled RR = 1.48, 95%CI: 1.28-1.71, seven arms). In males, overweight/obesity status correlated with increased meningioma risk (pooled RR = 1.58, 95%CI: 1.22-2.04, nine study arms), whereas the respective association with overall brain/CNS tumor or glioma risk was not statistically significant. Dose-response meta-regression analysis further validated the findings.
Our findings highlight obesity as a risk factor for overall brain/CNS tumors, meningiomas and gliomas among females, as well as for meningiomas among males.
A number of epidemiological studies have suggested that obesity is associated, albeit inconsistently, with the incidence of prostate cancer (PCa). In order to provide a quantitative assessment of this association, the present study examined the correlation between obesity and the incidence and associated mortalities of PCa in an updated meta-analysis of cohort studies. The cohort studies were identified by searching the EMBASE and MEDLINE databases on January 1, 2014. The summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated using random-effects models. In total, 17 studies, which included 3,569,926 individuals overall, were selected according to predefined inclusion criteria. Based upon the results of the random-effects models, obesity was not significantly correlated with the incidence of PCa (RR, 1.00; 95% CI, 0.95-1.06). However, further analysis revealed that obesity was significantly correlated with an increased risk of aggressive PCa (RR, 1.14; 95% CI, 1.04-1.25). Furthermore, an increased risk of PCa-associated mortality was significantly associated with obesity (RR, 1.24; 95% CI, 1.15-2.33), without any heterogeneity between the studies (I(2)=0.0%; P=0.847). The present study provides preliminary evidence to demonstrate that obesity is a significant risk factor for aggressive PCa and PCa-specific mortality. The low survival rates observed among obese males with PCa may be a likely explanation for this association.
To perform a systematic review and meta-analysis to investigate the impact of bariatric surgery and the risk of developing breast, ovarian and endometrial cancer in obese women. MEDLINE, EMBASE, LILACS and Cochrane databases were searched from inception until January 2019 to retrieve studies that assessed the risk of breast, ovarian or endometrial cancer in obese women submitted to bariatric surgery. There was no language restriction. We extracted and combined data from studies in order to assess the risk ratio (RR) of developing these neoplasms. A random-effects meta-analytic model was applied in all calculations. The New Castle Ottawa and GRADE were used to assess quality of the included studies and certainty of the evidence, respectively. This study is registered in PROSPERO (CRD42019112927). We found 188 articles and seven of those were included in our meta-analysis, which incorporated a total of 150,537 patients in the bariatric surgery arm and 1,461,938 women in the control arm. The total risk ratio of breast, ovarian and endometrial cancer was 0.41 (95%CI [0.31 to 0.56]; I²=90%; 7 studies). The risk of breast cancer was reduced by 49% [RR: 0.51 (95%CI [0.31 to 0.83]; I²= 92%; 6 studies). The risk of ovarian cancer was reduced by 53% [RR: 0.47 (95%CI [0.27 to 0.81]; I²= 0%; 3 studies). The risk of endometrial cancer was reduced by 67% [RR: 0.33 (95%CI [0.21 to 0.51]; I²= 88%; 7 studies). Bariatric surgery may have a protective effect reducing the risk of breast, ovarian and endometrial cancer in obese women. The high heterogeneity and other issues justify the need for further studies to deepen our knowledge.
Background:
Thyroid cancer incidence has increased in many parts of the world since the 1980s, as has the prevalence of obesity. Evidence suggests that people with greater body size have higher thyroid cancer risk. However, it is unclear whether this association is causal or is driven by over-diagnosis of indolent cancers because overweight/obese people use health services more frequently than those of normal weight conferring greater opportunity for incidental diagnosis. Assessing whether obesity is associated with higher-risk thyroid cancers might help clarify this issue.
Methods:
We recruited 1013 people diagnosed with thyroid cancer between 2013 and 2016 and 1057 population controls, frequency matched by sex and age group. We used logistic regression to assess the association between body mass index (BMI) and overall thyroid cancer risk as well as by tumor BRAF mutational status as a marker of potentially higher-risk cancer.
Results:
Overall, obesity was associated with greater risk of thyroid cancer (odds ratio [OR] = 1.72; 95% confidence interval [CI] 1.37 - 2.16 for obese vs. normal BMI). The association with obesity was significantly stronger for BRAF-mutation positive than BRAF-negative papillary thyroid cancers (OR = 1.71; 95% CI 1.17 - 2.50 for BRAF positive versus BRAF-negative cancers). The increased risks associated with overweight/obesity did not vary by histological subtypes or presence/absence of adverse tumor histologic features.
