Guowei Ma

Three-field vs two-field lymph node dissection for esophageal cancer: A meta-analysis

AIM To assess the effects of 3-field lymphadenectomy for esophageal carcinoma. METHODS We conducted a computerized literature search of the PubMed, Cochrane Controlled Trials Register, and EMBASE databases from their inception to present. Randomized controlled trials (RCTs) or observational epidemiological studies (cohort studies) that compared the survival rates and/or postoperative complications between 2-field lymphadenectomy (2FL) and 3-field lymphadenectomy (3FL) for esophageal carcinoma with R0 resection were included. Meta-analysis was conducted using published data on 3FL vs 2FL in esophageal carcinoma patients. End points were 1-, 3-, and 5-year overall survival rates and postoperative complications, including recurrent nerve palsy, anastomosis leak, pulmonary complications, and chylothorax. Subgroup analysis was performed on the involvement of recurrent laryngeal lymph nodes. RESULTS Two RCTs and 18 observational studies with over 7000 patients were included. There was a clear benefit for 3FL in the 1- (RR = 1.16; 95%CI: 1.09-1.24; P < 0.01), 3- (RR = 1.44; 95%CI: 1.19-1.75; P < 0.01), and 5-year overall survival rates (RR = 1.37; 95%CI: 1.18-1.59; P < 0.01). For postoperative complications, 3FL was associated with significantly more recurrent nerve palsy (RR = 1.43; 95%CI: 1.28-1.60; P = 0.02) and anastomosis leak (RR = 1.26; 95%CI: 1.05-1.52; P = 0.09). In contrast, there was no significant difference for pulmonary complications (RR = 0.93; 95%CI: 0.75-1.16, random-effects model; P = 0.27) or chylothorax (RR = 0.77; 95%CI: 0.32-1.85; P = 0.69). CONCLUSION This meta-analysis shows that 3FL improves overall survival rate but has more complications. Because of the high heterogeneity among outcomes, definite conclusions are difficult to draw.

Characteristics and Prognostic Analysis of 69 Patients With Pulmonary Sarcomatoid Carcinoma.

Background:Pulmonary sarcomatoid carcinoma (PSC) is a rare malignancy. Methods:A total of 69 patients with PSC treated at a single institution in southern China with long-term follow-up were evaluated in this study. We analyzed the clinical characteristics, immunohistochemical profiles, epidermal growth factor receptor mutation status, K-RAS mutation status, treatments, and prognosis. Results:PSC mainly occurred in young male patients with a history of smoking. Most patients received multimodality treatments and the majority had early-stage disease. The median survival time was 19.1 months, and the 5-year survival rate was 17.4%. The patients without distant metastasis, with normal or higher body mass index (≥18.5), with normal hemoglobin, with smaller tumor size (⩽4 cm), and those who received complete resection had significantly better overall survival (P<0.05). The patients with pleomorphic carcinoma had much worse prognosis. In a Cox regression model, M stage, pathology, and having received a complete resection were independent prognostic factors (P<0.05). Conclusions:PSC is a unique lung malignancy with poor prognosis. Patients receiving complete resection had better prognosis, likely a reflection of early-stage disease. Neither neoadjuvant nor adjuvant chemotherapy improved patient survival for those with early-stage disease. The retrospective design and small sample size limited the generalizability. Future multicenter collaborations may be necessary to determine the optimal treatment.

Prognostic role of neutrophil-lymphocyte ratio in operable esophageal squamous cell carcinoma

AIM To determine the prognostic significance of preoperative serum neutrophil-lymphocyte ratio (NLR) in esophageal squamous cell carcinoma (ESCC). METHODS Data from 371 eligible patients with ESCC who had undergone surgery with curative intent at our institution between October 2000 and May 2007 were retrospectively recruited for analysis. The cutoff value of NLR was 3.0 as determined by the receiver operating characteristic curve, which discriminated between survival and death; the area under the curve was 0.709, and the sensitivity and specificity were 66.1% and 69.1%, respectively, at the cutoff point. The correlation between the NLR and clinicopathological characteristics was analyzed using a χ(2) test. The prognostic influence of the NLR and other clinicopathological factors on cancer-specific survival (CSS) and recurrence-free survival (RFS) was studied using the Kaplan-Meier method. To evaluate the independent prognostic value of NLR, multivariate Cox regression models were applied. RESULTS The median age of the patients was 57.0 years, and 276/371 (74.4%) patients were male. The NLR was ≤ 3.0 in 80.1% (297/371) of the patients, and the remaining 19.9% (74/371) had an NLR > 3.0. Median postoperative follow-up was 66.0 mo [interquartile range (IQR): 49.0-76.0 mo], with a follow-up rate of 94%. Follow-up was not significantly different between patients with an NLR ≤ and > 3.0 (63.13 ± 1.64 vs 61.52 ± 3.66, P = 0.711). However, higher preoperative serum NLR was associated with significantly increased risks of higher pathological tumor status (P = 0.007). A significant, independent association between high preoperative serum NLR and poor clinical outcome was identified in a multivariate analysis for CSS (HR = 1.591; P = 0.007) and RFS (HR = 1.525; P = 0.013). Moreover, when patients were stratified by pathological tumor-node-metastasis (TNM) staging, the adverse effects of preoperative serum NLR on CSS (HR = 2.294; P = 0.008) and RFS (HR = 2.273; P = 0.008) were greatest in those patients with stage IIIA disease. CONCLUSION Preoperative serum NLR is a useful prognostic marker to complement TNM staging for operable ESCC patients, particularly in patients with stage IIIA disease.

