Weak grip, weak anastomosis? Handgrip strength and sarcopenia as predictors of anastomotic leakage after colorectal cancer surgery

Abstract

BACKGROUND

Anastomotic leakage is one of the most severe complications after colorectal cancer surgery. Sarcopenia and impaired functional muscle performance have been increasingly recognized as potential predictors of postoperative morbidity.

AIM

To investigate whether radiological sarcopenia and preoperative handgrip strength independently predict anastomotic leakage in patients undergoing colorectal cancer resection with primary anastomosis.

METHODS

This single-center retrospective study reviewed patients who underwent elective colorectal cancer surgery with primary anastomosis between January 2020 and June 2024. Preoperative handgrip strength was available for 117 patients who constituted the study group. Sarcopenia was defined using computed tomography-derived skeletal muscle index at the third lumbar vertebra level. Tumor-related and surgery-related variables were recorded. Independent predictors of anastomotic leakage were identified using multivariable logistic regression, and model discrimination was evaluated using receiving operator curve analysis.

RESULTS

Among the 117 analyzed patients, 14 (12.0%) developed anastomotic leakage. Patients with leakage had significantly lower skeletal muscle index and weaker handgrip strength. In multivariable analysis, sarcopenia, low handgrip strength, American Society of Anesthesiologists score, and operative time were independently associated with an increased risk of anastomotic leakage (all P < 0.05). The predictive model demonstrated good discrimination with an area under the curve of 0.83 (95% confidence interval: 0.76-0.91).

CONCLUSION

Radiological sarcopenia and reduced handgrip strength independently predict anastomotic leakage after colorectal cancer surgery, supporting the integration of muscle strength and computed tomography-based muscle mass measures for improved preoperative risk stratification.

Key Words: Colorectal neoplasms; Sarcopenia; Anastomotic leakage; Muscle strength; Risk prediction; Surgical outcomes

Core Tip: Anastomotic leakage remains a major cause of morbidity after colorectal cancer surgery, yet current risk stratification models rely predominantly on technical and anatomical factors. This study demonstrates that both radiological sarcopenia and reduced preoperative handgrip strength are strong and independently associated predictors of anastomotic leakage. Notably, functional muscle strength showed a particularly robust association with leakage risk, underscoring the importance of incorporating functional assessments alongside morphometric measures. Simple, low-cost handgrip testing may enhance preoperative risk evaluation and help identify patients who could benefit from targeted prehabilitation or protective surgical strategies.

INTRODUCTION

Burden of anastomotic leakage in colorectal cancer surgery

Colorectal cancer is among the most common malignancies worldwide, and surgical resection remains the cornerstone of curative treatment. Despite significant advances in surgical techniques and perioperative care, anastomotic leakage continues to be one of the most serious postoperative complications, with an incidence ranging from 2% to 20%[1]. Anastomotic leakage is associated with prolonged hospitalization, reoperation, sepsis, and reduced long-term survival, making its prevention a persistent challenge in colorectal surgery[2]. Because anastomotic leakage is multifactorial, accurate preoperative identification of high-risk patients is essential for targeted perioperative optimization and appropriate anastomotic planning.

Limitations of traditional risk assessment models

Previous research has predominantly focused on technical and anatomical factors contributing to anastomotic leakage, such as tumor location, anastomotic height, and intraoperative blood loss. However, these models often fail to account for the patient’s physiological and functional reserve, which may play an equally decisive role in anastomotic integrity. Emerging evidence suggests that morphometric parameters alone may not fully capture the complexity of surgical risk, underscoring the need to integrate functional measures - such as muscle strength - into preoperative assessment frameworks[3]. This paradigm shift reflects growing interest in frailty-related determinants of postoperative outcomes, particularly in older or physiologically vulnerable patients.

Sarcopenia as a prognostic factor in colorectal cancer

Sarcopenia, defined as the progressive loss of skeletal muscle mass and function, has recently emerged as an important prognostic factor in surgical oncology[4]. In patients with colorectal cancer, sarcopenia has been associated with increased postoperative morbidity, higher infection rates, and prolonged recovery[5]. Computed tomography (CT)-based assessment of skeletal muscle at the level of the third lumbar vertebra (L3) provides an objective and reproducible method for quantifying muscle depletion. However, most existing studies evaluate sarcopenia using static morphometric indices such as the skeletal muscle index, often overlooking the functional component of muscle performance that may better reflect physiological reserve[6]. Consequently, the predictive value of radiological sarcopenia alone remains limited in heterogeneous surgical populations.

