Transhiatal Esophagectomy for Esophageal Cancer

Abstract

Survival for esophageal cancer has improved over the past four decades, probably as a result of a combination of more accurate staging, improved surgical outcomes, advances in adjuvant and neoadjuvant therapies, and the increasing implementation of multimodality treatment. Surgical resection still remains the mainstay in the treatment of localized esophageal adenocarcinoma. Multiple techniques have been described for esophagectomy, which are based on either a transthoracic or transhiatal approach. Despite proponents of each technique touting potential advantages such as superior oncologic resection with more extensive transthoracic lymphadenectomy compared to the relatively limited morbidity and mortality with a transhiatal resection, the superiority of one technique over another is not clear and may be relegated to a topic of historical significance in the era of minimally invasive surgery. With the increased acceptance of neoadjuvant multimodality therapy, both approaches have been shown to have acceptable outcomes. And in the hands of experienced surgeons, both techniques can provide excellent short-term results. Moreover, surgeon and hospital volume have shown to be strongly associated with improved operative morbidity and oncologic outcomes, which may supersede the type of approach selected for an individual patient.

Introduction

Despite significant advances in the multimodality treatment of esophageal carcinoma—including chemotherapy, radiation, and targeted therapies—surgical resection remains the most effective means to achieve palliation and/or long-term disease-free survival in appropriately selected patients. Various operative approaches have been established with considerable improvements in reducing the perioperative morbidity and mortality of esophageal resection. However, surgery alone—regardless of the approach—is inadequate for cure in 84%–90% of cases at 5 years.^1,2

Transhiatal esophagectomy was first performed by Turner in 1933 with dismal outcomes leading to the adoption of transpleural esophageal resection.³ Forty years later, Orringer reintroduced the transhiatal technique with promising results in the setting of a rising incidence of distal esophageal adenocarcinoma.⁴ The principles of the transhiatal esophagectomy include meticulous dissection of the lower esophageal nodal stations, careful mediastinal dissection, creation of a viable gastric conduit, and a cervical anastomosis.

Proponents of the transhiatal esophagectomy, transthoracic (Ivor Lewis) esophagectomy, three-field (McKeown) esophagectomy, and minimally invasive esophagectomy (MIE) have touted the advantages of their respective techniques with regard to increased nodal clearance, decreased complications, and reduced hospital length of stay. Yet, solid evidence is still lacking that demonstrates a disease-free or overall survival benefit associated with one technique over another.^5–10

Transhiatal versus transthoracic esophagectomy

Two large meta-analyses have attempted to address the controversy surrounding the surgical approach by analyzing numerous individual studies that have compared transhiatal esophagectomy to transthoracic esophagectomy.^11,12 Most of the included studies were retrospective in nature and inconsistent with respect to both the surgical technique and the utilization of multimodality therapy. Nevertheless, the results of both meta-analyses were similar.

Rindani et al.¹¹ analyzed more than 5000 patients from 44 published series between 1986 and 1996. Despite the diverse nature of the series and the inclusion of only one prospective randomized trial, the descriptive analysis revealed that postoperative respiratory and cardiovascular complications were almost identical between the two groups. The transhiatal group had a higher incidence of anastomotic leaks and recurrent laryngeal nerve injuries. Thirty-day mortality was 6.3% after transhiatal and 9.5% after transthoracic resection, but survival at 5 years was equivalent between the two procedures.

The second meta-analysis by Hulscher et al.¹² included 7527 patients analyzed from 50 studies between 1990 and 1999. Six were prospective comparative studies, three of which were randomized, and all had relatively small sample sizes. None of these three randomized studies demonstrated a significant difference in morbidity, mortality, or long-term survival between the two surgical approaches.^5,6,13 When all 50 studies were analyzed, there was no significant difference in morbidity between transthoracic and transhiatal esophagectomy. Blood loss, risk of pulmonary complications, chylous leak (2.4% versus 1.4%), and wound infection (7.7% versus 4.3%) trended higher after transthoracic esophagectomy. In addition, length of stay in the intensive care unit and hospital was longer, with a significantly higher in-hospital mortality rate in the transthoracic group. As demonstrated in the previous meta-analysis, transhiatal esophagectomy had a higher incidence of anastomotic leak and recurrent laryngeal nerve injury. No difference in 5-year survival rates was observed between the two techniques.

