THE GROWING EVIDENCE OF THE RELATIONSHIP BETWEEN OBESITY AND CANCER AND THE ROLE OF BARIATRIC SURGERY.

SUMMARY OF THE MAIN RECOMMENDATIONS

• Obesity is recognized as a significant risk factor for various types of cancer.

• Although the incidence of some types of cancer at different primary sites is decreasing due to specific prevention measures (screening programs, smoking cessation), the incidence of neoplasms in the young population shows a significant increase associated with obesity.

• Bariatric surgery has been shown to significantly lower the risk of developing obesity-associated cancers, which are linked to metabolic dysregulation, chronic low-grade systemic inflammation, and hormonal alterations such as elevated insulin and sex hormone levels.

INTRODUCTION

The worldwide increase in obesity has been clearly observed. Kaidar-Person et al., back in 2011, stated that the 21 st century was dealing with 2 major epidemics: obesity and cancer 33 . The prevalence of obesity in the United States (U.S.) increased from 30.5 to 41.9% between 2000 and 2020, while the prevalence of severe obesity increased from 4.7 to 9.2% during the same period 64 . Another study found that the incidence of obesity increased by 18% between 2013 and 2017 compared to 2009 to 2013 42 . Obesity-related conditions, including heart disease, stroke, type 2 diabetes, and certain types of cancer, are among the leading causes of premature death and are preventable 12 .

Additionally, projections published in 2019 suggest that by 2030, nearly 1 in 2 adults in the U.S. will have obesity, with severe obesity becoming increasingly prevalent 69 , 72 . In the young population, the 2023 guidelines from the American Academy of Pediatrics reported that the percentage of U.S. children and adolescents affected by obesity has more than tripled, rising from 5% in 1963–1965 to 19% in 2017–2018 28 , 69 .

In Brazil, evidence indicates a significant increase in the prevalence of obesity over recent decades. A systematic review and meta-analysis by Kodaira et al. found that the pooled prevalence of obesity in Brazilian adults increased by 15% from 1974–1990 to 2011–2020. This trend was observed in both men and women across almost all periods 34 . Similarly, Estivaleti et al. reported that the prevalence of obesity in Brazilian adults rose from 11.8% in 2006 to 20.3% in 2019, with projections suggesting that obesity may affect 29.6% of adults by 2030.This study also highlighted that women, black and other minority ethnicities, and individuals with lower educational attainment are particularly at risk 24 .

Several medical conditions are associated with obesity, including heart disease, hypertension, stroke, type 2 diabetes, metabolic syndrome, and certain cancers 71 . These are among the leading causes of preventable premature death. The estimated annual medical cost of obesity in the U.S. was nearly $173 billion (in 2019 dollars), with medical costs for obese adults being $1,861 higher than for people at a healthy weight 60 .Other studies have shown that the cost of inpatient surgical procedures, both oncologic and benign, abdominal and non-abdominal, is higher in obese patients 56 .

Evidence of the relationship between obesity and cancer

Obesity is recognized as a significant risk factor for various types of cancer. According to the American Cancer Society, excess body fat contributes substantially to cancer risk, with approximately 10.9% of cancer cases in women and 4.8% in men in the U.S. attributed to overweight or obesity 61 . In the United Kingdom (UK), overweight and obesity were the second most common preventable causes of cancer, accounting for 6.3% of all cases in 2015. The proportion was higher in women (7.5%) than in men (5.2%), with the highest rates observed in Scotland (6.8%) and the lowest in Wales (5.4%). The type of cancer most strongly associated with overweight and obesity in women was uterine cancer (34.0%), while in men, it was esophageal cancer (31.3%) 9 .

The cause-and-effect relationship between obesity and cancer seems to be even more important 8 . Although the incidence of certain types of cancer at various primary sites is decreasing due to specific prevention measures ( e.g ., screening programs, smoking cessation), the incidence of neoplasms in younger populations has shown a significant increase associated with obesity.

A large British population-based study involving 5.24 million individuals with 166,955 new cases across 22 types of cancer noted a relationship between body mass index (BMI) and certain types of cancer. Of the more than 5 million individuals, 166,955 developed cancers. BMI was associated with 17 of the 22 types of cancer, though the effects varied substantially by site. Each 5 kg/m 2 increase in BMI was linearly associated with the incidence of uterine, cervical, thyroid, and leukemia cancers. High BMI was also associated with liver, colon, ovarian, and postmenopausal breast cancer in general (all p<0.0001), with these effects varying according to individual characteristics 22 , 36 . It is estimated that 41% of uterine cancers and 10% or more of gallbladder, kidney, liver, and colon cancers could be attributed to excess weight. A 1 kg/m 2 increase in BMI across the population could result in 3,790 additional cancer cases per year in the UK 7 .

A 2015 study reported the risk of cancer attributable to obesity by gender: in women, around 30% for breast and uterine cancers, around 10% for colon, rectum, and gallbladder cancers, 8.8% for kidney cancer, 3.4% for pancreas cancer, and 1.2% for esophageal cancer. In men, obesity was responsible for over 50% of colon and rectal cancers, 24.8% of kidney cancers, and around 10% for pancreatic and esophageal cancers 4 .

In addition to these types of cancer, other neoplasms associated with overweight and obesity include meningiomas, thyroid cancer, multiple myeloma, ovarian cancer, liver cancer, and esophagogastric junction cancer. From 1995 to 2014, the incidence of obesity-related neoplasms among adults aged 25–49 years increased significantly in 6 types of cancers: multiple myeloma, colorectal, uterine, gallbladder, kidney, and pancreatic cancer. This association was more evident in women, as described in a 17-year study (January 2000 to December 2016), which reported a shift in the age distribution of obesity-associated cancers, with 70.3% of patients being female. In fact, a BMI greater than or equal to 30 corresponds to an 86% increase in the relative risk of colorectal cancer in young women, with the risk increasing by 18% for every 5-unit rise in BMI, even in women with no family history of this type of cancer 41 .

