Keywords
BMI - endometrial cancer - obesity - surgery
Introduction
Obesity is a well-established risk factor for developing endometrial cancer, more
than any other cancer type.[1] Insulin resistance is responsible for releasing growth factors for cellular proliferation,
higher levels of interleukins, tumor necrosis factors, and adipokines causing an obesity-related
proinflammatory state, and high estrogen levels through increased aromatase activity
in adipose tissue are proposed as contributors to the increased risk of developing
endometrial cancer.[2] Endometrial cancer is known as a hormone-dependent type of cancer. Obesity affects
hormone metabolism by increasing the aromatization of androstenedione to estrone in
adipose tissues and causes an increase in the circulating levels of estrogen, creating
a favorable environment for tumor formation.[3] The incidence of endometrial cancer is projected to rise as women's obesity rates
continue to rise. In a study by Ward et al.[4] with 33,232 endometrial cancer patients, it was reported that the 10-year mortality
due to endometrial cancer was associated with death due to cardiovascular disease.
It was the most common reason related to morbid obesity. Obesity and endometrial cancer
have been linked in numerous research studies.[5]
[6]
[7]
[8] Although excess body fat is a significant risk factor for endometrial cancer, its
impact on survival is unclear.
Surgical procedures for treating endometrial cancer are hysterectomy, bilateral salpingo-oophorectomy,
and pelvic and para-aortic lymphadenectomy. Many studies have established that obese
patients are at a higher risk of perioperative and postoperative complications, such
as longer hospital stay and increased morbidity, even when minimally invasive surgeries
or laparotomy are performed.[9]
[10]
[11] Obesity is defined by the World Health Organization (WHO) by using the body mass
index (BMI) cutoff point of > 30 kg/m2, which is calculated as weight in kg divided by height in meters squared. Body mass
index has significant public health importance because it correlates well with morbidity
and/or mortality and endometrial cancer risk. Although surgery is the standard procedure
in the staging and treatment of endometrial cancer, obesity may affect surgical outcomes
due to its accompanying comorbid disorders. The impact of morbid obesity on endometrial
cancer patients' survival is crucial as postoperative complications among obese women
seem to be higher than among their normal-weight counterparts.[12]
The evaluation of the effects of obesity on surgical outcomes may help decrease morbidity
and improve prognosis in patients with endometrial cancer. However, there are insufficient
data in the current literature that explain the impact of morbid obesity on the surgical
outcomes of endometrial cancer and compare it with the endometrial cancer patients
with normal weight. This study aims to determine the link between BMI and surgical
outcomes in obese endometrial cancer patients.
Methods
Participants
This study was performed in accordance with the ethical standards of the Helsinki
declaration. Ethical approval was obtained for this retrospective, cross-sectional
study by the ethics committee of the University of Health Sciences, Sisli Hamidiye
Etfal Education and Research Hospital. Informed consent was obtained routinely. We
reviewed the records of patients older than 18 years with endometrial cancer admitted
to our hospital's gynecologic oncology department within a 72-month period from 2014
to 2020.
Inclusion and Exclusion Criteria
The inclusion criteria are listed below:
-
Patients with pathologically proven endometrial cancer.
-
Patients older than 18 years.
-
A detailed medical record including patient's history, clinical findings, laboratory
and pathology test results, treatment outcomes, etc.
The exclusion criteria are as follows:
-
Patients without a definite pathologic diagnosis
-
Patients with secondary cancer.
-
Patients with endometrial cancer who were treated conservatively.
Data Collection
The patients' demographic characteristics (age, sex), weight, height and body mass
index (BMI), surgical procedure (total hysterectomy-bilateral salpingo-oophorectomy
[via laparotomy or laparoscopy] with or without pelvic and para-aortic lymphadenectomy),
duration of hospital stay, lymph node involvement, the average number of lymph nodes
removed, routine biochemical examination, preoperative evaluation and preparation
for anesthesia, perioperative and postoperative complications, and follow-up data
were recorded. The patients were divided into three groups based on their BMI. Body
mass index [kg/height (m)]2 was calculated and classified according to the World Health
Organization (WHO) guidelines. Thus, patients with BMI < 25 were identified as normal
weight, patients with BMI from 25 to 30 were accepted as overweight, and those with
BMI ≥ 30 kg/m2 were identified as obese. Later, we compared the variables mentioned above and surgical
outcomes according to patients' BMI.