DeMeester et al. examined their single-institution experience with 263 patients who underwent either transhiatal or an en bloc esophagectomy with a thoracotomy and mediastinal lymph node dissection.¹⁴ In this retrospective analysis, the operative mortality did not differ between the two groups and actually trended higher in the transhiatal group (2.5% versus 5.6%, P = .33). However, they conceded the potential for selection bias as those patients with more comorbidities were offered the transhiatal surgery in an attempt to minimize postoperative complications. The R0 resection rate was 97% in the en bloc group compared to 87% in the transhiatal group, with improved overall survival in the en bloc esophagectomy group suggesting that the en bloc esophagectomy is a superior oncologic procedure. However, they did not find any difference in cancer-specific survival or overall survival in patients with stage II or III disease between the two techniques. Furthermore, only 29% of patients with pathologic stage II–IV disease received neoadjuvant therapy, which has been shown to improve survival in a randomized controlled trial and can be used to guide patient selection for surgical resection based on tumor response or progression.¹⁵ While large, single-institution series have great value in identifying trends in outcome, only level I evidence can yield scientifically sound data that can lead to defensible changes in management.

The largest and most recent randomized controlled trial compared the transhiatal esophagectomy to a transthoracic approach in 220 patients.⁷ Hulscher et al. demonstrated a shorter median duration of surgery in the transhiatal arm (3.5 hours versus 6.0 hours, P < .001) in addition to less blood loss (median, 1.0 versus 1.9 L, P < .001). Transhiatal resection was associated with fewer pulmonary complications, less chylous leakage, a shorter duration of mechanical ventilation, and shorter hospital length of stay. After an initial trend toward improved survival in the transthoracic arm, long-term follow-up revealed no difference in the 5-year survival between the two arms (34% transhiatal and 36% transthoracic, P = .71).¹⁶ In a subgroup analysis, the location of the primary tumor did not affect the survival of either approach, which fails to support the suggestion that a transthoracic lymphadenectomy may be more beneficial for patients with midesophageal tumors. There was evidence, however, that the transthoracic approach was associated with improved locoregional disease-free survival (23% versus 64%, P = .02) if there were a limited amount of involved lymph nodes (1–8 lymph nodes). However, the study was not adequately powered to draw any definitive conclusions from the subgroup analysis. Furthermore, none of the patients in this study received neoadjuvant chemoradiation, which is now considered the standard of care in the treatment of locally advanced esophageal carcinoma.¹⁷

In the argument for stage migration, there does appear to be a correlation between the number of lymph nodes examined and the possibility of under staging in esophageal carcinoma. It has been proposed that a minimum of 18 lymph nodes are required for an adequate lymph node yield.¹⁸ The American Joint Committee on Cancer staging manual, however, recommends resection of as many lymph nodes as possible for esophageal carcinoma, and that more nodes should be analyzed with increasing pT stage (≥10 for T1; ≥20 for T2; and ≥30 for T3 and T4).¹⁹ However, the role of extended lymphadenectomy in the setting of neoadjuvant chemoradiation remains unclear since the added value of extensive mediastinal lymph node dissection post-chemoradiotherapy has not been shown to improve long-term survival. This is likely due to the fact that most of the relevant draining lymph nodes—especially for the majority of tumors that arise in the distal esophagus—can be safely and completely dissected through a transabdominal approach (left gastric, common hepatic, splenic, celiac, inferior phrenic and paraesophageal stations). Furthermore, only 8% of patients will have additional metastatic tumor in the paratracheal or aortopulmonary nodes after an extended transthoracic lymphadenectomy, and dissection of these lymph node stations ultimately does not affect the final pathologic staging or impact outcome.²⁰ In the vast majority of patients, survival is not dictated by the size of the specimen or the number of lymph nodes retrieved, but rather the clinical stage of the tumor and its biologic behavior (i.e., response to neoadjuvant chemoradiation).

