Annals of Surgical Oncology Cite Track
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10.1245/ASO.2006.02.023
Annals of Surgical Oncology 13:340-346 (2006)
© 2006 Society of Surgical Oncology
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Original Article

Pathologic Nodal Status Predicts Disease-Free Survival After Neoadjuvant Chemoradiation for Gastroesophageal Junction Carcinoma

Jeffrey G. Gaca, MD1, Rebecca P. Petersen, MD, MSc1, Bercedis L. Peterson, PhD2, David H. Harpole, Jr., MD1, Thomas A. D’Amico, MD1, Theodore N. Pappas, MD1, Hilliard F. Seigler, MD1, Walter G. Wolfe, MD1 and Douglas S. Tyler, MD1

1 Departments of Surgery, Duke University Medical Center, Box 3118, Durham, North Carolina 27710
2 Departments of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina 27710

Correspondence: Address correspondence and reprint requests to: Douglas S. Tyler, MD; E-mail: tyler002{at}acpub.duke.edu.


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Background: The incidence of carcinoma of the gastroesophageal junction (GEJ) is rapidly increasing, and the prognosis remains poor. We examined outcomes in patients who received neoadjuvant chemoradiation for GEJ tumors to identify factors that predict disease-free (DFS) and overall (OS) survival.

Methods: A retrospective analysis was performed of 101 consecutive patients who received chemoradiation and surgery for GEJ carcinoma between 1992 and 2001.

Results: The median DFS and OS of all patients were 16 and 25 months, respectively. Twenty-eight patients with a complete histological response (T0N0) experienced greater DFS compared with all others (P =.02). Node-negative patients, regardless of T stage, experienced improved median DFS (24 months) compared with N1 patients (9 months; P = .01). Preoperative stage, age, tumor location, or Barrett’s esophagus did not independently predict OS by univariate analysis. Multivariate analysis demonstrated that only posttreatment nodal status (P = .03)—not the degree of primary tumor response—predicted DFS.

Conclusions: The nodal status of patients with GEJ tumors after neoadjuvant therapy is predictive of DFS after resection. The poor outcome in node-positive patients supports postneoadjuvant therapy nodal staging, because surgical aggressiveness should be tempered by the realization that cure is unlikely and median survival is short.

Key Words: Gastroesophageal junction • Carcinoma • Chemotherapy • Radiation


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
In contrast to the relatively stable incidence of squamous cell carcinoma of the esophagus and adenocarcinoma of the distal stomach, the incidence of neoplasms of the gastroesophageal junction (GEJ) is rapidly increasing.1–3 Despite the increasing incidence, the overall prognosis is poor, with 5-year survival rates of approximately 15%.4,5 Because of the poor prognosis, multiple different treatment regimens have attempted to improve survival, including the addition of chemotherapy and radiotherapy before surgical resection. Overall, however, multimodal therapy has not been conclusively shown to improve survival compared with surgery alone.6–9 Despite the lack of a proven overall benefit, improved survival rates have been observed in the subset of patients who have a complete pathologic response to neoadjuvant chemoradiation.6,10 As a result, numerous phase II studies are currently evaluating the efficacy of neoadjuvant therapy for patients with esophageal cancer.

Our institution began using neoadjuvant therapy for esophageal carcinoma in 1984.11,12 This study updates our experience with multimodality therapy for carcinoma of the GEJ treated since 1992. The purpose of this study was to identify factors that affect overall survival (OS) and disease-free survival (DFS) in patients receiving multimodality therapy for GEJ carcinoma.


   PATIENTS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Patients
Between July 1992 and February 2001, 101 consecutive patients with carcinoma of the GEJ received neoadjuvant chemoradiation followed by surgical resection at Duke University Medical Center. GEJ carcinoma was defined as a tumor within 5 cm of the GEJ, as determined by endoscopy. A retrospective chart review identified the cohort of patients who form the basis of this study.

