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20.1 Introduction

Esophageal cancer’s global incidence continues to increase rapidly. In Western society this is reflected by an increasing incidence of esophageal adenocarcinomas, with the epidemiological shift felt to be related to increased obesity, gastroesophageal reflux disease, and Barrett’s esophagus – the dominant risk factors for the development of this tumor. Surgical resection with radical lymphadenectomy, usually after the administration of neoadjuvant chemotherapy or chemoradiotherapy, remains the key component in the multimodality treatment of esophageal cancer. Esophagectomy is a complex surgical procedure for which the mortality rates have historically been significant [1]. In modern practice, in high-volume centers with appropriate multidisciplinary teams, the mortality rate after esophageal resection has been reduced significantly [2]. Despite this, it remains an operation associated with substantial rates of morbidity. During the previous three decades, minimally invasive surgery has been championed as providing a means of reducing postoperative morbidity for a variety of oncological gastrointestinal resections. With regard to esophageal resection, it has been hoped that the application of minimally invasive surgery may similarly reduce postoperative morbidity and mortality. By the early 1990s, some surgeons had developed and used protocols for thoracoscopic esophagectomy, initially restricting its use to T1 and T2 esophageal cancer without neoadjuvant chemoradiation [3, 4]. With time indications for minimally invasive esophageal resection have been expanded to include more advanced disease, irrespective of whether patients have received neoadjuvant treatments.

The techniques which have been described as minimally invasive approaches to esophageal resection vary widely. Many authors have described completely minimally invasive approaches, while others describe hybrid procedures where one stage of the operation is performed either by thoracoscopy or laparoscopy and the other by conventional open surgery. Unlike other minimally invasive procedures, minimally invasive esophagectomy (MIE) has not been broadly adopted. No matter what approach is used, MIE remains a very complex operation with many questions remaining unanswered as to the real advantages of applying a minimally invasive technique for resection of a disease which is often advanced at the time of surgery. Mortality, morbidity, oncological radicality, reproducibility of a minimally invasive approach, and the cost of the procedure are some of the topics under debate. Recent reviews [5–7] focusing on the role of MIE have emphasized that the benefits of this approach are controversial. Many comparative nonrandomized and retrospective studies have been conducted between MIE and open esophagectomy, but uncertainty remains about the advantages of any one technique compared to another. In the absence of meta-analyses of randomized controlled studies, this chapter appraises the available literature with regard to the short-term perioperative outcomes and longer-term oncological outcomes for patients undergoing minimally invasive resection for esophageal cancer.

20.2 MIE Techniques

As there has never been a consensus regarding the superiority of any of the various open esophagectomy techniques, it is unsurprising that there is no agreement on what constitutes the best minimally invasive approach.

Completely minimally invasive approaches to esophageal resection attempt to replicate established open procedures. A minimally invasive transhiatal technique utilizes laparoscopic abdominal dissection and preparation of the gastric conduit followed by a cervical anastomosis created via a traditional open approach in the neck. Mediastinal dissection of periesophageal lymph nodes, including those in the subcarinal station, can be assessed through the hiatus using the lighting and magnification afforded by the laparoscopic camera. The esophageal specimen can be removed through the neck incision. Some surgeons prefer to combine the laparoscopic transhiatal approach with a minilaparotomy to facilitate gastric tube creation as well as to remove the specimen. Finally, the esophagus can also be removed from the mediastinum via an inversion technique with or without division of the vagus nerve. As with open surgery, many surgeons prefer a thoracoscopic approach, typically performed through the right chest, with patients positioned in lateral decubitus or prone positions [8, 9]. Thoracoscopy can be used as a part of a three-stage MIE, where the procedure begins in the chest and ends with laparoscopy and a cervical anastomosis, or as part of the two-stage Ivor-Lewis esophagectomy where the esophagogastric anastomosis resides in the chest. In this procedure the specimen is removed through a mini-thoracotomy, and the anastomosis is created at the apex of the chest.

