Change in abdominal obesity after colon cancer surgery – effects of left-sided and right-sided colonic resection

doi:10.21203/rs.3.rs-2963612/v1

Background

Excess abdominal visceral adipose tissue (VAT) is associated with metabolic diseases and poor survival in colon cancer (CC). We assessed the impact of different types of CC surgery on changes in abdominal fat depots.

Material and Methods

Computed tomography (CT)-scans performed preoperative and 3 years after CC surgery were analyzed at L3-level for VAT, subcutaneous adipose tissue (SAT) and total adipose tissue (TAT) areas. We assessed changes in VAT, SAT, TAT and VAT/SAT ratio after 3 years and compared the changes between right-sided and left-sided resected patients in the total population and in men and women separately.

Results

A total of 134 stage I-III CC patients undergoing cancer surgery were included. Left-sided colonic resected patients had a 5% (95% CI: 2% - 9%, p<0.01) increase in abdominal VAT, a 4% (95% CI: 2% - 6%, p<0.001) increase in SAT and a 5% increase (95% CI: 2% - 7%, p<0.01) in TAT after 3 years. Right-sided colonic resected patients had no change in VAT, but a 6% (95% CI: 4% - 9%, p<0.001) increase in SAT and a 4% (95% CI: 1% - 7%, p<0.01) increase in TAT after 3 years. Stratified by sex, only males undergoing left-sided colonic resection had a significantly VAT increase of 6% (95% CI: 2% - 10%, p<0.01) after 3 years.

Conclusion

Left-sided CC resection was associated with a significant VAT increase after 3 years.

Health sciences/Endocrinology

Health sciences/Endocrinology/Endocrine system and metabolic diseases/Obesity

Health sciences/Endocrinology/Endocrine system and metabolic diseases/Metabolic syndrome

Colon cancer

colonic resection

visceral adipose tissue

subcutaneous adipose tissue

quantitative computed tomography (CT)-scan

Colon cancer (CC) is the fourth most common cancer worldwide (1) and it has a still increasing incidence rate (1, 2). Survival after a CC diagnosis is steadily improving due to early detection, diagnostic precision and more advanced cancer treatment, and today more than 70% of non-metastatic CC patients are alive after 5 years (3). Unfortunately, the risk of developing metabolic comorbidities as obesity, type 2 diabetes (T2D) and cardiovascular disease (CVD) after a CC diagnosis is also increasing (4, 5) with worsening of overall and cancer-specific prognosis in these patients (6).

Obesity and especially excess abdominal fat are factors increasing morbidity(7) and mortality (8) in CC survivors. The total amount of abdominal adipose tissue (TAT) consists of the visceral adipose tissue (VAT) and the subcutaneous adipose tissue (SAT) (9). Distribution of body fat varies between men and women (10). Men typically have a higher amount of VAT (10). The structure and functions of the two tissues are very different (11) with VAT being highly pro-inflammatory and a major risk factor of developing several diseases including T2D (12), CVD (13) and various cancer types (14, 15). Excess VAT is associated with CC development (16) and a meta-analysis from 2014 showed a linear association between CT-assessed VAT area and adenomas, a CC precursor (17). Moreover, excess VAT may increase CC relapse (18). In contrast excess SAT hasn’t been associated with worse outcomes of CC (19).

The ratio of VAT/SAT (V/S) can be used as a prognostic marker, and a high V/S ratio has been associated with an increased risk of metabolic disturbances and with cancer recurrence (20, 21), whereas weight loss, reducing VAT, decrease the risk of developing diseases such as T2D (22), CVD (23) and improve the prognosis of CC (24). We and others have shown that exercise training effectively reduce abdominal VAT (25), which supports the importance of exercise training in cancer survivors.

We recently found a post-treatment increase in VAT in colonic resected colorectal (CRC) survivors and speculated whether the surgical treatment per se may affect metabolism including fat deposits in the body (26).