Patient characteristics are listed in Table 1Go. The median age of patients in this study was 59 years, with 91 men and 10 women. Adenocarcinoma of the GEJ was the predominant diagnosis (96 of 101), with 5 squamous cell carcinomas. Most tumors were located in the distal esophagus (88 of 101), compared with the gastric cardia (13 of 101). Forty-two patients presented with a history of Barrett’s esophagus.


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  		TABLE 1. Patient characteristics (n = 101)
 
Preoperative Staging
Before beginning induction therapy, all patients underwent a metastatic screen that included chest, abdominal, and pelvic computed tomography. The local tumor stage was determined by using endoscopic ultrasonography in 39 patients (38%; Table 1Go). Twenty-six patients (25%) received a jejunostomy tube for enteral support before beginning neoadjuvant therapy.

Neoadjuvant Therapy
Neoadjuvant therapy consisted of combined chemoradiation in all patients. Most patients (69%) received three cycles of 5-fluorouracil (5-FU; 225 mg/m2) and cis-platinum (20 mg/m2; continuous infusion). Alternative chemotherapeutic regimens included three cycles of 5-FU (225 mg/m2), carboplatinum (AUC 5 [target dose for concentration versus time curve was 5 mg/ml/min]), and paclitaxel (135 mg/m2) in 29 patients. Two patients received three cycles of 5-FU (225 mg/m2) alone or in combination with doxorubicin and methotrexate. Radiotherapy began the first day of chemotherapy and was administered five times per week with a daily fraction of 180 cGy. Twenty-five treatments were delivered to a total dose of 45 Gy.

Surgical Therapy
Surgical treatment was performed 4 to 8 weeks after the completion of neoadjuvant chemoradiation. Surgical approaches included Ivor-Lewis, left thoracoabdominal, transhiatal, and transabdominal esophagogastrectomies (Table 2Go). Staging of the patients was performed according to the postoperative pathology report by using the tumor-node-metastasis system. OS, DFS, and recurrence were entered into a database.


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  		TABLE 2. Operative procedures (n = 101)
 
Statistical Analysis
The Kaplan-Meier method was used to plot OS and DFS for the entire sample. OS and DFS medians were presented with 95% confidence intervals (CIs), both for the entire sample and for subgroups of the sample. OS for each patient was calculated as the time from the date of diagnosis to the date of death from any cause (patients still alive at the time of analysis were censored at the date last seen alive). DFS was calculated as the time from the date of surgery to the date of recurrence or death, whichever came first (patients not yet relapsed at time of death or analysis were censored at that point).

The proportional hazards model was used to test the association of predictor variables with OS and DFS. The predictors of OS considered were preoperative stage, preoperative nodal (N) status, tumor location (cardia vs. esophagus), Barrett’s esophagus, and age at diagnosis. The predictors of DFS were age, stage at diagnosis, nodal status at diagnosis, Barrett’s esophagus, paclitaxel-based chemotherapy, posttreatment nodal status, and pathologic tumor (T) and N status. Preoperative stage and pathological T stage were tested as continuous variables by scoring the stages with equally spaced integers. Both of these variables, as well as age, were tested in the proportional hazards model as linear effects after first verifying with plots that a linear effect was a good fit. All predictors were tested as univariate associations. Additionally, pathologic T and N stage were tested together in the same model. Finally, results from the proportional hazards models were summarized by giving hazard ratios along with their 95% CIs. A two-sided type I error rate of .05 was used for all tests.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Results of Surgery
Complete resection of gross tumor was possible in all patients. Microscopically positive tumor margins were present in 8% of patients (9 of 101) at the proximal, distal, or radial margins. Of these nine patients, three patients had positive distal margins, one had a positive proximal margin, two had radial margins, and three had microscopic tumors at both the proximal and radial margins. In two patients, distant tumor nodules were present in the liver (n = 1) and lung (n = 1) at the time of resection. The lung nodule was an adenocarcinoma of a different histological pattern and was thought to be a primary lesion. There were no intraoperative deaths. In-hospital or 30-day mortality (whichever was longer) was 2.9% (3 of 101). One patient died of a pulmonary embolus, and two patients died from complications related to anastomotic leaks. There were no local recurrences; however, one patient did develop high-grade dysplasia in Barrett’s esophagus that necessitated re-resection and replacement with a colonic inter-position graft.

