Relation between Sarcopenia and Surgical Site Infection in Patients Undergoing Gastric Cancer Surgery

Abstract

Background:

Sarcopenia is a syndrome that can have negative consequences after gastric cancer (GC) surgery. This study aims to determine the effect of sarcopenia on surgical site infection (SSI) that develops after open GC surgery.

Patients and Methods:

In this retrospective design study, data were collected for patients who underwent GC surgery between January 2013 and August 2019. The diagnosis of sarcopenia was made according to the skeletal muscle index (SMI) calculated from pre-operative computed tomography images. Patients with sarcopenia and those without sarcopenia were compared in terms of SSIs; the risk factors for SSI were also analyzed.

Results:

One hundred forty-nine patients were included in the study and had a mean age of 59.3 years. Post-operative complications developed in 59 patients (39.6%) and SSIs in 28 patients (18.7%). Sarcopenia was detected in 57 (38.3%) patients; the mean age was 59.9 years in the sarcopenic group (SG) and 58.9 years in the non-sarcopenic group (NSG; p = 0.55). The mean SMI was 382.5 mm²/m² and 646.2 mm²/m² in the SG and NSG, respectively (p < 0.001). A relation between SSIs and sarcopenia was detected; 17 patients in the SG (29.8%) versus 11 patients in the NSG (11.9%; p = 0.007). Surgical site infection was not found to be statistically significantly related to obesity, hypoalbuminemia, intra-operative blood loss, or duration of operation, although the sarcopenic obesity patients were found to have the highest SSI rate (40%).

Conclusion:

The present study identified a relation between sarcopenia and SSIs occurring after GC surgery. The authors believe that studies seeking to reduce the incidence of SSIs, which are a leading cause of morbidity after GC surgery, should be supported.

Gastric cancer (GC) is the fifth most common type of cancer worldwide and the third leading cause of cancer-related death [1]. Gastrectomy with lymph node dissection is still the optimum treatment for potentially treatable GC [2].

Various studies have reported different rates of surgical site infection (SSI) after gastric surgery, ranging from 3% to 16% [3 –5]. In addition to increasing hospital costs, SSIs delay the patient's return to work or the continuation of oncologic treatment. Various studies have established body mass index (BMI), duration of operation, open surgery, and intra-operative blood transfusion as risk factors for the development of SSIs after elective gastrectomy [6,7].

Sarcopenia has been defined as a syndrome that causes generalized and progressive loss of skeletal muscle. This condition often develops with advanced age. In addition, sarcopenia can be detected in the presence of malnutrition, immobility, inflammatory disease, and cancer that can be seen at any age [8]. Recent studies have found sarcopenia to cause morbidity after GC surgery, although it is unclear how sarcopenia affects the development of SSIs after open GC surgery [9,10]. This retrospective study investigates the relation between sarcopenia and SSIs among patients undergoing elective open CG surgery.

Patients and Methods

This study is a retrospective review of the medical records of patients who underwent GC surgery in the gastrointestinal surgery clinic of the study center. The study was approved by the ethics committee of the study hospital (2020.2/01-289). The study was conducted following ethical standards defined in the Declaration of Helsinki, as revised in 2013. The hospital archive was used to review the files of patients who underwent GC surgery between January 2013 and August 2019. The study included patients who were 20 years and older, with an Eastern Cooperative Oncology Group (ECOG) performance status of ≤2, and who underwent open surgery because of GC. The study excluded patients with pathologic diagnoses other than adenocarcinoma, those who underwent a laparoscopic approach, those who had stage 4 disease, those who underwent palliative surgeries, those with no abdominal computed tomography (CT) scans acquired within the last pre-operative month, and those requiring an additional organ resection (including splenectomy). Antibiotic prophylaxis was utilized in all patients. Intravenous cefazolin 1–2 g was utilized for prophylaxis at induction of anesthesia and an additional dose was given every three hours as needed.

