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Superiority of extended en bloc esophagogastrectomy for carcinoma of the lower esophagus and cardia
General Thoracic Surgery
Superiority of extended en bloc esophagogastrectomy for carcinoma of the lower esophagus and cardia The belief that transhiatal esophagogastrectomy results in the same survival as a more extensive en bloc resection was tested in 69 patients with carcinoma in the distal esophagus and gastric cardia. Preoperative and intraoperative staging defined three distinct subgroups of patients. Those with apparently limited disease and good general health (group I, n = 30) underwent en bloc resection. Those with apparently limited disease but poor physiologic reserve (group II, n = 16) underwent transhiatal resection, as did those with evidence of more advanced disease (group III, n = 23). OveraU, survival was significantly better in the 30 patients who underwent en bloc resection (41 %) than in the 39 patients who underwent transhiatal resections (14%; p < 0.001, log-rank). Oinical staging showed apparently limited disease in 46 patients (groups I and 11). These groups differed only in the presence of poor physiologic reserve because the percentages of patients with tumors limited to the esophageal waD (group I 13/30, group II 6/16) and four or fewer lymph node metastases (group I 21/30, group II 15/16) at the time of pathologic staging were not significantly different. Survival after en bloc resection was, however, significantly better (41% versus 21 %; p < 0.05, log-rank). According to the WNM system of pathologic staging, 19 patients had early lesions defined as intramural lesions associated with four or fewer lymph node metastases, 26 had intermediate lesions defined as either transmural or associated with more than four lymph node metastases, and 24 had late lesions defined as both transmural and associated with fewer than four lymph node metastases. Survival was significantly better in patients with early lesions after en bloc resection compared with transhiatal resection (75 % versus 20%, p < 0.01), survival was also significantly better in patients with advanced lesions (27% versus 9%, p < 0.01). For intermediate lesions, the survival was similar (14% versus 20%), although the median survival after en bloc resection was longer (24 months versus 8 months). (J THoRAc CARDIOVASC SURG 1993;106:850-9)
Jeffrey A. Hagen, MD, Jeffrey H. Peters, MD (by invitation), and Tom R. DeMeester, MD, Los Angeles, Calif.
From the University of Southern California School of Medicine, Department of Surgery, Los Angeles, Calif. Read at the Seventy-third Annual Meeting of The American Association for Thoracic Surgery, Chicago, III., April 25-28, 1993. Address for reprints: Tom R. DeMeester, MD, University of Southern California School of Medicine, Department of Surgery, 1510 San Pablo St., Suite 514, Los Angeles, CA 90033-4612. Copyright w 1993 by Mosby-Year Book, Inc. 0022-5223/93 $1.00 +.10
850
12/6/49321
Current strategies for treatment of esophageal carcinoma limit the role of surgery to the removal of the primary tumor, with the hope that adjuvant therapy will increase cure rates by destroying systemic disease. This approach emphasizes the concept of biologic predeterminism; that is, the outcome of treatment in esophageal cancer is determined at the time of diagnosis, and surgical therapy aimed at removing more than the primary
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851
Length of tumor> 9 em on endoscopy Transmural invasion and obvious adenopathy on CT scan Unfavorable intraoperative evaluation (Figure 2) No
Yes
Age < 75, FEV, > 1.25, Adequate Cardiac Reserve
I
Yes
Transhiatal Esophagogastrectomy (n = 23)
No
En bloc Esophagogastrectomy (n = 30)
I
Transhiatal Esophagogastrectomy (n = 16)
Fig. 1. Algorithm of patient selection and procedure performed. CT, Computed tomographic; FEVj , forced expiratory volume in 1 second. Exploratory laparotomy
I
Inspect tumor, biopsy porta hepatis hepatic artery, and subpancreatic nodes
I
I
I
No evidence of wall penetration or lymph node involvement
Grossly evident wall penetration, and lymph node involvement
I I Right posterolateral thoracotomy I Inspect tumor, biopsy
I
Closure of abdomen
Transhiatal esophagogastrectomy
low paratracheal nodes
I
I
I
Grossly evident wall penetration, and lymph node involvement
Noevidence of wall penetration, or lymph node involvement
Simple esophagectomy
Enbloc dissection of esophagus
I I
I I
I
Re-open laparotomy incision
I Palliative case I Mobilize stomach for pullup for neck anastomosis
I
I
Curative case
I
En blocdissection of stomach, 2{3 proximal gastrectomy, mobilize colon for interposition to cervical esophagus
Fig. 2. Algorithm outlining surgical procedure and intraoperative decisions.
tumor is not helpful. Lymph node metastases are considered simply markers of systemic disease, and the systematic removal of involved nodes is not beneficial. Based on this concept is the belief that removal of the primary
tumor by transhiatal esophagogastrectomy results in the same survival as a more extensive en bloc resection. This belief was tested in the present study by comparing the outcome of extended en bloc esophagogastrectomy with
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Table I. Classification of esophageal carcinoma
Table III. Demographics
Wall penetration WO = Tumor penetration through the basement membrane of the mucosa but not through the muscularis mucosa WI = Tumor penetration through the muscularis mucosa and into but not through muscle layers W2 = Tumor penetration through muscle layers Lymph node involvement NO = No lymph node involvement N I = One to four lymph nodes involved N2 = Five or more lymph nodes involved Systemic metastasis MO = No metastasis M I = Distant metastasis
Groups Early
Subtotal Intermediate
Subtotal Late Subtotal Total
No. ofpatients
THE
WONO WONI WINO WINI
EBE I 0 5 4
1 0 5 3 9
WON2 WI N2 W2NO W2NI
10 0 0 6 8
14 W2N2 16 39
p
65.6 ± 1.7
59.8 ± 1.6
0.014
32/7
27/3
0.74 0.16
13 10 16 27/39 9/39
4 10 16 21/30 13/30
1.0 0.12
SCCA, Squamous cellcarcinoma. For other abbreviations, seeTableII.
THE Age ± standard error of mean Nodes ~4 Limited to wall
EBE
P
68.9 ± 2.6
59.8 ± 1.6
0.0026
15/16 6/16
21/30 13/30
0.063 1.0
For abbreviations, seeTableII. 0 3 2 7
12 16
Age ± standard error of mean Sex (M/F) Cell type SCCA Adenocarcinoma Barrett's esophagus Nodes ~4 Limited to wall
EBE
Table IV. Pathologic staging of tumors ofpatients who had limited disease at the time ofpreoperative clinical and intraoperative surgical evaluation
Table II. Staging WNM classification
THE
8 8 30
THE, Transhiatal esophagogastrectomy; ERE, en blocesophagogastrectomy.
