Transthoracic, thoracoabdominal, and transabdominal surgical approaches for gastric cardia adenocarcinomas: a survival evaluation based on a cohort of 7103 patients.

BACKGROUND: This study compared the survival outcomes of different surgical approaches to determine the optimal approach for gastric cardia adenocarcinoma (GCA) and aimed to standardize the surgical treatment guidelines for GCA. METHODS: A total of 7103 patients with GCA were enrolled from our previously established gastric cardia and esophageal carcinoma databases. In our database, when the epicenter of the tumor was at or within 2 cm distally from the esophagogastric junction, the adenocarcinoma was considered to originate from the cardia and was considered a Siewert type 2 cancer. The main criteria for the enrolled patients included treatment with radical surgery, no radio- or chemotherapy before the operation, and detailed clinicopathological information. Follow-up was mainly performed by telephone or through home interviews. According to the medical records, the surgical approaches included transthoracic, thoracoabdominal, and transabdominal approaches. Kaplan-Meier and Cox proportional hazards regression models were applied to correlate the surgical approach with survival in patients with GCA. RESULTS: There were marked differences in age and tumor stage among the patients who underwent the three surgical approaches (P < 0.001). Univariate analysis showed that survival was related to sex, age, tumor stage, and N stage (P < 0.001 for all). Cox regression model analysis revealed that thoracoabdominal approach (P < 0.001) and transabdominal approach (P < 0.001) were significant risk factors for poor survival. GCA patients treated with the transthoracic approach had the best survival (5-year survival rate of 53.7%), and survival varied among the different surgical approaches for different tumor stages. CONCLUSION: Thoracoabdominal approach and transabdominal approach were shown to be poor prognostic factors. Patients with (locally advanced) GCA may benefit from the transthoracic approach. Further prospective randomized clinical trials are necessary.

Vascular Endothelial Growth Factor is a Useful Predictor of Postoperative Distant Metastasis and Survival Prognosis in Esophageal Squamous Cell Carcinoma.

BACKGROUND: The correlation between vascular endothelial growth factor (VEGF) and prognosis for patients with esophageal squamous cell carcinoma (ESCC) is controversial. This study investigated the correlation of VEGF expression with distant metastases and prognosis in resectable ESCC to improve the identification of patients with increased risk of postoperative metastases. METHODS: Data from two centers were used to establish a training cohort (n = 319) and a validation cohort (n = 164). Tissue microarrays were generated for immunohistochemical evaluation. The correlations among VEGF expression, clinicopathologic variables, and prognosis were analyzed. The outcomes generated from the training cohort then were tested using the validation cohort. Multivariate analyses were used to test the independent factors that had an impact on postoperative distant metastases, overall survival (OS), and distant metastasis-free survival (DMFS). RESULTS: Tumor stages, tumor cell grade, and VEGF expression were prognostic factors independent of ESCC outcome. The data indicated that high levels of VEGF expression were correlated with a high risk of postoperative distant metastases (p = 0.013) in the training cohort. This result was confirmed by the validation cohort (p < 0.01) and logistic regression analyses. A high level of VEGF expression also was correlated with poor DMFS (p = 0.011) and OS (p = 0.033) in the training cohort, which also was confirmed by the validation cohort and Cox regression analyses. CONCLUSIONS: Expression of VEGF is a predictor of distant metastasis, OS, and DMFS in resectable ESCC patients. Using a combination of VEGF expression, tumor stages, and tumor cell grade, identification of patients with increased risk of postoperative metastases may become possible.

Proposed modification of the seventh American Joint Committee on Cancer staging system for esophageal squamous cell carcinoma in Chinese patients.

BACKGROUND: More data are essential to test the efficacy of the American Joint Committee on Cancer (AJCC) system for staging esophageal squamous cell carcinoma (ESCC). On the basis of previous studies, we propose a modification to this system to better represent the survival characteristics of ESCC in the Chinese population. METHODS: We used data from two centers to establish the generating (n = 1006) and validation (n = 783) cohorts. All of the patients underwent curative surgical treatment. On the basis of previous studies, we excluded tumor location as a variable in the modified pathological staging system and defined the modified nodal categories as follows: N0, node negative; N1, 1 positive node; N2, 2 to 3 positive nodes; and N3, >3 positive nodes. The pathological T categories, pathological M categories, and cell differentiation in the seventh AJCC staging system for adenocarcinoma were used in the modified pathological staging system for ESCC. RESULTS: The median survival times for ESCC patients with stage 0 and Ia, stage Ib, stage IIa, stage IIb, stage IIIa, stage IIIb, stage IIIc were as follows: not reached, 221.2, 151.8, 88.5, 25.0, 19.0, and 13.0 months, respectively, for the entire cohort of patients (n = 1789). The corresponding 5-year survival rates were 86.7, 76.4, 64.9, 55.3, 29.9, 16.9, and 9.7 %, respectively. The survival rates significantly differed between the modified staging groups (p < 0.01). CONCLUSIONS: This modified staging system better discriminates the survival differences between stages than the seventh edition of the AJCC staging system for ESCC in Chinese patients.