Combinations of open and minimally invasive techniques (hybrid techniques) are perhaps more widely utilized, such as laparoscopy with thoracotomy or thoracoscopy with laparotomy. These hybrid techniques are applied for a variety of reasons and may be necessitated by oncological considerations, prior surgery in either cavity, surgeon experience, and surgeon preference.

Although the goal of MIE is to perform an equivalent operation to the open procedure without omitting any critical steps, some aspects considered as routine for open esophagectomy have fallen out of favor with many surgeons, such as performance of a pyloroplasty and jejunostomy placement.

20.3 Early Results (Tables 20.1 and 20.2)

Table 20.1 Mortality and overall morbidity of minimally invasive and open esophagectomy
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Table 20.2 Comparison of rates of morbidities for MIE and open esophagectomy
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The primary goal of MIE is to decrease surgical morbidity associated with the open approach. In the setting of a randomized controlled trial, only a single direct comparison of open and minimally invasive approaches has been published [31] with the final results of the French MIRO (oesophagectoMIe pour cancer paR voie conventionnelle ou coeliO-assistée) trial awaited [32]. At present, the majority of data derives from retrospective nonrandomized series and suggests that mortality rates appear equivalent with some suggestion of benefit in terms of overall morbidity favoring a minimally invasive approach (Tables 20.1 and 20.2). It is likely that the benefits of MIE may be overshadowed by the persistent rate of significant morbidity which continues to occur independent of surgical approach. It seems conceivable that, in the absence of such complications, patients with a minimal access approach enjoy quicker recovery, quicker return to normal activities, and decreased long-term pain when compared to patients with similarly uncomplicated open procedures. This, however, has yet to be proven.

Results coming from three published meta-analyses, based on nonrandomized comparative data, are contradictory. Two did not find significant differences between the MIE and the open approaches [33, 34]. The third suggests that patients undergoing MIE had better operative and postoperative outcomes with no compromise in oncological outcomes (as assessed by lymph node retrieval) [7]. Patients undergoing MIE had significantly lower blood loss and shorter postoperative ICU and hospital stay. There was a 50 % decrease in total morbidity in the MIE group. Subgroup analysis of comorbidities demonstrated significantly lower incidence of respiratory complications after MIE; however, other postoperative outcomes such as anastomotic leak, anastomotic stricture, gastric conduit ischemia, chyle leak, vocal cord palsy, and 30-day mortality were comparable between the two techniques. The benefit of at least one endoscopic stage in hybrid techniques (thoracoscopy with laparotomy or laparoscopy with thoracotomy) was noted. Even with only one phase being minimally invasive, blood loss and respiratory complications were still found to be lower, consistent with open versus totally MIE analysis, and highlight the purported advantages of applying a minimally invasive approach to esophagectomy.

20.4 Long-Term Results (Table 20.3)

Table 20.3 Long-term oncological outcomes for MIE and open esophagectomy
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If MIE is to become the approach of choice, then it must be demonstrated not to compromise oncological outcomes. Improved lighting and visibility, along with the magnification afforded by minimally invasive equipment, may prove superior for meticulous dissection and lymph node harvest. However, until large series report long-term survival by stage or results of large randomized trials are published, the true oncologic value of MIE will remain controversial. Table 20.3 reflects the fact that no study to date has shown conclusive evidence of improved overall survival favoring a minimally invasive resection. While several studies have suggested a benefit in terms of lymph node harvest, many have failed to meet the broadly accepted recommendations of the number of lymph nodes which should be retrieved for optimum staging and prognosis (Table 20.3). This puts into some question the quality of resection in several studies and makes oncological comparisons difficult. More data is simply required in this regard from future randomized controlled trials.

