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Originally published as Ann Surg Oncol Early Release 10.1245/ASO.2004.09.002 on May 18, 2004

Annals of Surgical Oncology 11:629-635 (2004)
© 2004 Society of Surgical Oncology
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ORIGINAL ARTICLES

Gastric Cancer: Establishing Predictors of Biologic Behavior with Use of Population-Based Data

B.J. Dicken, MD, L.D. Saunders, PhD, G.S. Jhangri, MSc, C. de Gara, FRCSC, C. Cass, PhD, S. Andrews, MD and S.M. Hamilton, FRCSC

From the Departments of Surgery (BJD, CdeG, SMH), Public Health Sciences (LDS, GSJ), Laboratory Medicine and Pathology (SA), and Oncology (CC), University of Alberta and Cross Cancer Institute, Edmonton, Alberta, Canada.

Correspondence: Address correspondence and reprint requests to: Dr. S. M. Hamilton, 2D2 Walter C. Mackenzie Health Sciences Center, 8440-112 St. University of Alberta Hospital, Edmonton, Alberta, Canada T6G 2B7; Fax: 780-407-7394; e-mail: shamilto{at}cha.ab.ca


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: Tumor thickness and nodal status are important predictors of survival following curative resection for gastric cancer. Lymphovascular invasion (LVI) is a potential predictor of biological behavior. The relationship between LVI and tumor thickness (T status) has not been established in population-based studies.

Methods: Clinicopathological and survival data of 577 patients at nine centers, from between 1991 and 1997, was collected from patient records and a Provincial Cancer Registry. The primary endpoint of the study was death. A secondary analysis of a node-negative subgroup examined the significance of LVI with respect to T status.

Results: The population disease-specific survival was 28%. In a multivariate analysis, T, N, M, esophageal margin, tumor morphology, and residual tumor category were independent predictors of survival. LVI was documented in 58% of resected tumors. LVI correlated with advancing T and N status but was not significant in a multivariate population model. Subgroup analysis of node-negative gastric cancer found T status and LVI to be independent predictors of survival. LVI was associated with a 5-year survival of 8%, versus 43% among patients in whom it was absent (P < .001).

Conclusions: T status and N status were the most important independent predictors of survival in a population-based study of gastric cancer. LVI correlated with advancing N and T status. Multivariate analysis of node-negative patients showed LVI and T status are independent predictors of survival.

Key Words: Adenocarcinoma • Neoplasm invasiveness • Prognosis • Stomach neoplasm • Survival analysis


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Despite a declining incidence, gastric cancer is the second most common cancer worldwide and the third commonest cause of cancer deaths in Canada.1,2

Studies examining the biologic behavior of gastric cancer have relied upon clinicopathologic characteristics as a means of establishing prognosis.3–5 With a trend toward a standardized approach to gastric cancer, complete delineation of the predictors of biologic behavior in guiding surgical decision-making becomes increasingly important.6,7 Specialized oncology centers have played a key role in establishing prognostic predictors in western populations.8–12 Expertise and adherence to standard technique create a reference for population-based studies, thereby improving quality and compliance with standardized surgical and pathological techniques.6,7

Since most gastric cancer surgery is performed in nonspecialized centers in Canada, it is important to validate the results from specialized centers in population-based studies. Population-based studies overcome the issues of selection bias encountered by specialized hospital units.13–17 Population-based studies, by including all diagnosed cases, address surgical/pathological and patient heterogeneity, thereby allowing comparisons of survival estimates between geographically defined populations.14,16–17 Predictors of outcome identified in population studies may be used to guide management strategies and provide a platform from which future hypotheses can be generated and tested.13

We conducted a retrospective study to identify independent predictors of survival in a population-based cohort of Northern Alberta residents diagnosed with gastric adenocarcinoma. We present the results of a multivariate analysis, as well as a subgroup analysis of the relationship between tumor thickness (T status) and lymphovascular invasion (LVI).