transhiatal esophagogastrectomy for carcinoma of the distal esophagus and gastric cardia. Methods Study population. Between July 1983 and January 1992,69 patients underwent esophageal resection by the primary author (T. R. D.) for cancer of the distal esophagus or gastric cardia. Patients were excluded from the study if they had evidence of systemic metastatic disease or invasion of adjacent organs on assessment before operation or at the time of exploration. Preoperative chemotherapy had been given before referral in four patients. There were 17 patients with a squamous cell carcinoma, 20 with an adenocarcinoma of the cardia, and 32 with an adenocarcinoma in a Barrett's esophagus. Patient evaluation. The assessment of the extent of disease before operation included barium roentgenograms of the upper gastroesophageal tract, endoscopic examinations, and chest and abdominal computed tomographic scans. All patients had pulmonary function tests and a noninvasive assessment of cardiac function. The decision regarding the procedure to be performed was made according to the algorithm shown in Fig. 1. Patients who had early lesionson preoperative clinical and intraoperative surgical evaluation, who were under the ageof75 years, and who were free of significant cardiovascular or pulmonary disease
underwent extended en bloc esophagogastrectomy (n = 30). Transhiatal esophagogastrectomy was performed in patients with early lesions if they were over the age of 75 years or had significant cardiac or pulmonary disease (n = 16). Patients with advanced disease seen during preoperative clinical or intraoperative surgical evaluation underwent transhiatal esophagogastrectomy (n = 23). Operative approach. The operative procedure is summarized in Fig. 2. The operation begins with an abdominal exploration to assess the extent of the primary tumor and the regional node status. Ifthere was gross evidence of transmural extension of the tumor and multiple lymph node metastases or microscopic involvement of the porta hepatis or subpancreatic nodes, a transhiatal resection was done, and gastrointestinal continuity was reestablished with a cervical esophagogastrostomy.' In these patients, a systematic dissection of the lymph nodes along the hepatic, celiac, and splenic artery was performed, and as many paraesophageal and subcarinallymph nodes were removed as could safely be done with a transhiatal dissection. If the abdominal findings were favorable, the abdomen was closed, the patient was repositioned, and a right posterolateral thoracotomy was performed. An en bloc dissection of the intrathoracic esophagus was done in continuity with the adjacent low paratracheal, subcarinal, paraesophageal, and parahiatal lymph nodes. The block of tissue removed was bounded anteriorly by the membranous trachea and pericardium, laterally by the right and left pleural cavities, and posteriorly by the vertebral column and the aorta. After the completion of the thoracic dissection, the patient was turned again to the recumbent position, and the procedure was completed through the abdomen and an incision on the left side of the neck. The abdominal dissection entails en bloc removal of the proximal two thirds of the stomach, along with the greater omentum, the spleen, and the splenic artery with its associated nodes, a
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Hagen, Peters, DeMeester
Percent Alive 100%
80% 60%
.
..................... -+-......
40%
~~
.-_
20%
.......ESE
n=30
_~~
_. -. -- -tHE'
....
n~'39'
O%-+------.----,..-----,.-----,...------r-------,
o
10
20
30
50
40
60
Months 1 15 17
n
THE 39
p < 0.001 (Cox-Mantel)
EBE
30
2 3 15
3 1 9
4 1
4
5 1 2
Fig. 3. Survival probabilities calculated by Kaplan-Meier method according to type of procedure performed. EBE, En bloc esophagogastrectomy, THE, transhiatal esophagogastrectomy.
Percent Alive
100% ...... 80% -
K~'
60% .......-
ESE n = 30
40% -
H
THE n= 16
20% 0%
o
10
20
30
50
40
60
Months 2 3 4 5 2 1 1 1 EBE 30 17 15 9 4 2 n
1
THE 16 9
p < 0.05 (Cox-Mantel)
Fig. 4. Survival probabilities calculated by Kaplan-Meier method according to type of procedure performed in patients thought to have limited disease at time of preoperative clinical and intraoperative surgical evaluation. For abbreviations, see Fig. 3.
853
854
The Journal of ThoraCic and Cardiovascular Surgery November 1993
Hagen, Peters, DeMeester
Percent Alive
100% -
~
80%-
----
- . - - - - .. -
-""""'"
60% - " " " " " ' "
-
-
-
..-
ESE
-
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.
n=10
-
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- - . f--.. -
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0%
n=9
--
-. --
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.
-+----T'"'"""--~__,_----r_---_r---____,r----....,
o
10
20
30
40
60
50
Months 3
4
5
0 3
0
1
9
EBE
p < 0.025 (COX-Mantel)
2
6 0 0 10 8 7 5
n
TIIE
2
Fig. 5. Survival probabilities calculated by Kaplan-Meier method according to type of procedure performed in patients with early disease at time of pathologic classification of removed specimen. For abbreviations, see Fig. 3.
Percent Alive 100% -
80% -
60% .........
40% TH E
20% -
0%
n = 14
EBE n = 12
o
10
20
30
40
60
50
Months n
p
= 1.0
(Cox-Mantel)
1
2
3
4
5
THE 14 3 2 1 1 1 EBE 12 5 5 1 0 0
Fig. 6. Survival probabilities calculated by Kaplan-Meier method according to type of procedure performed in patients with intermediate disease at time of pathologic classification of removed specimen. For abbreviations, see Fig. 3.
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Hagen, Peters, DeMeester 855
Percent Alive 100%
80%
-
60% -
40%
t-
.,:....:
...-
-
20% 0%
-
EBE n = 8
I THE 1
o
10
20
n = 16
30
50
40
60
Months n
1
2
3
1HE 16 6 1 0 EBE 8 4 3 3
p < 0.05 (Cox-Mantel)
4 5 0 1
0 0
Fig. 7. Survival probabilities calculated by Kaplan-Meier method according to type of procedure performed in patients with late diseaseat time of pathologic classification of removed specimen. For abbreviations, see Fig. 3. systematic dissection of the lymphnodesaroundthe hepaticand celiac arteries, and the posterior peritoneal tissue from the esophageal hiatus downto the superiorborder of the pancreas. Gastrointestinal continuitywasreestablished withisoperistaltic colon interposition.I Postoperative staging. The specimens were examinedwith respect to the known prognostic indicators, that is,the extent of esophageal wall penetration and the presenceand location of lymph node spread.' Pathologic classification of the extent of disease wasdone according to the WNM systemadvocatedby Skinner and associates" (Table I). The patients' conditions were staged and separated into three categories: early, intermediate, andlate disease, as defined in Table II. Early lesions werethose in which the tumor was limited to the esophageal mucosa or muscle layers, withfour or fewerlymphnodemetastases. Intermediate lesions were thosewith either transmural invasion and four or fewer node metastases or those with nontransmural tumors with more advanced nodal disease. Late lesions were those with both transmural invasion and extensive (>4) node metastases. FoUow-up. All hospital survivors were followed-up at 3-month intervals forthe first3 yearsand then at every6 months with routine laboratory studies,a chest roentgenogram, and a chest and abdominalcomputedtomographic scan.All surviving patients wereeitherseenin personor contactedforfollow-up by telephone within3 monthsbeforethe preparationof thisarticle. Themedian follow-up timeof surviving patientswas 14months, with a range of I to 108 months. Statistical methods. Comparison of continuous variables was done by Student's t test. Fisher's exact test was used for comparison of proportions. Survival probabilities were calcu-
lated accordingto the method of Kaplan and Meier. Hospital deathswereincludedin allcalculations ofsurvival. Comparisons of survival between groups was performed with the log-rank method of Mantel and Cox.
Results Fig. 3 shows the survival analyses by type of procedure performed. En bloc esophagogastrectomy resulted in a 5-year survival of 40.6% with a median survival of 31 months. This was significantly better than survival after transhiatal esophagogastrectomy, for which the 5-year survival was 13.5% and the median survival was 11 months (x 2 = 10.15, p < 0.001). With the exception of age, no difference was found in the distribution of patient characteristics (including gender, cell types, depth of wall penetration, and extent of nodal metastases) between the two groups (Table III). Forty-six patients in the population studied had apparently limited disease at the time of preoperative clinical and intraoperative surgical evaluation. Thirty of these patients were in good health and underwent en bloc esophagogastrectomy. Sixteen had poor physiologic reserve and underwent transhiatal esophagogastrectomy. Their actuarial survival is shown in Fig. 4. En bloc esophagogastrectomy resulted in significantly better 5-year survival (41% versus 21%; x2 = 4.02, P < 0.05), despite
856
The Journal of Thoracic and Cardiovascular Surgery November 1993
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Percent Alive
100%
T
80%
1 ESE
..-
60%
......
