Annals of Surgical Oncology Cite Track
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
10.1245/s10434-006-9141-6
Annals of Surgical Oncology 14:954-959 (2007)
© 2007 Society of Surgical Oncology
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Prenzel, K. L.
Right arrow Articles by Hölscher, A. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Prenzel, K. L.
Right arrow Articles by Hölscher, A. H.

Original Article

Reduced Incidence of Nodal Micrometastasis after Major Response to Neoadjuvant Chemoradiation in Locally Advanced Esophageal Cancer

Klaus L. Prenzel, MD1,6, Alexandra König, MD2, Paul M. Schneider, MD1, Christian Schnickmann, MD1, Stephan E. Baldus, MD3, Wolfgang Schröder, MD1, Elfriede Bollschweiler, MD1, Hans P. Dienes, MD4, Rolf P. Mueller, MD5, Jakob R. Izbicki, MD2 and Arnulf H. Hölscher, MD1

1 Department of Visceral and Vascular Surgery, University of Cologne, Cologne, Germany
2 Department of General Surgery, University of Hamburg, Hamburg, Germany
3 Institute of Pathology, University of Duesseldorf, Duesseldorf, Germany
4 Institute of Pathology, University of Cologne, Cologne, Germany
5 Department of Radiation Oncology, University of Cologne, Cologne, Germany
6 Department of Visceral and Vascular Surgery, University of Cologne, Joseph-Stelzmann-Str. 9, 50931, Cologne, Germany

Correspondence: Address correspondence and reprint requests to: Klaus L. Prenzel, MD; Department of Visceral and Vascular Surgery, University of Cologne, Joseph-Stelzmann-Str. 9, 50931, Cologne, Germany; E-mail: Klausprenzel{at}hotmail.com


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: Neoadjuvant treatment modalities for esophageal cancer were developed to improve local tumor control as well as to reduce lymph node metastases and distant metastases in patients with locally advanced esophageal cancer. The influence on nodal micrometastasis has not yet been evaluated.

Methods: This study includes 52 patients with localized (cT2-4, Nx, M0) esophageal cancers (21 adenocarcinomas, 31 squamous cell cancers) who received neoadjuvant chemoradiation (36Gy, 5-FU, cisplatin) followed by transthoracic en bloc esophagectomy with two field lymphadenectomy. The extent of histomorphologic regression was categorized into major (< 10%) and minor response (>10% vital residual tumor cells) as recently reported. A total of 1186 lymph nodes were diagnosed as negative for metastases by routine histopathological analysis and were further examined for the presence of isolated tumor cells with the monoclonal anti-epithelial antibody AE1/AE3.

Results: Twenty-two tumors (42.3%) showed a major histopathologic response whereas in 30 tumors (57.7%) only a minor response was present.

Of 32 patients with a pN0 category, major response was present in 19 (59.4%) tumors, whereas 13 (40.6%) tumors showed minor response. Nine (69%) out of 13 patients with minor response had AE1/AE3-positive cells in their lymph nodes, whereas only four (21%) out of 19 pN0-patients with major response showed nodal micrometastasis (P = 0.013, {chi}2-test).

Conclusions: If tumors show a major histomorphologic response following neoadjuvant chemoradiation, the presence of nodal micrometastasis is significantly reduced compared to those with minor response.

Key Words: Esophageal cancer • Nodal micrometastasis • Neoadjuvant therapy


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Esophageal cancer is an aggressive tumor with a dismal prognosis. In recent years, the postoperative mortality has declined and rates of complete resection have improved, but the reported 5-year survival rates only range from 15% to 39% after potentially curative surgery.1 A main reason for this poor prognosis after complete resection of localized primary lesions is early metastatic relapse due to disseminated tumor cells.2,3 Therefore, neoadjuvant treatment strategies were developed to improve survival with the presumed advantages of reducing the tumor size and clearing of metastases and micrometastases in regional lymph nodes and distant organs. Results from phase III randomized trials are encouraging; however, it was shown that only patients with complete major histopathological response will potentially benefit from treatment.4–6 The coauthors of this paper recently reported a refined objective prognostic response classification system based on the extent of histomorphologic tumor regression and presence of lymph node metastases.7 Non-pretreated patients with histologically nodal negative esophageal cancer (pN0), but immunohistochemically detected tumor cells in their lymph nodes, have an unfavorable prognosis compared to patients without nodal micrometastasis.2 Additional evidence for the malignant potential of micrometastatic cancer cells was provided by establishing a cell line derived from immunohistochemically detected tumor cells, which shares the same cytogenetic characteristics than the primary tumor.8 The purpose of this study was to assess the effect of radiation and simultaneous cisplatin (CDDP), 5-fluorouracil (5-FU) therapy on nodal micrometastases in patients with locally advanced resectable esophageal cancer.


