En bloc resection for neoplasms of the esophagus and cardia

J THoRAc CARDIOVASC SURG 85:59-71, 1983

En bloc resection for neoplasms of the esophagus and cardia The principles of en bloc resection for carcinoma can be adapted to neoplasms of the esophagus. The techniques of the operation are described. Among the 80 patients undergoing radical resection, there were nine (Jl %) hospital deaths within 30 days of operation. The actuarial survival rate was 24 % at 3 years and 18% at 5 years. There have been no recurrences of cancer more than 3 years after operation. Results have been significantly worse among 12 patients receiving preoperative radiation therapy than in 68 in whom operation was the first treatment (1 year survival rates, 17% versus 60%). There have been no significant differences in results based upon cell type or tumor location, but patients with diseased lymph nodes or full-thickness wall penetration of the tumor had a significantly poorer survival at 2 years than patients without these determinants of prognosis. Radical en bloc resection for carcinoma of the esophagus can be performed with a mortality rate no greater than that from the less extensive standard esophagectomy. A few patients may become long-term survivors after this operation despite unfavorable prognosticfactors. The operation provides improved pathological staging as a guide to prognosis and needfor subsequent adjuvant therapy.

David B. Skinner, M.D., F.A.C.S., Chicago, Ill.

Standard esophagectomy for carcinoma usually consists of removing a portion of the esophagus and immediately adjacent lymph node tissue from the mediastinum. This type of surgical treatment for esophageal neoplasms rarely achieves more than 10% 5-year survivalrate among patients presenting with symptoms from the neoplasm. One reason for poor survival is the often advanced state of the cancer when the patient notices symptoms and seeks medical attention. Improved survival rates may be obtained by efforts at presymptomatic early case detection and treatment. 1 Another approach which might improve survival rates is to apply the principles of en bloc resection to esophageal neoplasms as they are used elsewhere in the alimentary tract. The standard esophagectomy as widely practiced for over 40 years" does not meet the criteria for en bloc surgical control of localized carcinoma in other organs. The more restricted type of resection applied to the

Readat the Sixty-second Annual Meeting of The American Association for Thoracic Surgery, Phoenix, Ariz., May 3-5, 1982. Address for reprints: David B. Skinner, M.D., Department of Surgery, The University of Chicago, Pritzker School of Medicine, 950 E. 59th St., Chicago, Ill. 60637.

esophagus undoubtedly stems from the difficult accessibility to this organ adjacent to other vital structures. However, an en bloc resection can be performed for carcinoma of the esophagus if one recognizes that the lower half of the organ has a mesoesophagus in the embryo which determines the direction of its vascular and lymphatic supply. 3 The lower esophageal longitudinal muscle fibers arise and insert in part from the subpleural and pericardial fibrous layers, so that these structures must be regarded as the serosa of the esophagus." The common derivation of the respiratory tract and esophagus from the foregut indicates a common lymphatic and vascular supply to the middle and upper portion of the esophagus and lungs. Because of these observations, a total removal of the esophagus should be designed to include as much adjacent tissue as possible within the anatomic constraints of the mediastinum. Particular attention should be paid to removing the local and regional lymphatic drainage, vascular supply, and serosa-like tissue abutting on the esophagus. In 1963, Logan" reported his experiences with en bloc resection for carcinoma of the cardia and lower third of the esophagus. Employing this more radical technique, he achieved an overall 16% 5-year survival rate, better than results previously reported and still among the best obtained. Logan's operation was not widely adopted, in part because of the 21% mortality.

0022-5223/83/010059+ 13$01.30/0 © 1983 The C. V. Mosby Co.

59

From the Department of Surgery, University of Chicago, Chicago, Ill.

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60 Skinner

Surgery

Table I. Overall management (1969-1981) of esophageal neoplasms in author's series Management Radical resection Palliative resection Bypass and exclusion Exploration and irradiation or chemotherapy Irradiation after biopsy Biopsy only Intubation only Total

I No. of cases 80 15 19 24 21 18 4 181

Since that time, improvements have been made in operative management, intensive care, and postoperative treatment following major operations so that more reasonable mortality rates can be anticipated. This report describes the techniques and results achieved from a modification of Logan's approach for en bloc resection of carcinomas of the distal esophagus and a new technique which applies these principles for carcinoma of the middle third of the esophagus. Since 1969, such radical resections have been my treatment of choice for neoplasms of the intrathoracic and intraabdominal esophagus. Being dissatisfied with results achieved by radiation therapy, my colleagues and I adopted the en bloc approach for carcinoma of the cervical esophagus as well in 1974. Patients and methods In the 12 years between June, 1969, and July, 1981, I have been asked to evaluate and treat 181 patients with esophageal neoplasms (Table 1). Following careful preoperative evaluation of the extent of the tumor and general condition of the patient, 119 patients (66%) underwent surgical exploration. Among these, 24 were found to have unresectable disease because of direct invasion of vital organs such as the aorta, trachea, or heart, or they were found to have multiple systemic metastases. Fifteen patients underwent a standard esophagectomy. In eight this was done because intraoperative staging demonstrated spread of disease beyond the limits of the radical resection, such as liver metastases in a few instances or remote diseased lymph nodes. The other seven patients had medical contraindications to the more extensive operation, including angina pectoris, thoracic aortic aneurysms, limited pulmonary function, or the presence of other chronic illness. Eighty patients underwent a radical en bloc resection of the tumor-bearing esophagus by the techniques to be described. Among the remaining 62 pa-

Table n. Cell type and tumor level in patients undergoing radical esophagectomy Level Type

Lower

Mid

Cervical

Total

Squamous cell Adenocarcinoma Adenocarcinoma (Barrett's) Sarcoma

7 18

12 (1)* 1 0

39 (I) 19 17

2

20 0 7 2

Totals

37

29

14 (I)

10

I

5 • 80 (I)

• Asymptomatic second primary in patient included in symptomatic midesophageal tumorgroup.

