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Eur J Cardiothorac Surg 2005;27:3-7
© 2005 Elsevier Science NL

Anastomotic leakage post-esophagogastrectomy for esophageal carcinoma: retrospective analysis of predictive factors, management and influence on longterm survival in a high volume centre

Department of Cardiothoracic Surgery, Derriford Hospital, Southwest Cardiothoracic Center, Plymouth PL6 8DH, UK

Received 1 July 2004; received in revised form 7 September 2004; accepted 17 September 2004.

^* Corresponding author. Tel.: +44 1752 517527; fax: +44 1752 763830. (E-mail: manfred.junemann{at}gmx.net).

	Abstract

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion References

 
Objective: Anastomotic leak post-gastro-esophagectomy for esophageal carcinoma remains an important issue in immediate as well as late morbidity and mortality. Several predictive factors such as patient and technical variables have been suggested with inconsistent findings. Our aim was to compare these factors and the results of treatment of anastomotic dehiscence on short and longterm survival in our center to published data. Methods: A retrospective study of 276 consecutive patients post-Ivor-Lewis gastro-esophagogastrectomy for esophageal carcinoma between 1992 and 1999. Explanatory variables taken into account for predicting anastomotic leak included preoperative weight loss, neoadjuvant therapy, inkwelling of the anastomosis, gastric drainage procedure and involvement of longitudinal resection margins. Incidence variation over time was compared. 5-year survival was assessed using the Kaplan–Meier method. Results: The anastomotic leak rate was 5.1% with only minor variation over time. The 30-day mortality with anastomotic leak was 35.7% compared to 4.2% for patients without leak (P<0.05). None of the suggested explanatory variables analyzed reached statistical significance at a 5% level. On multiple logistic regression there was a trend towards gastric outlet drainage procedure which might decrease the relative risk by 61% (P=0.099). After excluding the 30-day mortality the 5-year survival with anastomotic leak was not different to those without. Conclusions: None of the factors reported in the literature reached statistical significance in our series. High institutional and high surgeon volume seem to outweigh any other contributing factor. Aggressive management for substantial leaks is advocated by the authors as long term palliation does not seem to be affected once the leak has been successfully treated.

Key Words: Esophageal cancer • Esophageal surgery • Complications of surgery

	1. Introduction

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion References

 
Anastomotic dehiscence post-oesophagectomy for carcinoma of the oesophagus and cardia remains an important complication in postoperative morbidity and mortality following this procedure. It may result in mediastinitis and sepsis with a reported mortality of up to 64% [1]. In the past it has been responsible for 40% of the overall postoperative mortality for this procedure. The incidence of leak for intrathoracic anastomosis reported in the literature varies between 3 and 25% [2,3]. Surgeons have looked at patient and technical variables in the hope of identifying possible predictive factors and to develop surgical strategies to prevent this complication [4]. Variations in the incidence of leak has been suggested as an indicator for quality control.

The explanatory variables we have selected to identify possible predicting factors for anastomotic leak in our series include preoperative weight loss, neodjuvant therapy, gastric outlet drainage procedure, involvement of surgical resection margins and inkwelling of the anastomosis.

Routine postoperative screening to diagnose this complication is also controversial [5]. In view of the relatively high incidence and its implications for patient care, screening is common practice in our centre.

Management of this complication, whether conservative or surgical, also remains controversial. Factors influencing surgical decision process include the mode of presentation, symptomatic or asymptomatic and the postoperative course [6]. Keeping in mind the high mortality (>40%) for patients requiring a second intervention [7], careful consideration is necessary to decide if the patient might benefit from a second surgical intervention or not.

The impact on longterm survival of this complication has not been described before and might be of interest in this context in view of the palliative character of this type of surgery.

	2. Patients and methods

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion References

 
A retrospective analysis of all patients who underwent Ivor Lewis gastro-esophagectomy for carcinoma of the esophagus and cardia from January 1992 until March 1999, done by a single surgeon in the Thoracic and Esophageal Surgery Unit in Derriford Hospital, Plymouth, UK, was performed. The cut off date in march 1999 was determined for more accurate assessment of five year survival. This identified 276 consecutive patients. The hospital notes for these patients were reviewed and the recorded detailed information was transferred into a research database.

To assess possible changes in the incidence of anastomotic leak over time the patients were divided into three arbitrary groups of 92 consecutive procedures.

