Early postoperative systemic inflammatory response as predictor of anastomotic leakage after esophagectomy: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Postesophagectomy anastomotic leakage occurs in up to 16% of patients and is the main cause of morbidity and mortality. The leak severity is determined by the extent of contamination and the degree of sepsis, both of which are related to the time from onset to treatment. Early prediction based on inflammatory biomarkers such as C-reactive protein (CRP) levels, white blood cell counts, albumin levels, and combined Noble-Underwood (NUn) scores can guide early management. This review aimed to determine the diagnostic accuracy of these biomarkers. METHODS: This study was designed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered in the PROSPERO (International Prospective Register of Systematic Reviews) database. Two reviewers independently conducted searches across PubMed, MEDLINE, Web of Science, and Embase. Sources of bias were assessed, and a meta-analysis was performed. RESULTS: Data from 5348 patients were analyzed, and 13% experienced leakage. The diagnostic accuracy of the serum biomarkers was analyzed, and pooled cutoff values were identified. CRP levels were found to have good diagnostic accuracy on days 2 to 5. The best discrimination was identified on day 2 for a cutoff value < 222 mg/L (area under the curve = 0.824, sensitivity = 81%, specificity = 88%, positive predictive value = 38.6%, and negative predictive value = 98%). A NUn score of >10 on day 4 correlated with poor diagnostic accuracy. CONCLUSION: The NUn score failed to achieve adequate accuracy. CRP seems to be the only valuable biomarker and is a negative predictor of postesophagectomy leakage. Patients with a CRP concentration of <222 mg/L on day 2 are unlikely to develop a leak, and patients can safely proceed through their enhanced recovery after surgery protocol. Patients with a CRP concentration of <127 mg/L on day 5 can be safely discharged when clinically possible.

A real-world study was conducted to develop a nomogram that predicts the occurrence of anastomotic leakage in patients with esophageal cancer following esophagectomy.

BACKGROUND: The incidence of anastomotic leakage (AL) following esophagectomy is regarded as a noteworthy complication. There is a need for biomarkers to facilitate early diagnosis of AL in high-risk esophageal cancer (EC) patients, thereby minimizing its morbidity and mortality. We assessed the predictive abilities of inflammatory biomarkers for AL in patients after esophagectomy. METHODS: In order to ascertain the predictive efficacy of biomarkers for AL, Receiver Operating Characteristic (ROC) curves were generated. Furthermore, univariate, LASSO, and multivariate logistic regression analyses were conducted to discern the risk factors associated with AL. Based on these identified risk factors, a diagnostic nomogram model was formulated and subsequently assessed for its predictive performance. RESULTS: Among the 438 patients diagnosed with EC, a total of 25 patients encountered AL. Notably, elevated levels of interleukin-6 (IL-6), IL-10, C-reactive protein (CRP), and procalcitonin (PCT) were observed in the AL group as compared to the non-AL group, demonstrating statistical significance. Particularly, IL-6 exhibited the highest predictive capacity for early postoperative AL, exhibiting a sensitivity of 92.00% and specificity of 61.02% at a cut-off value of 132.13 pg/ml. Univariate, LASSO, and multivariate logistic regression analyses revealed that fasting blood glucose ≥7.0mmol/L and heightened levels of IL-10, IL-6, CRP, and PCT were associated with an augmented risk of AL. Consequently, a nomogram model was formulated based on the results of multivariate logistic analyses. The diagnostic nomogram model displayed a robust discriminatory ability in predicting AL, as indicated by a C-Index value of 0.940. Moreover, the decision curve analysis provided further evidence supporting the clinical utility of this diagnostic nomogram model. CONCLUSIONS: This predictive instrument can serve as a valuable resource for clinicians, empowering them to make informed clinical judgments aimed at averting the onset of AL.

Preoperative white blood cell count predicts anastomotic leakage in patients with left-sided colorectal cancer.