Two clinical-epidemiological studies revealed that patients treated with left-sided compared with right-sided colonic resection for CC and other colonic illnesses had an increased risk of developing T2D and CVD respectively (27, 28). These findings raise the intriguing question whether cancer surgery of CC, and especially left-sided colonic resections, contribute to metabolic disturbances in CC survivors. One possible explanation of the side-specific risk modification is that left-sided colonic resection removes enteroendocrine cells producing glucose regulatory and appetite suppressing hormones, predominantly located in the left-side of the colon. This may result in weight gain, VAT accumulation and hyperglycemia.

Due to the significant impact on CC prognosis, it may be of great clinical relevance to identify CC survivors with a particular risk of VAT accumulation in order to initiate preventive strategies or treatment. Despite the association between excess VAT and CC prognosis no specific follow up regimes or interventions are offered to overweight CC survivors.

The primary aim of this study was to investigate changes in abdominal VAT, SAT, TAT and V/S ratio in CC survivors after 3 years in right-sided compared with left-sided colonic resected patients. Secondary aim was to examine changes over time in VAT, SAT, TAT and in V/S ratio after both CC resection types.

Moreover, we aimed to examine the changes described above when stratifying subjects by sex.

Study design and population

We conducted a historical prospective study of stage I-III CC-survivors, who had undergone intended curative cancer treatment with right-sided colonic resection (right-sided hemicolectomy) or left-sided colonic resection (left-sided hemicolectomy, sigmoid resection) between 2014–2018 at Department of Surgical Gastroenterology at Copenhagen University Hospital – Herlev and Gentofte, Herlev, Denmark. All patients were included prior to cancer resection in the Danish REBECCA study (“Biomarkers in patients with colorectal cancer – can they provide new information on the diagnosis, treatment efficacy, adverse effects and prognosis?”), an ongoing cohort study initiated in July 2014. The cohort and study design have been described in detail previously (29). The current study is a subgroup analysis of patients that did not meet the exclusion criteria: UICC-stage IV tumors, rectal cancer (the border between the sigmoid colon and the rectum was defined as 15 cm beyond the anal verge), active cancer at any site during the 3 year postoperative follow-up period, previous colonic resection, a history of diabetes, cases where a stoma was performed peri-operatively or recurrence of cancer within the first 3 years after cancer treatment. A total of 134 CC patients were eligible for the study and were included in the analysis (Fig. 1).

All patients underwent abdominal CT-scans preoperatively for disease staging, which was repeated after 3 years according to the surveillance program to monitor cancer relapse (30). Medical records were reviewed for all patients and information on age, sex, height, weight, ECOG performance status, lifestyle comorbidities (chronic obstructive pulmonary disease, hypertension, dyslipidemia or cardiovascular disorders), antihypertensive or steroid medication, tobacco and alcohol consumption were collected preoperatively as well as tumor location in the colon, date of the CT-scans (preoperatively and 3-years postoperatively), date of surgery, potential postoperative adjuvant treatment, per- or postoperative complications to surgery and development of diabetes during the 3 years of surveillance. Additionally, medication lists were reviewed on a common medication server to make sure that outpatients diagnosed and treated with antidiabetic medication outside of hospitals were revealed. Clinical data were collected blinded to VAT and SAT measurements.

CT-scansVAT and SAT areas were measured using venous phase axial CT images at the L3-level of the lumbar spine, using the exact axial image where both transversal processes were visible. We used the open-source code software Horos™ (version 3.3.6., Annapolis, MD USA) to define the adipose tissue area, indicated by tissue with Hounsfield units (HU) between − 150 and − 50 HU (Fig. 2), which is an attenuation value specific for fatty tissues (31). We defined VAT as the compartment limited anteriorly and laterally by the abdominal musculature and posteriorly by the vertebral column and paraspinal musculature as previously described (32). SAT was defined as adipose tissue located external to the abdominal and back musculature. Total adipose tissue (TAT) was calculated as the sum of the two areas. The use of CT images to determine abdominal fat depots is widely used (33) and images at L3-level of the lumbar spine has been shown to offer the highest prediction of total SAT and VAT depots in the body compared with CT images at other levels of the lumbar spine (34).