In an interesting review article, Pati et al. focused on the epidemiology and relationship between obesity and cancer. They concluded that around 4 to 8% of all cancers can be attributed to obesity, which is now recognized as a risk factor for several types of cancer, including postmenopausal breast, liver, gallbladder, pancreas, colon and rectum, endometrial, kidney, and esophageal cancer. They also noted that excess body fat resulted in an increased risk of approximately 17% in cancer-specific mortality 46 .

A large cohort study in Spain, involving more than 2.5 million individuals from 2009 to 2018, analyzed individuals over 45 years of age who were cancer-free in 2009. After 9 years of follow-up, 225,396 participants were diagnosed with cancer. This analysis demonstrated that longer duration and higher degrees of obesity, particularly in younger individuals and those who became overweight or obese during early adulthood, increased the risk of 18 types of cancer, including leukemia and non-Hodgkin lymphoma. Among never-smokers, head and neck and bladder cancers, not yet recognized as obesity-related cancers in the literature, were also linked to obesity. The authors emphasized the importance of including obesity prevention strategies in public health programs 49 .

In summary, according to the literature, increased body weight and obesity are related to at least 13 types of cancer, 6 of which are located in the digestive system ( Table 1 ).

The relationship between BMI and the risk of developing and dying from cancer is so direct that it is estimated that, in a hypothetical situation where the American population did not exceed a BMI of 25 kg/m 2 , 90,000 fewer cancer-related deaths would occur each year in the U.S. 7 , 11 , 70 .

The mechanisms linking obesity to cancer are multifactorial. Obesity is associated with metabolic dysregulation, chronic low-grade systemic inflammation 27 , and hormonal changes, including elevated insulin and sex hormones, which can promote carcinogenesis. Increased circulating estrogens, tumor cell growth and migration, modification of the tumor microenvironment, and neoangiogenesis have also been implicated. Obesity induces a variety of systemic changes, including altered levels of insulin, insulin-like growth factor-1 (IGF-1), leptin, adiponectin, steroid hormones, and cytokines, creating an environment that favors tumor initiation and progression. Chronic low-grade inflammation, driven by adipose tissue dysfunction and macrophage infiltration, is a hallmark of obesity and contributes to both cancer risk and progression. Adipose tissue in obese individuals secretes a large number of biologically active substances termed adipokines, which include pro-inflammatory cytokines like IL-6 and TNF-α. These adipokines can induce pathological alterations in insulin pathways and promote a pro-inflammatory state, both of which are linked to increased cancer risk. Additionally, obesity-related changes in the gut microbiome and adipokine pathways further contribute to cancer risk 30 , 32 , 59 , 62 .

One hypothesis is that adipose tissue acts as an organ capable of releasing enzymes and other chemical mediators, such as estrogens, whose increase results from heightened aromatase activity in adipose tissue 50 . Obesity also impacts the tumor microenvironment by modulating immune cell infiltration, influencing cancer progression and response to therapy 15 .

Therefore, the pathophysiology of the relationship between obesity and cancer is quite complex and not yet fully understood, as it involves two multifactorial conditions encompassing genetic, environmental, and social factors in a highly interconnected manner. However, several obesity-related changes have been shown to influence carcinogenesis, including hyperinsulinemia, elevated leptin levels, chronic inflammation, oxidative stress, HIF-1α activation, cytokine secretion, DNA methylation, visceral adipose dysfunction, release of adiponectin, exosome miRNA release, and changes in the metabolism of sex hormones 74 .

As for weight loss, studies have shown a reduced risk of breast, endometrial, colorectal, and prostate cancers in patients who lost weight. A large prospective study with postmenopausal women showed that intentional loss of more than 5% of body weight was associated with a lower risk of obesity-related neoplasms, though this effect was not observed when weight loss was unintentional 39 , 65 . Lifestyle modifications could prevent a substantial proportion of cancer cases. A study found that adherence to a healthy lifestyle — defined as non-smoking, moderate alcohol consumption, maintaining a BMI between 18.5 and 27.5, and engaging in regular physical activity — could prevent 25% of cancer cases in women and 33% in men 9 , 16 , 51 , 63 .

Obesity negatively impacts all phases of cancer treatment, increasing the incidence of at least 13 types of cancer and delaying diagnosis due to technical difficulties in the surgical treatment, difficulties in accessing diagnostic methods, or the stigma that obese patients face, which may discourage them from seeking medical attention. Obesity also increases therapeutic complications (surgeries, radiotherapy, chemotherapy, etc.) and adversely affects survival rates in cancer patients. It compromises quality of life, increases the likelihood of cancer recurrence and progression, and raises the risk of developing new neoplasms 10 , 11 , 25 , 57 , 66 .

In conclusion, there seems to be sufficient evidence to link obesity to cancer. The question that follows is: does bariatric surgery reduce cancer risk?

Does Bariatric Surgery reduce cancer risk?

Obesity surgery reduces the incidence of cancer. Bariatric surgery has been shown to significantly lower the risk of developing obesity-associated cancers, which are linked to metabolic dysregulation, chronic low-grade systemic inflammation, and hormonal alterations such as elevated insulin and sex hormone levels.

A systematic review and meta-analysis demonstrated that bariatric surgery is associated with a reduced overall incidence of cancer (RR 0.62, 95%CI 0.46–0.84) and obesity-related cancer (RR 0.59, 95%CI 0.39–0.90). Another study found that bariatric surgery was associated with a significantly lower incidence of obesity-associated cancer (adjusted HR 0.68, 95%CI 0.53–0.87) and cancer-related mortality (adjusted HR 0.52, 95%CI 0.31–0.88) 74 .