40%
THE
20% 0%
o
n =13
~
10
n =9
20
30
50
40
60
Months 1 9 6 13 9 n
TIlE
p < 0.05 (Cox-Mantel)
EBE
2
3
4
5
0
0
0
0
8
5
3
2
Fig. 8. Survival probabilities calculated by Kaplan-Meier method according to type of procedure performed in patients with intramural tumors. For abbreviations, see Fig. 3.
the fact that postoperative pathologic staging showed that patients who underwent transhiatal esophagogastrectomy tended to have an earlier stage of disease (Table IV). Comparison of the actuarial survival after en bloc esophagogastrectomy and transhiatal esophagogastrectomy with regard to pathologic classification and stage of disease is shown in Figs. 5, 6, and 7. A clear survival advantage was observed in patients with early lesions after en bloc esophagogastrectomy, for which the 5-year survival was 75%. Survival was lower for intermediate and late lesions. Survivals after transhiatal esophagogastrectomy for early and intermediate disease were similar-19.8% and 21.0% at 2 years, respectively-and were not much better than the 8.6% for late disease. Because the depth of tumor penetration of the esophageal wall and the number of metastatic lymph nodes are the most important independent variables affecting survival, we compared survival with regard to the method of resection in patients with intramural tumors and with four or fewer metastatic lymph nodes (Figs. 8 and 9). A clear survival advantage was associated with en bloc esophagogastrectomy in patients with tumors limited to the esophageal wall (x 2 = 4.45,p < 0.05). The validity of this observation is underscored by the fact that the proportion of patients with four or fewer involved nodes was similar
in both groups (9/9 transhiatal esophagogastrectomy versus 10/13 en bloc esophagogastrectomy, p = 0.54). Comparison of survival in patients with four or fewer metastatic nodes also demonstrated a significant advantage for en bloc esophagogastrectomy (x 2 = 9.38, p < 0.005). The validity of this observation was underscored by the fact that the proportion of tumors limited to the esophageal wall was similar in both groups (9/27 transhiatal esophagogastrectomy versus 10/21 en bloc esophagogastrectomy; p = 0.38). The argument could be made that the previouslymentioned results are due to a staging bias, that is, less accurate lymph node staging was done in the patients who had a transhiatal resection. Because a similar abdominal lymph node dissection was performed in both procedures, we used the relationship between the pathologic characteristics of abdominal and thoracic lymph nodes in patients after an en bloc resection to support the adequacy of staging thoracic nodes in patients who underwent a transhiatal resection. Only one of the 22 patients who had four or fewer nodal metastases in the abdomen after en bloc esophagogastrectomy had evidence of lymph node metastases during the thoracic node dissection. This would strongly indicate that, when a thorough abdominal lymph node dissection shows four or fewer involvednodes,
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857
Percent Alive 100%
rt
-1
80%
~ f-
>------<
60%
EBE n=21
40%
r--< ~
THE n= 27
20%
0%
o
10
20
30
50
40
60
Months
p < 0.005 (Cox-Mantel)
mE EBE
n 27 21
1 12 14
2 3 2 1 13 8
4 1 4
5 1 2
Fig. 9. Survival probabilities calculated by Kaplan-Meier method according to type of procedure performed in patients with four or fewer lymph node metastases. For abbreviations, see Fig. 3.
the thoracic nodes are free of metastases and the staging of early disease in patients after a transhiatal resection is dependable. We also investigated the possibility that the previously mentioned results were due to the fact that patients who underwent transhiatal resection were older, near the end of their life span, and would be more likely to die of physiologic causes than recurrent tumor. This supposition appears invalid because the hospital mortality for each procedure was similar (transhiatal esophagogastrectomy = 12.8%) en bloc esophagogastrectomy = 10%; P = 1.0) and the analysis of deaths occurring during the follow-up period showed that all patients, irrespective of the surgical procedure, died with recurrent disease. Discussion This study shows that for early cancers of the lower esophagus and cardia, en bloc esophagogastrectomy results in significantly better survival than does transhiatal esophagogastrectomy. This finding cannot be explained by a bias in the staging of disease, a difference in operative mortality, or death from causes other than tumor. Rather, improved survival appears to be due to the type of operation performed. The results in patients with
intermediate and advanced disease are less clear: a survival advantage was present with advanced disease but not with intermediate disease. We suspect that the explanation for this outcome is the imprecision in assigning a stage of esophageal cancer to patients or the evaluation of too few patients with intermediate disease. We have chosen to use the WNM system because it allows stratification of patients according to the number of lymph nodes involved, a factor shown to be important in survival.3,4 In contrast, the TNM system stratifies only on the basis of lymph node metastases being present or absent; consequently, the patients most apt to benefit from an en bloc esophagogastrectomy (i.e., those with limited nodal disease) are included with patients with more extensive nodal disease, obscuring any potential benefit. Orringer, Marshall, and Stirling' recently reviewed their results with transhiatal esophagogastrectomy for esophageal cancer. Patients with tumor confined to the submucosa and no lymph node involvement had a 5-year survival of 63%. Once lymph nodes were involved, the survival dropped to 38%. In contrast, our early disease group had a survival of 75% despite the inclusion of patients with tumor limited to the wall of the esophagus,
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some of whom also had four or fewer lymph node metastases (Table II). Several possible explanations exist for the failure of a transhiatal resection to achieve the results obtained with an en bloc resection in patients with favorable stage of disease. First, it is possible to disseminate tumor cells at the time of the blunt dissection of the thoracic esophagus. Second, an inadequate distal tumor margin may be accepted in an effort to preserve a full length of the stomach and the blood supply to it to reestablish gastrointestinal continuity with a cervical esophagogastrostomy. This inadequate margin can result in the development of recurrent disease along the gastric suture line," Third, unrecognized perigastric metastatic nodes are transferred into the thorax with the gastric pull-up. Fourth, it is possible that the transhiatal dissection leaves residual nodal metastasis in the mediastinum. An en bloc esophagogastrectomy effectively eliminates all of these potential causes of recurrence. Ideally, the question of which procedure is more beneficial should be resolved by a prospective randomized study, although several obstacles exist. The number of patients seen with early disease is small, and thus the accrual time would be long. In addition, preoperative staging is inaccurate and would make stratification by stage difficult. Finally, there is a moral problem for advocates of an en bloc esophagogastrectomy to, in good conscience, perform more limited resections. Until a randomized study is completed, support of an en bloc resection for early disease will depend on studies, such as the present and others.?'? that have demonstrated a benefit with this approach. On the basis of this experience, we conclude that survival after surgical removal of a carcinoma in the distal esophagus or cardia is dependent on the method of resection (i.e., transhiatal or en bloc esophagogastrectomy), and patients with early lesions have significantly better survival after extended en bloc resection.
REFERENCES 1. Orringer MB. Transhiatal esophagectomy without thoracotomy for carcinoma of the thoracic esophagus. Ann Surg 1984;200:282-8. 2. DeMeester TR, Zaninotto G, Johansson K-K. Selective therapeutic approach to cancer of the lower esophagus and cardia. J THORAC CARDIOVASC SURG 1988;95:42-54. 3. Skinner DB, Dowlatshahi KD, DeMeester TR. Potentially curable cancer of the esophagus. Cancer 1982;50:2571-5. 4. Skinner DB, Ferguson MK, Soriano A, Little AG, Staszak VM. Selection of operation for esophageal cancer based on staging. Ann Surg 1986;204:391-401. 5. Orringer MB, Marshall B, Stirling MC. Transhiatal esoph-
6. 7.