The VAT/SAT-ratios (V/S ratio) were calculated by dividing the mean VAT-area with the mean SAT-area.

All analyses were performed blinded to type of surgery (right- or left-sided resection) and were performed by two independent investigators, one of them being a radiographer. The average adipose tissue area measured by the two investigators was used in subsequent statistical analyses.

Biomarker analysis

Blood was drawn just prior to planned cancer surgery. The blood samples were centrifuged at 2300 g at 4˚C for 10 minutes, and serum was then aliquoted and stored at − 80⁰C. C-reactive protein (CRP) was measured as high-sensitive CRP using a sensitive CRP ultra-ready-to-use, liquid assay reagent by an immunoturbidimetric method on a fully automated chemistry analyzer (Kit-test SENTINEL CRP Ultra (UD), 11508 UD-2.0/02 2015/09/23). Interleukin-6 (IL-6) was measured using a high-sensitive enzyme-linked immunosorbent assay (ELISA) (Quantikine HS600B, R&D Systems, Abingdon, UK) in accordance with the manufacturer's instructions.

Statistical analyses

The primary analysis compared difference in changes in VAT, SAT, TAT and V/S ratio preoperatively to 3 years after cancer surgery. The primary analysis was based on a mixed effect model using data from all patients and performed with time, group and preoperative values as fixed effects, individual subjects as random effects and the ‘time x group’ interaction was the primary readout. For all study outcomes, the raw means and standard errors of the means (SEMs) were reported for each group for the preoperative and 3 years timepoint, along with the estimated in-group changes and between-group changes with 95% confidence intervals (CI) extracted from the mixed effects model. All variables were log-transformed to improve model compliance, accordingly the estimated in-group changes and between-group difference were analysed on a log-scale and were reported as back-transformed relative ratios with 95% CIs. As the specified mean changes are based on estimates from the mixed effects models it might not reflect the numerical change Thus, for example a back-transformed estimate of 0.95 corresponds to a median relative change of -5%. Differences in baseline characteristics between the right-sided and left-sided resected patients preoperatively were analyzed using unpaired t-tests. Results were considered statistically significant if p < 0.05. All the statistical analyses were performed using R-software (version 1.3.1056).

Ethics statement

This study is conducted in accordance with the Declaration of Helsinki. All experimental protocols (The REBECCA study protocol (VEK j.nr. H-2-2013-078) and additional protocol for current project (78485)) were approved by “The ethical committee of the capital region of Denmark” and the Danish Data Protection Agency in Copenhagen, Denmark (j. No. HEH-2014-044, I-suite No. 02771 and PACTIUS P-2019-614). Informed consent was obtained from all subjects included in the REBECCA study.

Baseline characteristics

Baseline characteristics of the 134 stage I-III CC patients were similar in the two resection groups (Table 1). Although not statistically significant, patients who had undergone left-sided resection (n = 80) were more likely men, had a better ECOG performance status and had more likely completed chemotherapy than right-sided resected patients (n = 54). The cancer stage was similar in the groups except from stage 3b, which was more common in the left-sided resection group.

On average, the patients were overweight preoperatively defined by a BMI > 25 kg/m2 (left-sided resected patients: BMI 26.8, right-sided resected patients: BMI 25.6).

When stratifying the patients by sex, baseline characteristics were similar across the left-sided and right-sided resected men and women (Supplementary table 1 and 2), except that women in the right-sided resection group were older, had a lower cancer stage and received chemotherapy to a lesser extent than the left-sided resected women (Supplementary table 2).

Changes in VAT, SAT, TAT and V/S in the total population

Changes within each resection group are presented in Table 2 and Fig. 3. Left-sided resected CC survivors had a 5% (p < 0.01) increase in VAT, a 4% (p < 0.001) increase in SAT and a 5% (p < 0.01) in TAT after 3 years. For right-sided resected CC survivors, there was no change in VAT, but a 6% (p < 0.001) increase in SAT and a 4% (p < 0.01) increase in TAT after 3 years. V/S ratio decreased 4% (p = 0.02) after 3 years in right-sided resected patients, whereas left-sided resected patients had no change in V/S ratio.