To determine whether preoperative white blood cell (WBC) counts reflect risk of anastomotic leak (AL) for patients with colorectal cancer (CRC), we retrospectively examined data from records of 208 consecutive patients who had undergone resections for left-sided CRC, including their clinicopathological parameters and preoperative laboratory data. The diagnostic value of WBC count for AL was evaluated and compared with those of neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, lymphocyte-monocyte ratio and platelet count × C-reactive protein level multiplier (P-CRP) value; optimal cut-off values were derived from receiver operating characteristic curves. AL was observed in 11 of the 208 patients (5.3%). Compared with the no-AL group, the AL group had a significantly higher mean WBC count and smoking rate. In multivariate analysis, WBC count and smoking were independent risk factors for AL. Compared with the other tested inflammatory indicators, the cut-off value for WBC (6,200/µL) had the highest sensitivity (81.8%) and negative predictive value (98.4%), as well as the lowest likelihood ratio (0.289). Preoperative WBC count could therefore be a convenient predictor of AL in patients with left-sided CRC.

The Predictive Value of Inflammatory Biomarkers in Esophageal Anastomotic Leaks.

BACKGROUND: This study investigated the role of the neutrophil-to-lymphocyte ratio (NLR) in predicting anastomotic leak (AL) after esophagectomy for esophageal adenocarcinoma. METHODS: This is a retrospective analysis of a prospectively collected database from the McGill University Health Center. Included were all patients with esophageal adenocarcinoma who underwent esophagectomy between 2005 and 2016. Patients with chronic infections, concurrent active malignancies, and autoimmune conditions were excluded. NLR values were obtained on postoperative days (POD) 0, 1, 2, and 3. Receiver operating characteristic curve study and multivariable logistic analysis were conducted to evaluate the diagnostic value of NLR. RESULTS: The study included 330 patients, and AL developed in 16%. Mean NLR values on POD1, 2, and 3 were higher in patients with leaks (20 vs 14 on POD1, P < .001; 20 vs 12 on POD2, P < .001; and 19 vs 10 on POD3, P < .001). The NLR value on POD3 was associated with an area under the curve of 70% and a negative predictive value of 92.4%. Multivariable analyses identified higher American Society of Anesthesiologists Physical Status Classification, increasing NLR trend (between POD1 and POD3), POD1 NLR, POD2 NLR, and POD3 NLR as independent factors associated with AL. CONCLUSIONS: Patients who developed AL demonstrate higher mean NLR values in the early postoperative period with rising trends. Conversely a low NLR is associated with a high negative predictive value for AL. This simple metric allows risk stratification that may guide treatment decisions in esophagectomy patients.

[C-reactive protein as early predictor of anastomotic leakage after surgery for colorectal cancer. Systematic review and meta-analysis]. / S-reaktivnyi belok kak rannii marker nesostoyatel'nosti shvov tolstokishechnogo anastomoza posle rezektsii tolstoi kishki po povodu raka. Sistematicheskii obzor i metaanaliz.

OBJECTIVE: Systematic review and meta-analysis of data on C-reactive protein (CRP) as a predictor of anastomotic leakage (AL) after surgery for colorectal cancer. MATERIAL AND METHODS: Literature searching was performed in Medline, Elibrary, Scopus, Web of Science databases. Literature request consisted of keywords «CRP¼, «colorectal surgery¼, «anastomotic leakage¼ for the period 2008-2018. Meta-analysis included 2 manuscripts for the second postoperative day, 7 articles for the third postoperative day and 6 articles for the fourth postoperative day. ROC-analysis was made to determine optimal prognostic values. RESULTS: ROC-curve for the second postoperative day - AUC 0.758; optimal CRP value - 154 mg/l (sensitivity 70.1%, specificity 55.6%), 95% confidence interval 0.698-0.819. ROC-curve for the third postoperative day - AUC 0.715; optimal CRP value - 144.5 mg/l (sensitivity 79.1% specificity 60.3%), 95% confidence interval 0.68-0.75. ROC-curve for the fourth postoperative day - AUC 0.767; optimal CRP value - 122.91 mg/l (sensitivity 72.3% specificity 60%), 95% confidence interval 0.73-0.804. CONCLUSION: Increased CRP is an early predictor of AL after surgery for colorectal cancer. CRP level ≥144.5 mg/l on the third postoperative day can predict AL (sensitivity 79%, specificity 60%).