tients who did not undergo surgical exploration of the tumor, all had evidence of advanced systemic disease. Nineteen were treated by an esophageal bypass and tumor exclusion, 21 by irradiation following biopsy, 18 by biopsy only (most after previous radiation had failed), and four moribund patients by endoluminal intubation. This report describes the experience with the 80 patients undergoing radical resection. Description of patients and their tumors. Among the 80 patients, there were 61 men and 19 women. Sixty-six patients were white and 14 black. Ages ranged from 38 to 79 years with 14 patients being between 38 and 50 years old, 31 between 51 and 60, 24 between 61 and 70, and 11 over 70 years of age. Thirty-nine patients had squamous carcinoma, in several cases multifocal. Thirty-six had a primary adenocarcinoma of the esophagus, 17 of the tumors arising in Barrett's epithelium. Five of the cancers were sarcomas. In 37 patients, the tumor involved the lower third of the esophagus or cardia. Twenty-nine were located in the middle third, and 14 in the cervical esophagus. One patient had three separate primary tumors in the middle third and cervical esophagus simultaneously and was analyzed among the middle third group since this was the symptomatic tumor (Table II). All squamous carcinomas of the cardia and lower esophagus were assumed to be of esophageal origin. Adenocarcinoma was attributed to esophageal origin if it clearly arose in the distal tubular esophagus, normally lined by columnar epithelium. Patients with Barrett's epithelium and adenocarcinoma were considered to have primary carcinoma of the esophagus. Those patients in whom the main tumor mass was centered within the stomach but encroaching upon or involving the cardia were considered to have primary gastric carcinoma and were not included in this analysis. All patients were symptomatic, with dysphagia bein the principal complaint in all but five. Among the lat

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Neoplasms of esophagus and cardia

61

Fig. 1. This diagram shows the structures immediately adjacent to the esophagus in the posterior mediastinum and outlines the extent of the radical resection to include removal of adjacent pericardium, pleura bilaterally, arterial and venous supply to the esophagus, lymphatic drainage through the thoracic duct, and the azygos vein system in the posterior mediastinum. When complete, the dissection leaves only the myocardium, lungs, aorta, and vertebral bodies remaining in the posterior mediastinum. ter, the presentations were pain and heartburn in three, bleeding in one, and mediastinal perforation with pain and fever in one. Preoperative workup and staging. After the diagnosis is made by endoscopic biopsy (all but two patients), the workup includes a thorough evaluation of general condition and specific organ functions. Nutritional status is assessed. Those patients who have more than a 10 pound weight loss or demonstrate hypoalbuminemia are begun on enteral or parenteral hyperalimentation during the preoperative workup. Such patients requiring nutritional supplementation undergo 10 days to 2 weeks or more of such treatment prior to operation. Medical reasons for excluding patients from consideration for radical procedures include cirrhosis of the liver, diminished pulmonary function with the forced expiratory volume in 1 second (FEY l ) being less than 1 L, symptomatic angina pectoris or evidence of cardiac valve disease causing limitation of activity (exercise stress testing is done when indicated), or the presence of generalized debility in patients over 70 years of age. No absolute upper limit for age is established, but the two oldest patients undergoing resection at ages 82 and 84 both had a standard rather than radical resection. Studies are undertaken to detect evidence of tumor spread beyond the primary location. For neoplasms of the middle and upper esophagus, bronchoscopy is done to look for evidence of respiratory tract invasion. Liver/spleen scan and bone scan are performed to search for distant organ metastases. The gallium scan often reveals squamous cell carcinoma and is helpful in detecting nodal or mediastinal spread. Computed axial tomography (CT) has been used in recent years to de-

tect direct spread into adjacent organs and to note the presence of enlarged lymph nodes. The validity of CT scan findings is still under investigation, and this modality is not used yet as a reason to avoid exploration. Similarly, azygography is currently under investigation as a means to detect extraesophageal spread but is not yet employed as a criterion of operability. When preoperative investigations for spread of disease and the status of other organs are complete, all patients thought to have localized disease and to be fit for operation are advised to undergo an en bloc resection. Colon and complete upper gastrointestinal radiographs are obtained as a guide to reconstruction. A 3 day mechanical and 12 hour oral antibiotic (neomycin and erythromycin base) bowel preparation is given. Operative techniques Approach. Final staging for extent of disease is performed as the initial stage of the operation. If the tumor is localized to the region planned for resection, radical operation is performed regardless of the size of the tumor or presence of palpable lymph nodes within the region to be removed. The objective of en bloc resection is total removal of the digestive tract for 10 em on either side of the tumor whenever possible along with complete excision of immediately adjacent tissues, the vascular supply, and the lymphatic draining of the tumor (Fig. 1). For a neoplasm whose proximal extent is 10 em or more below the aortic arch indentation noted at esophagoscopy, the resection is performed through a left thoracotomy. This approach is chosen to provide optimal exposure for the radical dissection of the lower mediastinum and diaphragmatic tunnel through which the

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62 Skinner

Thoracic and Cardiovascular Surgery

/

Fig. 2. An outline of the extent of radical dissection in the mediastinum performed through a left thoracotomy is shown to include pericardium, pleura, and a cuff of diaphragm on the lateral aspect of the esophagus.

tumor-bearing esophagus passes (Fig. 2). Forty-two radical resections were performed through the left thoracic approach. For intrathoracic carcinoma closer than 10 em distal to the aortic arch, a right thoracotomy incision is made through the fifth intercostal space. Twenty-four en bloc resections were done through this approach. In patients in whom the distal extent of the palpable tumor is more than 10 em above the diaphragm, who are thin, and who have had no previous abdominal operation, the entire operation may be performed through the right thoracotomy without a separate laparotomy incision, as described by Belsey and Hiebert." If any of the aforementioned factors are unfavorable, a separate midline laparotomy is performed to mobilize the abdominal esophagus and stomach. Eight patients underwent resection through an exclusive right thoracotomy incision without concomitant laparotomy, whereas the remainder had a two team approach through a laparotomy and right thoracotomy. En bloc resection of lower tbird neoplasms through left thoracotomy. The patient is in a straight left lateral thoracotomy position, and the incision is made through the sixth intercostal space. A 1 inch segment of the seventh rib is resected posteriorly. The costal margin is not divided. After exploration within the thorax to exclude metastases, the diaphragm is incised peripherally from beneath the sternum to the spleen. This incision affords excellent exposure of the left upper abdomen.

