Abstract
-
Purpose
- We aimed to develop a predictive tool for anastomotic leakage (AL) following colon cancer surgery by combining a clinical early warning score (EWS) with the C-reactive protein (CRP) level.
-
Methods
- The records of 1,855 patients who underwent colon cancer surgery at the Oxford University Hospitals NHS Foundation Trust between January 2013 and December 2018, with or without AL, were retrospectively reviewed. EWS and CRP levels were assessed daily from the first postoperative day until discharge. AL was defined as an anastomotic defect observed at reoperation, the presence of feculent fluid in a pelvic drain, or evidence of AL on computed tomography. The tool incorporated postoperative EWS and CRP levels for the accurate early detection of AL.
-
Results
- From postoperative days 3 to 7, the mean CRP level exceeded 200 mg/L in patients with AL and was under 200 mg/L in those without AL (P<0.05). From postoperative days 1 to 5, the mean EWS among patients with leakage exceeded 2, while scores were below 2 among those without leakage (P<0.05). Receiver operating characteristic curve analysis identified postoperative day 3 as the most predictive of early leakage, with cutoff values of 2.4 for EWS and 180 mg/L for CRP; this yielded an area under the curve of 0.89 (sensitivity, 90%; specificity, 70%).
-
Conclusion
- We propose using an EWS of 2.4 and a CRP level of 180 mg/L on postoperative day 3 following colon surgery with anastomosis as threshold values to prompt investigation and treatment of AL.
-
Keywords: C-reactive protein; Anastomotic leak; Colon cancer; Early warning score
Graphical abstract
INTRODUCTION
Anastomotic leakage (AL) is a serious complication following colorectal surgery, carrying risks of severe outcomes such as sepsis, the need for reoperation, stoma creation, and even mortality [1–3]. AL can manifest in a delayed fashion, often becoming evident with the onset of sepsis at a median of approximately 7 days after surgery [3–5]. This delay may result in postponed intervention [2]. Notably, a Dutch study reported a 30-day mortality rate of 3% for elective surgery and 7% for emergency surgery associated with AL [6]. The substantial morbidity and mortality rates linked to AL have spurred research efforts to identify early markers [1, 3, 4, 7–10]. The objective is to identify reliable indicators that could enable swift identification and intervention in cases of AL [2], thus facilitating the safe early discharge of low-risk patients who are candidates for enhanced recovery protocols [1].
C-reactive protein (CRP) has become a focal point of research, with numerous studies employing a range of threshold values to predict AL [1, 3, 4, 7–9, 11, 12]. These studies have consistently highlighted the high negative predictive value (NPV) of CRP as a diagnostic tool for AL, which is relevant for both open and laparoscopic surgery [13]. While CRP levels naturally rise following the stress response to surgery, they typically peak within 48 hours and then decline [9]. Consequently, a marked increase in CRP levels beyond the 3rd postoperative day (POD) should prompt a diagnostic workup for AL and other major complications [11]. Procalcitonin (PCT) has also demonstrated high sensitivity, specificity, and NPV, often exceeding those of CRP, although it is not commonly included in routine measurements [1, 7, 8].
Although various scoring systems have been proposed to predict, diagnose, or assess the severity of AL, they generally lack precision in pinpointing instances of the condition. A team of Dutch researchers combined key clinical parameters with CRP level to develop the Dutch Leakage (DULK) score. Initially a 13-point system, the DULK score was later simplified to a 4-point tool to enhance its practicality in clinical settings [14].
A multicenter prospective observational study investigated AL following elective colorectal surgery, evaluating the efficacy of DULK, PCT, and CRP measurements on POD 2, 3, and 6 in a cohort of 1,546 patients [15]. The incidence of AL was 5%, with morbidity and mortality rates of approximately 30% and 1%, respectively. Positive DULK, elevated PCT level, and elevated CRP concentration corresponded to probabilities of 21% at POD 2, 33% at POD 3, and 47% at POD 6 for the detection of AL. Notably, negative results for these markers ruled out AL in over 99% of cases at POD 2, 3, and 6, indicating a relatively low positive predictive value (PPV). Consequently, none of the laboratory markers or scoring systems evaluated have demonstrated adequate reliability to gain widespread acceptance or incorporation into routine clinical practice.