Regarding minimally invasive surgical approaches to esophagectomy, many surgeons have adopted this technique as equivalent, if not superior, to open esophagectomy as a result of single-institution series and meta-analyses demonstrating lower pulmonary complications rates, reduced blood loss, shorter hospital length of stays, and respectable R0 resection rates and lymph node yields.^10,21–26 The first randomized controlled trial examining MIE versus open techniques by Biere et al. reported reduced pulmonary infection rates, reduced blood loss, and some improved short-term quality-of-life factors in 115 patients.²⁷ They did not, however, report their perioperative mortality, total morbidity, or anastomotic leak rates. With initial reports, including this randomized trial in addition to the extensive experience of Luketich et al., more focused on short-term perioperative outcomes, long-term oncologic outcomes of MIE have not yet proven to be equivalent to open esophagectomy.²⁸ Until long-term data are available, the generalizability of these results outside of individual, high-volume centers should be approached with caution.

Perioperative complications

Although the transhiatal esophagectomy is generally well tolerated by patients, each phase of the procedure—abdominal, cervical, and mediastinal—has the potential for significant complications in inexperienced hands. The most dreaded complication of the abdominal phase is ischemia of the gastric conduit that most commonly manifests as an anastomotic leak, but in rare instances can lead to gastric necrosis. Anastomotic leaks occur in 9%–14% of cases, with some small series reporting an incidence as low as 1.8% regardless of whether it is placed in the neck or the chest.^29–31 Cervical anastomotic leaks can be easily managed with local wound care and rarely result in septic complications. However, compared to cervical leaks, thoracic anastomotic leaks lead to more severe complications secondary to potentially life-threatening mediastinitis requiring chest drainage, antibiotics, and prolonged enteral or parenteral nutritional support. An anastomotic leak increases the risk of a subsequent anastomotic stricture, which occurs in up to 30% of cases. Strictures resulting in dysphagia are managed with serial dilations. Although some have suggested a decreased incidence of anastomotic leaks with a hand-sewn anastomosis compared to a stapled anastomosis, the reports are all retrospective in nature.^30,32 The careful creation and transposition of the gastric conduit is probably the most important aspect in the prevention of anastomotic leaks.

In the cervical phase, injury to the recurrent laryngeal nerve injury can occur in ∼2%–24% of patients undergoing an esophagectomy.³³ The incidence of this complication is substantially lower in the transthoracic approach, but can be minimized by careful retraction through the cervical incision, minimizing dissection in the tracheoesophageal groove, and maintaining dissection on the periadventitial plane of the esophagus to avoid injury to the contralateral (right) recurrent laryngeal nerve. Most injuries result in temporary hoarseness. However, dysphagia leading to aspiration can result in significant complications for the patient.

In the mediastinal phase, the concern for mediastinal bleeding during the blunt periesophageal dissection necessitates adequate exposure and meticulous hemostasis, with the majority of bleeding easily controlled with packing. Initial critics of this approach were concerned about inadequate hemostasis when utilizing a “blind” mediastinal mobilization. However, the vast majority of resectable cancers can be safely and adequately performed through the transhiatal approach as demonstrated by decreased perioperative complications, including perioperative blood loss and transfusion requirements, compared to the transthoracic approach.^7,12,31

The proposed advantages of the transhiatal esophagectomy include less pulmonary complications with the avoidance of a thoracotomy, and the relatively benign nature of cervical esophagogastric anastomotic leaks.^7,29 Although uncommon, the only contraindications to a transhiatal approach are documented tracheobronchial invasion of an upper- or middle-third esophageal carcinoma or severe adherence of the esophagus to vital structures (secondary to a locally advanced tumor or from prior surgery), encountered during mediastinal exploration, which may preclude a safe dissection and therefore require additional exposure through the chest.

Surgeon and hospital volume

At this time, open esophageal resection regardless of approach remains the standard of care for esophageal adenocarcinoma. Probably more important than the surgical technique are the surgeon and hospital operative volume, the surgeon's training, the ability to individualize the procedure based on the patient's performance status, tumor location and extent, and the ability to rescue patients from life-threatening complications.^34–36 An analysis of the Surveillance, Epidemiology and End Results-Medicare linked database³⁷ suggests that in addition to perioperative outcomes, long-term survival is also volume dependent. Birkemeyer et al. reported a 17% absolute 5-year survival advantage in patients undergoing esophagectomy in high-volume (>14 esophagectomies per year) centers (34%) compared to low-volume hospitals (17%), which reflected the greatest difference among all cancer resections surveyed. This volume-dependent discrepancy in the 5-year survival was independent of the use of adjuvant therapy. Therefore, both short-term perioperative outcomes and long-term oncologic outcomes may be affected by surgeon and hospital experience with esophageal resection regardless of technique. The basis for this improved survival has not been clearly defined and requires further investigation.