Between group differences in VAT, SAT, TAT and V/S are presented in Table 2 as well. When comparing VAT, SAT, TAT and V/S ration in right-sided vs. left-sided resected patients preoperatively no difference was found. Moreover, when evaluating VAT in the main analysis, the group x time interaction was insignificant (p = 0.24). Accordingly, when comparing changes in SAT, TAT and V/S ratio within the two resection groups preoperatively to 3 years after surgery we found no significant difference between the two resection groups.

Changes in VAT, SAT, TAT and V/S in men and women separately

Within group differences in VAT, SAT, TAT and V/S for men and women respectively are presented in Table 2. Left-sided colonic resected men had a 6% (p < 0.01) increase and women no change in VAT, men a 4% (p < 0.01) and women a 5% (p < 0.01) increase in SAT and men a 4% (p = 0.01) and women a 5% (p < 0.01) increase in TAT after 3 years respectively.

For both men and women, who had undergone right-sided cancer resection, no changes in VAT were observed after 3 years. In men a 6% (p < 0.01) increase in SAT and no change in TAT was observed after 3 years. In right-sided resected women a 7% (p < 0.001) increase in SAT and a 5% (p = 0.01) increase in TAT was observed after 3 years. In right-sided resected men the V/S ratio 3 years after cancer surgery had decreased 4% (p = 0.02) while unchanged in the left-sided resected group. In women, the V/S-ratio did not change over time in any of the resection groups.

Between group differences in men and women separately are also presented in Table 2. When comparing VAT, SAT, and TAT in right-sided vs. left-sided resected patients preoperatively no difference was found in either men or women. Accordingly, when comparing changes in SAT, TAT and V/S ratio within the two resection groups preoperatively to 3 years after surgery we found no significant difference between the two resection groups in either men or women.

Diabetes development

After reviewing medical records, none of the patients have received a T2D diagnosis or was prescribed anti-diabetic medication during 3 years of surveillance. Thus, it was not possible to assess changes in diabetes development across the groups.

This study of patients operated for stage I-III CC showed an increase in abdominal VAT after 3 years in left-sided colonic resected patients. Moreover, V/S ratio decreased after 3 years in right-sided resected patients. When stratifying by sex VAT increased only significantly after 3 years in men after left-sided resection, but the same tendency was observed in women. The VAT increase in women may have been significant if more patients were included. For both sexes no changes in VAT within the groups was observed after right-sided resection. No subjects in the present study developed T2D during the 3 years of follow-up.

Due to the prognostic significance of increased VAT left-sided resected CC survivors may constitute a population at risk of developing metabolic disturbances and having an inferior cancer prognosis. The overall increase in VAT after surgical cancer treatment is in line with our prior findings (26). In that study it was speculated whether the type of resection per se has the potential to alter metabolism.

Our data indicate that left-sided colonic resected CC survivors may constitute a risk population. This is in line with two recent epidemiological studies. In 2018 Jensen and coworkers showed that left-sided colonic resection compared with right-sided colonic resection was associated with an increased risk of T2D in CC patients and non-cancer patients suffering from inflammatory bowel disease etc. (27). Later, a study from Taiwan explored the association between resection type and metabolic disturbances in patients without CC and found a higher CVD risk after left-sided resection, and a reduction in T2D after right-sided resection when compared with non-colectomy subjects (35). However, the most recent epidemiological study found an increased T2D risk after colectomy compared with small bowel resection, but when stratifying by resection type, they found no difference in T2D risk (36).

One explanation of the changes in fat depots in this study and the metabolic disturbances in the first two abovementioned epidemiological studies may be an altered gut hormone secretion after left-side colonic resection. The hormones Glucagon Like Peptide 1 (GLP-1) and Peptide YY (PYY) are produced by intestinal L-cells located in the small intestine, but also in the colon. The density of L-cells increases from the proximal to the distal colon, thus from right to left colon (37). GLP-1 is an important regulator of glucose homeostasis and both GLP-1 and PYY have strong appetite suppressing effects (38). Thus, in theory removal of a tumor and surrounding tissue in the left side of the colon may result in removal of several glucose regulatory and appetite suppressing hormone-producing cells. This may eventually result in increased appetite and fat accumulation including VAT in addition to glycemia.

