Use of C-reactive protein for the early prediction of anastomotic leak after esophagectomy: Systematic review and Bayesian meta-analysis.
ABSTRACT: BACKGROUND:Early suspicion, diagnosis, and timely treatment of anastomotic leak after esophagectomy is essential. Retrospective studies have investigated the role of C-reactive protein (CRP) as early marker of anastomotic leakage. The aim of this systematic review and meta-analysis was to evaluate the predictive value of CRP after esophageal resection. METHODS:A literature search was conducted to identify all reports including serial postoperative CRP measurements to predict anastomotic leakage after elective open or minimally invasive esophagectomy. Fully Bayesian meta-analysis was carried out using random-effects model for pooling diagnostic accuracy measures along with CRP cut-off values at different postoperative day. RESULTS:Five studies published between 2012 and 2018 met the inclusion criteria. Overall, 850 patients were included. Ivor-Lewis esophagectomy was the most common surgical procedure (72.3%) and half of the patients had squamous-cell carcinoma (50.4%). The estimated pooled prevalence of anastomotic leak was 11% (95% CI = 8-14%). The serum CRP level on POD3 and POD5 had comparable diagnostic accuracy with a pooled area under the curve of 0.80 (95% CIs 0.77-0.92) and 0.83 (95% CIs 0.61-0.96), respectively. The derived pooled CRP cut-off values were 17.6 mg/dl on POD 3 and 13.2 mg/dl on POD 5; the negative likelihood ratio were 0.35 (95% CIs 0.096-0.62) and 0.195 (95% CIs 0.04-0.52). CONCLUSION:After esophagectomy, a CRP value lower than 17.6 mg/dl on POD3 and 13.2 mg/dl on POD5 combined with reassuring clinical and radiological signs may be useful to rule-out leakage. In the context of ERAS protocols, this may help to avoid contrast radiological studies, anticipate oral feeding, accelerate hospital discharge, and reduce costs.
Project description:Disturbance of intestinal wound closure leads to insufficient anastomotic healing and is associated with considerable morbidity following colorectal resections. Matrix metalloproteinases (MMPs) play a crucial role in regulation of wound closure. Here fluorescence endoscopy was evaluated for assessment of MMP-2/-9 expression during failed intestinal anastomotic healing.Distal colonic anastomoses were performed as a model for disturbed healing in 36 Balb/c mice. Healing was evaluated endoscopically, macroscopically, and histologically after 1, 3 and 5 days. For detection of MMP-2/-9 expression fluorescence endoscopy (FE) was used following i.v.-administration of a Cy5.5-labeled MMP-2/-9 specific tracer. FE was complemented by quantification of the fluorescence signal using the MS-FX PRO Optical Imaging System. An overall leakage score was calculated and correlated with the results of FE.With increasing incidence of anastomotic leakage from POD1 (17%) to POD5 (83%) the uptake of the MMP tracer gradually increased (signal-to-noise ratio (SNR), POD1: 17.91 ± 1.251 vs. POD3: 30.56 ± 3.03 vs. POD5: 44.8 ± 4.473, P<0.0001). Mice with defective anastomotic healing showed significantly higher uptake compared to non-defective (SNR: 37.37± 3.63 vs. 26.16± 3.635, P = 0.0369). White light endoscopy and FE allowed evaluation of anastomotic healing and visualization of mucosal MMPs in vivo. Using FE based detection of MMPs in the anastomosis, an overall positive predictive value of 71.4% and negative predictive value of 66.6% was calculated for detection of anastomotic leakage.During disturbed anastomotic healing increased expression of MMP-2/-9 was observed in the anastomotic tissue. Fluorescence endoscopy for detection of MMP-2/-9 during the healing process might be a promising tool for early identification of anastomotic leakage.
Project description: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.
Project description: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.