Role of functional muscle strength in surgical risk

Functional muscle strength, particularly when assessed using simple handgrip or manometric techniques, provides a direct measure of metabolic resilience and surgical tolerance[7]. Handgrip strength reflects not only muscle quantity but also muscle quality and neuromuscular function, factors that are critical for postoperative healing and anastomotic integrity. Therefore, combining radiologic and functional assessments may offer a more comprehensive and clinically relevant understanding of surgical risk[8]. This integrated approach is especially pertinent in colorectal cancer surgery, where tissue perfusion, host immunity, and collagen synthesis capacity play key roles in anastomotic healing.

Study rationale and objectives

In this context, the present study aimed to investigate whether preoperative sarcopenia and reduced functional muscle strength independently predict anastomotic leakage in patients undergoing elective colorectal resection with primary anastomosis. We hypothesized that diminished preoperative muscle strength, together with radiologically defined sarcopenia, would be associated with an increased risk of anastomotic leakage following colorectal cancer surgery.

MATERIALS AND METHODS

Study design and ethical approval

This retrospective study analyzed the medical records of patients who underwent elective colorectal cancer surgery with primary anastomosis at Malatya Training and Research Hospital (affiliated with Malatya Turgut Özal University) in Malatya, Türkiye, between January 2020 and June 2024. This study was approved by the Ethics Committee of Malatya Turgut Özal University (Approval No. E-30785963-020-329253) and was conducted in accordance with the principles of the Declaration of Helsinki.

Patient selection

All patients who underwent elective colorectal cancer surgery with primary anastomosis at Malatya Training and Research Hospital in Malatya (Türkiye) between January 2020 and June 2024 were identified. During this period, 388 patients underwent colorectal resection for malignancy. Because preoperative handgrip strength measurement is not a component of the standard colorectal cancer workup at our institution, these data were not uniformly available for all surgical candidates.

To obtain functional muscle strength information retrospectively, the medical records of these 388 patients were reviewed from the date of colorectal cancer diagnosis backward over the preceding 12 months. Patients who, within this 1-year interval, had presented to the outpatient clinics of physical medicine and rehabilitation, orthopedics, or neurosurgery for complaints such as extremity weakness, musculoskeletal pain, functional limitation, or gait imbalance were identified. In these clinics, standardized handgrip dynamometry is performed as part of routine clinical evaluation. Handgrip strength data derived from these visits were retrieved from the electronic medical record system.

Among the 388 patients, 117 had both a documented handgrip strength measurement obtained within 12 months prior to surgery and a preoperative contrast-enhanced abdominal CT scan performed as part of the routine oncologic staging workup that was suitable for assessment of skeletal muscle area at the L3 vertebral level. These 117 patients constituted the analytic group. Because handgrip strength assessment is not part of routine preoperative evaluation for colorectal cancer at our institution, the functional dataset represents a clinically relevant but inherently selected subgroup. Therefore, the study group represents a selected subgroup of patients, and a degree of selection bias cannot be excluded.

Patients were excluded if they met any of the following criteria: Emergency colorectal surgery for obstruction, perforation, or uncontrolled bleeding; absence of a primary anastomosis (e.g., Hartmann procedure, permanent diversion, or abdominoperineal resection); lack of a preoperative CT scan adequate for skeletal muscle index calculation; absence of retrievable handgrip strength data within the defined 1-year interval; non-adenocarcinoma colorectal malignancies (e.g., neuroendocrine tumors or lymphoma); metastatic (stage IV) disease; hereditary colorectal cancer syndromes (e.g., Lynch syndrome or familial adenomatous polyposis); inflammatory bowel disease; or incomplete clinical, operative, or postoperative documentation.

Inclusion criteria

Patients were included if they were 18 years or older, had histologically confirmed colorectal adenocarcinoma, underwent elective colorectal resection with primary anastomosis, had a preoperative abdominal CT scan suitable for skeletal muscle index calculation, and had a recorded handgrip strength measurement obtained within the 12 months before surgery.