Additionally, a multi-center population-based study reported that the cumulative incidence of cancers among patients who experienced obesity recurrence was significantly lower in the bariatric surgery group compared to the nonsurgical control group (HR 0.482, 95%CI 0.459–0.507). This protective effect extends to specific cancers such as breast, endometrial, and colorectal cancers 2 , 13 .

Other studies have shown that surgical treatment of obesity is associated with reduced risks of neoplasms in general, hormone-dependent cancers (breast, endometrium, and prostate), and obesity-related cancers (postmenopausal breast, endometrium, and colorectal) 40 , 54 , 68 .

In summary, bariatric surgery not only aids in weight loss but also significantly reduces the risk of developing various obesity-associated cancers by mitigating the underlying metabolic and inflammatory pathways that promote carcinogenesis. The benefits attributed to bariatric surgery in reducing cancer incidence also extend to other aspects of cancer treatment, including improved outcomes in adjuvant treatments (chemo and radiotherapy), lower recurrence rates, and increased overall survival. Therefore, there is substantial evidence that bariatric surgery positively affects the key pathophysiological mechanisms linking obesity and cancer 12 . The mechanisms include reduction in insulin and leptin levels, chronic inflammation, and oxidative stress, as well as the restoration of sex hormone levels, especially estradiol. Additionally, bariatric surgery has a significant impact on the intestinal microbiome and serum proteomics 60 .

In 2004, a study involving 1,035 patients who underwent bariatric surgery, compared with a cohort of more than 5,000 non-operated patients, demonstrated a significant decrease in cancer cases. In those who underwent surgery, the incidence was 2.03%, while in the non-surgical group, it was 8.49%, indicating that bariatric surgery reduced cancer incidence fourfold. There was also a large decrease in the number of hospitalizations for cancer: 54.95/1,000 person-years in the non-operated group versus only 11.80 in the operated group 16 . In the same year, an epidemiological evaluation of 15,850 patients, 7,925 of whom underwent surgery compared to an equal number of controls, showed a 60% decrease in cancer mortality 11 .

A few years later, a prospective, controlled analysis carried out in Sweden, involving more than 4,000 patients, about half of whom underwent bariatric surgery compared to controls, revealed the occurrence of 47 cases of cancer in the non-operated group compared to 29 in the operated group 61 . In 2017, another observational study with the impressive number of 18,355 operated patients, compared to more than 40,000 non-operated controls, revealed a significant decrease in cancer mortality, with greater weight loss associated with lower mortality 55 .

A recent systematic review and meta-analysis of 32 studies involving patients with obesity who underwent bariatric surgery compared to controls managed with conventional treatment analysis suggested that bariatric surgery was associated with a reduced overall incidence of cancer (RR 0.62, 95%CI 0.46–0.84, p<0.002), obesity-related cancer (RR 0.59, 95%CI 0.39–0.90, p=0.01), and cancer-associated mortality (RR 0.51, 95%CI 0.42–0.62, p<0.00001). For specific cancers, bariatric surgery was associated with a reduction in the future incidence of hepatocellular carcinoma (RR 0.35, 95%CI 0.22–0.55, p<0.00001), colorectal cancer (RR 0.63, 95%CI 0.50–0.81, p=0.0002), pancreatic cancer (RR 0.52, 95%CI 0.29–0.93, p=0.03), and gallbladder cancer (RR 0.41, 95%CI 0.18–0.96, p=0.04), as well as female-specific cancers, including breast cancer (RR 0.56, 95%CI 0.44–0.71, p<0.00001), endometrial cancer (RR 0.38, 95%CI 0.26–0.55, p<0.00001), and ovarian cancer (RR 0.45, 95%CI 0.31–0.64, p<0.0001). There was no significant reduction in the incidence of esophageal, gastric, thyroid, kidney, prostate cancer or multiple myeloma after bariatric surgery as compared to patients with morbid obesity who did not have bariatric surgery. The authors concluded that bariatric surgery might decrease future overall cancer incidence and mortality, particularly in relation to seven obesity-related cancers 74 .

Regarding cancers of the upper digestive tract, with the exception of colon cancer, hundreds of thousands of bariatric surgeries have been performed to date. However, a systematic review analyzing the relationship between bariatric surgeries and the reduction of digestive cancer specifically revealed that only a few cases of cancer after the operations were described. Therefore, there is no conclusive evidence supporting a correlation between obesity surgery and upper gastrointestinal cancer 23 . Åkerström et al. evaluated 748,932 participants diagnosed with obesity, of whom 91,731 underwent bariatric surgery, predominantly gastric bypass (n=70,176; 76.5%). The adjusted risk of esophageal cancer decreased over time after gastric bypass, from 2.2 (95%CI 0.9–4.3) after 2 to 5 years to 0.6 (95%CI <0.1–3.6) after 10 to 40 years. Gastric bypass patients also had a reduced risk of adenocarcinoma of the cardia compared with non-operated patients with obesity (adjusted HR 0.6, 95%CI 0.4–1.0 (0.98)), with point estimates decreasing over time. Gastric bypass was followed by a strongly decreased adjusted risk of esophageal adenocarcinoma (HR 0.3, 95%CI 0.1–0.8) but not of cardia adenocarcinoma (HR 0.9, 95%CI 0.5–1.6) when analyzed separately 29 .

