ABCD Arq Bras Cir Dig

2024;37:e1838 REVIEW ARTICLE - POSITION PAPER

https://doi.org/10.1590/0102-6720202400044e1838

ATHE
QUEDA DA PRESSÃO
GROWING EVIDENCE PORTAL
OF THE APÓS DESVASCULARIZAÇÃO
RELATIONSHIP BETWEEN OBESITY
AND CANCER AND THE
ESOFAGOGÁSTRICA ROLE OF BARIATRIC
E ESPLENECTOMIA SURGERY
INFLUENCIA A VARIAÇÃO
DO CALIBRE
A CRESCENTE DASDA
EVIDÊNCIA VARIZES E ASOBESIDADE
RELAÇÃO ENTRE TAXASE DECÂNCERRESSANGRAMENTO NA
E O PAPEL DA CIRURGIA BARIÁTRICA

ESQUISTOSSOMOSE
Paulo KASSAB , Álvaro AntônioNO
1
SEGUIMENTO
Bandeira EMHebling
FERRAZ , Anna Clara LONGO PRAZO?
MITIDIERI , Luiz Vicente BERTI ,
2 3 3

Marco Aurélio SANTO4 , Tiago SZEGO5 , Caio de Carvalho ZANON1 , Osvaldo Antônio Prado CASTRO1 ,
Does theRodrigues
Wilson de FREITAS
drop in portal JUNIOR
pressure , Elias Jirjoss ILIAS
after esophagogastric , Carlos Alberto
devascularization andMALHEIROS
splenectomy ,
1 1 1

variation of variceal calibers and the rebleeding rates in schistosomiasis in late follow-up? Surgery (CBCD) and
Antônio Carlos VALEZI , Antônio Carlos Ligocki CAMPOS , Brazilian College of Digestive
6 7

Brazilian Society of Bariatric and Metabolic Surgery (SBCBM).

Walter de Biase SILVA-NETO1 , Claudemiro QUIRESE1 , Eduardo Guimarães Horneaux de MOURA2 ,
Fabricio Ferreira COELHO3 , Paulo HERMAN3

RESUMO
ABSTRACT-– Racional: O tratamento
Obesity is recognized de escolha
as a significant para for
risk factor pacientes comofhipertensão
various types cancer. Althoughportal
the incidence of some types of cancer across various primary
esquistossomótica
sites is decreasing due com sangramento
to specific preventionde varizes(screening
measures é a desconexão ázigo-portal
programs, smoking mais
cessation), the incidence of neoplasms in the young population shows a
esplenectomia (DAPE)
significant increase associada
associated with à terapia
obesity. endoscópica.
There is sufficientPorém,
evidenceestudos mostram
to say that bariatricaumento
surgery has been shown to significantly lower the risk of developing
obesity-associated
do calibre das varizescancers, which are
em alguns linked to
pacientes metabolic
durante dysregulation,
o seguimento emchronic
longolow-grade systemic inflammation, and hormonal alterations such as elevated
prazo. Objetivo:
levels of insulin and sex hormones.
Avaliar o impacto da DAPE e tratamento endoscópico pós-operatório no comportamento
HEADINGS: Obesity. Bariatric surgery. Neoplasms.
das varizes esofágicas e recidiva hemorrágica, de pacientes esquistossomóticos. Métodos:
Foram estudados 36 pacientes com seguimento superior a cinco anos, distribuídos em
dois grupos:
RESUMO queda da
– A obesidade pressão portal
é reconhecida comoabaixo dede
um fator 30% e significativo
risco acima de 30% paracomparados
vários tipos decom o Embora a incidência de alguns tipos de câncer de vários
câncer.
locais primários
calibre esteja
das varizes diminuindo
esofágicas devido a medidasprecoce
no pós-operatório específicas de prevenção
e tardio além do(programas de triagem, cessação do tabagismo), a incidência de neoplasias na
índice de recidiva
população jovem mostra um aumento significativo associado à obesidade. Há evidências suficientes para dizer que a cirurgia bariátrica demonstrou reduzir
hemorrágica. Resultados
significativamente o risco de desenvolver cânceres associados à obesidade, que estão ligados à desregulação metabólica, inflamação sistêmica crônica de baixo
esofágicas que, durante
grau e alterações hormonais,o seguimento aumentaram
como níveis elevados de calibre
de insulina e foram
e hormônios controladas com
sexuais.
DESCRITORES: Obesidade. Cirurgia bariátrica. Neoplasias. Evolução do calibre das varizes no período pré e pós-
o comportamento do calibre das varizes no pós-operatório precoce nem tardio nem os operatório precoce e tardio
índices de recidiva hemorrágica. Conclusão

operatórios precoces ou tardios. A comparação entre a queda de pressão do portal e as Mensagem central
A desconexão ázigo-portal e esplenectomia
DESCRITORES: Esquistossomose mansoni. Hipertensão portal. Cirurgia. Pressão na veia porta. Varizes esofágicas apresenta importante impacto na diminuição
e gástricas. precoce do calibre das varizes esofágicas na
esquistossomose; entretanto, parece que a
associação com a terapia endoscópica é a maior
responsável pelo controle da recidiva hemorrágica.
ABSTRACT - Background: The treatment of choice for patients with schistosomiasis with
previous episode of varices is bleeding esophagogastric devascularization and splenectomy
(EGDS) in association with postoperative endoscopic therapy. However, studies have shown Perspectiva
varices recurrence especially after long-term follow-up. Aim: To assess the impact on Este estudo avaliou o impacto tardio no índice
behavior of esophageal varices and bleeding recurrence after post-operative endoscopic de ressangramento de pacientes submetidos ao
treatment of patients submitted to EGDS. Methods: Thirty-six patients submitted to EGDS tratamento cirúrgico e endoscópico. A queda na

portal pressure drop, more or less than 30%, and compared with the behavior of esophageal variação do calibre das varizes quando comparado
varices and the rate of bleeding recurrence. Results o seu diâmetro no pré e pós-operatório precoce e
tardio. A comparação entre a queda de pressão
late post-operative varices caliber when compared the pre-operative data was observed portal e as taxas de ressangramento, também
despite an increase in diameter during follow-up that was controlled by endoscopic therapy.
Conclusion evidenciar se apenas a terapia endoscópica, ou
variceal calibers when comparing pre-operative and early or late post-operative diameters. operações menos complexas poderão controlar o
The comparison between the portal pressure drop and the rebleeding rates was also not sangramento das varizes.

HEADINGS: Schistosomiasis mansoni. Portal hypertension. Surgery. Portal pressure.

Esophageal and gastric varices.
instagram.com/revistaabcd/ twitter.com/revista_abcd facebook.com/Revista-ABCD-109005301640367 linkedin.com/company/revista-abcd

From 1Santa Casa de São Paulo, Faculdade de Ciências Médicas, Department of Surgery – São Paulo (SP), Brazil; 2Universidade Federal de Pernambuco, Hospital
www.facebook.com/abcdrevista www.instagram.com/abcdrevista www.twitter.com/abcdrevista
Universitário, Department of Surgery – Recife (PE), Brazil; 3Santa Casa de Misericórdia de São Paulo, Department of Surgery – São Paulo (SP), Brazil; 4Universidade
de São Paulo, Faculty of Medicine, Gastroenterology Department – São Paulo (SP), Brazil; 5Santa Casa de São Paulo, Faculdade de Ciências Médicas – São Paulo (SP),
Brazil; 6Universidade
Trabalho Estadual
realizado no 1Serviço dede Londrina,
Cirurgia GeralDepartment of Surgery,
e Aparelho Digestivo, Digestive System
Departamento Surgery
de Clínica – Londrina
Cirúrgica, (PR),de
Faculdade Brazil; 7
Universidade
Medicina, Federal
Universidade dode
Federal Paraná,
Goiás,Faculdade de
Goiânia, GO,
Medicina
Brasil; 2 de de
Serviço Curitiba, Department
Endoscopia, Hospitalof Surgery
das Clínicas–eCuritiba (PR), Brazil.
Departamento de Gastroenterologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil; 3Serviço de
Cirurgia do Fígado, Hospital das Clínicas e Departamento de Gastroenterologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil
How to cite this article: Kassab P, Ferraz AAB, Mitidieri ACH, Berti LV, Santo MA, Szego T, et al. The growing evidence of the relationship between obesity and cancer
and the
Como citarrole
esseofartigo:
bariatric surgery.
de Biase ABCDWB,
Silva-Neto ArqQuirese
Bras Cir Dig.
C, De 2024;37e1838.
Moura EGH, Coelhohttps://doi.org/10.1590/0102-6720202400044e1838.
FF, Herman P. A queda da pressão portal após desvascularização esofagogástrica e esplenectomia
Correspondence: Financial source: None
/10.1590/0102-672020210001e1581
Paulo Kassab. Conflict of interests: None
Email: [email protected] Received: 09/24/2024
Correspondência:
Accepted: 10/02/2024
Walter De Biase da Silva Neto
Preprint:10/28/2024
E-mail: [email protected]; Recebido para publicação: 17/09/2020
Editorial Support: National Council for Scientific
[email protected] andpublicação:
Aceito para Technological Development (CNPq).
14/12/2020

ABCD Arq Bras Cir Dig 2021;34(2):e1581 1/4

1/8
REVIEW ARTICLE - POSITION PAPER

SUMMARY OF THE MAIN men in the U.S. attributed to overweight or obesity61. In the
United Kingdom (UK), overweight and obesity were the second
RECOMMENDATIONS most common preventable causes of cancer, accounting for
6.3% of all cases in 2015. The proportion was higher in women
• Obesity is recognized as a significant risk factor for (7.5%) than in men (5.2%), with the highest rates observed in
various types of cancer. Scotland (6.8%) and the lowest in Wales (5.4%). The type of
• Although the incidence of some types of cancer at cancer most strongly associated with overweight and obesity
different primary sites is decreasing due to specific prevention in women was uterine cancer (34.0%), while in men, it was
measures (screening programs, smoking cessation), the incidence esophageal cancer (31.3%)9.
of neoplasms in the young population shows a significant The cause-and-effect relationship between obesity
increase associated with obesity. and cancer seems to be even more important8. Although the
• Bariatric surgery has been shown to significantly lower incidence of certain types of cancer at various primary sites is
the risk of developing obesity-associated cancers, which are decreasing due to specific prevention measures (e.g., screening
linked to metabolic dysregulation, chronic low-grade systemic programs, smoking cessation), the incidence of neoplasms in
inflammation, and hormonal alterations such as elevated insulin younger populations has shown a significant increase associated
and sex hormone levels. 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
INTRODUCTION (BMI) and certain types of cancer. Of the more than 5 million

T
individuals, 166,955 developed cancers. BMI was associated
he worldwide increase in obesity has been clearly with 17 of the 22 types of cancer, though the effects varied
observed. Kaidar-Person et al., back in 2011, stated that substantially by site. Each 5 kg/m2 increase in BMI was linearly
the 21st century was dealing with 2 major epidemics: associated with the incidence of uterine, cervical, thyroid,
obesity and cancer33. The prevalence of obesity in the United and leukemia cancers. High BMI was also associated with
States (U.S.) increased from 30.5 to 41.9% between 2000 and liver, colon, ovarian, and postmenopausal breast cancer in
2020, while the prevalence of severe obesity increased from general (all p<0.0001), with these effects varying according
4.7 to 9.2% during the same period64. Another study found that to individual characteristics22,36. It is estimated that 41% of
the incidence of obesity increased by 18% between 2013 and uterine cancers and 10% or more of gallbladder, kidney,
2017 compared to 2009 to 201342. Obesity-related conditions, liver, and colon cancers could be attributed to excess weight.
including heart disease, stroke, type 2 diabetes, and certain A 1 kg/m2 increase in BMI across the population could result
types of cancer, are among the leading causes of premature in 3,790 additional cancer cases per year in the UK7.
death and are preventable12. A 2015 study reported the risk of cancer attributable to
Additionally, projections published in 2019 suggest that obesity by gender: in women, around 30% for breast and uterine
by 2030, nearly 1 in 2 adults in the U.S. will have obesity, with cancers, around 10% for colon, rectum, and gallbladder cancers,
severe obesity becoming increasingly prevalent69,72. In the young 8.8% for kidney cancer, 3.4% for pancreas cancer, and 1.2% for
population, the 2023 guidelines from the American Academy esophageal cancer. In men, obesity was responsible for over
of Pediatrics reported that the percentage of U.S. children and 50% of colon and rectal cancers, 24.8% of kidney cancers, and
adolescents affected by obesity has more than tripled, rising around 10% for pancreatic and esophageal cancers4.
from 5% in 1963–1965 to 19% in 2017–201828,69. In addition to these types of cancer, other neoplasms
In Brazil, evidence indicates a significant increase in the associated with overweight and obesity include meningiomas,
prevalence of obesity over recent decades. A systematic review thyroid cancer, multiple myeloma, ovarian cancer, liver cancer,
and meta-analysis by Kodaira et al. found that the pooled and esophagogastric junction cancer. From 1995 to 2014, the
prevalence of obesity in Brazilian adults increased by 15% from incidence of obesity-related neoplasms among adults aged
1974–1990 to 2011–2020. This trend was observed in both 25–49 years increased significantly in 6 types of cancers: multiple
men and women across almost all periods34. Similarly, Estivaleti myeloma, colorectal, uterine, gallbladder, kidney, and pancreatic
et al. reported that the prevalence of obesity in Brazilian adults cancer. This association was more evident in women, as described
rose from 11.8% in 2006 to 20.3% in 2019, with projections in a 17-year study (January 2000 to December 2016), which
suggesting that obesity may affect 29.6% of adults by 2030. reported a shift in the age distribution of obesity-associated
This study also highlighted that women, black and other minority cancers, with 70.3% of patients being female. In fact, a BMI
ethnicities, and individuals with lower educational attainment greater than or equal to 30 corresponds to an 86% increase
are particularly at risk24. in the relative risk of colorectal cancer in young women, with
Several medical conditions are associated with obesity, the risk increasing by 18% for every 5-unit rise in BMI, even in
including heart disease, hypertension, stroke, type 2 diabetes, women with no family history of this type of cancer41.
metabolic syndrome, and certain cancers71. These are among the In an interesting review article, Pati et al. focused on the
leading causes of preventable premature death. The estimated epidemiology and relationship between obesity and cancer.
annual medical cost of obesity in the U.S. was nearly $173 They concluded that around 4 to 8% of all cancers can be
billion (in 2019 dollars), with medical costs for obese adults attributed to obesity, which is now recognized as a risk factor
being $1,861 higher than for people at a healthy weight60. for several types of cancer, including postmenopausal breast,
Other studies have shown that the cost of inpatient surgical liver, gallbladder, pancreas, colon and rectum, endometrial,
procedures, both oncologic and benign, abdominal and non- kidney, and esophageal cancer. They also noted that excess
abdominal, is higher in obese patients56. body fat resulted in an increased risk of approximately 17% in
cancer-specific mortality46.
Evidence of the relationship between obesity and cancer A large cohort study in Spain, involving more than 2.5
Obesity is recognized as a significant risk factor for various million individuals from 2009 to 2018, analyzed individuals over
types of cancer. According to the American Cancer Society, 45 years of age who were cancer-free in 2009. After 9 years of
excess body fat contributes substantially to cancer risk, with follow-up, 225,396 participants were diagnosed with cancer.
approximately 10.9% of cancer cases in women and 4.8% in This analysis demonstrated that longer duration and higher

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

degrees of obesity, particularly in younger individuals and changes in the gut microbiome and adipokine pathways further
those who became overweight or obese during early adulthood, contribute to cancer risk30,32,59,62.
increased the risk of 18 types of cancer, including leukemia One hypothesis is that adipose tissue acts as an organ
and non-Hodgkin lymphoma. Among never-smokers, head capable of releasing enzymes and other chemical mediators,
and neck and bladder cancers, not yet recognized as obesity- such as estrogens, whose increase results from heightened
related cancers in the literature, were also linked to obesity. aromatase activity in adipose tissue50. Obesity also impacts the
The authors emphasized the importance of including obesity tumor microenvironment by modulating immune cell infiltration,
prevention strategies in public health programs49. influencing cancer progression and response to therapy15.
In summary, according to the literature, increased body Therefore, the pathophysiology of the relationship between
weight and obesity are related to at least 13 types of cancer, 6 obesity and cancer is quite complex and not yet fully understood,
of which are located in the digestive system (Table 1). as it involves two multifactorial conditions encompassing genetic,
The relationship between BMI and the risk of developing environmental, and social factors in a highly interconnected
and dying from cancer is so direct that it is estimated that, in a manner. However, several obesity-related changes have been
hypothetical situation where the American population did not shown to influence carcinogenesis, including hyperinsulinemia,
exceed a BMI of 25 kg/m2, 90,000 fewer cancer-related deaths elevated leptin levels, chronic inflammation, oxidative stress,
would occur each year in the U.S.7,11,70. HIF-1α activation, cytokine secretion, DNA methylation, visceral
The mechanisms linking obesity to cancer are multifactorial. adipose dysfunction, release of adiponectin, exosome miRNA
Obesity is associated with metabolic dysregulation, chronic release, and changes in the metabolism of sex hormones74.
low-grade systemic inflammation27, and hormonal changes, As for weight loss, studies have shown a reduced risk of
including elevated insulin and sex hormones, which can promote breast, endometrial, colorectal, and prostate cancers in patients
carcinogenesis. Increased circulating estrogens, tumor cell growth who lost weight. A large prospective study with postmenopausal
and migration, modification of the tumor microenvironment, and women showed that intentional loss of more than 5% of body
neoangiogenesis have also been implicated. Obesity induces a weight was associated with a lower risk of obesity-related
variety of systemic changes, including altered levels of insulin, neoplasms, though this effect was not observed when weight
insulin-like growth factor-1 (IGF-1), leptin, adiponectin, steroid loss was unintentional39,65. Lifestyle modifications could prevent
hormones, and cytokines, creating an environment that favors a substantial proportion of cancer cases. A study found that
tumor initiation and progression. Chronic low-grade inflammation, adherence to a healthy lifestyle — defined as non-smoking,
driven by adipose tissue dysfunction and macrophage infiltration, moderate alcohol consumption, maintaining a BMI between
is a hallmark of obesity and contributes to both cancer risk and 18.5 and 27.5, and engaging in regular physical activity — could
progression. Adipose tissue in obese individuals secretes a large prevent 25% of cancer cases in women and 33% in men9,16,51,63.
number of biologically active substances termed adipokines, Obesity negatively impacts all phases of cancer treatment,
which include pro-inflammatory cytokines like IL-6 and TNF-α. increasing the incidence of at least 13 types of cancer and
These adipokines can induce pathological alterations in insulin delaying diagnosis due to technical difficulties in the surgical
pathways and promote a pro-inflammatory state, both of which treatment, difficulties in accessing diagnostic methods, or
are linked to increased cancer risk. Additionally, obesity-related the stigma that obese patients face, which may discourage

Table 1 - Evidence of the relationship between high body mass index and types of cancer37.
Strength of evidence for a cancer-preventive effect of the absence of excess body fat according to the site or type of cancer
Location or type of cancer Strength of evidence in humans Relative risk of higher versus normal BMI (95%CI)
Esophagus adenocarcinoma Sufficient 4.8 (3.0-7.7)
Cardia Sufficient 1.8 (1.3-2.5)
Colorectal Sufficient 1.3 (1.3-1.4)
Liver Sufficient 1.8 (1.6-2.1)
Gallbladder Sufficient 1.3 (1.2-1.4)
Pancreas Sufficient 1.5 (1.2-1.8)
Breast, post-menopausal Sufficient 1.1 (1.1-1.2)
Uterus (body) Sufficient 7.1 (6.3-8.1)
Ovary Sufficient 1.1 (1.1-1.2)
Kidney (renal cell) Sufficient 1.8 (1.7-1.9)
Meningioma Sufficient 1.5 (1.3-1.8)
Thyroid Sufficient 1.1 (1.0-1.1)
Myeloma Sufficient 1.5 (1.2-2.0)
Male Breast Cancer Limited Not applicable
Prostate Cancer (fatal) Limited Not applicable
Diffuse Large B-cell Lymphoma Limited Not applicable
BMI: body mass index; 95%CI: 95% confidence interval. A five-point increase in BMI has an impact on the relative risk (RR) of several cancers associated with excess weight,
including cervical cancer (worldwide RR – 1.5), esophageal cancer (RR in Europe and North America – 1.48), liver cancer (European RR – 1.59), pancreatic cancer (RR in
Europe, Australia, and North America – 1.14), and stomach cancer (RR in Europe and North America – 1.31)67. Additionally, evidence suggests that obesity exacerbates
several aspects related to cancer survival, including quality of life, recurrence, progression, and prognosis, while also increasing the risk of a second primary neoplasm.
During cancer treatment itself, obesity is related to complications such as lymphedema in breast cancer and incontinence in prostate cancer following radical surgical
resection. Even in hematologic malignancies, such as multiple myeloma, patients with higher BMI face a higher risk of death31.

ABCD Arq Bras Cir Dig 2024;37:e1838 3/8

REVIEW ARTICLE - POSITION PAPER

them from seeking medical attention. Obesity also increases In 2017, another observational study with the impressive
therapeutic complications (surgeries, radiotherapy, chemotherapy, number of 18,355 operated patients, compared to more than
etc.) and adversely affects survival rates in cancer patients. 40,000 non-operated controls, revealed a significant decrease
It compromises quality of life, increases the likelihood of cancer in cancer mortality, with greater weight loss associated with
recurrence and progression, and raises the risk of developing lower mortality55.
new neoplasms10,11,25,57,66. A recent systematic review and meta-analysis of 32 studies
In conclusion, there seems to be sufficient evidence to link involving patients with obesity who underwent bariatric surgery
obesity to cancer. The question that follows is: does bariatric compared to controls managed with conventional treatment
surgery reduce cancer risk? analysis suggested that bariatric surgery was associated with a
reduced overall incidence of cancer (RR 0.62, 95%CI 0.46–0.84,
Does Bariatric Surgery reduce cancer risk? p<0.002), obesity-related cancer (RR 0.59, 95%CI 0.39–0.90,
Obesity surgery reduces the incidence of cancer. p=0.01), and cancer-associated mortality (RR 0.51, 95%CI
Bariatric surgery has been shown to significantly lower the 0.42–0.62, p<0.00001). For specific cancers, bariatric surgery was
risk of developing obesity-associated cancers, which are associated with a reduction in the future incidence of hepatocellular
linked to metabolic dysregulation, chronic low-grade systemic carcinoma (RR 0.35, 95%CI 0.22–0.55, p<0.00001), colorectal
inflammation, and hormonal alterations such as elevated insulin cancer (RR 0.63, 95%CI 0.50–0.81, p=0.0002), pancreatic cancer
and sex hormone levels. (RR 0.52, 95%CI 0.29–0.93, p=0.03), and gallbladder cancer
A systematic review and meta-analysis demonstrated that (RR 0.41, 95%CI 0.18–0.96, p=0.04), as well as female-specific
bariatric surgery is associated with a reduced overall incidence cancers, including breast cancer (RR 0.56, 95%CI 0.44–0.71,
of cancer (RR 0.62, 95%CI 0.46–0.84) and obesity-related cancer p<0.00001), endometrial cancer (RR 0.38, 95%CI 0.26–0.55,
(RR 0.59, 95%CI 0.39–0.90). Another study found that bariatric p<0.00001), and ovarian cancer (RR 0.45, 95%CI 0.31–0.64,
surgery was associated with a significantly lower incidence of p<0.0001). There was no significant reduction in the incidence of
obesity-associated cancer (adjusted HR 0.68, 95%CI 0.53–0.87) and esophageal, gastric, thyroid, kidney, prostate cancer or multiple
cancer-related mortality (adjusted HR 0.52, 95%CI 0.31–0.88)74. myeloma after bariatric surgery as compared to patients with
Additionally, a multi-center population-based study reported morbid obesity who did not have bariatric surgery. The authors
that the cumulative incidence of cancers among patients who concluded that bariatric surgery might decrease future overall
experienced obesity recurrence was significantly lower in the cancer incidence and mortality, particularly in relation to seven
bariatric surgery group compared to the nonsurgical control obesity-related cancers74.
group (HR 0.482, 95%CI 0.459–0.507). This protective effect Regarding cancers of the upper digestive tract, with the
extends to specific cancers such as breast, endometrial, and exception of colon cancer, hundreds of thousands of bariatric
colorectal cancers2,13. surgeries have been performed to date. However, a systematic
Other studies have shown that surgical treatment of review analyzing the relationship between bariatric surgeries
obesity is associated with reduced risks of neoplasms in and the reduction of digestive cancer specifically revealed that
general, hormone-dependent cancers (breast, endometrium, only a few cases of cancer after the operations were described.
and prostate), and obesity-related cancers (postmenopausal Therefore, there is no conclusive evidence supporting a correlation
