13: Surgical Approach to Esophagogastric Junction Cancers

Esophageal cancer is ranked among the top 10 most common cancers in the world, with more than 480,000 new cases diagnosed annually.¹ The proportion of cases involving the two most common histopathological entities, adenocarcinoma and squamous cell carcinoma, is changing. While adenocarcinoma of the esophagus is rising rapidly in Western countries; squamous cell carcinoma remains unchanged.² The true incidence of adenocarcinoma is difficult to determine because cancer of the esophagogastric junction (EGJ) is classified by some as a gastric cancer while by others as an esophageal cancer (see Chapter 12). This explains, in part, the ongoing controversy over which strategy to follow when it comes to surgical approach and technique.

In an effort to rationalize what had been a rather indiscriminate approach to EGJ tumors and to provide clearer guidelines, in 1998, Siewert and Stein³ published a classification for adenocarcinoma of the esophagogastric junction (AEG). Tumors of the AEG were defined as tumors with an epicenter equal to or less than 5 cm proximal and distal to the anatomic EGJ (anatomic cardia).

Three entities were distinguished:

1. Adenocarcinoma of the distal esophagus, usually arising in Barrett intestinal metaplasia,

2. True carcinoma of the EGJ, which may arise from the cardiac epithelium or from Barrett intestinal metaplasia, and

3. Subcardial adenocarcinoma arising from the gastric fundus.

Using this classification and drawing on their own data, Siewert and Stein proposed guidelines on which surgical strategy to use according to each of the above-described subtypes. This classification is based entirely on identifying the “anatomical” cardia and measuring the center of the tumor in relation to this anatomical cardia on the resected specimen (i.e., pathological staging). However, measuring the center of the tumor turns out to be impractical if not impossible for the purposes of clinical staging. It is important to have accurate clinical staging because it ensures the appropriateness of the therapeutic decision (e.g., in the presence of a hiatal hernia). Not surprisingly, Omloo et al.⁴ recently reported a substantial discrepancy between the clinical and pathological staging when using the Siewert classification.

The 7th edition of the TNM classification system,⁵ which is based on evidence derived from a large international multinational database, also addressed this issue. It classifies and stages tumors that have their epicenter in the EGJ, or within the proximal 5 cm of the stomach and extending into the EGJ or esophagus, similarly to an adenocarcinoma of the esophagus. Tumors centered in the stomach that are located more than 5 cm from the EGJ, or tumors within 5 cm of the EGJ but without extension into the esophagus, are classified and staged as gastric tumors.⁶

As a result, the strategies related to surgical approaches and techniques are, in general, similar to those intended for cancers of the esophagus. These strategies in particular are related to the patterns of lymphatic spread observed with esophageal cancer.

Lymphatic dissemination is an early event and has a negative influence on survival. Lymph node metastases are found in less than 5% of intramucosal tumors, but in as many as 30% to 40% of submucosal tumors, that is, when the tumor spreads beyond the mucosa. The esophageal wall is characterized by an extensive submucosal lymphatic plexus, which not only supplies a drainage route for early dissemination, but also gives rise to jump metastases (i.e., lymph nodes adjacent to the primary tumor are not affected, but more distantly located lymph nodes contain metastases).⁷

The pattern of lymphatic dissemination therefore is difficult to predict. Nevertheless, carcinomas of the proximal and middle thirds of the esophagus tend to metastasize to the cervical region, whereas more distal-lying tumors and tumors of the EGJ more commonly metastasize to the lymph nodes around the celiac trunk. This is also the case for adenocarcinoma of the EGJ. These tumors typically drain by an extraperitoneal route into the retropancreatic area and into the left renal hilum.⁸ Adenocarcinoma of the EGJ also has a tendency to spread to the thoracic lymph nodes including subcarinal, paratracheal, and aortopulmonary window nodes. Lagarde et al.⁹ evaluated a group of 50 patients with a EGJ tumor that underwent extensive lymphadenectomy through a transthoracic approach and found that 22% of them had lymph node involvement of the more proximal nodes. These findings need to be taken into consideration when determining surgical strategies.