Fig. 3. Following division of the splenic vessels and removal of the mediastinum from the colon and mesocolon, the stomach and spleen are retracted anteriorly to provide exposure to the celiac axis and hiatus. The left gastric artery is ligated at its origin, and the left inferior phrenic artery is divided as it comes from under the adrenal gland. A cuff of diaphragm is resected surrounding the tumor mass. Through the enlarged hiatus, the thoracic duct and azygos vein are divided near the aortic hiatus.

The omentum is mobilized by dividing adhesions as necessary and is separated from the transverse colon and mesocolon but left attached to the stomach. The spleen is elevated from its posterior and lateral attachments. The splenic artery and vein are divided at the tip of the pancreas. The spleen is left attached to the stomach by the short gastric vessels. The stomach, spleen, and omentum are retracted upward to expose the region of the celiac axis. Retroperitoneal lymph nodes and fatty tissue cephalad to the pancreas are dissected upward toward the hiatus. The origin of the left gastric artery is identified, ligated, and divided. The coronary vein is similarly divided. The tissue overlying the left adrenal gland is dissected toward the hiatus, and the left inferior phrenic artery is ligated as it passes from beneath the adrenal gland toward the diaphragmatic hiatus. By means of electrocautery, a cuff of diaphragm muscle surrounding the hiatus is detached and left with the esophagus. In this way, the intraabdominal portion of the esophagus is not seen or dissected close to the tumor. With the hiatus so enlarged, the distal thoracic aorta down to the aortic hiatus can be

Volume 85 Number 1 January, 1983

Neoplasms of esophagus and cardia

63

Fig. 4. The extent of the en bloc resection of the posterior mediastinum through a right thoracotomy for middle third carcinoma is shown. The azygos vein is divided flush with the vena cava, and the branches to the azygos are divided as they pass onto the vertebral bodies. The pericardium is incised anteriorly to the pulmonary ligament and onto the pulmonary veins. The subcarinallymph nodes are removed with the specimen.

readily seen. The thoracic duct is doubly ligated and divided as it passes through the aortic hiatus. The two ascending lumbar veins which join to form the azygos vein are similarly divided at this level (Fig. 3). The dissection is carried up on the vertebral bodies, and several intercostal arteries and veins are ligated and divided behind the esophagus to clear the surface of the lower thoracic vertebrae. The operation is continued in the chest. An incision is made through the parietal pleura overlying the aorta from the diaphragm to the arch. This dissection is carried on the surface of the aorta anteriorly and medially, with the several esophageal or bronchoesophageal arteries encountered being ligated and divided. The previously started prevertebral dissection from the hiatus is encountered medially at the lower end of the aortic dissection. The mediastinal mobilization is carried upward on the vertebral bodies by systematically ligating the intercostal vessels to free up the azygos vein and the lymphatic trunks entering the thoracic duct. The azygos vein and thoracic duct are left in continuity within the mediastinal envelope enclosing the esophagus. This dissection is carried cephalad until a 10 em margin is obtained above the tumor. At this point the thoracic duct and stump of azygos vein are again ligated. The esophagus itself is exposed for the first time as it passes under the aortic arch. Anteriorly, the pulmonary ligament is divided up to the inferior pulmonary vein. The pericardium is entered on the surface of the inferior pulmonary vein, and pericardium is incised distally as far as the diaphragm

along a line anterior to the pleuropericardial junction. The pericardial incision is taken across the back of the heart at the upper end until the right pulmonary veins are identified. The right pleural cavity is entered by incising outward through the pericardial sleeve on the right pulmonary veins. All of the lymph nodes under the bifurcation of the carina are freed and left with the specimen. This dissection goes from the upper lobe bronchus on the left lung over to the upper lobe bronchus on the right lung. Several bronchial vessels coursing through this tissue are ligated. The incision in the right pleura and pericardium anterior to the esophagus is carried distally down to the diaphragm in front of the right pulmonary ligament. The right pleura is incised distally where it reflects off the vertebral body, and the posterior incision in the right pleura is carried cephalad on the vertebral bodies. The right pulmonary ligament is divided flush with the lung tissue to join the anterior and posterior right pleural incisions. This procedure necessitates the ligation of the distal ends of the previously divided right intercostal vessels as they pass off the anterior vertebral bodies toward the right intercostal spaces. The en bloc resection of the posterior mediastinum 10 em proximal to the tumor is now complete. Upper abdominal exposure is resumed. The omentum is removed from the lower two thirds of the stomach, the right gastroepiploic artery and vein being left intact along the greater curvature of the stomach. The gastrohepatic omentum is divided close to the liver. Points for division of the stomach are selected 10

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64 Skinner

Fig. S. Following completion of the posterior mediastinal dissection, all tissues surrounding the esophagus are left with the specimen, and the aorta, vertebral body, bifurcation of the trachea, and posterior myocardium are cleanly dissected.

ern down the lesser curve from the distal extent of the tumor and similarly 10 em down the greater curvature. Usually most of the lesser curvature is resected but only approximately one third of the greater curvature. The stomach is transected between these points and closed. The proximal stomach, spleen, omentum, and intraabdominal portion of the mediastinal dissection are passed through the hiatus into the chest and retracted upward onto the chest wall. If the primary tumor is squamous carcinoma, the dissection on the wall of the esophagus is carried underneath the aortic arch up into the cervical region. In such cases, the final anastomosis is done in the neck after removal of the specimen, preparation of the reconstruction, and closure of the thoracotomy incision. When the primary tumor is an adenocarcinoma and 10 em margins are achieved, the anastomosis is generally done just beneath the aortic arch through the left thoracotomy incision. Reconstruction is accomplished by a direct end-to-side esophagogastric anastomosis or by interposition of a segment of colon based on the ascending branch of the left colic artery if the stomach is not suitable for use in the reconstruction. All anastomoses are performed with a single full-thickness suture of running 5-0 monofilament wire interrupted in three places around the circumference of the anastomosis. The diaphragm is reattached to its cuff on the chest wall. The chest incision is closed with bilateral pleural drainage.

