INTRODUCTION

Colorectal cancer (CRC) contributes substantially to the healthcare burden worldwide[1], and is the fourth most commonly diagnosed malignancy and second most common cause of cancer-related death in Australia[2]. Obesity is a rising global pandemic associated with systemic disease and poor health outcomes[3]. Body mass index (BMI) is an overall measure of total body fat, and is an easily calculable and accepted surrogate marker of obesity[4]. The World Health Organization (WHO) defines obesity in adults as a BMI of ≥ 30 kg/cm

[5].

The increasing prevalence of obesity is of particular concern to colorectal surgeons, as it is not only implicated in the pathogenesis of CRC but also may have an impact on post-operative outcomes[6].However, with several studies reporting inconsistent findings[7-9], there remains no consensus. The Clavien-Dindo Classification is a standardized system of grading post-operative complications, ranging from grade I (minor events) to grade V (death)[10]. With objective criteria, it is a highly reproducible method of grading post-operative complications, and is validated across several surgical disciplines including colorectal surgery[11].

In this study, we conducted a retrospective cohort study to outline and compare the clinical characteristics of obese and non-obese patients undergoing surgical resection of CRC at our institution, as well as to evaluate the impact of obesity on post-operative outcomes using the Clavien-Dindo Classification of Surgical Complications. The secondary aim was to determine the impact of obesity on post-operative outcomes in the subgroup of patients undergoing laparoscopic CRC resection.

MATERIALS AND METHODS

Study design

The Prince Charles Hospital (TPCH) CRC Database includes all patients who have undergone CRCresection at our institution. The criteria for inclusion in TPCH CRC Database were all patients who had histologically confirmed CRC (including appendiceal cancers as per the International Classification of Diseases-10 classification) and underwent an operation at TPCH between January 2010 and December 2020. As per the WHO definition, patients were grouped into an obese group (BMI ≥ 30) or non-obese group (BMI < 30), and the demographic features, comorbidities, and surgical features in each group were reported and compared. In addition, the post-operative outcomes of patients in each group were also compared.

Ethics approval

Approval for the TPCH Colorectal Cancer Database was granted by TPCH Human Research Ethics Committee (HREC/17/QPCH/295).

Demographics and comorbidities

Demographic data documented in this study included age, sex, BMI, smoking, and alcohol status.Patient comorbidities were categorized into cardiac, respiratory and metabolic etiologies, with specific diseases recorded in each category if present. The American Society of Anesthesiologists (ASA) grade was also recorded (Table 1).

Surgical features

It is widely recognized that visceral obesity is associated with increased intra-operative technical difficulty by reducing access and visualization from thickened omentum and mesentery, distorting surgical planes, and increasing the risk of bleeding from both difficult mobilization of vessels and friable fatty tissue[20]. Our finding of poorer post-operative outcomes in obese patients undergoing laparoscopic surgery and not the obese cohort in general may be due to the fact that these aforementioned issues are aggravated in a laparoscopic approach, where increased intra-abdominal adiposity may severely restrict the already small working space available during a minimally-invasive resection. In addition, obese patients are pre-disposed to having a reduced physiologic reserve, and are thus at a greater risk of hemodynamic compromise during pneumoperitoneum from both increased intraabdominal pressure and systemic acidosis secondary to carbon dioxide absorption[21].

Post-operative outcomes

Post-operative outcomes recorded included the occurrence of any post-operative complication, which were each graded by the Clavien-Dindo Classification of Surgical Complications (Supplementary material). Complications were also classified as either no complication/low-grade and high-grade,defined as Clavien-Dindo grades I-II and III-V respectively. In addition, complications were attributed to either a surgical or medical cause, with specific surgical and medical complications also recorded if they occurred (Table 3).