8.
9.
agectomy for benign and malignant disease. J THORAC CARDIOVASC SURG 1993;105:265-77. Wong J. Esophageal resection for cancer: the rationale of current practice. Am J Surg 1987;153:18-24. Akiyama H, Tsurumaru M, Kawanura T, Ono Y. Principles of surgical treatment for carcinoma of the esophagus:analysisoflymph node involvement. Ann Surg 1981;194:435-46. Skinner DB. En bloc resection for neoplasms of the esophagus and cardia. J THORAC CARDIOVASC SURG 1983;85:5971. Lerut T, DeLeyn P, Coosmans W, Van Raemdonck D, Scheys I, Lesaffre E. Surgical strategies in esophageal carcinoma with emphasis on radical lymphadenectomy. Ann Surg 1992;216:583-90.
Discussion Dr. Toni Lerut (Leuven, Belgium). We also have been in favor of more radical resection and extensive lymph node dissection.In this respect, we have been recently reviewing our results for carcinoma of the thoracic esophagus in 198 patients who underwent a resection transthoracically. In the group of patients in whom we had the impressionat the end of the operation that a potential curative intervention was performed, the radical versus nonradical approach was compared, revealing results similar to those in your series with an overa1l5-year survival of 48% after radical resection, We have been using the TNM system for staging, which has the disadvantage of not taking into account the number of lymph nodes involved and therefore perhaps inadequately differentiates between early and advanced disease. In TNM staging, however, the distance between tumor and involved lymph node is considered as an important prognostic index for carcinoma of the gastroesophageal junction. In gastroesophageal junction tumors, celiac lymph nodes are N2 disease, which is a more favorable classificationthan in the distal esophagus, where the same lymph nodes are classified as distant metastases. This raises the question whether one may compare a tumor of the gastroesophagealjunction with a tumor of the distal esophagus. Therefore, gastroesophageal junction tumors and distal esophageal carcinoma are perhaps not the same disease, and I wonder whether survivalcurvesin the gastroesophagealjunction and distal esophagus were different. Second, we have begun performing bilateral cervical lymph node dissection for carcinoma of the esophagus and have seen that as many as 25% of patients with distal esophagealcarcinoma have diseased lymph nodes in the neck, which perhaps may explain, in part, the similar outcome in intermediate disease after en bloc and transhiatal resection. Third, it has been shown (e.g., within the GEEMO group) by a multicenter study led by Perrachia that there is no difference in morbidity and mortality between transthoracic and transhiatal resections. Given this fact and your survivalcurves,do you still believethat a patient over 75 years of age with an early stage carcinoma and with a forced expiratory volumeof, perhaps, 1.1 L should undergo a transhiatal resection rather than an en bloc resection? Finally, you said that age was not a discriminating factor and that there was no bias by age because all patients who died, died of recurrent disease. But I wonder whether a patient whois over 75 years old and who gets a recurrent disease is not going to die
The Journal of Thoracic and Cardiovascular Surgery Volume 106. Number 5
earlier because of concomitant diseases such as cardiovascular diseases or diabetes. Dr. Mark B. Orringer (Ann Arbor, Mich.). I do not agree with your conclusions. I am concerned that your series is highly selective and that the validity of your statistics must be influenced by this bias. In a nonrandomized fashion, you have compared a group of patients with localized esophageal cancer treated by extended esophagectomy with another group treated by transhiatal resection; 23 of these 39 latter patients had advanced disease. Your results then reflect more the influence of tumor stage on survival in these patients rather than the operation performed. When patients with operable esophageal cancer are truly randomized to different surgical techniques, as for example was the case with the recent presentation from the M. D. Anderson Hospital by Putnam and Roth at the Society of Thoracic Surgeons meeting, in which patients were randomized to transhiatal versus transthoracic resection, no real difference in survival could be found. I would like to ask you this question: Why do you believe that esophageal carcinoma is the only cancer in which the magnitude of resection is important in survival? We have moved away from radical resections for breast cancer after carefully controlled randomized studies compared survival after limited resection and radical mastectomy and found no advantage. We have similarly abandoned radical resections of most pancreatic cancers and melanomas. What is different about esophageal cancer that makes the bigger operation the better operation? Dr. Hagen. Dr. Lerut, in answer to your question regarding the inclusionof the gastroesophageal junction tumors with those of the lower esophagus, the survival curves for patients with adenocarcinoma, squamous cell carcinoma, and adenocarcima arising arising in Barrett's esophagus are essentially identical in our series. Their survival curves are virtually superimposable. With regard to your comments regarding cervical nodes, I would emphasize that our article deals with distal esophageal cancers. In our experience with en bloc esophagogastrectomy in these patients with lower third tumors, the presence of lymph nodes at the subcarinal or paratracheallevels was infrequent, except in those patients in whom there was advanced disease in the abdomen, with multiple node metastases at different sites. As a result, we do not perform routine cervical lymph node dissections. Your point, however, is well taken; that is, that the presence of cervical node disease could account for some of the local recurrences, especially in patients with intermediate stage of disease. For the most part, patients were in the intermediate stage because of the presence of more than four lymph node metastases rather than a transmural tumor with fewer than four lymph node metastases.
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Regarding your question whether we would perform this procedure (the en bloc esophagogastrectomy) in a patient who is over the age of 75 years and has significant pulmonary disease, in our experience, the operative mortality and morbidity are similar for the transhiatal and en bloc esophagogastrectomy. However, this may be related to the fact that we are carefully screening the patients before subjecting them to a more extensive operation. I think we sould still be reluctant to perform the en bloc esophagogastrectomy in an older patient with cardiopulmonary disease. With regard to Dr. Orringer's question about the possibility of a selection bias when using an algorithm that assigns the patients with advanced disease to the transhiatal esophagectomy group, I would agree that that could explain the difference if you take into consideration only the overall survival curves. When the groups are separated by the postoperative pathologic stage or when they are classified on the basis of our preoperative clinical assessment to have early disease, we have two groups of patients who have equivalent extent of disease. The only motivation to perform the transhiatal esophagectomy was the presence of advanced age or cardiopulmonary disease. Consequently, we considered the two groups, to the best of anyone's ability to determine, to have equivalent stage disease. This was also the point of the table that shows the postoperative pathologic stage in patients with clinically early stage disease. The majority of the patients who had a transhiatal esophagogastrectomy were found to have limited lymph node disease-15 of 16 patients-and nearly half had intramural tumors. As a result, I think the groups are comparable, and there was a survival advantage associated with the en bloc esophagogastrectomy. The same conditions existed in patients with early disease staged after the operation. These patients all had intramural tumors and limited lymph node disease. Any bias in selection for transhiatal esophagectomy, because of a clinical impression of advanced disease, is eliminated because these patients would be excluded from this particular analysis. Your final question was why we should consider esophageal cancer different from other cancers. I believe there still are cancers for which it is believed to be important to remove lymph node metastases. Cancer of the lung comes to mind. I do not believe that many surgeons would remove a lung cancer without sampling lymph nodes or at least removing obviously involved nodes. Thus, I do not believe it is correct to say that surgeons in general have completely abandoned the concept of aggressive operations for patients with cancer.
