Background: Anastomotic leakage is generally defined as disruption of the integrity of a surgically created intestinal connection resulting in leakage of luminal contents into the surrounding tissues or peritoneal cavity. Early identification of patients at increased risk is essential for optimizing perioperative management. The neutrophil-to-lymphocyte ratio (NLR), an inexpensive and readily available marker of systemic inflammation, has emerged as a potential predictor of adverse surgical outcomes. Objectives: To evaluate the association between preoperative neutrophil-to-lymphocyte ratio and the occurrence of postoperative leak following small bowel surgeries, and to assess variations in NLR between elective and emergency surgical settings. Methods: A prospective cohort study was conducted in the Department of General Surgery at Dr. D. Y. Patil Medical College, Hospital and Research Institute, Kolhapur. Forty-five adult patients undergoing elective or emergency small bowel surgeries with primary anastomosis were enrolled and followed prospectively. Preoperative NLR was calculated from complete blood counts obtained within 24 hours before surgery. Patients were monitored throughout hospitalization for development of postoperative leak. Statistical analyses included comparison of NLR between leak and non-leak groups and receiver operating characteristic (ROC) curve analysis to determine predictive performance. Results: Mean age observed was 48.04 ± 18.09 years. Emergency surgeries constituted 80.0% of cases. Postoperative leak occurred in 7 patients. Patients without leak demonstrated a significantly higher median preoperative NLR than those who developed leak (7.96 vs. 2.34; p=0.0068). The ROC analysis showed that pre-operative NLR had an AUC of 0.827, with a 95% CI of 0.676–0.978. The associated p-value was 0.0068, indicating statistically significant diagnostic performance. An optimal NLR cutoff value of 4.09 yielded a sensitivity of 71.4%, specificity of 81.6%, accuracy of 80.0%, positive predictive value of 41.7%, and negative predictive value of 93.9%. The mean time to leak occurrence was 5.4 days postoperatively. Conclusions: Preoperative NLR demonstrated significant discriminatory ability in identifying patients at risk of postoperative leak following small bowel surgery. Although patients who developed leaks exhibited lower NLR values than those without leaks, the high negative predictive value suggests that NLR may be useful for identifying patients at lower risk of postoperative leak. Preoperative NLR should be considered an adjunctive tool for perioperative risk stratification and clinical surveillance rather than a standalone predictor.
Small bowel surgery represents an essential component of gastrointestinal surgical practice and is frequently performed for a wide range of benign and malignant conditions, including intestinal obstruction, inflammatory disease, perforation, trauma, neoplasms, and congenital anomalies.[1] Despite advances in operative techniques, perioperative care, and postoperative monitoring, anastomotic leakage continues to be one of the most serious and feared complications following intestinal surgery.[2] Early identification of patients at risk for anastomotic leakage is therefore of paramount importance in improving surgical outcomes and guiding timely therapeutic interventions.[3]
Anastomotic leakage may present with the appearance of enteric contents or pus in surgical drains, formation of intra-abdominal collections detected on imaging, or direct evidence of anastomotic dehiscence during reoperation.[4] If diagnosis is delayed, leakage can progress rapidly to generalized peritonitis, septic shock, multiple organ dysfunction, and death. Furthermore, delayed initiation of appropriate treatment has been shown to significantly reduce survival rates, highlighting the importance of early recognition and prediction of this complication.[5]
Recent investigations have demonstrated that the neutrophil-to-lymphocyte ratio may serve as a more reliable predictor of postoperative outcomes than absolute neutrophil or lymphocyte counts alone.[6] The ratio integrates two opposing components of the inflammatory response and therefore provides a more comprehensive assessment of immune status.[6] Several studies evaluating patients undergoing gastrointestinal surgery have reported significantly higher neutrophil-to-lymphocyte ratio values in individuals who subsequently developed anastomotic leakage compared with those who did not experience this complication.[7] These findings suggest that neutrophil-to-lymphocyte ratio may have an important role in identifying high-risk patients in the perioperative period.[7]
Neutrophil-to-lymphocyte ratio (NLR) has been evaluated alongside markers such as C-reactive protein, white blood cell count, platelet-to-lymphocyte ratio, and serum albumin for predicting anastomotic leakage.[7,8] Although several biomarkers are associated with leakage, NLR offers a favorable combination of diagnostic accuracy, cost-effectiveness, and ease of availability.[7] Unlike procalcitonin, which is relatively expensive, NLR can be readily calculated from routine blood investigations, making it particularly useful in resource-limited clinical settings.[7,8]