It is well known that excess VAT is accompanied by low-grade inflammatory changes within the fat depot. This contributes to chronic systemic inflammation with enhanced concentrations of circulating cytokines such as CRP and IL-6 and adipokines (39), which is associated with cancer progression and poor survival in patients with CC (40). In the present study CRP and IL-6 levels were only available preoperatively and values were within the normal range in both resection groups and in men and women respectively.

Our data revealed that SAT was increased independent of resection type and in both sexes after 3 years. In contrast to VAT, the role of abdominal SAT in development of diabetes, CVD and cancer recurrence and death after cancer resection is not fully understood (41, 42). Nonetheless, an increase in VAT is highly correlated with an increase in SAT (41, 42).

Until recently the impact of adiposity on CC prognosis has been confusing (43). The divergent results may be due to the various ways to measure adiposity in former studies (eg BMI, waist-circumference, bioelectrical impedance, quantitative CT-scans etc.) (44). However, since excess adipose tissue is believed to be involved in the underlying pathogenesis of CC (45), it seems plausible that adiposity is associated with more aggressive cancers with increased rates of recurrence. This was confirmed in a recent and the largest metanalysis including 45 studies and 607,266 patients with stage I to IV colorectal cancer as they reported a significant increase in colorectal cancer (OR = 1.27; 95% CI 1.11–1.45) and overall (OR = 1.20; 95% CI 1.06–1.36) mortality in patients with obesity compared with normal-weight patients (43). Moreover, increased waist circumference, which is strongly correlated to VAT (46), was associated with increased colorectal cancer mortality (43).

Increased VAT expressed as an increased V/S ratio is sometimes used as a negative prognostic marker. Thus, in a prior study by Hyeong-Gon Moon et al they included 161 CRC resected patients (both men and women) with an average preoperative V/S ratio of 0.83 which is comparable to our data (average V/S-ratio preoperatively was 0.83 in our study) and showed that patients with V/S ratio > 50% percentiles had significantly lower cumulative disease-free survival rate compared to patients with low V/S ratio during the 8 years of post-operative follow up (21). Based on this study CC survivors who had undergone left-sided colonic resection in the present study may have a worse prognosis. However, in a prospective observational study, overall survival was reduced in right-sided compared with left-sided CRC (47), and similar studies suggest that tumor location have no impact on overall survival (48).

Due to the strong association between excess VAT and morbidity and mortality in CC survivors, identifying CC survivors with increased amounts of VAT may be of great clinical relevance. Our study revealed a moderately increased VAT after left-sided CC resection. This is in line with two prior epidemiological studies showing that left-sided colonic resected patients may constitute a risk population. The underlying mechanisms remain unclear, but changes in gut hormone secretion after left-sided resection could be at play.

A strength of the present work is that the method used as quantitative computed tomography (CT) to determine VAT, SAT and TAT in CC is well established. CT scans were consistently performed before surgery in relation to cancer staging and later until 3 years postoperatively to detect disease recurrence. Furthermore, all analyses were performed blinded to type of surgery (right or left-sided resection) and were performed by two independent investigators. Another strength of this study is the prospective nature of the study allowing us to detect changes in abdominal fat depots over time. Moreover, the two groups were comparable preoperatively. On the other hand, a limitation of the present study included lack of all other variables except for CT-scan results after 3 years.

Our data revealed an increase in abdominal VAT after CC surgery with left-sided colonic resection only. When stratifying by sex only left-sided colonic resected men had a significantly increased VAT after 3 years. The underlying mechanisms behind this side-specific difference remains to be explored in future studies.

ACKNOWLEDGEMENT AND FUNDING

This work was supported by the Danish Diabetes Association and the Danish Diabetes Academy, which is funded by the Novo Nordisk Foundation under grant number NNF17SA0031406.