Superiority of extended en bloc esophagogastrectomy for carcinoma of the lower esophagus and cardia The belief that transhiatal esophagogastrectomy results in the same survival as a more extensive en bloc resection was tested in 69 patients with carcinoma in the distal esophagus and gastric cardia. Preoperative and intraoperative staging defined three distinct subgroups of patients. Those with apparently limited disease and good general health (group I, n = 30) underwent en bloc resection. Those with apparently limited disease but poor physiologic reserve (group II, n = 16) underwent transhiatal resection, as did those with evidence of more advanced disease (group III, n = 23). OveraU, survival was significantly better in the 30 patients who underwent en bloc resection (41 %) than in the 39 patients who underwent transhiatal resections (14%; p < 0.001, log-rank). Oinical staging showed apparently limited disease in 46 patients (groups I and 11). These groups differed only in the presence of poor physiologic reserve because the percentages of patients with tumors limited to the esophageal waD (group I 13/30, group II 6/16) and four or fewer lymph node metastases (group I 21/30, group II 15/16) at the time of pathologic staging were not significantly different. Survival after en bloc resection was, however, significantly better (41% versus 21 %; p < 0.05, log-rank). According to the WNM system of pathologic staging, 19 patients had early lesions defined as intramural lesions associated with four or fewer lymph node metastases, 26 had intermediate lesions defined as either transmural or associated with more than four lymph node metastases, and 24 had late lesions defined as both transmural and associated with fewer than four lymph node metastases. Survival was significantly better in patients with early lesions after en bloc resection compared with transhiatal resection (75 % versus 20%, p < 0.01), survival was also significantly better in patients with advanced lesions (27% versus 9%, p < 0.01). For intermediate lesions, the survival was similar (14% versus 20%), although the median survival after en bloc resection was longer (24 months versus 8 months). (J THoRAc CARDIOVASC SURG 1993;106:850-9)
Jeffrey A. Hagen, MD, Jeffrey H. Peters, MD (by invitation), and Tom R. DeMeester, MD, Los Angeles, Calif.
From the University of Southern California School of Medicine, Department of Surgery, Los Angeles, Calif. Read at the Seventy-third Annual Meeting of The American Association for Thoracic Surgery, Chicago, III., April 25-28, 1993. Address for reprints: Tom R. DeMeester, MD, University of Southern California School of Medicine, Department of Surgery, 1510 San Pablo St., Suite 514, Los Angeles, CA 90033-4612. Copyright w 1993 by Mosby-Year Book, Inc. 0022-5223/93 $1.00 +.10
850
12/6/49321
Current strategies for treatment of esophageal carcinoma limit the role of surgery to the removal of the primary tumor, with the hope that adjuvant therapy will increase cure rates by destroying systemic disease. This approach emphasizes the concept of biologic predeterminism; that is, the outcome of treatment in esophageal cancer is determined at the time of diagnosis, and surgical therapy aimed at removing more than the primary
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851
Length of tumor> 9 em on endoscopy Transmural invasion and obvious adenopathy on CT scan Unfavorable intraoperative evaluation (Figure 2) No
Yes
Age < 75, FEV, > 1.25, Adequate Cardiac Reserve
I
Yes
Transhiatal Esophagogastrectomy (n = 23)
No
En bloc Esophagogastrectomy (n = 30)
I
Transhiatal Esophagogastrectomy (n = 16)
Fig. 1. Algorithm of patient selection and procedure performed. CT, Computed tomographic; FEVj , forced expiratory volume in 1 second. Exploratory laparotomy
I
Inspect tumor, biopsy porta hepatis hepatic artery, and subpancreatic nodes
I
I
I
No evidence of wall penetration or lymph node involvement
Grossly evident wall penetration, and lymph node involvement
I I Right posterolateral thoracotomy I Inspect tumor, biopsy
I
Closure of abdomen
Transhiatal esophagogastrectomy
low paratracheal nodes
I
I
I
Grossly evident wall penetration, and lymph node involvement
Noevidence of wall penetration, or lymph node involvement
Simple esophagectomy
Enbloc dissection of esophagus
I I
I I
I
Re-open laparotomy incision
I Palliative case I Mobilize stomach for pullup for neck anastomosis
I
I
Curative case
I
En blocdissection of stomach, 2{3 proximal gastrectomy, mobilize colon for interposition to cervical esophagus
Fig. 2. Algorithm outlining surgical procedure and intraoperative decisions.
tumor is not helpful. Lymph node metastases are considered simply markers of systemic disease, and the systematic removal of involved nodes is not beneficial. Based on this concept is the belief that removal of the primary
tumor by transhiatal esophagogastrectomy results in the same survival as a more extensive en bloc resection. This belief was tested in the present study by comparing the outcome of extended en bloc esophagogastrectomy with
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Table I. Classification of esophageal carcinoma
Table III. Demographics
Wall penetration WO = Tumor penetration through the basement membrane of the mucosa but not through the muscularis mucosa WI = Tumor penetration through the muscularis mucosa and into but not through muscle layers W2 = Tumor penetration through muscle layers Lymph node involvement NO = No lymph node involvement N I = One to four lymph nodes involved N2 = Five or more lymph nodes involved Systemic metastasis MO = No metastasis M I = Distant metastasis
Groups Early
Subtotal Intermediate
Subtotal Late Subtotal Total
No. ofpatients
THE
WONO WONI WINO WINI
EBE I 0 5 4
1 0 5 3 9
WON2 WI N2 W2NO W2NI
10 0 0 6 8
14 W2N2 16 39
p
65.6 ± 1.7
59.8 ± 1.6
0.014
32/7
27/3
0.74 0.16
13 10 16 27/39 9/39
4 10 16 21/30 13/30
1.0 0.12
SCCA, Squamous cellcarcinoma. For other abbreviations, seeTableII.
THE Age ± standard error of mean Nodes ~4 Limited to wall
EBE
P
68.9 ± 2.6
59.8 ± 1.6
0.0026
15/16 6/16
21/30 13/30
0.063 1.0
For abbreviations, seeTableII. 0 3 2 7
12 16
Age ± standard error of mean Sex (M/F) Cell type SCCA Adenocarcinoma Barrett's esophagus Nodes ~4 Limited to wall
EBE
Table IV. Pathologic staging of tumors ofpatients who had limited disease at the time ofpreoperative clinical and intraoperative surgical evaluation
Table II. Staging WNM classification
THE
8 8 30
THE, Transhiatal esophagogastrectomy; ERE, en blocesophagogastrectomy.