Exclusion criteria

Patients were excluded if they underwent emergency colorectal surgery due to perforation, obstruction, or acute bleeding, as emergency physiology may significantly influence postoperative outcomes. Individuals in whom a primary anastomosis was not created, including those undergoing Hartmann procedure, intraoperative permanent diversion, or abdominoperineal resection, were also excluded. Cases without adequate preoperative CT imaging that allowed accurate assessment of skeletal muscle area at the L3 level, as well as patients without recorded handgrip strength measurements, were not eligible. Patients with metastatic (stage IV) disease, non-adenocarcinoma colorectal malignancies such as neuroendocrine tumors or lymphoma, hereditary cancer syndromes including Lynch syndrome or familial adenomatous polyposis, and inflammatory bowel diseases such as Crohn’s disease or ulcerative colitis were excluded to avoid confounding. Individuals with incomplete clinical, operative, or postoperative data were similarly excluded. To evaluate potential selection bias related to the availability of handgrip strength measurements, baseline demographic and clinical characteristics of included and excluded patients were compared (Table 1). Because handgrip dynamometry in these outpatient clinics is typically performed in patients presenting with functional or musculoskeletal complaints, the available handgrip dataset reflects a clinically selected subgroup.

Table 1 Comparison of baseline demographic and clinical characteristics between included and excluded patients, mean ± SD/n (%).

Variable	Included, n = 117	Excluded, n = 271	P value
Age in years	64.8 ± 12.9	66.1 ± 13.5	0.370
BMI (kg/m2)	26.7 ± 2.6	26.3 ± 2.8	0.175
ASA score	2.5 ± 0.7	2.6 ± 0.8	0.217
Female sex	44 (37.6)	108 (39.9)	0.762
Tumor location: Right/Left/rectum	42/20/55	96/44/131	0.964
Anastomotic leakage, 30-day	14 (12.0)	29 (10.7)	0.726

Excluded patients primarily lacked retrievable preoperative handgrip strength data. Continuous variables are presented as mean ± SD, and categorical variables as n (%) or n. Between-group comparisons were performed using Welch’s t-test for continuous variables and Pearson’s χ² test or Fisher’s exact test for categorical variables, as appropriate. BMI: Body mass index; ASA: American Society of Anesthesiologists.

Sarcopenia assessment

Sarcopenia was assessed using the CT-derived skeletal muscle index at the level of the L3. Because European Working Group on Sarcopenia in Older People 2 emphasizes muscle strength and does not prescribe universal CT-based cut-off values, sex-specific L3-skeletal muscle index thresholds that were originally derived and have been widely applied in oncologic populations were used (< 52.4 cm²/m² for men and < 38.5 cm²/m² for women), as described by Prado et al[9] and supported by subsequent gastrointestinal oncology literature[10,11]. The CT image analysis was performed retrospectively by a single experienced radiologist; blinding to clinical outcomes was not feasible due to the retrospective study design.

Functional muscle strength evaluation

Handgrip strength was measured using a calibrated Jamar^® hydraulic dynamometer following standardized American Society of Hand Therapists protocol. Three measurements were obtained from the dominant hand, and the highest value was recorded. Because handgrip and CT assessments were obtained as part of routine care rather than a controlled protocol, minor timing variability occurred; however, all values were obtained in the preoperative period within the predefined institutional windows for functional assessment and oncologic staging.

Operative and clinical variables

Demographic characteristics including age, sex, and body mass index (BMI), as well as comorbidity burden expressed by American Society of Anesthesiologists (ASA) score, were recorded. Tumor location was categorized as right colon, left colon, or rectum. For rectal cancer, anastomotic level was classified as high colorectal (> 10 cm from the anal verge), mid colorectal (5-10 cm), low colorectal (< 5 cm), or coloanal. For colon resections, anastomosis type was categorized as ileocolic or colocolic.

All operations in this group were performed using an open surgical approach; no laparoscopic or robotic procedures were included during the study period. The decision to create a diverting stoma, when applicable, was recorded. Operative time was defined as the interval between skin incision and closure. Neoadjuvant chemoradiotherapy status was documented for rectal cancer patients.

Outcome definition

The primary outcome was anastomotic leakage, defined as a clinically or radiologically confirmed disruption of anastomotic integrity resulting in leakage of luminal contents within 30 days after surgery.

