Using preoperative C-reactive protein levels to predict anastomotic leaks and other complications after elective colorectal surgery: A systematic review and meta-analysis.

AIM: While postoperative C-reactive protein (CRP) is used routinely as an early indicator of anastomotic leak (AL), preoperative CRP remains to be established as a potential predictor of AL for elective colorectal surgery. The aim of this systematic review and meta-analysis is to examine the association between preoperative CRP and postoperative complications including AL. METHOD: MEDLINE, EMBASE, Web of Science, PubMed, Cochrane Library and CINAHL databases were searched. Studies with reported preoperative CRP values and short-term surgical outcomes after elective colorectal surgery were included. An inverse variance random effects meta-analysis was performed for all meta-analysed outcomes to determine if patients with or without complications and AL differed in their preoperative CRP levels. Risk of bias was assessed with MINORS and certainty of evidence with GRADE. RESULTS: From 1945 citations, 23 studies evaluating 7147 patients were included. Patients experiencing postoperative infective complications had significantly greater preoperative CRP values [eight studies, n = 2421 patients, mean difference (MD) 8.0, 95% CI 3.77-12.23, p < 0.01]. A significant interaction was observed with subgroup analysis based on whether patients were undergoing surgery for inflammatory bowel disease (X2 = 8.99, p < 0.01). Preoperative CRP values were not significantly different between patients experiencing and not experiencing AL (seven studies, n = 3317, MD 2.15, 95% CI -2.35 to 6.66, p = 0.35), nor were they different between patients experiencing and not experiencing overall postoperative morbidity (nine studies, n = 2958, MD 4.54, 95% CI -2.55 to 11.62, p = 0.31) after elective colorectal surgery. CONCLUSION: Higher preoperative CRP levels are associated with increased rates of overall infective complications, but not with AL alone or with overall morbidity in patients undergoing elective colorectal surgery.

Procalcitonin and C-reactive protein as early markers of anastomotic leakage in intestinal resections for advanced ovarian cancer (EDMOCS).

INTRODUCTION: Serum levels of procalcitonin and C-reactive protein (CRP) have been used to predict anastomotic leakage after colorectal surgery, but information is scarce in advanced ovarian cancer (AOC) surgery with bowel resection. This study aimed to assess the predictive value of procalcitonin and CRP in detecting anastomotic leakage after AOC surgery with bowel resection. The study also aimed to determine the optimal postoperative reference values and the best day for evaluating these markers. MATERIAL AND METHODS: This prospective, observational and multicentric trial included 92 patients with AOC undergoing debulking surgery with bowel resection between 2017 and 2020 in 10 reference hospitals in Spain. Procalcitonin and CRP levels were measured at baseline and on postoperative days 1-6. Receiver operating characteristic analysis was performed to evaluate the predictive value of procalcitonin and CRP at each postoperative day. Sensitivity, specificity, positive and negative predictive values were calculated. RESULTS: Anastomotic leakage was detected in six patients (6.5%). Procalcitonin and CRP values were consistently higher in patients with anastomotic leakage at all postoperative days. The maximum area under the curve (AUC) for procalcitonin was observed at postoperative day 1 (AUC = 0.823) with a cutoff value of 3.8 ng/mL (83.3% sensitivity, 81.3% specificity). For CRP, the maximum AUC was found at postoperative day 3 (AUC = 0.833) with a cutoff level of 30.5 mg/dL (100% sensitivity, 80.4% specificity). CONCLUSIONS: Procalcitonin and C-reactive protein are potential biomarkers for early detection of anastomotic leakage after ovarian cancer surgery with bowel resection. Further prospective studies with a larger sample size are needed to confirm these findings.

Peritoneal infection after colorectal cancer surgery induces substantial alterations in postoperative protein levels: an exploratory study.