transhiatal esophagogastrectomy for carcinoma of the distal esophagus and gastric cardia. Methods Study population. Between July 1983 and January 1992,69 patients underwent esophageal resection by the primary author (T. R. D.) for cancer of the distal esophagus or gastric cardia. Patients were excluded from the study if they had evidence of systemic metastatic disease or invasion of adjacent organs on assessment before operation or at the time of exploration. Preoperative chemotherapy had been given before referral in four patients. There were 17 patients with a squamous cell carcinoma, 20 with an adenocarcinoma of the cardia, and 32 with an adenocarcinoma in a Barrett's esophagus. Patient evaluation. The assessment of the extent of disease before operation included barium roentgenograms of the upper gastroesophageal tract, endoscopic examinations, and chest and abdominal computed tomographic scans. All patients had pulmonary function tests and a noninvasive assessment of cardiac function. The decision regarding the procedure to be performed was made according to the algorithm shown in Fig. 1. Patients who had early lesionson preoperative clinical and intraoperative surgical evaluation, who were under the ageof75 years, and who were free of significant cardiovascular or pulmonary disease
underwent extended en bloc esophagogastrectomy (n = 30). Transhiatal esophagogastrectomy was performed in patients with early lesions if they were over the age of 75 years or had significant cardiac or pulmonary disease (n = 16). Patients with advanced disease seen during preoperative clinical or intraoperative surgical evaluation underwent transhiatal esophagogastrectomy (n = 23). Operative approach. The operative procedure is summarized in Fig. 2. The operation begins with an abdominal exploration to assess the extent of the primary tumor and the regional node status. Ifthere was gross evidence of transmural extension of the tumor and multiple lymph node metastases or microscopic involvement of the porta hepatis or subpancreatic nodes, a transhiatal resection was done, and gastrointestinal continuity was reestablished with a cervical esophagogastrostomy.' In these patients, a systematic dissection of the lymph nodes along the hepatic, celiac, and splenic artery was performed, and as many paraesophageal and subcarinallymph nodes were removed as could safely be done with a transhiatal dissection. If the abdominal findings were favorable, the abdomen was closed, the patient was repositioned, and a right posterolateral thoracotomy was performed. An en bloc dissection of the intrathoracic esophagus was done in continuity with the adjacent low paratracheal, subcarinal, paraesophageal, and parahiatal lymph nodes. The block of tissue removed was bounded anteriorly by the membranous trachea and pericardium, laterally by the right and left pleural cavities, and posteriorly by the vertebral column and the aorta. After the completion of the thoracic dissection, the patient was turned again to the recumbent position, and the procedure was completed through the abdomen and an incision on the left side of the neck. The abdominal dissection entails en bloc removal of the proximal two thirds of the stomach, along with the greater omentum, the spleen, and the splenic artery with its associated nodes, a
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Hagen, Peters, DeMeester
Percent Alive 100%
80% 60%
.
..................... -+-......
40%
~~
.-_
20%
.......ESE
n=30
_~~
_. -. -- -tHE'
....
n~'39'
O%-+------.----,..-----,.-----,...------r-------,
o
10
20
30
50
40
60
Months 1 15 17
n
THE 39
p < 0.001 (Cox-Mantel)
EBE
30
2 3 15
3 1 9
4 1
4
5 1 2
Fig. 3. Survival probabilities calculated by Kaplan-Meier method according to type of procedure performed. EBE, En bloc esophagogastrectomy, THE, transhiatal esophagogastrectomy.
Percent Alive
100% ...... 80% -
K~'
60% .......-
ESE n = 30
40% -
H
THE n= 16
20% 0%
o
10
20
30
50
40
60
Months 2 3 4 5 2 1 1 1 EBE 30 17 15 9 4 2 n
1
THE 16 9
p < 0.05 (Cox-Mantel)
Fig. 4. Survival probabilities calculated by Kaplan-Meier method according to type of procedure performed in patients thought to have limited disease at time of preoperative clinical and intraoperative surgical evaluation. For abbreviations, see Fig. 3.
853
854
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Percent Alive
100% -
~
80%-
----
- . - - - - .. -
-""""'"
60% - " " " " " ' "
-
-
-
..-
ESE
-
--
.
n=10
-
40% - ..... - . . . . . . .. .. t-THE
- - . f--.. -
20% -
0%
n=9
--
-. --
-. -
.
-+----T'"'"""--~__,_----r_---_r---____,r----....,
o
10
20
30
40
60
50
Months 3
4
5
0 3
0
1
9
EBE
p < 0.025 (COX-Mantel)
2
6 0 0 10 8 7 5
n
TIIE
2
Fig. 5. Survival probabilities calculated by Kaplan-Meier method according to type of procedure performed in patients with early disease at time of pathologic classification of removed specimen. For abbreviations, see Fig. 3.
Percent Alive 100% -
80% -
60% .........
40% TH E
20% -
0%
n = 14
EBE n = 12
o
10
20
30
40
60
50
Months n
p
= 1.0
(Cox-Mantel)
1
2
3
4
5
THE 14 3 2 1 1 1 EBE 12 5 5 1 0 0
Fig. 6. Survival probabilities calculated by Kaplan-Meier method according to type of procedure performed in patients with intermediate disease at time of pathologic classification of removed specimen. For abbreviations, see Fig. 3.
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Hagen, Peters, DeMeester 855
Percent Alive 100%
80%
-
60% -
40%
t-
.,:....:
...-
-
20% 0%
-
EBE n = 8
I THE 1
o
10
20
n = 16
30
50
40
60
Months n
1
2
3
1HE 16 6 1 0 EBE 8 4 3 3
p < 0.05 (Cox-Mantel)
4 5 0 1
0 0
Fig. 7. Survival probabilities calculated by Kaplan-Meier method according to type of procedure performed in patients with late diseaseat time of pathologic classification of removed specimen. For abbreviations, see Fig. 3. systematic dissection of the lymphnodesaroundthe hepaticand celiac arteries, and the posterior peritoneal tissue from the esophageal hiatus downto the superiorborder of the pancreas. Gastrointestinal continuitywasreestablished withisoperistaltic colon interposition.I Postoperative staging. The specimens were examinedwith respect to the known prognostic indicators, that is,the extent of esophageal wall penetration and the presenceand location of lymph node spread.' Pathologic classification of the extent of disease wasdone according to the WNM systemadvocatedby Skinner and associates" (Table I). The patients' conditions were staged and separated into three categories: early, intermediate, andlate disease, as defined in Table II. Early lesions werethose in which the tumor was limited to the esophageal mucosa or muscle layers, withfour or fewerlymphnodemetastases. Intermediate lesions were thosewith either transmural invasion and four or fewer node metastases or those with nontransmural tumors with more advanced nodal disease. Late lesions were those with both transmural invasion and extensive (>4) node metastases. FoUow-up. All hospital survivors were followed-up at 3-month intervals forthe first3 yearsand then at every6 months with routine laboratory studies,a chest roentgenogram, and a chest and abdominalcomputedtomographic scan.All surviving patients wereeitherseenin personor contactedforfollow-up by telephone within3 monthsbeforethe preparationof thisarticle. Themedian follow-up timeof surviving patientswas 14months, with a range of I to 108 months. Statistical methods. Comparison of continuous variables was done by Student's t test. Fisher's exact test was used for comparison of proportions. Survival probabilities were calcu-
lated accordingto the method of Kaplan and Meier. Hospital deathswereincludedin allcalculations ofsurvival. Comparisons of survival between groups was performed with the log-rank method of Mantel and Cox.
Results Fig. 3 shows the survival analyses by type of procedure performed. En bloc esophagogastrectomy resulted in a 5-year survival of 40.6% with a median survival of 31 months. This was significantly better than survival after transhiatal esophagogastrectomy, for which the 5-year survival was 13.5% and the median survival was 11 months (x 2 = 10.15, p < 0.001). With the exception of age, no difference was found in the distribution of patient characteristics (including gender, cell types, depth of wall penetration, and extent of nodal metastases) between the two groups (Table III). Forty-six patients in the population studied had apparently limited disease at the time of preoperative clinical and intraoperative surgical evaluation. Thirty of these patients were in good health and underwent en bloc esophagogastrectomy. Sixteen had poor physiologic reserve and underwent transhiatal esophagogastrectomy. Their actuarial survival is shown in Fig. 4. En bloc esophagogastrectomy resulted in significantly better 5-year survival (41% versus 21%; x2 = 4.02, P < 0.05), despite
856
The Journal of Thoracic and Cardiovascular Surgery November 1993
Hagen, Peters, DeMeester
Percent Alive
100%
T
80%
1 ESE
..-
60%
......