Conclusions:
Greater risk of BRAF-mutated papillary thyroid cancers among those with high BMI suggests that the association may not merely reflect greater healthcare service use and indicates an independent relationship between obesity and clinically important thyroid cancer.
Objective:
This retrospective cohort study examined whether bariatric surgery is associated with reduced risk of breast cancer among pre- and postmenopausal women.
Background:
Obesity is associated with increased risk of breast cancer, but the impact of weight loss on breast cancer risk has been difficult to quantify.
Methods:
The cohort included obese (body mass index ≥35 kg/m) patients enrolled in an integrated health care delivery system between 2005 and 2012 (with follow-up through 2014). Female bariatric surgery patients (N = 17,998) were matched on body mass index, age, study site, and comorbidity index to 53,889 women with no bariatric surgery. Kaplan-Meier curves and Cox proportional hazards models were used to examine incident breast cancer up to 10 years after bariatric surgery. Pre- and postmenopausal women were examined separately, and further classified by estrogen receptor (ER) status.
Results:
The analysis included 301 premenopausal and 399 postmenopausal breast cancer cases. In multivariable adjusted models, bariatric surgery was associated with a reduced risk of both premenopausal (HR = 0.72, 95% CI, 0.54-0.94) and postmenopausal (HR = 0.55, 95% CI, 0.42-0.72) breast cancer. Among premenopausal women, the effect of bariatric surgery was more pronounced among ER-negative cases (HR = 0.36, 95% CI, 0.16-0.79). Among postmenopausal women, the effect was more pronounced in ER-positive cases (HR = 0.52, 95% CI, 0.39-0.70).
Conclusions:
Bariatric surgery was associated with a reduced risk of breast cancer among severely obese women. These findings have significant public health relevance because the prevalence of obesity continues to rise, and few modifiable breast cancer risk factors have been identified, especially for premenopausal women.
Background
Although obesity is an established risk factor for postmenopausal breast cancer, the results of weight loss and breast cancer studies are inconsistent. Therefore, we evaluated associations between weight change and breast cancer risk in postmenopausal women in the Women’s Health Initiative Observational Study.
Methods
Postmenopausal women (n = 61,335) who had no prior breast cancer and a normal mammogram had body weight and height measured and body mass index (BMI) calculated at baseline and year 3. Weight change at year 3 was categorized as stable (<5%), loss (≥5%), or gain (≥5%) with further assessment of weight loss intentionality by self‐report. Multivariable Cox proportional hazard regression models were used to evaluate relationships between weight change and subsequent breast cancer incidence.
Results
During a mean follow‐up of 11.4 years with 3061 incident breast cancers, women with weight loss (n = 8175) had a significantly lower risk of breast cancer compared with women whose weight remained stable (n = 41,139) (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.78‐0.98; P = .02) with no interaction by BMI. Adjustment for mammography did not alter findings (HR, 0.88; 95% CI, 0.78‐0.99) with no significant difference by weight loss intentionality. Weight gain (≥5%) (n = 12,021) was not associated with breast cancer risk (HR, 1.02; 95% CI, 0.93‐1.11) but was associated with higher triple‐negative breast cancer incidence (HR, 1.54; 95% CI, 1.16‐2.05).
Conclusions
Postmenopausal women who lose weight have lower breast cancer risk than those with stable weight. These findings suggest that postmenopausal women who lose weight may reduce their breast cancer risk.
Currently, there are no effective preventive strategies for pancreatic cancer. Obesity has been increasingly recognized as a strong but modifiable risk factor of pancreatic cancer. In this article, we aim to review the literature regarding weight loss on prevention of pancreatic cancer. Epidemiological and laboratory studies have shown that obesity is associated with increased incidence of pancreatic cancer and potentially worse cancer outcome. Whereas the underlying pathomechanisms remain unclear, chronic inflammation, insulin resistance, and altered intestinal microbiota are all implicated in the carcinogenic effect of obesity. Weight loss, especially the durable and significant weight loss after bariatric surgery, has been shown to reduce the risks of multiple cancers and may become a good intervention for pancreatic cancer prevention.
Objective:
To determine whether bariatric surgery is associated with a lower risk of cancer.
Background:
Obesity is strongly associated with many types of cancer. Few studies have examined the relationship between bariatric surgery and cancer risk.
