Hao Xian Yang

An Evaluation of the Number of Lymph Nodes Examined and Survival for Node-Negative Esophageal Carcinoma: Data from China

BackgroundThe current American Joint Committee on Cancer (AJCC) staging system for esophageal cancer does not define the minimum number of lymph nodes (LNs) necessary for accurate nodal staging. This study aimed to seek the minimum number of LNs examined for adequate nodal staging of patients with node-negative esophageal cancer.MethodsWe conducted a retrospective review of 592 patients undergoing R0 resection with node-negative esophageal carcinoma between December 1996 and December 2004. The relationship between the total number of examined LNs and death from esophageal cancer was investigated by means of a scatterplot of this variable versus Martingale residuals from a Cox proportional hazard regression model without the variable of interest. A smoothed line fit of the scatterplot was applied to detect the reasonable cutoff point.ResultsThe patients were classified into four categories according to the number of examined LNs: ≤5, 6 to 9, 10 to 17, and ≥18. A reduced hazard ratio of death was observed with an increasing number of LNs examined. The 5-year cancer-specific survival rate was 42.8% among patients with ≤5 LNs examined, compared with 52.6, 56.8, and 75% for those with 6–9 LNs, 10–17 LNs, and ≥18 LNs, respectively. Multivariate Cox regression analysis suggested that female sex, lower grade of cell differentiation, lower T category and increasing number of examined LNs were independent factors favoring cancer-specific survival.ConclusionsAt least 18 LNs should be resected for accurate staging of operable esophageal carcinoma. However, a validation from other institute is warranted.

High Expression of p300 Has an Unfavorable Impact on Survival in Resectable Esophageal Squamous Cell Carcinoma

BACKGROUND p300 is a transcriptional regulator that is involved in fundamental processes such as cell proliferation, cell differentiation, and tumor progression. However, its role and clinical significance in resectable esophageal squamous cell carcinoma (ESCC) has not been elucidated. The purpose of this study was to explore whether there was a correlation between the expression of p300 by immunohistochemistry and the clinical outcome of a group of patients with ESCC treated with surgical resection. METHODS Tissue microarray that included 240 surgically resected ESCC specimens and 56 cases of paracancerous tissues was successfully generated for immunohistochemical evaluation. The clinical and prognostic significance of p300 expression was analyzed statistically. Kaplan-Meier analysis was used to compare the postoperative survival between groups. RESULTS The expression frequency and expression levels of p300 were significantly higher in ESCC specimens (62.5%, 150 of 240) than in normal esophageal mucosa (8.9%, 5 of 56; p<0.001). Increased p300 expression was associated with higher histologic grade (p=0.012), T category (p=0.032), and N category (p=0.013). Patients with low expression of p300 demonstrated higher overall survival compared with those with high expression of p300 (mean, 80.0 months versus 56.9 months; p<0.001). A similar result was observed for disease-free survival (mean, 78.3 months versus 53.1 months; p<0.001). Furthermore, p300 expression could stratify the patient survival (disease-free survival and overall survival) in stage II (p=0.002, 0.003, respectively). Multivariate analysis showed that the level of p300 expression was an independent prognostic factor in ESCC (relative risk, 1.658; p=0.017). CONCLUSIONS High expression of p300 suggests poor prognosis for patients with resectable ESCC.

Survival and Risk Factors of Surgically Treated Mediastinal Invasion T4 Non-Small Cell Lung Cancer

BACKGROUND Surgical treatment of T4 non-small cell lung cancer (NSCLC) patients with mediastinal involvement is controversial. This study was conducted to propose subgroups of patients with T4 NSCLC with mediastinal involvement who are more likely to benefit from resection. METHODS Consecutive patients with T4 NSCLC with mediastinal involvement who underwent thoracotomy (n = 146) were retrospectively analyzed. Actuarial survival was calculated. Factors associated with overall survival were identified. RESULTS Four operative deaths occurred in pneumonectomy patients. The overall 5-year survival rate was 22.7%; median survival was 24.8 months. Factors favoring survival included complete resection (p < 0.001), N2-negative disease (p < 0.001), and pulmonary great vessel invasion (p < 0.001). Multivariate analysis of 131 patients undergoing lung resection found three factors associated with increased survival: pulmonary great vessel involvement (relative risk [RR] of death, 0.365; 95% confidence interval [CI], 0.208 to 0.639; p < 0.001), R0 resection (RR, 0.387; 95% CI, 0.209 to 0.714; p = 0.002), and postoperative chemotherapy (RR, 0.255; 95% CI, 0.134 to 0.487; p < 0.001). Male sex (RR, 2.962; 95% CI, 1.479 to 5.934; p = 0.002) and N2-positive disease (RR, 3.220; 95% CI, 1.640 to 6.323; p < 0.001) were associated with decreased survival. CONCLUSIONS N2-positive, T4 NSCLC with mediastinal involvement is not suitable for resection. T4 NSCLC patients with pulmonary great vessel involvement had better survival rates than other T4 subgroups. Pneumonectomy should be done with caution due to a high mortality risk and poor prognosis. Further studies are warranted to assess the role of sex on survival.

Tumor location does not impact long-term survival in patients with operable thoracic esophageal squamous cell carcinoma in China.