Given the serious consequences of anastomotic leakage and the limitations of existing diagnostic methods the study was conducted to evaluate the role of neutrophil-to-lymphocyte ratio in predicting leakage after small bowel surgery may therefore contribute to improved postoperative surveillance, earlier intervention, and better overall surgical outcomes.[7]
The prospective cohort study was conducted in the Department of General Surgery at Dr. D. Y. Patil Medical College, Hospital and Research Institute, Kolhapur, for a period of 18 months after receiving ethical clearance from the Institutional Ethics Committee. Consecutive sampling technique was employed and a total of 45 patients were recruited for the study. Inclusion Criteria Patients aged 18 years and above who underwent elective or emergency small bowel surgeries with primary anastomosis, availability of complete preoperative blood count within 24 hours prior to surgery, ready to provide written informed consent. Exclusion Criteria Patients with presence of pre-existing inflammatory diseases such as rheumatoid arthritis or inflammatory bowel disease, hematological disorders or hematological malignancies affecting leukocyte counts, receiving corticosteroids, chemotherapy, or immunosuppressive therapy prior to surgery, and pregnant ladies. Patients admitted for small bowel surgeries were screened according to eligibility criteria. After confirming suitability for inclusion, written informed consent was obtained from each participant in their local language. Pre-operative complete blood count investigations were performed within 24 hours before surgery as part of routine clinical evaluation. Neutrophil and lymphocyte values obtained from these investigations were used to calculate the neutrophil-to-lymphocyte ratio. Patients subsequently underwent small bowel surgery with primary anastomosis as per standard surgical indications. All procedures were performed according to institutional surgical protocols without modification for research purposes. Following surgery, patients were monitored in surgical wards or intensive care units depending on clinical condition. Postoperative surveillance included monitoring of abdominal signs, systemic parameters, and drain output for evidence of intestinal content suggestive of leak. Patients who developed leak received standard management for enteric fistula or anastomotic leak as per institutional treatment guidelines. Data were collected using a structured proforma and entered into Microsoft Excel. Statistical analysis was performed using the SPSS 26.0 version. Results were interpreted using appropriate statistical methods to evaluate the relationship between inflammatory status and postoperative outcomes.
Table 1: Demographic and Clinical Characteristics of the Study Population
|
Variable |
Category/Parameter |
Frequency (%) / Mean ± SD |
|
Age |
Mean age (years) |
48.04 ± 18.09 |
|
Median age (years) |
46 |
|
|
Range (years) |
19–80 |
|
|
Age Category |
≤20 years |
3 (6.7%) |
|
21–40 years |
15 (33.3%) |
|
|
41–60 years |
15 (33.3%) |
|
|
>60 years |
12 (26.7%) |
|
|
Gender |
Male |
28 (62.2%) |
|
Female |
17 (37.8%) |
|
|
Primary Diagnosis |
Duodenal perforation |
14 (31.1%) |
|
Ileal perforation |
12 (26.7%) |
|
|
Small bowel obstruction |
9 (20.0%) |
|
|
O/c/o exploratory laparotomy with ileostomy |
4 (8.9%) |
|
|
Ileal polyp |
2 (4.4%) |
|
|
Ileocecal polyp |
2 (4.4%) |
|
|
Jejunal perforation |
2 (4.4%) |
|
|
Type of Surgery |
Exploratory laparotomy with Graham’s patch repair |
24 (53.3%) |
|
Resection and anastomosis |
17 (37.8%) |
|
|
Ileostomy reversal |
4 (8.9%) |
|
|
Pre-operative CBC Profile |
Lymphocyte (%) |
13.84 ± 9.92 |
|
Neutrophil (%) |
77.01 ± 11.61 |
The study population comprised 45 patients with a mean age of 48.04 ± 18.09 years, indicating that small bowel surgical pathologies predominantly affected middle-aged and older adults. A male predominance was observed (62.2%), suggesting a higher burden of these conditions among men. Most patients were admitted on an emergency basis (80.0%), reflecting the acute presentation of small bowel disorders requiring urgent surgical intervention. Duodenal perforation and ileal perforation were the most common underlying diagnoses, collectively accounting for more than half of the cases, while exploratory laparotomy with Graham’s patch repair was the most frequently performed procedure. Pre-operative hematological evaluation demonstrated elevated neutrophil counts and relatively low lymphocyte counts, indicative of a systemic inflammatory response commonly associated with intra-abdominal sepsis, perforation, and bowel pathology. Overall, the demographic and clinical profile represents a cohort of predominantly emergency surgical patients with significant inflammatory burden at presentation.