Thoracic and Cardiovascular Surgery

En bloc resection for middle third neoplasms through right thoracotomy. Through the fifth intercostal space, an incision is made through the parietal pleura overlying the right side of the vertebral bodies. This incision extends from just above the diaphragm up to the level of the clavicles so that a 10 em margin if possible is achieved above and below the palpable tumor. Intercostal vessels lying on the vertebral body are ligated and divided, and the vertebrae are cleared across the midline by elevating the azygos system and thoracic duct with its tributaries anteriorly with the esophagus. As this dissection is carried medially, the aortic wall is encountered, and the right intercostal arteries and bronchoesophageal arteries are ligated flush with the aorta. Care is taken not to go posterior to the aorta and injure the left intercostal vessels. If the tumor is close to the aortic arch, the left recurrent laryngeal nerve may be divided if necessary. The vagus is divided distal to the arch. Anteriorly, the azygos arch is divided and oversewn flush with the vena cava (Fig. 4). The esophagus is separated from the membranous portion of the trachea such that its anterior blood supply remains intact. Subcarinallymph nodes are dissected from right upper lobe bronchus around to the left upper lobe bronchus with several bronchial vessels being divided. The pericardium is entered on the right pulmonary vein and a pericardial window is excised with the specimen from the level of the pulmonary veins down to the diaphragm. The left thoracic cavity is entered through the reflection of the pericardium onto the left pulmonary veins anteriorly and, where the left pleura is reflected off the aorta, posteriorly. This approach allows resection of the left pulmonary ligament along with the mediastinum. In this fashion, the entire posterior mediastinal tissue envelope surrounding the esophagus is resected, with myocardium left anteriorly, vertebral bodies posteriorly, and aorta and lungs laterally (Fig. 5). When a point 10 em distal to the esophagus is reached, the dissection is brought onto the wall of the esophagus, usually in the esophageal hiatus. If the patient is a suitable candidate, the stomach is mobilized through the hiatus, the left gastric artery being divided as close to the celiac axis as possible through the enlarged hiatus. The omentum is detached from the stomach and right gastroepiploic vessels and receives its blood supply from the left gastroepiploic vessels after the short gastric arteries and veins are divided. 6 If the abdomen is opened, a similar dissection is performed to advance the stomach into the chest for reconstruction, or a long segment of left and transverse

Volume 85

Neoplasms of esophagus and cardia

Number 1

January, 1983

colon may be prepared for reconstruction based upon the left colic artery. 7 Proximally, the dissection is carried to the neck or 10 em above the tumor. The right vagus is divided distal to the right recurrent nerve. In most cases, the anastomosis is done in the neck even though it may be technically possible to construct it through the thoracotomy. The esophagus is transected at the upper level of the dissection and closed temporarily. The organ to be used for reconstruction, colon or stomach, is attached to the closed stump of the esophagus with sufficient intrathoracic slack to allow delivery through a subsequent neck incision. The stomach or colon reconstruction is sutured to the margins of the hiatus to prevent herniation of other organs through the hiatus. The chest is closed with bilateral pleural drainage. If the anastomosis is to be done in the neck, a transverse cervical incision is made toward the side of the thoracotomy. The incision is carried anterior to the sternocleidomastoid muscle and carotid sheath to reach the prevertebral space. The previously mobilized esophagus is identified and delivered into the wound with the attached organ for reconstruction, and anastomosis is performed. Carcinoma of the cricopharyngeus and cervical esophagus. Since 1974, 14 patients with carcinoma involving the cricopharyngea1 sphincter and cervical esophagus were treated by total esophagectomy, bilateral modified radical neck dissections, and laryngectomy. These procedures often were performed in conjunction with head and neck surgical colleagues. In four of these patients, a concomitant right thoracotomy through the fourth intercostal space was necessary to continue the en bloc dissection of the esophagus distally to gain a satisfactory margin beyond the tumor. In the remaining 10 patients, the tumor was localized to the cricopharyngeal region and the radical dissection was limited to the neck. Tumors at this level have their lymphatic spread bilaterally in the neck, but less frequently downward into the mediastinum. The intrathoracic esophagus in these 10 patients was removed by blunt dissection through the neck incision and through a separate laparotomy incision, as initially described by Turner. 8 The organ chosen for reconstruction was prepared through the laparotomy incision. The entire stomach was advanced through the posterior mediastinum for the reconstruction in 13 patients, and a long segment of isoperistaltic left and transverse colon was used in one. Anastomosis was carried out to the midpharynx or higher depending upon the level of transection necessary to obtain a clear margin above the tumor. If a total thyroidectomy was necessary as part of the resec-