The patients were initially divided into two groups based on the presence of sarcopenia. Sarcopenia diagnoses were based on pre-operative CT imaging. The total psoas area (TPA) of the bilateral psoas muscles in the sequence visualizing the two transverse processes at the level of lumbar 3 (L3) vertebra was measured and summed by the consulting radiologist. The Hounsfield unit scale (−29 to +150) was used to identify skeletal muscles within the remaining structures. The total calculated area was proportioned to the square of the patient's height. According to the international consensus definition, sarcopenia refers to a skeletal muscle index (SMI) of <545 mm²/m² in males and <385mm²/m² in females [11,12]. The demographic data and post-operative SSIs were then compared between the two patient groups. The surgical site was assessed for the presence of infection, according to the diagnostic criteria set by the U.S. Centers for Disease Control and Prevention (CDC). Surgical site infections were classified into three groups: superficial, deep, or organ/space [13]. Patients were measured for weight and height within the last week before surgery, and body mass indices were calculated (BMI ≥30 was considered obese). The patients were further divided into sarcopenic obesity, sarcopenic non-obesity, non-sarcopenic obesity, and non-sarcopenic non-obesity groups based on the presence of sarcopenia and obesity for the SSI comparison. Pre-operative hemoglobin, albumin, C-reactive protein (CRP), carcinoembryonic antigen (CEA), and CA 19-9 values were recorded. Patients receiving treatment for diabetes mellitus, those with coronary artery disease, and those receiving neoadjuvant therapy were recorded. Patients who had smoked within the last month were classified as active smokers.

Duration of operation, amount of intra-operative blood loss, resection type, pathologic stage, post-operative complications (Clavien-Dindo classification ≥1), and length of hospital stay were all recorded.

Statistical analysis

Continuous variables with a normal distribution were expressed as mean and standard deviation (SD). Categorical data were expressed as numbers and percentages. The clinical parameters were compared using a Student t-test and Pearson χ² test. Factors with an effect on SSI were evaluated with a univariable analysis. A p value of <0.05 was considered statistically significant. All analyses were performed by SPSS version 25.0 (IBM, Armonk, NY) software package.

Results

The study included 149 patients who underwent GC surgery with available pre-operative CT images. Excluded from the study were 10 patients whose pre-operative CT images could not be accessed. The mean age of the patients was 59.3 years, and there were 98 (65.8%) male patients. In addition, 22 patients (14.8%) had diabetes mellitus and 43 patients (28.9%) were active smokers. A total gastrectomy was performed in 87 patients (58.4%), whereas the remainder underwent a subtotal gastrectomy. Post-operative complications were detected in 59 (39.6%) patients, whereas 28 (18.7%) patients developed SSIs. The demographic data of the patients are presented in Table 1.

Table 1.

Clinical Characteristics of the Patients

	Total (n = 149)
Age (y)
Mean ± SD	59.3 ± 11.9
Range	28–84
Gender; n (%)
Male	98 (65.8)
Female	51 (34.2)
BMI (kg/m²); mean ± SD	27.1 ± 4.8
ASA grade (%)
1	3 (2)
2	34 (22.8)
3	111 (74.5)
4	1 (0.7)
Diabetes mellitus (yes); n (%)	22 (14.8)
Coronary artery disease (yes); n (%)	48 (32.2)
Smoker (yes); n (%)	43 (28.9)
History of neoadjuvant therapy; n (%)	44 (29.5)
Sarcopenia (yes); n (%)	57 (38.3)
Type of resection; n (%)
Subtotal gastrectomy	62 (41.6)
Total gastrectomy	87 (58.4)
Post-operative complication; n (%)	59 (39.6)
Surgical site infection (yes); n (%)	28 (18.7)

Values are presented as mean ± SD or n (%) are presented.

SD = standard deviation; BMI = body mass index; ASA = American Society of Anesthesiologists.

Sarcopenia was detected in 57 (38.3%) patients. The mean age was 59.9 years in the sarcopenic group (SG) and 58.9 years in the non-sarcopenic group (NSG) (p = 0.55). Total psoas area and SMI were found to be associated with sarcopenia (p < 0.001 and p < 0.001, respectively). There was no statistically significant difference in the distribution of factors across the groups that could be a risk factor for SSI, such as diabetes mellitus, smoking, history of neoadjuvant therapy, pre-operative hemoglobin and albumin levels, amount of intra-operative blood loss, duration of operation, resection type, and lymph node dissection width (Table 2). Post-operative complications were more common in the SG, although the difference was not statistically significant: 26 patients (45.6%) in SG and 31 (33.6%) patients in NSG (p = 0.23). The SG was associated with longer hospital stays than the NSG (13.7 days vs. 12.5 days; p = 0.28; Table 3).

Table 2.

