Metabolic Surgery and Cancer Risk: An Opportunity for Mechanistic Research
Abstract
:Simple Summary
Abstract
1. Introduction
2. Animal Models of MBS
3. The National Institutes of Health (NIH) Focus on Obesity
3.1. Role of the NIH in MBS
- Patients seeking effective therapy for severe obesity for the first time should participate in a nonsurgical program, including a dietary regimen, appropriate exercise, and behavior modification. Transient success of very low-calorie diets, behavioral modification, and limited pharmacologic intervention was also noted.
- Gastric restrictive or bypass procedures could be considered for well-informed and motivated patients with acceptable operative risks.
- Patients who were candidates for surgical procedures should undergo evaluation by a multidisciplinary team.
- The operation should be performed by an experienced surgeon in an appropriate clinical setting.
- Lifelong medical surveillance after surgical therapy is a necessity.
- Specific criteria for operative intervention were determined to be patients with a BMI > 40 kg/m2 as well as patients with a BMI 35–40 kg/m2 who have high risk comorbid conditions, such as cardiopulmonary disease, severe diabetes, and physical problems that interfered with their lifestyle (for example, employment, family functioning, and ambulation).
3.2. National Cancer Institute (NCI) Emphasis on Obesity
4. Impact of MBS on Cancer Risk and Mortality
4.1. Gender May Influence MBS Benefit
4.2. Does MBS Increase the Risk of CRC?
4.3. Do Race and Ethnicity Influence the Effect of MBS on Cancer Risk?
4.4. Does the Specific MBS Procedure Influence Benefit?
5. Proposed Mechanisms Leading to Cancer Risk Reduction after MBS
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
Disclaimer
References
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Title | Dates | Institute(s) | Purpose | Focus of Surgical Procedures Discussed | Outcomes |
---|---|---|---|---|---|
Consensus Development Conference on Surgical Treatment of Morbid Obesity | 12.4–5.1978 | NIDDK | Establish agreement among experts on use of emerging technologies for morbid obesity | GB, JI bypass | 1. Improvement in CV and T2DM with weight loss after BS; 2. GB has fewer side effects than JI bypass; 3. surgery should be limited to patients with morbid obesity; 4. the mechanism(s) of the effect of MBS needs more attention |
Consensus Conference on the Health Implications of Obesity | 2.11–13.1985 | NIDDK, NHLBI | What is obesity; what is the evidence that obesity adversely affects health; for what medical indications can weight loss be recommended; what is the evidence that obesity affects longevity; what should be the directions of future research in the area | Primary conference focus not on BS | Increased risk of CV disease, dyslipidemia, T2DM, gallbladder disease, increased prevalence of and mortality from cancer |
Gastrointestinal surgery for severe obesity. Proceedings of an NIH Consensus Development Conference | 3.25–27.1991 | NIDDK | Assess the MBS treatments for obesity, the criteria for selection of MBS, the efficacy and risks of MBS, and the need for further research on MBS therapies | VBG, RYGB | (1) MBS restrictive or bypass (malabsorptive) procedures could be considered for candidates who are good surgical risks; (2) MBS surgical candidates should be evaluated by multiple disciplines with medical, surgical, psychiatric and nutritional expertise; (3) the MBS procedure should be performed in a setting with adequate support for all aspects of MBS care; (4) specific BMI criteria for surgery; (5) lifelong medical surveillance after MBS in needed |
Expert Panel on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults | Panel convened May 1995 | NHLBI, NIDDK | To evaluate published randomized clinical trials published between 1980 and 1997 to determine optimal treatment for overweight and obesity | VBG, RYGB | MBS is an option for subjects with BMI > 40 or > 35 kg/m2 with comorbid conditions when medical management has failed |
Managing Overweight and Obesity in Adults: Systematic Evidence Review from the Obesity Expert Panel | 2008 | NHLBI | Expert panels were convened to update the existing clinical guidelines on cholesterol, blood pressure, and overweight/obesity, by conducting rigorous systematic evidence reviews. | VBG, adjustable gastric banding, RYGB, SG | MBS produces greater initial and maintained weight loss than other weight loss approaches. In obese adults, MBS generally results in a more favorable impact on obesity-related comorbid conditions than that produced by usual care, conventional medical treatment, lifestyle intervention, or medically supervised weight loss. MBS results in greater improvement in obesity-related comorbid conditions than nonsurgical approaches. Complications, weight loss and remission-related comorbidities following MBS vary by procedure. |