PURPOSE: Peritoneal infection, due to anastomotic leakage, after resection for colorectal cancer have been shown to associate with increased cancer recurrence and mortality, as well as cardiovascsular morbidity. Alterations in circulating protein levels could help shed light on the underlying mechanisms, prompting this exploratory study of 64 patients operated for colorectal cancer with anastomosis. METHODS: Thirty-two cases who suffered a postoperative peritoneal infection were matched with 32 controls who had a complication-free postoperative stay. Proteins in serum samples at their first postoperative visit and at one year after surgery were analysed using proximity extension assays and enzyme-linked immunosorbent assays. Multivariate projection methods, adjusted for multiple testing, were used to compare levels between groups, and enrichment and network analyses were performed. RESULTS: Seventy-seven proteins, out of 270 tested, were differentially expressed at a median sampling time of 41 days postoperatively. These proteins were all normalised one year after surgery. Many of the differentially expressed top hub proteins have known involvement in cancer progression, survival, invasiveness and metastasis. Over-represented pathways were related to cardiomyopathy, cell-adhesion, extracellular matrix, phosphatidylinositol-3-kinase/Akt (PI3K-Akt) and transforming growth factor beta (TGF-ß) signaling. CONCLUSION: These affected proteins and pathways could provide clues as to why patients with peritoneal infection might suffer increased cancer recurrence, mortality and cardiovascular morbidity.

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.

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.

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.

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.

[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%).

The Predictive Value of Coefficient of PCT × BG for Anastomotic Leak in Esophageal Carcinoma Patients With ARDS After Esophagectomy.

Anastomotic leak was a potentially severe life-threatening complication of esophagectomy, which drew attention in consequence of progressive dyspnea until acute respiratory distress syndrome (ARDS) due to the early asymptomatic presentation. Respiratory failure, caused by ARDS as the severe presentation of anastomotic leak, is the most common organ failure. CRP (C-reactive protein), procalcitonin (PCT), and Blood G (BG) test are the sensitivity markers for inflammatory, sepsis, and fungemia, respectively. Early recognition and intervention treatment of anastomotic leak may alleviate complication and improve outcome. We retrospectively analyzed 71 patients, accepting mechanical ventilation support because of ARDS as the complication after radical resection of esophagus cancer. Clinical data were collected from the patients' electronic medical records, including their clinically hematological examination, drainage fluid cultures, and sputum culture. Accord to appearance of anastomotic leak or not, all patients were divided into 2 groups, leak group and no-leak group. Inflammatory markers, such as CRP, PCT, and the coefficient of BG and PCT, were significantly different between the 2 groups. Respiratory index, white blood cell, hemoglobin (HBG), platelet (PLT), and other clinical factors were not significantly different between the 2 groups. Receiver operating characteristic curves were constructed to calculate the sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve for various cutoff levels of several factors. Blood G tests presented the better predicting value for anastomotic leak. Blood G tests and PCT should be tested after esophagectomy. The coefficient of PCT and BG (>260) is of great significance, and clinical value to predict anastomotic leak for patients with postesophagectomy ARDS, early PCT and BG test, and especially, dynamic variation may alleviate complication and improve outcome.

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.

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.

The importance of presepsin value in detection of gastrointestinal anastomotic leak: a pilot study.

BACKGROUND: Early diagnosis of anastomotic leakage is the most important factor in reducing its morbidity and mortality. Anastomotic integrity monitoring of the leukocyte count (WBC), C-reactive protein (CRP), and neutrophil-lymphocyte ratio (NLR) are commonly used laboratory parameters. The availability of follow-up presepsin anastomotic integrity was investigated in this study. MATERIALS AND METHODS: This study included patients who had gastrointestinal anastomosis due to major abdominal surgery between January 2016 and February 2017. Blood samples were collected to determine the WBC, CRP, NLR, and presepsin values before the anastomosis was performed and then taken on postoperative days 1, 3, and 5. RESULTS: This is a prospective nonrandomized study with 100 consecutive patients enrolled in the anastomosis group (male/female, 42:58). WBC, CRP, NLR, and presepsin values are based on certain days in the complication group, and the complication group increased with statistical significance. Presepsin had a specificity of 98.63% in determining anastomotic leak. CONCLUSIONS: Presepsin can be used as a supplemental marker with CRP and NLR for anastomotic integrity.

Neutrophil to Lymphocyte Ratio and C-Reactive Protein as Two Predictive Tools of Anastomotic Leak in Colorectal Cancer Open Surgery.

