Ann Thorac Surg 2011;92:2034-2040. doi:10.1016/j.athoracsur.2011.05.121
© 2011 The Society of Thoracic Surgeons
Original Articles: General Thoracic
Morbidity and Mortality After Esophagectomy Following Neoadjuvant Chemoradiation
Robert E. Merritt, MD*,
Richard I. Whyte, MD,
Nicole T. D'Arcy, BS,
Chuong D. Hoang, MD,
Joseph B. Shrager, MD
Division of Thoracic Surgery, Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, California
Accepted for publication May 31, 2011.
* Address correspondence to Dr Merritt, 300 Pasteur Dr, Falk Cardiovascular Research Bldg, Stanford, CA 94305-5407 (Email: rmerritt{at}stanford.edu).
Presented at the Poster Session of the Forty-seventh Annual Meeting of The Society of Thoracic Surgeons, San Diego, CA, Jan 31–Feb 2, 2011.
 |
Abstract
|
|---|
Background: Neoadjuvant chemoradiation (CRT) is an accepted treatment for locally advanced esophageal carcinoma. A survival benefit has not been definitively established, and there is concern that chemoradiation may increase postoperative morbidity and mortality.
Methods: A retrospective review was made of 138 patients treated for esophageal carcinoma between January 1999 and December 2009. Fifty-four patients who underwent CRT followed by esophagectomy were compared with 84 patients who underwent esophagectomy alone.
Results: The chemoradiation and esophagectomy alone cohorts were well matched on all preoperative variables. There was a higher percentage of Ivor Lewis procedures in the esophagectomy alone cohort (82.0%) compared with the CRT cohort (59.3%; p = 0.006). Thirty-five percent of the CRT group underwent transhiatal esophagectomy. Thirty-day mortality was 6.0% (5 of 84) in the esophagectomy alone cohort compared with 1.9% (1 of 54) in the CRT cohort (p = 0.5). Similarly, mean intensive care unit stay (4.7 versus 6.5 days; p = 0.5), ventilator time (2.4 versus 4.2 days; p = 0.5), and length of stay (13.5 versus 17 days; p = 0.2) did not differ significantly between the groups. The overall major complication rates were similar in the CRT and esophagectomy alone cohorts: 57.4% versus 56% (p = 0.98). Multivariate analysis determined that coronary artery disease (p = 0.01; odds ratio 3.5) and transthoracic esophagectomy (p = 0.05; odds ratio 1.4) were predictive of development of postoperative complications. Only cervical anastomotic location (p = 0.04; odds ratio 3.0) was predictive of anastomotic leak on multivariate analysis.
Conclusions: Neoadjuvant chemoradiation does not appear to increase postoperative morbidity or mortality after esophagectomy. Major postoperative complications are associated with the transthoracic approach and preoperative coronary artery disease.
|
Introduction
|
|---|
The results of surgical resection as a single modality for the treatment of esophageal cancer remain disappointing. The overall 5-year survival rate for all esophageal carcinoma cases remains relatively low at 17% [1]. The utilization of a neoadjuvant combination of chemotherapy and concurrent radiation therapy has become more prevalent at many centers with substantial experience treating esophageal carcinoma. This multimodality therapeutic approach is commonly used in patients with locally advanced disease consisting of a T2 or greater primary tumor or evidence of locoregional lymph node metastases on preoperative evaluation. The theoretic benefits of neoadjuvant chemoradiation (CRT) include the following: local disease downstaging resulting in a higher complete resection rate, earlier administration of chemotherapy allowing likelier elimination of micrometastatic disease, and more effective delivery of radiation when the target is clear and the tumor is well vascularized. The results of two randomized clinical trials [2, 3] and two meta-analyses [4, 5] suggest that there may in fact be a survival benefit of neoadjuvant chemoradiation followed by esophagectomy over esophagectomy alone, although the data on this are not yet considered conclusive.