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
From January 1, 1991, to December 31, 1997, all patients residing in northern Alberta, Canada, with a histological diagnosis of gastric adenocarcinoma were recorded in the Northern Alberta Cancer Registry, as mandated by the Alberta Health Act. Cases (n = 577) were coded according to the site of malignancy, as defined in the ICD-0 codes (C-16), and classified according to the World Health Organization (WHO) histological criteria.1 The Cancer Registry serves a population of 1.57 million residents in northern Alberta and is updated monthly with respect to survival status and histopathology. The registry includes age, gender, diagnosis, and survival status. A gastric cancer database was created and supplemented the registry with tumor- and patient-related prognostic variables obtained from chart audits of all 577 identified cases. Prognostic factors were selected from the English literature published between 1970 and 2003. The study included all patients diagnosed or treated in nine participating hospitals (five community and four tertiary).

Resection was considered curative if both macroscopic and microscopic margins were free of tumor (R0) according to the American Joint Committee on Cancer (AJCC) guidelines.18 Lymph node status was coded according to the AJCC TNM staging criteria (5th edition).18 Patients with at least 15 nodes resected and found to be free of tumor were considered to be adequately staged and were specified as node-negative.18 LVI was defined as the presence of tumor emboli within either vascular or lymphatic channels. No attempt was made to differentiate between lymphatic and microvascular invasion. Neural invasion was not reliably recorded and therefore was not analyzed. All patients with a histological diagnosis were included in the primary analysis. Patient demographics (age, gender), tumor-related characteristics (T, N, M, histological grade, WHO histological classification, tumor size, stage, and LVI), treatment factors (type of gastric resection, surgical resection margins), and survival data were recorded. Follow-up for the entire population with respect to survival status was complete for 99% of patients. Disease-specific survival was the primary outcome of interest. To date, 85% of patients included are deceased. Ethics approval was provided by the Health Ethics Research Board at the University of Alberta.

Analyses were undertaken with statistical software (SPSS, version 11.0; SPSS, Inc., Chicago, IL). Survival curves were constructed by means of the Kaplan-Meier method and then compared with the log-rank test. Population-based prognostic factors were assessed by univariate Cox’s regression. In multivariate analysis, variables were entered into the model according to a purposeful selection method.19 Continuous variables were assessed for linearity and, where appropriate, transformed into categorical variables. Missing values were coded as missing and entered into the model. The significance of the covariates was tested with the Wald test.

No variables included in the final model violated the proportional hazard assumption. Association between categorical variables was tested with {chi}2.

A subgroup analysis was undertaken to examine the relationship between LVI and T status. To avoid the confounding effects of nodal status, only patients with node-negative gastric cancer (n = 94) were included in the subgroup analysis. A P value < .05 was considered statistically significant.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Population-Based Model
The clinicopathological characteristics of the entire population (n = 577) are shown in Table 1. The mean age at the time of surgery was 72.6 years (range, 27–106); 344 (60%) were male and 233 (40%) were female. There was no significant difference in age between males and females (P = .27). Median follow-up for the entire cohort was 58 months (range, 1–108). At the time of analysis, 81 patients (14%) were alive, 492 (85%) were dead, and 4 (1%) were lost to follow-up. The 5-year crude survival rate was 12% (95% CI, 8.9–14.9). The overall 5-year disease-specific survival was 28% (95% CI, 21.9–33.2).


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  		TABLE 1. Baseline characteristics of the entire population and the subgroup of node-negative patients
 
Thirty-seven (6.4%) had T1 tumors, 57 (9.8%) had T2 tumors, 202 (35.0%) had T3 tumors, and 101 (17.5%) had T4 tumors, whereas 164 (28.4%) were unresectable at operation and therefore had incomplete T staging. Overall, 94 (16.3%) were N0, 183 (31.7%) were N1, 89 (15.4%) were N2, and 16 (2.8%) were N3 tumors. Distant metastasis was absent in 125 cases (21.6%) and present in 216 (37.4%), whereas in 236 cases (40.9%), distant metastasis was not assessed. Tumor stage and accompanying 5-year disease-specific survival for the entire population cohort are presented in Table 2. Mean tumor size was 5.9 cm (range, 0.5–19.0). LVI was noted in 250 patients (43%) and absent in 92 (16%). LVI was not recorded in 88 cases (15%) for which surgical specimens were available for pathological review. LVI status could not be assessed in 147 cases (25.5%) in which no resection was performed.


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  		TABLE 2. Disease-specific 5-year survival by AJCC/UICC stage in the population cohort and node-negative subgroup of patients
 
Surgical therapies with curative intent included total gastrectomy (16%) and subtotal gastrectomy (38%). Palliative surgery was performed in 80 cases (14%) and resulted in 29 surgical bypasses (5%) and 51 laparotomy-only procedures (9%).