Table 2: Distribution of Admission Type (Elective vs. Emergency)
|
Category |
Frequency |
Percentage |
|
ELECTIVE |
9 |
20 |
|
EMERGENCY |
36 |
80 |
|
Total |
45 |
100 |
Among the 45 patients, 36 patients (80.0%) were admitted as emergency cases, while 9 patients (20.0%) underwent elective admission. This indicates that the majority of patients undergoing small bowel surgeries in the study were managed under emergency conditions, with elective cases forming a smaller proportion of the total sample.
Table 3: Descriptive Statistics of Pre-operative NLR
|
Parameter |
Sample (N) |
Mean |
Median |
Std. Dev |
IQR |
Min - Max |
|
NLR |
45 |
11.24 |
7.51 |
12.14 |
3.76 - 13.17 |
1.27 - 62.73 |
Among 45 patients, the mean pre-operative neutrophil-to-lymphocyte ratio was 11.24, with a median of 7.51. The standard deviation was 12.14, showing wide variability in NLR values. The interquartile range was 3.76–13.17, while the minimum and maximum NLR values were 1.27 and 62.73, respectively.
Table 4: Overall Incidence of Anastomotic Leak
|
Category |
Frequency |
Percentage |
|
NO |
38 |
84.4 |
|
YES |
7 |
15.6 |
|
Total |
45 |
100.0 |
Among 45 patients, anastomotic leak was absent in 38 patients (84.4%) and present in 7 patients (15.6%). This shows that the overall incidence of anastomotic leak in the study population was 15.6%, while the majority of patients did not develop leak following small bowel surgery.
Table 5: Shapiro-Wilk Test of Normality for NLR
|
Variable |
Test.Statistic..W. |
P. Value |
Conclusion |
|
Pre-operative NLR |
0.7251 |
<0.001 |
Non-Normal Distribution |
The Shapiro-Wilk test for pre-operative NLR showed a test statistic value of 0.7251 with a p-value <0.001. Since the p-value was statistically significant, the distribution of pre-operative NLR was classified as non-normal. Therefore, non-parametric statistical testing was used for comparison of NLR between study groups.
Table 6: Comparison of NLR (Leak vs. No Leak)
|
Group |
Sample (N) |
Median NLR |
IQR |
P-Value (Mann-Whitney) |
|
NO |
38 |
7.96 |
4.86 - 16.75 |
0.0068 |
|
YES |
7 |
2.34 |
1.77 - 4.77 |
|
Among 45 patients, the no leak group included 38 patients with a median NLR of 7.96 and IQR of 4.86–16.75. The leak group included 7 patients with a median NLR of 2.34 and IQR of 1.77–4.77. The Mann-Whitney test showed a statistically significant difference with p=0.0068.
Table 7: Comparison of NLR (Elective vs. Emergency)
|
Group |
Sample (N) |
Median NLR |
IQR |
P-Value (Mann-Whitney) |
|
ELECTIVE |
9 |
2.41 |
1.51 - 3.4 |
0.0052 |
|
EMERGENCY |
36 |
7.96 |
5.16 - 15.5 |
|
Among 45 patients, the elective group included 9 patients with a median NLR of 2.41 and IQR of 1.51–3.4. The emergency group included 36 patients with a median NLR of 7.96 and IQR of 5.16–15.5. The difference was statistically significant with a Mann-Whitney p-value of 0.0052.
Table 8: Area Under the Curve (AUC) for NLR
|
Test_Variable |
AUC |
Lower 95% CI |
Upper 95% CI |
P-Value |
|
Pre-operative NLR |
0.827 |
0.676 |
0.978 |
0.0068 |
The ROC analysis showed that pre-operative NLR had an AUC of 0.827, with a 95% CI of 0.676–0.978. The associated p-value was 0.0068, indicating statistically significant diagnostic performance. This suggests that pre-operative NLR showed good accuracy in differentiating patients with and without anastomotic leak.
Table 9: Diagnostic Performance of NLR at Optimal Cutoff
|
Metric |
Value |
|
Optimal NLR Cutoff |
4.09 |
|
Sensitivity (%) |
71.40 |
|
Specificity (%) |
81.60 |
|
Accuracy (%) |
80.00 |
|
Positive Predictive Value (%) |
41.70 |
|
Negative Predictive Value (%) |
93.90 |
The optimal pre-operative NLR cutoff was 4.09. At this cutoff, sensitivity was 71.40%, specificity was 81.60%, and overall accuracy was 80.00%. The positive predictive value was
41.70%, while the negative predictive value was 93.90%, indicating stronger ability of NLR to identify patients unlikely to develop leak.