Lazzati et al. showed that the incidence of esophagogastric cancer in patients undergoing bariatric surgery is statistically lower when compared with a population that did not undergo the procedure. The incidence of esophageal-gastric cancer fell from 6.9 to 4.9 per 100,000 population per year, with a reduction in esophageal cancer from 2.3 to 1.5 and in gastric cancer from 4.6 to 3.3 per 100,000 population per year 38 .

The association between upper digestive tract cancers after bariatric surgery remains controversial, as several procedures can increase the incidence of pre-neoplastic conditions in the esophagus 58 . A French national study evaluated the incidence of colorectal cancer by comparing nearly 2 million individuals who did not undergo bariatric surgery with more than 100,000 who did. The incidence of colorectal cancer has fallen by half in the patients subjected to bariatric surgery 5 .

In the Surgical Procedures and Long-term Effectiveness in Neoplastic Disease Incidence and Death (SPLENDID) matched cohort study, adult patients with a BMI of 35 or greater who underwent bariatric surgery at a U.S. health system between 2004 and 2017 were included 73 . Patients who underwent bariatric surgery were matched in a 1:5 ratio with patients who did not undergo surgery for their obesity, resulting in a total of 30,318 patients. Bariatric surgery (n=5053) included Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). During follow-up, 96 patients in the bariatric surgery group and 780 patients in the nonsurgical control group had an incident obesity-associated cancer (incidence rate of 3.0 events vs . 4.6 events, respectively, per 1,000 person-years). The cumulative incidence of the primary endpoint at 10 years was 2.9% (95%CI 2.2–3.6%) in the bariatric surgery group and 4.9% (95%CI 4.5–5.3%) in the nonsurgical control group (absolute risk difference, 2.0% [95%CI 1.2–2.7%]; adjusted HR 0.68 [95%CI 0.53–0.87], p=0.002, p<0.05). Cancer-related mortality occurred in 21 patients in the bariatric surgery group and 205 patients in the nonsurgical control group (incidence rate of 0.6 events vs . 1.2 events, respectively, per 1,000 person-years). The cumulative incidence of cancer-related mortality at 10 years was 0.8% (95%CI 0.4–1.2%) in the bariatric surgery group and 1.4% (95%CI 1.1–1.6%) in the nonsurgical control group (absolute risk difference, 0.6% [95%CI 0.1–1.0%]; adjusted HR 0.52 [95%CI 0.31–0.88], p=0.01, p<0.05). The authors concluded that, among adults with obesity, bariatric surgery compared with no surgery was associated with a significantly lower incidence of obesity-associated cancer and cancer-related mortality 2 .

Does the bariatric surgery technique — Roux-en-Y gastric bypass, sleeve gastrectomy, or single anastomosis mini gastric bypass — influence the risk of cancer after the operation?

Bariatric surgery has become a widely performed procedure globally, with approximately 1 million surgeries estimated to occur each year. Among the procedures performed, SG and RYGB account for approximately 80% of surgeries performed in the U.S. Mini gastric bypass (OAGB) is another technique that has been gaining a lot of attention and has a growing number of followers, becoming the most performed procedure in some countries 17 , 43 .

These three procedures raise some concerns regarding potential carcinogenic characteristics. Specifically, SG is associated with a higher incidence of reflux, esophagitis, and Barrett’s esophagus. RYGB raises concerns due to the exclusion of the stomach, while OAGB is linked to alkaline reflux. The major concern among these issues would be the development of esophageal cancer in this population 47 .

Sleeve gastrectomy

The incidence of cancer after SG has been a subject of investigation in several studies. According to a systematic review and meta-analysis, bariatric surgery, including SG, is associated with a significant reduction in overall cancer incidence compared to nonsurgical treatment. Specifically, the odds ratio (OR) for cancer incidence in patients undergoing SG was 0.44 (95%CI 0.27–0.70) 14 .

However, there are specific concerns regarding the risk of esophageal cancer post SG due to the potential for increased gastroesophageal reflux disease (GERD) and consequently esophagitis and risk of Barrett’s esophagus. One study found that the crude incidence rate of esophageal cancer in patients undergoing reflux-prone procedures like SG was higher than in nonsurgical controls, but this difference was not significant after adjusting for confounders 3 .

Some case studies reported an incidence of approximately 18% for Barrett’s esophagus, 52% for the need for stomach-protective medication, and 41% for esophagitis within 5 years of evolution 58 . The shape of the gastric tube appears to influence the incidence of reflux, especially when it is made in a twisted manner 26 . However, the incidence of Barrett’s in patients undergoing SG varies widely in the literature. Dantas et al., in an endoscopic evaluation with more than 5 years of follow-up, did not identify any cases of Barrett’s esophagus in their case study 18 . In summary, while sleeve gastrectomy is associated with a reduced overall cancer incidence, there is a notable concern for esophageal cancer due to increased GERD and Barrett’s esophagus. Therefore, SG is generally lower for most cancer types, vigilance for esophageal cancer remains necessary.

Roux-en-Y gastric bypass

The creation of an excluded gastric chamber in this type of surgery raises concerns mainly due to the difficulty in accessing the excluded stomach. Some studies, in which the excluded chamber was accessed through double-balloon endoscopy, showed an incidence of atrophic gastritis of 14.3%, metaplasia in 11.4%, and H. pylori presence in 20% of cases. In addition to the changes mentioned, there appear to be changes in the microenvironment that may predispose to oncogenic molecular mutations 48 , 52 , 53 .

The incidence of gastric cancer after RYGB is rare but has been documented in the medical literature. According to a systematic review by Chemaly et al., the occurrence of gastroesophageal cancer post-RYGB is primarily reported through case studies, with 27 out of 44 cases of gastroesophageal cancer occurring in the gastric tube after RYGB 13 . Another systematic review by Dong et al. identified 21 cases of remnant gastric cancer after RYGB, with a median time to diagnosis of 11 years postoperatively 20 . Additionally, Doukas et al. 21 reported an increasing trend of gastric cancer cases in the excluded stomach post-RYGB, with 77% of these cancers diagnosed at an advanced stage 13 , 20 , 21 .