40%
THE
20% 0%
o
n =13
~
10
n =9
20
30
50
40
60
Months 1 9 6 13 9 n
TIlE
p < 0.05 (Cox-Mantel)
EBE
2
3
4
5
0
0
0
0
8
5
3
2
Fig. 8. Survival probabilities calculated by Kaplan-Meier method according to type of procedure performed in patients with intramural tumors. For abbreviations, see Fig. 3.
the fact that postoperative pathologic staging showed that patients who underwent transhiatal esophagogastrectomy tended to have an earlier stage of disease (Table IV). Comparison of the actuarial survival after en bloc esophagogastrectomy and transhiatal esophagogastrectomy with regard to pathologic classification and stage of disease is shown in Figs. 5, 6, and 7. A clear survival advantage was observed in patients with early lesions after en bloc esophagogastrectomy, for which the 5-year survival was 75%. Survival was lower for intermediate and late lesions. Survivals after transhiatal esophagogastrectomy for early and intermediate disease were similar-19.8% and 21.0% at 2 years, respectively-and were not much better than the 8.6% for late disease. Because the depth of tumor penetration of the esophageal wall and the number of metastatic lymph nodes are the most important independent variables affecting survival, we compared survival with regard to the method of resection in patients with intramural tumors and with four or fewer metastatic lymph nodes (Figs. 8 and 9). A clear survival advantage was associated with en bloc esophagogastrectomy in patients with tumors limited to the esophageal wall (x 2 = 4.45,p < 0.05). The validity of this observation is underscored by the fact that the proportion of patients with four or fewer involved nodes was similar
in both groups (9/9 transhiatal esophagogastrectomy versus 10/13 en bloc esophagogastrectomy, p = 0.54). Comparison of survival in patients with four or fewer metastatic nodes also demonstrated a significant advantage for en bloc esophagogastrectomy (x 2 = 9.38, p < 0.005). The validity of this observation was underscored by the fact that the proportion of tumors limited to the esophageal wall was similar in both groups (9/27 transhiatal esophagogastrectomy versus 10/21 en bloc esophagogastrectomy; p = 0.38). The argument could be made that the previouslymentioned results are due to a staging bias, that is, less accurate lymph node staging was done in the patients who had a transhiatal resection. Because a similar abdominal lymph node dissection was performed in both procedures, we used the relationship between the pathologic characteristics of abdominal and thoracic lymph nodes in patients after an en bloc resection to support the adequacy of staging thoracic nodes in patients who underwent a transhiatal resection. Only one of the 22 patients who had four or fewer nodal metastases in the abdomen after en bloc esophagogastrectomy had evidence of lymph node metastases during the thoracic node dissection. This would strongly indicate that, when a thorough abdominal lymph node dissection shows four or fewer involvednodes,
The Journal of Thoracic and Cardiovascular Surgery Volume 106, Number 5
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857
Percent Alive 100%
rt
-1
80%
~ f-
>------<
60%
EBE n=21
40%
r--< ~
THE n= 27
20%
0%
o
10
20
30
50
40
60
Months
p < 0.005 (Cox-Mantel)
mE EBE
n 27 21
1 12 14
2 3 2 1 13 8
4 1 4
5 1 2
Fig. 9. Survival probabilities calculated by Kaplan-Meier method according to type of procedure performed in patients with four or fewer lymph node metastases. For abbreviations, see Fig. 3.
the thoracic nodes are free of metastases and the staging of early disease in patients after a transhiatal resection is dependable. We also investigated the possibility that the previously mentioned results were due to the fact that patients who underwent transhiatal resection were older, near the end of their life span, and would be more likely to die of physiologic causes than recurrent tumor. This supposition appears invalid because the hospital mortality for each procedure was similar (transhiatal esophagogastrectomy = 12.8%) en bloc esophagogastrectomy = 10%; P = 1.0) and the analysis of deaths occurring during the follow-up period showed that all patients, irrespective of the surgical procedure, died with recurrent disease. Discussion This study shows that for early cancers of the lower esophagus and cardia, en bloc esophagogastrectomy results in significantly better survival than does transhiatal esophagogastrectomy. This finding cannot be explained by a bias in the staging of disease, a difference in operative mortality, or death from causes other than tumor. Rather, improved survival appears to be due to the type of operation performed. The results in patients with
intermediate and advanced disease are less clear: a survival advantage was present with advanced disease but not with intermediate disease. We suspect that the explanation for this outcome is the imprecision in assigning a stage of esophageal cancer to patients or the evaluation of too few patients with intermediate disease. We have chosen to use the WNM system because it allows stratification of patients according to the number of lymph nodes involved, a factor shown to be important in survival.3,4 In contrast, the TNM system stratifies only on the basis of lymph node metastases being present or absent; consequently, the patients most apt to benefit from an en bloc esophagogastrectomy (i.e., those with limited nodal disease) are included with patients with more extensive nodal disease, obscuring any potential benefit. Orringer, Marshall, and Stirling' recently reviewed their results with transhiatal esophagogastrectomy for esophageal cancer. Patients with tumor confined to the submucosa and no lymph node involvement had a 5-year survival of 63%. Once lymph nodes were involved, the survival dropped to 38%. In contrast, our early disease group had a survival of 75% despite the inclusion of patients with tumor limited to the wall of the esophagus,
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some of whom also had four or fewer lymph node metastases (Table II). Several possible explanations exist for the failure of a transhiatal resection to achieve the results obtained with an en bloc resection in patients with favorable stage of disease. First, it is possible to disseminate tumor cells at the time of the blunt dissection of the thoracic esophagus. Second, an inadequate distal tumor margin may be accepted in an effort to preserve a full length of the stomach and the blood supply to it to reestablish gastrointestinal continuity with a cervical esophagogastrostomy. This inadequate margin can result in the development of recurrent disease along the gastric suture line," Third, unrecognized perigastric metastatic nodes are transferred into the thorax with the gastric pull-up. Fourth, it is possible that the transhiatal dissection leaves residual nodal metastasis in the mediastinum. An en bloc esophagogastrectomy effectively eliminates all of these potential causes of recurrence. Ideally, the question of which procedure is more beneficial should be resolved by a prospective randomized study, although several obstacles exist. The number of patients seen with early disease is small, and thus the accrual time would be long. In addition, preoperative staging is inaccurate and would make stratification by stage difficult. Finally, there is a moral problem for advocates of an en bloc esophagogastrectomy to, in good conscience, perform more limited resections. Until a randomized study is completed, support of an en bloc resection for early disease will depend on studies, such as the present and others.?'? that have demonstrated a benefit with this approach. On the basis of this experience, we conclude that survival after surgical removal of a carcinoma in the distal esophagus or cardia is dependent on the method of resection (i.e., transhiatal or en bloc esophagogastrectomy), and patients with early lesions have significantly better survival after extended en bloc resection.
REFERENCES 1. Orringer MB. Transhiatal esophagectomy without thoracotomy for carcinoma of the thoracic esophagus. Ann Surg 1984;200:282-8. 2. DeMeester TR, Zaninotto G, Johansson K-K. Selective therapeutic approach to cancer of the lower esophagus and cardia. J THORAC CARDIOVASC SURG 1988;95:42-54. 3. Skinner DB, Dowlatshahi KD, DeMeester TR. Potentially curable cancer of the esophagus. Cancer 1982;50:2571-5. 4. Skinner DB, Ferguson MK, Soriano A, Little AG, Staszak VM. Selection of operation for esophageal cancer based on staging. Ann Surg 1986;204:391-401. 5. Orringer MB, Marshall B, Stirling MC. Transhiatal esoph-
6. 7.