One hundred eighty-three patients (32%) with a histological diagnosis of gastric cancer were unresectable according to preoperative investigations and were not offered surgical intervention. Residual tumor status was documented in 314 (79.7%) of 394 resected cases: 263 (83.7%) were R0 and 51 (16.2%) were R1/R2. With respect to esophageal margin status, 399 (69%) of 577 had surgical specimens for review, of which 280 (70%) were microscopically negative, 34 (8.5%) were positive, and 85 (21.3%) lacked a record of margin status. Disease-specific 5-year survival was significantly worse in the esophageal margin–positive group than in the margin-negative group (8.8 ± 3% vs. 27.6 ± 5%; P < .001). At least 15 lymph nodes were resected in 199 (34%), whereas the remaining 378 (66%) were classified as unresectable or inadequately staged.

Table 3 shows the results of the univariate and multivariate Cox’s proportional hazard model. Nodal status was the most significant independent prognostic factor (P < .0001), followed by T status (P < .0001, Fig. 1), histological classification (P = .006), M status (P = .03), residual tumor category (P = .01), and esophageal margin status (P = .01). Tumor size was not significant (P = .11) but was found to be a confounding variable and therefore was included in the final model as an important predictor of survival.


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  		TABLE 3. Population-based model: independent multivariate predictors of long-term survival (n = 577)
 


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  		FIG. 1. Relationship between T status and disease-specific survival. No significant difference exists between T1 and T2 tumors (P = .11). There was a significant difference between T1, T3 (P < .001), and T4 (P < .001) and between T2, T3 (P< .001), and T4 tumors (P< .001).

 
No significant 5-year survival difference was observed between T1 and T2 tumors (64 ± 18% vs. 53 ± 7%, respectively; P = .11). T3 tumors were associated with a significantly worse 5-year survival (11 ± 5%) than were both T1 (P < .001) and T2 (P < .001) tumors (Fig. 1). LVI, tumor grade, type of surgical resection, age, and gender were not significant predictors of survival in the population-based model. There was a significant difference in 5-year survival between node-negative and node-positive tumors (58 ± 11% vs. 9.8 ± 4%, respectively; P < .001, Fig. 2).



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  		FIG. 2. Relationship between node-negative and node-positive resected gastric cancer. There was a significant difference in disease-specific 5-year survival between node-positive (n = 288) and node-negative (n = 94) patients (9.8 ± 4% vs. 58 ± 11%, respectively; P < .001).

 
Chi-square tests demonstrated a significant association between T status and LVI (P < .001), between T status and N status (P < .001), and between N status and LVI (P < .001). A subgroup analysis was conducted to explore the relationship between T status and LVI in a subset of node-negative patients.

Node-Negative Model
At least 15 lymph nodes were assessed in 199 (34.4%) of 577 cases, of which 94 (47%) were node-negative (Table 1). Among node-negative patients, 56 (60%) were men and 38 (40%) women, with a mean age of 73 years (range, 41–97). The median tumor size was 4.0 cm (range, 0.5–13.0). LVI was absent in 59 (62.7%), present in 22 (23.4%), and not recorded in 13 cases (13.8%).

In this subgroup of node-negative patients, Cox’s regression showed T status (P < .001) and LVI (P = .03) to be independent predictors of survival. With T4 tumors removed (n = 6), because of small sample size, reanalysis showed only LVI (HR = 2.42; 95% CI, 1.06–5.53) to be an independent predictor of disease-specific survival. T stage, gender, histological classification, tumor grade, esophageal and duodenal margin status, type of surgical resection, year of surgery, age, tumor size, and residual tumor status had no influence on long-term survival. The 5-year disease-specific survival for stage in the subgroup of node-negative patients is shown in Table 2.

There was a significant difference in the disease-specific 5-year survival in the presence or absence of LVI (34 ± 20% vs. 65 ± 14%, respectively; P = .016, Fig. 3). A significant association was found between T stage (T1–T3) and LVI (P = .003). In the node-negative subgroup, the 5-year survival for T1 (64 ± 17%) and T2 (53 ± 14%) was not significantly different (P = .11); however, it was significantly worse (P < .001) for both T3 (11 ± 5%) and T4 tumors (1 ± 1%). After stratifying by negative LVI, there was no significant difference between T stages (P = .33; Fig. 4).