65

Table TIL Reconstruction Anastomosis Organ

Thorax

Stomach Colon None Totals

35

I

Neck

Total

33

34

67

2

10

I

12 I

45

80

tion, the parathyroid glands were dissected sterilely from the specimen in the operating room and transplanted, after being minced, into the sternocleidomastoid muscle. Reconstruction after resection (Table III). A portion or all of the stomach is used as the organ of choice for reconstruction in the majority of patients. Because its mobilization may be completed as part of the tumor dissection, fewer anastomoses are required, and hence its use shortens a lengthy operation. When sufficient stomach is not available after the resection, or if previous gastric operation is noted, an isoperistaltic colon segment is used. Four patients in this series had a substernal colon bypass as a first stage in their treatment prior to planned preresectional radiation 'therapy. One patient who had the nephrotic syndrome preoperatively underwent a radical en bloc resection of the esophagus through a left thoracotomy on the chance that removal of the tumor might reverse the nephrotic syndrome. Reconstruction was not attempted because of hypoalbuminemia at the time of operation, and the patient subsequently died of renal failure several months later before reconstruction was performed. Postoperative care. The removal of all posterior mediastinal lymphatic tissue as well as dissection of the carina and both main-stem bronchi makes careful respiratory care essential early after operation. Large volumes of crystalloid fluid infusion are required during the first 48 hours after operation, presumably because of sequestration of fluid in abdominal and extremity lymphatics. Engorgement of pulmonary lymphatics makes the effort of breathing significantly greater. All patients are maintained on positive-pressure respirator support with a positive end-expiratory pressure of 10 em H20 for at least 48 hours after the operation or until a significant diuresis indicates mobilization of sequestered fluid. Pulmonary artery pressure monitoring (Swan-Ganz catheter) simplifies the decisions regarding fluid replacement requirements. After mobilization of fluid and diuresis, the patient is slowly weaned off the respirator. The bilateral chest tubes are left in place until the

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Thoracic and Cardiovascular Surgery

Skinner

Table IV. Nonfatal complications No.

Early complications (30 days), 37/71 patients Persistent pleural effusion Chylothorax Aspiration pneumonia Arrhythmia Congestive heart failure Hypocalcemia Leaks Colon infarction Perforated stomach Postoperative bleeding Wound infection Bilateral recurrent nerve palsy Late complications Esophagitis Duodenal ulcer, bleeding, perforation Anastomotic dysfunction Local recurrence

4 2 6 5 I 2 5 2 2 2 6 2 6 I I 3

drainage through each tube decreases to under 200 ml daily. Continued chest tube drainage for up to 7 days is routine following this extensive dissection. Prophylactic antibiotics started 6 hours preoperatively are given during the operation and for 24 hours thereafter. The nasogastric tube is left in place until intestinal function is evident by the passage of flatus. If parenteral hyperalimentation is given prior to operation, this is continued during the postoperative recovery. Other aspects of postoperative care are those routinely used in the management of patients having major thoracic and abdominal operations.

Results Mortality. Among the 80 patients, there were nine deaths (11%) within 30 days following operation. Acute myocardial infarction caused the deaths of three patients aged 54, 76, and 76 years from 3 to 10 days after operation. In one, hypotension heralding the infarction developed during the operation, and in the other two the event occurred in the intensive care unit. The deaths of four patients were caused by technical complications of the operation including necrosis of the trachea following too extensive mobilization for resection of a cervical squamous cell carcinoma in a 65year-old man, undetected intraoperative bleeding into the dependent thoracic cavity causing hypotension and cardiac arrest in a 63-year-old woman with achalasia and squamous carcinoma of the mid-esophagus, and an anastomotic leak from an intrathoracic esophagogastrostomy causing aortic erosion and massive hemorrhage 2 weeks after operation in a 46-year-old man with

adenocarcinoma of the lower esophagus. The fourth death attributed to technical complications was caused by sudden aortic rupture on the planned day of discharge 10 days after operation in a 39-year-old women with adenocarcinoma of the distal esophagus. A barium swallow performed 3 days previously showed no evidence of anastomotic leakage or mediastinal abscess, and the patient was eating a regular diet. While in the process of being discharged, she had sudden chest pai~, hematemesis, and rapid bleeding and collapsed. Operative repair of the aortic injury was temporarily successful, but subsequent delayed hemorrhage was fatal. The remaining two postoperative deaths were caused by pneumonia 21 and 29 days after radical resection in 55- and 56-year-old men both having squamous carcinoma in the mid-esophagus. In one patient the resection had been preceded by conventional and neutron beam radiation therapy, and evidence of radiation pneumonitis as well as bacterial pneumonia and residual carcinoma was found at autopsy. In the other patient, the pneumonia was caused by a major bout of aspiration after the early postoperative course had been uncomplicated. Postoperative mortality rates were not significantly different between patients with adenocarcinoma (11%) and squamous carcinoma (13%), nor among patients whose primary carcinoma was in the cervical esophagus (7%), mid-esophagus (17%), or distal esophagus (8%). Deaths following operation were not significantly correlated to the age of the patient. Mortality was 14% in the fourth and fifth decades, 10% in the sixth decade, 8% in the seventh decade, and 18% in patients in the eighth decade of life. Early postoperative deaths following initial recovery. From 1 to 6 months following radical resection, 11 of71 patients surviving operation died. Among these were five patients who died of recurrent carcinoma, and in each extensive lymph node involvement was noted at operation and in the resected specimen. Four patients died of pneumonia. All had had irradiation and/or chemotherapy before the radical resection, and one had marginal pulmonary function prior to operation. The tenth patient returned 3 months after radical resection for adenocarcinoma of the lower third of the esophagus with fever, dehydration, and septic shock. A subphrenic abscess was diagnosed upon admission to the hospital, but the patient and his family refused surgical drainage and he died 1 day later. The final patient in this group presented with severe renal dysfunction, nephrotic syndrome, and protein-losing uropathy preoperatively. In the hopes that the process might be reversed by resecting his tumor, operation

