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The Heart, Lung, and Esophageal Surgery Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
* Address correspondence to Dr Luketich, The Heart, Lung, and Esophageal Surgery Institute, University of Pittsburgh Medical Center, 200 Lothrop St, Ste C-800, Pittsburgh, PA 15213-3221 (Email: luketichjd{at}upmc.edu).
Presented at the Minimally Invasive Thoracic Surgery Summit, New York, NY, June 8–9, 2007.
| Abstract |
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| Introduction |
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Surgical resection is the primary curative therapy for patients with resectable esophageal cancer. There are, however, several controversies in the optimal management of esophageal cancer, including the surgical approach, extent of resection, and the role of multimodality treatment. Optimal surgical treatment strategies include appropriate patient selection, accurate staging, risk assessment, selection of an appropriate surgical approach, and the use of multimodality treatment in the management of these patients. In addition, other factors such as hospital and surgeon volume are important in reducing the risks of esophagectomy. The objective of this article is to discuss our approach and review the literature on these aspects that have an impact on the outcomes after esophagectomy. This review is not intended to be a comprehensive review of these issues but rather to give the reader an overview of the important factors that may have an impact on the outcomes after esophagectomy.
| Methods |
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| Patient Selection |
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Computed tomography scanning for staging of esophageal cancer should include an assessment of the extent of esophageal involvement, assessment of regional and distant lymph node involvement, tumor invasion of the periesophageal fat and adjacent structures, and metastases to distant organs such as the liver. Computed tomography scanning is not very accurate for establishing the T status or the N status. Endoscopic ultrasound is extremely useful in evaluation of T status, and EUS-guided fine needle aspiration (EUS-FNA) biopsy is valuable in assessing locoregional and celiac nodal metastases [3].
Positron emission tomography scanning is more accurate than conventional CT imaging, particularly in the detection of distant metastases [4, 7]. Minimally invasive surgical staging is practiced in some institutions such as ours and is a very useful in staging selected patients [2, 4–6]. We have reported an increased accuracy of MIS staging compared with PET scans [4]. In an analysis of 100 consecutive PET scans from the University of Pittsburgh, we reported that although PET scanning was more accurate than CT scanning, its sensitivity was only 69%, specificity was 94%, and an overall accuracy was 84% compared with MIS.
Similarly, we have reported an increase in accuracy with MIS staging compared with EUS in the diagnosis of lymph node metastases [5]. In this study comparing EUS with MIS staging, the overall accuracy of EUS in assessment of lymph node metastases in esophageal cancer was 65%. With advances in technique and use of EUS-FNA, a more recent study in our institution that compared EUS and laparoscopy found the accuracy for nodal staging improved, but overall staging accuracy of EUS was only 72% compared with laparoscopy [6]. However, MIS is not practiced universally. We have however found that MIS with laparoscopy is particularly valuable in detection of occult distant metastases and exclusion of these patients from definitive surgical resection. This can be performed prior to performing a laparotomy and definitive resection.
Risk Assessment
The patients physiologic status should be thoroughly evaluated to make an assessment of the risks of esophagectomy. This evaluation should include an assessment of the patients performance status, cardiovascular function, pulmonary function, and nutritional status. Patient risk assessment at the University of Pittsburgh includes an assessment of comorbidities, evaluation of cardiopulmonary function, and nutritional status.
Pulmonary complications, particularly pneumonia, are an important determinant of early postoperative outcome [10]. In a study of preoperative risk assessment by Ferguson and colleagues [11], pulmonary complications were associated with more than a fourfold increase in mortality. Multivariate analysis showed that age and decreased forced expiratory volume in 1 second (FEV1) were predictive of pulmonary complications. These authors developed a scoring system based on this retrospective analysis, incorporating age, spirometry, and performance status to predict the likelihood of cardiovascular and pulmonary complications [11]. Avendano and colleagues [12] similarly identified age, decreased FEV1, and preoperative chemoradiation as risk factors for development of pneumonia. These criteria, however, need to be prospectively validated. The risk assessment should be individualized, taking into consideration a complete assessment of the patients physiologic status by the surgeon, and treatment should be individualized according to the risks.