When postoperative recovery deviates from the expected trajectory, repeated evaluation by experienced clinicians remains a reliable method for the early detection of AL. However, ensuring objective and consistent monitoring of patients with suspected leakage can be challenging, particularly when the surgeon who performed the anastomosis is responsible for the assessment.
The use of early warning scoring (EWS) systems, also known as physiological, weighted aggregate track, or trigger systems, has been recommended in various UK reports for the early detection and management of patient deterioration [16–23]. These systems allocate points to patients based on the extent to which their vital signs, such as pulse rate, respiratory rate, and blood pressure, deviate from normal ranges. The sum of these points constitutes the EWS, with scores within specified ranges prompting staff to review the patient’s condition. EWS systems are widely used in UK hospitals, although variations exist in the physiological variables measured, the weights assigned to them, and the thresholds that trigger specific responses [24, 25].
The objective of this study was to perform a retrospective analysis of patients who underwent surgery for colon cancer, both with and without AL, until discharge. Our goal was to compare their postoperative EWS and CRP levels to aid in the development of a diagnostic tool for predicting AL.
METHODS
Ethics statement
The study was approved by the Institutional Research Review Board of Oxford University Hospital (No. svb40/2020) prior to data collection. Informed consent was waived due to the retrospective nature of the study. The need for ethical approval from the medical ethics committee was exempted by the local Institutional Review Board, as all patient and hospital data were de-identified.
Study population
This study included all patients who underwent colon cancer resection at Oxford University Hospitals NHS Foundation Trust (Oxford, UK) between January 2013 and December 2018. Comprehensive patient demographics were recorded, such as age, sex, and body mass index, as well as details on comorbidities, operative techniques (laparoscopic, open, or converted), anastomosis site, instances of return to the operating theater, readmission, and the duration of hospitalization. Patients with rectal cancer, patients who did not have a primary anastomosis, and cases involving resection performed for inflammatory bowel disease were excluded from the analysis. The exclusion criteria also encompassed individuals younger than 18 years, cases of emergency surgery, anastomoses that involved a defunctioning stoma, and patients with ongoing infections such as perforated tumors. Surgical resections were classified into types, including right and extended right hemicolectomy, left hemicolectomy, high anterior resection, and subtotal colectomy. Postoperative care followed a standardized protocol throughout the study period, which included Enhanced Recovery After Surgery (ERAS) protocols for all patients. The perioperative use of drains was not standardized.
A retrospective review of medical records was conducted for patients with and without AL to obtain their daily EWS and CRP levels throughout the postoperative period until discharge. The reference value for CRP was set at <5.0 mg/L. AL was defined as the identification of a defect at the anastomosis site during reoperation, the presence of feculent fluid in a pelvic drain, or evidence of AL on computed tomography.
The applied EWS is used to monitor patient deterioration, with the potential to trigger intensified clinical observation and swift action from critical care teams. It incorporates key vital signs, including respiration rate, heart rate, temperature, and blood pressure, to reflect the patient’s physiological state through a cumulative score. Further details are available in Fig. 1.
Statistical analysis
For statistical analysis, R ver. 4.3.3 (R Project for Statistical Computing) was employed. The normality of the data was first assessed using the Shapiro-Wilk test. The median was then used as the measure of central tendency for continuous variables. To evaluate the accuracy of CRP level and EWS in detecting AL on successive PODs, receiver operating characteristic (ROC) curve analysis was performed. The area under the curve (AUC) values were compared using z-tests, both over time and between patients meeting CRP and EWS criteria. At the optimal cutoff points, as determined by the Youden method, the PPV and NPV for CRP and EWS were calculated based on the ROC curves for each POD.