Statistical analysis

Normality of continuous variables was assessed using the Shapiro-Wilk test. Depending on distribution, continuous variables were reported as mean ± SD or median (interquartile range) and compared using Student’s t-test or the Mann-Whitney U test. Categorical variables were compared using χ² or Fisher’s exact test. Univariate logistic regression was initially performed to identify variables associated with anastomotic leakage. Variables with P < 0.10 were subsequently entered into a multivariate logistic regression model to determine independent predictors. Results were expressed as odds ratios (ORs) with 95% confidence intervals (CIs). Model performance was evaluated using the area under the receiver operating characteristic (ROC) curve. All analyses were performed using SPSS version 25.0 (IBM Corp., Armonk, NY, United States). No imputation was performed for missing data, as patients without handgrip measurements were excluded from the analysis. Given the limited number of anastomotic leakage events, an additional reduced multivariable logistic regression model was constructed to assess the robustness of the association between handgrip strength, sarcopenia, and anastomotic leakage, excluding operative time to minimize potential overfitting.

RESULTS

Patient characteristics

During the study period, 388 patients underwent colorectal cancer surgery. Among these, 117 patients had both preoperative L3-level CT imaging and documented handgrip strength measurements and were included in the final analysis (Figure 1). All patients underwent open colorectal resection with primary anastomosis. Anastomotic leakage developed within 30 days after surgery in 14 patients (12.0%). The median interval between handgrip strength assessment and surgery was 4.2 months (2.1-7.6 months).

Figure 1 Axial computed tomography image at the third lumbar vertebra level showing the segmented skeletal muscle area (outlined in green). Skeletal muscle index was calculated as the cross-sectional area of the psoas, paraspinal, and abdominal wall muscles at the third lumbar vertebra level, normalized for height squared (cm²/m²).

The demographic and clinical characteristics of patients included in the analytic group (n = 117) were compared with those of excluded patients who lacked preoperative handgrip strength data (n = 271). There were no statistically significant differences between included and excluded patients with respect to age, BMI, ASA score, sex distribution, tumor location, or 30-day anastomotic leakage rates (all P > 0.05). These findings suggest that the study group was broadly representative of the overall colorectal cancer population treated during the study period, despite the selective availability of handgrip strength measurements (Table 1).

Patients who developed anastomotic leakage exhibited a more compromised physiological profile, including significantly higher ASA scores (3.1 ± 0.8 vs 2.4 ± 0.7, P = 0.02), longer operative times (211.5 ± 27.8 minutes vs 178.6 ± 24.3 minutes, P = 0.010), and markedly reduced handgrip strength (19.4 ± 3.8 kg vs 27.5 ± 4.9 kg, P < 0.001). Sarcopenia was also more prevalent in the anastomotic leakage group (64.3% vs 37.8%, P = 0.04). Although sarcopenia occurred in 39 of the 103 patients without anastomotic leakage, its substantially higher frequency in those who developed leakage suggests that impaired muscle mass may contribute to anastomotic vulnerability in the presence of additional physiological stressors (Table 2).

Table 2 Demographic, clinical, and operative characteristics according to anastomotic leakage status, mean ± SD/n (%).

Variable	No AL (n = 103)	AL (n = 14)	P value
Age in years	64.5 ± 12.8	67.2 ± 13.4	0.360
Female sex	36 (35.0)	8 (57.1)	0.130
BMI (kg/m2)	26.9 ± 2.5	25.4 ± 2.1	0.090
ASA score	2.4 ± 0.7	3.1 ± 0.8	0.020
Sarcopenia	39 (37.8)	9 (64.3)	0.040
Handgrip strength (kg)	27.5 ± 4.9	19.4 ± 3.8	< 0.001
Operative time (minutes)	178.6 ± 24.3	211.5 ± 27.8	0.010
Anastomosis type
Ileocolic	41 (39.8)	1 (7.1)
Colocolic	19 (18.4)	1 (7.1)
High colorectal	21 (20.4)	1 (7.1)
Mid colorectal	14 (13.6)	2 (14.3)
Low colorectal	7 (6.8)	6 (42.9)
Coloanal	1 (1.0)	3 (21.4)

Anastomosis type: P values were not calculated for anastomosis type due to small cell counts across categories. BMI: Body mass index; ASA: American Society of Anesthesiologists; AL: Anastomotic leakage.

Univariate analysis

On univariate logistic regression analysis, several variables demonstrated significant associations with anastomotic leakage. Sarcopenia increased the odds of leakage nearly threefold (OR = 2.75, 95%CI: 1.10-6.89, P = 0.03). Higher ASA scores and prolonged operative duration were also associated with increased leakage risk. Handgrip strength demonstrated a strong inverse relationship, with each 1 kg reduction associated with a higher likelihood of anastomotic leakage (OR = 0.89, 95%CI: 0.81-0.99, P = 0.031). Age, sex, and BMI did not show statistically significant associations (Table 3).