Project description:BACKGROUND AND OBJECTIVES:As a well-established technique for postoperative pain relief, the benefits of epidural analgesia (EDA) have been under debate recently. This study aimed to determine whether EDA could improve perioperative outcomes and survival in patients undergoing esophagectomy. METHODS:From January 2010 to December 2012, 587 consecutive cases undergoing McKeown-type esohpageactomy were retrospectively identified from a prospectively maintained database. RESULTS:After propensity-matching, incorporating baseline characteristics, 178 cases were included in each group, and patients characteristics distributions were well-balanced between two groups. Compared with intravenous analgesia, the use of EDA significantly decreased the incidence of pneumonia from 32% to 19.7% (P = 0.008), and anastomotic leakage from 23.0% to 14.0% (P = 0.029). The change in CRP level of EDA group was significantly decreased (preoperative, 6.2 vs. 6.2; POD 1, 108.1 vs. 121.3; POD 3, 131.5 vs. 137.8; POD 7, 69.3 vs. 82.1 mg/L; P = 0.044). EDA patients had a significantly longer duration of indwelling urinary catheter (P<0.001), and lower levels in both systolic (P = 0.001) and diastolic blood pressure (P<0.001). There weren't significant differences in overall survival (log-rank P = 0.47) and recurrence (Gray-test P = 0.46) between two groups. CONCLUSIONS:These findings revealed that EDA could attenuate inflammatory response and reduce the incidence of pneumonia and anastomotic leakage after esophagectomy, at the price of delayed urinary catheter removal and lower blood pressure. EDA remains an important component of multimodal perioperative management after esophagectomy.
Project description:Background:Anastomotic leakage (0-30%) after esophagectomy is a severe complication and is associated with considerable morbidity and mortality. The aim of this study was to determine which treatment for anastomotic leakage after esophagectomy have the best clinical outcome, based on the currently available literature. Methods:A systematic literature search was performed in Medline, Embase, and Web of Science until April 2017. All studies reporting on the specific treatment of cervical or intrathoracic anastomotic leakage following esophagectomy with gastric tube reconstruction for esophageal or cardia cancer were included. The primary outcome parameter was postoperative mortality. Methodological quality was assessed by the Newcastle-Ottawa Quality Assessment Scale. Results:Nineteen retrospective cohort studies including 273 patients were identified. Methodological quality of all studies was poor to moderate. Mortality rates of intrathoracic anastomotic leakages in the treatment groups were as follows: conservative (14%), endoscopic stent (8%), endoscopic drainage (8%), endoscopic vacuum-assisted closure system (0%), and surgery treatment group (50%). Mortality rates of cervical anastomotic leakages in the treatment groups were as follows: conservative (8%), endoscopic stent (29%), and endoscopic dilatation (0%). Discussion:Due to small cohorts, heterogeneity between studies, and lack of data regarding leakage characteristics, no evidence supporting a specific treatment for anastomotic leakage after esophagectomy was found. A severity score based on leakage characteristics instead of treatment given is essential for determining the optimal treatment of anastomotic leakage. In the absence of robust evidence-based treatment guidelines, we suggest customized treatment depending on sequelae of the leak and clinical condition of the patient. PrDepartment of Surgery, Radboudumc, P.O.B. 9101/618 NLactical advices are provided. Trial registration:Registration number PROSPERO: CRD42016032374.