8.
9.
agectomy for benign and malignant disease. J THORAC CARDIOVASC SURG 1993;105:265-77. Wong J. Esophageal resection for cancer: the rationale of current practice. Am J Surg 1987;153:18-24. Akiyama H, Tsurumaru M, Kawanura T, Ono Y. Principles of surgical treatment for carcinoma of the esophagus:analysisoflymph node involvement. Ann Surg 1981;194:435-46. Skinner DB. En bloc resection for neoplasms of the esophagus and cardia. J THORAC CARDIOVASC SURG 1983;85:5971. Lerut T, DeLeyn P, Coosmans W, Van Raemdonck D, Scheys I, Lesaffre E. Surgical strategies in esophageal carcinoma with emphasis on radical lymphadenectomy. Ann Surg 1992;216:583-90.
Discussion Dr. Toni Lerut (Leuven, Belgium). We also have been in favor of more radical resection and extensive lymph node dissection.In this respect, we have been recently reviewing our results for carcinoma of the thoracic esophagus in 198 patients who underwent a resection transthoracically. In the group of patients in whom we had the impressionat the end of the operation that a potential curative intervention was performed, the radical versus nonradical approach was compared, revealing results similar to those in your series with an overa1l5-year survival of 48% after radical resection, We have been using the TNM system for staging, which has the disadvantage of not taking into account the number of lymph nodes involved and therefore perhaps inadequately differentiates between early and advanced disease. In TNM staging, however, the distance between tumor and involved lymph node is considered as an important prognostic index for carcinoma of the gastroesophageal junction. In gastroesophageal junction tumors, celiac lymph nodes are N2 disease, which is a more favorable classificationthan in the distal esophagus, where the same lymph nodes are classified as distant metastases. This raises the question whether one may compare a tumor of the gastroesophagealjunction with a tumor of the distal esophagus. Therefore, gastroesophageal junction tumors and distal esophageal carcinoma are perhaps not the same disease, and I wonder whether survivalcurvesin the gastroesophagealjunction and distal esophagus were different. Second, we have begun performing bilateral cervical lymph node dissection for carcinoma of the esophagus and have seen that as many as 25% of patients with distal esophagealcarcinoma have diseased lymph nodes in the neck, which perhaps may explain, in part, the similar outcome in intermediate disease after en bloc and transhiatal resection. Third, it has been shown (e.g., within the GEEMO group) by a multicenter study led by Perrachia that there is no difference in morbidity and mortality between transthoracic and transhiatal resections. Given this fact and your survivalcurves,do you still believethat a patient over 75 years of age with an early stage carcinoma and with a forced expiratory volumeof, perhaps, 1.1 L should undergo a transhiatal resection rather than an en bloc resection? Finally, you said that age was not a discriminating factor and that there was no bias by age because all patients who died, died of recurrent disease. But I wonder whether a patient whois over 75 years old and who gets a recurrent disease is not going to die
The Journal of Thoracic and Cardiovascular Surgery Volume 106. Number 5
earlier because of concomitant diseases such as cardiovascular diseases or diabetes. Dr. Mark B. Orringer (Ann Arbor, Mich.). I do not agree with your conclusions. I am concerned that your series is highly selective and that the validity of your statistics must be influenced by this bias. In a nonrandomized fashion, you have compared a group of patients with localized esophageal cancer treated by extended esophagectomy with another group treated by transhiatal resection; 23 of these 39 latter patients had advanced disease. Your results then reflect more the influence of tumor stage on survival in these patients rather than the operation performed. When patients with operable esophageal cancer are truly randomized to different surgical techniques, as for example was the case with the recent presentation from the M. D. Anderson Hospital by Putnam and Roth at the Society of Thoracic Surgeons meeting, in which patients were randomized to transhiatal versus transthoracic resection, no real difference in survival could be found. I would like to ask you this question: Why do you believe that esophageal carcinoma is the only cancer in which the magnitude of resection is important in survival? We have moved away from radical resections for breast cancer after carefully controlled randomized studies compared survival after limited resection and radical mastectomy and found no advantage. We have similarly abandoned radical resections of most pancreatic cancers and melanomas. What is different about esophageal cancer that makes the bigger operation the better operation? Dr. Hagen. Dr. Lerut, in answer to your question regarding the inclusionof the gastroesophageal junction tumors with those of the lower esophagus, the survival curves for patients with adenocarcinoma, squamous cell carcinoma, and adenocarcima arising arising in Barrett's esophagus are essentially identical in our series. Their survival curves are virtually superimposable. With regard to your comments regarding cervical nodes, I would emphasize that our article deals with distal esophageal cancers. In our experience with en bloc esophagogastrectomy in these patients with lower third tumors, the presence of lymph nodes at the subcarinal or paratracheallevels was infrequent, except in those patients in whom there was advanced disease in the abdomen, with multiple node metastases at different sites. As a result, we do not perform routine cervical lymph node dissections. Your point, however, is well taken; that is, that the presence of cervical node disease could account for some of the local recurrences, especially in patients with intermediate stage of disease. For the most part, patients were in the intermediate stage because of the presence of more than four lymph node metastases rather than a transmural tumor with fewer than four lymph node metastases.
Hagen, Peters, DeMeester
859
Regarding your question whether we would perform this procedure (the en bloc esophagogastrectomy) in a patient who is over the age of 75 years and has significant pulmonary disease, in our experience, the operative mortality and morbidity are similar for the transhiatal and en bloc esophagogastrectomy. However, this may be related to the fact that we are carefully screening the patients before subjecting them to a more extensive operation. I think we sould still be reluctant to perform the en bloc esophagogastrectomy in an older patient with cardiopulmonary disease. With regard to Dr. Orringer's question about the possibility of a selection bias when using an algorithm that assigns the patients with advanced disease to the transhiatal esophagectomy group, I would agree that that could explain the difference if you take into consideration only the overall survival curves. When the groups are separated by the postoperative pathologic stage or when they are classified on the basis of our preoperative clinical assessment to have early disease, we have two groups of patients who have equivalent extent of disease. The only motivation to perform the transhiatal esophagectomy was the presence of advanced age or cardiopulmonary disease. Consequently, we considered the two groups, to the best of anyone's ability to determine, to have equivalent stage disease. This was also the point of the table that shows the postoperative pathologic stage in patients with clinically early stage disease. The majority of the patients who had a transhiatal esophagogastrectomy were found to have limited lymph node disease-15 of 16 patients-and nearly half had intramural tumors. As a result, I think the groups are comparable, and there was a survival advantage associated with the en bloc esophagogastrectomy. The same conditions existed in patients with early disease staged after the operation. These patients all had intramural tumors and limited lymph node disease. Any bias in selection for transhiatal esophagectomy, because of a clinical impression of advanced disease, is eliminated because these patients would be excluded from this particular analysis. Your final question was why we should consider esophageal cancer different from other cancers. I believe there still are cancers for which it is believed to be important to remove lymph node metastases. Cancer of the lung comes to mind. I do not believe that many surgeons would remove a lung cancer without sampling lymph nodes or at least removing obviously involved nodes. Thus, I do not believe it is correct to say that surgeons in general have completely abandoned the concept of aggressive operations for patients with cancer.