Table 3 Univariate logistic regression analysis for predictors of anastomotic leakage.

Variable	OR (95%CI)	P value
Sarcopenia	2.75 (1.10-6.89)	0.030
ASA score	1.68 (1.01-2.93)	0.046
Operative time (minutes)	1.01 (1.00-1.02)	0.041
Handgrip strength (kg)	0.89 (0.81-0.99)	0.031
BMI (kg/m2)	0.92 (0.82-1.03)	0.140
Age in years	1.02 (0.98-1.07)	0.290
Male sex	0.76 (0.31-1.89)	0.540

ASA: American Society of Anesthesiologists; BMI: Body mass index; OR: Odds ratio; CI: Confidence interval.

Multivariate analysis

Variables with P < 0.10 in univariate analysis (sarcopenia, ASA score, operative time, handgrip strength) were entered into the multivariate logistic regression model. All four variables remained independent predictors of anastomotic leakage. Sarcopenia remained a significant risk factor (OR = 2.89, 95%CI: 1.18-7.04, P = 0.018). Higher ASA scores and longer operative duration also independently increased the risk of leakage. Handgrip strength retained its protective association, with each 1 kg increase reducing anastomotic leakage risk by approximately 9% (OR = 0.91, 95%CI: 0.83-1.00, P = 0.049) (Table 4). To address concerns regarding model stability, a reduced multivariable model including handgrip strength, sarcopenia, and ASA score was additionally evaluated. In this reduced model, the direction of the associations between reduced handgrip strength, sarcopenia, and anastomotic leakage remained consistent with the primary analysis, supporting the robustness of the observed relationships despite the limited number of events.

Table 4 Multivariate logistic regression for independent predictors of anastomotic leakage.

Variable	OR (95%CI)	P value
Sarcopenia	2.89 (1.18-7.04)	0.018
ASA score	1.74 (1.02-3.01)	0.043
Operative time (minutes)	1.01 (1.00-1.02)	0.036
Handgrip strength (kg)	0.91 (0.83-1.00)	0.049

ASA: American Society of Anesthesiologists; OR: Odds ratio; CI: Confidence interval.

Model performance

The multivariate model incorporating sarcopenia, ASA score, operative duration, and handgrip strength demonstrated strong predictive performance, with an area under the curve of 0.83 (95%CI: 0.76-0.91). The ROC curve for the model is shown in Figure 2.

Figure 2 Receiver operating characteristic curve demonstrating the predictive accuracy of the multivariate logistic regression model incorporating sarcopenia, American Society of Anesthesiologists score, operative time, and handgrip strength. The model was developed for exploratory purposes; therefore, no specific clinical cut-off value was defined. AUC: Area under the curve.

Model calibration was satisfactory, as indicated by the Hosmer-Lemeshow test (P = 0.62), demonstrating good agreement between predicted and observed outcomes. These results highlight that combining handgrip strength with CT-derived skeletal muscle index improves discrimination for anastomotic leakage risk and enhances the accuracy of predicting postoperative anastomotic failure. Accordingly, the multivariate model should be interpreted as exploratory and hypothesis-generating rather than as a definitive clinical prediction tool.

Skeletal muscle index and muscle strength distribution

Skeletal muscle index was significantly lower in the anastomotic leakage group [42.3 cm²/m² (8.4-46.1 cm²/m²)] than in the non-anastomotic leakage group [median 46.7 cm²/m² (43.5-50.4 cm²/m²), P = 0.03]. Handgrip strength demonstrated an even more robust separation between groups, with markedly reduced values in patients who developed leakage [19 kg (16-23 kg)] compared with those without leakage [27 kg (24-31 kg), P < 0.001; Figure 3]. These findings emphasize that functional muscle impairment may provide stronger prognostic information than radiological muscle mass alone.

Figure 3 Box-and-whisker plots demonstrating the distribution of skeletal muscle index and handgrip strength according to anastomotic leakage status. A: Patients who developed anastomotic leakage (n = 103) exhibited significantly lower skeletal mass index (cm²/m²) values (P = 0.03) compared with those without anastomotic leakage (n = 14); B: Patients who developed anastomotic leakage (n = 103) exhibited reduced handgrip strength (kg; P < 0.001) compared with those without anastomotic leakage (n = 14). SMI: Skeletal mass index.

