Volume 31, Issue 1 (3-2024)
RJMS 2024, 31(1): 1-16 |
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Keramati M R, Fazeli A R, Karimi A M, Ahmadi‐Tafti S M, Behboudi B, Keshvari A, et al . Evaluation of the Relationship between Serum CRP Level and Pelvic Anastomotic Leakage in the First Days after Low Anterior Resection Surgery in Patients with Rectal Cancer. RJMS 2024; 31 (1) :1-16
URL: http://rjms.iums.ac.ir/article-1-8871-en.html
URL: http://rjms.iums.ac.ir/article-1-8871-en.html
Mohammad Reza Keramati 
, Amir Reza Fazeli , Amir Masoud Karimi , Seyed Mohsen Ahmadi‐Tafti , Behnam Behboudi , Amir Keshvari , Mohammad Sadegh Fazeli , Alireza Kazemeini
, Amir Reza Fazeli , Amir Masoud Karimi , Seyed Mohsen Ahmadi‐Tafti , Behnam Behboudi , Amir Keshvari , Mohammad Sadegh Fazeli , Alireza Kazemeini
Division of Colorectal Surgery, Colorectal Research Center, Department of Surgery, Tehran University of Medical Sciences, Tehran, Iran , mr-keramati@tums.ac.ir
Abstract: (169 Views)
Background & Aims: Colorectal cancer is the third leading cause of cancer-related deaths globally. Despite advancements in chemotherapy and radiotherapy for rectal cancer, surgical resection remains the primary treatment. Among various surgical techniques, low anterior resection (LAR) is particularly common. However, the procedure’s complication rates are significant. Anastomotic leakage, a serious complication post-rectal resection, occurs in 1-19% of cases and can result in prolonged hospital stays, infections, permanent stoma formation in 25% of patients, and even mortality. Patients with anastomotic leakage often require surgical intervention to prevent death. In such cases, most surgeons choose anastomosis takedown with the Hartmann procedure, which is complex and carries significant risks. Consequently, many patients face permanent stomas, negatively impacting their quality of life. Therefore, preventing anastomotic leakage is crucial. Diagnosing anastomotic leakage is challenging and often delayed. Clinical assessments by surgeons have low predictive value for this complication, and there is frequently a lag between the onset of leakage and changes in vital signs or leukocyte counts. C-reactive protein (CRP), an acute phase serum protein, rises following rectal resection and may indicate postoperative infectious complications, including anastomotic leakage. This study aims to evaluate serum CRP levels post-LAR in rectal cancer patients, assessing its association with anastomotic leakage.
Methods: This prospective cohort study included rectal cancer patients who underwent LAR surgery at Imam Khomeini Hospital in Tehran during 2021-2022. Based on inclusion and exclusion criteria, 66 patients were selected. Inclusion criteria involved patients undergoing LAR for rectal cancer, while exclusion criteria included immunodeficiency, previous abdominal surgeries, and incomplete data. Eligible patients were followed post-surgery, and demographic data (age, sex, BMI, diabetes history, smoking, distant metastases, neoadjuvant chemoradiotherapy history, TNM staging, leukocyte levels on postoperative days two, four, and six, complications, hospital stay length, and mortality rate) were collected. Serum CRP levels were assessed on postoperative days two, four, and six. Anastomotic leakage was identified based on clinical and radiological findings, and patients were categorized into leakage and non-leakage groups. The incidence of anastomotic leakage and its relationship with clinical/laboratory factors were statistically analyzed. The predictive value of postoperative serum CRP levels for early detection of anastomotic leakage was assessed using receiver operating characteristic (ROC) curves, and CRP levels were compared between the two groups across different postoperative days.
Results: The study included 66 patients (43 men, 23 women), aged 25-77. Anastomotic leakage occurred in 23.3% of men and 26.1% of women. Among the participants, 10.6% had diabetes and 16.7% smoked. Notably, 57.1% of diabetics and 27.3% of smokers experienced anastomotic leakage. 75.8% received neoadjuvant chemotherapy, and 80.3% had neoadjuvant radiotherapy, with leakage observed in 28% and 26.4%, respectively. 15.2% had distant metastases, with anastomotic leakage in 40% of these cases. Two patients (3.86%) died within 30 days post-surgery, both with a history of leakage and infection. Anastomotic leakage incidence by TMN stage was 33.3% for stage one, 23.5% for stage two, 41.2% for stage three, and 80% for stage four. Chi-square tests assessed the correlation between postoperative pelvic anastomotic leakage and factors like sex, diabetes history, smoking, neoadjuvant chemotherapy, neoadjuvant radiotherapy, postoperative complications, in-hospital mortality, and distant metastasis. Significant associations were found between leakage and postoperative complications and in-hospital mortality (p=0.000 and 0.001, respectively). No significant associations were observed for other factors. No significant correlation was found between leakage and TMN stage (p=0.148), but a significant association was observed between leakage and age groups (p=0.001). Independent t-tests comparing mean serum leukocyte levels indicated no statistical significance (p-values of 0.20, 0.07, and 0.06 on days two, four, and six, respectively). Mean CRP levels were 100.5 mg/L (leakage group) and 72.42 mg/L (non-leakage group) on day two, 105.68 mg/L and 75.92 mg/L on day four, and 153.12 mg/L and 103.16 mg/L on day six. Independent t-tests comparing CRP levels indicated significance (p-values of 0.0001, 0.0100, and 0.0000) across these days. ROC curve analysis established cut-off values of 98 mg/L for CRP on days two, four, and six, maximizing sensitivity and specificity for predicting leakage.