Volume 85 Number 1

January, 1983

was performed, Renal function did not improve and the patient died 2 months later of continued renal failure. Early complications. Among the 71 operative survivors, 37 (52%) had one or more complications during recovery in the hospital (Table IV). In six patients the extensive lymphatic dissection resulted in recurrent pleural effusion necessitating chest tube reinsertion and drainage beyond the first postoperative week. The drainage was clearly chylous in two of these but was serous in the other four. Six patients had severe aspiration pneumonia during the postoperative recovery, including four in whom the anastomosis was in the neck near the cricopharyngeal sphincter. Five patients had troublesome cardiac arrhythmias and one had congestive heart failure despite the routine use of digoxin. Two patients required treatment for postoperative hypocalcemia. In one a total thyroidectomy was part of the resection for cervical carcinoma, and parathyroid transplantation had been performed. In both cases, the hypocalcemia was temporary and reversed as parathyroid function resumed. Two patients had bilateral recurrent laryngeal nerve palsy. Both had high intrathoracic tumors and in each the left recurrent laryngeal nerve was divided as part of the radical resection. The injury to the right nerve was temporary in both and both regained the ability to speak. Other technical complications included five leaks from the esophageal anastomosis. All occurred in cervical anastomoses, involving the stomach in four instances and a colon interposition in one. Four of the five leaks were minor and healed spontaneously, but one required debridement and prolonged drainage. This latter patient had persistent laryngeal dysfunction necessitating tracheostomy. Two patients undergoing long segment colon interposition to the neck had venous infarctions of the colon segment necessitating removal. Both were subsequently managed by an extracorporeal esophagogastric tube through a cervical esophagostomy and gastrostomy. 9 Two patients had perforations of the stomach distal to an esophagogastric anastomosis. One was managed successfully by drainage through the neck and feeding jejunostomy. The other had a gastrobronchial fistula and required subsequent flap interposition for closure. Other complications included reexploration for early postoperative bleeding in two patients, and drainage of a wound infection or empyema in six. Late complications. Eleven patients returned for treatment of late complications months or years after resection. Six had symptomatic reflux esophagitis above the esophagogastric anastomosis, which presented as bleeding in two and a peptic stricture neces-

Neoplasms of esophagus and cardia

67

sitating dilatation in three. One 79-year-old patient returned 5 months after radical resection for adenocarcinoma of the lower esophagus with a bleeding duodenal ulcer necessitating operative suture. Five months later he returned again with an esophageal ulcer that had perforated into the trachea and caused his eventual death. At autopsy, no gastrinoma in the pancreas could be found. One patient had anastomotic dysfunction caused by sharp angulation of the cervical esophagogastric anastomosis. Operative revision was successful in restoring normal swallowing. Three patients returned with localized recurrence of their carcinoma interfering with anastomotic function. They are the only patients in the series in whom operation failed to control local disease. Survival. All 80 patients have been followed up to the time of death, until 5 year survival was achieved, or to within the past 6 months. The overall survival curve as determined by the actuarial method is shown in Fig. 6. The 3 year survival rate in the entire series is 24%, and there are no instances of recurrent carcinoma detected to date among 3 year survivors. Two late deaths from cardiovascular disease between the fourth and fifth years after operation lower the 5 year survival rate to 18%. A total of 52 patients underwent radical resection more than 3 years ago, and 10 (19%) survived more than 3 years free of disease. Twelve of the 80 patients had received preoperative radiation therapy (3,000 to 6,600 rads) , generally completed 4 to 8 weeks prior to radical resection. In six, the preoperative radiation was given as part of a clinical trial (subsequently abandoned) to evaluate the role of radiation therapy followed by surgical resection. In the other six, the preoperative radiation therapy was prescribed by a referring physician who later sent the patient for surgical resection as part of an overall treatment plan or because of concern that the tumor was not responding promptly to irradiation. Radical resection was accomplished without increased difficulty in these 12 patients, and there was only one postoperative death (8%) compared to a 12% 30 day mortality among 68 patients without preoperative irradiation. However, the survival curve of patients undergoing preoperative irradiation was worse than that of those without preoperative radiation, and only 17% (two patients) lived for 1 year after operation, a significantly poorer rate (p < 0.01) than the 60% 12 month survival rate in patients who did not undergo preoperative irradiation therapy. There were no significant differences in survival among patients treated for adenocarcinoma, adenocarcinoma in Barrett's epithelium, squamous cell carci-

The Journal of

68

Skinner

Thoracic and Cardiovascular Surgery

C)

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10

8

20

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12

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24

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MONTHS

48

60

Fig. 6. The actuarial survival curve for 80 consecutive patients undergoing radical esophagectomy (1969-1981) is portrayed. The numbers by each point indicate patients at risk at that time. The two patients who died in the fourth year after operation both died of cardiovascular disease without evident recurrence of cancer.

noma, or sarcoma. Three-year actuarial survival rates were 24%, 33%, 19%, and 40%, respectively. Similarly, there were no significant differences in survival for patients whose cancer was in the cervical esophagus (27% at 3 years), mid-esophagus (14%), and lower esophagus (33%). In a previous study analyzing the pathological findings in 91 resected esophageal cancer specimens (including 61 cases in this series), metastases to lymph nodes and the extent of esophageal muscle penetration were found to be independent significant variables affecting survival. I 0 Size of the tumor did not correlate to prognosis. Among the 80 patients undergoing radical operation, the median number of lymph nodes examined in the resected specimen was 24 with the maximum being 127 in one specimen. Twenty-eight had no nodal metastases. Among patients at risk for 2 years or more fol-

lowing operation, survival rate was 49% when lymph nodes were all normal compared to 12% (p < 0.05) when more than four lymph nodes were involved with cancer. Among 30 patients with one to four lymph abnormal nodes, three were free of disease less than 2 years after operation, and nine others survived more than 2 years following operation, of whom three are known to be without evident disease at 2 years, 21,1 years, and 3 1/ 2 years. Only one of22 patients with more than four abnormal lymph nodes has survived for as long as 2 years. The resected specimens showed full-thickness penetration of the cancer through the esophageal wall in 52 patients and no or partial penetration of the muscle in 28 patients. At 2 years, the survival rate of 56% among those without full wall penetration was significantly greater (p < 0.01) than the 21% survival in patients with tumor penetration through the esophageal wall. All 10 patients living more than 3 years after radical esophagectomy have no evidence of recurrent disease, including one patient with four abnormal lymph nodes and another with full-thickness wall penetration who died of cardiac disease 4V2 years after operation. The other eight patients who survived more than 3 years have both normal lymph nodes and less than fullthickness tumor penetration. Among these ten 3 year survivors without recurrence, the resected tumors measured more than 4 em in greatest dimension in five of the patients, with the largest tumor measuring 9 ern. This emphasizes that tumor size is not a good prognostic indicator. Altogether, 21 of 62 patients who survived operation more than 2 years ago have lived at least 2 years after operation. Among these, 14 are without evident disease including four with full-thickness wall penetration and three with abnormal lymph nodes. One patient in this group was treated with preoperative radiotherapy, and one patient received adjuvant chemotherapy for adenocarcinoma after operation. Thirteen of 14 have received no treatment subsequent to their surgical resection. Seven additional patients survived more than 2 years following radical resection but did have recurrences. All had diseased lymph nodes (one to six) and four had full-thickness wall penetration. They have received chemotherapy or radiation therapy subsequent to developing recurrences, depending upon symptoms and distribution of recurrent disease. None have anastomotic recurrences. Discussion