RESULTS
Patient demographics
A total of 1,855 patients underwent colon surgery that included an anastomosis. AL was recorded in 57 patients (3.1%), with 52.6% of those cases following laparoscopic procedures and 47.4% occurring after open surgery. Older age, greater body mass index, and higher American Society of Anesthesiologists (ASA) physical status were associated with an increased rate of AL (Table 1).
Leak timing and treatment
Of the 57 leaks noted, 92.0% were diagnosed within 7 days postoperatively, with a peak incidence on POD 3. No leaks were detected on POD 1, while 2 leaks were identified on POD 2, 20 leaks on POD 3, 23 leaks on POD 4, 6 leaks on POD 5, 5 leaks on POD 6, and 2 leaks on POD 7.
Forty-nine patients required operative reintervention, while 8 were managed conservatively. The 90-day mortality rate was 3.5% (n=2).
Of the leaks, 15.0% were classified as Clavien-Dindo grade I or II, while 85.0% were categorized as grade III or IV. More severe leakage was associated with higher CRP and EWS values, although this association did not reach statistical significance (P=0.08).
CRP level and EWS
Following surgical procedures complicated by leakage, the mean CRP level exceeded 200 mg/L (range, <5–600 mg/dL) on POD 3 through 7, whereas patients without AL maintained CRP levels below 200 mg/L during the same period (P<0.05) (Fig. 2). From POD 1 to 5, the mean EWS among patients with AL consistently exceeded 2, while those without AL maintained a mean score below 2 (P<0.05) (Fig. 2). No significant associations were observed between the AL rate and the rate of increase or the ratio of baseline to intervention levels of CRP or EWS. ROC curves were generated for POD 1 through 7 to evaluate the performance of CRP and EWS in predicting AL. These ROC curves were then analyzed to ascertain the AUC values and determine the optimal cutoff values for CRP and EWS, along with the associated sensitivity and specificity. Notably, ROC curve analysis revealed that POD 3 displayed the highest predictive value for early AL, with an AUC of 0.89 (sensitivity, 90.0%; specificity, 70.0%) using a cutoff EWS of 2.4 and a CRP of 180 mg/L (Table 2, Fig. 3).
When comparing the AUC values across days, no significant differences in AUC were identified for EWS. However, for CRP, the AUC on POD 2 was significantly lower than on either POD 3 or 4 (P=0.04 for both). In a comparison between EWS and CRP, no significant differences in AUC were detected on any POD.
DISCUSSION
AL represents a serious adverse event in colon surgery, with implications for both short- and long-term outcomes, including increased morbidity, mortality, and the risk of cancer recurrence [26–31]. A review of the literature—including prospective, retrospective, and population-based series—indicates that reported rates of leakage vary widely, ranging from 1.0% to 39.0% [32].
Extensive efforts have been directed toward developing tools to assist clinicians in detecting and suspecting AL during the postoperative phase. This endeavor is crucial for interrupting the cycle of physiological deterioration that patients can experience, which ultimately increases the risk of mortality [29, 33].
This study presents comprehensive data from a diverse patient population at a tertiary referral center, demonstrating an AL rate of 3.1%. Notably, EWS has been effectively incorporated into daily clinical practice at our center, resulting in complete registration.
In the United Kingdom, the implementation of EWS systems is encouraged nationally, yet no definitive diagnostic tool is available for detecting AL. Although systematic reviews have investigated the effects of these systems on patient outcomes, their assessment in surgical settings has been limited [34–36]. When EWS systems are integrated with rapid response protocols, they show promise in reducing cardiac arrests and preventing unplanned admissions to intensive care units [37]. This is consistent with a review of 18 randomized studies that examined the use of rapid response teams in hospitals [38].