The Centre for Physical Activity Research (CFAS) is supported by TrygFonden (grants ID 101390, ID 20045, and ID 125132).

The VELUX foundation (Grant project number 00018310, salary to TGD) is acknowledged.

Chief physician Benny Vittrup is acknowledged for his important contribution to the REBECCA study.

AUTHOR CONTRIBUTIONS

Conceptualization LLL. Methodology LLL, TIAS, JFC, MSS, YKM and TGD. Access to and verified the raw data and formal analysis LLL, MSS, YKM. Resources LLL and MSS. Writing – original draft LLL and YKM. Writing – review and editing, all authors contributed. All authors approved the final version for publication, and LLL had final responsibility for the decision to submit.

DISCLOSURE

The authors declare there are no competing interests to declare.

DATA SHARING

The data that support the findings of this study are available from [[email protected]] but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of [[email protected]].

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TABLE 1: Baseline characteristics for all patients
	All n = 134	Left sided resection n = 80	Right sided resection n = 54	P value
Sex, n (%)
Male	62 (46.3)	40 (50.0)	22 (40.7)	0.07
Female	72 (53.7)	40 (50.0)	32 (59.3)	0.07
Age, year, mean (SD)	67 (8.9)	66 (8.7)	69 (9.0)	0.06
T-stage, n (%)
T1	16 (11.9)	9 (11.3)	7 (13.0)	0.77
T2	34 (25.4)	17 (21.3)	17 (31.5)	0.20
T3	74 (55.2)	47 (58.8)	27 (50.0)	0.32
T4	10 (7.5)	7 (8.8)	3 (5.6)	0.48
N-stage, n (%)
N0	94 (70.1)	53 (66.3)	41 (75.9)	0.22
N1	34 (25.4)	22 (27.5)	12 (22.2)	0.49
N2	6 (4.5)	5 (6.3)	1 (1.9)	0.18
Overall stage, n (%)
1	38 (28.4)	21 (26.3)	17 (31.5)	0.52
2a	51 (38.1)	29 (36.3)	22 (40.7)	0.60
2b	5 (3.7)	3 (3.8)	2 (3.7)	0.99
3a	12 (9.0)	5 (6.3)	7 13.0)	0.21
3b	28 (20.9)	22 (27.5)	6 (11.1)	0.01
ECOG performance status¹, n (%)
0	111 (82.8)	70 (87.5)	41 (75.9)	0.10
1	17 (12.7)	9 (11.3)	8 (14.8)	0.56
2	6 (4.5)	1 (1.3)	5 (9.3)	0.06
Anthropometrics, mean (SD)
Weight, kg	78.4 (15.7)	79.6 (15.8)	76.6 (15.6)	0.29
Height, cm	172.5 (9.8)	172.4 (9.8)	172.6 (9.9)	0.91
BMI, kg/m²	26.3 (4.6)	26.8 (4.8)	25.6 (4.2)	0.16
Smoking, n (%)
Never	64 (47.8)	40 (50.0)	24 (44.4)	0.53
Former	51 (38.1)	31 (38.8)	20 (37.0)	0.84
Current	14 (10.4)	5 (6.3)	9 (16.7)	0.08
Not known	5 (3.7)	4 (5.0)	1 (1.9)	0.50
Alcohol, n (%)
Never	32 (23.9)	21 (26.3)	11 (20.4)	0.43
Normal	78 (58.2)	45 (56.3)	33 (61.1)	0.58
Overuse	20 (14.9)	11 (13.8)	9 (16.7)	0.65
Previous overuse	1 (0.7)	1 (1.3)	0 (0.0)	0.32
Not known	3 (2.2)	2 (2.5)	1 (1.9)	0.8
Adjuvant chemotherapy, n (%)
Yes	47 (35.1)	33 (41.3)	14 (25.9)	<0.01
No	87 (64.9)	47 (58.8)	40 (74.1)	<0.01
Comorbidities, n (%)
Hypertension	44 (32.8)	25 (31.3)	19 (35.2)	0.64
Hyperlipidaemia	29 (21.6)	16 (20.0)	13 (24.1)	0.58
COPD	10 (7.5)	5 (6.3)	5 (9.3)	0.53
Cardiovascular disease	8 (6.0)	4 (5.0)	4 (7.4)	0.58
Others	3 (2.2)	2 (3)	1 (1.9)	0.8
Clavien-Dindo score², n (%)
0	122 (91.0)	74 (92.5)	48 (88.9)	0.49
1	5 (3.7)	2 (3.0)	3 (5.6)	0.40
2	2 (1.5)	2 (3.0)	0 (0.0)	0.16
3a	0 (0.0)	0 (0.0)	0 (0.0)	NA
3b	4 (3.0)	2 (3.0)	2 (3.7)	0.70
4a	1 (0.7)	0 (0.0)	1 (1.9)	0.32
Pharmacological treatment, n (%)
Prednisolone	4 (3.0)	2 (3.0)	2 (3.7)	0.70
Antihypertensive medication	89 (66.4)	51 (63.8)	38 (70.4)	0.43
Biochemical values, median (range)
IL6, ng/L	2.2 (0.6-71.9)	2.0 (0.6-59.6)	2.4 (0.9-71.9)	0.47
CRP, mg/L	1.0 (0.0-76.0)	0.8 (0.0-76.0)	1.0 (0.0-51.9)	0.86
IL-6, Interleukin-6; CRP, C-reactive protein. An unpaired t-test was used to calculate P values. ECOG performance status definitions: 0: Fully active, able to carry on all pre-disease performance without restriction; 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work; and 2: Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours (48). Clavien-Dindo score definitions: 1: Any deviation from the normal postoperative course without the need for pharmacological treatment or surgical, endoscopic and radiological interventions. Allowed therapeutic regimens are: drugs as antiemetics, antipyretics, analgetics, diuretics and electrolytes and physiotherapy. This grade also includes wound infections opened at the bedside; 2: Requiring pharmacological treatment with drugs other than such allowed for grade 1 complications. Blood transfusions and total parenteral nutrition are also included; 3: Requiring surgical, endoscopic or radiological intervention; 3a: Intervention not under general anesthesia; 3b: Intervention under general anesthesia; 4: Life-threatening complication (including CNS complications) requiring IC/ICU-management; 4a: Single organ dysfunction (including dialysis) (49).

TABLE 2: Changes in size of fat depots

Size of fat depots

In-group differences

Between-group

differences

PreOP

Mean

3 years

Mean

PreOP vs. 3 years

PreOP

Change

(PreOP-3 years)

± SEM

𝚫 (95% CI)

p-value

Diff.(95% CI)

p-value

Diff.(95% CI)

p-value

ALL PATIENTS

VAT, cm²

Left-sided

158 ± 12.76

172 ± 12.92

1.05

(1.02 – 1.09)

<0.01

1.02

(0.97 – 1.09)

0.42

1.03

(0.98 – 1.09)

0.24

Right-sided

145 ± 14.78

147 ± 14.99

1.02

(0.98 – 1.06)

0.38

SAT, cm²

Left-sided

199 ± 10.75

215 ± 10.98

1.04

(1.02 – 1.06)

<0.001

1.02

(0.97 – 1.09)

0.87

1.03

(0.98 – 1.09)

0.24

Right-sided

182 ± 11.10

208 ± 12.38

1.06

(1.04 – 1.09)

<0.001

TAT, cm²

Left-sided

353 ± 19.26

386 ± 18.80

1.05

(1.02 – 1.07)

<0.01

1.02

(0.98 – 1.06)

0.77

1.03

(0.98 – 1.09)

0.92

Right-sided

325 ± 20.95

354 ± 21.68

1.04

(1.01 – 1.07)

<0.01

V/S ratio

Left-sided

0.85 ± 0.07

0.88 ± 0.07

1.01

(0.98 – 1.03)

0.59

1.05

(0.93 – 1.18)

0.41

1.05

(1.00 – 1.09)

0.03

Right-sided

0.80 ± 0.09

0.75 ± 0.09

0.96

(0.93 – 0.99)