Methods:
We conducted a retrospective cohort study of patients undergoing bariatric surgery between 2005 and 2012 with follow-up through 2014 using data from a large integrated health insurance and care delivery systems with 5 study sites. The study included 22,198 subjects who had bariatric surgery and 66,427 nonsurgical subjects matched on sex, age, study site, body mass index, and Elixhauser comorbidity index. Multivariable Cox proportional-hazards models were used to examine incident cancer up to 10 years after bariatric surgery compared to the matched nonsurgical patients.
Results:
After a mean follow-up of 3.5 years, we identified 2543 incident cancers. Patients undergoing bariatric surgery had a 33% lower hazard of developing any cancer during follow-up [hazard ratio (HR) 0.67, 95% confidence interval (CI) 0.60, 0.74, P < 0.001) compared with matched patients with severe obesity who did not undergo bariatric surgery, and results were even stronger when the outcome was restricted to obesity-associated cancers (HR 0.59, 95% CI 0.51, 0.69, P < 0.001). Among the obesity-associated cancers, the risk of postmenopausal breast cancer (HR 0.58, 95% CI 0.44, 0.77, P < 0.001), colon cancer (HR 0.59, 95% CI 0.36, 0.97, P = 0.04), endometrial cancer (HR 0.50, 95% CI 0.37, 0.67, P < 0.001), and pancreatic cancer (HR 0.46, 95% CI 0.22, 0.97, P = 0.04) was each statistically significantly lower among those who had undergone bariatric surgery compared with matched nonsurgical patients.
Conclusions:
In this large, multisite cohort of patients with severe obesity, bariatric surgery was associated with a lower risk of incident cancer, particularly obesity-associated cancers, such as postmenopausal breast cancer, endometrial cancer, and colon cancer. More research is needed to clarify the specific mechanisms through which bariatric surgery lowers cancer risk.
The association between obesity and ovarian cancer risk has been extensively investigated, but studies have yielded inconsistent findings. This review aims to summarise and discuss the evidence generated to date. Articles published in English prior to August 2016 were retrieved from PubMed. Keywords included obesity, overweight, body size, body mass index, waist-hip ratio, waist circumference, body weight, ovarian cancer, ovarian carcinoma, ovarian neoplasm, and ovarian tumour. Eligible studies compared two or more groups of women, with at least one group in the overweight or obese category and one comprising normal weight controls. Summary data in the form of relative risk, hazard ratio, or odds ratio for each comparison group from individual studies were collated and reviewed. Forty-three studies were included in the final analysis, with a total of 3,491,943 participants. All studies included body mass index as an exposure measure, and a majority relied on self-reported measures from participants; 14 studies found a statistically significant positive association between ovarian cancer risk and higher body mass index, 26 studies found no significant association, and 3 studies found a negative association between ovarian cancer risk and higher body mass index. This review concludes that there is limited, inconsistent evidence of a positive association between obesity and ovarian cancer risk.
Low levels of gonadal circulating estrogen observed in post-menopausal women can adversely impact a diverse range of physiological factors, with clinical implications for brain cognition, gut health, the female reproductive tract and other aspects of women’s health. One of the principal regulators of circulating estrogens is the gut microbiome. This review aims to shed light on the role of the gut microbiota in estrogen-modulated disease. The gut microbiota regulates estrogens through secretion of β-glucuronidase, an enzyme that deconjugates estrogens into their active forms. When this process is impaired through dysbiosis of gut microbiota, characterized by lower microbial diversity, the decrease in deconjugation results in a reduction of circulating estrogens. The alteration in circulating estrogens may contribute to the development of conditions discussed herein: obesity, metabolic syndrome, cancer, endometrial hyperplasia, endometriosis, polycystic ovary syndrome, fertility, cardiovascular disease (CVD) and cognitive function. The bi-directional relationship between the metabolic profile (including estrogen levels) and gut microbiota in estrogen-driven disease will also be discussed. Promising therapeutic interventions manipulating the gut microbiome and the metabolic profile of estrogen-driven disease, such as bariatric surgery and metformin, will be detailed. Modulation of the microbiome composition subsequently impacts the metabolic profile, and vice versa, and has been shown to alleviate many of the estrogen-modulated disease states. Last, we highlight promising research interventions in the field, such as dietary therapeutics, and discuss areas that provide exciting unexplored topics of study.
Objective:
Excess body weight is associated with increased risk of developing hepatocellular cancer (HCC), but its effect on HCC-related mortality remains unclear. We performed a systematic review and meta-analysis to assess the association between premorbid obesity and HCC-related mortality.