Can Lymph Node Ratio Replace pN Categories in the Tumor-Node-Metastasis Classification System for Esophageal Cancer?

Background: We evaluated the prognostic value of lymph node ratio (LNR) in esophageal squamous cell carcinoma (ESCC) patients after tri-incisional esophagectomy by making comparisons with pN categories in the UICC/AJCC (International Union Against Cancer/American Joint Committee on Cancer) classification system (seventh edition). Methods: Seven hundred ESCC patients underwent tri-incisional esophagectomy at our center (1988–2008) without neoadjuvant therapy. The adjusted X-tile cutoff values for LNR of 0 and 0.25 were compared with those in UICC/AJCC pN categories. Results: Univariate and multivariate analyses identified LNR as a significant prognostic factor regardless of the number of retrieved LNs. Spearman’s correlation analysis showed close linear correlations between the number of examined and metastatic LNs (r = 0.205, p < 0.001), but not between the number of examined LNs and LNR (r = 0.058, p = 0.123). Significant prognostic differences were seen among LNR categories in all pT categories (p < 0.05), but not in pN categories stratified by tumor status (except T3: p < 0.001). Significant prognostic difference was seen among LNR categories in all pN categories (p < 0.05), but not between pN categories in all LNR categories (p > 0.05). Significant differences in 5-year cancer-specific survival rates were found among retrieved-node groups in the same pN category (except N2+3: p = 0.733), but not within the same LNR category (except N0: p < 0.001). Conclusions: LNR is an independent prognostic factor after tri-incisional esophagectomy, regardless of the number of retrieved LNs. In ESCC, LNR might reduce stage migration, have more potential for predicting patient outcomes, and compensate for deficiencies in UICC/AJCC pN categories.

Surgical treatment for limited-stage primary small cell cancer of the esophagus.

BACKGROUND Primary small cell cancer of the esophagus (PSCCE) is a rare, aggressive, and highly metastatic disease. Surgical intervention, radiotherapy, and chemotherapy have been used alone or in combination to improve survival. This retrospective study tried to evaluate the significance of surgical procedures for the treatment of limited-stage PSCCE. METHODS We retrospectively evaluated 44 patients with limited-stage PSCCE who received esophagectomy with lymphadenectomy in our center between 1994 and 2011. The clinical and pathologic characteristics, median survival time (MST), overall survival (OS), and relevant prognostic factors were analyzed. RESULTS The MST in our cohort was 18.0 months (95% confidence interval [CI], 9.6-26.4 months), and the 6-, 12-, 24-, 36-, and 60-month OS rates were 73%, 58%, 39%, 30%, and 18%, respectively. The MST of patients with positive lymph nodes was significantly shorter than that of those with negative lymph nodes (14 months versus 47 months; p = 0.031). Survival analysis confirmed that regional lymph node involvement (relative risk [RR], 5.287; 95% CI, 1.036-26.978; p = 0.045) was an independent prognostic factor. CONCLUSIONS Although the standard treatment protocol for PSCCE has not been established, the results of our study indicated that radical esophagectomy with extended lymphadenectomy should be considered as the primary treatment for patients with limited-stage PSCCE, particularly for those without regional lymph node involvement.

Stage migration and therapy modification after thoracoscopic internal mammary lymph node dissection in breast cancer patients

Although internal mammary lymph node (IMN) status is a major prognostic factor in breast cancer, it is not routinely assessed. To evaluate the impact of IMN status on staging and treatment of breast cancer, we enrolled 50 consecutive patients with inner or central tumors who received IMN dissection by video-assisted thoracoscopic surgery (VATS) after breast surgery. Of the 50 patients, 20 (40%) had IMN metastases. Of the 20 patients, 6 (12%) were upstaged from N0 to N2b and 5 (10%), 3 (6%) and 6 patients (12%) were upstaged from N1a, N2a, and N3a, respectively, to N3b. Because of the upstaging, 6 patients (12%) with only IMN metastases received more aggressive adjuvant chemotherapy. Because the whole IMN chain was removed in all patients, radiotherapy on IMN field was not required in our cohort independent of IMN status. In conclusion, VATS IMN dissection might lead to stage migration and therapy modification.

