1 INTRODUCTION

Rectosigmoid resections are associated with a high risk of postoperative complications causing morbidity and mortality.^{1, 2} Major complications occur in 15%–18% of the patients, with anastomotic leakage being the most frequent with an incidence of up to 10%.^3-5 However, risk stratification is challenging, given that multiple studies have shown that a wide variety of factors correlate with risk of postoperative complications.⁶ This highlights the importance of accurate prediction models, that use robust clinical parameters to assess frailty and the associated surgical risk for these patients.^{6, 7} This is particularly important given that, with the increasing age of patients undergoing this type of surgery, the number of frail older adult patients increases.⁸ Preoperative selection of frail patients and subsequent targeted interventions, such as physical prehabilitation programs, have been shown to be potentially beneficial, leading to a reduction of postoperative complication rates.^9-11

Recently, some studies are reporting that skeletal muscle and psoas muscle volumes can be used as a proxy for patient frailty.⁷ Low skeletal muscle volume or psoas muscle volume is defined as sarcopenia, which can be relatively easily assessed using computed tomography (CT). Studies have shown that CT-based measurements of abdominal muscles, including the psoas muscle, have the potential in predicting adverse outcome in surgical patients.^{12, 13}

This study explores the potential prognostic value and clinical use of CT-based preoperative muscle measurements, such as skeletal muscle index (SMI) and psoas muscle index (PMI), in an attempt to predict anastomotic leakage after oncological rectosigmoid resections.

2 METHODS

2.2 CT-based measurements

All included patients had a preoperative contrast-enhanced (CE) abdominal CT in portal venous phase of no more than 3 months before surgery. Analysis of CT-scans was performed using Vitrea (version 7.14.2.227, Canon Medical). Muscle areas were determined by manually segmenting a region of interest (ROI) in the skeletal- and psoas muscles on the portovenous phase of the CE-CT images. The CT slice at the level of the inferior part of L3 was chosen for analysis, which is conform the criteria of previous studies.^{7, 13} Subsequently, the skeletal muscles and psoas muscle areas determined from the segmented ROIs (mm²).^{7, 13, 14} Total abdominal muscle area (TAMA) was categorized into specific abdominal muscle groups; psoas muscles, back muscles (erector spinae and quadratus lumborum muscles), lateral muscle (external- and internal oblique and transversus abdominis) and rectus abdominis (Figure 1). Additionally, total psoas area (TPA) was calculated by the sum of both psoas muscles. Two researchers (RTK and CJR) independently performed the image segmentation after ensuring an interobserver variability correlation of at least 0.8 in a training set, under supervision of a radiologist (ANC). Disagreements regarding measurements were resolved by discussion, with ANC acting as a third observer when necessary. The muscle areas were adjusted by patient's height (m) to standardize the measurement between patients. The height-normalized muscle areas (muscle indices) of the psoas and skeletal muscles (TAMA), PMI and SMI were used for further analysis. The units for muscle areas were cm² and muscle indexes, cm²/m².

3 RESULTS

3.1 Patient characteristics

A total of 215 patients underwent a sigmoid or rectal resection between 2016 and 2020 of which 48 were excluded because a CT scan was not present (Figure 2). Additionally, patients with emergency surgery (n = 3) and patients with stoma construction during primary surgery (n = 18) were excluded. Of the in total 146 included patients, 13 (8.9%) suffered from anastomotic leakage. There was a significant difference between the group of patients that suffered from anastomotic leakage and the group that did not with respect to age and the use of minimally invasive techniques (Table 1). There were no significant differences observed in comorbidities.

Table 1. Patient characteristics

	No anastomotic leakage	Anastomotic leakage	p-value
	n = 133 (91.1%)	n = 13 (8.9%)
Age (median)	59 (50–71)	68 (37–86)	<0.01
Gender (male)	80 (60.2%)	5 (38.5%)	0.22
ASA score			0.95
1–2	26 (19.5%)	3 (23.1%)
3–4	12 (9.0%)	10 (76.9%)
Comorbidity	74 (55.6%)	10 (76.9%)	0.24
BMI (median)	25.0 (19.5–41.3)	25.9 (17.5–34.7)	0.93
pT-stage			0.69
0	1 (0.8%)	0 (0.0%)
1–2	58 (43.6%)	6 (46.2%)
3–4	74 (55.6%)	7 (53.8%)
pN-stage			0.74
0	81 (60.9%)	9 (69.2%)
≥1	52 (39.1%)	4 (30.8%)
Neo-adjuvant chemoradiotherapy (CRT)	23 (17.3%)	4 (30.8%)	0.41
Type of surgery			0.25
Low-anterior resection (LAR)	64 (48.1%)	9 (69.2%)
Sigmoid resection	69 (51.9%)	4 (30.8%)
Minimally invasive			<0.01
Open	4 (3.0%)	2 (15.4%)
Laparoscopic	129 (97.0%)	11 (84.6%)

3.3 Nomograms

For preoperative prediction of anastomotic leakage regression model-based prediction models, using clinically- and statistically relevant parameters (age, gender, comorbidity, chemoradiotherapy, and SMI or PMI), were made. The prediction model using PMI had an AUC of 79.8% (Figure 3A) and using SMI as muscle parameter had an AUC of 79.0% (Figure 3B), respectively. Additionally, clinically usable nomograms were constructed using these prediction models with using PMI (Figure 4A) as muscle parameter and one using SMI (Figure 4B).