Despite the apparent oncologic benefits of neoadjuvant CRT, a number of reports have identified an increased incidence of respiratory and septic complications after esophageal resection in this setting [6–9]. In addition, a variety of reports have demonstrated an increase in postoperative mortality in patients who received neoadjuvant CRT compared with a cohort of patients who underwent esophagectomy alone [3, 4, 10, 11]. In contrast, the recent report from The Society of Thoracic Surgeons General Thoracic Surgery Database demonstrated that neoadjuvant therapy did not appear to be an important predictor of major morbidity and mortality after esophagectomy [12]. Two additional reports by Rice and colleagues [13] and Lin and associates [14] also found that neoadjuvant CRT did not result in increased postoperative morbidity and mortality. In short, the current published literature contains conflicting data on the impact of neoadjuvant CRT on the morbidity and mortality after esophagectomy. We, therefore, carried out this retrospective review to determine the impact of preoperative chemoradiation on the rates of morbidity and mortality after esophagectomy at our institution.
|
Material and Methods
|
|---|
This study is a retrospective review of 138 patients who underwent esophagectomy for esophageal carcinoma on the general thoracic surgery service at Stanford Hospitals and Clinics between January 1999 and December 2009. The charts and electronic medical records of all patients identified were reviewed, and data were collected in deidentified fashion. The study was approved by the Stanford Institutional Review Board, and the requirement for informed consent was waived.
One hundred thirty-eight patients were identified: 84 patients (60.9%) underwent esophagectomy alone, and 54 (39.1%) received neoadjuvant chemoradiation followed by esophagectomy. The following preoperative patient demographics were recorded (Table 1): age, sex, albumin level (g/dL), creatinine level (mg/dL), weight loss (kg), diabetes mellitus rate (%), coronary artery disease rate (%), and smoking (pack-years). The neoadjuvant chemoradiation treatment regimen consisted of primarily cisplatin-based doublet therapy or carboplatin-doublet therapy with concurrent radiotherapy (Table 2), which was administered at the Stanford Cancer Center or in the community with oversight by the radiation oncologists and medical oncologists at Stanford. The mean radiotherapy dose was 47.89 Gy ± 3.7 Gy, and the median radiotherapy dose was 45 Gy (range, 40 to 60 Gy). In a few cases, patients were referred to our institution for surgical resection after they had completed neoadjuvant chemoradiation therapy prescribed solely by community-based oncologists.
Esophagectomy was typically performed 4 to 8 weeks after the completion of chemoradiation therapy. The majority of the esophagectomy procedures were performed using the Ivor-Lewis technique in both the neoadjuvant chemoradiation cohort and esophagectomy alone cohort (Table 3). Three anastomotic techniques are represented in the study. The completely handsewn technique, end-to-end anastomosis (EEA) circular stapled technique, and the "Orringer hybrid anastomosis" [15] were performed with almost equivalent frequency in the study population. The proximal and distal resection margins were routinely evaluated with intraoperative frozen section. A complete two-field lymphadenectomy was performed routinely at the time of esophagectomy. A pyloromyotomy or pyloroplasty and feeding jejunostomy were performed in most of the cases as well.
All of the patients were clinically staged before the initiation of treatment with endoscopy, computed tomography scans, and clinical history and examination. Endoscopic ultrasonography (EUS) and positron emission tomography scans were performed selectively at the discretion of the surgeon and oncologist. Preoperative EUS was performed in 48.6% of patients in the neoadjuvant chemoradiation cohort compared with 42% of the patients in the esophagectomy alone group (p = 0.6). Similarly, preoperative positron emission tomography scans were performed in 65% of the neoadjuvant chemoradiation cohort and 62% of the esophagectomy alone cohort (p = 0.86). The clinical staging is not reported in our study because accurate T staging with EUS was not available for every patient, and preoperative positron emission tomography scans were not performed uniformly in either cohort. Pathologic staging was determined by reviewing postoperative pathology reports and was based on the TNM classification of the American Joint Committee for Cancer Staging, sixth edition [16]. Patients who did not have detectable viable tumor in there resected pathology specimen were classified as complete responders to neoadjuvant chemoradiation therapy.