| Surgical Approaches |
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Multiple retrospective studies have compared the various approaches to esophagectomy, and no significant differences in outcome have been found [19]. Very few randomized trials, however, have compared transthoracic vs transhiatal esophagectomy. Hulscher and colleagues [20] conducted a randomized trial comparing transthoracic vs transhiatal esophagectomy in patients with mid-distal and gastroesophageal junction neoplasms. Although the perioperative morbidity rate was higher in the transthoracic group, the difference in the mortality rate between the two groups was not significant. During a median follow-up of 4.7 years, there was a trend toward a better 5-year overall (39% vs 29%) and disease free survival (39% vs 27%) in the transthoracic group, although this did not reach statistical significance. These investigators concluded that transhiatal esophagectomy was associated with a lower morbidity and noted a trend towards improved long-term survival at 5 years with an extended transthoracic approach.
Other controversies include the extent of lymph node dissection. Proponents of extended three-field lymph node dissection point out the low recurrence rates and the benefits of accurate staging. Nishihara and colleagues [21] conducted a randomized trial of 62 patients comparing two-field lymphadenectomy (thoracic and abdominal) with three fields, including cervical and superior mediastinal lymphadenectomy. Complications were significantly increased in the extended lymphadenectomy group, including a 53% tracheostomy rate and 13% incidence of phrenic nerve palsy, although a trend towards better survival was noted on long-term follow-up. Three-field lymph node dissection is primarily practiced in Japan and in very few selected centers in the West.
| Minimally Invasive Esophagectomy |
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We reported our results of a series of 222 consecutive MIEs [22]. Minimally invasive esophagectomy was successfully completed in 206 (92.8%) of patients. The median lengths of stay were 1 day in the intensive care unit and 7 days in the hospital. The operative mortality rate was 1.4%. Stage-specific survival was similar to open esophagectomy series.
With advances made in surgical techniques and perioperative critical care, a decrease in the mortality and morbidity from esophagectomy has been achieved. However, the long-term quality of life (QOL) after esophagectomy is being increasingly recognized as an important factor in determining the treatment modality. This study used the Medical Outcomes Study Short-Form 36 (SF-36) Health Survey to measure the QOL [22]. Preoperative and postoperative scores were available in 57 patients, and no significant differences were found indicating preservation of QOL. In addition, the Gastroesophageal Reflux Disease Health-Related Quality of Life (HRQOL) scale was used to assess reflux related QOL. The range of this score varies from 0 (no symptoms) to 45 (most severe symptoms). The mean HRQOL score was 4.6, indicating a normal (no reflux) score. Dysphagia scores were excellent, with a mean score of 1.4 using a scale of 1 (no dysphagia) to 5 (severe dysphagia). Thus, the QOL after minimally invasive esophagectomy is well preserved.
After MIE in our center, we observed a short hospital stay, a low mortality rate, preserved QOL, and good oncologic results. Our current approach is to perform a minimally invasive Ivor-Lewis esophagectomy with lymph node dissection in most patients with resectable esophageal cancer. A minimally invasive approach to esophagectomy is practiced in selected centers but is not practiced routinely in several institutions. A phase II study is currently in progress by the Eastern Cooperative Oncology Group (ECOG 2202) to evaluate the results of MIE in a multi-institutional setting.
| Multimodality Therapy |
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Most of the 70 patients we enrolled had locally advanced disease: 80% of patients had preoperative pathologically proven N1 disease, and 99% of patients had either a T3 or N1 lesion. Esophagectomy was performed in 63 patients. The operative mortality rate was 0%. The median overall survival of the entire group was 27.4 months, 17 patients are alive at a median follow-up of 62.8 months (range, 39.1 to 142 months), and 14 patients are alive without recurrence at a median follow-up of 79 months (range, 39 to 138 months). Patients who were downstaged experienced a significantly improved survival.
Randomized studies have not shown a consistent benefit, however. Kelsen and colleagues [24] reported the results of a prospective randomized study in North America in 400 patients comparing preoperative chemotherapy, followed by surgery, vs surgery alone. The two arms had s similar median survival: 16.1 months in the surgical arm and 14.9 months in the treatment arm. The 2-year survival was 37% in the surgery alone arm and 35% in the treatment arm.