The outcomes as above were also undertaken in the subgroup of patients undergoing laparoscopic surgery (Table 4). Patients who underwent laparoscopic surgery who were converted to an open procedure intra-operatively were excluded from this subgroup. Furthermore, post-operative outcomes of obese

non-obese patients were compared in subgroups divided by cancer location. Patients were divided into a right sided colon cancer (caecum to transverse colon) subgroup (Table 5), left sided colon cancer (splenic flexure to sigmoid colon) subgroup (Table 6) and a rectal cancer subgroup (Table 7).

Statistical analysis

Statistical analysis was performed using Stata v17 (StataCorp, La Jolla, CA, United States). Categorial variables are presented as frequencies, and continuous variables are presented as medians and interquartile ranges. Groups were assessed using the

-test,

χ

test or Fisher’s exact test as appropriate.Statistically significant results were defined as

≤ 0.05.

RESULTS

Patient demographics and comorbidities

A total of 472 patients (76.7%) underwent laparoscopic and laparoscopic-assisted surgery; among them,336 (71.2%) had a BMI < 30, and 136 (28.8%) had a BMI ≥ 30. Obese patients in the laparoscopic surgerysubgroup similarly had a higher ASA grade (ASA I-II:36.8%

48.1%, ASA ≥ III:63.2%

51.9%;

=0.03), and a higher prevalence of pre-existing cardiac comorbidities (72.8%

56.3%;

< 0.001) and respiratory comorbidities (38.2%

26.9%;

= 0.02) compared to non-obese patients.

We recognize that as an anthropometric measure, BMI has its limitations in the ability to identify visceral obesity, and also is distributed differently among ethnic groups[26]. Our rationale for using BMI as opposed to more specific volumetric measures of intra-abdominal adiposity such as visceral fat area, is that BMI is a much more commonly used definition of obesity in the literature. This enabled us to compare our outcomes directly against a larger number of studies. In addition, given that BMI is indicative of whole-body fat, it also allows for the analysis of general adipose-associated pathophysiological processes[19].

This research has demonstrated that although obese patients were more likely to experience conversion to an open procedure (P = 0.002), they did not experience more post-operative complications (P = 0.06)or high-grade complications (P = 0.11). There were also no differences in in-hospital mortality (P = 0.06)or length of stay (P = 0.42). In the laparoscopic subgroup however, patients were more likely to experience a post-operative complication (P = 0.05), but did not experience more high-grade complications(P = 0.07).

Surgical features

Table 2 outlines and compares the surgical features between the obese and non-obese groups. Both groups had a similar proportion of elective and emergency procedures (88.5%

82.9% and 11.5%

17.1% respectively;

= 0.09). The obese group had a higher proportion of patients requiring conversion to an open procedure (12.8%

5.1%;

= 0.002). Both groups had a similar percentage of patients requiring peri-operative blood transfusion (15.4%

15.0%;

= 0.90).

Post-operative outcomes

Table 3 outlines and compares the post-operative outcomes and complications between the obese and non-obese groups. There were no significant differences between groups in terms of the prevalence ofpost-operative complications (51.6%

44.1%;

= 0.06) or high-grade complications (19.2%

14.1%;

=0.11). In-hospital mortality (Clavien-Dindo V) occurred in 1 obese patient (0.5%) and 8 non-obese patients (1.8%). There were no differences between both groups in the incidence of surgical complications (26.4%

22.9%;

= 0.35), including, but not limited to, anastomotic leak (3.8%

2.8%;

= 0.46),wound infection (3.8%

4.4%;

= 0.83) and return to theatre (3.8%

3.0%;

= 0.62). The prevalence of post-operative medical complications was also similar between both groups (20.3%

22.2%;

= 0.67),and there were no differences in the prevalence of specific medical complications. The median postoperative length of stay was also similar between both groups (7 d

6 d;

= 0.42).

The first day went really well; Kelly only fell over twice. After several days of carrying her to and from the yard, I thought, Why not encourage her to walk down the hallway a little by herself? I asked Kelly if she would like to try it, and she became very excited. The next day I sent the class out to the yard with my two assistants, and Kelly began her first journey down the hallway. She walked all the way to the next classroom, a total of ten feet. We were both thrilled! But my assistants were aghast that I was encouraging this poor child to walk. They pleaded with me to carry her outside and seat her on the bench so she could watch the other children run and play. It would be so much easier, they murmured. But Kelly was persistent10 and eager to give it her best shot.