OS and DFS
For all patients, the median OS was 25 months (95% CI, 19–34 months; Fig. 1Go), and the median DFS was 16 months (95% CI, 11–41 months; Fig. 2Go). A complete histological response was defined as no residual tumor or involved regional lymph nodes. Twenty-eight patients (27%) had a complete histological response (T0N0), with a median DFS of 50 months (Table 3Go). In the other groups of patients, the median DFS by pathologic stage was as follows: stage I (n = 7), 35 months; stage IIa (n = 29), 16 months; stage IIb (n = 15), 8 months; and stage III (n = 21), 10 months. In a small subset of seven patients who had complete primary tumor responses but had positive regional lymph nodes at the time of resection (T0N1), the median DFS was 8 months. Comparing the DFS of patients by pathologic stage confirmed the advantage of complete pathologic response because stage 0 (T0N0) patients experienced a longer DFS survival compared with all other patients (P = .02).


Figure 1
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  		FIG. 1. Overall survival after multimodality therapy (n = 101). The median overall survival in all patients was 25 months (solid line) (95% confidence interval, 19–34 months, dotted lines).

 

Figure 2
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  		FIG. 2. Disease-free survival after multimodality therapy (n = 101). The median disease-free survival in all patients was 16 months (solid line) (95% confidence interval, 11–41 months, dotted lines).

 

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  		TABLE 3. Median disease-free survival by pathologic stage (n = 101)
 
Results of Univariate and Multivariate Analysis
Factors that affected OS and DFS were assessed by univariate and multivariate analyses. In univariate analysis, no variables were significantly associated with OS (Table 4Go). When factors predictive of DFS were analyzed, however, only pathologic N status (P = .01) and pathologic T status (P = .05) were significantly associated with DFS (Table 4Go). When these variables were tested by multivariate analysis, pathologic N status was the only significant predictor of DFS (P = .03; Table 4Go).


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  		TABLE 4. Hazard ratios for overall survival and disease-free survival
 
DFS by Nodal Status
The importance of pathologic nodal status was confirmed when the DFS of the patients who were node positive at resection (N1) was compared with that of those who were node negative (N0). Node-negative patients, regardless of T status, experienced a longer DFS (median, 24 months; 95% CI, 14–88 months) compared with those who were node positive (median, 9 months; 95% CI, 6–23 months; P = .01; Fig. 3Go).


Figure 3
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  		FIG. 3. Disease-free survival by pathologic nodal status. The median disease-free survival in node-negative patients (n = 65; solid line) was 24 months. Node-positive patients (n = 36; dotted line), in contrast, had a median disease-free survival of 9 months (P = .01).

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
CONCLUSIONS
 REFERENCES
 
In this study, we defined tumors of the GEJ as neoplasms within 5 cm of the anatomical junction between the esophagus and stomach.13 Despite the rapid increase in the incidence of GEJ carcinoma, controversy exists about whether these tumors are of gastric or esophageal origin.14,15 They are considered separate entities by the American Joint Committee on Cancer, which classifies carcinoma of the gastric cardia as gastric cancer and carcinoma of the distal 8 cm of the esophagus as esophageal cancer.16 Mounting evidence exists that tumors of gastric cardia and distal esophagus share a common etiology, epidemiology, pathology, and natural history. 17,18 As a result, revisions to the current staging system of esophageal cancer have been proposed to more accurately stage GEJ neoplasms.19 In this study, all nodal disease detected in the resected specimen was designated as N1 disease. For tumors involving the gastric cardia, this included perigastric nodes, nodes of the greater and lesser curvature, and celiac nodes. In contrast, the nodes resected for tumors of the distal esophagus involved the mediastinal and perigastric nodes but excluded the celiac nodes.