PURPOSE: To assess the prognostic value of postoperative C-reactive protein (CRP) and neutrophil to lymphocyte ratio (NLR) in the development of anastomotic leak (AL) in patients after surgery for colorectal cancer (CRC). METHODS: Patients operated on for CRC between 2010 and 2014 were enrolled into the study. The sensitivity, specificity, positive predictive value (PPV) and negative predictive values (NPVs) were calculated for the CRP and NLR measured on the 4th postoperative day (POD). RESULTS: Among 724 patients, AL was diagnosed in 33 (4.6%). The accuracy of CRP in the detection of AL using area under curve was 0.83 with the optimal cut-off value of 180 mg/L, sensitivity 75%, specificity 91%, PPV 52% and NPV 87%. Also, NLR on POD4 was higher in the AL group: 9.03 ± 4.13 vs. 4.45 ± 2.25; p = 0.0012; sensitivity 69%, specificity 78%, PPV 49%, NPV 88% at cut-off point of 6.5. Moreover, CRP and NLR on POD4 were significantly higher in patients who died in the postoperative period: 239 ± 24 mg/L vs. 199 ± 41 mg/L; p = 0.034 and 10.71 ± 2.08 vs. 8.65 ± 4.67; p = 0.029, respectively). CONCLUSIONS: CRP and NLR on POD4 possess the ability to predict the development of AL and postoperative mortality after CRC operation. Based on our results, high NPV might be indicative of patients with low risk of AL in their postoperative period.

Utility of C-reactive protein as predictive biomarker of anastomotic leak after minimally invasive esophagectomy.

BACKGROUND: Early detection of anastomotic leakage after esophagectomy has the potential to reduce morbidity and mortality. Prompt suspicion of leak may help to exclude patients from fast-track protocols, thereby avoiding early oral feeding and early hospital discharge which could aggravate the prognosis of a clinically occult leak. PATIENTS AND METHODS: Observational retrospective cohort study. Patients with diagnosis of esophageal cancer who underwent elective minimally invasive esophagectomy were included. The following data were collected: age, gender, BMI, comorbidities, ASA score, tumor histology, TNM staging, use of neo-adjuvant therapy, type of operation, operative time, morbidity, and 90-day mortality. A panel of biomarkers including C-reactive protein (CRP), procalcitonin (PCT), white blood cells (WBC), and percentage of neutrophils (PN) were measured at baseline and on postoperative days 3, 5, and 7. RESULTS: Two hundred forty-three patients operated between 2012 and 2017 were included in the study. Anastomotic leakage occurred in 29 patients. There was a statistical association over time between anastomotic leakage and CRP (p < 0.001), PCT (p < 0.001), WBC (p = 0.019), and PN (p = 0.007). The cut-off value of CRP on POD 5 was 8.3 mg/dL, AUC = 0.818, negative LR = 0.176. CONCLUSIONS: Increased serum CRP, PCT, WBC, and PN after minimally invasive esophagectomy are associated with anastomotic leakage. A CRP value lower than 8.3 mg/dL, combined with reassuring clinical and radiological signs, may be useful to exclude leakage on postoperative day 5.

Minimally invasive esophagectomy in the prone position improves postoperative outcomes: role of C-reactive protein as an indicator of surgical invasiveness.

BACKGROUND: The aim of the study was to assess serum C-reactive protein (CRP) level immediately after minimally invasive esophagectomy (MIE) as a surrogate of surgical invasiveness in patients who underwent esophagectomy. METHODS: In total, 104 patients were enrolled in the study: 37 patients underwent MIE in the left lateral decubitus position (MIE-LP) and 67 patients underwent MIE in the prone position (MIE-PP). Serum CRP levels were assessed on POD 1, 3, 5, and 7 after MIE, and were compared with surgical outcomes and duration of systemic inflammatory response syndrome (SIRS) to investigate less invasiveness of the MIE. RESULTS: Reduced serum CRP level on POD 1 was associated with PP during MIE (P < 0.001) and decreased blood loss (P = 0.03). MIE-PP was identified as a significant independent predictor of reduced CRP level on POD 1 (odds ratio 3.65, P = 0.042). CRP level on POD 7 was associated with gender (P = 0.02), position of MIE (P = 0.011), blood loss (P = 0.02), and respiratory complications and/or anastomotic leakage (P < 0.001). Postoperative respiratory and/or anastomotic complication was identified as a significant predictor of elevated serum CRP level on POD 7 (odds ratio 3.44, P = 0.048). Shorter duration of SIRS was shown in the patients with reduced serum CRP level on POD 1 and 7 (P = 0.03 and P < 0.001, respectively). CONCLUSION: Serial assessments of serum CRP level immediately after MIE may be a possible indicator that can reflect surgical invasiveness and postoperative complications.