C-reactive protein trajectory to predict colorectal anastomotic leak: PREDICT Study.

BACKGROUND: Anastomotic leak is a common complication after colorectal surgery, associated with increased morbidity and mortality, and poorer long-term survival after oncological resections. Early diagnosis improves short-term outcomes, and may translate into reduced cancer recurrence. Multiple studies have attempted to identify biomarkers to enable earlier diagnosis of anastomotic leak. One study demonstrated that the trajectory of C-reactive protein (CRP) levels was highly predictive of anastomotic leak requiring intervention, with an area under the curve of 0·961. The aim of the present study was to validate this finding externally. METHODS: This was a prospective international multicentre observational study of adults undergoing elective colorectal resection with an anastomosis. CRP levels were measured before operation and for 5 days afterwards, or until day of discharge if earlier than this. The primary outcome was anastomotic leak requiring operative or radiological intervention. RESULTS: Between March 2017 and July 2018, 933 patients were recruited from 20 hospitals across Australia, New Zealand, England and Scotland. Some 833 patients had complete CRP data and were included in the primary analysis, of whom 41 (4·9 per cent) developed an anastomotic leak. A change in CRP level exceeding 50 mg/l between any two postoperative days had a sensitivity of 0·85 for detecting a leak, and a high negative predictive value of 0·99 for ruling it out. A change in CRP concentration of more than 50 mg/l between either days 3 and 4 or days 4 and 5 after surgery had a high specificity of 0·96-0·97, with positive likelihood ratios of 4·99-6·44 for a leak requiring intervention. CONCLUSION: This study confirmed the value of CRP trajectory in accurately ruling out an anastomotic leak after colorectal resection.

ANTECEDENTES: La fuga anastomótica es una complicación frecuente después de la cirugía colorrectal que se asocia con morbilidad y mortalidad, con una peor supervivencia a largo plazo tras resecciones oncológicas. El diagnóstico precoz mejora los resultados a corto plazo y puede traducirse en una reducción de la recidiva del cáncer. Múltiples estudios han tratado de identificar biomarcadores para lograr un diagnóstico precoz de la fuga anastomótica. Un estudio demostró que la evolución de la proteína C reactiva (PCR) era altamente predictiva de una fuga anastomótica que requería intervención, con un área bajo la curva de 0,961. Nuestro estudio tuvo como objetivo validar externamente este hallazgo. MÉTODOS: Se llevó a cabo un estudio internacional prospectivo observacional y multicéntrico de pacientes adultos sometidos a resección colorrectal electiva con anastomosis. Los niveles de PCR se midieron antes de la operación y diariamente hasta el día 5 después de la cirugía, o hasta el día del alta si fue anterior. El criterio de valoración principal fue la fuga anastomótica que requirió intervención quirúrgica o radiológica. RESULTADOS: Entre marzo de 2017 y julio de 2018, se reclutaron 933 pacientes de 20 hospitales de Australia, Nueva Zelanda, Inglaterra y Escocia. Se obtuvieron datos completos de PCR en 833 pacientes y se incluyeron en el análisis primario, de los cuales 41 (4,9%) presentaron una fuga anastomótica. Un aumento de la PCR > 50 mg/L entre dos días del postoperatorio fue sensible para detectar una fuga (0,85) y tuvo un alto valor predictivo negativo para descartarla (0,99). El porcentaje de cambio de PCR > 50 mg/L por día entre los días 3-4 o 4-5 después de la operación fue altamente específico (0,96) con un cociente de probabilidad positivo > 5,0 para las fugas que requirieron una intervención. CONCLUSIÓN: Este estudio confirma la utilidad de la evolución de la PCR para descartar con precisión una fuga anastomótica después de una resección colorrectal.

Blood cell count indexes as predictors of anastomotic leakage in elective colorectal surgery: a multicenter study on 1432 patients.