Study Design | Study Groups/Numbers | Treatment Procedure(s) | Cancer Incidence +/- Mortality | Cancer Effect | Reference | |||
---|---|---|---|---|---|---|---|---|
Overall | Cancer | Females | Males | |||||
Prospective matched cohort | T: 2010; C: 2037; F: 2867; M: 1180 | GB, VBG, RYGB | Cancer incidence, mortality | Incidence HR = 0.67 (p < 0.01); mortality HR = 0.77, p < 0.01 | Melanoma HR = ND, p < 0.01; Hematologic HR = 0.16, p = 0.015; Other cancers HR = 0.40; p = 0.04 | GB HR = 0.54, p = 0.026; VBG = 0.60, p < 0.01; RYGB HR = 0.54, p = 0.11 | HR = 0.97, NS | [25,26] |
Retrospective matched cohort | T: 22,198; C: 66,427; F: >80% | Various MBS procedures | Cancer incidence | HR = 0.67, p < 0.01; obesity related cancers HR: 0.59, p < 0.01 | Postmenopausal breast HR = 0.58, p < 0.01; colon HR = 0.59; p = 0.04; endometrial HR = 0.50, p < 0.01; pancreatic cancer HR = 0.46, p = 0.04 | HR = 0.64, p < 0.01), obesity associated cancers (HR = 0.58, p < 0.01), not obesity associated (HR 0.74, p < 0.01) | No significant cancer reduction for any cancer type | [24] |
Meta analysis | T: 304,516; C: 8,492,408; both M/F | Various MBS procedures | Cancer incidence, mortality | Incidence OR = 0.56, p < 0.01; mortality OR = 0.56, p < 0.01 | Breast HR = 0.49, p < 0.01; CRC 0.82, p,0.01; Endometrial HR = 0.43, p = 0.01 | Not studied | [23] | |
Retrospective matched cohort | T: 8794; C: 8794 | Bypass (including RYGB), GB, SG | Cancer incidence | Focus on obesity related cancers | Hormone related cancers OR = 0.23 (RYGB OR = 0.16), breast OR = 0.25; endometrium OR:0.21, prostate OR:0.37; CRC OR = 2.63 (RYGB) | Hormone related cancers OR = 0.22; CRC OR = 3.01 (RYGB) | Hormone related cancers OR = 0.37; CRC OR = 2.01 (RYGB) | [27] |
Retrospective observational cohort | T: 39,747 (F: 76.6%); C: 962,860 (F: 62.9%) | 52% restrictive, 48% restrictive & malabsorptive | Cancer incidence | Focus on obesity related cancers | Breast SIR = 0.76; Uterus SIR = 2.98; Kidney SIR = 3.06; Lung SIR = 0.70; CRC SIR = 1.26; restrictive CRC SIR = 1.41; restrictive & malabsorptive CRC SIR = 1.05 | CRC SIR = 1.19 | CRC SIR = 1.41 | [28] |
Retrospective observational cohort | T: 13,123 (F: 77%); C: Swedish national registry | GB, VBG, Bypass (including RYGB) | Cancer incidence | Focus on obesity related cancers | Obesity related cancers SIR = 1.04; CRC SIR = 1.52; Kidney SIR = 2.68; Bypass SIR = 1.01; VBG SIR = 1.05; GB SIR = 1.05 | Breast SIR = 0.54; Endometrial SIR = 2.15; CRC SIR = 1.28 | Prostate SIR = 0.84; CRC SIR = 2.34 | [29] |
Retrospective observational cohort | T: 74,131(F: 77.9%); C: 971,217(F: 49.4%) | GB, SG, Bypass (including RYGB) | Cancer incidence | Focus on CRC | CRC SIR = 0.75 | CRC SIR = 0.79 | CRC SIR = 0.77 | [30] |
Proposed Mechanism | How the Mechanism Influences Obesity Related Cancer | Reference |
---|---|---|
↓ Cell Proliferation | Lower cell proliferation→lower cell division→lower mutation rate | [36] |
↓ Chronic Inflammation | ↓ growth factors and cytokines→↓cell proliferation, cell survival and migration | [36,37] |
↓ Oxidative Stress | ↓chronic inflammation→↓oxidative stress→↑antioxidant enzymes, ↓OS byproducts, ↓ cancer risk | [38] |
↓ Insulin Resistance | Decreased cell proliferation and increased apoptosis | [36,39] |
↑ IGN | IGN improves insulin sensitivity, energy homoeostasis and exerts anti-obesity effects | [10,40] |
↓ IGF-1 | ↓growth factor expression→↓cell proliferation, cell survival and migration↓ | [37] |
↓ Adipocyte Size | Normalizes adipocyte function | [41] |
Epigenetic ∆ in Adipocytes | Favorable changes in obesity epigenome after MBS | [42] |
∆ Adipokine Expression | ↓ growth-promoting adipokines, ↑ adiponectin decreases IGF-1 | [41] |
∆ Gut Microbiome | Gut microbiota types influence obesity; levels change after bariatric surgery | [14,43] |
↓ Aromatase | Fewer adipocytes→lower aromatase levels Lower hormone receptor levels leads to lower cell proliferation from hormone signaling | [44] |
↓ ER, PR ↑ Bile Acid Concentration ∆ Concentrations of Gut Hormones | May increase colonic proliferation Influences brain-gut crosstalk | [45] [9] |
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Sauter, E.R.; Heckman-Stoddard, B. Metabolic Surgery and Cancer Risk: An Opportunity for Mechanistic Research. Cancers 2021, 13, 3183. https://doi.org/10.3390/cancers13133183
Sauter ER, Heckman-Stoddard B. Metabolic Surgery and Cancer Risk: An Opportunity for Mechanistic Research. Cancers. 2021; 13(13):3183. https://doi.org/10.3390/cancers13133183
Chicago/Turabian StyleSauter, Edward R., and Brandy Heckman-Stoddard. 2021. "Metabolic Surgery and Cancer Risk: An Opportunity for Mechanistic Research" Cancers 13, no. 13: 3183. https://doi.org/10.3390/cancers13133183