Post-operative outcomes in patients undergoing laparoscopic surgery

From January 2010 to December 2020, 615 patients at our institution fulfilled the inclusion criteria and were included in the database. In all, 182 patients (29.6%) had a BMI ≥ 30 (obese group), and 433 patients (70.4%) had a BMI < 30 (non-obese group). Table 1 outlines and compares the demographic features and comorbidities in both groups.

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Post-operative outcomes of the patients in the cohort undergoing laparoscopic surgery are shown in Table 4. Obese patients were more likely to experience a post-operative complication (47.8%

39.3%;

= 0.05); however, there was no differences between both groups in the incidence of high-grade complications (17.6%

11.0%;

= 0.07). There were similarly no major differences between both groups in the percentage of patients who experienced a surgical complication (27.2%

20.2%;

= 0.11) or medical complication (15.4%

19.6%;

= 0.36). The median post-operative length of stay was equivalent between both groups (6 d

6 d;

= 0.15).

In the daytime she sat down once more beneath the windows of the castle, and began to card with her golden carding-comb; and then all happened as it had happened before

Post-operative outcomes of obese vs non-obese patients based on cancer location

Obese and non-obese patients in the right-sided colon cancer subgroup had equivalent outcomes, with no differences in the incidence of post-operative complications (52.2%

54.1%;

= 0.61), high-grade complications (17.4%

15.6%;

= 0.73), surgical complications (23.9%

25.4%;

= 0.88), or medical complications (27.2%

26.8%;

= 1.00). Similarly in the left-sided colon cancer subgroup there were no differences between obese and non-obese patients in the percentage of post-operative complications(47.5%

37.1%;

= 0.09), high-grade complications (18.0%

9.8%;

= 0.11), surgical complications(27.9%

20.3%;

= 0.27), or medical complications (9.8%

19.6%;

= 0.10). In the rectal cancer subgroup, there were also no differences between obese and non-obese patients in the prevalence of post-operative complications (70.0%

54.2%;

= 0.68), high-grade complications (35.0%

31.2%;

=0.78), surgical complications (35.0%

37.5%;

= 1.00), or medical complications (25.0%

27.1%;

=1.00).

DISCUSSION

We found that despite patients with an obese BMI having significantly higher rates of cardiac comorbidities, respiratory comorbidities, type II diabetes mellitus, and conversion to open surgery compared to patients with a non-obese BMI, there was no increased prevalence of post-operative complications (51.6%

44.1%;

= 0.06) or high-grade complications (19.2%

14.1%;

= 0.11)following CRC surgery. Our findings are concordant with Genser

[12], who reported that in patients undergoing emergency colon cancer surgery, obese patients did not experience a higher proportion of post-operative complications (54%

52%;

= 0.86) or high-grade complications (20%

17%;

= 0.47).Despite our obese cohort having a higher burden of medical comorbidities, we did not observe an increased rate of specific post-operative medical complications. Smith

[13] also showed that obese patients are not at an increased risk of post-operative pneumonia or renal failure, and Merkow

[14]showed that obese patients are similarly not at increased risk of post-operative pneumonia, cardiac arrest, myocardial infarction, or stroke. Obesity may not be an independent predictor of peri-operative cardiac complications, with the latter more accurately related to functional status rather than traditional cardiovascular risk factors[15].

Importantly, we determined that the impact of obesity on post-operative outcomes may only manifest in patients undergoing laparoscopic resection, with obese patients in this subgroup having a significantly increased prevalence of post-operative complications (47.8%

39.3%;

= 0.05). It should be noted that these findings were not influenced by patients who underwent laparoscopic converted to open surgery given that they were excluded from this subgroup.

In contrast to our findings, a Chinese study by Xia

[16] reported that following laparoscopic CRC resection, patients with a BMI ≥ 30 had a higher but non-significant incidence of Clavien-Dindo grade III complications compared to patients with a BMI of < 25 (14.3%

5.1%;

= 0.178). Similarly, a Korean study on laparoscopic CRC outcomes by Park

[17] also showed that obesity was not associated with an increased rate of major post-operative complications including ileus, bleeding and anastomotic leak(7.4%

5.3%;

= 0.889). Non-significant results in both these studies may be related to the lower prevalence of obesity in Asian countries, which is reflected by both studies having only 2.7% of their cohorts categorized as BMI ≥ 30. Two systematic reviews of laparoscopic CRC surgery outcomes in the obese by Fung

[18] and He

[19] have both reported obesity to be associated with increased overall post-operative morbidity [odds ratio (OR) = 1.54, 95% confidence interval (CI):1.21-1.97 and OR= 1.40, 95%CI:1.18-1.66 respectively].

Surgical features recorded included cancer location, operative urgency, operative approach, colorectal operation performed, requirement for stoma, and peri-operative requirement for transfusion (Table 2).

In the modern era, laparoscopic surgery has been established as the standard of care in CRC surgery[22]. Although we have shown that utilizing this approach is associated with an increased prevalence of general post-operative complications in obese patients, we acknowledge that there are circumstances where the well-recognized benefits of laparoscopic surgery such as earlier restoration of gut motility,reduced post-operative pain and shorter length of stay may outweigh the perceived risks[23,24]. Martin and Stocchi[25] have proposed several practical strategies during laparoscopic colectomy in the obese such as the use of a 30-degree laparoscope to facilitate exposure and 10 mm instruments to allow for greater leverage during retraction, as well as the use of intra-corporeal vessel ligation given potential difficulties in exteriorizing thickened omentum. Surgeons attempting a laparoscopic approach in obese patients should be adequately experienced and aware that the benefits of laparoscopic surgery likely diminish if meaningful progress in the operation is not made.

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We found that despite patients with an obese BMI having significantly higher rates of cardiac comorbidities, respiratory comorbidities, type II diabetes mellitus, and conversion to open surgery compared to patients with a non-obese BMI, there was no increased prevalence of post-operative complications (51.6%

44.1%;

= 0.06) or high-grade complications (19.2%

14.1%;

= 0.11)following CRC surgery.

We couldn t escape being hit, with two ME-109s firing at us point-blank. Looking out the left window, I saw the left wing covered with a sheet of flame from the cockpit to the wing tip. Frank, in the ball turret12, called on the interphone, We re on fire!

I suppose it was strange for a boy s father to wear an apron – even one with race cars – but I never thought much of it until the day that Dad broke with tradition. It was the last Sunday in August. My father seemed in an expansive（，） mood as we walked home from church together.

The dolphins sported in the waves, and the great whales spouted29 water from their nostrils30 till it seemed as if a hundred fountains were playing in every direction

CONCLUSION

Surgical resection of CRC in obese individuals is safe. A higher prevalence of post-operative complications in obese patients appears to only be in the context of laparoscopic surgery.

ARTICLE HIGHLIGHTS

Research background

Obesity is a worldwide epidemic of increasing significance. Although the colorectal surgeons of today manage a greater number of obese patients with colorectal cancer (CRC), the current literature reports inconsistent findings on whether this phenomenon impacts post-operative outcomes following CRC surgery.

Research motivation

This research was conducted to determine whether obese patients had equivalent outcomes compared to non-obese patients following CRC surgery. This is an important issue, as there is no consensus on whether obesity truly impacts post-operative outcomes, yet obese patients are at risk of having their surgery withheld or delayed based on this factor alone.

Research objectives

The primary aim of this study was to compare the post-operative outcomes of obese vs non-obese patients following CRC surgery. With laparoscopic surgery now recognized as the standard of care in CRC management, post-operative outcomes between obese and non-obese patients were also analyzed in the subgroup of patients undergoing laparoscopic CRC surgery.

Research methods

Patients who underwent CRC resection between January 2010 and December 2020 at the Prince Charles Hospital, Queensland, Australia were included in this study. As per the World Health Organization definition, this study defined obesity as a body mass index (BMI) ≥ 30 mg/kg2. Patients were divided into an obese and non-obese group, and post-operative outcomes were compared between these two groups using parametric and non-parametric tests. This study also analyzed the post-operative outcomes of obese vs non-obese patients in the subgroup undergoing laparoscopic CRC surgery.

Tsarevitch Ivan seated himself on the back of the Wolf joyfully26 enough. Take me, Gray Wolf, he said, to the Fire Bird that stole my father s golden apples, and instantly the Wolf sped away, twenty times swifter than the swiftest horse. In the middle of the night he stopped at a stone wall.

Research results

Patients in both groups were of similar age (obese group, 70 years

non-obese group, 71 years;

=0.45) and sex (45.6% male

53.6% male;

= 0.08). By contrast, the obese group had a greater proportion of patients graded at a higher ASA grade (ASA I-II:29.7%

45.7%, ASA ≥ III:70.3%

54.3%;

<0.001), and also had a higher prevalence of cardiac comorbidities (73.1%

56.8%;

< 0.001) and respiratory comorbidities (37.4%

26.8%;

= 0.01) compared to patients in the non-obese group. Obesepatients were more likely to have type II diabetes mellitus (28.6%

12.7%;

< 0.001).

Research conclusions

Our study has determined that obesity is no barrier to adequate post-operative outcomes following CRC surgery, with obese patients having equivalent post-operative outcomes compared to their non-obese counterparts. Caution is advised however, when attempting a laparoscopic approach in obese patients.

Research perspectives

Ethics approval for this database was granted by the Prince Charles Hospital Human Research Ethics Committee (Approval No. HREC/17/QPCH/295).

Not long after, the king of the country suffered from thedeepest melancholy17. He was diligent18 and industrious19, but employmentdid him no good. They read deep and learned books to him, and then the lightest and most trifling20 that could be found, but all to no purpose.

Mao D designed the study, performed the research, and wrote the manuscript; Flynn DE designed the study methodology and helped perform the research; Yerkovich S helped with data collection,statistical analysis, and manuscript review; Tran K and Gurunathan U helped with data collection, clinical advice,data analysis, and manuscript review; Chandrasegaram MD helped with design methodology and conceptualization,study supervision, manuscript editing and finalization.

Although BMI is a well-recognized and accepted surrogate marker of obesity, further studies in this area should analyze post-operative outcomes using other markers of visceral obesity. In addition, the effect of nutritional status and body composition on post-operative outcomes can be explored.

Your grandchild, Little Red Riding Hood, replied the wolf, counterfeiting4 her voice; who has brought you a cake and a little pot of butter sent you by mother.

I certify that patients were not required to give informed consent to the study because the analysis used anonymous clinical data that was obtained after each patient agreed to treatment by written consent.

All the authors report no relevant conflicts of interest for this article.

No additional data are available.

This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BYNC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is noncommercial. See:https://creativecommons.org/Licenses/by-nc/4.0/

Australia

The prince, however, replied that he was there for one thing only; that his first duty was to beat the drums and announce himself as a suitor, when he would be taken, as such, to the king, who would then give him proper lodgment

Derek Mao 0000-0002-3979-734X; David E Flynn 0000-0003-2150-3849; Stephanie Yerkovich 0000-0003-4163-4782; Kayla Tran 0000-0002-9216-6774; Usha Gurunathan 0000-0002-0336-872X; Manju D Chandrasegaram 0000-0002-4826-5038.

Wang JJ

But life did not depart from him- the thread would not break,but the thread of memory was severed; the thread of his mind hadbeen cut through, and what was still more grievous, a body remained- a living healthy body that wandered about like a troubled spirit.

Filipodia

Wang JJ

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