BACKGROUND: The aim of this study was to evaluate a series of blood count inflammation indexes in predicting anastomotic leakage (AL) in elective colorectal surgery. METHODS: Demographic, pathologic, and clinical data of 1432 consecutive patients submitted to colorectal surgery in eight surgical centers were retrospectively evaluated. The neutrophil to lymphocyte (NLR), derived neutrophil to lymphocyte (dNLR), lymphocyte to monocyte (LMR), and platelet to lymphocyte (PLR) ratios were calculated before surgery and on the 1st and 4th postoperative days, in patients with or without AL. RESULTS: There were 106 patients with AL (65 males, mean age 67.4 years). The NLR, dNLR, and PLR were significantly higher in patients with AL in comparison to those without, on both the 1st and 4th postoperative days, but significance was greater on the 4th postoperative day. An NLR cutoff value of 7.1 on this day showed the best area under the curve (AUC 0.744; 95% CI 0.719-0.768) in predicting AL. CONCLUSIONS: Among the blood cell indexes of inflammation evaluated, NLR on the 4th postoperative day showed the best ability to predict AL. NLR is a low cost, easy to perform, and widely available index, which might be potentially used in clinical practice as a predictor of AL in patients undergoing elective colorectal surgery.

Which obesity-associated parameters can better reflect the risk of the occurrence of the anastomotic leakage?

Purpose: We investigated which obesity-associated parameters can better predict the risk of anastomotic leakage (AL) in rectal cancer patients that underwent anterior resection of the rectum.Method: Patients (n = 589) who underwent anterior resection of the rectum with a primary anastomosis were included in this study, including 44 patients with AL and 545 without AL. Univariate analysis was used to compare demographic characteristics and to select risk factors that were used in one-to-one propensity score matching (PSM). Obesity-associated parameters, including preoperative body mass index (BMI), visceral fat area (VFA), subcutaneous fat area (SFA), total fat area (TFA), VFA/TFA ratio, serum cholesterol, and triglycerides, were compared between the two groups after PSM.Results: Sex, neoadjuvant chemotherapy, operation time, and anastomosis level from the anal verge were risk factors for AL (p < .05). After the PSM, BMI, VFA, SFA, TFA, VFA/TFA, and serum cholesterol showed no significant difference between the two group (p > .05). However, the level of serum triglycerides was an independent risk factor for AL (p = .024, odds ratio = 2.95).Conclusions: Serum triglycerides have potential as a predictive indicator for AL, which may improve the treatment and outcomes of patients with AL.

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.

BACKGROUND: The purpose of this study was to test use of the Dutch leakage score (DLS), serum C-reactive protein (CRP) and serum procalcitonin (PCT) in the diagnosis of anastomotic leakage (AL) after elective colorectal resection in a prospective observational study. METHODS: Patients undergoing elective colorectal resection with anastomosis in 19 centres were enrolled over a 1-year period from September 2017. The DLS and CRP and PCT levels were evaluated on postoperative day (POD) 2, POD3 and POD6. Statistical analysis, including determination of the area under the receiver operating characteristic (ROC) curve (AUC), was performed for the primary endpoint of AL; secondary endpoints were morbidity and mortality rates ( ClinicalTrials.gov identifier: NCT03560180). RESULTS: Among 1546 patients enrolled, the AL rate was 4·9 per cent. Morbidity and mortality rates were 30·2 and 1·3 per cent respectively. With respect to AL, DLS performed better than CRP and PTC levels on POD2 and POD3 (AUC 0·75 and 0·84), whereas CRP levels were documented with better AUC values on POD6 (AUC 0·81). Morbidity was poorly predicted, whereas mortality was best predicted by PCT on POD2 (AUC 0·83) and by DLS on POD3 and POD6 (AUC 0·87 and 0·98 respectively). Overall, the combination of positive PCT, CRP and DLS values resulted in a probability of AL of 21·3 per cent on POD2, 33·4 per cent on POD3, and 47·1 per cent on POD6. However, the combination of their negative values excluded AL in 99·0 per cent of cases on POD2, 99·3 per cent on POD3, and 99·2 per cent on POD6. CONCLUSION: DLS and CRP level are good positive and excellent negative predictors of AL; the addition of PCT improved the predictive value for diagnosis of AL.