Project description:BACKGROUND:Esophagectomy with extended lymphadenectomy remains the mainstay of treatment for localized esophageal cancer. Currently, transthoracic and abdominal esophagectomy with cervical anastomosis (McKeown esophagectomy) is a frequently used technique in Japan. However, cervical anastomosis is still an invasive procedure with a high incidence of anastomotic leakage. The use of a drainage tube to treat anastomotic leakage is effective, but the routine placement of a closed suction drain around the anastomosis at the end of the operation remains controversial. The objective of this study is to evaluate the postoperative anastomotic leakage rate, duration to oral intake, hospital stay, and analgesic use with nonplacement of a cervical drainage tube as an alternative to placement of a cervical drainage tube. METHODS:This is an investigator-initiated, investigator-driven, open-label, randomized controlled parallel-group, noninferiority trial. All adult patients (aged??20 and??85?years) with histologically proven, surgically resectable (cT1-3?N0-3 M0) squamous cell carcinoma, adenosquamous cell carcinoma, or basaloid squamous cell carcinoma of the intrathoracic esophagus, and European Clinical Oncology Group performance status 0, 1, or 2 are assessed for eligibility. Patients (n?=?110) with resectable esophageal cancer who provide informed consent in the outpatient clinic are randomized to either nonplacement of a cervical drainage tube (n?=?55) or placement of a cervical drainage tube (n?=?55). The primary outcome is the percentage of Clavien-Dindo grade 2 or higher anastomotic leakage. DISCUSSION:This is the first randomized controlled trial comparing nonplacement versus placement of a cervical drainage tube during McKeown esophagectomy with regards to the usefulness of a drain for anastomotic leakage. If our hypothesis is correct, nonplacement of a cervical drainage tube will be recommended because it is associated with a similar anastomotic leakage rate but less pain than placement of a cervical drainage tube. TRIAL REGISTRATION:UMIN-CTR, 000031244. Registered on 1 May 2018.
Project description:OBJECTIVES:To conduct a systematic review and meta-analysis of studies comparing the gastric-tube vs. whole-stomach for esophageal cancer in order to determine the optimal surgical technique of esophagectomy. METHODS:A comprehensive literature search was performed using PubMed, EMBASE, ScienceDirect, Ovid MEDLINE, Cochrane Library, Web of Science, Google Scholar, and Scopus. Clinical trials that compared the gastric-tube versus whole-stomach for esophageal cancer were selected. The clinical endpoints included anastomotic leakage, anastomotic stenosis, reflux esophagitis, pneumonia, delayed gastric emptying, and thoracic stomach syndrome. RESULTS:A total of 6 articles (1571 patients) were included. Compared to the whole-stomach approach, the gastric-tube approach was associated with a lower incidence of reflux esophagitis (95% confidence interval [CI]: 0.16 to 0.81, p = 0.01) and thoracic stomach syndrome (95% CI: 0.17 to 0.55, p < 0.0001). The rates of anastomotic leakage, anastomotic stenosis, pneumonia, and delayed gastric emptying did not significantly differ between the two groups. CONCLUSIONS:The gastric-tube esophagectomy is superior to the whole-stomach approach, as it is associated with a lower incidence of postoperative reflux esophagitis and thoracic stomach syndrome. Our findings must be validated in large-scale randomized controlled trials.
Project description:BACKGROUND:According to previously published studies, esophagectomy with modified Collard anastomosis has been reported to have low incidences of anastomotic leak and stricture. However, the optional anastomotic method after esophagectomy is still controversial. We conducted this study to compare the incidence of postoperative anastomotic stricture formation and dysphagia over three years after an esophagectomy with modified Collard anastomosis (MC) or end-to-side (ETS) hand-sewn anastomosis. Meanwhile, the early postoperative anastomotic leakage and other complications, hospital stay and 30- and 90-day mortality were also evaluated. METHODS:The clinical data of 905 patients undergoing McKeown esophagectomy were retrospectively reviewed. The rate of postoperative stricture formation after three years was demonstrated by stricture-free survival which is the primary end-point of this study. The incidence of dysphagia, first time of onset of stricture and number of dilatations were also recorded during follow-up. RESULTS:The incidence of anastomotic leak tended to be higher in the MC group compared with that in the ETS group (13.0% vs. 8.7%, P = 0.064). The rates of anastomotic stricture in the MC group were significantly less than in the ETS group (P =?0.004). The number of dilatations in the MC group were significantly greater than those in the ETS group (2.34 vs. 2.46, P = 0.011). CONCLUSIONS:A modified Collard cervical esophagogastric anastomosis was associated with lower rates of anastomotic stricture and dysphagia, compared with ETS hand-sewn anastomosis. However, the modified Collard anastomosis is accompanied by an increased anastomotic leakage rate.