Materials and methods:
Through a systematic literature search-up to March 2016, we identified 9 observational studies (1,599,453 individuals, 5705 HCC-related deaths) reporting the association between premorbid body mass index (BMI), and HCC-related mortality. We estimated summary adjusted hazard ratio (aHR) with 95% confidence intervals (CIs), comparing obese (BMI>30 kg/m) and overweight (BMI, 25 to 29.9 kg/m) individuals with normal BMI individuals using random-effects model.
Results:
On meta-analysis, compared with individuals with normal BMI, obese (aHR, 1.95; 95% CI, 1.46-2.46), but not overweight individuals (aHR, 1.08; 95% CI, 0.97-1.21), had higher HCC-related mortality, with moderate heterogeneity. On subgroup analysis, magnitude of increased mortality was higher in obese men (aHR, 2.50; 95% CI, 2.02-3.09; 3 studies) as compared with obese women (aHR, 1.45; 95% CI, 1.08-1.97; 2 studies). The impact of premorbid obesity on HCC-related mortality was observed only in western populations (aHR, 2.10; 95% CI, 1.77-2.48; 4 studies), but not Asian populations (aHR, 1.10; 95% CI, 0.63-1.92; 1 study). There was limited assessment of competing risk because of advanced liver disease.
Conclusions:
On the basis of this meta-analysis, premorbid obesity may be independently associated with a 2-fold risk of HCC-related mortality. This association was more pronounced in men and western populations. Strategies targeting obesity-associated metabolic abnormalities may provide novel pathways for HCC therapy.
Objective:
To examine the long-term effects of bariatric surgery on female-specific cancer in women with obesity.
Methods:
The prospective, matched Swedish Obese Subjects (SOS) study was designed to examine outcomes after bariatric surgery. This study includes 1420 women from the SOS cohort that underwent bariatric surgery and 1447 contemporaneously matched controls who received conventional obesity treatment. Age was 37-60years and BMI was ≥38kg/m(2). Information on cancer events was obtained from the Swedish National Cancer Registry. Median follow-up time was 18.1years (interquartile range 14.8-20.9years, maximum 26years). This study is registered with ClinicalTrials.gov, NCT01479452.
Results:
Bariatric surgery was associated with reduced risk of overall cancer (hazard ratio=0.71; 95% CI 0.59-0.85; p<0.001). About half of the observed cancers were female-specific, and the incidence of these were lower in the surgery group compared with the control group (hazard ratio=0.68; 95% CI 0.52-0·88; p=0.004). The surgical treatment benefit with respect to female-specific cancer was significantly associated with baseline serum insulin (interaction p value=0.022), with greater relative treatment benefit in patients with medium or high insulin levels. Separate analyses of different types of female-specific cancers showed that bariatric surgery was associated with reduced risk of endometrial cancer (hazard ratio=0.56: 95% CI 0.35-0.89; p=0.014).
Conclusions:
In this long-term study, bariatric surgery was associated with reduced risk of female-specific cancer, especially in women with hyperinsulinemia at baseline.
Funding:
This project was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under Award Number R01DK105948 (the content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health), the Swedish Research Council K2013-99X-22279-01, K2013-54X-11285-19, Sahlgrenska University Hospital ALF research grant and Swedish Diabetes Foundation.
Purpose
Although obesity is an established endometrial cancer risk factor, information about the influence of weight loss on endometrial cancer risk in postmenopausal women is limited. Therefore, we evaluated associations among weight change by intentionality with endometrial cancer in the Women’s Health Initiative (WHI) observational study.
Patients and Methods
Postmenopausal women (N = 36,794) ages 50 to 79 years at WHI enrollment had their body weights measured and body mass indices calculated at baseline and at year 3. Weight change during that period was categorized as follows: stable (change within ± 5%), loss (change ≥ 5%), and gain (change ≥ 5%). Weight loss intentionality was assessed via self-report at year 3; change was characterized as intentional or unintentional. During the subsequent 11.4 years (mean) of follow-up, 566 incident endometrial cancer occurrences were confirmed by medical record review. Multivariable Cox proportional hazards regression models were used to evaluate relationships (hazard ratios [HRs] and 95% CIs) between weight change and endometrial cancer incidence.
Results
In multivariable analyses, compared with women who had stable weight (± 5%), women with weight loss had a significantly lower endometrial cancer risk (HR, 0.71; 95% CI, 0.54 to 0.95). The association was strongest among obese women with intentional weight loss (HR, 0.44; 95% CI, 0.25 to 0.78). Weight gain (≥ 10 pounds) was associated with a higher endometrial cancer risk than was stable weight, especially among women who had never used hormones.