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  		FIG. 3. The relationship between LVI and disease-specific survival in a subgroup of node-negative patients. The presence of LVI was associated with a significantly worse 5-year survival in comparison with LVI-negative patients (34 ± 20% vs. 65 ± 14%, respectively; P = .016).

 


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  		FIG. 4. Relationship between T status and disease-specific survival in a subgroup of node-negative, LVI-negative patients. There was no significant difference between T1, T2, and T3 in the absence of LVI (P = .33). T4 tumors (n = 6) have been omitted due to small sample size.

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
The Dutch gastric cancer and British MRC trials, while attempting to settle the controversy with regard to appropriate lymphadenectomy, demonstrated the difficulty, even under the most controlled conditions, with compliance when performing standardized surgical procedures.3,8 This difficulty has been a point of contention with respect to survival differences observed at specialized versus nonspecialized centers, where the effects of stage migration have impaired study comparability.4 Studies at specialized western centers applying standardized extended (D2) resections have supported reports from Asian centers5,20–21 demonstrating that extended resections may be conducted safely and are associated with better long-term survival than are limited resections.10–12,22–24 These studies have confirmed lymph node status as the most important predictor of long-term survival. Despite these results, standardization and compliance with extended resections continues to be a problem.6,7,25 Although specialized centers have been successful in achieving adequate lymph node resections (>15 nodes),11,12,22 the same cannot be said of nonspecialized institutions. Mullaney et al.6 demonstrated that 31% of surgically resected cases in the United Kingdom could be accurately staged as described, whereas Hundahl et al.25 showed only 18% of resected cases in the United States could be adequately staged for lymph node involvement.

This study examined the biologic predictors of long-term survival in a population-based cohort with the aim of establishing generalizability with European population-based studies and determining if the results obtained at specialized western institutions also apply to nonspecialized centers. In addition, potential surrogate predictors of survival that may improve prognostication in the face of inadequate lymph node staging were examined.

Our results showed that 34% of cases in an unselected population had an adequate lymph node resection. This was consistent with findings in European population studies, which in a similar time period showed adequate lymph node resections of 23.2%13 and 25.5%15. We report a 5-year disease-specific survival of 28% in completely resected cases. This is in agreement with several European studies14,15,17 that showed 5-year survivals of 20% to 30.6% among unselected patients who underwent surgery with curative intent.

Our results confirmed that N status and T status were the most important independent predictors of long-term survival, followed by M status, histological classification, and residual tumor status. These findings are consistent with published results obtained at both specialized and community-based centers12,13,15,20,22 and provide a basis for ongoing validity testing and generalizability of results among North American centers. Although we document the same independent predictors of survival, both the percentage of patients who had an adequate node resection and the disease-specific survival differed markedly from those reported by specialized centers.12,18,20,22 This discrepancy would support the importance of instituting standardized extended lymph node resection procedures in nonspecialized centers to achieve optimum survival rates, similar to the situation in centers with dedicated gastric cancer resection protocols. However, the majority of North American and European centers do not perform adequate lymph node resections and are unlikely to formally adopt this practice in the near future. 6,13,25 Because the ability to accurately predict outcome following surgery is limited when staging information is incomplete, additional markers of biologic behavior should be explored for their predictive ability.

Although LVI was significant by univariate analysis, it was not significant in a multivariate model. We believe that LVI loses its predictive ability in a population model because of the overwhelming significance of lymph node metastasis and deeply penetrating tumors (advanced N and T status). The fact that node status has the greatest impact on survival may merely reflect an end stage in the natural progression of gastric cancer. We hypothesize that in early gastric cancer, T status and LVI are the most important determinants of subsequent nodal involvement. In keeping with this concept, we found a high correlation between advancing T and N status and the presence of LVI. This finding prompted us to examine a subgroup of node-negative patients to further evaluate the relationship of LVI with T and N status. Our findings are consistent with those of several studies26–28 in which in a subgroup of node-negative patients, T status and LVI were found to be independent predictors of long-term survival.