Beyond demographic information, we recorded tumor histologic type, preoperative diagnostic tests, intraoperative data, postoperative hospital course, complications, mortality, and esophageal tumor recurrence. In addition, ventilator days, intensive care unit days, and length of stay were recorded. Postoperative complications were classified as anastomotic leak, pneumonia, respiratory failure, chylothorax, pulmonary embolus, myocardial infarction, arrhythmia, and recurrent nerve palsy. Anastomotic leaks were diagnosed by observing extravasation of oral contrast at the esophagogastric anastomosis on a contrast esophagram or by direct clinical observation. Respiratory failure was defined as the need for reintubation for isolated respiratory dysfunction during the postoperative period or ventilator support for more than 48 hours. Pneumonia was diagnosed if patients had an infiltrate on chest imaging studies with associated fever and received antibiotic therapy. Postoperative mortality was defined as death occurring during hospitalization or within 30 days of esophagectomy. Deaths were verified with the Social Security Death Index.
Categorical variables were analyzed with the 
2 test, and continuous variables were analyzed with an unpaired Student t test. Univariate analyses were performed to determine the potential preoperative risk factors for overall postoperative complications and for anastomotic leak. The independent variables with a p less than 0.2 on univariate analysis were entered into a backward stepwise multiple logistic regression analysis. Overall survival of the neoadjuvant chemoradiation and esophagectomy alone cohorts was estimated by the Kaplan-Meier method. The statistical analyses were performed using the MedCalc (MedCalc Software, Mariakerke, Belgium). Differences were considered significant when the probability was less than 0.05. The biostatistics department at Stanford University was consulted for review of statistical methods.
|
Results
|
|---|
A total of 138 patients underwent esophagectomy for esophageal carcinoma during our study. Fifty-four patients received neoadjuvant chemoradiation followed by esophagectomy compared with 84 patients who underwent esophagectomy alone. The patient demographics are listed in Table 1. There was no significant difference between the neoadjuvant chemoradiation cohort and the esophagectomy alone cohort on any preoperative variable recorded. Importantly, there were significantly more transhiatal esophagectomy procedures (Table 3) in the neoadjuvant chemoradiation cohort (35.2%) compared with the esophagectomy alone cohort (10.7%; p = 0.003). Similarly, there were significantly more Ivor-Lewis procedures in the esophagectomy alone cohort (83.3%) compared with the neoadjuvant chemoradiation cohort (59.3%; p = 0.003). The operative time (p = 0.63) and estimated blood loss (p = 0.60) during esophagectomy were not significantly affected by neoadjuvant chemoradiation (Table 3).
The overall complication rate (Table 4) for the neoadjuvant chemoradiation cohort was 57.4% compared with 56% for the esophagectomy alone group (p = 0.98). Specifically, the anastomotic leak rate (p = 0.65) and respiratory failure rate (p = 0.87) were not significantly different between the neoadjuvant chemoradiation cohort and the esophagectomy alone cohort on univariate analysis. Only the incidence of chylothorax was significantly higher in the neoadjuvant chemoradiation group (p = 0.04). Other markers of morbidity such as mean and median ventilator days (p = 0.5), intensive care unit days (p = 0.48), and length of stay (p = 0.30) were also not significantly different in the neoadjuvant chemoradiation cohort compared with patients undergoing esophagectomy alone (Table 5). The 30-day operative mortality rate was actually lower in the neoadjuvant chemoradiation cohort (1.9%) than in the esophagectomy alone cohort (6%; p = 0.10). The single postoperative death in the neoadjuvant chemoradiation cohort was related to acute respiratory distress syndrome. There were 5 operative deaths in the esophagectomy alone cohort: 1 patient died of sepsis and multiple organ dysfunction syndrome, and 4 patients died of prolonged respiratory failure.