Demographic and Clinical Factors Associated with Sarcopenia

	Sarcopenic (n = 57)	Non-sarcopenic (n = 92)	p
Age (y); mean ± SD	59.9 ± 12.7	58.9 ± 11.4	0.55
Gender; n (%)			0.21
Male	34 (59.6)	64 (69.5)
Female	23 (40.4)	28 (30.5)
BMI (kg/m²); mean ± SD	25.4 ± 5.2	28.2 ± 4.2	0.30
TPA (mm²); mean ± SD	1057.1 ± 292.7	1793.9 ± 492.2	<0.001
SMI (mm²/m²); mean ± SD	382.5 ± 86.3	646.2 ± 154.3	<0.001
ASA; n (%)			0.65
1–2	13 (22.8)	24 (35.2)
3–4	44 (77.2)	68 (64.8)
Diabetes mellitus (yes); n (%)	7 (12.2)	15 (16.3)	0.50
Smoker (yes); n (%)	21 (36.8)	22 (23.9)	0.09
Coronary artery disease (yes); n (%)	16 (28)	32 (34.7)	0.39
History of neoadjuvant therapy; n (%)	16 (28)	28 (30.4)	0.75
Pre-operative albumin (<3.5 mg/dL); n (%)	9 (17.3)	7 (7.6)	0.11
Pre-operative CRP (>3 mg/dL); n (%)	14 (24.5)	11 (11.9)	0.045
Pre-operative hemoglobin (<10 mg/dL); n (%)	13 (22.8)	18 (19.5)	0.63
Pre-operative CEA (>5 ng/mL); n (%)	13 (22.8)	18 (19.5)	0.63
Pre-operative CA 19-9 (>37 U/mL); n (%)	10 (17.5)	21 (22.8)	0.44

SD = standard deviation; BMI = body mass index; TPA = total psoas area; SMI = skeletal muscle index; ASA = American Society of Anesthesiologists; CEA = carcinoembryonic antigen.

Table 3.

Surgical Procedure and Post-Operative Course

	Sarcopenic (n = 57)	Non-sarcopenic (n = 92)	p
Intra-operative blood loss (≥250 mL); n (%)	7 (12.2)	13 (14.1)	0.74
Surgical duration (min); mean ± SD	282.2 ± 55.4	283.2 ± 61.9	0.67
Type of resection			0.26
Subtotal gastrectomy	27 (47.3)	35 (38.1)
Total gastrectomy	30 (52.7)	57 (61.9)
Extent of lymph node dissection			0.26
D1	1 (1.7)	5 (5.4)
D2	56 (98.3)	87 (94.5)
Pathologic stage; n (%)			0.72
1	12 (21)	16 (17.4)
2	22 (38.6)	33 (35.9)
3	23 (40.3)	43 (46.7)
Length of hospital stay (d); mean ± SD	13.7 ± 8.9	12.5 ± 8.6	0.28
Post-operative complication; n (%)	26 (45.6)	31 (33.6)	0.23
SSI; n (%)	17 (29.8)	11 (11.9)	0.007
Superficial incisional	4 (7)	5 (5.3)	0.018
Deep incisional	8 (14)	2 (2.2)
Organ/space	5 (8.8)	4 (4.4)

SD = standard deviation; SSI = surgical site infetion.

Surgical site infection was observed in 28 patients, but was not associated with age, gender, obesity, intra-operative blood loss, duration of operation, or diabetes mellitus. Only sarcopenia was found to be a risk factor for SSIs (29.8% in SG; 11.9% in NSG; p = 0.007). Table 4 provides data on SSIs and risk factors. Surgical site infections were detected as superficial incisional in nine patients, deep incisional in 10 patients, and organ/space in nine patients. Although obesity was not found to be a risk factor for SSIs, the sarcopenic obesity group had the highest SSI rate (40%), whereas the non-sarcopenic non-obesity group had the lowest (9%; p = 0.024). No statistically significant association was established between sarcopenic obesity and the layer affected by the infection (superficial, deep, or organ/space; p = 0.055; Table 5).

Table 4.