Conclusion
Intentional weight loss in postmenopausal women is associated with a lower endometrial cancer risk, especially among women with obesity. These findings should motivate programs for weight loss in obese postmenopausal women.
Context:
The mechanisms mediating the short- and long-term improvements in glucose homeostasis following bariatric/metabolic surgery remain incompletely understood.
Objective:
To investigate whether a reduction in adipose tissue inflammation plays a role in the metabolic improvements seen after bariatric/metabolic surgery, both in the short-term and longer-term.
Design:
Fasting blood and subcutaneous abdominal adipose tissue were obtained before (n=14), at one month (n=9), and 6-12months (n=14) after bariatric/metabolic surgery from individuals with obesity who were not on insulin or anti-diabetes medication. Adipose tissue inflammation was assessed by a combination of whole-tissue gene expression and flow cytometry-based quantification of tissue leukocytes.
Results:
One month after surgery, body weight was reduced by 13.5±4.4kg (p<0.001), with improvements in glucose tolerance reflected by a decrease in area-under-the-curve (AUC) glucose in 3-h oral glucose tolerance tests (-105±98mmol/L * min; p=0.009) and enhanced pancreatic β-cell function (insulinogenic index: +0.8±0.9pmol/mmol; p=0.032), but no change in estimated insulin sensitivity (Matsuda insulin sensitivity index [ISI]; p=0.720). Furthermore, although biomarkers of systemic inflammation and pro-inflammatory gene expression in adipose tissue remained unchanged, the number of neutrophils increased in adipose tissue 15-20 fold (p<0.001), with less substantial increases in other leukocyte populations. By the 6-12month follow-up visit, body weight was reduced by 34.8±10.8kg (p<0.001) relative to baseline, and glucose tolerance was further improved (AUC glucose -276±229; p<0.001) along with estimated insulin sensitivity (Matsuda ISI: +4.6±3.2; p<0.001). In addition, improvements in systemic inflammation were reflected by reductions in circulating C-reactive protein (CRP; -2.0±5.3mg/dL; p=0.002), and increased serum adiponectin (+1358±1406pg/mL; p=0.003). However, leukocyte infiltration of adipose tissue remained elevated relative to baseline, with pro-inflammatory cytokine mRNA expression unchanged, while adiponectin mRNA expression trended downward (p=0.069).
Conclusion:
Both the short- and longer-term metabolic improvements following bariatric/metabolic surgery occur without significant reductions in measures of adipose tissue inflammation, as assessed by measuring the expression of genes encoding key mediators of inflammation and by flow cytometric immunophenotyping and quantification of adipose tissue leukocytes.
Ovarian cancer is the most fatal gynecologic cancer and is an important source of cancer-related mortality, particularly in developed countries. Despite substantial research examining adiposity (primarily adult body mass index [BMI]), the overall evidence suggests only a weak positive association between adiposity and risk of ovarian cancer, with stronger associations observed for population-based case–control studies compared to prospective studies. Ovarian cancer is not one disease and emerging data suggest that higher BMI may only be associated with risk of certain histologic subtypes, including low-grade serous and invasive mucinous tumors. Interestingly, some larger studies and meta-analyses have reported a stronger relationship with premenopausal ovarian cancers, which are more likely to be of these subtypes. Relatively few studies have conducted detailed examinations of other adiposity-related factors such as measures of abdominal adiposity, early-life body size and weight change. While the underlying mechanisms that may relate adiposity to risk are unclear, increased inflammatory biomarkers have been associated with risk and hormonal factors, including androgen levels, may be important for the development of mucinous tumors. Future research should leverage the large sample sizes of consortia to evaluate associations by key tumor characteristics as well as consider patterns of weight change over the life course with both ovarian cancer risk and survival.