On multivariate analysis, only preoperative coronary artery disease (p = 0.01, odds ratio 3.5) and use of the transthoracic approach (Ivor-Lewis, p = 0.05, odds ratio 1.43) were independent variables that were significantly associated with the development of postoperative complications after esophagectomy. In the multivariate analysis, neoadjuvant chemoradiation was not a significant predictive risk factor for postoperative complications.
A multivariate analysis was also performed to determine the preoperative risk factors for anastomotic leak. Only cervical anastomosis was significantly associated with postoperative anastomotic leak (p = 0.04, odds ratio 3.0). Neoadjuvant chemoradiation was not a significant risk factor for the development of anastomotic leak.
A review of the postoperative pathology reports revealed that adenocarcinoma was the predominant histologic type (Table 6). The complete response rate in the neoadjuvant chemoradiation group was 22.2%. The complete TNM pathologic staging is listed in Table 6. The esophagectomy alone group had significantly more patients with stage III esophageal carcinoma, which may be related to observed downstaging in the neoadjuvant chemoradiation cohort. The complete resection rate (R0) was 92.6% for the neoadjuvant chemoradiation cohort compared with the 86% for the esophagectomy alone cohort (p = 0.36). The Kaplan-Meier overall survival curve is illustrated in Figure 1
. The overall 5-year survival was 33.6% for the neoadjuvant chemoradiation cohort compared with 27% for the esophagectomy alone cohort (log rank test p = 0.66). The median survival was 26 months compared with 25 months, respectively. The overall 5-year survival was 57.1% for patients who achieved a complete pathologic response after neoadjuvant chemoradiation (Fig 2).
View larger version (26K):
[in this window]
[in a new window]
|
Fig 1. Kaplan-Meier survival curve comparing the overall survival rates for patients who received neoadjuvant chemoradiation therapy (CRT) followed by esophagectomy (dashed line) and patients undergoing esophagectomy alone (solid line; log rank test, p = 0.66).
|
|
View larger version (26K):
[in this window]
[in a new window]
|
Fig 2. Kaplan-Meier survival curve comparing overall survival for patients who achieved a complete pathologic response to neoadjuvant chemoradiation (CR [dashed line]) and patients undergoing esophagectomy alone (solid line; log rank test, p = 0.2).
|
|
|
Comment
|
|---|
In recent years, multimodality treatment for esophageal carcinoma has become more commonplace because the long-term survival rates that are achieved with esophagectomy alone have been unacceptably poor, with survival rates as low as 6% at 3 years [3]. Although neoadjuvant chemoradiation has been shown to increase esophageal tumor downstaging and the complete resection (R0) rates [4, 7], only two randomized prospective studies have demonstrated an overall survival benefit for neoadjuvant chemoradiation. The CALGB 9781 phase III trial randomly allocated patients to either trimodality therapy with cisplatin, fluorouracil, and radiotherapy followed by esophagectomy or to esophagectomy alone. Overall survival in the trimodality therapy group was 39% versus 16% in the surgery alone group (p = 0.002) [2]. An earlier prospective, randomized trial by Walsh and associates [3] also achieved a significant improvement in overall survival in a trimodality group (32% versus 6%, p = 0.01). Two meta-analyses reviewing randomized clinical trials comparing neoadjuvant chemoradiation and esophagectomy to esophagectomy alone [4, 5] also concluded that neoadjuvant chemoradiation resulted in a higher rate of complete (R0) resection and improved survival.
These potential benefits of induction chemoradiation in esophageal cancer may come with consequences, however, related to postoperative morbidity and mortality. Reynolds and colleagues [8] reported a significant increase in postoperative respiratory failure (p = 0.03), adult respiratory distress syndrome (p = 0.008), and sepsis (p = 0.007) in patients who underwent esophagectomy after neoadjuvant chemoradiation therapy. Similarly, Avendano and colleagues [9] demonstrated that patients who had been treated preoperatively with chemoradiotherapy had significantly more pulmonary complications and a longer duration of mechanical ventilation compared with a cohort of patients who received preoperative chemotherapy. Swisher and colleagues [7] also demonstrated a greater number of perioperative adverse events after preoperative chemoradiation therapy, with significantly more patients developing respiratory insufficiency, atrial arrhythmias, and anastomotic leaks after esophagectomy. Bailey and colleagues [11] reported a cohort of 1,777 patients undergoing esophagectomy at 109 Veterans Affairs hospitals that demonstrated that neoadjuvant therapy was an independent predictor of mortality (p = 0.010) after esophagectomy. The observed increase in postoperative morbidity and mortality may be directly related to the adverse effects of chemoradiation, such as myelosuppression, nutritional depletion, edema, inflammation, and fibrosis. These factors could directly hamper wound healing and predispose patients to anastomotic leaks, sepsis, and respiratory complications.