Previous studies suggest that vascular invasion may be an indicator of biologic aggressiveness, independent of T status.27 After excluding T4 tumors, we found that LVI alone emerged as an independent predictor of long-term survival (P = .03). When T4 tumors were included in the model, both LVI (P = .04) and T status (P < .001) retained predictive significance; however, given the small number of T4 tumors, a larger study is needed to fully establish the importance of T4 tumors in association with LVI. Overall, the documentation of LVI provides an additional source of information in predicting long-term survival. In nonspecialized centers where many patients who are offered surgical therapy may not have an adequate node resection (>15 nodes), the combined use of LVI and T status may be used to improve prognostication.

Two separate studies7,13 previously revealed a threshold value above which the number of resected nodes no longer significantly raised the proportion of tumors classified as node positive. These studies suggest that staging is reliable when at least 10 lymph nodes are removed and assessed by a pathologist. We propose that the addition of LVI to T status and N status might improve staging and prognostication. With increasing experience with cases in which at least 10 lymph nodes are resected, the addition of factors such as LVI may allow for more accurate prognostication, thereby reducing the requirement for extended resection, with its attendant increase in morbidity and mortality outside of specialized units.

Our results provide a population-based validation of independent predictors of long-term survival of patients with gastric cancer and support the importance of standardizing surgical approaches to gastric cancer if population-based survival rates are to equal those of specialized oncology centers. In addition, we showed that LVI is highly correlated with advancing T and N status and is an independent predictor of survival in a subgroup of patients with node-negative gastric cancer. We suggest that LVI, when combined with available lymph node data, may improve prognostication when lymph node stage is questionable. Future studies examining the significance of LVI will provide important insight into the role of LVI as a potential surrogate to lymph node staging.29


   ACKNOWLEDGMENTS
 
The acknowledgments are available online in the fulltext version at www.annalssurgicaloncology.org. They are not available in the PDF version.

Dr C. Cass is Canada Research Chair in Oncology. Research support was provided by the University of Alberta Hospital Foundation and the Alberta Cancer Board.


   FOOTNOTES
 
This study, using population-based gastric cancer data, examines biological predictors of survival. Cox’s proportional hazard confirmed T and N status as significant predictors of survival. In node-negative patients, lymphovascular invasion was an independent predictor of survival in a multivariate subgroup analysis.