0.02

MEN

VAT, cm²

Left-sided

206 ± 19.21

224 ± 18.89

1.06

(1.02 – 1.10)

<0.01

1.02

(0.94 – 1.11)

0.59

1.05

(0.98 – 1.13)

0.14

Right-sided

214 ± 25.95

212 ± 27.58

1.01

(0.95 – 1.06)

0.84

SAT, cm²

Left-sided

163 ± 11.62

176 ± 10.78

1.04

(1.01 – 1.07)

<0.01

0.99

(0.94 – 1.05)

0.85

0.99

(0.94 – 1.03)

0.52

Right-sided

152 ± 13.71

172 ± 16.47

1.06

(1.02 – 1.09)

<0.01

TAT, cm²

Left-sided

367 ± 29.18

398 ± 27.07

1.04

(1.01 – 1.08)

0.01

1.01

(0.94 – 1.08)

0.82

1.02

(0.96 – 1.07

0.66

Right-sided

366 ± 36.59

384 ± 38.80

1.03

(0.99 – 1.08)

0.14

V/S ratio

Left-sided

1.27 ± 0.09

1.01

(0.98 – 1.04)

0.54

1.00

(0.89 – 1.13)

0.94

1.05

(1.01 – 1.10)

0.03

Right-sided

1.30 ± 0.15

1.21 ± 0.16

0.96

(0.93 – 0.99)

0.02

WOMEN	VAT, cm²
	Left-sided	110 ± 13.17	119 ± 13.3	1.04 (0.99 – 1.10)	0.12	1.01 (0.93 – 1.10)	0.81	1.02 (0.94 – 1.10)	0.69
	Right-sided	98 ± 11.86	101 ± 11.50	1.03 (0.97 – 1.09)	0.37
	SAT, cm²
	Left-sided	234 ± 16.34	257 ± 17.12	1.05 (1.01 – 1.08)	<0.01	1.00 (0.96 – 1.05)	0.83	0.98 (0.93 – 1.03)	0.38
	Right-sided	205 ± 15.38	236 ± 16.28	1.07 (1.03 – 1.11)	<0.001
	TAT, cm²
	Left-sided	339 ± 25.39	373 ± 26.27	1.05 (1.01 – 1.08)	<0.01	1.01 (0.96 – 1.06)	0.78	0.99 (0.94 – 1.05)	0.79
	Right-sided	292 ± 23.48	332 ± 24.55	1.05 (1.01 – 1.10)	0.01
	V/S ratio
	Left-sided	0.45 ± 0.05	0.46 ± 0.05	1.01 (0.96 – 1.05)	0.79	1.00 (0.89 – 1.13)	0.99	1.04 (0.97 – 1.12)	0.27
	Right-sided	0.41 ± 0.04	0.40 ± 0.04	0.97 (0.92 – 1.02)	0.23

VAT, Visceral adipose tissue; SAT, Subcutaneous adipose tissue; TAT, Total adipose tissue; V/S, VAT/SAT ratio. PreOP, Preoperative. Means (SEM) are based on available data (PreOp, 3 years) for left-sided and right-sided colonic cancer resected patients.

In-group and between-group differences were analyzed using a unified linear mixed effects model. Logarithmic values were used. In group and between group changes don’t reflect the numerical difference between preoperative and 3 years, given that mean change is estimated based on mixed-model analysis.

There is NO conflict of interest to disclose

SuplementalInt.JournalofObesity.docx

Change in abdominal obesity after colon cancer surgery – effects of left-sided and right-sided colonic resection

Status:

Journal Publication

Version 1

Abstract

Figures

INTRODUCTION

METHODS

Study design and population

Biomarker analysis

Statistical analyses

Ethics statement

RESULTS

Baseline characteristics

Changes in VAT, SAT, TAT and V/S in the total population

Changes in VAT, SAT, TAT and V/S in men and women separately

Diabetes development

DISCUSSION

CONCLUSION

Declarations

References

Tables

Additional Declarations

Supplementary Files

Status:

Journal Publication

Version 1