ANTECEDENTES: El objetivo de este estudio fue evaluar el sistema de puntuación de dehiscencia holandés (Dutch Leakage Score, DLS), la proteína C reactiva sérica (PCR) y la procalcitonina sérica (PCT) con el objetivo de diagnosticar la fuga anastomótica (anastomotic leakage, AL) después de una resección colorrectal electiva en un estudio prospectivo observacional. MÉTODOS: En este estudio multicéntrico, se incluyeron las resecciones colorrectales electivas con anastomosis efectuadas durante 1 año. El DLS, la PCR y la PCT se evaluaron en el postoperatorio al segundo día (post-operative day, POD) 2, al tercer día POD3 y al sexto día POD6. El análisis estadístico, que incluye las características operativas del receptor (receiver-operating characteristics, ROC) y el área bajo la curva (area under the curve, AUC) se realizó con la AL como criterio de valoración principal; los criterios de valoración secundarios fueron las tasas de morbilidad y mortalidad (ClinicalTrials.gov: NCT03560180). RESULTADOS: En los 1.546 pacientes incluidos en el estudio, la tasa de AL fue del 4,92%. Las tasas de morbilidad y mortalidad fueron del 30,20% y 1,29%, respectivamente. Con respecto a la AL, el DLS se comportó mejor que la PCR y la PCT en el POD2 y POD3 (AUC-ROC: 0,74 y 0,83), mientras que los niveles de PCR se asociaron con mejores valores de AUC en el POD6 (AUC-ROC: 0,81). La predicción de la morbilidad fue mala, mientras que la mortalidad se predijo mejor mediante la PCT en el POD2 (AUC-ROC: 0,83) y el DLS en el POD3 y POD6 (AUC-ROC: 0,87 y 0,98). En conjunto, la combinación de valores positivos de PCT, PCR y DLS resultó en una probabilidad de AL del 21,3% en POD2, 33,4% en POD3 y 47,1% en POD 6. Por otro lado, la combinación de sus valores negativos excluyó la AL en el 99,0% de los casos en el POD2, 99,3% en el POD3 y 99,2% en el POD6. CONCLUSIÓN: El DLS y la PCR son buenos predictores positivos y excelentes predictores negativos de AL. La adición de la PCT a los predictores anteriores mejora el valor predictivo para el diagnóstico de AL.

Serum C-reactive protein is a useful marker to exclude anastomotic leakage after colorectal surgery.

Anastomotic leakage is a complication of colorectal surgery. C-reactive protein (CRP) is an acute-phase marker that can indicate surgical complications. We determined whether serum CRP levels in patients who had undergone colorectal surgery can be used to exclude the presence of anastomotic leakage and allow safe early discharge. We included 90 patients who underwent colorectal surgery with primary anastomosis. Serum CRP levels were measured retrospectively on postoperative days (PODs) 1 - 7. Patients with anastomotic leakage (n = 11) were compared to those without leakage (n = 79). We statistically analysed data and plotted receiver operating characteristic curves. The incidence of anastomotic leakage was 12.2%. Diagnoses were made on PODs 3 - 24. The overall mortality rate was 3.3% (18.2% in the leakage group, 1.3% in the non-leakage group; P < 0.045). CRP levels were most accurate on POD 4, with a cutoff level of 180 mg/L, showing an area under the curve of 0.821 and a negative predictive value of 97.2%. Lower CRP levels after POD 2 and levels <180 mg/L on POD 4 may indicate the absence of anastomotic leakage and may allow safe discharge of patients who had undergone colorectal surgery with primary anastomosis.

Validation of the NUn score as a predictor of anastomotic leak and major complications after Esophagectomy.