breast, endometrium, and colorectal)40,54,68. between obesity surgery and upper gastrointestinal cancer23.
In summary, bariatric surgery not only aids in weight loss but Åkerström et al. evaluated 748,932 participants diagnosed
also significantly reduces the risk of developing various obesity- with obesity, of whom 91,731 underwent bariatric surgery,
associated cancers by mitigating the underlying metabolic and predominantly gastric bypass (n=70,176; 76.5%). The adjusted
inflammatory pathways that promote carcinogenesis. The benefits risk of esophageal cancer decreased over time after gastric
attributed to bariatric surgery in reducing cancer incidence also bypass, from 2.2 (95%CI 0.9–4.3) after 2 to 5 years to 0.6 (95%CI
extend to other aspects of cancer treatment, including improved <0.1–3.6) after 10 to 40 years. Gastric bypass patients also had
outcomes in adjuvant treatments (chemo and radiotherapy), a reduced risk of adenocarcinoma of the cardia compared with
lower recurrence rates, and increased overall survival. Therefore, non-operated patients with obesity (adjusted HR 0.6, 95%CI
there is substantial evidence that bariatric surgery positively 0.4–1.0 (0.98)), with point estimates decreasing over time.
affects the key pathophysiological mechanisms linking obesity Gastric bypass was followed by a strongly decreased adjusted
and cancer12. The mechanisms include reduction in insulin and risk of esophageal adenocarcinoma (HR 0.3, 95%CI 0.1–0.8) but
leptin levels, chronic inflammation, and oxidative stress, as well not of cardia adenocarcinoma (HR 0.9, 95%CI 0.5–1.6) when
as the restoration of sex hormone levels, especially estradiol. analyzed separately29.
Additionally, bariatric surgery has a significant impact on the Lazzati et al. showed that the incidence of esophagogastric
intestinal microbiome and serum proteomics60. cancer in patients undergoing bariatric surgery is statistically
In 2004, a study involving 1,035 patients who underwent lower when compared with a population that did not undergo
bariatric surgery, compared with a cohort of more than 5,000 the procedure. The incidence of esophageal-gastric cancer fell
non-operated patients, demonstrated a significant decrease in from 6.9 to 4.9 per 100,000 population per year, with a reduction
cancer cases. In those who underwent surgery, the incidence was in esophageal cancer from 2.3 to 1.5 and in gastric cancer from
2.03%, while in the non-surgical group, it was 8.49%, indicating 4.6 to 3.3 per 100,000 population per year38.
that bariatric surgery reduced cancer incidence fourfold. There was The association between upper digestive tract cancers after
also a large decrease in the number of hospitalizations for bariatric surgery remains controversial, as several procedures
cancer: 54.95/1,000 person-years in the non-operated group can increase the incidence of pre-neoplastic conditions in the
versus only 11.80 in the operated group16. In the same year, an esophagus58. A French national study evaluated the incidence
epidemiological evaluation of 15,850 patients, 7,925 of whom of colorectal cancer by comparing nearly 2 million individuals
underwent surgery compared to an equal number of controls, who did not undergo bariatric surgery with more than 100,000
showed a 60% decrease in cancer mortality11. who did. The incidence of colorectal cancer has fallen by half
A few years later, a prospective, controlled analysis in the patients subjected to bariatric surgery5.
carried out in Sweden, involving more than 4,000 patients, In the Surgical Procedures and Long-term Effectiveness in
about half of whom underwent bariatric surgery compared to Neoplastic Disease Incidence and Death (SPLENDID) matched
controls, revealed the occurrence of 47 cases of cancer in the cohort study, adult patients with a BMI of 35 or greater who
non-operated group compared to 29 in the operated group61. underwent bariatric surgery at a U.S. health system between