Previous research has indicated that patients with AL are more susceptible to postoperative respiratory complications than those without leakage, with frequencies of 55% and 24%, respectively [39]. However, the specific timing of these respiratory issues has not been reported. A smaller study by Sutton et al. [40] revealed that the initial clinical signs of AL often present as cardiopulmonary symptoms, and fever and tachycardia are well-documented indicators of AL. A study from 2007 suggests that while abnormal vital signs are common in the 1st postoperative week, they have limited predictive value for AL [41]. Consequently, diagnosing AL is a complex challenge, necessitating careful consideration of factors such as biomarkers and their temporal patterns.
The PREDICT Study included CRP data from 833 patients, with 41.0% experiencing AL [42]. Notably, a change in CRP levels exceeding 50 mg/L between 2 consecutive PODs demonstrated a sensitivity of 0.85 in detecting leakage along with a high NPV, at 0.99. Furthermore, an increase in CRP concentration of more than 50 mg/L between POD 3 and 4 or between POD 4 and 5 exhibited high specificity for AL requiring intervention (ranging from 0.96 to 0.97), with positive likelihood ratios of 4.99 to 6.44. Another recent multicenter prospective study, which included 2,501 patients undergoing colorectal resection with anastomosis and without a defunctioning stoma, evaluated CRP, PCT, and neutrophil levels on POD 4, in addition to 60-day AL, morbidity, and mortality rates [43]. The overall morbidity and mortality rates were 30% and 1%, respectively, with an AL frequency of 9%. The AUC values for detecting AL were 0.84 (95% confidence interval [CI], 0.81–0.87) for CRP, 0.75 (95% CI, 0.72–0.79) for PCT, and 0.70 (95% CI, 0.66–0.74) for neutrophil level. The optimal cutoff level for CRP was identified as 119 mg/L, yielding a sensitivity of 70.0%, a specificity of 81.0%, and an NPV of 97.0%. Our data align with these findings, further supporting the utility of monitoring CRP trajectory to accurately rule out AL after colonic resection. Additionally, our findings suggest a benefit in combining vital signs with CRP levels to stratify patients into high or low-risk categories for anastomotic failure. An EWS of 2.4 and a CRP level of 180 mg/L on POD 3 should prompt further investigation for AL.
Several limitations of this study warrant consideration. First and foremost, this research was conducted as a retrospective analysis at a single institution. Additionally, the retrospective diagnosis of AL raises the possibility that some patients in the non-AL group could have experienced subclinical leaks, which may explain their adverse clinical events during the postoperative period. Moreover, due to the retrospective design of the study, no power calculation was performed, suggesting that certain findings may have reached statistical significance with a larger sample size. Finally, it should be noted that this study was focused on identifying signs and symptoms that contribute to the early diagnosis of AL following colon surgery, rather than predicting the occurrence of leakage.
In efforts to present a preoperatively homogeneous patient population, rectal resections were excluded from this study. This approach was taken to avoid the well-established effects of neoadjuvant radiotherapy as a predisposing factor for AL.
Furthermore, the frailty of patients undergoing surgery is a risk factor for AL, which may be reflected by the EWS due to its incorporation of physiological parameters. Although our selection process did not account for this, we adjusted for confounding by including the time trajectory of EWS development and its relationship with CRP levels.
In the event of unexpected deterioration in vital signs accompanied by increased or unchanged CRP levels by POD 3, a thorough assessment by a medical professional is warranted to evaluate the clinical risk of AL. Despite the low incidence of events recorded on POD 1 and 2, the emergence of a leak on POD 3 could result from a series of events that began on POD 1, but were not detectable using outcome measures that would trigger a CRP or EWS response.
Based on our findings, we propose adopting an EWS of 2.4 and a CRP level of 180 mg/L on the third day after anastomosis formation as specific thresholds for initiating further investigation and intervention in cases of suspected AL.
ARTICLE INFORMATION
-
Conflict of interest
No potential conflict of interest relevant to this article was reported.
-
Funding
None.