Predicting major anastomotic leak (AL) and major complications (Clavien-Dindo 3-5) following esophagectomy improves postoperative management of patients. The role of the NUn score in their prediction is controversial. This study aims to evaluate the predictive ability of this simple score. Data were retrospectively collected for consecutive esophagectomies over a 10-year period, and NUn scores were retrospectively calculated for each patient from informatics data. A standardized definition of major AL was used, excluding minor asymptomatic, radiologically detected leaks. The predictive accuracy of the NUn score and its constituent parts, for major AL and major complications, was assessed using area under receiver operating characteristics curves (AUROCs). Of 382 patients, 48 (13%) developed major AL and 123 (32%) developed major complications. The NUn score calculated on postoperative day 4 was significantly predictive of both outcomes, with AUROCs of 0.77 and 0.71, respectively (both P < 0.001). A NUn score cut-off of 10 had a negative predictive value of 95% for major AL. The NUn score was predictive of major complications on multivariable analysis. The NUn score was found to be a significant predictor of major AL, suggesting that this is a useful early warning score for major AL. The score may also be useful in identifying patients that are the most likely to benefit from enhanced recovery protocols.

Serial CRP levels following oesophagectomy: a marker for anastomotic dehiscence.

BACKGROUND: Following oesophagectomy, the most concerning complication is that of anastomotic leak (AL). Prompt diagnosis and intervention are crucial to facilitate an optimal outcome. Other complications, particularly respiratory, are not infrequent. Early identification of AL versus other sources of the inflammatory response can be problematic. AIMS: To evaluate the role of serial CRP as a prognosticator for oesophagogastric AL. METHODS: All oesophagectomies carried out at our institution from 2010 to 2017 were included. Serial C-reactive protein (CRP) and white cell count (WCC) were recorded pre-operatively and on each consecutive day up to day 10 post-op. All complications were recorded and the timing of diagnosis compared with serial CRP and WCC measurements to determine any correlation. RESULTS: One hundred and two patients underwent oesophagectomy (84 male, 18 female) with a mean age of 62.5 years (± 9.8). Forty-seven patients developed post-operative complications, with pulmonary (n = 28) the most common. There were 5 cases of AL. Patients in the AL group (n = 5) had a significantly higher mean CRP compared to those who did not develop AL (n = 97) pre-operatively (50 vs. 14, p = 0.046), on post-op day 3 (300 vs. 218, p = 0.02) and on post-op day 4 (279 vs. 184, p = 0.009). There was no significant difference in mean daily CRP between patients with pulmonary complications (PC, n = 29) and those who did not develop complications (NC, n = 54). CONCLUSIONS: Elevated CRP may be a useful marker in facilitating the prompt diagnosis of AL following oesophagectomy. Serial CRP may not contribute to identifying lower respiratory tract infections, partly as a result of the pro-inflammatory response following surgery.

Preoperative C-reactive protein-to-albumin ratio predicts anastomotic leak in elderly patients after curative colorectal surgery.

BACKGROUND: Anastomotic leak (AL), as one of the most devastating complications, is the leading cause of mortality in colorectal cancer (CRC) patients after resection. This study was aimed to investigate potential risk factors for AL in elderly surgical CRC patients. METHODS: A total of 1068 elderly subjects who underwent elective curative colorectal surgery from 2012 to 2018 were retrospectively evaluated and enrolled into this study population. The predictive value of C-reactive protein-to-albumin ratio (CAR) for AL in surgical CRC patients was evaluated by receiver operating characteristic (ROC) curve analysis. Potential risk factors for AL were assessed by the univariate and multivariate logistic regression analyses. RESULTS: Of all the 1068 enrolled patients, 81 patients have developed AL with an incidence of 7.6% (81/1068). Preoperative CAR was an effective predictor for AL with an area under the curve (AUC) of 0.758, 95% CI of 0.700-0.817, a cut-off value of 2.44, a sensitivity of 61.09% and a specificity of 80.25%, respectively (P< 0.001). Duration of operation (OR: 2.05, 95% CI: 1.21-3.44, P= 0.013) and preoperative CAR (OR: 1.94, 95% CI: 1.21-3.11, P= 0.007) were two independent risk factors for AL by the multivariate logistic regression analysis. CONCLUSIONS: Our study indicate that preoperative CAR level and duration of operation were two independent predictors for AL among elderly surgical CRC patients.

Systematic use of the serum C-reactive protein concentration and computed tomography for the detection of intestinal anastomotic leaks.