Received for publication September 3, 2003. Accepted for publication January 30, 2004.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Fenogilo-Preiser C, Carneiro F, Correa P, et al. Gastric carcinoma. In: Hamilton SR, Aaltonen LA, eds. Pathology and Genetics of Tumors of the Digestive System. Lyon: IARC Press, 2000: 39–52.
  2. Canadian Cancer Statistics, 2001. www.hc-sc.gc.ca. Accessed September 10, 2003.
  3. Cuschieri A, Weeden S, Fielding J, et al. Patient survival after D1 and D2 resections for gastric cancer: long-term results of the MRC randomized surgical trial. Br J Cancer 1999; 79: 1522–30.[CrossRef][Medline]
  4. Davis PA, Sano T. The differences in gastric cancer between Japan, USA and Europe: What are the facts? What are the suggestions? Crit Rev Oncol Hematol 2001; 40: 77–94.[Medline]
  5. Adachi Y, Shiraishi N, Suematsu T, et al. Most important lymph node information in gastric cancer: multivariate prognostic study. Ann Surg Oncol 2000; 7: 503–7.[Abstract]
  6. Mullaney PJ, Wadley MS, Hyde C, et al. Appraisal of compliance with the UICC/AJCC staging system in the staging of gastric cancer. Br J Surg 2002; 89: 1405–8.[CrossRef][Medline]
  7. Ichikura T, Ogawa T, Chochi K, et al. Minimum number of lymph nodes that should be examined for the International Union Against Cancer/American Joint Committee on Cancer TNM Classification of Gastric Carcinoma. World J Surg 2003; 27: 330–33.[Medline]
  8. Bonenkamp JJ, Hermans J, Sasako M, et al. Extended lymph-node dissection for gastric cancer. N Engl J Med 1999; 340: 908–14.[Abstract/Free Full Text]
  9. Volpe CM, Driscoll DL, Douglass HO. Outcome of patients with proximal gastric cancer depends on extent of resection and number of resected lymph nodes. Ann Surg Oncol 2000; 7: 139–44.[Abstract]
  10. Roviello F, Marrelli D, Morgagni P, et al. Survival benefit of extended D2 lymphadenectomy in gastric cancer with involvement of second level lymph nodes: a longitudinal multicenter study. Ann Surg Oncol 2002; 9: 894–900.[Abstract/Free Full Text]
  11. Siewert JR, Bottcher K, Stein HJ, et al. Relevant prognostic factors in gastric cancer: ten-year results of the German Gastric Cancer Study. Ann Surg 1998; 228: 449–59.[CrossRef][Medline]
  12. Karpeh MS, Leon L, Klimstra D, et al. Lymph node staging in gastric cancer: is location more important than number? Ann Surg 2000; 232: 362–71.[CrossRef][Medline]
  13. Bouvier AM, Haas O, Piard F, et al. How many nodes must be examined to accurately stage gastric carcinomas? Results from a population based study. Cancer 2002; 94: 2862–8.[CrossRef][Medline]
  14. Faivre J, Forman JE, Gatta G, et al. Survival of patients with oesophageal and gastric cancers in Europe. Eur J Cancer 1998; 34: 2167–75.[CrossRef][Medline]
  15. Barchielli A, Amorosi A, Balzi D, et al. Long-term prognosis of gastric cancer in a European country: a population-based study in Florence (Italy). 10-year survival of cases diagnosed in 1985-1987. Eur J Cancer 2001; 37: 1674–80.[CrossRef][Medline]
  16. Hansson LE, Ekstrom AM, Bergstrom R, et al. Surgery for stomach cancer in a defined Swedish population: current practices and operative results. Eur J Surg 2000; 166: 787–95.[CrossRef][Medline]
  17. Miska S, Benhamiche AM, Jouve JL, et al. Prognostic factors after curative resection for gastric cancer. A population-based study. Eur J Cancer 2000; 36: 390–6.
  18. AJCC Cancer Staging Manual. Chicago: Lippincott-Raven, 1997.
  19. Hosmer DW, Lemeshow S. Applied Survival Analysis. New York: Wiley, 1999.
  20. Otsuji E, Toma A, Kobayashi S, et al. Long-term benefit of extended lymphadenectomy with gastrectomy in distally located early gastric carcinoma. Am J Surg 2000; 180: 127–32.[CrossRef][Medline]
  21. Maehara Y, Kakeji Y, Koga T, et al. Therapeutic value of lymph node dissection and the clinical outcome for patients with gastric cancer. Surgery 2002; 131: S85–91.
  22. Marubini E, Bozzetti F, Miceli R, et al. Lymphadenectomy in gastric cancer: prognostic role and therapeutic implications. EJSO 2002; 28: 406–12.
  23. Ramacciato G, Aurello P, D’Angelo F, et al. Does extended lymphadenectomy influence prognosis of gastric carcinoma after curative resection? Hepato-Gastroenterology 2000; 47: 1470–4.[Medline]
  24. Onate-Ocana LF, Aiello-Crocifoglio V, Mondragon-Sanchez R, et al. Survival benefit of D2 lymphadenectomy in patients with gastric adenocarcinoma. Ann Surg Oncol 2000; 7: 210–7.[Abstract]
  25. Hundahl SA, Phillips JL, Menck HR. The National Cancer Data Base report on poor survival of US gastric carcinoma patients treated with gastrectomy. Cancer 2000; 88: 921–32.[CrossRef][Medline]
  26. Yokota T, Kunii Y, Teshima S, et al. Significant prognostic factors in patients with node-negative gastric cancer. Int J Surgery 1999; 84: 331–6.
  27. Hyung WJ, Lee JH, Choi SH, et al. Prognostic impact of lymphatic and/or blood vessel invasion in patients with node-negative advanced gastric cancer. Ann Surg Oncol 2002; 9: 562–7.[Abstract/Free Full Text]
  28. Kooby DA, Suriawinata A, Klimstra DS, et al. Biologic predictors of survival in node-negative gastric cancer. Ann Surg 2003; 237: 828–37.[CrossRef][Medline]
  29. Hayashi H, Ochiai T, Suzaki T, et al. Superiority of a new UICC-TNM staging system for gastric carcinoma. Surgery 2000; 127: 129–35.[CrossRef][Medline]



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