-
Author contributions
Conceptualization: all authors; Data curation: RJ, UD, SM, IN; Formal analysis: PR, RJ, UD, SM, IN, IL; Investigation: PR, RJ, IN, IL; Methodology: all authors; Validation: IN, IL; Writing–original draft: PR, RJ, IN; Writing–review & editing: all authors. All authors read and approved the final manuscript.
Fig. 1.Early warning score (EWS) flowchart: physiological parameters and the corresponding actions needed based on the EWS.
Fig. 2.Comparison of patients with and without anastomotic leak (AL). Medians of postoperative (A) early warning score (EWS) and (B) C-reactive proten (CRP) levels. The mean difference between the with AL and without AL groups is statistically significant (during postoperative day [POD] 3 through 7).
Fig. 3.Predictive analysis using receiver operating characteristic curves for anastomotic leakage using (A–C) the early warning score and (D–F) C-reactive protein levels at (A, D) postoperative day 2, (B, E) postoperative day 3, and (C, F) postoperative day 4.
Table 1.Study population demographics stratified according to the presence or absence of an anastomotic leak (n=1,855)
Variable |
Anastomotic leak
|
P-value |
Yes (n=57) |
No (n=1,798) |
Sex |
|
|
0.09 |
Male |
29 (50.8) |
935 (52.0) |
|
Female |
28 (49.2) |
863 (48.0) |
|
Age (yr) |
71.0 (64.0–77.0) |
69.0 (52.0–75.5) |
0.05 |
Body mass index (kg/m2) |
27.7 (22.9–30.9) |
25.4 (22.9–29.1) |
0.63 |
ASA physical status |
|
|
0.09 |
I |
4 (4.0) |
108 (96.0) |
|
II |
27 (2.4) |
1,079 (97.6) |
|
III |
24 (3.8) |
593 (96.2) |
|
IV |
2 (10.0) |
18 (90.0) |
|
Surgical platform |
|
|
0.55 |
Laparoscopic |
30 (1.8) |
1,654 (98.2) |
|
Open |
27 (15.8) |
144 (84.2) |
|
Surgical procedure |
|
|
0.01 |
Right-sided hemicolectomy |
39 (4.2) |
899 (95.8) |
|
Extended right-sided hemicolectomy |
13 (2.1) |
611 (97.9) |
|
Left-sided hemicolectomy |
5 (2.5) |
198 (97.5) |
|
Sigmoid resection |
0 (0) |
90 (100) |
|
Length of stay (day) |
10.1 (3.2–21.2) |
3.1 (2.9–5.1) |
0.01 |
pT category |
|
|
0.07 |
pT1 |
7 (2.2) |
306 (97.8) |
|
pT2 |
7 (3.1) |
216 (96.9) |
|
pT3 |
37 (3.1) |
1,168 (96.9) |
|
pT4 |
6 (5.3) |
108 (94.7) |
|
Table 2.Predictive analysis of anastomotic leakage using EWS and CRP at POD 2, 3, and 4
Variable |
EWS
|
CRP
|
POD 2 |
POD 3 |
POD 4 |
POD 2 |
POD 3 |
POD 4 |
Optimal cutoff point (95% CI) |
3.10 (3.0–4.0) |
2.40 (2.0–3.0) |
2.64 (2.0–4.0) |
131 (87–203) |
180 (110–219) |
180 (110–219) |
AUC (95% CI) |
0.86 (0.80–0.91) |
0.88 (0.84–0.92) |
0.83 (0.78–0.88) |
0.80 (0.72–0.87) |
0.89 (0.84–0.93) |
0.89 (0.85–0.93) |
AUC at cutoff point (95% CI) |
0.63 (0.52–0.73) |
0.61 (0.53–0.68) |
0.51 (0.41–0.62) |
0.50 (0.40–0.59) |
0.66 (0.57–0.76) |
0.67 (0.50–0.76) |
Prevalence (%) |
25.4 |
25.4 |
25.4 |
25.4 |
25.4 |
25.4 |
Sensitivity (95% CI) |
0.77 (0.65–0.87) |
0.94 (0.77–0.99) |
0.75 (0.50–0.84) |
0.75 (0.54–0.93) |
0.79 (0.65–0.94) |
0.79 (0.66–0.94) |
Specificity (95% CI) |
0.85 (0.79–0.95) |
0.67 (0.60–0.84) |
0.74 (0.70–0.97) |
0.75 (0.55–0.93) |
0.88 (0.70–0.98) |
0.88 (0.70–0.97) |
REFERENCES