In summary, while the exact incidence rate is not well-defined due to the rarity and the nature of case reports, available data suggest that gastric cancer can occur in the remnant stomach or gastric tube after RYGB, typically many years postoperatively. Although rare, this warrants awareness and long-term surveillance in high-risk patients.

Mini gastric bypass

Despite being a relatively recent procedure in the arsenal of surgical treatment for obesity, OAGB brings with it a problem already faced in gastrectomy surgery with B-II reconstruction, which is alkaline reflux. Alkaline reflux can cause changes in the gastric mucosa and esophageal mucosa, with some studies reporting its presence in 21% of cases, potentially increasing cancer incidence 35 . Gastroesophageal cancer appears to be the most commonly reported type of cancer following mini gastric bypass (OAGB), although the incidence is not significantly higher compared to RYGB. According to a systematic review and meta-analysis by Chemaly et al., 37.5% of gastroesophageal cancers after OAGB were located in the gastric tube, compared to 61% after RYGB, with an odds ratio of 0.38, indicating no significant increase in cancer occurrence in the gastric tube after OAGB compared to RYGB 13 .

The arguments that bile reaches the terminal ileum diluted are unfounded, since physiology studies show that 90% of bile reaches that location intact, where it is later reabsorbed. This technique should be used with great caution, since the potential harmful effects, such as the development of cancer in the gastric remnant and esophagus, may only become apparent 30 to 40 years postoperatively 1 , 6 , 19 , 35 .

In conclusion, the incidence of cancer in patients undergoing bariatric surgery is low. Large systematic reviews and meta-analyses list a small number of cases relative to the total number of surgeries performed worldwide, demonstrating that the benefits of surgery, in terms of cancer incidence reduction, outweigh the risks, regardless of the surgical technique employed 43 , 44 , 45 . Therefore, while the incidence of cancer in patients undergoing bariatric surgery remains numerically low, it is a concern, and surgeons must remain vigilant to avoid understanding symptoms and delaying diagnosis. On the other hand, there is sufficient evidence to suggest that bariatric surgery reduces the incidence of many types of cancer. However, indications for surgery should be thoroughly discussed with multidisciplinary teams, avoiding exaggeration and sensationalism, especially regarding procedures that increase the incidence of gastroesophageal reflux.

Financial source: None

REFERENCES

1. Ahn HS Kim JW Yoo MW Park DJ Lee HJ Lee KU Clinicopathological features and surgical outcomes of patients with remnant gastric cancer after a distal gastrectomy Ann Surg Oncol 2008 15 6 1632 9 10.1245/s10434-008-9871-8 18379851

2. Aminian A Wilson R Al-Kurd A Tu C Milinovich A Kroh M Association of bariatric surgery with cancer risk and mortality in adults with obesity JAMA 2022 327 24 2423 33 10.1001/jama.2022.9009 35657620 PMC9166218

3. Andalib A Bouchard P Demyttenaere S Ferri LE Court O Esophageal cancer after sleeve gastrectomy: a population-based comparative cohort study Surg Obes Relat Dis 2021 17 5 879 87 10.1016/j.soard.2020.12.011 33547014

4. Arnold M Pandeya N Byrnes G Renehan PAG Stevens GA Ezzati PM Global burden of cancer attributable to high body-mass index in 2012: a population-based study Lancet Oncol 2015 16 1 36 46 10.1016/S1470-2045(14)71123-4 25467404 PMC4314462

5. Bailly L Fabre R Pradier C Iannelli A Colorectal cancer risk following bariatric surgery in a nationwide study of french individuals with obesity JAMA Surg 2020 155 5 395 402 10.1001/jamasurg.2020.0089 32159744 PMC7066530

6. Basso L Gallo G Biacchi D Carati MV Cavallaro G Esposito l Role of new anatomy, biliopancreatic reflux, and helicobacter pylori status in postgastrectomy stump cancer J Clin Med 2022 11 6 1498 10.3390/jcm11061498 35329824 PMC8952228

7. Bhaskaran K Douglas I Forbes H dos-Santos-Silva I Leon DA Smeeth L Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5·24 million UK adults Lancet 2014 384 9945 755 65 10.1016/S0140-6736(14)60892-8 25129328 PMC4151483

8. Brenner DR Ruan Y Shaw E O’Sullivan D Poirier AE Heer E Age-standardized cancer-incidence trends in Canada, 1971-2015 CMAJ 2019 191 46 E1262 73 10.1503/cmaj.190355 31740536 PMC6861145

9. Brown KF Rumgay H Dunlop C Ryan M Quartly F Cox A The fraction of cancer attributable to modifiable risk factors in England, Wales, Scotland, Northern Ireland, and the United Kingdom in 2015 Br J Cancer 2018 118 8 1130 41 10.1038/s41416-018-0029-6 29567982 PMC5931106

10. Calle EE Kaaks R Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms Nat Rev Cancer 2004 4 8 579 91 10.1038/nrc1408 15286738

11. Calle EE Rodriguez C Walker-Thurmond K Thun MJ Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S adults. N Engl J Med 2003 348 17 1625 38 10.1056/NEJMoa021423 12711737

12. Castagneto-Gissey L Casella-Mariolo J Casella G Mingrone G Obesity surgery and cancer: what are the unanswered questions? Front Endocrinol (Lausanne) 2020 11 213 10.3389/fendo.2020.00213 32351453 PMC7174700

13. Chemaly R Diab S Khazen G Al-Hajj G Gastroesophageal cancer after gastric bypass surgeries: a systematic review and meta-analysis Obes Surg 2022 32 4 1300 11 10.1007/s11695-022-05921-4 35084611

14. Chen ZW Jin T Liang PP Li ZD He FJ Chen ZH Incidence of cancer for patients after bariatric surgery: evidence from 33 cohort studies Surg Obes Relat Dis 2024 20 5 467 81 10.1016/j.soard.2023.11.010 38151417

15. Chittajallu V Mansoor E Perez J Omar YA Firkins SA Yoo H Association of bariatric surgery with risk of incident obesity-associated malignancies: a multi-center population-based study Obes Surg 2023 33 12 4065 9 10.1007/s11695-023-06926-3 37971573

16. Christou NV Sampalis JS Liberman M Look D Auger S McLean APH Surgery decreases long-term mortality, morbidity, and health care use in morbidly obese patients Ann Surg 2004 240 3 416 23 discussion 423-4 10.1097/01.sla.0000137343.63376.19 15319713 PMC1356432

17. Clapp B Ponce J Corbett J Ghanem OM Kurian M Rogers AM American Society for Metabolic and Bariatric Surgery 2022 estimate of metabolic and bariatric procedures performed in the United States Surg Obes Relat Dis 2024 20 5 425 31 10.1016/j.soard.2024.01.012 38448343

18. Dantas ACB Coutinho JL Meira JD Jr De Moura DTH Pajecki D Santo MA Lots of reflux, but no Barrett: real-world data on the incidence of gastroesophageal reflux on routine endoscopic follow-up more than 5 years after sleeve gastrectomy J Gastrointest Surg 2024 28 7 1177 8 10.1016/j.gassur.2024.04.023 38705371

19. Diogo A Filho Botelho LF Nishiyama A Zumpano LE Monte RC Rosa SC Gastric stump cancer after gastrectomy by gastroduodenal peptic ulcer Arq Bras Cir Dig 2016 29 1 65 10.1590/0102-6720201600010017 27120745 PMC4851156

20. Dong SL Liang YL Wang CC Dong ZY Occurrence of gastric cancer after laparoscopic Roux-en-Y gastric bypass: a systematic review Zhonghua Wei Chang Wai Ke Za Zhi 2022 25 9 834 9 10.3760/cma.j.cn441530-20211221-00515 36117376

21. Doukas SG Doukas PG Vageli DP Broder A Gastric cancer after Bariatric Bypass Surgery. Do they relate? (a systematic review) Obes Surg 2023 33 6 1876 88 10.1007/s11695-023-06567-6 37041375

22. Doumouras AG Lovrics O Paterson JM Sutradhar R Paszat L Sivapathasundaram B Residual risk of breast cancer after bariatric surgery JAMA Surg 2023 158 6 634 41 10.1001/jamasurg.2023.0530 37043196 PMC10099105

23. Ebrahimi R Kermansaravi M Khalaj A Eghbali F Mousavi A Pazouki A Gastro-intestinal tract cancers following bariatric surgery: a narrative review Obes Surg 2019 29 8 2678 94 10.1007/s11695-019-04007-y 31175561

24. Estivaleti JM Guzman-Habinger J Lobos J Azeredo CM Claro R Ferrari G Time trends and projected obesity epidemic in Brazilian adults between 2006 and 2030 Sci Rep 2022 12 1 12699 10.1038/s41598-022-16934-5 35882969 PMC9315079

25. Feigelson HS Bodelon C Powers JD Curtis RE Buist DSM Veiga LHS Body mass index and risk of second cancer among women with breast cancer J Natl Cancer Inst 2021 113 9 1156 60 10.1093/jnci/djab053 33823007 PMC8757319

26. Ferraz AAB Silva JTD Santa-Cruz F Aquino MAR Siqueira LT Kreimer F The impact of the gastric twist on esophagitis progression after sleeve gastrectomy: mid-term endoscopic findings Obes Surg 2020 30 11 4452 8 10.1007/s11695-020-04838-0 32661958

27. Freitas WR Jr Oliveira LVF Perez EA Ilias EJ Lottenberg CP Silva AS Systemic inflammation in severe obese patients undergoing surgery for obesity and weight-related diseases Obes Surg 2018 28 7 1931 42 10.1007/s11695-017-3104-9 29497960 PMC6018580

28. Hampl SE Hassink SG Skinner AC Armstrong SC Barlow SE Bolling CF Clinical practice guideline for the evaluation and treatment of children and adolescents with obesity Pediatrics 2023 151 2 e2022060640 10.1542/peds.2022-060640 36622115

29. Åkerström JH Santoni G von Euler Chelpin M Chidambaram S Markar SR Maret-Ouda J Decreased risk of esophageal adenocarcinoma after gastric bypass surgery in a cohort study from 3 nordic countries Ann Surg 2023 278 6 904 9 10.1097/SLA.0000000000006003 37450697

30. Hopkins BD Goncalves MD Cantley LC Obesity and cancer mechanisms: cancer metabolism J Clin Oncol 2016 34 35 4277 83 10.1200/JCO.2016.67.9712 27903152 PMC5562429

31. Islami F Sauer AG Gapstur SM Jemal A Proportion of cancer cases attributable to excess body weight by US state, 2011-2015 JAMA Oncol 2019 5 3 384 92 10.1001/jamaoncol.2018.5639 30589925 PMC6521676

32. Iyengar NM Gucalp A Dannenberg AJ Hudis CA Obesity and cancer mechanisms: tumor microenvironment and inflammation J Clin Oncol 2016 34 35 4270 6 10.1200/JCO.2016.67.4283 27903155 PMC5562428

33. Kaidar-Person O Bar-Sela G Person B The two major epidemics of the twenty-first century: obesity and cancer Obes Surg 2011 21 11 1792 7 10.1007/s11695-011-0490-2 21842287

34. Kodaira K Abe FC Galvão TF Silva MT Time-trend in excess weight in Brazilian adults: a systematic review and meta-analysis PLoS One 2021 16 9 e0257755 10.1371/journal.pone.0257755 34582470 PMC8478247

35. Kondo K Akiyama S Ito K Yokoyama Y Takagi H Risk of cancer development in the gastric remnant by B-II resection. In: Takahashi T eds Recent advances in management of digestive cancers Tokyo Springer 1993 218 20 10.1007/978-4-431-68252-3_47

36. Kristensson FM Andersson-Assarsson JC Peltonen M Jacobson P Ahlin S Svensson PA Breast cancer risk after bariatric surgery and influence of insulin levels: a nonrandomized controlled trial JAMA Surg 2024 159 8 856 63 10.1001/jamasurg.2024.1169 38748431 PMC11097101

37. Lauby-Secretan B Scoccianti C Loomis D Grosse Y Bianchini F Straif K Body fatness and cancer--viewpoint of the IARC Working Group N Engl J Med 2016 375 8 794 8 10.1056/NEJMsr1606602 27557308 PMC6754861

38. Lazzati A Poghosyan T Touati M Collet D Gronnier C Risk of esophageal and gastric cancer after bariatric surgery JAMA Surg 2023 158 3 264 71 10.1001/jamasurg.2022.6998 36630108 PMC9857712

39. Luo J Hendryx M Manson JE Figueiredo JC LeBlanc ES Barrington W Intentional weight loss and obesity-related cancer risk JNCI Cancer Spectr 2019 3 4 pkz054 10.1093/jncics/pkz054 31737862 PMC6795232

40. Mackenzie H Markar SR Askari A Faiz O Hull M Purkayastha S Obesity surgery and risk of cancer Br J Surg 2018 105 12 1650 7 10.1002/bjs.10914 30003539

41. Center for Disease Control and Prevention Obesity and cancer 2019 Available at: https://www.cdc.gov/cancer/risk-factors/obesity.html Accessed: Jan. 08, 2024

42. Nielsen J Narayan KV Cunningham SA Incidence of obesity across adulthood in the United States, 2001-2017-a national prospective analysis Am J Clin Nutr 2023 117 1 141 8 10.1016/j.ajcnut.2022.10.012 36789933 PMC10196588

43. Onzi TR Salgado W Júnior Bastos ELS Dantas ACB Silva LB Oliveira AA Neto Efficacy and safety of one anastomosis gastric bypass in surgical treatment of obesity: systematic review and meta-analysis of randomized controlled trials Arq Bras Cir Dig 2024 37 e1814 10.1590/0102-6720202400021e1814 39230117 PMC11363908

44. Parmar C Pouwels S Oesophageal and gastric cancer after bariatric surgery: an up-to-date systematic scoping review of literature of 324 cases Obes Surg 2022 32 12 3854 62 10.1007/s11695-022-06304-5 36241765

45. Parmar C Zakeri R Abouelazayem M Shin TH Aminian A Mahmoud T Esophageal and gastric malignancies after bariatric surgery: a retrospective global study Surg Obes Relat Dis 2022 18 4 464 72 10.1016/j.soard.2021.11.024 35065887

46. Pati S Irfan W Jameel A Ahmed S Shahid RK Obesity and cancer: a current overview of epidemiology, pathogenesis, outcomes, and management Cancers (Basel) 2023 15 2 485 10.3390/cancers15020485 36672434 PMC9857053

47. Plat VD Kasteleijn A Greve JWM Luyer MDP Gisbertz SS Demirkiran A Esophageal cancer after bariatric surgery: increasing prevalence and treatment strategies Obes Surg 2021 31 11 4954 62 10.1007/s11695-021-05679-1 34494230 PMC8490213

48. Ravacci GR Ishida R Torrinhas RS Sala P Machado NM Fonseca DC Potential premalignant status of gastric portion excluded after Roux en-Y gastric bypass in obese women: a pilot study Sci Rep 2019 9 1 5582 10.1038/s41598-019-42082-4 30944407 PMC6447527

49. Recalde M Pistillo A Davila-Batista V Leitzmann M Romieu I Viallon V Longitudinal body mass index and cancer risk: a cohort study of 2.6 million Catalan adults Nat Commun 2023 14 1 3816 10.1038/s41467-023-39282-y 37391446 PMC10313757

50. Renehan AG Zwahlen M Egger M Adiposity and cancer risk: new mechanistic insights from epidemiology Nat Rev Cancer 2015 15 8 484 98 10.1038/nrc3967 26205341

51. Rock CL Thomson C Gansler T Gapstur SM McCullough ML Patel AV American Cancer Society guideline for diet and physical activity for cancer prevention CA Cancer J Clin 2020 70 4 245 71 10.3322/caac.21591 32515498

52. Safatle-Ribeiro A Kuga R Iriya K Ribeiro U Jr Faintuch J Ishida RK What to expect in the excluded stomach mucosa after vertical banded Roux-en-Y gastric bypass for morbid obesity J Gastrointest Surg 2007 11 2 133 7 10.1007/s11605-006-0047-1 17390161

53. Safatle-Ribeiro AV Ribeiro U Jr Is gastric cancer after bariatric surgery on the rise? Will history repeat itself? Chin J Cancer Res 2023 35 1 11 4 10.21147/j.issn.1000-9604.2023.01.02 36910856 PMC9993001

54. Schauer DP Feigelson HS Koebnick C Caan B Weinmann S Leonard AC Bariatric surgery and the risk of cancer in a large multisite cohort Ann Surg 2019 269 1 95 101 10.1097/SLA.0000000000002525 28938270 PMC6201282

55. Schauer DP Feigelson HS Koebnick C Caan B Weinmann S Leonard AC Association between weight loss and the risk of cancer after bariatric surgery Obesity (Silver Spring) 2017 25 Suppl 2(Suppl 2) S52 S57 10.1002/oby.22002 29086527 PMC5722457

56. Schiel WA Peppe AP Neto Weiss AG Cortiano LGG Branco AJ Filho Almeida FE Laparoscopic and laparotomy bariatric surgery in a public hospital in Brazil: are there differences in costs and complications? Arq Bras Cir Dig 2023 36 e1739 10.1590/0102-672020230021e1739 37283394 PMC10237274

57. Schmitz KH Neuhouser ML Agurs-Collins T Zanetti KA Cadmus-Bertram L Dean LT Impact of obesity on cancer survivorship and the potential relevance of race and ethnicity J Natl Cancer Inst 2013 105 18 1344 54 10.1093/jnci/djt223 23990667 PMC3776266

58. Sebastianelli L Benois M Vanbiervliet G Bailly L Robert M Turrin N Systematic endoscopy 5 years after sleeve gastrectomy results in a high rate of Barrett’s esophagus: results of a multicenter study Obes Surg 2019 29 5 1462 9 10.1007/s11695-019-03704-y 30666544

59. Singh A Mayengbam SS Yaduvanshi H Wani MR Bhat MK Obesity programs macrophages to support cancer progression Cancer Res 2022 82 23 4303 12 10.1158/0008-5472.CAN-22-1257 36191083

60. Siqueira LT Wanderley MSO Silva RA Pereira ASA Lima JL Filho Ferraz AAB A screening study of potential carcinogen biomarkers after surgical treatment of obesity Obes Surg 2018 28 8 2487 93 10.1007/s11695-018-3191-2 29525938

61. Sjöström L Narbro K Sjöström CD Karason K Larsson B Wedel H Effects of bariatric surgery on mortality in Swedish obese subjects N Engl J Med 2007 357 8 741 52 10.1056/NEJMoa066254 17715408

62. Smith CJ Perfetti TA Hayes AW Berry SC Obesity as a source of endogenous compounds associated with chronic disease: a review Toxicol Sci 2020 175 2 149 55 10.1093/toxsci/kfaa042 32207534

63. Song M Giovannucci E Preventable incidence and mortality of carcinoma associated with lifestyle factors among white adults in the United States JAMA Oncol 2016 2 9 1154 61 10.1001/jamaoncol.2016.0843 27196525 PMC5016199

64. Stierman B Afful J Carroll MD Chen TC Davy O Fink S National Health and Nutrition Examination Survey 2017–March 2020 prepandemic data files-development of files and prevalence estimates for selected health outcomes Natl Health Stat Report 2021 158 10.15620/cdc:106273 https://doi.org/10.15620/cdc:106273 PMC11513744 39380201

65. Stroud AM Dewey EN Husain FA Fischer JM Courcoulas AP Flum DR Association between weight loss and serum biomarkers with risk of incident cancer in the Longitudinal Assessment of Bariatric Surgery cohort Surg Obes Relat Dis 2020 16 8 1086 94 10.1016/j.soard.2020.04.012 32471725

66. Sung H Hyun N Leach CR Yabroff KR Jemal A Association of first primary cancer with risk of subsequent primary cancer among survivors of adult-onset cancers in the United States JAMA 2020 324 24 2521 35 10.1001/jama.2020.23130 33351041 PMC7756242

67. Sung H Siegel RL Rosenberg PS Jemal A Emerging cancer trends among young adults in the USA: analysis of a population-based cancer registry Lancet Public Health 2019 4 3 e137 e147 10.1016/S2468-2667(18)30267-6 30733056

68. Tee MC Cao Y Warnock GL Hu FB Chavarro JE Effect of bariatric surgery on oncologic outcomes: a systematic review and meta-analysis Surg Endosc 2013 27 12 4449 56 10.1007/s00464-013-3127-9 23949484 PMC4018832

69. Trust for America’s Health State of obesity 2023: better policies for a healthier America Trust for America’s Health 2023 Available at: https://www.tfah.org/report-details/state-of-obesity-2023/ Accessed: Aug. 12, 2024

70. Tsui ST Yang J Zhang X Docimo S Jr Spaniolas K Talamini MA Development of cancer after bariatric surgery Surg Obes Relat Dis 2020 16 10 1586 95 10.1016/j.soard.2020.06.026 32737010

71. Valezi AC Campos ACL Von Bahten LC Brazilian multi-society position statement on emerging bariatric and metabolic surgical procedures Arq Bras Cir Dig 2023 36 e1759 10.1590/0102-672020230041e1759 37729276 PMC10510373

72. Ward ZJ Bleich SN Cradock AL Barrett JL Giles CM Flax C Projected U.S. state-level prevalence of adult obesity and severe obesity N Engl J Med 2019 381 25 2440 50 10.1056/NEJMsa1909301 31851800

73. Wilson R Aminian A Obesity-associated cancer risk reduction after metabolic surgery: insights from the SPLENDID study and the path forward Surg Obes Relat Dis 2023 19 7 788 93 10.1016/j.soard.2023.01.027 36948974

74. Wilson RB Lathigara D Kaushal D Systematic review and meta-analysis of the impact of bariatric surgery on future cancer risk Int J Mol Sci 2023 24 7 6192 10.3390/ijms24076192 37047163 PMC10094585