In our retrospective review, we analyzed the impact of neoadjuvant chemoradiation, among other factors, in a cohort of patients who underwent esophagectomy either with or without prior induction chemoradiation. We observe that the overall complication rates were similar between patients who received neoadjuvant chemoradiation compared with patients who underwent esophagectomy alone (57.4% versus 56%, p = 0.98). We did not observe any significant difference in individual complications, such as anastomotic leak, pneumonia, respiratory failure, pulmonary embolism, myocardial infarction, or arrhythmias on the basis of whether the patients received induction chemoradiation. Only chylothorax was significantly more prevalent in the neoadjuvant therapy cohort. This finding might be explained by either a more difficult dissection of the esophagus and associated lymph nodes secondary to radiation-induced fibrosis and edema, or, alternatively, by the possibility that the induction regimen was being administered to patients with more extensive lymph node disease that required more extensive dissection around the thoracic duct.
The 30-day operative mortality rates between the neoadjuvant chemoradiation cohort and the esophagectomy alone cohort also were not significantly different (1.9% versus 6%, p = 0.10)—with, in fact, a fairly strong trend toward lower mortality in the group that received induction therapy. These results contrast with some of the findings reported previously by others [6–9, 11], although there are also several studies by others that report findings similar to ours. Lin and colleagues [14] reported a retrospective review of 170 esophagectomies in which 75 patients received preoperative chemoradiation therapy. The study concluded that induction therapy did not adversely influence the incidence of postoperative morbidity and mortality. In two contemporary randomized prospective trials comparing neoadjuvant chemoradiation followed by esophagectomy to esophagectomy alone, an increased incidence of postoperative morbidity and mortality also was not observed by the investigators in the neoadjuvant chemoradiation arms [2, 17].
In our multivariate analysis to determine independent risk factors for postoperative complications after esophagectomy, only preoperative coronary artery disease and a transthoracic esophagectomy approach were significantly associated with postoperative complications. Wright and colleagues [12] reported that significant predictors of major morbidity and mortality after esophagectomy among 2,315 patients from The Society of Thoracic Surgeons general thoracic surgery database [12] were coronary artery disease (odds ratio 1.31, p = 0.017) and congestive heart failure (odds ratio 2.3, p = 0.015). Presumably, patients with coronary artery disease and congestive heart failure are more likely to have pulmonary edema in the postoperative period from volume overload, which predisposes them to respiratory insufficiency. Moreover, a low cardiac output state may develop in patients with coronary artery disease and congestive heart failure that results in inadequate perfusion to the end organs. This low cardiac output state could have deleterious effects on the esophagogastric anastomosis as well.
Transthoracic esophagectomy has been associated with an increase in pulmonary complications, ventilator time, and intensive care unit days compared with transhiatal esophagectomy [18]. In our study, a significantly higher percentage of transhiatal esophagectomy procedures constituted the neoadjuvant chemoradiation cohort than the esophagectomy alone cohort. Although we cannot rule out in this retrospective study that patient selection factors—namely, selection of slightly more robust patients for trimodality therapy than surgery alone—played some role in our finding that induction therapy does not increase morbidity and mortality following esophagectomy, none of the preoperative differences between these patient cohorts even approached statistical significance. The higher percentage of transhiatal esophagectomies in the neoadjuvant chemoradiation group may have contributed to a lower incidence of postoperative complications in that cohort. The overall number transhiatal esophagectomies are relatively small in our report; therefore, we cannot not make any definitive statements about the outcomes of transhiatal esophagectomy versus the transthoracic approach.