The Esophageal Cancer Database was released for statistical evaluation as well as cross referencing to the Cancer Registry of the South and West Cancer Intelligence Service in Bristol (S and WCIS). Follow-up was complete for all patients to date of death or date of censoring, the 30th of April 2003. The minimum follow up was 4-years (1477 days).

2.1. Surgery
The preoperative nutritional status of the patient was assessed using preoperative weight loss as documented in the clinical notes on the day of admission of the patient into hospital.

Preoperative chemotherapy consisted of 5-fluorouracil (700mg/m²/day, on days 1–5), cisplatinum (70mg/m²/day, on day 1) and leucovorin (20mg/m²/day, on days 1 to 5). Preoperative chemo radiotherapy consisted of cisplatinum chemotherapy combined with radiotherapy (total dosage of 30–70Gy). The time span between the last session of neoadjuvant therapy and the date of the operation was 6 weeks.

The most frequent procedure in our center was the Ivor Lewis two stage gastro-esophagectomy (N=276). Radical resection with 2 field lymphadenectomy was performed in every case.

Anatomical position of the anastomosis in this procedure is the posterior mediastinum. Blood supply was based on the right gastric and right gastro-epiploic artery. The gastric tube was refashioned by transsecting it proximally along the gastric fundus using GIA Autosuture^® (now Tyco^®) 90 stapling device and the stapleline oversewn with a continuous 2.0 Silk suture. All anastomosis were performed using EEA Autosuture Anastomotic Gun^® circular stapling device. The diameter varied between 28 and 32mm. A nasogastric tube was placed past the anastomosis. All procedures were performed by the same surgeon (JSR).

The procedures performed for gastric drainage were Heineke–Mikulicz Pyloroplasty or Fredet–Ramstedt Pyloromyotomy. The decision to omit a gastric drainage procedure was done intraoperatively by the operating surgeon if the pylorus was judged to be widely open and the risk for gastric stasis therefore considered to be small.

Inkwelling (re-enforcement) of the anastomosis as performed achieving a two layer intrathoracic anastomosis. Following formation of the stapled anastomosis a second layer of four partial thickness horizontal mattress sutures, using 3–0 prolene, between the serosal surfaces of the esophagus and the stomach were performed, inkwelling the anastomoses within a cuff of the stomach [8]. Inkwelling of the anastomosis could be omitted by choice of the surgeon.

Patients were kept on total parenteral nutrition postoperatively. The nasogastric tube was kept on free drainage during this period. The nasogastric tube was not removed until the absence of anastomotic leak was established. Parenteral nutrition was continued if there was any doubt about the patency of the anastomosis.

Involved longitudinal resection margins are defined by the status reported on the histopathology report.

The diagnosis of an anastomotic leak was confirmed by a radiological water-soluble contrast study of the esophagus. Routine screening was performed on the fifth postoperative day before initiating oral intake. An anastomotic leak that was diagnosed by this routine postoperative screening, without showing clinical signs and symptoms of a leak, was defined as an ‘On-screening diagnosis’.

If the screening test was negative but the patient showed clinical signs of anastomotic leakage after oral intake was commenced, a repeat X-ray study was arranged to confirm the diagnosis. This was defined as ‘clinical diagnosis’ of the anastomotic leak.

Therapeutic option was defined differentiating conservative treatment against surgical intervention at any time.

Outcome assessment was done by comparing immediate 30-day postoperative mortality along with late mortality using the Kaplan–Meier method.

2.2. Statistics
Explanatory variables for anastomotic leak analysis were deducted from previous reports and data available from our database.

The explanatory variables and groups were assessed as categorical independent variables against anastomotic leakage as the dependent variable. Significance was assessed in univariate analysis using Fisher's exact test and by multiple logistic regression analysis (Backward Wald) at P<5% and <10% level of significance. Odds ratios, relative risk as well as relative risk reduction were obtained by cross tabulation.

Life expectancy was assessed using the Kaplan–Meier method for survival analysis and Log Rank test for significance in difference of survival times. To evaluate the impact of survived anastomotic leaks on longterm outcome the 30 day mortality was excluded in both groups (leak and no leak).

Assessment of therapeutic options and their respective outcomes using 30 day mortality was done in a descriptive manner due to the very low numbers involved and the consequent lack of statistical power.

All data analysis was performed using the SPSS for Windows, Version 9.0 software package.