Table 10: Comparison of Pre-operative NLR According to Anastomotic Leak Status and Final Clinical Outcome
|
Final Outcome |
Anastomotic Leak |
Sample (N) |
Median NLR |
IQR |
Mortality Timing (Post-operative Day) |
P-value (Mann–Whitney) |
|
Death (n=8) |
No |
6 |
15.27 |
8.95–21.04 |
2–5 |
0.2433 |
|
Yes |
2 |
4.65 |
3.07–6.23 |
3–5 |
||
|
Discharge (n=37) |
No |
32 |
7.70 |
4.72–13.45 |
NA |
0.0155 |
|
Yes |
5 |
2.34 |
2.04–3.76 |
NA |
Among patients who died, the median pre-operative NLR was higher in those without anastomotic leak compared to those with leak; however, this difference was not statistically significant (p = 0.2433). In contrast, among discharged patients, a significant difference in NLR was observed between leak and non-leak groups (p = 0.0155). These findings suggest that the relationship between pre-operative NLR and anastomotic leak may vary according to clinical outcome. The lack of statistical significance among mortality cases is likely attributable to the small sample size, whereas the significant difference observed among discharged patients indicates a potential association between pre-operative inflammatory status and postoperative leak occurrence.
Table 11: Point-Biserial Correlation Results
|
Metric |
Value |
|
Point-Biserial Correlation Coefficient (r) |
-0.287 |
|
P-Value |
0.056 |
Point-biserial correlation analysis between pre-operative NLR and anastomotic leak among 45 patients showed a correlation coefficient of r = -0.287. The p-value was 0.056, indicating a weak negative correlation that did not reach statistical significance. This suggests that the direct correlation between NLR and leak incidence was not statistically significant.
Anastomotic leak is one of the most serious postoperative complications following bowel surgery and is associated with increased morbidity, sepsis, prolonged hospital stays, need for re-intervention, and mortality. Early identification of patients at risk is therefore essential for improving postoperative surveillance and timely management. The aim of the present study was to evaluate the role of pre-operative neutrophil-to-lymphocyte ratio in predicting anastomotic leak after small bowel surgeries. The present study included 45 patients undergoing small bowel surgery, with a mean age of 48.04 ± 18.09 years and a predominance of middle-aged adults. Males constituted 62.2% of the study population, demonstrating a male predominance similar to that reported by Chiarelli et al. [9]. Emergency admissions accounted for 80% of cases, reflecting the acute nature of the underlying surgical conditions. Duodenal perforation (31.1%) and ileal perforation (26.7%) were the most common diagnoses, while exploratory laparotomy with Graham’s patch repair was the most frequently performed procedure. These findings indicate that the study population largely comprised emergency surgical patients with significant inflammatory burden. Pre-operative hematological evaluation revealed neutrophil predominance and relative lymphopenia, resulting in an elevated mean NLR of 11.24, suggesting the presence of systemic inflammatory response. Similar associations between inflammatory markers and gastrointestinal surgical pathology have been described by Xie et al. [10], Köksal et al. [11], and Chiarelli et al. [9]. The mean pre-operative NLR was 11.24 with considerable variability (SD 12.14), reflecting heterogeneous inflammatory status among patients. The Shapiro–Wilk test demonstrated a non-normal distribution (W=0.7251, p<0.001), necessitating the use of non-parametric statistical methods. The observed NLR values were higher than several previously reported cutoffs for leak prediction, likely reflecting the predominance of emergency cases and perforation-related pathology in the present cohort. Similar elevations in NLR have been associated with severe bowel pathology and intestinal compromise by Xie et al. [10] and Rădulescu et al. [12]. The incidence of anastomotic leak was 15.6%, with 7 of 45 patients developing postoperative leakage. This rate is comparable to that reported by Wu et al. [13] and He et al. [14], who observed leak rates of approximately 15% in upper gastrointestinal surgery. The relatively high incidence may be attributed to the predominance of emergency surgeries, perforation-related pathology, contamination, and the heterogeneous nature of small bowel procedures included in the study. A statistically significant difference in pre-operative NLR was observed between leak and no-leak groups (p=0.0068). Interestingly, patients who developed anastomotic leak demonstrated a lower median NLR compared with those who did not develop leakage. This finding contrasts with previous studies by Miyakita et al. [15], Rădulescu et al. [12], and Haghi et al. [16], which reported higher NLR values among leak patients. The opposite trend observed in the present study may be explained by the disproportionately high inflammatory burden among emergency patients who ultimately did not develop leaks. Therefore, while NLR showed significant discriminatory ability, the direction of association differed from that commonly reported in the literature. Emergency patients demonstrated significantly higher NLR values than elective patients (p=0.0052), supporting the concept that acute surgical