This experience demonstrates that the principles of en bloc resection for cancer control can be applied to the esophagus at all levels. The 30 day operative mor-

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Neoplasms of esophagus and cardia

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January, 1983

tality of 11% in this series is comparable to many reports of operative mortality from standard or palliative esophagectomy. The absolute 3 year survival rate of 19% (actuarial 24%) for patients without recurrent disease compares favorably with nearly all of the previously reported series of standard esophagectomy for carcinoma. The results confirm Logan's experience that worthwhile survival can be obtained by en bloc resection, but with a more reasonable mortality. Certain technical aspects of the operation require careful attention to reduce morbidity and mortality further. These include meticulous ligation of lymphatic trunks, careful postoperative respiratory care, use of preoperative digoxin and antibiotics, and careful performance of the reconstructive portion of the operation. These results also point to the importance of preoperative selection of patients, including the avoidance of operation in patients with serious cardiovascular disease or preexisting respiratory dysfunction. Since long-term survival rates are significantly poorer in patients with multiple diseased lymph nodes or extensive direct mediastinal invasion, preoperative and operative staging is important to avoid the unnecessary performance of an extended resection in patients who are doomed to die of their tumor and may be better treated by a standard or palliative esophagectomy or other types of therapy. The argument for radical en bloc resection to treat carcinoma of the esophagus is based upon three considerations. Improved pathological staging of the disease serves as a guide to prognosis and the need for subsequent adjuvant therapy. 10 Analyses of the extensive tissue removed by the en bloc resection allows more detailed pathological staging, which is helpful in comparing future modification in treatment. The operation can be performed with a mortality rate no greater than that from the less extensive standard esophagectomy, and causes of death do not appear to be the direct result of the more radical dissection. A few patients (perhaps 5% to 10%) can become long-term survivors free of disease after radical resection in spite of unfavorable prognostic factors such as metastases to lymph nodes or tumor penetration through the wall of the esephagus into adjacent tissue, so that survival rates may be improved somewhat. Disadvantages include a more lengthy and difficult operation and greater need for intensive postoperative care. The poor results achieved following preoperative radiation therapy in this series, although not a randomized trial, point to the need for control groups of patients treated by operation alone when adjuvant therapy is advocated for patients with carcinoma of the esophagus. In this study, postoperative adjuvant ther-

69

apy was not used consistently and did not apparently influence the number of long-term survivors. Surgical resection alone without preoperative therapy, demonstrating a 27% 3 year survival rate among 68 patients, suggests a reasonable standard against which modifications in treatment should be measured, since preoperative or postoperative therapy has the potential to hasten death as well as prolong survival. I am grateful to all of my residents, fellows, and faculty colleagues at The Johns Hopkins Hospital and the University of Chicago Medical Center who contributed so much to the care of these patients.

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REFERENCES Huang KC, et al: Diagnosis and surgical treatment of early esophageal carcinoma, Medical and Surgical Problems of the Esophagus, Vol. 43, Serona Symposia. S Stipa, RHR Belsey, A Moraldi, eds., New York, 1981, Academic Press Inc., pp 296-299 Adams WE, Phemister DB: Carcinoma of the lower thoracic esophagus. Report of a successful resection and esophagogastrostomy. J THORAC SURG 7:621-632, 1938 Arey LB: Development Anatomy. A Textbook and Laboratory Manual of Embryology, ed. 6, Philadelphia, 1954, W. B. Saunders Company Laimer E: Beitrag zur Anatomie des Oesophagus. Med Jahrbucher Jahrg, 1883, pp 333-338, Wien Logan A: The surgical treatment of carcinoma of the esophagus and cardia. J THORAC CARDIOVASC SURG 46:150-161,1963 Belsey R, Hiebert CA: An exclusive right thoracic approach for cancer of the middle third of the esophagus. Ann Thorac Surg 18: 1-15, 1974 Belsey R: Reconstruction of esophagus with left colon. J THORAC CARDIOVASC SURG 49:33-55, 1965 Turner GG: The George Haliburton Hume Memorial Lectures, London, 1946, Cassell & Co., Ltd. Skinner DB, DeMeester TR: Permanent extracorporeal esophagogastric tube for esophageal replacement. Ann Thorac Surg 22: 107-Ill, 1976 Skinner DB, Dowlatshahi KD, DeMeester TR: Potentially curable cancer of the esophagus. Cancer (in press)

Discussion DR. JOHN R. HANKINS Baltimore. Md.

Since 1958, our group at the University of Maryland has seen and treated 438 patients with carcinoma of the esophagus, of whom 407 had squamous cell carcinoma. Prior to 1969, 234 patients were treated principally by radical therapeutic regimens, of whom 54 were managed according to a protocol that called for radiation therapy followed by resection. Of this entire series, only six, or 2.6%, survived 5 years. In the 12 year period 1969 to 1981, we have used as our primary method of treatment a limited, or palliative, resection for middle- and lower-third carcinomas, with radiation ther-