For decades surgeons have been combining transthoracic and abdominal esophagectomy to remove the esophagus and cardia, together with the primary tumor and adjacent lymph nodes, under direct vision.¹⁰ It has been suggested that long-term survival might benefit from a more radical resection and a more extensive lymphadenectomy in the thorax and abdomen.¹¹

The Radical En Bloc Resection

The radical en bloc resection extends the standard treatment to encompass a wide local resection of the primary tumor with a radical lymph node dissection of the middle and distal thirds of the posterior mediastinum.¹² The concept of extensive en bloc resection was first reported in 1963, but the associated mortality of more than 20% discouraged its general acceptance.

Skinner and Akiyama reintroduced this method in the 1980s. Ultimately, they were able to reduce operative mortality to 5%, with 5-year survival rates of 18% and 42% respectively.^13,14 Over time the results steadily improved worldwide. Today, mortality rates are well below 5%, and 5-year survival figures routinely reach 40% at experienced centers.

The Two-Field Lymph Node Dissection

Early lymphatic dissemination, characterized by longitudinal spread of tumor along the esophagus via the submucosal plexus to the upper mediastinum and abdomen, was the rationale for advancing to a two-field lymphadenectomy.⁷ This approach, which originated in Japan, adds the following elements to a wide local excision of the primary tumor: lymphadenectomy of the entire posterior mediastinum, the lymph nodes along the celiac trunk, common hepatic and splenic arteries, as well as the lymph nodes along the lesser gastric curvature and in the lesser omentum.

Transhiatal Resection

Despite some indication that surgical techniques with extensive lymph node dissections tend to improve long-term survival, a less radical transhiatal approach was developed to decrease early postoperative risk by eliminating the need for thoracotomy. This approach has been popularized in the Western world by Orringer.¹⁵

Attempting to close the ongoing debate between advocates of radical esophagectomy via the transthoracic approach versus advocates of the less radical esophagectomy via the transhiatal approach, Hulscher et al.¹⁶ of The Netherlands instituted a multi-institutional randomized clinical trial. This trial compared limited transhiatal resection to transthoracic resection with extended en bloc lymph node dissection for adenocarcinoma of the esophagus and EGJ. The results revealed no statistically significant overall difference between the two surgeries, but there was a clear long-term trend in favor of the more extensive approach which yielded a 39% 5-year survival compared with a 29% 5-year survival for the more limited resection. Particularly for adenocarcinoma of the distal esophagus, a subsequent analysis revealed a 17% survival benefit in favor of the more extensive transthoracic approach.¹⁷ This trial remains the only randomized study to compare these two approaches, but several other studies have supported the overall findings that long-term survival may benefit from a more radical esophagectomy combined with extensive two-field lymphadenectomy. Indeed, data from many centers seem to endorse a better overall 5-year outcome, often exceeding 40% after two-field lymphadenectomy, as compared with the less radical lymphadenectomy with 5-year survival figures in the range of 20% to 25%.¹⁸

Concerning the recommended number of lymph nodes to be dissected, there is no general agreement. Historically, 15 nodes have been considered the minimum. However, a recent multivariate analysis by Peyre et al.¹⁹ in a large patient population found that the absolute number of lymph nodes removed during esophagectomy was a strong independent predictor of survival. They reported an optimal survival benefit required resection of at least 23 lymph nodes, and this finding was not the result of stage migration. Within every tumor stage (I–III), patients with more than 23 resected lymph nodes had better survival than patients with less than 23 resected nodes, thus strongly emphasizing the importance of performing an adequate lymph node dissection.

Within the compartments of a two-field dissection (thoracic and superior abdominal compartment), in addition to the nodes along the lesser curvature and left gastric artery, the celiac, hepatic, and splenic artery nodes also should be routinely removed during the abdominal stage of any en bloc resection. Since 1994 lymph node dissection in the chest has been defined as standard (lower periesophageal and subcarinal nodes), extended (including some upper mediastinal nodes, i.e., right paratracheal nodes), and total thoracic lymph node dissection (including the uppermost mediastinal nodes, i.e., left and right paratracheal and aortopulmonary window nodes).²⁰ In a classic two-field lymphadenectomy at least the periesophageal and subcarinal nodes should be removed and preferably also the node at the aortopulmonary window and the right paratracheal nodes.