The positive lymph node ratio predicts long-term survival in patients with operable thoracic esophageal squamous cell carcinoma in China.

BACKGROUND: Controversy exists concerning the optimal cutoff points for the positive lymph node ratio (PLNR) to predict overall survival. We aim to propose reasonable PLNR categories for the discrimination of the survival difference between groups. METHODS: We used data from two centers to establish a training (n = 1006) and a validation (n = 783) cohort. All of the patients underwent curative surgical treatment. Martingale residuals from a Cox proportional hazards regression model were used to determine the optimal cutoff points for PLNR to predict overall survival. The survival rate was calculated using the Kaplan-Meier method, and a log-rank test was used to assess the survival differences between groups. The results obtained from the training cohort were tested with the validation cohort at each step. RESULTS: We classified the patients into four revised nodal categories: R-pN0 (PLNR = 0), R-pN1 (0< PLNR ≤0.1), R-pN2 (0.1< PLNR ≤0.3), and R-pN3 (PLNR >0.3). Subgroup analysis for the pT2 and pT3 cases showed that the survival differences could be well discriminated between groups based on PLNR in both the training cohort and validation cohort. When we modified the current staging system using revised nodal categories (based on PLNR) instead of the AJCC nodal categories, the survival rate could also be easily distinguished between patients in different stages in both cohorts of patients. CONCLUSIONS: The survival rate of ESCC can be discriminated between four groups: PLNR = 0, 0< PLNR ≤0.1, 0.1< PLNR ≤0.3, and PLNR >0.3. Further studies are required to confirm these results.

[Surgical treatment of primary esophageal adenocarcinoma].

OBJECTIVE: To summarize the surgical treatment and clinical bio-characteristics of primary esophageal adenocarcinoma (PEAC). METHODS: Clinical data of 43 cases with PEAC who had undergone operation from February 1980 to December 2000 in Linzhou City Esophageal Tumor Hospital were retrospectively analyzed. RESULTS: Forty-three cases PEAC were reported in this study, which were 0.8% out of 5638 cases pathologically confirmed esophageal carcinoma treated during this period. Twelve cases (27.9%) were in the middle 1/3 of esophagus, thirty-one cases (72.1%) in the lower 1/3, which were significantly different from esophageal squamous cell carcinoma (ESCC). Fourteen cases were pure esophageal adenocarcinoma (32.6%), twenty-nine cases were adenosquamous cell carcinoma and adenoacanthoma cell carcinoma (67.4%). The ratio of lymph node metastasis of PEAC was higher than that of ESCC (65.1% vs. 31.6%, P < 0.001). The overall survival rates of 1, 3 and 5-year of PEAC were 81.4%, 46.5% and 28.2%, respectively, which were lower than those of ESCC (89.7%, 68.2% and 39.4%, respectively; chi 2 = 4.846, P = 0.028). CONCLUSIONS: Compared with ESCC, PEAC, mainly located in the inferior 1/3 of esophagus, is a malignant disease with higher frequency of lymph node metastasis and poor prognosis. Surgical resection should be the first choice of treatment. Early diagnosis and early treatment as well as curative operation could improve prognosis. The long-term survival may be increased by adjunct multi-modality treatment.

Cyclin D1 expression predicts postoperative distant metastasis and survival in resectable esophageal squamous cell carcinoma.