Surgery in the era of multimodality therapy

The impact of surgery in the setting of multimodality therapy with neoadjuvant chemoradiotherapy, perioperative chemotherapy, or adjuvant radiation therapy continues to be examined in ongoing clinical trials that attempt to improve on the historically dismal outcomes for esophageal carcinoma. With strong evidence for improved median survival, increased R0 resection rates, and no increased risk of perioperative complications, neoadjuvant chemoradiotherapy, followed by esophagectomy, remains the accepted standard of care for locally advanced resectable disease in the United States.^15,17,38

The reasons for the recent trend in improved outcomes for esophageal cancer are surely multifactorial and may include more accurate preoperative staging, widespread acceptance, and implementation of multimodality treatment approaches, improved perioperative outcomes, and advances in systemic chemotherapy and radiotherapy.

In the setting of squamous cell carcinoma (SCC) of the esophagus, it can be reasonably argued, based on level I evidence, that the addition of surgery to an effective regimen of chemoradiotherapy may not improve outcomes. Two prospective randomized trials have tested chemoradiotherapy alone versus chemoradiotherapy followed by surgery in patients with SCC. The results of the German Esophageal Cancer Study Group³⁹ and the Fédération Francophone de Cancérologie 9102 trial⁴⁰ showed equivalent overall survival between the two treatment groups although better short-term, local, progression-free survival (at a cost of increased treatment-related mortality) was associated with surgical resection.

In contrast to SCC, the controversy regarding patients with esophageal adenocarcinoma has centered on the added value of preoperative combined modality therapy and not on the necessity of surgical resection. Numerous phase III trials^38,41,42 comparing preoperative chemoradiotherapy followed by surgery to surgery alone have noted improved outcomes in the combined modality arm, which has led to increased acceptance and implementation.¹⁷

The largest randomized trial to date, the Chemoradiotherapy for Oesophageal Cancer Followed by Surgery Study trial,³⁸ which utilized a modern-day chemotherapy regimen of carboplatin and Taxol, analyzed the outcomes of 366 patients and demonstrated a 92% R0 resection rate after surgery in the chemoradiotherapy group compared to 69% in the surgery-only group (P < .001). Almost a third of patients were found to have a pathologic complete response. Postoperative complications and in-hospital mortality (4%) were similar in the two treatment groups. After a median follow-up for surviving patients of 84.1 months,¹⁵ the median overall survival was significantly longer in the neoadjuvant chemoradiotherapy plus surgery group (48.6 months) compared to the surgery-alone group (24.0 months). Median overall survival benefit was greater for patients with SCC; however, the benefit of neoadjuvant chemoradiation was also observed in patients with adenocarcinoma (43.2 versus 27.1 months, P = .038).

Improved survival has been consistently demonstrated in those patients who are down-staged and have a substantial response (complete or major pathologic response) to preoperative chemoradiotherapy. In the context of combined modality therapy, surgery remains a crucial component to eliminate residual macro- or microscopic disease following neoadjuvant chemoradiotherapy resulting in improved locoregional control and improved long-term survival. However, even in the era of multimodality therapy, failure at distant sites is still the most common (>40%) and most frequent cause of death.⁴³

Conclusions

A safe, oncologically sound esophageal resection remains an integral part of multimodality therapy for esophageal carcinoma. There have been significant improvements in the perioperative outcomes for patients after esophagectomy due to advances in patient selection, techniques, and the perioperative management of complications. Based on results from a mature randomized trial, no survival difference has been demonstrated between the transhiatal approach and an extended en bloc thoracic resection. Transhiatal esophagectomy, however, is better tolerated than an approach via thoracotomy, especially in patients with significant comorbidities. Although in the era of minimally invasive approaches to esophagectomy, any real or perceived advantage to the transhiatal procedure may become insignificant if long-term outcomes of MIE demonstrate equivalence to standard open techniques. Therefore, focus should be placed on the surgeon's experience, patient selection, and the incorporation of multimodality therapy—not the operative approach—as the most important drivers of patient outcomes in esophageal carcinoma.

Footnotes

Disclosure Statement

No competing financial interests exist.

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