   PATIENTS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Study Population, Demographic Data and Neoadjuvant Therapy
Patients were recruited from a prospective observation trial between July 1996 and August 2003 as recently reported.7 Paraffin embedded material for evaluation of the presence of disseminated nodal tumor cells was available from 52 patients who received neoadjuvant chemoradiation followed by potentially curative resection for esophageal cancer at the Department of Visceral and Vascular Surgery of the University of Cologne. Patients’ characteristics are shown in Table 1Go. Patients scheduled for induction therapy were required to have a Karnofsky Index ≥ 70% and normal to moderate risk factors for esophageal surgery according to a standardized score.9 Creatinine clearance had to be at least 60 ml/min. Patients with liver cirrhosis were excluded from this type of treatment. All patients with previous malignancies were excluded from the study, except those with cured basal cell cancer of the skin or carcinoma in situ of the cervix.


View this table:
[in this window]
[in a new window]

  		TABLE 1. Patients’ characteristics
 
TNM staging was performed according to the criteria of the International Union Against cancer (UICC).10 Clinical staging was based on endoscopy, endoscopic ultrasound, barium swallow and computed tomography (CT) of chest and abdomen (4 mm sections), and a technetium bone scan. Endoscopic ultrasound was performed by a single experienced examiner in all patients.

Radiochemotherapy Regimen and Surgical Resection
Cisplatin (20mg/m2/day) was given as short-term infusion on days 1–5 and 5-fluorouracil (1000mg/m2/d) as continuous infusion over 24 hours on days 1–5. Radiation therapy was administered by linear accelerators with 10–15-MV photons. Radiation therapy was simulated to encompass the tumor volume with 5 cm cephalocaudal-margins, and 2 cm radial margins and treatment ports were designed to include enlarged regional nodes based on CT evaluation and endoscopic ultrasound. Radiation was delivered in daily fractions of 1.8 Gy (days 1–5, 8–12, 15–19 and 22–26) to a total dose of 36 Gy using a multiple field technique. Surgical resection was performed 4–5 weeks following completion of chemoradiation after clinical restaging using the same procedures as for staging, except for laparoscopy. Standardized trans-thoracic en bloc esophagectomy with radical 2-field lymphadenectomy as previously described.11,12 In brief: after laparotomy, in all patients, lymphadenectomy of compartment II was performed including dissection of lymph nodes along the left gastric artery (group No.7), common hepatic artery (group No.8), coeliac trunc (group No.9), and splenic artery (group No.11). Partial lymphadenectomy of compartment I was achieved by dissecting lymph node groups 1–3. Abdominal lymph nodes were classified according to the Japanese Gastric Cancer Association.13 Consecutively, an anterolateral thoracotomy through the fifth intercostal space was performed followed by an en bloc resection of the esophagus. Lymph node dissection of the upper mediastinum included the right sided paratracheal nodes partially with the right and left recurrent nerve chain if the tumor was at or above the tracheal bifurcation. Lymph nodes at the tracheal bifurcation (subcarinal group) were dissected separately. Mediastinal lymph nodes were separated into 3 groups: lymph nodes of the lower mediastinum, lymph nodes at the level of the tracheal bifurcation (carinal, left and right bronchial lymph nodes), and lymph nodes of the upper mediastinum (paratracheal lymph nodes and recurrent nerve lymph nodes).

Reconstruction was performed by gastric tube (n = 50; 96.2%) or colon interposition (n = 2; 3.8%) with either left cervical (n = 3; 5.8%) or high intra-thoracic anastomosis (n = 49; 94.2%).