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apy being the primary treatment for carcinomas of the upper third. During this latter period, which parallels Dr. Skinner's series, 126 patients with middle- and lower-third squamous cell lesions were seen; limited resection was performed in 78. The operative mortality for the entire series, extended to March, 1982, is approximately 9%, but there has been only one death among the last 35 consecutive patients having esophagogastrectomy and none among the last 24. In our patients, staging was done according to the criteria of the American Joint Committee for Cancer Staging. Sixtyone, or nearly 80%, of the 78 patients who underwent esophagogastrectomy had Stage III disease. We have used postoperative radiotherapy in patients in whom small deposits of neoplasm are left behind in the mediastinum. Statistically we were not able to show improved survival with postoperative radiotherapy, but our statistician tells us that there was a trend in that direction and that if we had had more patients in each category, there probably would have been an increased survival in patients with Stage III (Ml ) middle-third carcinomas. The entire series of patients seen in consultation between 1969 and 1981 totalled 161. There were only 54 patients who were excluded from the primary protocol, and of these 25, or about half, received palliation. Of 107 patients treated according to the primary protocol, 95 achieved satisfactory deglutition-the major criterion of palliation. Radiotherapy was not effective in three of 20 patients with upper-third lesions, and there were nine operative deaths. Since we made palliation our primary goal, the survival rates have remained at least as high as they had been previously. For patients with middle- and lower-third carcinomas treated by esophagogastrectomy, our 1 year survival rate is 38% and our 2 year survival rate, 20%. I have two questions. How are patients selected at the time of operation for radical resection? Do you perform a radical resection in patients who are found to have adherent perinodal metastases, for example, in the mediastinum or in the celiac area? Second, do you believe that the survival rate you report is sufficiently high to offset the operative mortality rate? Our operative mortality rate has become progressively lower and is now approximately 3% (one death in 35 consecutive resections). I wonder if your survival rate is really sufficiently improved to justify the 11% mortality rate cited. DR. HANS GEORG BORST Hannover. Federal Republic of Germany

We have used azygography, mediastinoscopy, and computed tomography (CT) in a substantial number of our 200 esophageal resections. We do not believe that azygography is a very valuable method. In fact, the azygos vein courses in an area which generally does not determine resectability. We had hoped that CT might help to delineate these tumors from the surrounding organs, in particular from the aorta. However, the present techniques in our hands do not seem to be particularly useful in assessing operability. On the other hand, lymph nodes are nicely demonstrated by this method. If

Thoracic and Cardiovascular Surgery

the CT scan shows no metastases, it is very unlikely that any lymph node metastasis will be found during the operation. We therefore have given up mediastinoscopy when the cr scan is negative for lymph node metastases. Finally, CT has been extremely helpful in sorting out those patients with tumor in the thoracic inlet, particularly the liver and the spleen. DR. J. ERNESTO MOLINA Minneapolis. Minn.

We undertook a review of the last 10 years in the treatment of only adenocarcinoma of the cardia at three institutions: the Marshfield Clinic in Wisconsin, the University of Minnesota, and the Veterans Administration Medical Center in Minneapolis. Three basic treatments have been used in the past for this disease. In the first, a left thoracotomy was usually performed with esophageal resections below the left inferior pulmonary vein. The second approach was a more radical but staged resection in which patients were sent home and brought back later for a colon or intestinal interposition. The third approach entailed subtotal esophagectomy with simultaneous reconstruction; however, our resection was not as radical as the one Dr. Skinner is proposing. The third group is the one that I would like to discuss. This study, which included microscopic reexamination of the specimens, often showed that in less than radical resections of almost the entire thoracic esophagus, the incidence of residual tumor within 5 mm of the line of resection was very high. Because of the elasticity of the esophagus when the first two approaches were used, the surgeon overestimated at operation the extent of tumor-free margin in the esophagus. Consequently, there were many patients in whom tumor was found within 5 mm of the line of resection. The survival with the third approach (operation alone with no added treatment) was 25% at 2 years. I fully agree with a more radical approach, which will give us a chance to cure some of these patients and, if not, at least to palliate them more effectively. I would like to ask a question of Dr. Skinner: The statement was made that adenocarcinomas and squamous carcinomas behave very much the same, so that we would expect the same results on our resections. I wonder if he has definite data comparing lymph node metastases and invasiveness in these two types. DR. SKI NNE R (Closing) I appreciate the discussion of Drs. Hankins, Borst and Molina. Dr. Hankins showed us the results that are achievable by a palliative or standard approach to esophagectomy. His results are fairly representative of the results that can be expected from that operation, which has been practiced for over 40 years, since it was introduced by Adams and Phemister. His statement that he obtained poor results from a radical resection prior to 1969 prompts me to emphasize the need to be precise about what is meant by radical resections. It is for that reason I chose the term "en bloc resection" instead of "radi-

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January, 1983

cal resection, " since the degrees of radicalism obviously vary a great deal among surgeons. Dr. Hankins pointed out the importance of staging. I believe that we must break down results by staging when we begin comparing results. Dr. Wu, in his Honored Guest's Address, clearly showed the effect of having a large number of Stage I cases in one's experience. Dr. Hankins asked about the selection of patients at operation. Only those whose disease extends beyond the possible margins of a radical resection are excluded at operation. That group usually includes patients with liver metastases or nodesthat are beyond the limits that can be removed en bloc. In those cases we convert to a palliative resection. He commented about mortality. I would only say that our II % mortality is no different from his 9% mortality. He has had a 2.4% mortality in recent patients, and we too have seriesof 20 or 25 consecutive patients without a death. I think one must report mortality figures from an overall series and not select out subgroups when comparing mortality rates between different operative approaches.

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Dr. Borst asked about azygography and CT scanning. Drs. DeMeester, Little, and I are using these approaches in our patients currently. It is not the azygos arch that we are concerned about as an indicator of inoperability, but rather the azygos in the posterior mediastinum where it runs up along the vertebral bodies. We agree completely with Dr. Borst that the CT scan so far has not been helpful in delineating tumor adherence to the aorta, but that it is very useful in detecting large lymph nodes at the celiac axis or liver metastases. Dr. Molina presented his experience with adenocarcinoma of the cardia and provided support for our thesis that one should have a 10 cm margin proximal to the tumor. His operative mortality ranging from 9% to 17% again is comparable to many reports in the literature. He asked about the differences between adenocarcinoma and squamous carcinoma with regard to staging. We find no significant difference in survival rates for adenocarcinoma versus squamous carcinoma.