Statistical Analysis
Data were analyzed using the IBM SPSS Statistics for Windows, version 23.0 software
(IBM Corp., Armonk, NY, USA). Descriptive statistics (mean, standard deviation, frequency,
and percentage) were used for the demographic and clinical characteristics. The analysis
of variance (ANOVA) test followed by Tukey multiple comparison methods among these
three BMI groups was performed. The categorical variables were compared using the
Chi-squared test. A p-value of < 0.05 was considered to be statistically significant.
Results
During the 6-year period, 142 patients were operated on for endometrial cancer. These
surgical procedures were performed via laparotomy or conventional laparoscopy, which
were performed at our hospital's gynecologic oncology unit. The mean age of the subjects
was 60.52 ± 9.89 years (range, 18–82 years). The in-hospital mortality rate was 0%.
The number of patients with BMI < 25 (normal weight) was 42 (29.6%), those with BMI
from 25 to 30 (overweight) were 55 (38.7%), and patients with BMI > 30 (obese) were
45 (31.7%).
The demographic and clinical characteristics of patients with a comparison between
the three groups are demonstrated in [Table 1]. There was no significant difference between the groups regarding age, surgical
procedures, presence of menopause, intraoperative bleeding, preoperative health status
(ASA), the mean duration of hospital stay, CA125 level, and the number of metastatic
nodes. However, duration of surgery, the number of total nodes and non-metastatic
nodes differed significantly and were higher in the group of patients with BMI > 30
(p = 0.02, p = 0.00, and p = 0.00, respectively). [Table 2] shows the posthoc Tukey test results of these variables.
Table 1
Demographic and clinical characteristics of patient groups
|
Variables
|
BMI < 25
(normal weight)
|
BMI from 25 to 30 (overweight)
|
BMI > 30
(obese)
|
P-value
|
|
Number of patients
|
42 (29.6%)
|
55 (38.7%)
|
45 (31.7%)
|
−
|
|
Age
|
61.00 ± 11.15
|
60.00 ± 10.56
|
60.44 ± 10.42
|
0.901
|
|
Surgical procedure
|
|
Laparotomy
|
25 (17.6%)
|
31 (21.8%)
|
26 (18.3%)
|
0.952
|
|
Laparoscopy
|
17 (12.0%)
|
24 (16.9%)
|
19 (13.4%)
|
|
Menopause
|
|
Premenopause
|
7 (4.9%)
|
10 (7.0%)
|
9 (6.3%)
|
0.922
|
|
Postmenopause
|
35 (24.6%)
|
45 (31.7%)
|
36 (25.4%)
|
|
Estimated blood loss (ml)
|
253.81 ± 89.25
|
263.64 ± 108.77
|
273.33 ± 111.88
|
0.685
|
|
Surgery time (minutes)
|
142.14 ± 25.50
|
158.27 ± 36.69
|
169.89 ± 44.18
|
0.002
|
|
ASA
|
1.62 ± 0.66
|
1.49 ± 0.57
|
1.47 ± 0.59
|
0.451
|
|
Duration of hospital stay (days)
|
5.64 ± 1.91
|
5.16 ± 1.75
|
5.56 ± 2.03
|
0.404
|
|
Pre-CA125
|
23.98 ± 34.58
|
48.58 ± 139.33
|
54.16 ± 132.77
|
0.436
|
|
Number of total dissected
pelvic lymph nodes
|
19.10 ± 10.62
|
23.47 ± 11.74
|
34.84 ± 14.31
|
0.000
|
|
Metastatic nodes
|
1.21 ± 2.08
|
1.05 ± 2.38
|
0.93 ± 2.06
|
0.837
|
|
Non-metastatic nodes
|
18.00 ± 10.76
|
22.42 ± 12.03
|
33.91 ± 13.90
|
0.000
|
Table 2
The posthoc comparisons using Tukey's HSD
|
Factor
|
Pairwise Comparison
|
P-value
|
|
Surgery time (minutes)
|