Pathology Examination and Histomorphologic Grading of Tumor Regression
The pathologic examination of the resected surgical specimens followed a standardized protocol in close cooperation of the operating surgeon and an experienced pathologist as reported.7 Briefly, the macroscopically visible tumor or the suspected area was localized, measured, and completely embedded. All specimens were fixed in neutral-buffered formaldehyde and embedded in paraffin. Apart from the resection margins (oral, aboral, deep margins), macroscopically normal mucosa close and distant to the tumor was examined. Lymph nodes were extensively scrutinized as previously described in detail.12 Abdominal lymph node stations were classified according to the Japanese Gastric Cancer Association13 and mediastinal lymph nodes were separated into 3 groups: lower mediastinal, bifurcational (carinal, left and right mainstem bronchus), and upper mediastinal nodes. Histopathological findings were classified according to the UICC TNM Classification System.10

For evaluation of radiochemotherapy-induced regression, serial 5-µm sections were stained with hematoxylin and eosin and, in case of diagnostic uncertainties, further staining procedures (PAS, Elasticavan Gieson) or immunohistochemical analysis for cytokine expression was performed to identify individual cells. Therapy-induced changes included reactive changes like necrosis, fibrosis, foamy histiocytes, and giant cell reactions.14,15 To account for the clinical response evaluation system according to WHO,16 a classification system based on the estimated percentage of vital residual tumor cells (VRTC) was used as reported.7 Briefly, the degree of histomorphologic regression was initially classified into 4 categories: grade I: > 50% vital residual tumor cells (VRTC), grade II: 10–50% VRTC (partial response), grade III: nearly complete response (NCR) with < 10% VRTC, and grade IV: complete response (pCR, ypT0). This analysis was performed by two staff pathologists who were blinded for all other clinical data. According to Schneider et al.,7 regression grades III and IV were classified as major histomorphologic response (MaHR) compared to grades I and II constituting minor histopathologic response (MiHR).

Immunhistochemistry
Formalin fixed and paraffin-embedded tumor and lymph node specimens were cut (5 µm) and deparaffinized according to standard histological techniques. Six sections were cut per lymph node. Presence of nodal micrometastasis was assessed using the anti-cytoceratin antibody AE1/AE3 (Dako, Glostrup, Denmark), diluted 1:50 (v/v) by the biotin-streptavidin method as described earlier.17

Sections of normal colonic mucosa served as positive staining. Positive staining for AE1/AE3 of N1 lymph nodes was considered as micrometastatic involvement of these nodes if at least three sections of one lymph node were positive after evaluation by two independent investigators.

Statistical Analysis
Associations between clinicopathological parameters were evaluated using {chi}2-analysis applying Fisher’s exact testing for significance. Kaplan-Meier plots were used to describe the survival distribution by important clinical parameters.18 The log-rank test was used to evaluate survival differences.19 The level of significance was set to P < 0.05. Unless otherwise specified, P-values were given for 2-sided testing.

All statistical tests were performed using the Software Package SPSS for Windows, Version 12.0, Chicago, IL, USA.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Presence of Nodal Micrometastasis
A total of 1270 lymph nodes (24.4 lymph nodes per patient, range 5–55) were resected in 52 patients with esophageal cancer. Of these nodes, 1186 (93.4%) were diagnosed as free of metastasis by conventional histopathological analysis. AE1/AE3 staining was positive in all primary tumors. In 19 (36.5%) patients, AE1/AE3 positive cells were found in lymph nodes that were considered to be metastasis-free according to the standard histopathological criteria. Overall, 33 (2.6%) lymph nodes that were diagnosed as tumor free by routine histopathology showed positive AE1/AE3 staining. Of 33 patients who were diagnosed as ypN0 by routine histopathology, 13 (39.4%) showed AE1/AE3 positive cells in their lymph nodes. In total, 23 (2.7%) out of 849 resected lymph nodes of ypN0 patients (26,5 per patient range 6–55) had nodal micrometastasis.

Influence of Neoadjuvant Therapy on Survival and Nodal Micrometastasis
A major histomorphological response (MaHR) of the tumor could be detected in 22 (42.3%) patients whereas 30 (57.7%) patients showed only a minor histomorphological response (MiHR). Patients with MaHR had a significantly better median survival compared to patients with MiHR (3.3 vs. 1.15 years, P < 0.04) (Fig. 1Go).