Monitoring of procalcitonin but not interleukin-6 is useful for the early prediction of anastomotic leakage after colorectal surgery.

BACKGROUND: Early recognition of patients who have developed anastomotic leakage (AL) after colorectal surgery is crucial for the successful treatment of this complication. The aim of this study was to assess the usefulness of the assessment of procalcitonin (PCT) and interleukin-6 (IL-6) levels in the prognosis of AL. METHODS: This observational study included 157 patients who underwent major elective colorectal surgery. The most common indications for surgery were cancer and inflammatory bowel diseases. Serum samples were obtained directly before surgery (D0) and 1 day (D1) after surgery, and the relationships between the serum concentrations of PCT and IL-6 and development of AL were assessed. RESULTS: In total, 10.2% of patients developed post-surgical infections due to AL. PCT levels on D1 were significantly higher in patients who developed AL [2.73 (1.40-4.62)] than in those who recovered without complications [0.2 (0.09-0.44)]. The area under the ROC curve for PCT on D1 was 0.94, 95% CI (0.89-0.98). The sensitivity and specificity of the prediction of an infection were 87% and 87%, respectively, for PCT on D1, which was higher than 1.09 ng/mL. The increase in PCT concentration between D0 and D1 was significantly higher in patients with AL (p<0.001). Patients who developed AL had higher concentrations of IL-6 on D1, but the difference was not significant (p=0.28). CONCLUSIONS: This study confirms that surgical trauma increases serum PCT concentrations and that the concentration of PCT on D1 can predict AL after colorectal surgery. However, IL-6 is not a good early marker for developing AL.

Peripheral blood leucocytes show differential expression of tumour progression-related genes in colorectal cancer patients who have a postoperative intra-abdominal infection: a prospective matched cohort study.

AIM: Anastomotic leak is associated with higher rates of recurrence after surgery for colorectal cancer. However, the mechanisms responsible are unknown. We hypothesized that the infection-induced inflammatory response may induce overexpression of tumour progression-related genes in immune cells. The aim was to investigate the effect of postoperative intra-abdominal infection on the gene expression patterns of peripheral blood leucocytes (PBL) after surgery for colorectal cancer. METHOD: Prospective matched cohort study. Patients undergoing surgery for colorectal cancer were included. Patients who had anastomotic leak or intra-abdominal abscess were included in the infection group (n = 23) and matched with patients without complications for the control group (n = 23). PBL were isolated from postoperative blood samples. Total RNA was extracted and hybridized to the Affymetrix Human Gene 1.0 ST microarray. RESULTS: Patients in the infection group displayed 162 upregulated genes and 146 downregulated genes with respect to the control group. Upregulated genes included examples coding for secreted cytokines involved in tumour growth and invasion (S100P, HGF, MMP8, MMP9, PDGFC, IL1R2). Infection also upregulated some proangiogenic genes (CEP55, TRPS1) and downregulated some inhibitors of angiogenesis (MME, ALOX15, CXCL10). Finally, some inhibitors (HP, ORM1, OLFM4, IRAK3) and activators (GNLY, PRF1, FGFBP2) of antitumour immunity were upregulated and downregulated, respectively, suggesting that the inflammatory environment caused by a postoperative infection favours immune evasion mechanisms of the tumour. CONCLUSION: Analysis of PBL shows differential expression of certain tumour progression-related genes in colorectal cancer patients who have a postoperative intra-abdominal infection, which in turn may promote the growth of residual cancer cells to become recurrent tumours.

Relation between postoperative ileus and anastomotic leakage after colorectal resection: a post hoc analysis of a prospective randomized controlled trial.