Normal weight vs Overweight
|
0.083
|
|
Overweight vs Obese
|
0.256
|
|
Normal weight vs Obese
|
0.002
|
|
Total nodes
|
Normal weight vs Overweight
|
0.196
|
|
Overweight vs Obese
|
0.000
|
|
Normal weight vs Obese
|
0.000
|
|
Non-metastatic
|
Normal vs Overweighted
|
0.190
|
|
Overweight vs Obese
|
0.000
|
|
Normal weight vs Obese
|
0.000
|
Patient complaints at the time of admission and complications to our outpatient clinic
according to patient groups were summarized in [Table 3]. The reasons for patients' admissions were vaginal bleeding, abdominal pain, itching,
and routine examination. The symptoms for hospital admission did not differ according
to patients' BMI. Anemia (5.6%), fever (1.4%), intestinal injury (0.7%), deep vein
thrombosis (0.7%), fascial dehiscence (0.7%), rupture of veins (0.7%), surgical site
infections (0.7%), and urinary infection (2.8%) were common perioperative (intraoperative
and postoperative) complications among all patients. There was no significant difference
between the groups according to the perioperative complications.
Table 3
Perioperative data and complications according to patient groups
|
Clinical features
|
BMI < 25
(normal weight)
|
BMI from 25–30 (overweight)
|
BMI > 30
(obese)
|
Total
(n)
|
|
Symptoms for hospital admission
|
Bleeding
|
37 (26.1%)
|
38
(26.8%)
|
31 (21.8%)
|
106 (74.6%)
|
|
Abdominal pain
|
0 (0.0%)
|
1 (0.7%)
|
1 (0.7%)
|
2 (1.4%)
|
|
Itching
|
0 (0.0%)
|
1 (0.7%)
|
1 (0.7%)
|
2 (1.4%)
|
|
Routine examination
|
5 (3.5%)
|
15 (10.6%)
|
12 (8.5%)
|
32 (22.5%)
|
|
Perioperative
complications
|
Atrial fibrillation
|
1 (0.7%)
|
0 (0.0%)
|
0 (0.0%)
|
1 (0.7%)
|
|
Anemia
|
3 (2.1%)
|
2 (1.4%)
|
3 (2.1%)
|
8 (5.6%)
|
|
Fever
|
0 (0.0%)
|
1 (0.7%)
|
1 (0.7%)
|
2 (1.4%)
|
|
Intestinal injury
|
0 (0.0%)
|
0 (0.0%)
|
1 (0.7%)
|
1 (0.7%)
|
|
Deep vein thrombosis
|
0 (0.0%)
|
0 (0.0%)
|
1 (0.7%)
|
1 (0.7%)
|
|
Fascial dehiscence
|
0 (0.0%)
|
0 (0.0%)
|
1 (0.7%)
|
1 (0.7%)
|
|
Rupture of the iliac vein
|
0 (0.0%)
|
1 (0.7%)
|
0 (0.0%)
|
1 (0.7%)
|
|
Bleeding of obturator vein
|
0 (0.0%)
|
1 (0.7%)
|
0 (0.0%)
|
1 (0.7%)
|
|
Urinary infection
|
1
(0.7%)
|
2
(1.4%)
|
1 (0.7%)
|
4
(2.8%)
|
|
Surgical site infections
|
0
(0.0%)
|
1
(0.7%)
|
0 (0.0%)
|
1
(0.7%)
|
|
None
|
37
(26.1%)
|
47
(33.1%)
|
37
(26.1%)
|
121
(85.2%)
|
Discussion
The current study aimed to demonstrate the surgical outcomes pertaining to the management
of endometrial cancer patients according to their BMI and to explore which variables
were significant in patient morbidity. Our statistical analysis demonstrated that
duration of surgery, number of total dissected pelvic lymph nodes, and non-metastatic
nodes were higher in endometrial cancer patients with obesity. Demographic, clinical,
and laboratory findings, such as patient's age, presence of menopause, blood loss,
preoperative health status, hospital stay, and CA125 levels, were not related to patients'
BMI. Moreover, our results indicate that surgical procedures which were performed
via laparotomy or laparoscopy had no significant relationship with the subjects' weight.