Figure 1
View larger version (11K):
[in this window]
[in a new window]

  		FIG. 1. Survival curves of patients with major (n = 22) compared to those with minor (n = 30) histopathological response (P < 0.04).

 
Incidence of nodal micrometastasis showed a clear trend towards a reduction if MaHR was present. Fourteen (46.7%) out of 30 patients with MiHR showed AE1/AE3-positive cells in their lymph nodes, whereas only 5 (22.7%) out of 22 patients with MaHR were nodal positive for AE1/AE3 (P = 0.068; {chi}2-test) (Fig. 2Go).


Figure 2
View larger version (23K):
[in this window]
[in a new window]

  		FIG. 2. Trend towards a reduced incidence of nodal micrometastasis in patients with esophageal cancer (n = 52) and major response to neoadjuvant chemoradiation (P < 0.068; {chi}2-test).

 
Thirty-two patients (61.5%) were staged as ypN0. In this group, MaHR was found in 19 (59.4%) patients, whereas 13 (40.6%) patients showed MiHR. Nine of 13 (69%) patients with MiHR showed AE1/AE3-positive cells in their lymph nodes, compared to only four of 19 (20%) pN0-patients with MaHR (P = 0.013, {chi}2-test) (Fig. 3Go).


Figure 3
View larger version (22K):
[in this window]
[in a new window]

  		FIG. 3. Reduced incidence of nodal micrometastasis in ypN0-patients (n = 33) and major response to neoadjuvant chemoradiation (P < 0.013, {chi}2-test).

 
Response to neoadjuvant therapy was not different between adeno- and squamous cell carcinoma (major: minor response, 7:14 (AC), 15:16 (SCC); P = 0.39, {chi}2-test). The incidence of nodal micrometastasis after neoadjuvant therapy showed no statistically significant difference between AC and SCC (data not shown).


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
One of the most important adverse prognostic factors in patients with esophageal cancer is the presence of lymph-node metastasis. The clinical significance of nodal micrometastasis has already been shown in several reports20 in non-pretreated, primarily resected esophageal cancers. Coauthors of this paper have previously assessed and confirmed the malignant potential of nodal micrometastatic cancer cells.8

Neoadjuvant therapeutic regimens including pre-operative administration of chemotherapy, or combined chemoradiation also aimed at reducing lymphatic tumor spread by eliminating micrometastasis in node negative tumors, thereby potentially prolonging survival. The results from phase II and III trials are controversial, but several authors have shown that patients with complete remissions in both neoadjuvant chemotherapy or chemoradiation trials benefit from these therapeutic regimens with 5-year survival rates up to 60%.1,21–23 Coauthors of this paper recently reported that histomorphologic tumor regression and lymph node status (ypN) are significant prognostic parameters for patients with complete resections (R0) following neoadjuvant radiochemotherapy for esophageal cancer. A regression classification based on the two parameters was established for objective response evaluation.7

Whether this survival benefit also results from reduction of nodal micrometastasis thereby preventing systemic tumor dissemination has not been examined in detail. This is the first report that provides preliminary evidence that indeed the incidence of isolated tumor cells in lymph nodes, detected by immunohistochemical analysis, is decreased in patients with resectable esophageal cancers with a major response to neoadjuvant chemoradiation. Nevertheless, our result is limited by the fact that assessment of nodal micrometastases prior surgery is not possible. Natsugoe et al.24 found in a study of 40 patients with esophageal cancer that neoadjuvant chemotherapy reduced the rate of nodal microinvolvement without stromal reaction, whereas no influence on micrometastasis with stromal reaction was evident. In our study, both chemo-and radiation therapy was administered prior to surgery. Therefore, the significant reduction of nodal micrometastasis in patients with major response to neoadjuvant therapy is likely to be related to the additionally administered radiotherapy. We found it difficult to further differentiate between micrometastasis with and without stromal reaction, especially because stromal reaction is one of the criteria that define the presence of occult nodal metastasis. It was previously postulated that disseminated tumor cells in the bone marrow are resistant to antiproliferative agents because of tumor cell dormancy.25,26 On the other hand, Kienle et al.27 have demonstrated a decreased detection rate of disseminated tumor cells in blood and bone marrow of rectal cancer patients after preoperative chemoradiation. In contrast to blood and bone marrow it is difficult, if not impossible, to detect disseminated tumor cells in lymph nodes preoperatively, even if endosonographically guided fine needle aspiration is administered. The impact of neoadjuvant chemoradiation on nodal micrometastasis in esophageal cancer has not been assessed in the literature so far. Several reports on preoperative chemoradiation show an improvement in local tumor control and a shift in recurrence from local to primarily systemic recurrence, which emphasizes the contribution of chemotherapy to radiosensitization and local tumor control.28 In conclusion, our results provide evidence that the survival benefit from neoadjuvant chemoradiation in patients with major response might also be related to a decreased incidence of nodal micrometastasis.