Incidence and Univariable Analysis of Factors Associated with SSI

	Patients with SSI
	n	(%)	p
Age; y
<65	18/101	(17.8)	0.66
≥65	10/48	(20.8)
Gender			0.79
Male	19/98	(19.3)
Female	9/51	(17.6)
BMI; kg/m²			0.37
≥30	9/38	(23.6)
<30	19/111	(17.1)
Serum albumin (g/dL)			0.17
<3.5	5/16	(31.2)
≥3.5	23/133	(17.2)
Intra-operative blood loss; mL			0.09
≥250	1/20	(5)
<250	27/129	(20.9)
Operation time, min			0.70
≥280	20/102	(19.6)
<280	8/47	(17)
Diabetes mellitus			0.60
Yes	5/22	(22.7)
No	23/127	(18.1)
Smoker			0.97
Yes	8/43	(18.6)
No	20/106	(18.8)
Neoadjuvant therapy			0.73
Yes	9/44	(20.4)
No	19/105	(18)
Type of resection			0.48
Subtotal gastrectomy	10/62	(16.1)
Total gastrectomy	18/87	(20.6)
Extent of lymph node dissection			0.22
D1	0	0
D2	28/143	(19.5)

SSI = surgical site infection; BMI = body mass index.

Table 5.

Relation between Sarcopenia-Obesity and Localization of SSI

	All (n = 149)	SO (n = 10)	SN (n = 47)	NO (n = 26)	NN (n = 66)	p
Superficial incisional (%)	9 (6)	1 (10)	3 (6.4)	3 (11.5)	2 (3)	0.055
Deep incisional (%)	10 (6.7)	1 (10)	7 (14.8)	0	2 (3)
Organ/space (%)	9 (6)	2 (20)	3 (6.4)	2 (7.7)	2 (3)
Total (%)	28 (18.7)	4 (40)	13 (27.6)	5 (19.2)	6 (9)	0.024

SSI = surgical site infection; SO = sarcopenic obesity group; SN = sarcopenic nonobesity group; NO = nonsarcopenic obesity group; NN = nonsarcopenic nonobesity group.

Discussion

Surgical site infections are a leading cause of morbidity after gastric surgery, with reported rates of up to 28% [3,4,14]. The present study found the rate of SSIs to be 18.7%. There are few studies examining the link between SSIs after GC surgery and sarcopenia. In the study by Nishigori et al. [10] including 157 patients who underwent laparoscopic gastrectomy, the incidence of SSIs was 20%, with sarcopenic obesity increasing the risk. The present study also established a negative effect of sarcopenia on SSIs (p = 0.007). A direct effect of obesity on SSIs could not be found, although sarcopenic obese patients had the highest SSI rate (40%), followed by the sarcopenic non-obesity, non-sarcopenic obesity, and non-sarcopenic non-obesity groups in terms of frequency (27.6%, 19.2%, and 9%, respectively). This was statistically significant when considered together with the sarcopenia-obesity and SSI association (p = 0.024).

The consensus of the European Working Group on Sarcopenia in Older People (EWGSOP) categorizes sarcopenia into primary sarcopenia and secondary sarcopenia [8]. Age-related sarcopenia is called primary sarcopenia, whereas sarcopenia related to such causes as inflammatory disease, malnutrition, and cancer is called secondary sarcopenia. In the present study, the mean age was higher in the SG than in the NSG, although not to a statistically significant degree (p = 0.55). Secondary sarcopenia, which was detected in 38.3% of the patients and caused by cancer, resulted in SSIs after gastric surgery at a rate of 29.8%. Sarcopenia is a modifiable risk factor. We believe that protein supplementation and exercise in the pre-operative period may reduce post-operative morbidity in patients with sarcopenia.

The mechanism by which sarcopenia leads to SSIs after GC surgery is not fully known. One possible cause is the fact that increased metabolic activity resulting in muscle loss caused by sarcopenia leads to severe systemic inflammation [15]. As an alternative mechanism, the loss of skeletal muscle was demonstrated to have a negative impact on proinflammatory cytokines, and such causes are believed to increase the incidence of SSIs [16].

Computed tomography assessment has become almost the standard method for the detection of sarcopenia. Diagnosis is established in surgical candidates through CT for pre-operative routine staging, providing savings in cost and more radiation.

The study by Migita et al. [7] reported an SSI rate of 16.8% after elective gastrectomy among 842 patients, with superficial incisional, deep incisional, and organ/space SSIs of 5.9%, 0.2%, and 10.7%, respectively. The present study established similar rates (6%, 6.7%, and 6%, respectively). In SG, the rate of deep incisional SSIs was 14%, followed by organ/space (8.8%), and superficial incisional SSIs (7%).

The primary result of the present study is that the development of SSIs after GC surgery is affected by the presence of sarcopenia. Although obesity alone was not identified as a risk factor, the rate of SSIs increased to 40% in the presence of sarcopenic obesity. In planning the research, the priority was not to examine the effect of sarcopenic obesity on SSIs, however, SSI was found to increase further in the presence of sarcopenic obesity. Based on these two results, such risks should be taken into consideration in terms of SSI development during the planning of GC surgery.