Endometrial cancer is the sixth most common cancer in women worldwide and the most common gynecologic malignancy in the developed world. This chapter explores the current epidemiologic evidence on the association between obesity and endometrial cancer risk and mortality. Using body mass index (BMI) as a measure of obesity, we found that obesity (defined as BMI > 30 and < 35 kg/m2) was associated with a 2.6-fold increase in endometrial cancer risk, while severe obesity (BMI > 35 kg/m2) was associated with a 4.7-fold increase compared to normal-weight women (BMI < 25 kg/m2). Increased central adiposity also increased endometrial cancer risk by 1.5- to twofold. Among both healthy and endometrial cancer patient populations, obesity was associated with a roughly twofold increase in endometrial cancer-specific mortality. This risk reduction was also observed for obesity and all-cause mortality among endometrial cancer patients. In the few studies that assessed risk associated with weight change, an increased endometrial cancer risk with weight gain and weight cycling was observed, whereas some evidence for a protective effect of weight loss was found. Furthermore, early-life obesity was associated with a moderately increased risk of endometrial cancer later in life. There are several mechanisms whereby obesity is hypothesized to increase endometrial cancer risk, including increased endogenous sex steroid hormones, insulin resistance, chronic inflammation and adipokines. Further research should focus on histological subtypes or molecular phenotypes of endometrial tumors and population subgroups that could be at an increased risk of obesity-associated endometrial cancer. Additionally, studies on weight gain, loss or cycling and weight loss interventions can provide mechanistic insight into the obesity–endometrial cancer association. Sufficient evidence exists to recommend avoiding obesity to reduce endometrial cancer risk.
Gastrointestinal (GI) cancers are the leading cause of mortality worldwide. These cancers are the end result of a complex interplay between gene and environment. Bacteria, parasites, and viruses have been implicated in some cancers. Recent data have put at focus the gut microbiome as the key player firing tumorigenesis. Experimental and human studies have provided evidence on the role of microbiota in cancer development. Although subject to changes in different settings such as antibiotic treatment, diet or lifestyle, our microbiome is quite stable and is capable of increasing susceptibility to cancer or decrease and halt its progression. The crucial event in carcinogenesis triggered by microbiome seems to be chronic inflammation influencing the genomic stability of host cells and activating immune mechanisms. Infection-related cancers represent 5.5% of the global cancer burden. Chronic inflammation predisposes to cancer in various GI organs, including hepatocellular carcinoma caused by hepatitis B or hepatitis C virusrelated chronic hepatitis, gastric cancer (GC) caused by Helicobacter pylori-associated chronic gastritis, colorectal cancer caused by inflammatory bowel disease, bile duct cancer by primary sclerosing cholangitis, and esophageal cancer caused by Barrett esophagus. Apart from its impact in GI cancer development microbiota can also play an important role in the progression of cancer, response to chemotherapy or cancer prevention. In this review we will discuss the role of microbiome in GI cancers in the light of the current literature and the possible therapeutic options targeting microbiota in the near future.
Ovarian cancer is the most common cause of gynecological cancer death in United States women.Efforts to improve progression free survival (PFS) and quality of life (QoL) after treatment for ovarian cancer are necessary.Observational studies suggest that lifestyle behaviors, including diet and physical activity, are associated with lower mortality in this population.The Lifestyle Intervention for Ovarian Cancer Enhanced Survival (LIVES) NRG 0225 study is a randomized, controlled trial designed to test the hypothesis that a 24 month lifestyle intervention will significantly increase PFS after oncological therapy for stage II-IV ovarian cancer.Women are randomized 1:1 to a high vegetable and fiber, low-fat diet with daily physical activity goals or an attention control group.Secondary outcomes to be evaluated include QoL and gastrointestinal health.Moreover an a priori lifestyle adherence score will be used to evaluate relationships between adoption of the diet and activity goals and PFS.Blood specimens are collected at baseline, 6, 12 and 24 months for analysis of dietary adherence (carotenoids) in addition to mechanistic biomarkers (lipids, insulin, telomere length).Women are enrolled at NRG clinic sites nationally and the telephone based lifestyle intervention is delivered from The University of Arizona call center by trained health coaches.A study specific multi-modal telephone, email, and SMS behavior change software platform is utilized for information delivery, coaching and data capture.When completed, LIVES will be the largest behavior-based lifestyle intervention trial conducted among ovarian cancer survivors.
Background:
Analytical morphometric assessment has recently been proposed to improve preoperative risk stratification. However, the relationship between body composition and outcomes following pancreaticoduodenectomy is still unclear. The aim of this study was to assess the impact of body composition on outcomes in patients undergoing pancreaticoduodenectomy for cancer.
Methods:
Body composition parameters including total abdominal muscle area (TAMA) and visceral fat area (VFA) were assessed by preoperative staging CT in patients undergoing pancreaticoduodenectomy for cancer. Perioperative variables and postoperative outcomes (mortality or postoperative pancreatic fistula) were collected prospectively in the institutional pancreatic surgery database. Optimal stratification was used to determine the best cut-off values for anthropometric measures. Multivariable analysis was performed to identify independent predictors of 60-day mortality and pancreatic fistula.