   FOOTNOTES
 
Klaus L. Prenzel and Alexandra König contributed equally

Received for publication June 17, 2006. Accepted for publication June 26, 2006.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Refaely Y, Krasna MJ. Multimodality therapy for esophageal cancer. Surg Clin North Am 2002; 82(4):729–46.[CrossRef][Medline]
  2. Izbicki JR, Hosch SB, Pichlmeier U, et al. Prognostic value of immunohistochemically identifiable tumor cells in lymph nodes of patients with completely resected esophageal cancer. N Engl J Med 1997; 337(17):1188–94.[Abstract/Free Full Text]
  3. Hosch SB, Stoecklein NH, Pichlmeier U, et al. Esophageal cancer: the mode of lymphatic tumor cell spread and its prognostic significance. J Clin Oncol 2001; 19(7):1970–5.[Abstract/Free Full Text]
  4. Urba SG, Orringer MB, Turrisi A, et al. Randomized trial of preoperative chemoradiation versus surgery alone in patients with locoregional esophageal carcinoma. J Clin Oncol 2001; 19(2):305–13.[Abstract/Free Full Text]
  5. Walsh TN, Noonan N, Hollywood D, et al. A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med 1996; 335(7):462–7.[Abstract/Free Full Text]
  6. Group MRCOCW. Surgical resection with or without preoperative chemotherapy in oesophageal cancer: a randomised controlled trial. Lancet 2002; 359(9319):1727–33.[CrossRef][Medline]
  7. Schneider PM, Baldus SE, Metzger R, et al. Histomorphologic tumor regression and lymph node metastases determine prognosis following neoadjuvant radiochemotherapy for esophageal cancer: implications for response classification. Ann Surg 2005; 242(5):684–92.[CrossRef][Medline]
  8. Scheunemann P, Izbicki JR, Pantel K. Tumorigenic potential of apparently tumor-free lymph nodes. N Engl J Med 1999; 340(21):1687.[Free Full Text]
  9. Bollschweiler E, Schroder W, Holscher AH, Siewert JR. Pre-operative risk analysis in patients with adenocarcinoma or squamous cell carcinoma of the oesophagus. Br J Surg 2000; 87(8):1106–10.[CrossRef][Medline]
  10. Sobin LH, Wittekind C. (1997) International Union Against Cancer (UICC) TNM Classification Of Malignant Tumors5 Wiley, New York, .
  11. Holscher AH, Schroder W, Bollschweiler E, et al. How safe is high intrathoracic esophagogastrostomy?. Chirurg 2003; 74(8):726–733.[CrossRef][Medline]
  12. Schroder W, Monig SP, Baldus SE, et al. Frequency of nodal metastases to the upper mediastinum in Barrett’s cancer. Ann Surg Oncol 2002; 9(8):807–11.[Abstract/Free Full Text]
  13. Japanese Gastric Cancer A. Japanese Classification of Gastric Carcinoma - 2nd English Edition. Gastric Cancer 1998; 1(1):10–24.[Medline]
  14. Baldus SE, Monig SP, Schroder W, et al. Regression of oesophageal carcinomas after neoadjuvant radiochemotherapy: criteria of the histopathological evaluation. Pathologe 2004; 25(6):421–427.[CrossRef][Medline]
  15. Darnton SJ, Allen SM, Edwards CW, Matthews HR. Histopathological findings in oesophageal carcinoma with and without preoperative chemotherapy. J Clin Pathol 1993; 46(1):51–5.[Abstract/Free Full Text]
  16. Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. Cancer 1981; 47(1):207–14.[CrossRef][Medline]
  17. Baldus SE, Zirbes TK, Engel S, et al. Correlation of the immunohistochemical reactivity of mucin peptide cores MUC1 and MUC2 with the histopathological subtype and prognosis of gastric carcinomas. Int J Cancer 1998; 79(2):133–8.[CrossRef][Medline]