The present study has a number of limitations. The first is its single-center and retrospective study design, which may have biased patient selection and affected the collection of study data. Despite its retrospective design, some data were collected prospectively, without changing the follow-up strategy, although such parameters as the patients' grip strength, walking speed, and fatigue were not evaluated. In addition, 10 ineligible patients with no records of CT scans carried out within the 30 days prior to the operation could not be evaluated for sarcopenia. Prospective studies involving a larger number of patients may reduce the complications. Another condition that can be regarded as a limitation is that no cutoff values were used to determine the skeletal muscle index. It was performed with a universally accepted value because of the differences in sarcopenia according to race, gender, and age group.

In conclusion, the present study observed sarcopenia as a risk factor for the development of SSIs after GC surgery. The authors believe that further study into reducing the incidence of SSIs, which are still a substantial cause of morbidity after CG surgery, should be supported.

Footnotes

Funding Information

No funding was received.

Author Disclosure Statement

No competing financial interests exist.

References

Torre

, Bray

, Siegel

, et al. Global cancer statistics, 2012. CA Cancer J Clin, 2015; 65:87–108.

Japanese Gastric Cancer Association. Japanese Gastric Cancer Treatment Guidelines 2018 (5th edition). Gastric Cancer [Epub ahead of print; DOI: 10.1007/s10120-020-01042-y].

Jeong

, Ann

, Kim

, et al. Incidence and risk factors for surgical site ınfection after gastric surgery: A multicenter prospective cohort study. Infect Chemother, 2013; 45:422–430.

Hirao

, Tsujinaka

, Imamura

, et al. Overweight is a risk factor for surgical site infection following distal gastrectomy for gastric cancer. Gastric Cancer, 2013; 16:239–244.

Hennessey

, Burke

, Ni-Dhonochu

, et al. Preoperative hypoalbuminemia is an independent risk factor for the development of surgical site infection following gastrointestinal surgery. A multi-institutional study. Ann Surg. 2010; 252:325–329.

Tovar

, Oller

, Llavero

, et al. Pre-operative and early post-operative factors associated with surgical site infection after laparoscopic sleeve gastrectomy. Surg Infect, 2013; 14:369–373.

Migita

K TT

, Matsumoto

, et al. Risk factors for surgical site infections after elective gastrectomy. J Gastrointest Surg, 2012; 16:1107–1115.

Cruz-Jentoft

, Baeyens

, Bauer

, et al. Sarcopenia: European consensus on definition and diagnosis: Report of the European working group on sarcopenia in older people. Age Ageing, 2010; 39:412–423.

Zhang

, Lin

, Chen

, et al. Sarcopenic obesity is associated with severe postoperative complications in gastric cancer patients undergoing gastrectomy: A prospective study. J Gastrointest Surg, 2018; 22:1861–1869.

10.

Nishigori

, Tsunoda

, Okabe

, et al. Impact of sarcopenic obesity on surgical site infection after laparoscopic total gastrectomy. Ann Surg Oncol, 2016; 23:524–531.

11.

Olmez

, Karakose

, Bozkurt

, et al. Sarcopenia is associated with increased severe postoperative complications after colon cancer surgery. Arch Med Sci [Epub ahead of print: DOI: 10.5114/aoms.2019.88621].

12.

Fearon

, Strasser

, Anker

, et al. Definition and classification of cancer cachexia: An international consensus. Lancet Oncol, 2011; 12:489–495.

13.

National Healthcare Safety

Network

. Surgical Site Infection (SSI) Event. Centers for Disease Control and Prevention; Atlanta

: 2013. www.cdc.gov/nhsn/PDFs/pscMa (Last accessed October 29, 2020).

14.

Ozalp

, Zulfikaroglu

, Gocmen

, et al. Risk factors for surgical site infection after gastrectomy with D2 lymphadenectomy. Surg Today, 2009; 39:1013–1015.

15.

Dodson

, Baracos

, Jatoi

, et al. Muscle wasting in cancer cachexia: Clinical implications, diagnosis, and emerging treatment strategies. Annu Rev Med, 2011; 62:265–279.

16.

Miyamoto

, Hanna

, Zhang

, et al. Molecular pathways: Cachexia signaling: A targeted approach to cancer treatment. Clin Cancer Res, 2016; 22:3999–4004.