Despite the controversy in the proper staging of esophageal and GEJ carcinoma, these tumors are often included together in studies evaluating patient survival. Historically, therapy for tumors of the esophagus and GEJ has consisted of surgery alone. Five-year survivals from surgery alone have approached 80% for stage I tumors.20 Unfortunately, most patients present at an advanced stage, and 3- year survival from surgery alone for cancer of the esophagus and GEJ in randomized trials has not exceeded 26%.6–8 Because of the poor prognosis with surgery alone, attempts to improve survival from esophageal carcinoma have included neoadjuvant chemotherapy with or without radiotherapy before surgery for locally advanced tumors. This approach has been applied in other tumors, such as those of the pancreas21,22 and rectum.23 The theoretical advantages of multimodality therapy include the following: (1) larger tumors may be downstaged, (2) radiotherapy is more effective in well-oxygenated tissues, (3) surgical complications may delay or prevent the completion of adjuvant therapy, and (4) the primary tumor and the surrounding nodes are sterilized (complete response). Despite these theoretical advantages, multimodality therapy has not been conclusively demonstrated to improve survival from esophageal or GEJ neoplasms.6,8

In our series, 28 patients (27%) achieved a complete pathologic response from preoperative chemoradiation and experienced greater DFS compared with all other patients. This rate of complete response is consistent with rates reported by Walsh et al.8 (25%) and Urba et al.6 (28%) in previous randomized trials that evaluated multimodality therapy. Our series, consisting solely of GEJ carcinoma, demonstrated that residual pathologic nodal disease, regardless of T stage, was a predictor of decreased DFS (median DFS, 9 months) compared with patients without nodal disease (median DFS, 24 months).

Previous studies have considered GEJ and esophageal carcinoma together when evaluating multimodality therapy. Urba et al.6 reported on 43 patients with adenocarcinoma (75%) or squamous cell carcinoma (25%) of the esophagus treated with multimodality therapy. In this study, nodal involvement did not independently predict survival. In another study, Swans on et al.24 reported on 342 patients with esophageal carcinoma (68% adenocarcinoma and 31% squamous), of whom 81% received multimodality therapy. Multivariate analysis demonstrated that age >65 years, postoperative lymph node involvement, and postoperative tumor status were predictors of survival. The initial report from our own institution’s experience with multimodality therapy for esophageal carcinoma demonstrated a survival advantage for patients with Barrett’s esophagus.12 The survival advantage was attributed to the effect of endoscopic surveillance permitting earlier diagnosis and treatment. This current series, however, did not demonstrate a survival advantage in patients with Barrett’s esophagus. This difference most likely results from our current practice of offering surgery alone to patients with high-grade dysplasia or early-stage cancer (stage I). Therefore, the current study group consisted of intermediate-stage (IIa and IIb) and late-stage (III and IV) patients.

In view of an extremely poor prognosis in node-positive patients, increased efforts to develop restaging modalities after chemoradiation in an attempt to identify those who would benefit the least from surgical resection seem warranted. This issue was examined in a study by Alexander et al.25 who treated 34 patients with stage III esophageal cancer with preoperative chemoradiation. These patients underwent restaging with endoscopy, endoscopic ultrasonography, and computed tomographic scan before surgery. The authors found that restaging with these modalities overestimated the number of complete responders by 2-fold when compared with the pathologic stage. In addition, this study also demonstrated the importance of pathologic nodal status: 57% of node-negative patients were alive at 36 months, compared with 0% of node-positive patients.

Positron emission tomography scanning in esophageal cancer has also been evaluated for use as a restaging tool26; however, the ability to evaluate small nodes remains in question. Recent advances in radiographical modalities such as positron emission tomography/computed tomography and noninvasive surgical techniques offer future promise; however, the optimal method of restaging for esophageal cancer is clearly not yet established and warrants further investigation.