BACKGROUND: This study aimed to characterize the time-dependent relationship between serum C-reactive protein (CRP) and anastomotic integrity in the early post-operative period and to develop a systematic use of CRP and computed tomography. METHODS: Patients aged 18 years or over who had the formation of a left-sided colonic or a colorectal anastomosis, in Royal Sussex County Hospital, were included. The post-operative day (POD) CRP cut-off values were calculated according to receiver operating characteristic analysis to evaluate the sensitivities and specificities of the proposed cut-off parameters. RESULTS: A total of 125 left-sided colonic and colorectal anastomoses were recruited and analysed. When comparing to POD1 CRP cut-off, the calculated CRP ratio cut-off values of all the rest of PODs (2-5) were highly significant in the laparoscopic group and the overall group (P < 0.001). This statistically significant ratio was also demonstrated in the open group at POD2 (P < 0.0001). CONCLUSION: CRP and CRP ratios cut-off values were sensitive to detect an anastomotic leak in the early post-operative period. The cut-off values could facilitate the development of systematic use of CRP and computed tomography.

Monocytic HLA-DR Expression for Prediction of Anastomotic Leak after Colorectal Surgery.

BACKGROUND: Earlier detection of anastomotic leakage (AL) after colorectal procedures could minimize the detrimental clinical impact of AL and thereby reduce morbidity and mortality. STUDY DESIGN: We conducted a prospective study with assessment of the diagnostic accuracy of monocytic HLA-DR (mHLA-DR) expression compared with WBCs, C-reactive protein (CRP), and procalcitonin (PCT) in predicting AL in patients undergoing elective colorectal operation with anastomosis. RESULTS: Comparison of the blood marker values on postoperative day (POD) 4 revealed significant differences for all markers, but the difference for mHLA-DR was highly significant (15% expression of monocytes in AL patients vs 34% in patients without AL; p = 0.001). Together with WBC (p = 0.026), mHLA-DR expression was the only test to show significance on day 3 (14% vs 31%; p < 0.001). Receiver operating characteristic analysis revealed that mHLA-DR expression had superior diagnostic accuracy compared with all other diagnostic markers both on POD 3 (mHLA-DR area under the curve [AUC] 0.928; WBC AUC 0.734; CRP AUC 0.707; PCT AUC 0.672) and POD 4 (mHLA-DR AUC 0.887; WBC AUC 0.738; CRP AUC 0.709; PCT AUC 0.696). Monocytic HLA-DR had a negative predictive value of at least 94% on PODs 3 and 4, as well as specificity and positive predictive values of 100% at a threshold of 23% on POD 3 and 24% on POD 4, respectively. CONCLUSIONS: Expression of mHLA-DR appears to be a more accurate predictor for AL after colorectal operation compared with WBC, CRP, and PCT. It represents a promising test to precisely monitor the perioperative course of high-risk patients and contribute to safer discharge.

Early diagnosis of anastomotic leakage after colorectal surgery by the Dutch leakage score, serum procalcitonin and serum C-reactive protein: study protocol of a prospective multicentre observational study by the Italian ColoRectal Anastomotic Leakage (iC.

BACKGROUND: Anastomotic leakage (AL) is a dreaded major complication after colorectal surgery. There is no uniform definition of anastomotic dehiscence and leak. Over the years many risk factors have been identified (distance of anastomosis from anal verge, gender, BMI, ASA score) but none of these allows an early diagnosis of AL. The DUtch LeaKage (DULK) score, C reactive protein (CRP) and procalcitonin (PCT) have been identified as early predictors for anastomotic leakage starting from postoperative day (POD) 2-3. The study was designed to prospectively evaluate AL rates after colorectal resections, in order to give a definite answer to the need for clear risk factors, and testing the diagnostic yeld of DULK score and of laboratory markers. Methods and analysis. A prospective enrollment for all patients undergoing elective colorectal surgery with anastomosis carried out from September 2017 to September 2018 in 19 Italian surgical centers. OUTCOME MEASURES: preoperative risk factors of anastomotic leakage; operative parameters; leukocyte count, serum CRP, serum PCT and DULK score assessment on POD 2 and 3. Primary endpoint is AL; secondary endpoints are minor and major complications according to Clavien-Dindo classification; morbidity and mortality rates; readmission and reoperation rates, length of postoperative hospital stay (Retrospectively registered at ClinicalTrials.gov Identifier: NCT03560180, on June 18, 2018). Ethics. The ethics committee of the "Comitato Etico Regionale delle Marche - C.E.R.M." reviewed and approved this study protocol on September 7, 2017 (protocol no. 2017-0244-AS). All the participating centers submitted the protocol and obtained authorization from the local Institutional Review Board.