In our report, the anastomotic leak rate was slightly higher in the neoadjuvant chemoradiation cohort compared with the esophagectomy alone cohort, but the difference was not statistically significant. Neoadjuvant chemoradiation has the potential to cause immunosuppression, esophagitis, and poor nutrition, any of which could result in poor wound healing and an increased rate of anastomotic leak after esophagectomy. On multivariate analysis, however, the only independent risk factors for the development of anastomotic leak after esophagectomy was use of a cervical anastomosis (odds ratio 3.0, p = 0.04), and not the use of induction therapy. In a review of anastomotic leaks complicating esophagectomy by Urschel [19], cervical anastomoses consistently had a higher leak rate than intrathoracic anastomoses, and the cervical anastomotic leak rate ranged from 10% to 25%. Conversely, Swisher and colleagues [7] demonstrated an increased anastomotic leak rate in a patient cohort who underwent transthoracic esophagectomy after preoperative chemoradiation therapy, which the authors attribute to the effects a radiation therapy. The cervical anastomotic leak rate was independent of whether the anastomotic technique was completely handsewn or partially stapled and partially sewn.
Finally, the Kaplan-Meier survival curve in our study did not show a statistically significant survival advantage for neoadjuvant chemoradiation. The overall Kaplan-Meier survival in our study is prone to inherent bias on the basis of several factors. First, this report is retrospective study with inherent selection bias. Although the two cohorts are well-matched, the chemoradiation regimens, preoperative staging, and surgical techniques were not uniform. Second, many of the pathologic stage III patients in the esophagectomy alone group received postoperative chemoradiation or chemotherapy alone, which could theoretically have provided some survival benefit to the esophagectomy alone cohort. We cautiously did not make any definitive statements that preoperative chemoradiation improves survival as that can only be proven in a well-designed randomized prospective study, such as CALGB 9781 [2]. The subset of 12 patients in our study who achieved a complete pathologic response with neoadjuvant chemoradiation did have a more than twofold increase in overall survival; however, the log rank test did not yield a statistically significant difference, probably because of lack of adequate statistical power. The 5-year overall survival was 57.1% for the complete response group compared with 27% for the esophagectomy alone group (p = 0.2).
In summary, this retrospective study demonstrates that neoadjuvant chemoradiation did not increase the postoperative complication rate or the mortality rate after esophagectomy. Multivariate analysis demonstrated that only coronary artery disease and the utilization of a transthoracic esophagectomy approach were independent risk factors for the development of postoperative complications. A cervical location, and not the use of neoadjuvant chemoradiation, was a significant independent risk factor for the development of postoperative esophagogastric anastomotic leak. Although our findings are susceptible to all of the potential biases inherent in a retrospective study, we believe that the data are relatively strong. A broad interpretation of these results, in the context of other data published in the past several years regarding both surgical and adjuvant therapies for esophageal carcinoma, suggests to us that neoadjuvant chemoradiation is on the whole beneficial in patients with resectable, locally advanced disease.
|
References
|
|---|
- Altekruse SF, Kosary CL, Krapcho M, et al. SEER cancer statistics review, 1975–2007Bethesda, MD: National Cancer Institutehttp://seer.cancer.gov/csr/1975–2007/Accessed on December 14, 2010.