- 1. Zawadzki M, Czarnecki R, Rzaca M, Obuszko Z, Velchuru VR, Witkiewicz W. C-reactive protein and procalcitonin predict anastomotic leaks following colorectal cancer resections: a prospective study. Wideochir Inne Tech Maloinwazyjne 2016;10:567–73.ArticlePubMedPMC
- 2. Doeksen A, Tanis PJ, Vrouenraets BC, Lanschot van JJ, Tets van WF. Factors determining delay in relaparotomy for anastomotic leakage after colorectal resection. World J Gastroenterol 2007;13:3721–5.ArticlePubMedPMC
- 3. Straatman J, Cuesta MA, Gisbertz SS, Van der Peet DL. Value of a step-up diagnosis plan: CRP and CT-scan to diagnose and manage postoperative complications after major abdominal surgery. Rev Esp Enferm Dig 2014;106:515–21.PubMed
- 4. Straatman J, Harmsen AM, Cuesta MA, Berkhof J, Jansma EP, van der Peet DL. Predictive value of C-reactive protein for major complications after major abdominal surgery: a systematic review and pooled-analysis. PLoS One 2015;10:e0132995.ArticlePubMedPMC
- 5. Platt JJ, Ramanathan ML, Crosbie RA, Anderson JH, McKee RF, Horgan PG, et al. C-reactive protein as a predictor of postoperative infective complications after curative resection in patients with colorectal cancer. Ann Surg Oncol 2012;19:4168–77.ArticlePubMedPDF
- 6. Bakker IS, Grossmann I, Henneman D, Havenga K, Wiggers T. Risk factors for anastomotic leakage and leak-related mortality after colonic cancer surgery in a nationwide audit. Br J Surg 2014;101:424–32.ArticlePubMedPDF
- 7. Garcia-Granero A, Frasson M, Flor-Lorente B, Blanco F, Puga R, Carratalá A, et al. Procalcitonin and C-reactive protein as early predictors of anastomotic leak in colorectal surgery: a prospective observational study. Dis Colon Rectum 2013;56:475–83.ArticlePubMed
- 8. Giaccaglia V, Salvi PF, Antonelli MS, Nigri G, Pirozzi F, Casagranda B, et al. Procalcitonin reveals early dehiscence in colorectal surgery: the PREDICS study. Ann Surg 2016;263:967–72.ArticlePubMed
- 9. Straatman J, Cuesta MA, Tuynman JB, Veenhof AA, Bemelman WA, van der Peet DL. C-reactive protein in predicting major postoperative complications are there differences in open and minimally invasive colorectal surgery? Substudy from a randomized clinical trial. Surg Endosc 2018;32:2877–85.ArticlePubMedPMCPDF
- 10. Gans SL, Atema JJ, van Dieren S, Groot Koerkamp B, Boermeester MA. Diagnostic value of C-reactive protein to rule out infectious complications after major abdominal surgery: a systematic review and meta-analysis. Int J Colorectal Dis 2015;30:861–73.ArticlePubMedPMCPDF
- 11. McSorley ST, Roxburgh CS, Horgan PG, McMillan DC. The impact of preoperative dexamethasone on the magnitude of the postoperative systemic inflammatory response and complications following surgery for colorectal cancer. Ann Surg Oncol 2017;24:2104–12.ArticlePubMedPMCPDF
- 12. Ortega-Deballon P, Radais F, Facy O, d’Athis P, Masson D, Charles PE, et al. C-reactive protein is an early predictor of septic complications after elective colorectal surgery. World J Surg 2010;34:808–14.ArticlePubMedPMCPDF
- 13. Yeung DE, Peterknecht E, Hajibandeh S, Hajibandeh S, Torrance AW. C-reactive protein can predict anastomotic leak in colorectal surgery: a systematic review and meta-analysis. Int J Colorectal Dis 2021;36:1147–62.ArticlePubMedPDF