Do tumor location and grade affect survival in pT2N0M0 esophageal squamous cell carcinoma

BACKGROUND The TNM staging system for esophageal cancer in the seventh edition of the AJCC Cancer Staging Manual incorporates tumor grade and location for staging pT2-3N0M0 esophageal squamous cell carcinoma. Patients with pT2N0M0, classified as stage IIA according to the sixth edition of the AJCC Cancer Staging Manual, can now be classified as stage IB, IIA, or IIB. We discuss whether these changes lead to a better prediction of the prognosis of these patients and aimed to find out other factors to forecast patient prognosis. METHODS We retrospectively analyzed 317 patients with postoperative pathologic stage T2N0M0 who underwent esophagectomy between 1990 and 2005 at Sun Yat-sen University Cancer Center. We performed univariate and multivariate analyses to identify prognostic factors for survival and used the Kaplan-Meier method to demonstrate the prognostic efficacy of each prognostic factor, including tumor grade and location. RESULTS The 5-year overall survival was 57%, with a median survival of 84.5 months (6.94 years). Univariate analysis indicated that age, alcohol consumption, and tumor grade were associated with survival. Multivariate Cox proportional hazard regression analysis revealed that alcohol consumption and tumor grade were independent prognostic factors. Survival analysis using the Kaplan-Meier method demonstrated age, cigarette smoking, alcohol consumption, tumor grade, and location as prognostic factors. CONCLUSIONS For pT2N0M0 esophageal squamous cell carcinoma, the seventh edition of the AJCC Cancer Staging Manual does not provide a more distinguishable prediction of prognosis compared with the sixth edition. Tumor grade is an independent prognostic factor in patients with pT2N0M0 esophageal squamous cell carcinoma, whereas tumor location is not. Furthermore, alcohol consumption is an independent prognostic factor that may imply a worse prognosis.

Prognostic significance of the pN classification supplemented by body mass index for esophageal squamous cell carcinoma.

Body mass index (BMI) has been associated with the risk of esophageal cancer. But the influence of BMI on postoperative complications and prognosis has always been controversial.

Detection of rearrangement of anaplastic lymphoma kinase (ALK) and mutation of epidermal growth factor receptor (EGFR) in primary pulmonary lymphoepithelioma-like carcinoma.

BACKGROUND Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is a distinct rare subtype of lung cancer. The prevalence of anaplastic lymphoma kinase (ALK) rearrangement and epidermal growth factor receptor (EGFR) mutation in primary pulmonary LELC had not been thoroughly investigated. METHODS We investigated a cohort of 42 patients with primary pulmonary LELC and genotyped for ALK rearrangement and EGFR mutation. ALK rearrangement was detected by fluorescence in situ hybridization (FISH). EGFR mutational analysis of exons 18 through 21 was analyzed by TaqMan real-time polymerase chain reaction (PCR). RESULTS Epstein-Barr virus-encoded RNAs (EBERs) showed positive signals in all 42 patients. By immunohistochemistry staining, all patients demonstrated positive expression of CK5/6 and P63, but almost all patients were negative for TTF-1 (34/34, 100%) or CK7 (34/35, 97.1%). None of the 42 patients had ALK rearrangement. Of 42 patients tested, only one patient (2.4%) harbored L858R mutation and gefitinib was applied to this case, however no objective response was observed and the progression free survival (PFS) time was only 1 month. CONCLUSIONS Primary pulmonary LELC is a unique histological subtype of lung cancer. ALK rearrangement and EGFR mutation are lack and they may not be the oncogenic driver gene in pulmonary LELC. Future efforts should be made to explore other oncogenic driver gene to guide targeted therapy in this rare disease to determine the optimal treatment.

A novel multivariate scoring system for determining the prognosis of lymph node-negative esophageal squamous cell carcinoma following surgical therapy: An observational study

BACKGROUND Identifying patients with esophageal squamous cell carcinoma (ESCC) with negative prognostic factors, which have an extremely low survival rate, has been problematic. METHODS We retrospectively collected clinical data for 648 patients with lymph node-negative ESCC who were treated at the Sun Yat-Sen University Cancer Center from 1990 to 2005. Survival difference was compared using Kaplan-Meier analysis and multivariate Cox regression analysis. RESULTS We identified advancing age, smoking history, alcohol consumption history, decreased forced expiratory volume in 1 s (FEV1), surgical procedure, tumor location, number of resected lymph nodes, poor tumor differentiation, and surgical stage as independent prognostic risk factors. Furthermore, based on the results of multivariate analysis, we constructed a novel scoring system that included the factors of age, smoking history, alcohol consumption history, number of resected lymph nodes, tumor differentiation, and surgical stage. Risk score (RS) was computed with the scoring system, and patients were divided into Class A (RS: 0-5) and Class B (RS: 6-10). P < 0.001 indicated statistical significance. A significant difference (p < 0.001) demonstrated that Class B was strongly related to a low survival rate and poor prognosis. CONCLUSION We developed a new simple flexible scoring system of high prognostic significance, which has the potential to guide postoperative therapeutic strategies and follow-up frequency and to provide better prognostic information for patients and their families.