  18. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53:187–220.
  19. Mantel N. Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep 1966; 50(3):163–70.[Medline]
  20. Jiao X, Krasna MJ. Clinical significance of micrometastasis in Lung and esophagela cancer: a new paradigm in thoracic oncology. Ann Thorac Surg 2002; 74:278–284.[Abstract/Free Full Text]
  21. Ancona E, Ruol A, Santi S, et al. Only pathologic complete response to neoadjuvant chemotherapy improves significantly the long term survival of patients with resectable esophageal squamous cell carcinoma: final report of a randomized, controlled trial of preoperative chemotherapy versus surgery alone. Cancer 2001; 91(11):2165–74.[CrossRef][Medline]
  22. Urschel JD, Vasan H. A meta-analysis of randomized controlled trials that compared neoadjuvant chemoradiation and surgery to surgery alone for resectable esophageal cancer. Am J Surg 2003; 185(6):538–43.[CrossRef][Medline]
  23. Kaklamanos IG, Walker GR, Ferry K, et al. Neoadjuvant treatment for resectable cancer of the esophagus and the gastroesophageal junction: a meta-analysis of randomized clinical trials. Ann Surg Oncol 2003; 10(7):754–61.[Abstract/Free Full Text]
  24. Natsugoe S, Matsumoto M, Nakshima S, et al. Effect of neoadjuvant chemotherapy for lymph node micrometastasis and tumor cell microinvolvement in patients with esophageal carcinoma. Cancer Letters 2000; 159:119–125.[CrossRef][Medline]
  25. Pantel K, Schlimok G, Braun S. Differential expression of proliferation-associated molecules in individual micrometastatic carcinoma cells. N Engl J Med 1993; 85:1419–1424.
  26. Braun S, Kentenich C, Janni W, et al. Lack of effect of adjuvant chemotherapy on the elimination of single dormant tumor cells in bone marrow of high-risk breast cancer patients. J Clin Oncol 2000; 18:80–86.[Abstract/Free Full Text]
  27. Kienle P, Koch M, Autschbach F, et al. Decreased detection rate of disseminated tumor cells of rectal cancer patients after preoperative chemoradiation: a first step towards a molecular surrogate marker for neoadjuvant treatment in colorectal cancer. Ann Surg 2003; 238(3):324–331.[Medline]
  28. Koshy M, Esiashvilli N, Landry JC, et al. Multiple managemet modalities in esophageal cancer: combined modality management approaches. The Oncologist 2004; 9:147–159.[Abstract/Free Full Text]



This article has been cited by other articles:


Home page
 Ann OncolHome page
E. Bollschweiler, R. Metzger, U. Drebber, S. Baldus, D. Vallbohmer, M. Kocher, and A. H. Holscher
Histological type of esophageal cancer might affect response to neo-adjuvant radiochemotherapy and subsequent prognosis
Ann. Onc., February 1, 2009; 20(2): 231 - 238.
[Abstract] [Full Text] [PDF]

Home page
 J. Thorac. Cardiovasc. Surg.Home page
C. Rizzetto, S.R. DeMeester, J.A. Hagen, C.G. Peyre, J.C. Lipham, and T.R. DeMeester
En bloc esophagectomy reduces local recurrence and improves survival compared with transhiatal resection after neoadjuvant therapy for esophageal adenocarcinoma.
J. Thorac. Cardiovasc. Surg., June 1, 2008; 135(6): 1228 - 1236.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Prenzel, K. L.
Right arrow Articles by Hölscher, A. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Prenzel, K. L.
Right arrow Articles by Hölscher, A. H.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS