3.1 General demographic and clinicopathologic Characteristics
Of the 5349 esophageal cancer patients treated by surgery alone with the Sweet approach, the male to female sex ratio was 2.1 :1 and the mean age at diagnosis was 53.3 years old. Regarding tumor location of esophageal cancer, the tumor was in the upper third in 225 of 5349 cases (4.2%), in the middle third in 3969 (74.2%), and in the lower third in 1155 (21.6%). Histologically 98.6% of esophageal cancer is squamous cell carcinoma, of which 57.1% were poorly differentiated.
3.2.1. The overall resectability rate with the 5349 cases of esophageal cancer undergoing resection with curative intent was 96.0% (5136/5349). The resectability rates increased significantly over the four time periods (90.7%, 97.1%, 98.7%, 99.8% , P<0.01). (Table 1)
3.2.2. The mean age of esophageal cancer patients undergone resection increased significantly (51.6, 52.0, 53.7, 60.0 years old, P<0.01); the proportion of patients in preoperative co-morbidity with cerebral or cardiovasicular disease increased significantly ( 0.4%, 2.6%, 3.5% , 13.3%, P<0.01); the proportion of esophageal cancer patients with tumor located in the upper third of the thoracic esophagus increased significantly (1%, 1.2%, 3.4% , 5.4% , P<0.01).
3. 3. Lymph node metastasis and dissection
3.3.1. Proportion of lymph node metastasis
The proportion of patients with lymph node metastasis by post operative pathological examination decreased significantly (69.1%, 69.0%,64.5%, 47.1%, P<0.001 ). Or according to the UICC/AJCC 7th staging system, the proportion of patients with PTNM stageⅠB -ⅡA disease increased significantly ( 30.9%, 31.0%, 35.5%,52.9%, P<0.001); in contrast, those with IIIC (T4bN3) - IV disease (surgically non-resectable) decreased significantly ( 28.2%, 21.8%, 18.9% to 11.1%, P<0.001); however, the proportion of patients with advanced but still resectable lesion, e.g., in the stage ofⅡB/III A/III B/IIIC (excluding T4bN3), remained constant (53.5%, 56.7%, 56.4% , 53.6%, P>0.25, Fig 1).
3.3.2. Number of lymph node harvested
The average number of lymph nodes harvested in mediastinal and abdominal lymph node dissection increased significantly ( 3.93, 4.03, 4.51 , 5.07,P<0.001), but the median number of that increased non-significantly (4.0, 4.0, 4.0, 5.0, P=0.18 ) (Table 1).
3.4 Operative mortality
Of the 5136 patients resected, 242 patients died within 90 days of surgery, for a 3-month mortality rate of 4.7% (242/5136). The 3-month mortality rate decreased significantly over the four time periods, from 6.0%, 5.4%, 3.3% to 3.1% (P<0.01). 128 patients died within 30 days of surgery, for a 1-month mortality rate of 2.5% (128/5136). The 1-month mortality rate also decreased significantly from 3.2%, 3.0%, 1.7% to 1.3% (P<0.01, Table 1).
3.5. Postoperative complication
Of the 5136 cases resected, postoperative complication occurred in 9.4% (483/5136). The rate decreased significantly over the four time periods, from 11.4%, 9.7%, 8.9% to 5.2% (P<0.01). Anastomotic leakage occurred in 3.1% (158/5136) and was the most common complication, and Pulmonary complication developed in 2.3% (119/5136) and was the second most common complication. Both rates decreased significantly over the four time period (3.2%, 3.9%, 2.3% to 1.9%, P<0.05; 5.6%, 1.1%, 1.6% to 0.3%, P<0.01 ). However, the rate of cerebro or cardiavasicular complication increased significantly (0.3%, 1.0%, 0.7%, 2.1%, P<0.05) (Table 2).
3.5.2. Death rate of complication and anastomotic leakage
In contrast to the decreasing rates of postoperative complication and operative mortality, the death rate of complication remained the same as 52.9%, 55.2%, 36.9%, and 59.4% over the four time periods (P>0.05) however，and so did the death rate of anastomotic leakage(77.3%, 85.7%, 96.9%, 75.0%, P>0.05) (Table 2).
3.6 . Improvement in five year survival rates
The overall 5-year survival rate was 36% and the 5-year survival rate progressed significantly from 32%, 35%, 38% to 43% (P<0.001) (Table 3, Fig 2). When the significance of improvement in 5-year survival rate between consecutive decades was tested, that from 1970s to 1980s and from 1980s to 1990-1994 were non-significant, but the progression from 1990-1994 to 2008 was significant (Table 3, Fig 2).
When improvement in 5-year survival over the four time periods was analyzed according to pTNM stage, significant improvement was observed only among patients in the stage ofⅠB/ⅡA /ⅡB/III A/III B/IIIC (excluding T4bN3) (Fig 3), not among patients in the stage of IIIC (T4bN3)/IV (Fig 4).
3.7 Multivariate Cox regression analyses
Of the 7 demographic or clinicopathologic characteristics found to be significant by univariate Cox regression analysis, five were identified as significant independent prognostic factors by the backwards multivariate model. These were pTNM stage (P<0.001), postoperative complications (P<0.001), the percent of lymph node metastasized (P<0.001), decade of surgery (P<0.01), and the average age of the patients(P<0.05).However, sex and the median number of lymph nodes harvested did not reached significant level as independent prognostic factor. Of the five significant prognostic factors, three had changed significant over the four decades; e g., pTNM stage and rate of postoperative complications decreased significantly (both P<0.001), but the average age of patients resected increased significantly (P<0.05). Of note, the median number of lymph node retrieved was eliminated in step 2 backwards regression from significant prognostic factors (Table 4).