4 DISCUSSION

This study investigated the value of CT-based cross-sectional measurements of abdominal and psoas muscles as a prognostic factor for anastomotic leakage after curative intended oncological sigmoid or rectal resection. Cross-sectional measured abdominal and psoas muscle area were significantly lower in patients that suffered from anastomotic leakage. Furthermore, both PMI and SMI are both prognostic factors for anastomotic leakage following sigmoid and rectal resection.

Recent studies have shown an association between lower muscle volumes and short-term surgical outcomes after colorectal surgery.^{7, 12, 13} Literature reports that cross-sectional lumbar muscle areas are well correlated with muscle mass in the whole body.^{15, 16} However, analysis of CT images using a single-muscle approach such as the psoas major muscle, might be less laborious and therefore more realistic in a clinical setting, validation is, however, still lacking.¹⁷ As shown by Jones et al.,⁷ TPA and TAMA on the L3 level correlates well with clinical outcomes.⁷ However, these reports also showed that TAMA was more reproducibly measured by CT analysis than TPA. This is also observed in our study as the interobserver variability is higher in the TPA.

The association between low muscle mass and anastomotic leakage might be partly explained by frailty, since previous studies have shown an association between frailty and anastomotic leakage following colorectal surgery as well.^{7, 18, 19} However, there is no consensus on markers for determining patient frailty at this time, and identification of frail patients is still difficult.^{20, 21}

Skeletal muscle depletion is defined as a decrease in muscle mass, and it occurs when protein degradation exceeds protein synthesis. Potential causes of muscle atrophy are ageing, malnutrition, long-term immobilization, as well as various serious and often chronic diseases, such as chronic heart failure, chronic obstructive lung disease, renal failure, AIDS, sepsis, anorexia nervosa, and muscular dystrophies among others. Furthermore, skeletal muscle depletion may be the result from cancer too, as part of the cancer-cachexia syndrome.^22-24 Cancer cachexia is a wasting syndrome characterized by weight loss, anorexia, asthenia, and anemia. The pathogenicity of this syndrome is multifactorial, due to a complex interaction of tumor and host factors leading to muscle protein breakdown, thus to cachexia-related sarcopenia.^{23, 25} Several studies have shown a clear correlation between lower muscle mass and an increased inflammatory state due to tumor cachexia and frailty.^{26, 27} This might explain the association between sarcopenia and anastomotic leakage as well since a more katabolic and inflammatory state may hamper healing capacity in tissues such as bowel tissue resulting in anastomotic leakage.^{28, 29}

Additionally, aging in patients might explain this association, since CT-based muscle measurement may be more accurate than just age since it is more representative for biological age compared with calendar age. Ageing leads to trunk muscle attenuation, but such age-related differences vary widely between muscle groups.³⁰ Thicknesses of rectus abdominis, internal oblique, and external oblique muscles were 36%–48% smaller for older than younger adults.³¹ Additionally, trunk muscle deficits with increasing age may have important implications for physical function, disability, pain, and risk of injury in older adults.³²

Accurate prediction of postoperative complications and especially anastomotic leakage could improve preoperative patient selection, treatment decision and shared-decision making. An important dilemma in patients undergoing sigmoid or rectal resection is whether or not to construct an anastomosis and/or (temporary) stoma.³³ An important consideration is the risk of anastomotic leakage since a (temporary) diverting stoma can reduce the rate of clinical symptomatic anastomotic leakage.^{6, 34} Furthermore, measuring a low muscle mass on the preoperative CE-CT could be an indication for prehabilitation programs, since low muscle mass may be reversible.^{9, 11, 35} Especially, in rectal cancer patients undergoing neo-adjuvant chemo(radio)therapy, there is a greater window of preoperative optimization by physical exercise, which has been shown to be safe and feasible.³⁶ Prehabilitation programs have been shown to objectively improve physical fitness.³⁷ Additionally, since patients with lower skeletal muscle mass may experience more chemotherapy toxicity, this might be used in shared decision-making and treatment planning as well.^{38, 39}

5 CONCLUSION

In this exploratory analysis, low SMI and PMI were predictive for anastomotic leakage and show potential in treatment planning, shared decision making and engaging in prehabilitation programs. Since abdominal CT scans are routinely being performed for preoperative staging and treatment planning, they can easily be used to quantify muscle volumes without additional examinations or costs.

CONFLICTS OF INTEREST

The authors declare no conflicts of interest.

SYNOPSIS

Oncological sigmoid and rectal resections are accompanied with substantial risk of anastomotic leakage, preoperative risk assessment remains difficult. This study shows that using enhanced (CE) computed tomography (CT) – based muscle measurements can predict anastomotic leakage following oncological sigmoid and rectal resections.