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

2004 and 2017 were included73. Patients who underwent bariatric patients undergoing SG varies widely in the literature. Dantas
surgery were matched in a 1:5 ratio with patients who did not et al., in an endoscopic evaluation with more than 5 years of
undergo surgery for their obesity, resulting in a total of 30,318 follow-up, did not identify any cases of Barrett’s esophagus
patients. Bariatric surgery (n=5053) included Roux-en-Y gastric in their case study18. In summary, while sleeve gastrectomy
bypass (RYGB) and sleeve gastrectomy (SG). During follow-up, is associated with a reduced overall cancer incidence, there
96 patients in the bariatric surgery group and 780 patients is a notable concern for esophageal cancer due to increased
in the nonsurgical control group had an incident obesity- GERD and Barrett’s esophagus. Therefore, SG is generally
associated cancer (incidence rate of 3.0 events vs. 4.6 events, lower for most cancer types, vigilance for esophageal cancer
respectively, per 1,000 person-years). The  cumulative incidence remains necessary.
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%) Roux-en-Y gastric bypass
in the nonsurgical control group (absolute risk difference, The creation of an excluded gastric chamber in this
2.0% [95%CI 1.2–2.7%]; adjusted HR 0.68 [95%CI 0.53–0.87], type of surgery raises concerns mainly due to the difficulty
p=0.002, p<0.05). Cancer-related mortality occurred in 21 in accessing the excluded stomach. Some studies, in which
patients in the bariatric surgery group and 205 patients in the the excluded chamber was accessed through double-balloon
nonsurgical control group (incidence rate of 0.6 events vs. 1.2 endoscopy, showed an incidence of atrophic gastritis of 14.3%,
events, respectively, per 1,000 person-years). The cumulative metaplasia in 11.4%, and H. pylori presence in 20% of cases. In
incidence of cancer-related mortality at 10 years was 0.8% addition to the changes mentioned, there appear to be changes
(95%CI 0.4–1.2%) in the bariatric surgery group and 1.4% in the microenvironment that may predispose to oncogenic
(95%CI 1.1–1.6%) in the nonsurgical control group (absolute molecular mutations48,52,53.
risk difference, 0.6% [95%CI 0.1–1.0%]; adjusted HR 0.52 [95%CI The incidence of gastric cancer after RYGB is rare but
0.31–0.88], p=0.01, p<0.05). The authors concluded that, among has been documented in the medical literature. According
adults with obesity, bariatric surgery compared with no surgery to a systematic review by Chemaly et al., the occurrence of
was associated with a significantly lower incidence of obesity- gastroesophageal cancer post-RYGB is primarily reported through
associated cancer and cancer-related mortality2. case studies, with 27 out of 44 cases of gastroesophageal cancer
occurring in the gastric tube after RYGB13. Another systematic
Does the bariatric surgery technique — Roux-en-Y review by Dong et al. identified 21 cases of remnant gastric
gastric bypass, sleeve gastrectomy, or single anastomosis cancer after RYGB, with a median time to diagnosis of 11
mini gastric bypass — influence the risk of cancer after years postoperatively20. Additionally, Doukas et al.21 reported
the operation? an increasing trend of gastric cancer cases in the excluded
Bariatric surgery has become a widely performed procedure stomach post-RYGB, with 77% of these cancers diagnosed at
globally, with approximately 1 million surgeries estimated to an advanced stage13,20,21.
occur each year. Among the procedures performed, SG and In summary, while the exact incidence rate is not well-
RYGB account for approximately 80% of surgeries performed defined due to the rarity and the nature of case reports,
in the U.S. Mini gastric bypass (OAGB) is another technique available data suggest that gastric cancer can occur in the
that has been gaining a lot of attention and has a growing remnant stomach or gastric tube after RYGB, typically many
number of followers, becoming the most performed procedure years postoperatively. Although rare, this warrants awareness
in some countries17,43. and long-term surveillance in high-risk patients.
These three procedures raise some concerns regarding
potential carcinogenic characteristics. Specifically, SG is associated Mini gastric bypass
with a higher incidence of reflux, esophagitis, and Barrett’s Despite being a relatively recent procedure in the arsenal
esophagus. RYGB raises concerns due to the exclusion of the of surgical treatment for obesity, OAGB brings with it a problem
stomach, while OAGB is linked to alkaline reflux. The major already faced in gastrectomy surgery with B-II reconstruction,
concern among these issues would be the development of which is alkaline reflux. Alkaline reflux can cause changes in
esophageal cancer in this population47. the gastric mucosa and esophageal mucosa, with some studies
reporting its presence in 21% of cases, potentially increasing
Sleeve gastrectomy cancer incidence35. Gastroesophageal cancer appears to be the
The incidence of cancer after SG has been a subject of most commonly reported type of cancer following mini gastric
investigation in several studies. According to a systematic bypass (OAGB), although the incidence is not significantly higher
review and meta-analysis, bariatric surgery, including SG, is compared to RYGB. According to a systematic review and meta-
associated with a significant reduction in overall cancer incidence analysis by Chemaly et al., 37.5% of gastroesophageal cancers
compared to nonsurgical treatment. Specifically, the odds ratio after OAGB were located in the gastric tube, compared to 61%
(OR) for cancer incidence in patients undergoing SG was 0.44 after RYGB, with an odds ratio of 0.38, indicating no significant
(95%CI 0.27–0.70)14. increase in cancer occurrence in the gastric tube after OAGB
However, there are specific concerns regarding the risk of compared to RYGB13.
esophageal cancer post SG due to the potential for increased The arguments that bile reaches the terminal ileum diluted
gastroesophageal reflux disease (GERD) and consequently are unfounded, since physiology studies show that 90% of
esophagitis and risk of Barrett’s esophagus. One study found bile reaches that location intact, where it is later reabsorbed.
that the crude incidence rate of esophageal cancer in patients This technique should be used with great caution, since the
undergoing reflux-prone procedures like SG was higher than potential harmful effects, such as the development of cancer in
in nonsurgical controls, but this difference was not significant the gastric remnant and esophagus, may only become apparent
after adjusting for confounders3. 30 to 40 years postoperatively1,6,19,35.
Some case studies reported an incidence of approximately In conclusion, the incidence of cancer in patients undergoing
18% for Barrett’s esophagus, 52% for the need for stomach- bariatric surgery is low. Large systematic reviews and meta-
protective medication, and 41% for esophagitis within 5 analyses list a small number of cases relative to the total number
years of evolution58. The shape of the gastric tube appears to of surgeries performed worldwide, demonstrating that the benefits
influence the incidence of reflux, especially when it is made of surgery, in terms of cancer incidence reduction, outweigh
in a twisted manner26. However, the incidence of Barrett’s in the risks, regardless of the surgical technique employed43-45.

ABCD Arq Bras Cir Dig 2024;37:e1838 5/8

REVIEW ARTICLE - POSITION PAPER

Therefore, while the incidence of cancer in patients undergoing 14. Chen ZW, Jin T, Liang PP, Li ZD, He FJ, Chen ZH, et al. Incidence
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