Project description:Minimally invasive esophagectomy (MIE) has consistently been associated with improved perioperative outcome and similar oncological safety compared to open esophagectomy. However, it is currently unclear what type of MIE is preferred for patients with resectable esophageal cancer.Literature was searched in Medline, Embase and the Cochrane library combining relevant search terms. Articles that included patients undergoing totally minimally invasive esophagectomy (TMIE) or hybrid minimally invasive esophagectomy (HMIE) and compared McKeown with Ivor Lewis procedures were included. Studies were excluded if they included >10% of patients undergoing a procedure other than MIE McKeown or MIE Ivor Lewis (i.e., transhiatal resections). The primary outcome parameter was anastomotic leakage. Secondary outcome parameters were: other complications, reinterventions, reoperations, hospital length of stay, ICU length of stay, postoperative mortality, operative time, blood loss, R0 resection rate, lymph nodes examined, quality of life and costs.Five studies with a total of 1,681 patients undergoing TMIE were included. There were no studies comparing HMIE McKeown versus HMIE Ivor Lewis. There were no randomized controlled trials and all included studies were cohort studies with a moderate risk of bias. No meta-analysis could be performed for R0 resection rate, survival, quality of life and costs because there was insufficient data available for these parameters. The incidence of anastomotic leakage did not differ between the groups [relative risk (RR) =1.39, 95% confidence interval (CI) =0.90-10.38, P=0.14]. TMIE Ivor Lewis was associated with a lower incidence of recurrent laryngeal nerve (RLN) trauma (RR =6.70, 95% CI =3.09-14.55, P<0.001), a shorter hospital length of stay [standardized mean difference (SMD) =0.17, 95% CI =0.06-0.28, P=0.002] and less blood loss (SMD =0.69, 95% CI =0.25-1.12, P=0.002).TMIE Ivor Lewis is associated with improved outcome regarding RLN trauma, hospital length of stay and blood loss as compared to TMIE-McKeown, but the incidence of anastomotic leakage is not different. The evidence is limited, of low quality and at risk for bias. A randomized controlled trial is currently being performed in order to demonstrate whether a McKeown or Ivor Lewis procedure should be preferred in patients undergoing MIE.
Project description:INTRODUCTION:Esophagectomy is a challenging procedure associated with considerable morbidity. Previous pulmonary diseases, such as histoplasmosis fungal infection, may interfere in operative and postoperative outcomes after esophagectomy. Anastomotic leakage is one of the most feared complications after esophagectomy. However, new therapies developed such as vacuum procedure and esophageal prosthesis have been provenly beneficial. PRESENTATION OF CASE:We present a case with squamous cell carcinoma of the mid esophagus portion on a young patient with a pulmonary histoplasmosis history. After a multidisciplinary board, the patient underwent transhiatal esophagectomy with gastric-pull up and cervical anastomosis due to pulmonary disease. The patient later developed an anastomotic leak with mediastinal abscess. We describe this complication's management via an endoscopic vacuum system, esophageal prosthesis, and exhibit a video illustrating the technique. DISCUSSION:We illustrate the management of esophageal cancer associated with previous pulmonary disease. Histoplasmosis may misunderstand the esophageal cancer staging, and it can contribute to anastomotic leakage occurrence. An endoscopic vacuum system is an excellent tool for treating esophagogastric anastomosis fistula after esophagectomy, even when the drainage is accumulated in the mediastinum. The esophageal prosthesis may be used after mediastinal abscess resolution. CONCLUSION:Treatment of the association of esophageal cancer and histoplasmosis is feasible. However, care should be taken to avoid highly potential postoperative complications.