   CONCLUSIONS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
REFERENCES
 
This study has demonstrated the importance of pathologic nodal status after chemoradiation and surgery for esophageal cancer and identified a subgroup of patients with a poor prognosis after surgical resection. The value of aggressive surgical resection in these patients must be tempered by the realization that cure is unlikely and median DFS is short. Future approaches in managing GEJ tumors include developing novel treatment strategies and optimizing imaging and staging technologies. For example, several immunohistochemical markers (P-gp, p53, c-erb B2, and transforming growth factor {alpha}) have been demonstrated to have prognostic value in esophageal cancer.27,28 Therefore, the optimal strategy for staging (and restaging) tumors of the GEJ and esophagus may involve a combination of imaging with immunohistochemical and/or molecular markers.


   FOOTNOTES
 
Presented at the 43rd Annual Meeting of the Society for Surgery of the Alimentary Tract, San Francisco, California, May 19–22, 2002.

Received for publication February 23, 2004. Accepted for publication September 22, 2005.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 

  1. Blot WJ, Devesa SS, Kneller RW, Fraumeni JF Jr. Rising incidence of adenocarcinoma of the esophagus, gastric cardia. JAMA 1991; 265:1287–9.[Abstract]
  2. Pera M, Cameron AJ, Trastek VF, Carpenter HA, Zinsmeister AR. Increasing incidence of adenocarcinoma of the esophagus, esophagogastric junction. Gastroenterology 1993; 104:510–3.[Medline]
  3. Wright CD, Mathisen DJ, Wain JC, et al. Evolution of treatment strategies for adenocarcinoma of the esophagus and gastroesophageal junction. Ann Thorac Surg 1994; 58:1574–8.[Abstract]
  4. Lund O, Hasenkam JM, Aagaard MT, Kimose HH. Timerelated changes in characteristics of prognostic significance in carcinomas of the oesophagus and cardia. Br J Surg 1989; 76:1301–7.[Medline]
  5. Papachristou D, Fortner JG. Adenocarcinoma of the gastric cardia: the choice of gastrectomy. Ann Surg 1980; 192:58–64.[Medline]
  6. Urba S, Orringer MB, Turrisi A, Iannetoni M, Forastiere A, Strawderman M. Randomized trial of preoperative chemoradiation versus surgery alone in patients with locoregional esophageal carcinoma. J Clin Oncol 2001; 19:305–13.[Abstract/Free Full Text]
  7. Kelson D, Ginsburg R, Pajak TF, et al. Chemotherapy followed by surgery compared to surgery alone for localized esophageal cancer. N Engl J Med 1998; 339:1979–84.[Abstract/Free Full Text]
  8. Walsh T, Noonan N, Hollywood D, Kelly A, Keeling N, Hennessy TPJ. A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med 1996; 335:462–7.[Abstract/Free Full Text]
  9. Nygaard K, Hagen S, Hansen HS, et al. Pre-operative radiotherapy prolongs survival in operable esophageal carcinoma: a randomized, multicenter study of pre-operative radiotherapy and chemotherapy. The second Scandinavian trial in esophageal cancer. World J Surg 1992; 16:1104–9.[CrossRef][Medline]
  10. Law S, Fok M, Chow S, Chu KM, Wong J. Preoperative chemotherapy versus surgical therapy alone for squamous cell carcinoma of the esophagus: a prospective randomized trial. J Thorac Cardiovasc Surg 1997; 114:210–7.[Abstract/Free Full Text]
  11. Wolfe WG, Burton GV, Seigler HF, Crocker IR, Vaughn AL. Early results with combined modality therapy for carcinoma of the esophagus. Ann Surg 1987; 205:563–71.[Medline]