As to safe margins, a wide peritumoral or en bloc resection should be attempted whenever possible to obtain an R0 status (clear circumferential, proximal, and distal margins on pathological examination). At the side of the esophagus a proximal gross length of at least 5 cm or even more to achieve a microscopically negative proximal margin is advocated. This is particularly true for the more advanced T3 and T4 cancers as shown recently by Ito et al.²¹

The extent of stomach resection will depend on the location and the length of the tumor. For adenocarcinoma of the distal esophagus and EGJ, a resection margin of 5 cm below the distal pole of the tumor will suffice. This permits use of the stomach for reconstruction after resection of the lesser curvature and its lymph nodes to create a gastric tube with an anastomosis high in the chest or the neck. If the tumor extends more than 5 cm over the fundus or lesser curve, a total gastrectomy with Roux-en-Y jejunal reconstruction is mandatory.

Currently, there are several approaches to the surgical treatment of adenocarcinoma of the distal esophagus and EGJ. These include the right-sided abdominotransthoracic approach with anastomosis high in the chest (Ivor Lewis) or in the neck (McKeown, also called 3-hole resection), a left-sided abdominotransthoracic approach with anastomosis in the chest (Sweet) or in the neck (Belsey), a transhiatal resection with anastomosis in the neck (Orringer), and the minimally invasive esophagectomy (MIE).

It is generally accepted that in patients who are medically fit for surgery, a radical esophagectomy with at least a two-field lymphadenectomy is the preferred intervention. The transhiatal resection is reserved for older patients and/or patients who are medically unfit for a radical resection.

The Ivor Lewis, McKeon, or 3-hole esophagectomy, and MIE are described in Chapters 15, 17, and 18 of this book. In this chapter we describe our approach to the transhiatal and the left-sided transthoracic technique for resection of EGJ tumors (also see Chapters 16, 21, and 22).

Transhiatal Esophagectomy

The transhiatal esophagectomy without thoracotomy has a number of practical advantages, that is, a short operative duration, probably lower incidence of pulmonary complications, and the avoidance of postthoracotomy pain. The method is particularly applicable to tumors of the distal esophagus and EGJ, where the lower mediastinum can be approached through a surgically widened hiatus. The stomach is preferred for reconstruction and is anastamosed to the remaining cervical esophagus. This can be achieved via the esophageal bed (the so-called prevertebral route) or via the retrosternal route. The latter is preferable if macroscopic locoregional tumor residue is left behind in the posterior mediastinum.

Operative Technique

The operation begins with a median laparotomy, the incision extending from the xiphoid process to just below the umbilicus. The abdominal cavity is inspected and palpated in search of distant metastases, as this would be a contraindication for proceeding to resection. After mobilizing the left lobe of the liver, the esophageal hiatus can be inspected and tumors of the EGJ can be assessed for invasion of adjacent organs. Subsequently, the stomach is mobilized. The esophagus is freed in the hiatus, and if necessary, a surrounding cuff of diaphragm can be included in the resection specimen (Fig. 13-1). Next, the central tendon of the right hemi-diaphragm is incised, thus opening the lower mediastinum (Fig. 13-2A).

The periesophageal fatty tissues, the left and right parietal pleura, and if needed the pericardium are included in the surgical specimen. This procedure can be advanced at least as far as the inferior pulmonary veins. The more proximal and unmobilized part of the (normal) esophagus is bluntly mobilized or stripped, using a vein stripper through a neck incision (Fig. 13-2B).

After the intra-abdominal dissection is complete, the lesser curvature is resected and a neoesophagus is created, by fashioning a narrow 3 to 4 cm wide gastric tube from the remainder of the stomach (Fig. 13-3).

In this manner the lymph nodes along the right and left gastric artery are also removed. The gastric tube is then pulled/pushed (Fig. 13-4) to the neck via the prevertebral route, where an esophagogastrostomy is created (Fig. 13-5A,B).

When the retrosternal route is used, a tunnel is created by blunt retrosternal dissection from the xiphoid process up to the jugular notch. This retrosternal tunnel must be spacious enough that it does not compromise the perfusion of the interposed conduit by undue compression. This may in some cases require resection of the sternoclavicular joint.