- Tepper J, Krasna MJ, Niedzwiecki D, et al. Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781 J Clin Oncol 2008;26:1086-1092.[Abstract/Free Full Text]
- Walsh TN, Noonan N, Hollywood D, et al. A comparison of multimodality therapy and surgery for esophageal adenocarcinoma N Engl J Med 1996;335:462-467.[Medline]
- Urschel JD, Vasan H. A meta-analysis of randomized controlled trials that compared neoadjuvant chemoradiation and surgery to surgery alone for resectable esophageal cancer Am J Surg 2003;185:538-543.[Medline]
- Gebski V, Burmeister B, Smithers BM, et al. Survival benefits from neoadjuvant chemoradiotherapy in oesophageal carcinoma: a meta-analysis Lancet Oncol 2007;8:226-234.[Medline]
- Luu TD, Gaur P, Force SD, et al. Neoadjuvant chemoradiation versus chemotherapy for patients undergoing esophagectomy for esophageal cancer Ann Thorac Surg 2008;85:1217-1224.[Abstract/Free Full Text]
- Swisher SG, Hofstetter W, Komaki R, et al. Improved long-term outcome with chemoradiotherapy strategies in esophageal cancer Ann Thorac Surg 2010;90:892-899.[Abstract/Free Full Text]
- Reynolds JV, Ravi N, Hollywood D, et al. Neoadjuvant chemoradiation may increase the risk of respiratory complications and sepsis after transthoracic esophagectomy J Thorac Cardiovasc Surg 2006;132;:549-555.[Abstract/Free Full Text]
- Avendano CE, Flume PA, Silvestri GA, et al. Pulmonary complications after esophagectomy Ann Thorac Surg 2002;73:922-926.[Abstract/Free Full Text]
- Stahl M, Walz MK, Stuschke M, et al. Phase III comparison of preoperative chemotherapy compared with chemoradiotherapy in patients with locally advanced adenocarcinoma of the esophagogastric junction J Clin Oncol 2009;27:851-856.[Abstract/Free Full Text]
- Bailey SH, Bull DA, Harpole DH, et al. Outcomes after esophagectomy: a ten-year prospective cohort Ann Thorac Surg 2003;75:217-222.[Abstract/Free Full Text]
- Wright CD, Kucharczuk JC, O'Brien S, et al. Predictors of major morbidity and mortality after esophagectomy for esophageal cancer: a Society of Thoracic Surgeons general thoracic surgery database risk adjustment model J Thorac Cardiovasc Surg 2009;137:587-596.[Abstract/Free Full Text]
- Rice DC, Correa AM, Vaporciyan AA, et al. Preoperative chemoradiotherapy prior to esophagectomy in elderly patients is not associated with increased Morbidity Ann Thorac Surg 2005;79:391-397.[Abstract/Free Full Text]
- Lin FCF, Durkin AE, Ferguson MK. Induction therapy does not increase surgical morbidity after esophagectomy for cancer Ann Thorac Surg 2004;78:1783-1789.[Abstract/Free Full Text]
- Orringer MB, Marshall B, Iannettoni, MD. Eliminating the cervical esophagogastric anastomotic leak with a side-to-side stapled anastomosis J Thorac Cardiovasc Surg 2000;199:277-288.
- Greene FL, Page DL, Fleming ID, et al. The AJCC cancer staging manual6th ed.. New York: Springer-Verlag; 2002. pp. 91-99.
- Urba SG, Orringer MB, Turrisi A, et al. Randomized trial of preoperative chemoradiation versus surgery alone in patients with locoregional esophageal carcinoma J Clin Oncol 2001;19:305-313.[Abstract/Free Full Text]
- Hulscher JBF, Van Sandick JW, De Boer Angela GEM, et al. Extended transthoracic resection compared with limited transhiatal resection of adenocarcinoma of the esophagus N Engl J Med 2002;347:1662-1669.[Medline]
- Urschel JD. Esophagogastrostomy anastomotic leaks complication esophagectomy: a review Am J Surg 1995;169:634-640.[Medline]
Related Article
-
Invited Commentary
- Mark D. Iannettoni
Ann. Thorac. Surg. 2011 92: 2040.
[Extract]
[Full Text]
[PDF]
This article has been cited by other articles:
|
|
|
|
 
M. D. Iannettoni
Invited Commentary
Ann. Thorac. Surg.,
December 1, 2011;
92(6):
2040 - 2040.
[Full Text]
[PDF]
|
|
|
Top
Abstract
Introduction