	3. Results

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion References

 
Clinicopathological characteristics are presented in Table 1. The rate of anastomotic leak was 5.1% (14 out of 276). The 30-day mortality with anastomotic leak was 35.7% (5 out of 14) compared to 4.2% (11 out of 262) for patients without a leak (P<0.05). Anastomotic leak accounted for 31.3% of the overall 30 day mortality.

In this series none of the explanatory variables analyzed for their predictive value reached statistical significance at P<5% level either on univariate or multiple logistic regression analysis (see Tables 2 and 3).

The sensitivity of the routine postoperative radiological screening on day 5 was 21.4%, with the majority of leaks presenting between day 6–10 and later.

Comparison of Kaplan–Meier Survival functions for patients with anastomotic leak surviving the first 30 days showed that the life expectancy is not different to those without this complication (Log Rank P=0.697; see Fig. 1).

View larger version (28K): [in this window] [in a new window]   Fig. 1. Kaplan–Meier survival function by anastomotic leak. Excluding 16 patients as within 30 days mortality. The initially inferior curve represents the survival of patients with anastomotic leak, the initially superior curve for those without. Censored events marked as Log Rank test indicates no significant difference in survival curves.

The following observations on patients who developed anastomotic leak can be made but due to the small numbers involved cannot be supported by statistical analysis:

The 3 patients diagnosed on routine postoperative radiological screening remained asymptomatic and did not fall under the 30 day mortality. These patients seem to have a better survival (median, 521 days) when compared to the 11 who were diagnosed on clinical grounds (median, 38 days).

The conservative treatment group (4 patients) appear to have better survival (median, 272 days) when compared with the surgical group (10 patients; median, 117.5 days).

Splitting up of the treatment options by mode of initial diagnosis revealed that out of 11 patients who were diagnosed on clinical grounds the 2 that were treated conservatively did not survive the first 30 postoperative days. The 3 patients diagnosed on routine postoperative screening did all survive the first 30 postoperative days regardless of their treatment option (1 surgical, 2 conservative).

	4. Discussion

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion References

 
Anastomotic dehiscence, if it occurs, is still associated with a very high postoperative mortality (see Table 1). Published guidelines do now recommend that the incidence of anastomotic leak should not exceed 5% [9]. Over the last years the incidence of reported anastomotic leak is constantly decreasing. This seems to underline the importance of high institutional and surgeon volume outweighing any other possible contributing factors [4,10–14]. The consistent leak rate over time observed in this series might also be a reflection of this. However, the small number of leaks render retrospective analysis difficult if not impossible.

Gastric drainage procedure might be a factor in decreasing the likelihood of anastomotic dehiscence. In this series statistical significance at P<5% was missed by one event.

The possible risk reduction found in our series may be explained by preventing early gastric stasis which may lead to dilatation of the gastric remnant and mechanical stress on the anastomosis. This dilatation of the gastric remnant could also explain impaired blood supply and increased venous congestion.

Improvement of gastric drainage by pyloroplasty has been suggested in various randomised trials (RCT) [15,16].

However, with regards to the possible risk reduction for anastomotic leak, a recent meta-analysis by Urschel et al. [17], did not find any evidence to support this hypothesis. On the other hand only 2 out of the 9 identified RCT reported in this meta-analysis provided information on postoperative anastomotic leaks. Out of these 2 only 1 RCT, by Fok et al. [15] is comparable to our study population in terms of the primary operative procedure. The leakrate reported in this RCT was 5% in each arm (5 out of 100).

In a theoretical model by Olak et al. the benefits of this procedure outweigh the associated morbidity without taking possible anastomotic dehiscence into account [18].

For the diagnosis of anastomotic leak a high index of clinical suspicion is required to compensate for the low sensitivity of routine postoperative screening. Nevertheless routine postoperative screening remains an essential part of the postoperative care as it carries important consequences. Early appropriate management, conservative or surgical, can be implemented once the diagnosis is established [19].

In view of the fact that none of the 2 symptomatic patients treated conservatively survived, and long-term outcome is not reduced if the Patient survives the first 30 days, aggressive management of this complication is advocated by the authors.

	References

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion References

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Junemann-Ramirez, M. Articles by Rahamim, J.S. Search for Related Content PubMed PubMed Citation Articles by Junemann-Ramirez, M. Articles by Rahamim, J.S. Related Collections Esophagus - cancer Esophagus - other