Results:
Of 202 included patients, 132 (65·3 per cent) were classified as sarcopenic. There were 12 postoperative deaths (5·9 per cent), major complications developed in 40 patients (19·8 per cent) and pancreatic fistula in 48 (23·8 per cent). In multivariable analysis, a VFA/TAMA ratio exceeding 3·2 and American Society of Anesthesiologists grade III were the strongest predictors of mortality (odds ratio (OR) 6·76 and 6·10 respectively; both P < 0·001). Among patients who developed major complications, survivors had a significantly lower VFA/TAMA ratio than non-survivors (P = 0·017). VFA was an independent predictor of pancreatic fistula (optimal cut-off 167 cm(2) : OR 4·05; P < 0·001).
Conclusion:
Sarcopenia is common among patients undergoing pancreaticoduodenectomy. The combination of visceral obesity and sarcopenia was the best predictor of postoperative death, whereas VFA was an independent predictor of pancreatic fistula.
Obesity is implicated as an important factor in the rising incidence of liver cancer in the USA. Bariatric surgery is increasingly used for treating morbid obesity and comorbidities. Using administrative data from UHC, a consortium of academic medical centers in the USA, we compared the prevalence of liver cancer among admissions with and without a history of bariatric surgery within a 3-year period. Admissions with a history of bariatric surgery had a 61 % lower prevalence of liver cancer compared to those without a history of bariatric surgery (prevalence ratio 0.39, 95 % confidence interval 0.35-0.44), and these inverse associations persisted within strata of sex, race, and ethnicity. This hospital administrative record-based analysis suggests that bariatric surgery could play a role in liver cancer prevention.
Background:
The relationship between preoperative body mass index (BMI) and the survival of postoperative gastric cancer patients is not clear. Furthermore, the survival impact with postoperative BMI is not known, even though weight loss is inevitable after gastrectomy.
Methods:
Patients who underwent gastrectomy for gastric cancer between 2000 and 2008 were included in the study (n = 1909). Patients were divided into three groups based on their BMIs: low (<18.5 kg/m(2)), normal (18.5-24.9 kg/m(2)), and high BMI (≥25.0 kg/m(2)). Patient survival was compared according to BMI at two time points: baseline and 1 year after surgery.
Results:
Regarding BMI 1 year after surgery, overall survival, disease-specific survival, and recurrence-free survival were longer in the high BMI group than the low and normal BMI groups. In a Cox proportional hazards model, adjusting for the patient's age, sex, type of surgery, tumour stage, histology, curative resection, and BMI at baseline, a high BMI 1 year after surgery was associated with lower overall mortality compared to normal BMI (hazard ratio 0.51; 95% confidence interval, 0.26-0.98). However, BMI at baseline was not an independent prognostic factor.
Conclusion:
BMI 1 year after surgery significantly predicted the long-term survival of patients with gastric cancer compared with the preoperative BMI.
Excess body weight, as defined by the body mass index (BMI), has been associated with several diseases and includes subjects who are overweight (BMI≥25-29.9 kg/m2) or obese (BMI≥30 kg/m2). Overweight and obesity constitute the fifth leading risk for overall mortality, accounting for at least 2.8 million adult deaths each year. In addition around 11% of colorectal cancer (CRC) cases have been attributed to overweight and obesity in Europe. Epidemiological data suggest that obesity is associated with a 30-70% increased risk of colon cancer in men, whereas the association is less consistent in women. Similar trends exist for colorectal adenoma, although the risk appears lower. Visceral fat, or abdominal obesity, seems to be of greater concern than subcutaneous fat obesity, and any 1 kg/m2 increase in BMI confers additional risk (HR 1.03). Obesity might be associated with worse cancer outcomes, such as recurrence of the primary cancer or mortality. Several factors, including reduced sensitivity to antiangiogenictherapeutic regimens, might explain these differences. Except for wound infection, obesity has no significant impact on surgical procedures. The underlying mechanisms linking obesity to CRC are still a matter of debate, but metabolic syndrome, insulin resistance and modifications in levels of adipocytokines seem to be of great importance. Other biological factors such as the gut microbita or bile acids are emerging. Many questions still remain unanswered: should preventive strategies specifically target obese patients? Is the risk of cancer great enough to propose prophylactic bariatric surgery in certain patients with obesity?