More recently, the Medical Research Council reported the results of a randomized study using cisplatin and 5-flurouracil, followed by resection vs resection alone [25]. In contrast to the study by Kelsen and colleagues [24], there was a significant improvement in the survival, with a 16.8-month median survival in the chemotherapy arm vs 13.3 months in the surgery arm, and the 2-year survival rates were 43% and 34%, respectively, at a median follow-up of 37 months.
Finally, the results of the Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial, using a strategy similar to our study with preoperative chemotherapy, surgery, and adjuvant chemotherapy favoring the treatment arm, has recently been published [26]. Only about a quarter of the patients had cancers of the distal esophagus or gastroesophageal junction, and most had gastric cancer. The overall 5-year survival in the treatment arm was 36% vs. 23% at a median follow-up of four years.
Neoadjuvant Chemotherapy and Radiotherapy
Another approach to the treatment of esophageal cancer involves the addition of preoperative radiation to chemotherapy [1]. In our institution, neoadjuvant chemotherapy is preferred in locally advanced tumors and neoadjuvant chemoradiation is used only in selected patients with bulky disease. Forastiere and colleagues [27] reported the results in 43 patients treated with chemoradiation, followed by transhiatal esophagectomy. In this series, 56% of patients were suspected to have nodal metastases preoperatively, and 8 patients (19%) had T1 disease. The median survival was 29 months, and the 5-year survival was 34%.
However, randomized trials with this approach have not shown a consistent benefit [28–30]. Urba and colleagues [28] subsequently reported the results of a randomized trial comparing preoperative chemoradiation, followed by surgery, vs surgery alone and did not find a significant survival benefit: median survival was 16.9 months in the treatment arm vs 17.6 months in the surgery arm. The one trial that showed a benefit was reported by Walsh and colleagues [29], which evaluated preoperative chemotherapy with 4000 Gy of radiation. With a median survival of 16 months vs 11 months and a 3-year survival of 32% vs 6%, chemoradiation was associated with survival benefit [29]. Their 6% probability of 3-year survival with surgery was lower than expected. Meta-analysis of trials evaluating neoadjuvant chemoradiation has, however, shown a benefit [31].
Although, neoadjuvant strategies are commonly used, further prospective studies are required to determine the role of neoadjuvant strategies in the management of esophageal cancer. Some of these trials are summarized in Table 1.
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A randomized trial by Ando and colleagues [32] of surgery with or without adjuvant chemotherapy (cisplatin and vindesine) for localized squamous cell neoplasm did not show a benefit for chemotherapy. Another randomized trial conducted by the Japanese Clinical Oncology group (JCOG9204) randomized 242 patients to surgery alone vs surgery and chemotherapy consisting of cisplatin and fluorouracil [33]. The 5-year disease-free survival rate was 45% in the surgery-only arm vs 55% in the surgery-plus-chemotherapy arm (one-sided p = 0.037). A further analysis of subgroups showed the N1 subgroup had a significantly improved 5-year disease-free survival rate of 38% in the surgery-alone arm vs 52% in the surgery-plus-chemotherapy arm (p = 0.04). The 5-year overall survival rate was not significantly different. These investigators concluded that postoperative chemotherapy might prevent relapse in patients better than surgery alone.
Armonias and colleagues [34] reported the results of the ECOG Phase II trial (E8296) of adjuvant chemotherapy consisting of cisplatinum and paclitaxel for resected adenocarcinoma of the esophagus. At a median follow-up of 4 years, the 2-year survival was 60%. The authors concluded that adjuvant therapy with this regimen might improve survival in completely resected patients with esophageal neoplasm. Further randomized trials are needed to determine if adjuvant chemotherapy after complete resection is beneficial. Adjuvant radiotherapy is generally used only with patients with residual disease. Randomized trials have not shown a benefit for routine adjuvant radiotherapy [35, 36].
| Reducing the Surgical Risks |
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Thus, the risks of esophagectomy can be significantly reduced by a variety of factors, which include a large-volume hospital, a high-volume surgeon, a surgeon with specialty training, and the daily involvement of critical care specialists.
| Conclusions |
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| References |
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