20.5 Randomized Controlled Trials

To date, only one multicenter randomized controlled trial (TIME) has been published comparing the results of minimally invasive and open esophagectomy [31]. This trial randomly assigned 56 patients to open esophagectomy and 59 to a minimally invasive operation with all patients receiving equivalent neoadjuvant chemotherapy or chemoradiotherapy regimes. Both minimally invasive and open surgical groups had a mixture of two-stage and three-stage operations with the majority of patients having a cervical anastomosis. The primary outcome measure chosen was pulmonary infection within 2 weeks of surgery defined by clinical manifestation of pneumonia confirmed by radiological imaging and a positive sputum sample. Sixteen (29 %) patients in the open surgical group and 5 (9 %) patients in the minimally invasive group (p = 0.005) developed pneumonia in the first two postoperative weeks. Prima facie this appears to suggest a significant benefit in terms of respiratory complications in favor of the minimally invasive approach. Several observations and qualifications do however need to be made. Intraoperative single-lung ventilation was practiced only for the open surgical group, and the open group had a very high level of recurrent laryngeal nerve palsy (14 %) compared to the minimally invasive group (2 %). Both of these factors clearly put the patients having an open operation at higher risk of postoperative respiratory complications. Further many non-studied variables – malnutrition, previous and current smoking, pulmonary comorbidities, functional status, and clinical TNM (tumor, node, metastases) stage – have all been shown to strongly influence the primary end point of this trial. More data is therefore required.

There are two other multicenter randomized controlled trials of interest. The French multicenter phase III MIRO trial [32] has randomized patients to either hybrid esophagectomy (laparoscopic gastric mobilization and open right thoracotomy) or open esophagectomy. The MIRO trial tests the impact of laparoscopic gastric conduit creation with open thoracotomy (hybrid procedure) on major 30-day postoperative morbidity, especially on pulmonary complications. It hypothesizes that hybrid MIE may decrease major postoperative morbidity without compromising oncological outcomes through an easily reproducible surgical procedure. Secondary objectives are to assess the overall 30-day morbidity, 30-day mortality, disease-free and overall survival, quality of life, and medico-economic analysis. The short-term results have been recently presented [35]. The trial randomly assigned 104 patients to open esophagectomy and 103 to a hybrid approach group. Sixty-seven (64.4 %) patients in the open group had major postoperative morbidity compared to 37 (35.9 %) in the hybrid group (OR 0 · 31, 95 % CI 0 · 18-0 · 55; p = 0 · 0001). Thirty-one (30.1 %) patients after an open operation had major pulmonary complications compared to 18 (17.7 %) after a hybrid approach (p = 0 · 037), whereas 30-day mortality was 5 (4.9 %) versus 5 (4.9 %), respectively. The MIRO results provide further evidence that a minimally invasive approach may reduce the short-term insult of esophagectomy. The longer-term oncological results are awaited with interest. In the United Kingdom, patients are currently being recruited into a phase II trial [36] comparing a totally minimally invasive operation, hybrid approach (laparoscopic gastric mobilization and open chest) and open esophagectomy. Results for phase II of this study are not yet accumulated and recruitment to the planned phase III trial not yet commenced.

Conclusions

MIE has been gaining in popularity, but, as with open surgery, no consensus has been reached regarding the superiority of any particular MIE adaptation. Even if some large comparative studies suggest a significantly better postoperative course following MIE, without compromise of oncological outcomes, more data is needed from randomized trials. Randomized trials are, however, difficult due to the wide variety of techniques available, the heterogeneity in surgeons’ preferences, the relative low number of procedures performed, the complexity of such surgery, and the variety and definition of postoperative complications after esophagectomy. Certainly the positive results of the TIME trial and the soon to be published MIRO trial add credence to what many surgeons find intuitive – that a less invasive approach can reduce morbidity after esophagectomy. Rates of postoperative mortality have fallen in specialist centers; focus must turn to minimizing the traditionally high level of morbidity associated with this operation.

To date, data coming from nonrandomized studies do suggest MIE is safe and at least comparable to open resection for both surgical and oncological outcomes. Data from meta-analyses suggest that MIE may have advantages in terms of less blood loss, less time in intensive care, fewer pulmonary complications, and shorter hospital stay. However, the effect of MIE on quality of life and return to normal activity has not been assessed nor have medico-economic analyses been performed. More large randomized controlled trials are required. Results from the MIRO trial will soon be published and will offer a higher level of evidence for this highly debated procedure.