The burden of hepatocellular carcinoma (HCC), the most common form of liver cancer, is steadily growing because obesity, type 2 diabetes, and nonalcoholic fatty liver disease (NAFLD) are replacing viral- and alcohol-related liver disease as major pathogenic promoters. The most worrisome aspects of these new risk factors are their large spread in the general population and their link with HCC arising in noncirrhotic livers. HCC may be the presenting feature of an asymptomatic nonalcoholic steatohepatitis (NASH), the progressive form of NAFLD. The HCC risk connected to metabolic factors has been underestimated so far, and a poorer surveillance has prevented an adequate treatment. Systemic and hepatic molecular mechanisms involved in obesity- and NAFLD-induced hepatocarcinogenesis as well as potential early markers of HCC are being extensively investigated. This review summarizes current evidence linking obesity, NAFLD and liver cancer, discusses its clinical impact and describes the main mechanisms underlying this complex relationship. Expected final online publication date for the Annual Review of Medicine Volume 67 is January 14, 2016. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.
Results from cohort studies of adult weight gain and risk of colorectal cancer are inconsistent. We conducted a systematic review and meta-analysis of prospective studies assessing the association of change in weight/body mass index with colorectal cancer risk. We searched Scopus and Web of Science up to June 2014 and supplemented the search with manual searches of the reference lists of the identified articles. Thirteen studies published between 1997 and 2014 were pooled by using a random-effects model, and potential heterogeneity was explored by fitting meta-regression models. The highest weight gain category, measured by weight/body mass index, compared with a reference category, was associated with increased risk of colorectal cancer (hazard ratio (HR) = 1.16, 95% confidence interval (CI): 1.08, 1.24), whereas no association was found for weight loss (HR = 0.96, 95% CI: 0.89, 1.05). There was no suggestion of heterogeneity across studies. For dose response, a 5-kg weight gain was associated with a slightly increased risk of colorectal cancer (HR = 1.03, 95% CI: 1.02, 1.05), with some heterogeneity observed (I(2) = 42%; P = 0.02), which was partially explained by sex (ratio of HRs = 1.03, 95% CI: 1.00, 1.07). In this meta-analysis, gain in weight/body mass index was positively associated with colorectal cancer risk.
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Background:
Bariatric procedures can induce a massive weight loss that lasts for >15 years after surgery; in addition, they achieve important metabolic effects including diabetes resolution in the majority of morbidly obese patients. However, some bariatric interventions may cause gastroesophageal reflux disease and other serious complications. The aim of our study is to evaluate the risk of cancer after bariatric surgery.
Methods:
We conducted a review of the literature about the cases of gastric cancer arising after any bariatric procedure, including a case of adenocarcinoma incidentally discovered by the authors 6 months after laparoscopic adjustable gastric banding.
Results:
Globally, 17 case reports describing 18 patients were retrieved, including the case study by the authors. The diagnosis of tumor was at a mean of 8.6 years after bariatric surgery, 9.3 years after RYGB, and 8.1 years after restrictive procedures. The adenocarcinoma represented most cases (15 patients, 83%). In the patients with RYGB, the adenocarcinoma was localized in the excluded stomach in 5 patients (83%) and in the pouch in 1 patient (17%). After a restrictive procedure, the cancer was localized in the pouch in 5 patients (62.5%), in the pylorus in 2 patients (25%), and in lesser curvature only in 1 patient (12.5%).
Conclusions:
There is a lack of evidence about a connection between the late occurrence of gastric adenocarcinoma and the bariatric surgery. For this reason, although the preoperative upper endoscopy is still mandatory, there is no need for a regular endoscopic evaluation of patients after surgery.
Over recent decades, the incidence of cancers of the gastroesophageal junction, including gastric cardia tumors, has increased markedly. This is a trend that has been well documented, especially in studies from the USA and northern Europe that have also demonstrated a concomitant rise in the ratio of cardia to distal gastric cancers. The rise in the prevalence of gastric cardia adenocarcinoma has been paralleled by the worldwide obesity epidemic, with almost all epidemiological studies reporting increased body mass index and obesity increase the risk of cardia cancer development. However, the strength of this association is less marked than the link between obesity and esophageal adenocarcinoma, and the mechanisms remain poorly understood. Other possible confounders of the relationship between obesity and cardia cancer include the decline in Helicobacter pylori infection and the widespread use of proton pump inhibitors, although these have rarely been controlled for in case-control and cohort studies investigating associations between obesity and cardia cancer. We review these epidemiological trends and discuss proposed mechanisms for the association, drawing attention to controversies over the difficulty of defining cardia cancer. The relative paucity of high-quality epidemiological studies from other regions of the world should prompt further investigation of this issue, especially in populations undergoing rapid socioeconomic change.