- 14. den Dulk M, Witvliet MJ, Kortram K, Neijenhuis PA, de Hingh IH, Engel AF, et al. The DULK (Dutch leakage) and modified DULK score compared: actively seek the leak. Colorectal Dis 2013;15:e528–33.ArticlePubMed
- 15. Italian ColoRectal Anastomotic Leakage (iCral) Study Group. Anastomotic leakage after elective colorectal surgery: a prospective multicentre observational study on use of the Dutch leakage score, serum procalcitonin and serum C-reactive protein for diagnosis. BJS Open 2020;4:499–507.ArticlePubMedPMCPDF
- 16. Department of Health. The national outreach report. NHS Modernisation Agency; 2003.
- 17. Department of Health. Comprehensive Critical Care: a review of adult critical care services. NHS Modernisation Agency; 2000.
- 18. National Confidential Enquiry into Patient Outcomes and Death (NCEPOD). An acute problem?. NCEPOD; 2005.
- 19. National Patient Safety Agency (NPSA). The fifth report from the Patient Safety Observatory. Safer care for the acutely ill patient: learning from serious incidents NPSA; 2007.
- 20. National Patient Safety Agency (NPSA). Recognizing and responding appropriately to early signs of deterioration in hospitalized patients. NPSA; 2007.
- 21. National Institute for Health and Clinical Excellence (NICE). NICE clinical guideline 50. Acutely ill patients in hospital: recognition of and response to acute illness in adults in hospital. NICE; 2007.
- 22. Ward D, Potter J, Ingham J, Percival F, Bell D. Acute medical care: the right person, in the right setting—first time: how does practice match the report recommendations? Clin Med (Lond) 2009;9:553–6.ArticlePubMedPMC
- 23. National Confidential Enquiry into Patient Outcome and Death (NCEPOD), Findlay GP, Shotton H, Kelly K, Mason M. Time to intervene? A review of patients who underwent cardiopulmonary resuscitation as a result of an in-hospital cardiorespiratory arrest. NCEPOD; 2012.
- 24. Gao H, McDonnell A, Harrison DA, Moore T, Adam S, Daly K, et al. Systematic review and evaluation of physiological track and trigger warning systems for identifying at-risk patients on the ward. Intensive Care Med 2007;33:667–79.ArticlePubMedPDF
- 25. Smith GB, Prytherch DR, Schmidt PE, Featherstone PI. Review and performance evaluation of aggregate weighted ‘track and trigger’ systems. Resuscitation 2008;77:170–9.ArticlePubMed
- 26. Park JS, Huh JW, Park YA, Cho YB, Yun SH, Kim HC, et al. Risk factors of anastomotic leakage and long-term survival after colorectal surgery. Medicine (Baltimore) 2016;95:e2890.ArticlePubMedPMC
- 27. Cong ZJ, Hu LH, Xing JJ, Bian ZQ, Fu CG, Yu ED, et al. Incidence and mortality of anastomotic dehiscence requiring reoperation after rectal carcinoma resection. Int Surg 2014;99:112–9.ArticlePubMedPMCPDF
- 28. Parthasarathy M, Greensmith M, Bowers D, Groot-Wassink T. Risk factors for anastomotic leakage after colorectal resection: a retrospective analysis of 17 518 patients. Colorectal Dis 2017;19:288–98.ArticlePubMedPDF
- 29. Gessler B, Eriksson O, Angenete E. Diagnosis, treatment, and consequences of anastomotic leakage in colorectal surgery. Int J Colorectal Dis 2017;32:549–56.ArticlePubMedPMCPDF
- 30. Branagan G, Finnis D; Wessex Colorectal Cancer Audit Working Group. Prognosis after anastomotic leakage in colorectal surgery. Dis Colon Rectum 2005;48:1021–6.ArticlePubMed
- 31. Khan AA, Wheeler JM, Cunningham C, George B, Kettlewell M, Mortensen NJ. The management and outcome of anastomotic leaks in colorectal surgery. Colorectal Dis 2008;10:587–92.ArticlePubMed
- 32. Bruce J, Krukowski ZH, Al-Khairy G, Russell EM, Park KG. Systematic review of the definition and measurement of anastomotic leak after gastrointestinal surgery. Br J Surg 2001;88:1157–68.ArticlePubMedPDF
- 33. Daams F, Wu Z, Lahaye MJ, Jeekel J, Lange JF. Prediction and diagnosis of colorectal anastomotic leakage: a systematic review of literature. World J Gastrointest Surg 2014;6:14–26.ArticlePubMedPMC
- 34. McGaughey J, Alderdice F, Fowler R, Kapila A, Mayhew A, Moutray M. Outreach and Early Warning Systems (EWS) for the prevention of intensive care admission and death of critically ill adult patients on general hospital wards. Cochrane Database Syst Rev 2007;(3):CD005529. Article
- 35. McNeill G, Bryden D. Do either early warning systems or emergency response teams improve hospital patient survival? A systematic review. Resuscitation 2013;84:1652–67.ArticlePubMed
- 36. Alam N, Hobbelink EL, van Tienhoven AJ, van de Ven PM, Jansma EP, Nanayakkara PW. The impact of the use of the Early Warning Score (EWS) on patient outcomes: a systematic review. Resuscitation 2014;85:587–94.ArticlePubMed
- 37. Royal College of Physicians (RCP). National Early Warning Score (NEWS): standardising the assessment of acute-illness severity in the NHS. Report of a working party. RCP; 2012.PDF
- 38. Chan PS, Jain R, Nallmothu BK, Berg RA, Sasson C. Rapid response teams: a systematic review and meta-analysis. Arch Intern Med 2010;170:18–26.ArticlePubMed
- 39. Isbister WH. Anastomotic leak in colorectal surgery: a single surgeon’s experience. ANZ J Surg 2001;71:516–20.ArticlePubMedPDF
- 40. Sutton CD, Marshall LJ, Williams N, Berry DP, Thomas WM, Kelly MJ. Colo-rectal anastomotic leakage often masquerades as a cardiac complication. Colorectal Dis 2004;6:21–2.ArticlePubMed
- 41. Hyman N, Manchester TL, Osler T, Burns B, Cataldo PA. Anastomotic leaks after intestinal anastomosis: it’s later than you think. Ann Surg 2007;245:254–8.ArticlePubMedPMC
- 42. Stephensen BD, Reid F, Shaikh S, Carroll R, Smith SR, Pockney P, et al. C-reactive protein trajectory to predict colorectal anastomotic leak: PREDICT Study. Br J Surg 2020;107:1832–7.ArticlePubMedPDF
- 43. Sala Hernandez A, Frasson M, García-Granero A, Hervás Marín D, Laiz Marro B, Alonso Pardo R, et al. Diagnostic accuracy of C-reactive protein, procalcitonin and neutrophils for the early detection of anastomotic leakage after colorectal resection: a multicentric, prospective study. Colorectal Dis 2021;23:2723–30.ArticlePubMedPDF
Citations
Citations to this article as recorded by
- Early detection of anastomotic leakage in colon cancer surgery: the role of early warning score and C-reactive protein
Gyung Mo Son
Annals of Coloproctology.2024; 40(5): 415. CrossRef