Sensitivity analysis

In a sensitivity analysis excluding patients whose handgrip strength measurements had been obtained more than 6 months before surgery (n = 47), the remaining group (n = 70) demonstrated a directionally consistent association between reduced handgrip strength and anastomotic leakage. Patients who developed leakage exhibited lower handgrip strength compared to those without leakage; however, statistical significance was not reached, likely due to the limited number of leakage events in this restricted group.

DISCUSSION

Principal findings

This study demonstrated that both radiological sarcopenia and reduced handgrip strength are independent predictors of anastomotic leakage after elective colorectal cancer surgery. While previous studies have largely focused on morphometric indices derived from CT imaging[12], our findings indicate that muscle function may provide complementary - and in some cases stronger - prognostic information. Functional capacity reflects the integrated metabolic, neuromuscular, and immunologic status of the patient, which may be more relevant to anastomotic healing than muscle mass alone.

Comparison with previous studies and leakage rates

The incidence of anastomotic leakage in this group (12%) is comparable to previously reported rates ranging between 8% and 15%[13]. The higher ASA scores, decreased muscle strength, and prolonged operative times observed among patients with anastomotic leakage support the notion that impaired physiological reserve contributes significantly to postoperative anastomotic failure. Sarcopenia, characterized by progressive loss of muscle mass and function, has been increasingly recognized as a marker of frailty and poor postoperative outcomes[14]. In the present analysis, patients who developed leakage exhibited both lower skeletal muscle index and markedly reduced handgrip strength, suggesting that deterioration in functional muscle performance may amplify the adverse consequences of structural muscle depletion.

Biological plausibility and potential mechanisms

Several biological pathways support the observed association between sarcopenia and impaired anastomotic healing. Chronic systemic inflammation and catabolic cytokine activation - including interleukin-6, tumor necrosis factor-α, and myostatin - promote protein breakdown, reduce collagen synthesis, and impair angiogenesis at the anastomotic site[15]. Furthermore, reduced muscle strength is associated with impaired microvascular perfusion and diminished metabolic reserve, both of which are essential for adequate oxygenation and tissue repair[16]. These mechanisms provide a plausible physiological explanation for why both muscle mass and functional strength emerged as independent predictors of anastomotic leakage in this study. Future prospective, multicenter groups with standardized preoperative handgrip assessment are needed to externally validate these findings and to determine whether incorporating functional sarcopenia into the enhanced recovery after surgery pathways or anastomotic decision-making can improve clinical outcomes.

Added value of combining morphometric and functional metrics

Previous literature has linked sarcopenia with postoperative complications, increased infection rates, and prolonged recovery after colorectal surgery[17]. However, only a limited number of studies have evaluated direct measures of muscle function alongside radiological muscle mass. Our study expands upon existing evidence by demonstrating that integrating skeletal muscle index and muscle strength improves discrimination of anastomotic leakage risk, as reflected by an area under the curve of 0.83 in ROC analysis. These findings support a more comprehensive approach to preoperative risk assessment, consistent with recent consensus emphasizing the importance of functional criteria in diagnosing clinically significant sarcopenia.

Clinical implications and role of prehabilitation

From a clinical perspective, these results underscore the potential value of prehabilitation programs that target both nutritional optimization and muscle strengthening. Interventions such as resistance training, protein supplementation, and metabolic optimization have been shown to improve postoperative outcomes[18]. Given that handgrip dynamometry is simple, inexpensive, and reproducible, incorporating functional strength assessment into routine preoperative evaluation may help identify vulnerable patients who would benefit most from targeted prehabilitation strategies[19].

Limitations

This study has several limitations that should be acknowledged when interpreting the findings. The retrospective, single-center design inherently limits causal inference and may reduce the generalizability of the results to other institutions with different patient populations and perioperative practices.

Preoperative handgrip strength assessment was not part of the routine colorectal cancer workup at our institution and was therefore available only in a selected subgroup of patients. Handgrip measurements were primarily obtained during visits to physical medicine and rehabilitation, orthopedics, or neurosurgery clinics, which were often prompted by functional or musculoskeletal complaints. As a result, the analyzed group represents a clinically selected subgroup, and selection bias cannot be excluded. Because patients presenting with functional complaints may have lower baseline muscle strength, the observed association between reduced handgrip strength and anastomotic leakage may be overestimated, and effect sizes should therefore be interpreted with caution. Although baseline demographic and clinical characteristics, including anastomotic leakage rates, did not differ significantly between included and excluded patients, unmeasured differences related to functional status or frailty may still exist.