BACKGROUND The seventh edition of the American Joint Committee on Cancer staging system considers tumor location as a factor in staging esophageal squamous cell carcinoma (ESCC). However, more data are essential to test its efficacy. The purpose of this study is to assess whether tumor location should be included as a factor in staging of thoracic ESCC in Chinese patients. METHODS A retrospective review of 1,220 patients with ESCC who underwent complete resection between December 1996 and December 2008 was conducted. Survival was calculated by the Kaplan-Meier method, and the log-rank test was used to assess survival differences between groups. Subgroup analysis and the Cox proportional hazards model were used to further determine the impact of tumor location on overall survival. RESULTS The median survival times for patients with ESCC in the upper third, middle third, and lower third of the esophagus were 45.1 months, 62.9 months, and 39.2 months, respectively, with corresponding 5-year survival rates of 44.8%, 50.5%, and 45.6%, respectively (p=0.191). Subgroup analysis also demonstrated that tumor location did not determine survival prognosis. Multivariate Cox regression analysis suggested that being female (p=0.001), being young (p<0.001), having a lower grade of cell differentiation (p=0.030), T category (p<0.001), and N category (p<0.001) were independent factors favoring overall survival, whereas tumor location (p=0.295) and surgical approaches (p=0.521) were not independent factors impacting prognosis. CONCLUSIONS Staging of ESCC in the Chinese population should be simplified by omitting tumor location as a variable. More data from Asian populations are warranted to verify these results.

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.

Skp2 expression unfavorably impacts survival in resectable esophageal squamous cell carcinoma

BackgroundThe correlation of S-phase kinase–associated protein 2 (Skp2) with metastasis and prognosis in esophageal squamous cell carcinoma (ESCC) is controversial. The purpose of this study was to explore whether there was a correlation between the expression of Skp2 evaluated by immunohistochemistry and the clinical outcome of patients with operable ESCC, and to further determine the possible mechanism of the impact of Skp2 on survival.MethodsTissue microarrays that included 157 surgically resected ESCC specimens was successfully generated for immunohistochemical evaluation. The clinical/prognostic significance of Skp2 expression was analyzed. Kaplan-Meier analysis was used to compare the postoperative survival between groups. The prognostic impact of clinicopathologic variables and Skp2 expression was evaluated using a Cox proportional hazards model. A cell proliferation assay and a colony formation assay were performed in ESCC cell lines to determine the function of Skp2 on the progression of ESCC in vitro.ResultsSkp2 expression correlated closely with the T category (p = 0.035) and the pathological tumor-node-metastasis (TNM) stage (p = 0.027). High expression of Skp2 was associated with poor overall survival in resectable ESCC (p = 0.01). The multivariate Cox regression analysis demonstrated that pathological T category, pathological N category, cell differentiation, and negative Skp2 expression were independent factors for better overall survival. In vitro assays of ESCC cell lines demonstrated that Skp2 promoted the proliferative and colony-forming capacity of ESCCs.ConclusionsNegative Skp2 expression in primary resected ESCC is an independent factor for better survival. Skp2 may play a pro-proliferative role in ESCC cells.

Peripheral Direct Adjacent Lobe Invasion Non-small Cell Lung Cancer Has a Similar Survival to That of Parietal Pleural Invasion T3 Disease

Introduction: The postoperative prognosis of peripheral adjacent lobe invasion non-small cell lung cancer (NSCLC) is unclear. The purpose of this study was to determine the postoperative prognosis of NSCLC with direct adjacent lobe invasion by comparing it with that of visceral pleural invasion (primary lobe) T2 disease, and parietal pleural invasion T3 disease, and hence determine its most appropriate T category. Methods: A retrospective analysis was conducted to assess the survival of patients with peripheral direct adjacent lobe invasion NSCLC (group A), and it was compared with that of patients with visceral pleural invasion of the primary lobe (group B) and parietal pleural invasion (group C). All patients were node-negative on pathologic examination. Kaplan-Meier method was used to compare the postoperative survival between groups. Results: A total of 263 patients were analyzed. The overall survival rates in groups A (n = 28), B (n = 167), and C (n = 68) at 5 years were 40.7, 54.6, and 41.9%, respectively; corresponding median survival in three groups were 53, 71, and 40 months, respectively. The survival difference among three groups was statistically significant (p = 0.031). A similar survival was observed between groups A and C, whereas group B had a much better survival than other groups. Conclusions: Peripheral adjacent lobe invasion NSCLC has a similar survival prognosis with that of parietal pleural invasion T3 disease and hence should be classified as T3 rather than T2. However, further studies are warranted.

Efficacy of Endoscopic Ultrasonography for Determining Clinical T Category for Esophageal Squamous Cell Carcinoma: Data From 1434 Surgical Cases

BackgroundThe efficacy of endoscopic ultrasonography (EUS) for determining T category is variable for esophageal squamous cell carcinoma (ESCC). We aimed to assess the efficacy of EUS in accurately identifying T category for ESCC based on the 8th AJCC Cancer Staging Manual.MethodsA retrospective analysis was conducted using a prospectively collected ESCC database from January 2003 to December 2015, in which all patients underwent EUS examination followed by esophagectomy. The efficacy of EUS was evaluated by sensitivity, specificity, and accuracy compared with pathological T category as gold standard. Overall survival of different EUS-T (uT) categories was assessed.ResultsIn total, 1434 patients were included, of whom 58.2% were correctly classified by EUS, with 17.9% being overstaged and 23.9% being understaged. The sensitivity and accuracy of EUS for Tis, T1a, T1b, T2, T3, and T4a categories were 15.8 and 98.8%, 16.3 and 95.7%, 33.1 and 89.3%, 56.8 and 65.0%, 65.8 and 70.0%, and 27.3 and 97.5%, respectively. The survival difference between uT1a and uT1b was not statistically significant (p = 0.90), nor was that between uT4a and uT4b (p = 0.34). However, when uT category was integrated as uTis, uT1, uT2, uT3, and uT4, overall survival was clearly distinguished between the categories (p < 0.01).ConclusionsEUS is in general feasible for classifying clinical T category for ESCC. However, EUS should be used with caution for discriminating between Tis, T1a, and T1b disease, as well as T4 disease.

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.