  12. Wolfe WG, Vaughn AL, Seigler HF, Hathorn JW, Leopold KA, Duhaylongsod FG. Survival of patients with carcinoma of the esophagus treated with combined-modality therapy. J Thorac Cardiovasc Surg 1993; 105:749–55.[Abstract]
  13. Siewert JR, Stein HJ. Carcinoma of the cardia: carcinoma of the gastroesophageal junction—classification, pathology, and extent of resection. Dis Esoph 1996; 9:173–82.
  14. Steup WH, De Leyn P, Deneffe G, Van Raemdonck D, Coosemans W, Lerut T. Tumors of the esophagogastric junction. Long-term survival in relation to the pattern of lymph node metastasis and a critical analysis of the accuracy or inaccuracy of pTNM classification. J Thorac Cardiovasc Surg 1996; 111:85–94.[Abstract/Free Full Text]
  15. Wijnhoven BP, Siersema PD, Hop WC, Dekken H, Tilanus HW. Adenocarcinomas of the distal oesophagus and gastric cardia are one clinical entity. Rotterdam Oesophageal Tumour Study Group. Br J Surg 1999; 86:529–35.[CrossRef][Medline]
  16. American Joint Committee on Cancer. Manual for Staging of Cancer. 5th ed. Philadelphia: JB Lippincott, 1997.
  17. Kalish RJ, Clancy PE, Orringer MB, Appelman HD. Clinical, epidemiologic, and morphologic comparison between adenocarcinomas arising in Barrett’s esophageal mucosa and in the gastric cardia. Gastroenterology 1984; 86:461–7.[Medline]
  18. Mendes de Almeida JC, Chaves P, Pereira AD, Altorki NK. Is Barrett’s esophagus the precursor of most adenocarcinomas of the esophagus and cardia? A biochemical study. Ann Surg 1997; 226:725–35.[CrossRef][Medline]
  19. Korst RJ, Rusch VW, Venkatraman E, et al. Proposed revision of the staging classification for esophageal cancer. J Thorac Cardiovasc Surg 1998; 115:660–9.[Abstract/Free Full Text]
  20. Entwsitle J, Goldberg M. Multimodality therapy for resectable cancer of the esophagus. Ann Thorac Surg 2002; 73:1009–15.[Abstract/Free Full Text]
  21. Evans DB, Rich TA, Byrd DR, et al. Preoperative chemoradiation and pancreatoduodenectomy for adenocarcinoma of the pancreas. Arch Surg 1992; 127:1335–9.[Abstract]
  22. Hoffman JP, Weese JL, Solin LJ, et al. A pilot study of preoperative chemoradiation for patients with localized adenocarcinoma of the pancreas. Am J Surg 1995; 169:71–7.[CrossRef][Medline]
  23. Higgins GA, Humphrey EW, Dwight RW, Roswit B, Lee LE Jr, Keehn RJ. Preoperative radiation and surgery for cancer of the rectum. Veterans Administration Surgical Oncology Group Trial II. Cancer 1986; 58:352–9.[CrossRef][Medline]
  24. Swanson SJ, Batirel HF, Bueno R, et al. Transthoracic esophagectomy with radical mediastinal and abdominal lymph node dissection and cervical esophagogastrostomy for esophageal carcinoma. Ann Thorac Surg 2001; 72:1918–24.[Abstract/Free Full Text]
  25. Alexander EP, Lipman T, Harmon J, Wadleigh R. Aggressive multimodality therapy for stage III esophageal cancer: a phase I/II study. Ann Thorac Surg 2000; 69:363–8.[Abstract/Free Full Text]
  26. Couper GW, McAteer D, Wallis F, et al. Detection of response to chemotherapy using positron emission tomography in patients with oesophageal and gastric cancer. Br J Surg 1998; 85:1403–6.[CrossRef][Medline]
  27. Aloia TA, Harpole DH Jr, Reed CE, et al. Tumor marker expression is predictive of survival in patients with esophageal cancer. Ann Thorac Surg 2001; 72:859–66.[Abstract/Free Full Text]
  28. Duhaylongsod FG, Gottfried MR, Iglehart JD, Vaughn AL, Wolfe WG. The significance of c-erb B-2 and p53 immunoreactivity in patients with adenocarcinoma of the esophagus. Ann Surg 1995; 221:677–83.[Medline]




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