Near-infrared fluorescence image-guidance in anastomotic colorectal cancer surgery and its relation to serum markers of anastomotic leakage: a clinical pilot study.

OBJECTIVE: Near-infrared fluorescence (NIRF) imaging using indocyanine green (ICG) might help reduce anastomotic leakage (AL) after colorectal surgery. This pilot study aims to analyze whether a relation exists between measured fluorescence intensity (FI) and postoperative inflammatory markers of AL, C-reactive protein (CRP), Intestinal fatty-acid binding protein (I-FABP), and calprotectin, to AL, in order to evaluate the potential of FI to objectively predict AL. METHODS: Patients scheduled for anastomotic colorectal cancer surgery were eligible for inclusion in this prospective pilot study. During surgery, at three time points (after bowel devascularization; before actual transection; after completion of anastomosis) a bolus of 0.2 mg/kg ICG was administered intravenously for assessment of bowel perfusion. FI was scored in scale from 1 to 5 based on the operating surgeon's judgment (1 = no fluorescence visible, 5 = maximum fluorescent signal). The complete surgical procedure was digitally recorded. These recordings were used to measure FI postoperatively using OsiriX imaging software. Serum CRP, I-FABP, and calprotectin values were determined before surgery and on day 1, 3, and 5 postoperative; furthermore, the occurrence of AL was recorded. RESULTS: Thirty patients (n = 19 males; mean age 67 years; mean BMI 27.2) undergoing either laparoscopic or robotic anastomotic colorectal surgery were included. Indication for surgery was rectal-(n = 10), rectosigmoid-(n = 2), sigmoid-(n = 10), or more proximal colon carcinomas (n = 8). Five patients (16.7%) developed AL (n = 2 (6.6%) grade C according to the definition of the International Study group of Rectal Cancer). In patients with AL, the maximum fluorescence score was given less often (P = 0.02) and a lower FI compared to background FI was measured at 1st assessment (P = 0.039). However, no relation between FI and postoperative inflammatory parameters could be found. CONCLUSION: Both subjective and measured FI seem to be related to AL. In this study, no relation between FI and inflammatory serum markers could yet be found.

C-reactive protein to albumin ratio is a key indicator in a predictive model for anastomosis leakage after esophagectomy: Application of classification and regression tree analysis.

BACKGROUND: Anastomotic leakage (AL), a serious complication after esophagectomy, might impair patient quality of life, prolong hospital stay, and even lead to surgery-related death. The aim of this study was to show a novel decision model based on classification and regression tree (CART) analysis for the prediction of postoperative AL among patients who have undergone esophagectomy. METHODS: A total of 450 patients (training set: 356; test set: 94) with perioperative information were included. A decision tree model was established to identify the predictors of AL in the training set, which was validated in the test set. A receiver operating characteristic curve was also created to illustrate the diagnostic ability of the decision model. RESULTS: A total of 12.2% (55/450) of the 450 patients suffered AL, which was diagnosed at median postoperative day 7 (range: 6-16). The decision tree model, containing surgical duration, postoperative lymphocyte count, and postoperative C-reactive protein to albumin ratio, was established by CART analysis. Among the three variables, the postoperative C-reactive protein to albumin ratio was identified as the most important indicator in the CART model with normalized importance of 100%. According to the results validated in the test set, the sensitivity, specificity, positive and negative predictive value, and diagnostic accuracy of the prediction model were 80%, 98.8%, 88.9%, 97.6%, and 96.8%, respectively. Moreover, the area under the receiver operating characteristic curve was 0.95. CONCLUSION: The decision model based on CART analysis presented good performance for predicting AL, and might allow the early identification of patients at high risk.