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147
Sleeve Gastrectomy and Cancer
Sulaiman Almazeedi and Ahmed Al-Khamis
1 Obesity and Cancer
It is without question today that obesity is directly attributed to an increased
risk of developing cancer. In the European Union alone, approximately 70,000
out of the 3.5 million (2.0%) new cases of cancer each year are linked to overweight or obesity, while in the United States, that number is around 85,000 out
of 1.4 million (5.8%) [1, 2]. It was initially thought that obesity increased only
hormone-dependent cancers, such as post-menopausal breast cancer, endometrial
cancer, prostate and colon cancer, however evidence is proving day by day that the
effect is much broader. As of the evidence available today, an elevated body mass
index (BMI) has also been proven to be linked with pancreatic, gallbladder, esophageal, renal, and thyroid cancers, as well as leukemia and non-Hodgkin lymphoma
[3–6]. Large population-based studies from Austria, Sweden and Denmark have
proven this but showed variations in the effect’s obesity had on individual cancer
types in addition to differences in incidence across age groups and genders [3–5].
A meta-analysis by Renehen et al., which included 282,137 patients across four
continents, showed that a 5 kg/m2 increase in BMI was strongly associated with
an increase in the incidence of the aforementioned cancers [6]. Obesity related
cancer incidence was higher in men than in women for colon and rectal cancers
(p < 0·0001 and p = 0·003 respectively), and were higher in women than in men for
renal cancer (p = 0·004). Interestingly, the incidence of two cancer types (lung and
S. Almazeedi (*) · A. Al-Khamis
Jaber Al-Ahmed Al-Sabah Hospital, South Surra, Kuwait
e-mail: al_mazeedi@yahoo.com
A. Al-Khamis
e-mail: alkhamis.md@gmail.com
© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer
Nature Switzerland AG 2021
S. Al-Sabah et al. (eds.), Laparoscopic Sleeve Gastrectomy,
https://doi.org/10.1007/978-3-030-57373-7_17
149
S. Almazeedi and A. Al-Khamis150
esophageal squamous cell cancers) were found to be negatively associated with
obesity.
Beyond the fact that obesity increases the incidence of certain cancers, it is also
evident today that it is also linked to an increase in cancer mortality. In one of the
largest studies of its kind, a collaborative analysis of 57 papers from Europe and
North America of approximately 900,000 patients observed that for each 5 kg/m2
increase in BMI, there was on average 10% increase in cancer mortality (HR 1.10
[1.06–1.15]) [7]. In addition, the authors found the BMI range 22.5–25 kg/m2 to
have the lowest all-cause mortality among both genders.
2 Pathogenesis of Cancer in the Obese
The underlying mechanism behind what predisposes obese patients to developing
certain cancers remains a topic of much debate. Because of the wide range of cancer types and different physiology of each, it is difficult to group them together
and draw conclusions of causality.
However, most studies on the subject have given rise to theories that mostly
centered around diet, hormonal theories, and chronic inflammation.
The high-calorie “western diet” is infamous today for being a root cause behind
many diseases. There are innumerable studies observing the detrimental health
effects of such diet, with numerous meta-analyses proving a direct association
with breast, colon and prostate cancer [8–10]. In addition, most of these studies
also observed a reduction in cancer risk with a more prudent dietary pattern (i.e.
high in fruits, vegetables, and low in fat, cholesterol and processed food).
The western diet is also related to an increase in insulin production, which is
one of the culprits behind obesity and cancer in the hormonal theory [1]. Insulin
and insulin-like growth factor 1 (IGF-1) both play a complex role in the initiation
of cellular pathways that ultimately lead to promote cellular proliferation and possible tumor growth [11].
Sex hormones also play a role in linking obesity and cancer, with recent
evidence showing that the excess estrogen produced from aromatization in the
adipose tissue can lead to stimulation of cell division and subsequent carcinogenesis [1].
Finally, adipose tissue itself has been found to increase the overall state of
chronic inflammation by the release of the so-called adipokine hormones, a group
of pro-inflammatory cytokines. From the many adipokines identified to-date,
leptin is one of the most widely studied in the literature, with research linking
elevated levels to colon, breast, and even prostate cancer [12]. Although the underlying pathogenesis remains to be well-established, it is believed the long-standing
overall state of inflammation in obese patients results in overwhelming oxidative
stress and subsequent direct DNA damage.
Sleeve Gastrectomy and Cancer
151
3 Current Literature
Before the emergence of sleeve gastrectomy (SG) as one of the most common
bariatric surgery procedures, the two most common procedures were Roux-en-Y
gastric bypass (RYGB) and adjustable gastric banding (AGB). Despite the recent
surge in SG popularity, it remains a relatively new standalone bariatric operation,
and to this day RYGB remains the gold standard bariatric procedure. As a result,
there is a lack of extensive data in the literature with appropriate sample size that
specifically study SG and its association with cancer risk. Furthermore, many
studies pool all bariatric procedures together in their analysis without differentiating patients who had SG from other procedures, or divide surgeries broadly into
either restrictive or malabsorptive. Below, we provide a summary of the evidence
regarding studies that specifically included patients undergoing SG in their cohort.