AIM: Anastomotic leakage (AL) following abdominal surgery is a critical determinant of postoperative recovery, of which the aetiology is largely unknown. Interestingly, interventions aimed at reducing the inflammatory response and postoperative ileus (POI) have an unexpected effect on AL. The aim of this study was to investigate the relation of POI with inflammation and AL after colorectal resection. METHOD: A post hoc analysis of a prospective randomized controlled trial in which patients underwent a colorectal resection was performed. Patients undergoing a colorectal resection were stratified into having or not having POI. The incidence of AL and other clinical parameters was registered prospectively. Intestinal fatty acid binding protein (I-FABP, a marker for tissue damage) and the inflammatory response in plasma and colon tissue were determined. RESULTS: AL was present in nine of 43 patients in the POI group, and in one of 65 in the group without POI (P < 0.001). There was a significant association between POI and AL (OR 12.57, 95% CI: 2.73-120.65; P = 0.0005). Patients with POI had significantly higher plasma levels of soluble tumour necrosis factor receptor 1 (TNFRSF1A) at 4 h postoperatively (0.89 ng/l, interquartile range 0.56) than patients without POI (0.80 ng/l, interquartile range 0.37; P = 0.04) and higher plasma levels of C-reactive protein on the second day postoperatively (234 ± 77 vs 163 ± 86 mg/l; P = 0.001). Patients who developed AL had significantly higher plasma levels of I-FABP compared with patients without AL at 24 h after onset of surgery. CONCLUSION: POI is associated with a higher prevalence of AL and an increased inflammatory response.

C-reactive protein, fibrinogen, and procalcitonin levels as early markers of staple line leak after laparoscopic sleeve gastrectomy in morbidly obese patients within an Enhanced Recovery After Surgery (ERAS) program.

INTRODUCTION: The performance of most bariatric procedures within an Enhanced Recovery After Surgery program has resulted in significant advantages, including a reduction in the length of hospital stay to 2-3 days. However, some postoperative complications may appear after the patient has been discharged. The aim of this study was to investigate the efficacy of various acute-phase parameters determined 24 h after a laparoscopic sleeve gastrectomy for predicting staple line leak in the postoperative course. PATIENTS AND METHODS: A prospective study of 208 morbidly obese patients undergoing laparoscopic sleeve gastrectomy as bariatric procedure between 2012 and 2015 was performed. Blood analysis was performed 24 h after surgery. Acute-phase parameters (C-reactive protein, procalcitonin, fibrinogen, and White Blood Cell count) were investigated. RESULTS: Staple line leak appeared in eight patients (3.8%). Using receiver operating characteristic analysis at 24 h postoperatively, a cutoff level of CRP at 9 mg/dL achieved 85% sensitivity and 90% specificity for predicting staple line leak, a cutoff level of procalcitonin at 0.85 ng/mL achieved 70% sensitivity and 90% specificity, and a cutoff level of fibrinogen at 600 mg/dL achieved 80% sensitivity and 87.5% specificity. CONCLUSION: An elevation of CRP > 9 mg/dL, procalcitonin > 0.85 ng/mL and fibrinogen > 600 mg/dL should alert the surgeon the possibility of occurrence of postoperative staple line leak.

C reactive protein as a predictor of anastomotic leakage in colorectal surgery. Comparison between open and laparoscopic surgery. / Proteína C reactiva como predictor de fuga anastomótica en cirugía colorrectal. Comparación entre cirugía abierta y laparoscópica.

INTRODUCTION: Anastomotic leak (AL) is a serious complication in colorectal surgery due to its increase in morbidity and mortality. The aim of this prospective non-randomised study is to determine whether C-reactive Protein (CRP) is useful as a predictor of AL in patients undergoing open versus laparoscopic surgery. METHODS: A total of 168 patients undergoing elective colorectal surgery were included. CRP was measured daily during the first 5postoperative days. Complications, specially AL, were analysed. RESULTS: Following an open approach 32 patients (45.7%) presented complications, 15 (18.7%) in the laparoscopic group and 12 (29.4%) in the converted group (P=0.153). Following open surgery 9 patients experienced AL, 5 were detected in the laparoscopic group and none in those converted (P=0.153). There were significant differences in CRP values between the 3 groups (P=0.03). ROC Curves showed AUC for the open and laparoscopic approach of 0.731 and 0.760 respectively. On day 4 the AUC was 0.867 for the open group and 0.914 for the laparoscopic group. Cut-off points on day 4 were: Open: 159.2mg/L; sensitivity 75%, specificity 89% and NPP 96% (P<0.001). Following laparoscopic surgery the cut-off point was 67.3%; sensitivity 100%, specificity 89.5% and NPP 100% (P=0.016). CONCLUSION: CRP on day 4 is useful to diagnose AL. Different cut-off values should be taken into account depending on the approach used.