The symptoms for hospital admission did not differ according to patients' BMI. In
addition, perioperative complications did not significantly differ among patient groups.
Kokts-Porietis et al.[13] reviewed the studies that included estimated body fat with BMI to evaluate the relationship
between obesity and mortality among endometrial cancer survivors. They reported that
endometrial cancer survivors who were obese at the time of diagnosis had a higher
risk of cancer recurrence and all-cause death but not endometrial cancer-specific
mortality. In our study sample, the in-hospital mortality rate was also 0%, and we
suggest that elevated BMI might not be related to mortality in endometrial cancer.
In a retrospective study by Ward et al.,[4] the authors evaluated the causes of death among women with endometrial cancer. They
found that cardiovascular diseases were the leading reason of death from endometrial
cancer. Although the causes of death in patients with endometrial cancer were not
the main concern of the current study, we found that the patients with BMI > 30 had
a lower preoperative health status, which shows the preoperative chronic medical conditions.
In a review by Onstad et al.,[14] the authors suggested that operating on obese patients was more difficult than on
normal-weight patients with endometrial cancer due to technical aspects of the surgery
that could affect visualization. In the current study, we detected that the duration
of surgery in the obese patient group was longer than in the normal-weighted and overweight
patients, which supports the researchers' conclusion. However, obesity did not significantly
impact the surgical procedures in the three groups of this study. Similar to our results,
Gabala et al.[10] reported that obesity did not affect the surgical techniques in endometrial cancer.
In a study by Erkanli et al.,[15] they investigated the effect of BMI on clinical and pathologic features and surgical
morbidity in 42 patients with endometrial cancer. The number of participants was higher
in the current study, and our findings support their results. They also did not find
any difference in length of hospital stay and intraoperative or postoperative complications.
It can be concluded that the surgical approach might be performed safely in morbidly
obese endometrial cancer patients.
There are mixed results in the retrospective studies regarding the impact of obesity
on operative complications in the current literature. Similar to previous studies,
we detected that postoperative complication rates did not differ significantly between
the obese and non-obese patient groups.[10]
[11]
[15]
[16] On the contrary, Bouwman et al.[17] reported that elevated BMI was associated with an increased risk of postoperative
surgical complications in morbidly obese patients who underwent laparotomy. Patients'
characteristics may explain these different results, and they also depend on surgeons'
experience and type of equipment. Only 14.8% of our patient sample had suffered from
perioperative complications. Arrhythmia, blood loss, high fever, intestinal injury,
deep vein thrombosis, fascial dehiscence, bleeding of veins, urinary infection and
surgical site infections were detected. Even though obesity did not affect the course
of surgery in this study, we believe that when considering endometrial cancer surgery,
it is critical to recognize these complications to avoid them.
Endometrial cancer continues to increase in incidence and mortality. Obesity is now
recognized as an independent risk factor for endometrial cancer, accounting for more
than half of all cases. Women diagnosed with endometrial cancer with a high BMI have
a higher probability of morbidity. For this reason, obesity may adversely affect surgery
outcomes. Therefore, we think that more studies determining this relationship between
endometrial cancer and obesity are needed in the medical literature.
This study has some limitations. First, only eligible data in the record were assessed
because of its retrospective nature. Second, the study was performed at a single center.
In addition, all the patients were operated on by the same experienced surgeons. However,
a long-term period and a relatively high number of participants are the strengths
of this study.
Conclusion
In conclusion, our findings indicate that increased BMI is related to higher surgery
time in patients with endometrial cancer. However, obesity did not impact surgical
outcomes such as blood loss, duration of hospital stay, and complication rates. Moreover,
mortality rates in endometrial cancer were not affected by BMI. Endometrial cancer
surgery can be safely and adequately managed among patients with obesity. Further
prospective studies evaluating the impact of obesity on long-term follow-up of endometrial
cancer surgery are warranted.