Most of the available data observed the effects on colorectal cancer (CRC), and
will therefore form the bulk of this section.
4 Bariatric Surgery and Cancer Risk
One of the more recent papers is by Schauer et al. who conducted a large retrospective study of 22,198 subjects undergoing bariatric surgery (61% RYGB, 27%
SG, and 5.6% AGB) who were matched to 66,427 non-surgical obese subjects
[13]. After a mean follow-up of 3.5 years, 2,543 cancer incidents were identified. They found patients who underwent bariatric surgery were 33% less likely
to develop any cancer during follow-up (HR 0.67 [CI 0.60–0.74, p < 0.001]) compared with matched patients with severe obesity who did not undergo bariatric
surgery. These included postmenopausal breast cancer (HR 0.58 [CI 0.44–0.77,
p < 0.001]), colon cancer (HR 0.59 [CI 0.36–0.97, p = 0.04]), endometrial cancer
(HR 0.50 [CI 0.37–0.67, p < 0.001]), and pancreatic cancer (HR 0.46 [CI 0.22–
0.97, p = 0.04]).
5 Colorectal Cancer (CRC)
CRC is one of the most common cancers all over the world and studying the
relationship between SG and the risk of its development is of great importance.
Interestingly, the data is at times controversial, especially with regard to RYGB
versus SG as well as colon versus rectal cancer. A recently published systemic
review and meta-analysis investigating the effect of bariatric surgery on the risk
of developing CRC included seven large studies involving 1,213,727 individuals
[14]. With a mean duration of follow-up of more than 7 years it was observed that
patients who underwent bariatric surgery had a greater than 35% reduction in the
risk of developing CRC compared with obese non-operated individuals (RR 0.64
[CI 0.42–0.98]).
S. Almazeedi and A. Al-Khamis152
Arvani et al. analyzed the data of over one million patients within the United
Kingdom national health service (NHS), of whom 39,747 patients (3.9%) underwent bariatric surgery [15]. Overall, they reported almost half the surgeries were
a purely restrictive procedures while the other half had a combined restrictive
and malabsorptive procedure. Compared to the background general population,
they found no significant increase in CRC in patients undergoing obesity surgery
(SIR 1.26 [CI 0.92–1.71]), while obese patients who did not undergo bariatric
surgery had a significant increase likelihood of developing CRC (SIR 1.12 [CI
1.08–1.16]). Breaking down the results according to type of surgery showed no
significant difference between restrictive and combined restrictive and malabsorptive procedures and the risk of CRC.
6 CRC in RYGB Versus SG and AGB
Recent evidence has emerged regarding the increase in CRC risk among patients
undergoing specific types of bariatric procedures. Mackenzie et al. performed
a propensity match control study comparing 8,794 obese patients who had
SG, RYGB, or AGB to obese patients who did not have obesity surgery [16].
Predominantly malabsorptive procedures (RYGB) but not predominantly restrictive procedures (SG and AGB) were associated with over two-fold increase in the
risk of CRC (OR 2.63 [CI 1.17–5.95]). Their findings emulate the results reported
by the two Swedish studies by Derogar et al. and Ostlund et al. who reported a
two-fold increase in the risk of CRC after RYGB specifically [17, 18]. The reason RYGB, but not SG or AGB, was associated with increased risk of CRC was
hypothesized to be related to significant changes in the gut microbiome and the
increase in specific inflammatory markers promoting hyper-proliferation of bowel
mucosa following RYGB. Kant et al. also observed that putative mucosal biomarkers of colorectal cancer risk and mucosal pro-inflammatory gene expression
(pro-tumorigenic cytokine macrophage migratory inhibitory factor) were increased
at least three years after RYGB compared with preoperative values [19]. These
findings, contrary to previous assumptions, are likely secondary to malabsorptive
effects of the procedure and appear to be increased more prominently in the rectal
compared to colonic mucosa. This translates to potential higher risk of rectal cancer following the malabsorptive procedures such as RYGB but not necessary the
predominantly restrictive procedures such as SG.
7 Breast and Endometrial Cancers
Studies looking at trends in reduction of breast and endometrial cancers after
bariatric surgery seem to mimic those for CRC. In the United Kingdom NHS
study, there was a reported lower risk of breast cancer in operated patients compared to non-operated ones across both restrictive and combined restrictive and
malabsorptive procedures (SIR 0.76 [CI 0.62–0.92] and SIR 1.08 [CI 1.04–1.11]
Sleeve Gastrectomy and Cancer
respectively) [15]. In addition, the Mackenzie et al. propensity score study found
patients who had bariatric surgery (56.6% RYGB, 33.6% AGB, and 9.8% SG)
exhibited a decreased risk of hormone-related cancers (OR 0⋅23 [CI 0.18–0.30]).