PURPOSE: We aim to identify esophageal squamous cell carcinoma patients with increased risk of postoperative metastases. RESULTS: A high level of cyclin D1 expression, together with poor tumor cell differentiation and advanced tumor stages, increased risk of postoperative metastasis and decreased distant metastasis-free survival in ESCC in both cohorts. A high level of cyclin D1 expression also decreased overall survival in the training cohort (p < 0.01) but not in the validation cohort (p = 0.415). However, when the two cohorts of patients were pooled to obtain a larger case number, a high level of cyclin D1 expression was again demonstrated as an independent predictor that decreased overall survival (p < 0.01). METHODS: We used data from two institutions to establish training (n = 319) and validation (n = 164) cohorts. Tissue microarrays were generated for immunohistochemical evaluation. The correlation among cyclin D1 expression, clinicopathologic variables, postoperative distant metastases, overall survival, and distant metastasis-free survival were analyzed. Multivariate analyses were used to test the independent factors impacting postoperative distant metastases and survival. The outcomes generated from the training cohort were then tested using the validation cohort and pooled dataset. CONCLUSIONS: High level of cyclin D1 expression increased distant metastasis, decreased overall survival and distant metastasis-free survival in resectable ESCC. Using a combination of cyclin D1 expression, tumor cell differentiation grade, and tumor stages, identifying patients with increased risk of postoperative metastases becomes possible.

Multidisciplinary modalities achieve encouraging long-term survival in resectable limited-disease esophageal small cell carcinoma.

BACKGROUND: The management of limited-disease esophageal small cell carcinoma is not well defined, and the role of surgery is still controversial. We aim to determine the optimal treatment strategy in limited-disease of esophageal small cell carcinoma. METHODS AND FINDINGS: We conducted a retrospective review of 141 patients with limited-disease esophageal small cell carcinoma from 3 institutions in China who underwent treatment between July 1994 and September 2008, July 1994 and July 2011, and June 2004 and December 2010, respectively. The survival rate was calculated by the Kaplan-Meier method, and the log-rank test was used to assess the survival differences between the groups. Cox proportional hazards model were used to further determine the independent factors impacting overall survival. The median survival time was 16.1 months for the entire cohort of patients, with a 5-year survival rate of 6.7%. The median survival times for surgery alone, surgery combined with chemotherapy, surgery combined with radiotherapy, surgery combined with chemotherapy and radiotherapy, chemotherapy plus radiotherapy, and chemotherapy alone were 18.0 months, 15.0 months, 23.0 months, 25.0 months, 17.1 months, and 6.1 months, respectively; the corresponding 5-year survival rates were 0%, 15.4%, 0%, 38.9%, 0%, and 0%, respectively. For the 105 patients who underwent R0 resection, the median disease-free survival time was 12.0 months, with a 95% confidence interval of 9.5 months to 14.5 months. The multivariate Cox regression analysis demonstrated that advanced pathological staging (p = 0.003), and pure esophageal small cell carcinoma (p = 0.035) were independent factors decreasing overall survival. CONCLUSIONS: Our data suggested that multidisciplinary modalities achieved encouraging long-term survival in patients with resectable limited-disease of esophageal small cell carcinoma.

Modification of nodal categories in the seventh american joint committee on cancer staging system for esophageal squamous cell carcinoma in Chinese patients.

BACKGROUND: More data are essential to test the efficacy of the American Joint Committee on Cancer (AJCC) system for staging esophageal squamous cell carcinoma. We tested the classifiers used in the AJCC staging system and propose a modification to this system to better represent the survival characteristics of esophageal squamous cell carcinoma in the Chinese population. METHODS: We used data from two centers, which established the training (n=1,006) and validation (n=783) cohorts. All the patients underwent curative surgical treatment. Survival was compared using AJCC classifiers to test the efficacy of this staging system. Martingale residuals from a Cox proportional hazards regression model were used to modify the nodal categories. The results obtained from the training cohort were validated with the validation cohort at each step. RESULTS: The evaluation of the patients' overall survival allowed only poor discrimination between AJCC IIIb and IIIc cancers in both cohorts. Also, in both cohorts, N2 and N3 classification cancers could not be well discriminated in terms of survival when AJCC nodal categories were used. Nevertheless, the survival rate could easily be distinguished when using the four modified categories: 0, 1, 2 to 3, and 4 or more positive nodes. The survival difference between IIIb and IIIc obtained using the modified nodal categories could easily be discriminated in both cohorts. CONCLUSIONS: Esophageal squamous cell carcinoma nodal staging for the Chinese population was more accurately classified using the following four categories: no positive node, 1 positive node, 2 to 3 positive nodes, and 4 or more positive nodes. Further studies are required to confirm these results.