Transthoracic Esophagectomy

The left thoracic approach is considered by many surgeons to be the standard approach for carcinoma of the lower esophagus and cardia. This operation was popularized by Sweet.²² The left posterolateral approach may be extended anteriorly across the costal margin as advocated by Belsey.²³ The latter provides a true thoracoabdominal exposure of both the superior abdominal compartment and posterior mediastinum.

When the transthoracic approach is used, double lumen endotracheal intubation with intraoperative deflation of the lung at the operative side greatly facilitates dissection in the posterior mediastinum. Advocates of the transthoracic approach emphasize that dissection under direct vision enables a wide peritumoral en bloc esophagectomy as well as meticulous intrathoracic lymph node dissection. The chief disadvantage is the probably higher incidence of pulmonary complications.

Operative Technique

In this operation the chest is entered through the sixth intercostal space (Fig. 13-6A). After dividing the costal margin, the diaphragm is incised at its periphery as an inverted T-shape incision, the short limb of the T incising the abdominal wall over a few centimeters. By incising the diaphragm at its periphery, innervation and consequently function are well preserved (Fig. 13-6B).

This approach permits optimal direct vision of both the abdomen and chest cavity through one single incision. As a result, some claim that by using this incision, maximum radicality can be achieved. The entire thoracic esophagus can be dissected through the left-sided approach. In case of a EGJ tumor it may be necessary to resect a cuff of the diaphragmatic muscle surrounding the tumor (Fig. 13-7).

Dissecting the esophagus from beneath the aortic arch, requires ligation and transection of the bronchial arteries just below the arch (Fig. 13-8). The mobilization is then continued by blunt finger dissection behind the aortic arch and up into the apex of the chest. The mediastinal pleura above the aortic arch is opened. After resecting the lesser curvature at a level well below the cardia, the esophagus is pulled and delivered through the opened mediastinal pleura above the aortic arch and transected as well.

At this point, lymphadenectomy in both the abdomen and posterior mediastinum as well as a resection of the thoracic duct is performed. Mobilizing the spleen and the tail-body of the pancreas can be performed by incising the peritoneal reflection dorsally behind the spleen (Fig. 13-9A). The spleen and pancreas are flipped over to the right side yielding a perfect exposure of the abdominal aorta and all its major ramifications, the left adrenal gland, and hilum of the kidney (Fig. 13-9B).

In the chest all lymph nodes in the mediastinum, subcarinal region, and aortopulmonary window are removed (Fig. 13-10A). For the latter great care must be taken to visualize and preserve the left recurrent nerve.

Transecting the fibrotic remnant of the ductus arteriosus opens the left paratracheal space for further lymph node clearance (Fig. 13-10B).

Finally, resection and ligation of the thoracic duct also is the best way to prevent a chyle leak postsurgery (Fig. 13-10C).

A narrow gastric tube is constructed and brought upward through the hiatus and behind the aortic arch and temporarily fixed to the esophageal stump in the apex of the chest (Fig. 13-11).

The incision is then closed and the patient is turned to supine position. Through a left cervicotomy the esophageal stump with the attached gastric tube is exteriorized into the operative field and a cervical esophagogastrostomy is performed. According to the use of vascular pedicle, several modes of creating a gastric tube have been described. Whether or not it is a good idea to perform a gastric drainage procedure (pyloroplasty, pyloromyotomy, or more recently by injecting the pylorus with Botox) remains controversial. There is, however, a tendency to leave the pylorus intact at the time of surgery. If a gastric outlet problem occurs after surgery, it is in general well managed with prokinetic drugs and/or by performing balloon dilatation of the pylorus.²⁴

In cases where the EGJ tumor extends greater than 5 cm onto the stomach, a total gastrectomy followed by a Roux-en-Y jejunal reconstruction with an intrathoracic infra-aortic esophagojejunostomy becomes mandatory.

Siewert classification was originally described to allow surgeons to approach each section of the distal esophagus and proximal stomach logically. With the advent of the 7th edition of the AJCC staging system, the location of the tumor is an innate and critical part of the system. Arbitrary pathological description of the location of the epicenter, less relevant for a therapeutic approach, has been abandoned in exchange for a clinically relevant description which needs only to clarify whether or not the EGJ tumor extends more than 5 cm distally into the stomach. The authors have described their preferred surgical approaches to these tumors. Other modifications of this approach, as described in Chapters 21 and 22, are also recommended.