This decrease was consistent for breast cancer (OR 0.25 [CI 0.19–0.33]) and endometrium cancer (OR 0.21 [CI 0.13–0.35]) [15]. In a study that included patients
who underwent RYGB, SG, and AGB, Linkov et al. collected blood samples of
107 obese female patients before and 6 months postoperatively [20]. They studied several biomarkers associated with endometrial cancer including insulin,
C-peptide, Leptin, adiponectin, C-reactive protein, and tumor necrosis factor
alpha. Interestingly, they reported normalization of the cancer markers in the
majority of their patients postoperatively.
153
8 SG and Gastro-esophageal Cancer
It has long been thought that the anatomical changes occurring around anastomotic sites in bariatric surgery predispose to neoplasia. This evidence came mostly
from studies looking at long-term effects of partial gastrectomies after peptic ulcer
surgeries [21]. The notion of whether or not this translates into bariatric surgery is
still a topic of much debate, with the main issue being lack of evidence due to the
scarcity of such cases. Most of the evidence is based solely on case reports, with
the focus being on malabsorptive surgeries mostly due to the bile reflux in the gastric pouch [22]. This trend however, is changing, and a few gastro-esophageal cancers have been reported now in post SG cases. In a review from 2019, a total of 37
papers were found from 1991 to 2018 reporting post-bariatric gastro-esophageal
cancers [23]. Of those, 19 cases occurred after gastric bypass procedures, 7 after
vertical banded gastroplasty, 7 after AGB, and 7 after SG. Interestingly, the cancer
cases reported after SG ranged in location from the distal esophagus to the antrum
of the stomach, which questions whether or not they occurred de nova or were
related to the actual surgery.
A recent finding that is gaining a lot of attention, however, is Barrett’s esophagus (BE) after SG. Thought to be secondary to the increased gastro-esophageal
reflux post-SG, a recent paper involving routine endoscopy post-SG observed an
18.8% prevalence of BE at least five years after SG [24]. Further research into the
subject is of vital importance to set future follow-up guidelines and insure optimal
and safe practice.
9 Conclusion
It is beyond any doubt that there exists a strong relationship between obesity and
the pathophysiology of cancer development. This relationship appears to translate
to an observed association between excess weight reduction and subsequent reduction in the risk of cancer. Bariatric surgery is today the most effective method of
achieving sustainable weight loss, but the heterogeneity in the mechanism this is
S. Almazeedi and A. Al-Khamis154
achieved across the different procedure types has yet to be explained in an optimal
way. SG being one of the relatively novel procedures to be utilized in managing
morbid obesity with increasing frequency, still lacks data differentiating it from
other techniques with regard to its effect on cancer development in obese patients.
More studies focusing on each surgical techniques’ outcomes rather than the
pooled analysis approach used by most studies is needed to explain the differences
in results observed today.
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155
Multidisciplinary Care Before and After Sleeve Gastrectomy
Mohammed Al Hadad
1 Introduction
Obesity is defined as a chronic progressive relapsing multifactorial neurobehavioral disease which results in excessive accumulation of body fat sufficient to impair
health and affect life expectancy [1]. The progressive relapsing and multifactorial
nature of the disease needs a multimodal life-long treatment approach. Bariatric
surgery is the only durable solution available at the time being with an acceptable success rate [2]. The success of bariatric surgery depends on many factors and
would require intervention from different specialties to maintain it and prevent and
manage possible complications.
Morbid obesity represents multiple challenges for medical, allied health, and
ancillary health care providers. Bariatric surgery is a behavioral surgery in some
aspects because of the fact that it helps the patients change their behavior by limiting the size of food portions, and more importantly, through the neuro-hormonal
changes that help the patient to “change their lifestyle and relationship with food”
which is more profound in the first year after surgery.
Management of the patient with obesity is a continuous process. It starts with
educating the patient about the nature of the disease, followed by discussing the
management plan, then providing guidance and motivational support that would
lead to lifestyle modification. All that happens before undergoing bariatric surgery, which will need life-long follow up. Weight loss is not the sole indicator of
success of bariatric surgery. Other factors like improvement or resolution of obesity related diseases and meeting the patient’s expectations are important factors
M. Al Hadad (*)
MD, FRCS Glasg, FACS, Head of Bariatric Surgery Department, Healthpoint Hospital,
Abu Dhabi, UAE
e-mail: more991@hotmail.com
© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer
Nature Switzerland AG 2021
S. Al-Sabah et al. (eds.), Laparoscopic Sleeve Gastrectomy,
https://doi.org/10.1007/978-3-030-57373-7_18
157