Conclusion: In our study, CRP levels on days two, four, and six were significantly higher in the leakage group. ROC analysis yielded cut-off values of 98 mg/L on postoperative days two, four, and six, demonstrating higher predictive power for leakage on day six. Previous studies also identified CRP as a predictor of anastomotic leakage. Ortega-Deballon et al. found CRP on days two and four as strong predictors of leakage and other septic complications, with day four showing areas under the curve of 0.804 and 0.787. Their cut-off of 125 mg/L on day four showed high sensitivity and negative predictive value for leakage. In our study, serum leukocyte levels in the leakage group exceeded those of the control group on all assessed days, though differences were not statistically significant. The consideration of WBC as a marker for leakage has been sparsely addressed, with some researchers reporting no significant correlation. Our findings revealed that 55.17% of patients with anastomotic leakage experienced other complications, and all patients with these complications also demonstrated leakage during hospitalization. Among those with leakage, 25% had diabetes, while 6% of the control group were diabetic, indicating a higher prevalence in the leakage group. Xiaoti Lin et al.’s meta-analysis linked diabetes independently with increased mortality risk due to leakage in colorectal surgeries, while Ziegler et al. found no impact on leakage but indicated higher mortality among diabetic patients with leakage. The average age of patients with leakage was significantly greater than that of the control group. Other studies also indicated that age correlates significantly with leakage risk. Lin et al. identified age over 70 as an independent risk factor for leakage.
Methods: This prospective cohort study included rectal cancer patients who underwent LAR surgery at Imam Khomeini Hospital in Tehran during 2021-2022. Based on inclusion and exclusion criteria, 66 patients were selected. Inclusion criteria involved patients undergoing LAR for rectal cancer, while exclusion criteria included immunodeficiency, previous abdominal surgeries, and incomplete data. Eligible patients were followed post-surgery, and demographic data (age, sex, BMI, diabetes history, smoking, distant metastases, neoadjuvant chemoradiotherapy history, TNM staging, leukocyte levels on postoperative days two, four, and six, complications, hospital stay length, and mortality rate) were collected. Serum CRP levels were assessed on postoperative days two, four, and six. Anastomotic leakage was identified based on clinical and radiological findings, and patients were categorized into leakage and non-leakage groups. The incidence of anastomotic leakage and its relationship with clinical/laboratory factors were statistically analyzed. The predictive value of postoperative serum CRP levels for early detection of anastomotic leakage was assessed using receiver operating characteristic (ROC) curves, and CRP levels were compared between the two groups across different postoperative days.
Results: The study included 66 patients (43 men, 23 women), aged 25-77. Anastomotic leakage occurred in 23.3% of men and 26.1% of women. Among the participants, 10.6% had diabetes and 16.7% smoked. Notably, 57.1% of diabetics and 27.3% of smokers experienced anastomotic leakage. 75.8% received neoadjuvant chemotherapy, and 80.3% had neoadjuvant radiotherapy, with leakage observed in 28% and 26.4%, respectively. 15.2% had distant metastases, with anastomotic leakage in 40% of these cases. Two patients (3.86%) died within 30 days post-surgery, both with a history of leakage and infection. Anastomotic leakage incidence by TMN stage was 33.3% for stage one, 23.5% for stage two, 41.2% for stage three, and 80% for stage four. Chi-square tests assessed the correlation between postoperative pelvic anastomotic leakage and factors like sex, diabetes history, smoking, neoadjuvant chemotherapy, neoadjuvant radiotherapy, postoperative complications, in-hospital mortality, and distant metastasis. Significant associations were found between leakage and postoperative complications and in-hospital mortality (p=0.000 and 0.001, respectively). No significant associations were observed for other factors. No significant correlation was found between leakage and TMN stage (p=0.148), but a significant association was observed between leakage and age groups (p=0.001). Independent t-tests comparing mean serum leukocyte levels indicated no statistical significance (p-values of 0.20, 0.07, and 0.06 on days two, four, and six, respectively). Mean CRP levels were 100.5 mg/L (leakage group) and 72.42 mg/L (non-leakage group) on day two, 105.68 mg/L and 75.92 mg/L on day four, and 153.12 mg/L and 103.16 mg/L on day six. Independent t-tests comparing CRP levels indicated significance (p-values of 0.0001, 0.0100, and 0.0000) across these days. ROC curve analysis established cut-off values of 98 mg/L for CRP on days two, four, and six, maximizing sensitivity and specificity for predicting leakage.
Conclusion: In our study, CRP levels on days two, four, and six were significantly higher in the leakage group. ROC analysis yielded cut-off values of 98 mg/L on postoperative days two, four, and six, demonstrating higher predictive power for leakage on day six. Previous studies also identified CRP as a predictor of anastomotic leakage. Ortega-Deballon et al. found CRP on days two and four as strong predictors of leakage and other septic complications, with day four showing areas under the curve of 0.804 and 0.787. Their cut-off of 125 mg/L on day four showed high sensitivity and negative predictive value for leakage. In our study, serum leukocyte levels in the leakage group exceeded those of the control group on all assessed days, though differences were not statistically significant. The consideration of WBC as a marker for leakage has been sparsely addressed, with some researchers reporting no significant correlation. Our findings revealed that 55.17% of patients with anastomotic leakage experienced other complications, and all patients with these complications also demonstrated leakage during hospitalization. Among those with leakage, 25% had diabetes, while 6% of the control group were diabetic, indicating a higher prevalence in the leakage group. Xiaoti Lin et al.’s meta-analysis linked diabetes independently with increased mortality risk due to leakage in colorectal surgeries, while Ziegler et al. found no impact on leakage but indicated higher mortality among diabetic patients with leakage. The average age of patients with leakage was significantly greater than that of the control group. Other studies also indicated that age correlates significantly with leakage risk. Lin et al. identified age over 70 as an independent risk factor for leakage.
Type of Study: Research |
Subject:
General Surgery
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