Handgrip strength and CT-based body composition measurements were obtained at variable time points before surgery, reflecting real-world clinical practice rather than a standardized assessment protocol. Muscle strength may have deteriorated during this interval, particularly in patients undergoing neoadjuvant chemoradiotherapy or experiencing disease-related decline, an issue that may be especially relevant in rectal cancer patients. To address this concern, a sensitivity analysis excluding patients whose handgrip measurements were obtained more than 6 months before surgery was performed and demonstrated directionally consistent associations, although statistical significance was not reached due to the limited number of leakage events.

The number of anastomotic leakage events in this group was limited, and the multivariable analyses should therefore be interpreted as exploratory and hypothesis-generating rather than definitive. To reduce the risk of overfitting, a reduced multivariable model excluding operative time was additionally evaluated, and the consistency of associations across models supports the robustness of the observed relationships despite limited statistical power.

Anastomotic level is a well-established determinant of leakage risk, particularly in low colorectal and coloanal anastomoses. Although substantial differences in leakage rates across anastomotic levels were observed, the small number of events within individual strata precluded reliable inclusion of anastomotic level in multivariable or subgroup analyses. Consequently, residual confounding related to anastomotic level cannot be fully excluded.

Sarcopenia was defined using sex-specific CT-derived skeletal muscle index thresholds that are widely applied in oncologic populations. However, the European Working Group on Sarcopenia in Older People 2 consensus does not prescribe universal CT-based cutoff values, and alternative thresholds have been proposed across different populations. Therefore, extrapolation of these findings to groups using different sarcopenia definitions or with distinct ethnic body composition profiles should be performed cautiously.

Finally, CT-based muscle measurements were performed by a single experienced radiologist, and inter-observer or intra-observer reliability could not be formally assessed. Prospective, multicenter studies with standardized assessment protocols, routine preoperative functional testing, and larger event numbers are warranted to validate these findings and to determine whether targeted interventions aimed at improving muscle strength can reduce anastomotic leakage after colorectal cancer surgery.

Clinical implications

This study emphasizes the value of incorporating functional muscle assessment into routine preoperative evaluation. Identifying patients with low muscle strength may enhance perioperative decision-making, particularly in low colorectal or coloanal anastomoses where leakage risk is highest. Integrating simple, inexpensive handgrip testing into surgical pathways may help guide targeted prehabilitation interventions - such as resistance training, nutritional optimization, and protein supplementation - which could improve muscle strength and potentially reduce the risk of anastomotic leakage. Because handgrip testing is inexpensive, rapid, and highly reproducible, it represents a practical tool that can be seamlessly incorporated into standard surgical workflows.

Recognizing functional sarcopenia before surgery enables clinicians to individualize perioperative management. Patients with low muscle strength may benefit from enhanced preoperative monitoring, more cautious intraoperative strategies - particularly in low colorectal or coloanal anastomoses - and proactive use of protective diversion when appropriate. Moreover, early identification of physiologically vulnerable patients allows for targeted implementation of prehabilitation protocols, including resistance training, nutritional optimization, protein supplementation, and correction of metabolic derangements. Such interventions have been shown to improve muscle strength, immune competence, and wound healing capacity, all of which may directly reduce the risk of anastomotic failure.

Integrating functional muscle assessment into perioperative pathways aligns with the goals of enhanced recovery after surgery and National Surgical Quality Improvement Program initiatives to improve outcome prediction and personalize surgical care. The present findings support incorporating handgrip strength alongside CT-based muscle assessment to enhance preoperative risk stratification and improve postoperative outcomes in colorectal surgery.

CONCLUSION

Preoperative sarcopenia and reduced muscle strength were independently associated with an increased risk of anastomotic leakage following colorectal resection. Among all evaluated parameters, impaired functional muscle strength demonstrated the strongest correlation with leakage, underscoring the importance of functional - rather than purely morphometric - assessments in preoperative risk evaluation. Incorporating muscle strength measurement into standard preoperative assessment may improve risk stratification and guide personalized perioperative optimization. Early implementation of prehabilitation strategies focusing on resistance training, nutritional support, and metabolic conditioning may enhance muscle function and reduce anastomotic complications. Future multicenter prospective studies are warranted to validate these findings and to determine whether correcting functional sarcopenia can directly improve surgical outcomes.