pathology is associated with heightened systemic inflammation. Similar findings have been reported by Xie et al. [10] and Köksal et al. [11], who observed elevated NLR values in patients with bowel compromise requiring urgent intervention. These findings suggest that admission type substantially influences baseline NLR and should be considered when interpreting its predictive role. ROC analysis demonstrated good discriminatory performance of pre-operative NLR for differentiating leak and no-leak groups, with an AUC of 0.827 (95% CI: 0.676–0.978; p=0.0068). An optimal cutoff value of 4.09 provided a sensitivity of 71.4%, specificity of 81.6%, and overall accuracy of 80%. Notably, the negative predictive value was high (93.9%), indicating that NLR may be more useful for identifying patients at low risk of leakage rather than confirming leak occurrence. Similar observations regarding the predictive utility of NLR have been reported by Ioannidis et al. [17], Wu et al. [13]. Among discharged patients, those who developed leaks had significantly lower NLR values than patients without leaks (p=0.0155), consistent with the overall study findings. Among mortality cases, although non-leak patients demonstrated higher median NLR values than leak patients, the difference was not statistically significant (p=0.2433), likely because of the small number of deaths and leak-related events. These findings suggest that elevated NLR may reflect overall systemic inflammatory burden and disease severity rather than leak occurrence alone. Similar observations regarding the relationship between inflammatory markers, postoperative complications, and mortality have been reported by Chiarelli et al. [9] and Manoğlu et al. [18]. Point-biserial correlation analysis demonstrated a weak negative correlation between pre-operative NLR and anastomotic leak (r = −0.287), which did not reach statistical significance (p=0.056). This finding supports the observed inverse relationship between NLR and leak occurrence in the present cohort. Although NLR demonstrated good discriminatory performance on ROC analysis, the absence of a significant linear correlation suggests that it should not be considered an independent predictor of leak. Similar findings have been reported by Pachajoa et al. [19], while prospective data included in the meta-analysis by Haghi et al. [16] also demonstrated inconsistent associations. Therefore, NLR should be interpreted as an adjunctive biomarker and used alongside clinical, operative, and postoperative parameters for risk stratification. A major strength of the present study is its evaluation of the neutrophil-to-lymphocyte ratio (NLR) as a readily available, cost-effective, and reproducible inflammatory biomarker for predicting anastomotic leak following small bowel surgery. The inclusion of both elective and emergency surgical cases enhances the clinical applicability of the findings and reflects routine surgical practice. Furthermore, the comprehensive analytical approach, incorporating demographic and clinical profiling, hypothesis testing, ROC curve analysis, and postoperative outcome assessment, provided a robust evaluation of the diagnostic performance of NLR. However, the study is limited by its relatively small sample size and the low number of anastomotic leak events, which may have reduced statistical power and restricted subgroup analyses. The heterogeneity of surgical procedures, predominance of emergency cases, and exclusive assessment of pre-operative NLR may have influenced the observed associations. Additionally, other potential determinants of anastomotic healing, including nutritional status, comorbidities, operative factors, and postoperative inflammatory markers, were not incorporated into the predictive model, thereby limiting the generalizability of the findings.
The present study evaluated the role of pre-operative neutrophil-to-lymphocyte ratio (NLR) in predicting anastomotic leak following small bowel surgeries and demonstrated a significant difference in NLR between patients with and without postoperative leak, with good diagnostic discrimination on ROC analysis. Interestingly, patients who developed anastomotic leak exhibited lower median NLR values than those without leak, suggesting that the relationship between pre-operative inflammatory status and leak occurrence is complex and influenced by factors such as emergency presentation, underlying bowel pathology, systemic inflammatory burden, operative findings, and disease severity. The predominance of emergency surgeries and perforation-related conditions may have substantially affected baseline inflammatory markers and postoperative outcomes. Although NLR showed good predictive performance and a high negative predictive value, indicating potential utility in identifying patients at lower risk of leak, clinical assessment, postoperative monitoring, and drain evaluation remain essential for early diagnosis. Therefore, pre-operative NLR should be considered an adjunctive tool for perioperative risk stratification rather than an independent predictor of anastomotic leak. Further large-scale prospective studies are required to validate the observed cutoff value and clarify the clinical significance of the inverse association identified in this cohort.